Cavitron ultrasonic surgical aspirator (CUSA) compared with conventional pancreatic transection in distal pancreatectomy: study protocol for the randomised controlled CUSA-1 pilot trial.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains the most common and serious complication after distal pancreatectomy. Many attempts at lowering fistula rates have led to unrewarding insignificant results as still up to 30% of the patients suffer from clinically relevant POPF. Therefore, the development of new innovative methods and procedures is still a cornerstone of current surgical research.The cavitron ultrasonic surgical aspirator (CUSA) device is a well-known ultrasound-based parenchyma transection method, often used in liver and neurosurgery which has not yet been thoroughly investigated in pancreatic surgery, but the first results seem very promising. METHODS: The CUSA-1 trial is a randomised controlled pilot trial with two parallel study groups. This single-centre trial is assessor and patient blinded. A total of 60 patients with an indication for open distal pancreatectomy will be intraoperatively randomised after informed consent. The patients will be randomly assigned to either the control group with conventional pancreas transection (scalpel or stapler) or the experimental group, with transection using the CUSA device. The primary safety endpoint of this trial will be postoperative complications ≥grade 3 according to the Clavien-Dindo classification. The primary endpoint to investigate the effect will be the rate of POPF within 30 days postoperatively according to the ISGPS definition. Further perioperative outcomes, including postpancreatectomy haemorrhage, length of hospital stay and mortality will be analysed as secondary endpoints. DISCUSSION: Based on the available literature, CUSA may have a beneficial effect on POPF occurrence after distal pancreatectomy. The rationale of the CUSA-1 pilot trial is to investigate the safety and feasibility of the CUSA device in elective open distal pancreatectomy compared with conventional dissection methods and gather the first data on the effect on POPF occurrence. This data will lay the groundwork for a future confirmatory multicentre randomised controlled trial. ETHICS AND DISSEMINATION: The CUSA-1 trial protocol was approved by the ethics committee of the University of Heidelberg (No. S-098/2022). Results will be published in an international peer-reviewed journal and summaries will be provided in lay language to study participants and their relatives. TRIAL REGISTRATION NUMBER: DRKS00027474.

Intraoperative Wound Irrigation for the Prevention of Surgical Site Infection After Laparotomy: A Randomized Clinical Trial by CHIR-Net.

Importance: Surgical site infections frequently occur after open abdominal surgery. Intraoperative wound irrigation as a preventive measure is a common practice worldwide, although evidence supporting this practice is lacking. Objective: To evaluate the preventive effect of intraoperative wound irrigation with polyhexanide solution. Design, Setting, and Participants: The Intraoperative Wound Irrigation to Prevent Surgical Site Infection After Laparotomy (IOWISI) trial was a multicenter, 3-armed, randomized clinical trial. Patients and outcome assessors were blinded to the intervention. The clinical trial was conducted in 12 university and general hospitals in Germany from September 2017 to December 2021 with 30-day follow-up. Adult patients undergoing laparotomy were eligible for inclusion. The main exclusion criteria were clean laparoscopic procedures and the inability to provide consent. Of 11 700 screened, 689 were included and 557 completed the trial; 689 were included in the intention-to-treat and safety analysis. Interventions: Randomization was performed online (3:3:1 allocation) to polyhexanide 0.04%, saline, or no irrigation (control) of the operative wound before closure. Main Outcome and Measures: The primary end point was surgical site infection within 30 postoperative days according to the US Centers for Disease Control and Prevention definition. Results: Among the 689 patients included, 402 were male and 287 were female. The median (range) age was 65.9 (18.5-94.9) years. Participants were randomized to either wound irrigation with polyhexanide (n = 292), saline (n = 295), or no irrigation (n = 102). The procedures were classified as clean contaminated in 92 cases (8%). The surgical site infection incidence was 11.8% overall (81 of 689), 10.6% in the polyhexanide arm (31 of 292), 12.5% in the saline arm (37 of 295), and 12.8% in the no irrigation arm (13 of 102). Irrigation with polyhexanide was not statistically superior to no irrigation or saline irrigation (hazard ratio [HR], 1.23; 95% CI, 0.64-2.36 vs HR, 1.19; 95% CI, 0.74-1.94; P = .47). The incidence of serious adverse events did not differ among the 3 groups. Conclusions and Relevance: In this study, intraoperative wound irrigation with polyhexanide solution did not reduce surgical site infection incidence in clean-contaminated open abdominal surgical procedures compared to saline or no irrigation. More clinical trials are warranted to evaluate the potential benefit in contaminated and septic procedures, including the emergency setting. Trial Registration: drks.de Identifier: DRKS00012251.

