Identification of liver metastases with probe-based confocal laser endomicroscopy at two excitation wavelengths.

BACKGROUND: Metastasis of colorectal cancer to the liver is the most common indication for hepatic resection in a western population. Incomplete excision of malignancy due to residual microscopic disease normally results in worse patient outcome. Therefore, a method aiding in the real time discrimination of normal and malignant tissue on a microscopic level would be of benefit. MATERIAL AND METHODS: The ability of fluorescent probe-based confocal laser endomicroscopy (pCLE) to identify normal and malignant liver tissue was evaluated in an orthotopic murine model of colorectal cancer liver metastasis (CRLM). To maximise information yield, two clinical fluorophores, fluorescein and indocyanine green (ICG) were injected and imaged in a dual wavelength approach (488 and 660 nm, respectively). Visual tissue characteristics on pCLE examination were compared with histological features. Fluorescence intensity in both tissues was statistically analysed to elucidate if this can be used to differentiate between normal and malignant tissue. RESULTS: Fluorescein (488 nm) enabled good visualisation of normal and CRLM tissue, whereas ICG (660 nm) visualisation was limited to normal liver tissue only. Fluorescence intensity in areas of CRLM was typically 53-100% lower than normal hepatic parenchyma. Using general linear mixed modelling and receiver operating characteristic analysis, high fluorescence intensity was found to be statistically more likely in normal hepatic tissue. CONCLUSION: Real time discrimination between normal liver parenchyma and metastatic tissue with pCLE examination of fluorescein and ICG is feasible. Employing two (rather than a single) fluorophores allows a combination of qualitative and quantitative characteristics to be used to distinguish between hepatic parenchyma and CRLM. Lasers Surg. Med. 49:280-292, 2017. © 2016 Wiley Periodicals, Inc.

Utilizing confocal laser endomicroscopy for evaluating the adequacy of laparoscopic liver ablation.

BACKGROUND: Laparoscopic liver ablation therapy can be used for the treatment of primary and secondary liver malignancy. The increased incidence of cancer recurrence associated with this approach, has been attributed to the inability of monitoring the extent of ablated liver tissue. METHODS: The feasibility of assessing liver ablation with probe-based confocal laser endomicroscopy (CLE) was studied in a porcine model of laparoscopic microwave liver ablation. Following the intravenous injection of the fluorophores fluorescein and indocyanine green, CLE images were recorded at 488 nm and 660 nm wavelength and compared to liver histology. Statistical analysis was performed to assess if fluorescence intensity change can predict the presence of ablated liver tissue. RESULTS: CLE imaging of fluorescein at 488 nm provided good visualization of the hepatic microvasculature; whereas, CLE imaging of indocyanine green at 660 nm enabled detailed visualization of hepatic sinusoid architecture and interlobular septations. Fluorescence intensity as measured in relative fluorescence units was found to be 75-100% lower in ablated compared to healthy liver regions. General linear mixed modeling and ROC analysis found the decrease in fluorescence to be statistically significant. CONCLUSION: Laparoscopic, dual wavelength CLE imaging using two different fluorophores enables clinically useful visualization of multiple liver tissue compartments, in greater detail than is possible at a single wavelength. CLE imaging may provide valuable intraoperative information on the extent of laparoscopic liver ablation.

The association between referral source and outcome in patients with colorectal cancer.

AIM: The colorectal two-week wait fast track (FT) referral system was nationally implemented in the UK in 2000 to ensure patients with colorectal cancer (CRC) received prompt access to specialized services. The aim of this study was to determine the association between the mechanism of referral to colorectal services and the 5-year outcomes for patients with CRC. METHODS: Consecutive patients with newly diagnosed CRC presenting between October 2002 and September 2004 were identified retrospectively. Analysis for survival and recurrence of disease at 5 years from presentation was undertaken. Outcomes for patients were compared between fast track (FT), non-fast track (NFT) and emergency referral (ER) routes, using Kaplan-Meier survival estimates. RESULTS: Out of 189 patients, 96 (51%) presented via the FT, 41 (22.5%) via the NFT and 52 (27.5%) via the ER referral route. The 5-year overall survival was 52.6% ± 5.1, 41.5% ± 7.7 and 38.5% ± 6.7 for the FT-, NFT- and ER groups respectively (p = 0.075). The 5-year cancer specific survival was 60.3% ± 5.2, 58.8% ± 5.3 and 43.5% ± 7.2 for the FT-, NFT- and ER groups respectively (p = 0.056). Patients referred as emergencies had worse 5-year overall survival; 49.3% ± 4.3 (FT&NFT) vs. 38.5% ± 6.7 (ER) (p = 0.042) and 5-year cancer specific survival 59.8% ± 4.4 (FT&NFT) vs. 43.5% ± 7.2 (ER) (p = 0.016). A total of 136 patients (FT n = 71, NFT n = 34, ER n = 31) underwent potentially curative surgery. Differences in 5-year survival did not reach statistical significance in these patients. CONCLUSION: Referral route to specialist services for patients with CRC via the fast track pathway compared to non-fast track pathway was not associated with improved survival.

