Diagnostic accuracy of different imaging modalities following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer

BACKGROUND: Periampullary cancer includes cancer of the head and neck of the pancreas, cancer of the distal end of the bile duct, cancer of the ampulla of Vater, and cancer of the second part of the duodenum. Surgical resection is the only established potentially curative treatment for pancreatic and periampullary cancer. A considerable proportion of patients undergo unnecessary laparotomy because of underestimation of the extent of the cancer on computed tomography (CT) scanning. Other imaging methods such as magnetic resonance imaging (MRI), positron emission tomography (PET), PET-CT, and endoscopic ultrasound (EUS) have been used to detect local invasion or distant metastases not visualised on CT scanning which could prevent unnecessary laparotomy. No systematic review or meta-analysis has examined the role of different imaging modalities in assessing the resectability with curative intent in patients with pancreatic and periampullary cancer. OBJECTIVES: To determine the diagnostic accuracy of MRI, PET scan, and EUS performed as an add-on test or PET-CT as a replacement test to CT scanning in detecting curative resectability in pancreatic and periampullary cancer. SEARCH METHODS: We searched MEDLINE, Embase, Science Citation Index Expanded, and Health Technology Assessment (HTA) databases up to 5 November 2015. Two review authors independently screened the references and selected the studies for inclusion. We also searched for articles related to the included studies by performing the "related search" function in MEDLINE (OvidSP) and Embase (OvidSP) and a "citing reference" search (by searching the articles that cite the included articles). SELECTION CRITERIA: We included diagnostic accuracy studies of MRI, PET scan, PET-CT, and EUS in patients with potentially resectable pancreatic and periampullary cancer on CT scan. We accepted any criteria of resectability used in the studies. We included studies irrespective of language, publication status, or study design (prospective or retrospective). We excluded case-control studies. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction and quality assessment using the QUADAS-2 (quality assessment of diagnostic accuracy studies - 2) tool. Although we planned to use bivariate methods for analysis of sensitivities and specificities, we were able to fit only the univariate fixed-effect models for both sensitivity and specificity because of the paucity of data. We calculated the probability of unresectability in patients who had a positive index test (post-test probability of unresectability in people with a positive test result) and in those with negative index test (post-test probability of unresectability in people with a positive test result) using the mean probability of unresectability (pre-test probability) from the included studies and the positive and negative likelihood ratios derived from the model. The difference between the pre-test and post-test probabilities gave the overall added value of the index test compared to the standard practice of CT scan staging alone. MAIN RESULTS: Only two studies (34 participants) met the inclusion criteria of this systematic review. Both studies evaluated the diagnostic test accuracy of EUS in assessing the resectability with curative intent in pancreatic cancers. There was low concerns about applicability for most domains in both studies. The overall risk of bias was low in one study and unclear or high in the second study. The mean probability of unresectable disease after CT scan across studies was 60.5% (that is 61 out of 100 patients who had resectable cancer after CT scan had unresectable disease on laparotomy). The summary estimate of sensitivity of EUS for unresectability was 0.87 (95% confidence interval (CI) 0.54 to 0.97) and the summary estimate of specificity for unresectability was 0.80 (95% CI 0.40 to 0.96). The positive likelihood ratio and negative likelihood ratio were 4.3 (95% CI 1.0 to 18.6) and 0.2 (95% CI 0.0 to 0.8) respectively. At the mean pre-test probability of 60.5%, the post-test probability of unresectable disease for people with a positive EUS (EUS indicating unresectability) was 86.9% (95% CI 60.9% to 96.6%) and the post-test probability of unresectable disease for people with a negative EUS (EUS indicating resectability) was 20.0% (5.1% to 53.7%). This means that 13% of people (95% CI 3% to 39%) with positive EUS have potentially resectable cancer and 20% (5% to 53%) of people with negative EUS have unresectable cancer. AUTHORS' CONCLUSIONS: Based on two small studies, there is significant uncertainty in the utility of EUS in people with pancreatic cancer found to have resectable disease on CT scan. No studies have assessed the utility of EUS in people with periampullary cancer.There is no evidence to suggest that it should be performed routinely in people with pancreatic cancer or periampullary cancer found to have resectable disease on CT scan

Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people

BACKGROUND: Peptic ulcer disease is the cause of dyspepsia in about 10% of people. Ninety-five percent of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H. pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. This is an update of Ford AC, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive patients. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003840. DOI: 10.1002/14651858.CD003840.pub4. OBJECTIVES: To assess the proportion of peptic ulcers healed and the proportion of participants who remained free from relapse with eradication therapy against placebo or other pharmacological therapies in H. pylori-positive people.To assess the proportion of participants that achieved complete relief of symptoms and improvement in quality of life scores.To compare the incidence of adverse effects/drop-outs (total number for each drug) associated with the different treatments.To assess the proportion of participants in whom successful eradication was achieved. SEARCH METHODS: In this update, we identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (1950 to March 2016) and Ovid EMBASE (1980 to March 2016). To identify further relevant trials, we handsearched reference lists from trials selected by electronic searching, and published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology). The search was last updated in March 2016. We contacted members of Cochrane Upper GI and Pancreatic Diseases, and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: We analysed randomised controlled trials of short- and long-term treatment of peptic ulcer disease in H. pylori-positive adults. Participants received at least one week of H. pylori eradication compared with ulcer healing drug, placebo or no treatment. Trials were included if they reported assessment from two weeks onwards. DATA COLLECTION AND ANALYSIS: We collected data on ulcer healing, recurrence, relief of symptoms and adverse effects. We calculated the risk ratio (RR) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with Review Manager software (RevMan 5.3) based on intention-to-treat analysis as far as possible. MAIN RESULTS: A total of 55 trials were included for one or more outcomes for this review.In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 participants, RR of ulcer persisting = 0.66, 95% confidence interval (CI) 0.58 to 0.76; 381/2286 (adjusted proportion: 12.4%) in eradication therapy plus UHD versus 304/1624 (18.7%) in UHD; low quality evidence) and no treatment (two trials, 207 participants, RR 0.37, 95% CI 0.26 to 0.53; 30/125 (adjusted proportion: 21.7%) in eradication therapy versus 48/82 (58.5%) in no treatment; low quality evidence).In gastric ulcer healing, the differences were imprecise between eradication therapy and UHD (15 trials, 1974 participants, RR 1.23, 95% CI 0.90 to 1.68; 220/1192 (adjusted proportion: 16.0%) in eradication therapy plus UHD versus 102/782 (13.0%) in UHD; very low quality evidence). In preventing duodenal ulcer recurrence the differences were imprecise between maintenance therapy with H.pylori eradication therapy and maintenance therapy with UHD (four trials, 319 participants, RR of ulcer recurring 0.73; 95% CI 0.42 to 1.25; 19/159 (adjusted proportion: 11.9%) in eradication therapy versus 26/160 (16.3%) in UHD; very low quality evidence), but eradication therapy was superior to no treatment (27 trials 2509 participants, RR 0.20, 95% CI 0.15 to 0.26; 215/1501 (adjusted proportion: 12.9%) in eradication therapy versus 649/1008 (64.4%) in no treatment; very low quality evidence).In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (12 trials, 1476 participants, RR 0.31, 95% CI 0.22 to 0.45; 116/697 (adjusted proportion: 16.3%) in eradication therapy versus 356/679 (52.4%) in no treatment; very low quality evidence). None of the trials reported proportion of people with gastric ulcer not healed after initial therapy between H.pylori eradication therapy and no active treatment or the proportion of people with recurrent gastric ulcer or peptic ulcers during maintenance therapy between H.pylori eradication therapy and ulcer healing drug therapy. AUTHORS' CONCLUSIONS: Adding a one to two-week course of H. pylori eradication therapy is an effective treatment for people with H. pylori-positive duodenal ulcer when compared to ulcer healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer healing drug. However, confidence intervals were wide and significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment, and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out

Development, Validation, and Modelling of Image Guidance Systems for Surgery

Image guidance systems for surgery enable the surgeon to make use of information from various sources during surgery. Such systems have the potential to improve outcomes for patients by allowing the surgeon to easily assimilate prior knowledge from pre-operative clinical scans as well as novel intra-operative imaging techniques. A key challenge is how to filter and process this information to allow it to be presented in an accurate, timely, and intuitive manner. Badly designed or poorly understood image guidance systems risk distracting the surgeon with irrelevant or incorrect information, leading to patient harm. The aim of my research is to develop tools to better quantify the performance of surgical image guidance systems, and measure how the system performance affects patient outcomes. I will present the results of my work developing the “SmartLiver”[1] image guidance system for minimally invasive liver surgery. I will follow this with a proposal for a generalised model of image guidance systems as multi input control systems

Performance of image guided navigation in laparoscopic liver surgery – A systematic review