Robotic versus open partial pancreatoduodenectomy (EUROPA): a randomised controlled stage 2b trial.

Background: Open partial pancreatoduodenectomy (OPD) represents the current gold standard of surgical treatment of a wide range of diseases of the pancreatic head but is associated with morbidity in around 40% of cases. Robotic partial pancreatoduodenectomy (RPD) is being used increasingly, yet, no randomised controlled trials (RCTs) of RPD versus OPD have been published, leaving a low level of evidence to support this practice. Methods: This investigator-initiated, exploratory RCT with two parallel study arms was conducted at a high-volume pancreatic centre in line with IDEAL recommendations (stage 2b). Patients scheduled for elective partial pancreatoduodenectomy (PD) for any indication were randomised (1:1) to RPD or OPD with a centralised web-based tool. The primary endpoint was postoperative cumulative morbidity within 90 days, assessed via the Comprehensive Complication Index (CCI). Biometricians were blinded to the intervention, but patients and surgeons were not. The trial was registered prospectively (DRKS00020407). Findings: Between June 3, 2020 and February 14, 2022, 81 patients were randomly assigned to RPD (n = 41) or OPD (n = 40), of whom 62 patients (RPD: n = 29, OPD: n = 33) were analysed in the modified intention to treat analysis. Four patients in the OPD group were randomised, but did not undergo surgery in our department and one patient was excluded in the RPD group due to other reason. Nine patients in the RPD group and 3 patients in the OPD were excluded from the primary analysis because they did not undergo PD, but rather underwent other types of surgery. The CCI after 90 days was comparable between groups (RPD: 34.02 ± 23.48 versus OPD: 36.45 ± 27.65, difference in means [95% CI]: -2.42 [-15.55; 10.71], p = 0.713). The RPD group had a higher incidence of grade B/C pancreas-specific complications compared to the OPD group (17 (58.6%) versus 11 (33.3%); difference in rates [95% CI]: 25.3% [1.2%; 49.4%], p = 0.046). The only complication that occurred significantly more often in the RPD than in the OPD group was clinically relevant delayed gastric emptying. Procedure-related and overall hospital costs were significantly higher and duration of surgery was longer in the RPD group. Blood loss did not differ significantly between groups. The intraoperative conversion rate of RPD was 23%. Overall 90-day mortality was 4.8% without significant differences between RPD and OPD. Interpretation: In the setting of a very high-volume centre, both RPD and OPD can be considered safe techniques. Further confirmatory multicentre RCTs are warranted to uncover potential advantages of RPD in terms of perioperative and long-term outcomes. Funding: Federal Ministry of Education and Research (BMBF: 01KG2010).

Effect of triclosan-coated sutures for abdominal wound closure on the incidence of abdominal wound dehiscence: a protocol for an individual participant data meta-analysis.

INTRODUCTION: Acute abdominal wound dehiscence (AWD) or burst abdomen is a severe complication after abdominal surgery with an incidence up to 3.8%. Surgical site infection (SSI) is the biggest risk factor for the development of AWD. It is strongly suggested that the use of triclosan-coated sutures (TCS) for wound closure reduces the risk of SSI. We hypothesise that the use of TCS for abdominal wound closure may reduce the risk of AWD. Current randomised controlled trials (RCTs) lack power to investigate this. Therefore, the purpose of this individual participant data meta-analysis is to evaluate the effect of TCS for abdominal wound closure on the incidence of AWD. METHODS AND ANALYSIS: We will conduct a systematic review of Medline, Embase and Cochrane Central Register of Controlled Trials for RCTs investigating the effect of TCS compared with non-coated sutures for abdominal wound closure in adult participants scheduled for open abdominal surgery. Two independent reviewers will assess eligible studies for inclusion and methodological quality. Authors of eligible studies will be invited to collaborate and share individual participant data. The primary outcome will be AWD within 30 days after surgery requiring reoperation. Secondary outcomes include SSI, all-cause reoperations, length of hospital stay and all-cause mortality within 30 days after surgery. Data will be analysed with a one-step approach, followed by a two-step approach. In the one-step approach, treatment effects will be estimated as a risk ratio with corresponding 95% CI in a generalised linear mixed model framework with a log link and binomial distribution assumption. The quality of evidence will be judged using the Grading of Recommendations Assessment Development and Evaluation approach. ETHICS AND DISSEMINATION: The medical ethics committee of the Amsterdam UMC, location AMC in the Netherlands waived the necessity for a formal approval of this study, as this research does not fall under the Medical Research involving Human Subjects Act. Collaborating investigators will deidentify data before sharing. The results will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019121173.