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 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.

Endothelial Ca2+ signal transduction is altered by postoperative serum from patients undergoing coronary surgery with cardiopulmonary bypass.

Endothelial dysfunction after surgery may be caused by alterations in the intracellular signaling properties of endothelial cells. Functional alterations are believed to be systemic and dependent on the amount of invasiveness. This led us to assume that there would be a mediator in the blood. Therefore, we investigated the influence of perioperative serum obtained from patients undergoing highly invasive surgical interventions (cardiac surgery [CS] with cardiopulmonary bypass) and less invasiveness (total joint arthroplasty [TJA]) on endothelial single cell Ca2+ responses. Aortic endothelial cells were incubated with preoperative and postoperative serum samples from 26 patients undergoing CS and from 15 patients undergoing TJA. Adenosine triphosphate (100 microM)-induced alterations in FURA-2 fluorescence was used to measure intracellular Ca2+ in single cells. In CS samples the induced [Ca2+]i signals were enhanced by postoperative serum (peak levels: 96 +/- 41 FU versus 116 +/- 45 FU; P < 0.05). These postoperative enhancements were absent in TJA patients serum. Preincubation of CS samples with nifedipine to block voltage gated Ca2+ channels did not alter this effect, but the absence of extracellular Ca2+ abolished the increased response from postoperative CS serum exposure. Ca2+ entry probed with Mn2+ quenching was increased in endothelial cells exposed with postoperative CS serum and Ca2+ entry correlated with postoperative circulating interleukin-6 levels (P < 0.007). Endothelial functional alterations after CS with cardiopulmonary bypass are attributable, in part, to systemic factors present in serum that lead to specific endothelial enhanced Ca2+-signaling. This enhancement can be separated in vitro as an increased Ca2+ entry not present in serum from patients recovering from TJA.

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.

A case-control study investigating factors of preoperative delay in emergency laparotomy.

BACKGROUND: Emergency laparotomy (EL) is a procedure that puts a strain on healthcare resources and is associated with a significant morbidity and mortality. Despite these implications little improvement in the outcome of patients undergoing this procedure has been made in the UK over the last few decades. A delay in transferring patients to theatre has been shown to negatively affect outcome of EL. A prospective case-control study was carried out to evaluate which preoperative factors may contribute towards a delay in theatre transfer. METHODS: The time between decision to operate and anaesthetic start time was recorded for all patients undergoing EL between April and September 2013 at Gloucestershire Royal Infirmary. Patient selection criteria were based on the National Emergency Laparotomy Audit guidelines. Patients were divided into two groups depending on whether the transfer to theatre was delayed or not. Binary logistic regression analysis was performed on perioperative factors to determine independent predictors of delay. RESULTS: A total of 84 EL were included for analyses with 31 classified as delayed. In the delayed group time for theatre transfer was increased at 6.9 vs. 2.3 h (p < 0.005) respectively. Unavailability of emergency theatres due to other cases taking priority was the most frequent cause for delay (n = 24). On binary logistic regression analysis, indication for laparotomy (OR 4.96, CI 1.4-17.6, p < 0.05), patient age (OR 1.04, CI 1.00-1.07, p < 0.04) and presence of a consultant surgeon (OR 0.16, CI 0.03-0.79, p < 0.03) were found to be independent predictors of delay in EL. CONCLUSION: In this study, factors that were associated with a delay in commencing EL were operative indication and patient age whereas the presence of a consultant surgeon made a delay less likely. These findings may highlight points of interest for researchers analysing and auditing the provision of EL in the UK.

Laparoscopic manipulation of a probe-based confocal laser endomicroscope using a steerable intravascular catheter.