Background: Compared to open surgery, minimally invasive liver resection has improved short term outcomes. It is however technically more challenging. Navigated image guidance systems (IGS) are being developed to overcome these challenges. The aim of this systematic review is to provide an overview of their current capabilities and limitations. Methods: Medline, Embase and Cochrane databases were searched using free text terms and corresponding controlled vocabulary. Titles and abstracts of retrieved articles were screened for inclusion criteria. Due to the heterogeneity of the retrieved data it was not possible to conduct a meta-analysis. Therefore results are presented in tabulated and narrative format. Results: Out of 2015 articles, 17 pre-clinical and 33 clinical papers met inclusion criteria. Data from 24 articles that reported on accuracy indicates that in recent years navigation accuracy has been in the range of 8–15 mm. Due to discrepancies in evaluation methods it is difficult to compare accuracy metrics between different systems. Surgeon feedback suggests that current state of the art IGS may be useful as a supplementary navigation tool, especially in small liver lesions that are difficult to locate. They are however not able to reliably localise all relevant anatomical structures. Only one article investigated IGS impact on clinical outcomes. Conclusions: Further improvements in navigation accuracy are needed to enable reliable visualisation of tumour margins with the precision required for oncological resections. To enhance comparability between different IGS it is crucial to find a consensus on the assessment of navigation accuracy as a minimum reporting standard

Multispectral tissue mapping: developing a concept for the optical evaluation of liver disease

Purpose: Alterations in the optical absorption behavior of liver tissue secondary to pathological processes can be evaluated by multispectral analysis, which is increasingly being explored as an imaging adjunct for use in liver surgery. Current methods are either invasive or have a limited wavelength spectrum, which restricts utility. This proof of concept study describes the development of a multispectral imaging (MSI) method called multispectral tissue mapping (MTM) that addresses these issues. Approach: The imaging system consists of a tunable excitation light source and a near-infrared camera. Following the development stage, proof of concept experiments are carried out where absorption spectra from colorectal cancer liver metastasis (CRLM), hepatocellular carcinoma (HCC), and liver steatosis specimen are acquired and compared to controls. Absorption spectra are compared to histopathology examination as the current gold standard for tissue assessment. Generalized linear mixed modeling is employed to compare absorption characteristics of individual pixels and to select wavelengths for false color image processing with the aim of visually enhancing cancer tissue. Results: Analysis of individual pixels revealed distinct absorption spectra therefore suggesting that MTM is possible. A prominent absorption peak at 1210 nm was found in lipid-rich animal tissues and steatotic liver specimen. Liver cancer tissue had a heterogeneous appearance on MSI. Subsequent statistical analysis suggests that measuring changes in absorption behavior may be a feasible method to estimate the pixel-based probability of cancer being present. In CRLM, this was observed throughout 1100 to 1700 nm, whereas in HCC it was concentrated around 1140 and 1430 nm. False color image processing visibly enhances contrast between cancer and normal liver tissues. Conclusions: The system’s ability to enable no-touch MSI at 1100 to 1700 nm was demonstrated. Preliminary data suggest that MTM warrants further exploration as a potential imaging tool for the detection of liver cancer during surger

Hand-eye calibration for rigid laparoscopes using an invariant point

PURPOSE: Laparoscopic liver resection has significant advantages over open surgery due to less patient trauma and faster recovery times, yet it can be difficult due to the restricted field of view and lack of haptic feedback. Image guidance provides a potential solution but one current challenge is in accurate "hand-eye" calibration, which determines the position and orientation of the laparoscope camera relative to the tracking markers. METHODS: In this paper, we propose a simple and clinically feasible calibration method based on a single invariant point. The method requires no additional hardware, can be constructed by theatre staff during surgical setup, requires minimal image processing and can be visualised in real time. Real-time visualisation allows the surgical team to assess the calibration accuracy before use in surgery. In addition, in the laboratory, we have developed a laparoscope with an electromagnetic tracking sensor attached to the camera end and an optical tracking marker attached to the distal end. This enables a comparison of tracking performance. RESULTS: We have evaluated our method in the laboratory and compared it to two widely used methods, "Tsai's method" and "direct" calibration. The new method is of comparable accuracy to existing methods, and we show RMS projected error due to calibration of 1.95 mm for optical tracking and 0.85 mm for EM tracking, versus 4.13 and 1.00 mm respectively, using existing methods. The new method has also been shown to be workable under sterile conditions in the operating room. CONCLUSION: We have proposed a new method of hand-eye calibration, based on a single invariant point. Initial experience has shown that the method provides visual feedback, satisfactory accuracy and can be performed during surgery. We also show that an EM sensor placed near the camera would provide significantly improved image overlay accuracy