Intraoperative visualisation of pancreatic leakage (ViP): study protocol for an IDEAL Stage I Post Market Clinical Study.

INTRODUCTION: Pancreatic resections are an important field of surgery worldwide to treat a variety of benign and malignant diseases. Postoperative pancreatic fistula (POPF) remains a frequent and critical complication after partial pancreatectomy and affects up to 50% of patients. POPF increases mortality, prolongs the postoperative hospital stay and is associated with a significant economic burden. Despite various scientific approaches and clinical strategies, it has not yet been possible to develop an effective preventive tool. The SmartPAN indicator is the first surgery-ready medical device for direct visualisation of pancreatic leakage already during the operation. Applied to the surface of pancreatic tissue, it detects sites of biochemical leak via colour reaction, thereby guiding effective closure and potentially mitigating POPF development. METHODS AND ANALYSIS: The ViP trial is a prospective single-arm, single-centre first in human study to collect data on usability and confirm safety of SmartPAN. A total of 35 patients with planned partial pancreatectomy will be included in the trial with a follow-up of 30 days after the index surgery. Usability endpoints such as adherence to protocol and evaluation by the operating surgeon as well as safety parameters including major intraoperative and postoperative complications, especially POPF development, will be analysed. ETHICS AND DISSEMINATION: Following the IDEAL-D (Idea, Development, Exploration, Assessment, and Long term study of Device development and surgical innovation) framework of medical device development preclinical in vitro, porcine in vivo, and human ex vivo studies have proven feasibility, efficacy and safety of SmartPAN. After market approval, the ViP trial is the IDEAL Stage I trial to investigate SmartPAN in a clinical setting. The study has been approved by the local ethics committee as the device is used exclusively within its intended purpose. Results will be published in a peer-reviewed journal. The study will provide a basis for a future randomised controlled interventional trial to confirm clinical efficacy of SmartPAN. TRIAL REGISTRATION NUMBER: German Clinical Trial Register DRKS00027559, registered on 4 March 2022.

Peridural analgesia does not impact survival in patients after colon cancer resection: a retrospective propensity score-adjusted analysis.

PURPOSE: To assess the putative impact of peridural analgesia on oncological outcome in patients undergoing resection of stages I-IV colon cancer. METHODS: In a single-center study, 876 patients undergoing resection for primary colon cancer (AJCC stages I-IV) between 2001 and 2014 were analyzed. Mean follow-up of the entire cohort was 4.2 ± 3.5 years. Patients who did and did not receive peridural analgesia were compared using Cox regression and propensity score analyses. RESULTS: Overall, 208 patients (23.7%) received peridural analgesia. Patients' characteristics were biased with regard to the use of peridural analgesia (propensity score 0.296 ± 0.129 vs. 0.219 ± 0.108, p < 0.001). After propensity score matching, the use of peridural analgesia had no impact on overall (HR 0.81, 95% CI 0.59-1.11, p = 0.175), cancer-specific (HR 0.72, 95% CI 0.48-1.09, p = 0.111), and disease-free survival (HR 0.89, 95% CI 0.66-1.19, p = 0.430). The 5-year overall survival after propensity score matching was 60.9% (95% CI 54.8-67.7%) for patients treated with peridural analgesia compared with 54.1% (95% CI 49.5-59.1%) for patients not treated with peridural analgesia. Cancer-specific and disease-free survival showed similar non-significant results. CONCLUSIONS: Peridural analgesia in patients after colon cancer resection was not associated with a better oncological outcome after risk adjusting in multivariable Cox regression and propensity score analyses. Hence, oncological outcome should not serve as a reason for the use of peridural analgesia in patients with colon cancer.