Probe-based confocal laser endomicroscopy is an emerging imaging modality that enables visualization of histologic details during endoscopy and surgery. A method of guiding the probe with millimeter accuracy is required to enable imaging in all regions of the abdomen accessed during laparoscopy. On the basis of a porcine model of laparoscopic liver resection, we report our experience of using a steerable intravascular catheter to guide a probe-based confocal laser endomicroscope.

Locally rigid, vessel-based registration for laparoscopic liver surgery.

PURPOSE: Laparoscopic liver resection has significant advantages over open surgery due to less patient trauma and faster recovery times, yet is difficult for most lesions due to the restricted field of view and lack of haptic feedback. Image guidance provides a potential solution but is challenging in a soft deforming organ such as the liver. In this paper, we therefore propose a laparoscopic ultrasound (LUS) image guidance system and study the feasibility of a locally rigid registration for laparoscopic liver surgery. METHODS: We developed a real-time segmentation method to extract vessel centre points from calibrated, freehand, electromagnetically tracked, 2D LUS images. Using landmark-based initial registration and an optional iterative closest point (ICP) point-to-line registration, a vessel centre-line model extracted from preoperative computed tomography (CT) is registered to the ultrasound data during surgery. RESULTS: Using the locally rigid ICP method, the RMS residual error when registering to a phantom was 0.7 mm, and the mean target registration error (TRE) for two in vivo porcine studies was 3.58 and 2.99 mm, respectively. Using the locally rigid landmark-based registration method gave a mean TRE of 4.23 mm using vessel centre lines derived from CT scans taken with pneumoperitoneum and 6.57 mm without pneumoperitoneum. CONCLUSION: In this paper we propose a practical image-guided surgery system based on locally rigid registration of a CT-derived model to vascular structures located with LUS. In a physical phantom and during porcine laparoscopic liver resection, we demonstrate accuracy of target location commensurate with surgical requirements. We conclude that locally rigid registration could be sufficient for practically useful image guidance in the near future.

Resection of giant gastric GIST with a new generation ultrasonic scalpel device.

Gastrointestinal stroma tumours (GIST) are the most common mesenchymal tumour in the digestive tract and commonly found in the stomach. The patient described in this report presented with collapse and a palpable abdominal mass. He was found to have a large gastric GIST that penetrated through the mesocolon. Resection of the GIST was technically challenging but facilitated by a new generation ultrasonic scalpel device. In resection of gastric cancer the use of ultrasonic scalpels has been shown to reduce operating time, blood loss and length of stay. We feel that in technically challenging cases of gastric GIST the use of an ultrasonic scalpel device may be justified as well.

Predicting blood transfusion in patients undergoing minimally invasive oesophagectomy.

AIM: To evaluate predictors of allogenic blood transfusion requirements in patients undergoing minimal invasive oesophagectomy at a tertiary high volume centre for oesophago-gastric surgery. METHODS: Retrospective analysis of all patients undergoing minimal access oesophagectomy in our department between January 2010 and December 2011. Patients were divided into two groups depending on whether they required a blood transfusion at any time during their index admission. Factors that have been shown to influence perioperative blood transfusion requirements in major surgery were included in the analysis. Binary logistic regression analysis was performed to determine the impact of patient and perioperative characteristics on transfusion requirements during the index admission. RESULTS: A total of 80 patients underwent minimal access oesophagectomy, of which 61 patients had a laparoscopic assisted oesophagectomy and 19 patients had a minimal invasive oesophagectomy. Perioperative blood transfusion was required in 28 patients at any time during hospital admission. On binary logistic regression analysis, a lower preoperative haemoglobin concentration (p < 0.01), suffering a significant complication (p < 0.005) and laparoscopic assisted oesophagectomy (p < 0.05) were independent predictors of blood transfusion requirements. DISCUSSION: It has been reported that requirement for blood transfusion can affect long-term outcomes in oesophageal cancer resection. Two factors which could be addressed preoperatively; haemoglobin concentration and type of oesophageal resection, may be valuable in predicting blood transfusions in patients undergoing minimally invasive oesophagectomy. CONCLUSION: Our analysis revealed that preoperative haemoglobin concentration, occurrence of significant complications and type of minimal access oesophagectomy predicted blood transfusion requirements in the patient population examined.

Recurrent cystic lymphangioma of the breast: case report and literature review.

Cystic lymphangioma is a rare congenital lymphatic malformation. We report a case of a 37-year-old female with recurrent cystic lymphangioma of the breast which has progressively developed during pregnancy and breast feeding.