Global rigid registration of CT to video in laparoscopic liver surgery

PURPOSE: Image-guidance systems have the potential to aid in laparoscopic interventions by providing sub-surface structure information and tumour localisation. The registration of a preoperative 3D image with the intraoperative laparoscopic video feed is an important component of image guidance, which should be fast, robust and cause minimal disruption to the surgical procedure. Most methods for rigid and non-rigid registration require a good initial alignment. However, in most research systems for abdominal surgery, the user has to manually rotate and translate the models, which is usually difficult to perform quickly and intuitively. METHODS: We propose a fast, global method for the initial rigid alignment between a 3D mesh derived from a preoperative CT of the liver and a surface reconstruction of the intraoperative scene. We formulate the shape matching problem as a quadratic assignment problem which minimises the dissimilarity between feature descriptors while enforcing geometrical consistency between all the feature points. We incorporate a novel constraint based on the liver contours which deals specifically with the challenges introduced by laparoscopic data. RESULTS: We validate our proposed method on synthetic data, on a liver phantom and on retrospective clinical data acquired during a laparoscopic liver resection. We show robustness over reduced partial size and increasing levels of deformation. Our results on the phantom and on the real data show good initial alignment, which can successfully converge to the correct position using fine alignment techniques. Furthermore, since we can pre-process the CT scan before surgery, the proposed method runs faster than current algorithms. CONCLUSION: The proposed shape matching method can provide a fast, global initial registration, which can be further refined by fine alignment methods. This approach will lead to a more usable and intuitive image-guidance system for laparoscopic liver surgery

In vivo estimation of target registration errors during augmented reality laparoscopic surgery

PURPOSE: Successful use of augmented reality for laparoscopic surgery requires that the surgeon has a thorough understanding of the likely accuracy of any overlay. Whilst the accuracy of such systems can be estimated in the laboratory, it is difficult to extend such methods to the in vivo clinical setting. Herein we describe a novel method that enables the surgeon to estimate in vivo errors during use. We show that the method enables quantitative evaluation of in vivo data gathered with the SmartLiver image guidance system. METHODS: The SmartLiver system utilises an intuitive display to enable the surgeon to compare the positions of landmarks visible in both a projected model and in the live video stream. From this the surgeon can estimate the system accuracy when using the system to locate subsurface targets not visible in the live video. Visible landmarks may be either point or line features. We test the validity of the algorithm using an anatomically representative liver phantom, applying simulated perturbations to achieve clinically realistic overlay errors. We then apply the algorithm to in vivo data. RESULTS: The phantom results show that using projected errors of surface features provides a reliable predictor of subsurface target registration error for a representative human liver shape. Applying the algorithm to in vivo data gathered with the SmartLiver image-guided surgery system shows that the system is capable of accuracies around 12 mm; however, achieving this reliably remains a significant challenge. CONCLUSION: We present an in vivo quantitative evaluation of the SmartLiver image-guided surgery system, together with a validation of the evaluation algorithm. This is the first quantitative in vivo analysis of an augmented reality system for laparoscopic surgery

Registration of Untracked 2D Laparoscopic Ultrasound Liver Images to CT Using Content-Based Retrieval and Kinematic Priors

Laparoscopic Ultrasound (LUS) can enhance the safety of laparoscopic liver resection by providing information on the location of major blood vessels and tumours. Since many tumours are not visible in ultrasound, registration to a pre-operative CT has been proposed as a guidance method. In addition to being multi-modal, this registration problem is greatly affected by the differences in field of view between CT and LUS, and thus requires an accurate initialisation. We propose a novel method of registering smaller field of view slices to a larger volume globally using a Content-based retrieval framework. This problem is under-constrained for a single slice registration, resulting in non-unique solutions. Therefore, we introduce kinematic priors in a Bayesian framework in order to jointly register groups of ultrasound images. Our method then produces an estimate of the most likely sequence of CT images to represent the ultrasound acquisition and does not require tracking information nor an accurate initialisation. We demonstrate the feasibility of this approach in multiple LUS acquisitions taken from three sets of clinical data

Perioperative antioxidants for adults undergoing elective non-cardiac surgery

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the benefits and harms of antioxidant use in the perioperative period in adults who undergo non‐cardiac surgery