Prophylactic mesh placement for the PREvention of paraSTOmal hernias: The PRESTO systematic review and meta-analysis.

BACKGROUND: Parastomal hernia (PH) is the most common complication after ostomy formation. Prophylactic mesh placement may be effective in reducing the rate of PH at the stoma site. The aims of this systematic review were to summarize the evidence with regard to the safety and effectiveness in comparison with the standard procedure without mesh placement and to identify important risk constellations. METHOD: A systematic literature search was performed in PubMed, EMBASE and the Cochrane library with no language or date restrictions. Randomized (RCTs) and non-randomized controlled trials (nRCTs) were included. The main outcomes of interest were PH (primary outcome) rate and stoma-related complications (secondary outcomes) such as stenosis or fistula. Statistical analysis included meta-analyses of pooled data and subgroup analyses. RESULTS: Eleven trials (eight RCTs; three nRCTs) with a total of 755 patients were included. PH rate varied from 0% to 59% in the intervention and from 20% to 94% in the control group. RCTs showed a significant reduction of PH rate in the mesh group (OR 0.24; 95% CI 0.10 to 0.58, p = 0.034), whereas included nRCTs did not. No significant differences were observed in postoperative complication rates. Subgroup analyses showed superiority of non-absorbable meshes and sublay mesh positioning in open surgery. CONCLUSION: Prophylactic mesh placement is safe and reduces PH rate. A recommendation for prophylactic non-absorbable meshes in a sublay position can be made for patients undergoing open colorectal operations with end-ostomies. Further research endeavors should focus on patient-oriented outcomes, not only PH rate, with respect to tailored treatment in specific patient populations.

Discovery of novel plasma proteins as biomarkers for the development of incisional hernias after midline incision in patients with colorectal cancer: The ColoCare study.

BACKGROUND: Ventral incisional hernia is the most common long-term complication after an abdominal operation. Among newly diagnosed colorectal cancer patients, we screened the preoperative plasma proteome to explore predictive markers for the development of an incisional hernia. METHODS: We utilized preoperative plasma samples of 72 newly diagnosed colorectal cancer patients who underwent midline incision for tumor resection between 2010 and 2013. A total of 21 patients with incisional hernia occurrence were matched with 51 patients with at least 18 months follow-up without an incisional hernia by sex, age, and body mass index. To assess predictive markers of incisional hernia risk, we screened the plasma proteome for >2,000 distinct proteins using a well-validated antibody microarray test. Paired t tests were used to compare protein levels between cases and controls. A gene-set-enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) was applied to test for differences in signaling pathways between the 2 groups. RESULTS: The proteome screen identified 25 proteins that showed elevated or reduced plasma levels in the hernia group compared to the control group (nominal P values < .05). Several proteins were in pathways associated with wound healing (CCL21, SHBG, BRF2) or cell adhesion (PCDH15, CDH3, EPCAM). CONCLUSION: Our study shows that there are multiple individual and groups of plasma proteins that could feasibly predict the personal hernia risk prior to undergoing an operation. Further investigations in larger, independent sample sets are warranted to replicate findings and validate clinical utility of potential biomarkers. After validation, such a biomarker could be incorporated into a multifactorial risk model to guide clinical decision-making.

Ischemic Colitis after Cardiac Surgery: Can We Foresee the Threat?

INTRODUCTION: Ischemic colitis (IC) remains a great threat after cardiac surgery with use of extracorporeal circulation. We aimed to identify predictive risk factors and influence of early catecholamine therapy for this disease. METHODS: We prospectively collected and analyzed data of 224 patients, who underwent laparotomy due to IC after initial cardiac surgery with use of extracorporeal circulation during 2002 and 2014. For further comparability 58 patients were identified, who underwent bypass surgery, aortic valve replacement or combination of both. Age ±5 years, sex, BMI ± 5, left ventricular function, peripheral arterial disease, diabetes and urgency status were used for match-pair analysis (1:1) to compare outcome and detect predictive risk factors. Highest catecholamine doses during 1 POD were compared for possible predictive potential. RESULTS: Patients' baseline characteristics showed no significant differences. In-hospital mortality of the IC group with a mean age of 71 years (14% female) was significantly higher than the control group with a mean age of 70 (14% female) (67% vs. 16%, p<0.001). Despite significantly longer bypass time in the IC group (133 ± 68 vs. 101 ± 42, p = 0.003), cross-clamp time remained comparable (64 ± 33 vs. 56 ± 25 p = 0.150). The majority of the IC group suffered low-output syndrome (71% vs. 14%, p<0.001) leading to significant higher lactate values within first 24h after operation (55 ± 46 mg/dl vs. 31 ± 30 mg/dl, p = 0.002). Logistic regression revealed elevated lactate values to be significant predictor for colectomy during the postoperative course (HR 1.008, CI 95% 1.003-1.014, p = 0.003). However, Receiver Operating Characteristic Curve calculates a cut-off value for lactate of 22.5 mg/dl (sensitivity 73% and specificity 57%). Furthermore, multivariate analysis showed low-output syndrome (HR 4.301, CI 95% 2.108-8.776, p<0.001) and vasopressin therapy (HR 1.108, CI 95% 1.012-1.213, p = 0.027) significantly influencing necessity of laparotomy. CONCLUSION: Patients who undergo laparotomy for IC after initial cardiac surgery have a substantial in-hospital mortality risk. Early postoperative catecholamine levels do not influence the development of an IC except vasopressin. Elevated lactate remains merely a vague predictive risk factor.

Anti-angiogenic activity of VXM01, an oral T-cell vaccine against VEGF receptor 2, in patients with advanced pancreatic cancer: A randomized, placebo-controlled, phase 1 trial.

VEGFR-2 is expressed on tumor vasculature and a target for anti-angiogenic intervention. VXM01 is a first in kind orally applied tumor vaccine based on live, attenuated Salmonella bacteria carrying an expression plasmid, encoding VEGFR-2. We here studied the safety, tolerability, T effector (Teff), T regulatory (Treg) and humoral responses to VEGFR2 and anti-angiogenic effects in advanced pancreatic cancer patients in a randomized, dose escalation phase I clinical trial. Results of the first 3 mo observation period are reported. Locally advanced or metastatic, pancreatic cancer patients were enrolled. In five escalating dose groups, 30 patients received VXM01 and 15 placebo on days 1, 3, 5, and 7. Treatment was well tolerated at all dose levels. No dose-limiting toxicities were observed. Salmonella excretion and salmonella-specific humoral immune responses occurred in the two highest dose groups. VEGFR2 specific Teff, but not Treg responses were overall increased in vaccinated patients. We furthermore observed a significant reduction of tumor perfusion after 38 d in vaccinated patients together with increased levels of serum biomarkers indicative of anti-angiogenic activity, VEGF-A, and collagen IV. Vaccine specific Teff responses significantly correlated with reductions of tumor perfusion and high levels of preexisting VEGFR2-specific Teff while those showing no antiangiogenic activity had low levels of preexisting VEGFR2 specific Teff, showed a transient early increase of VEGFR2-specific Treg and reduced levels of VEGFR2-specific Teff at later time points - pointing to the possibility that early anti-angiogenic activity might be based at least in part on specific reactivation of preexisting memory T cells.

A rapid and accurate new bedside test to assess maximal liver function: a case report.

BACKGROUND: In liver surgery, appropriate preoperative evaluation and preparation of the patient is of cardinal importance. The up-to-date, preoperative prediction of residual liver function has thus far been limited. As post-hepatectomy liver failure is a major cause of mortality, a new and simple bedside test (LiMAx) has been developed to predict postoperative liver function in conjunction with preoperative volumetric analysis of the liver. CASE PRESENTATION: A 45-year-old patient presented with a cecal carcinoma and a large synchronous liver metastasis for major liver surgery. Liver function was determined by the LiMAx-test for the enzymatic capacity of cytochrome P450 1A2, which is ubiquitously and solely active in the liver. A solution of 2 mg/kg body weight (13)C-labeled methacetin was injected as a bolus into an intravenous catheter and, thereafter, was metabolized into acetaminophen and (13)CO2 and pulmonarily exhaled. The analysis of the (13)CO2/(12)CO2 ratio was performed using online breath sampling over a period of maximally 60 minutes. Based on this test, a value of more than 315 µg/kg/h represents normal liver function. A laparoscopic right hemihepatectomy was planned during virtual resection with a residual liver volume of 48% and a preoperative anticipated residual LiMAx of 301 µg/kg/h. After successful resection, the initial postoperative LiMAx value was 316 µg/kg/h, indicating good liver function and a correct prediction of the outcome. CONCLUSION: In the presented patient, residual liver function could be accurately predicted preoperatively using a combination of the new LiMax test with CT-volumetry. This test might significantly improve preoperative evaluation and postoperative outcomes in liver surgery.

Liver tissue sparing resection using a novel planning tool.

PURPOSE: Accurate preoperative prediction of liver function, volume, and vessel anatomy is essential in preventing postoperative liver failure, optimizing safety, and ensuring optimal outcome in patients undergoing hepatic surgery. We propose that preoperative resection planning provides useful anatomical and volumetric data, allowing for sparing of liver tissue in surgical resections. The purpose of the present study was to evaluate the use of a novel resection planning tool. METHODS: Thirteen patients undergoing hemihepatectomy were included. Preoperative resection planning was performed using the commercially available software Mint Liver. During resection planning, virtual resections were calculated based on Couinaud classification, Cantlie's line (standard), and individually by the operating surgeon (individual). Intraoperatively, volume and weight of the resected specimen were measured. A 14-day follow-up was conducted, and laboratory parameters were collected. Statistical analysis was performed, comparing virtual resection volumes (i.e., standard vs. individual) and secondarily virtual vs. actual resection volume. RESULTS: We found a significant difference (p = 0.001) in the comparison of standard vs. individual in all 13 cases, with an average 92.8 mL smaller resected volume, sparing 11.3% of liver parenchyma with virtual resection. No patients suffered from acute liver failure. Perioperative mortality was 0%. CONCLUSION: Mint Liver is capable of acquiring exact anatomical and volumetric knowledge prior to hepatic resections. Liver parenchyma can be spared by preoperative assessment of the resection plan. We propose that this tool could be an important addition to preoperative patient evaluation, especially in complex liver surgery and living donor liver transplantation where precise volumetry is the decisive factor.

Computer-based liver volumetry in the liver perfusion simulator.

BACKGROUND: An exact preoperative liver volume calculation is important prior to liver surgery and living-related liver transplantation. However, CT or MRI assessment of preoperative liver volume is associated with an estimation error of 1.2% to 36%, and little data is available on its accuracy on the segmental level. The aim of this study was to validate arterial and portal venous flow rates and gain information on liver volumetry, including liver segments, in the liver perfusion simulator and compare it to in vivo measurements in a porcine model. MATERIAL AND METHODS: The arterial and portal venous flow rates and liver volumes of 10 pigs were measured in vivo and compared with the flow rates and volumes ex vivo. CT scans were performed and the volume of the liver and its lobes calculated by water displacement or computer-assistance based on the CT scans. The right lateral lobe was plasticized and reconstructed for the volume calculation. RESULTS: In the liver perfusion simulator, arterial and portal venous flow rates comparable to the in vivo rates were achieved. The liver volume had a mean difference of 10.3% between in vivo and ex vivo measurements. In the liver perfusion simulator, the mean deviation in liver volume between the computer calculation and water displacement was 2.8%. On the segmental level, the Heidelberg algorithm provided an accuracy of 97.7%. CONCLUSION: The liver perfusion simulator is an excellent device for studies in liver perfusion and volumetry. Furthermore, the simulator is applicable for teaching and performing interventions and surgeries in livers.

On combining internal and external fiducials for liver motion compensation.

This paper presents an in-vivo accuracy study on combining skin markers (external fiducials) and fiducial needles (internal fiducials) for motion compensation during liver interventions. We compared the target registration error (TRE) for different numbers of skin markers n(s) and fiducial needles n(f), as well as for different transformation types, in two swine using the tip of an additional tracked needle as the target. During continuous breathing, n(f) had the greatest effect on the accuracy, yielding mean root mean square (RMS) errors of 4.8 +/- 1.1 mm (n(f) = 0), 2.0 +/- 0.9 mm (n(f) = 1) and 1.7 +/- 0.8 mm (n(f) = 2) when averaged over multiple tool arrangements (n = 18, 36, 18) with n(s) = 4. These values correspond to error reductions of 11%, 64% and 70%, respectively, compared to the case when no motion compensation is performed, i.e., when the target position is assumed to be constant. At expiration, the mean RMS error ranged from 1.1 mm (n(f) = 0) to 0.8 mm (n(f) = 2), which is of the order of magnitude of the target displacement. Our study further indicates that the fiducial registration error (FRE) of a rigid transformation reflecting tissue motion generally correlates strongly with the TRE. Our findings could be used in practice to (1) decide on a suitable combination of fiducials for a given intervention, considering the trade-off between high accuracy and low invasiveness, and (2) provide an intra-interventional measure of confidence for the accuracy of the system based on the FRE.

Respiratory motion compensation for CT-guided interventions in the liver.

Computed tomography (CT) guided minimally invasive procedures in the liver, such as tumor biopsy and thermal ablation therapy, require precise targeting of hepatic structures that are subject to breathing motion. To facilitate needle placement, we introduced a navigation system which uses needle-shaped optically tracked navigation aids and a real-time deformation model to continuously estimate the position of a moving target. In this study, we assessed the target position estimation accuracy of our system in vitro with a custom-designed respiratory liver motion simulator. Several real-time compatible transformations were compared as a basis for the deformation model and were evaluated in a set of experiments using different arrangements of three navigation aids in two porcine and two human livers. Furthermore, we investigated different placement strategies for the case where only two needles are used for motion compensation. Depending on the transformation and the placement of the navigation aids, our system yielded a root mean square (RMS) target position estimation error in the range of 0.7 mm to 2.9 mm throughout the breathing cycle generated by the motion simulator. Affine transformations and spline transformations performed comparably well (overall RMS < 2 mm) and were considerably better than rigid transformations. When two navigation aids were used for motion compensation instead of three, a diagonal arrangement of the needles yielded the best results. This study suggests that our navigation system could significantly improve the clinical treatment standard for CT-guided interventions in the liver.

In vivo accuracy assessment of a needle-based navigation system for CT-guided radiofrequency ablation of the liver.

Computed tomography (CT)-guided percutaneous radiofrequency ablation (RFA) has become a commonly used procedure in the treatment of liver tumors. One of the main challenges related to the method is the exact placement of the instrument within the lesion. To address this issue, a system was developed for computer-assisted needle placement which uses a set of fiducial needles to compensate for organ motion in real time. The purpose of this study was to assess the accuracy of the system in vivo. Two medical experts with experience in CT-guided interventions and two nonexperts used the navigation system to perform 32 needle insertions into contrasted agar nodules injected into the livers of two ventilated swine. Skin-to-target path planning and real-time needle guidance were based on preinterventional 1 mm CT data slices. The lesions were hit in 97% of all trials with a mean user error of 2.4 +/- 2.1 mm, a mean target registration error (TRE) of 2.1 +/- 1.1 mm, and a mean overall targeting error of 3.7 +/- 2.3 mm. The nonexperts achieved significantly better results than the experts with an overall error of 2.8 +/- 1.4 mm (n=16) compared to 4.5 +/- 2.7 mm (n=16). The mean time for performing four needle insertions based on one preinterventional planning CT was 57 +/- 19 min with a mean setup time of 27 min, which includes the steps fiducial insertion (24 +/- 15 min), planning CT acquisition (1 +/- 0 min), and registration (2 +/- 1 min). The mean time for path planning and targeting was 5 +/- 4 and 2 +/- 1 min, respectively. Apart from the fiducial insertion step, experts and nonexperts performed comparably fast. It is concluded that the system allows for accurate needle placement into hepatic tumors based on one planning CT and could thus enable considerable improvement to the clinical treatment standard for RFA procedures and other CT-guided interventions in the liver. To support clinical application of the method, optimization of individual system modules to reduce intervention time is proposed.