Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study.

BACKGROUND: Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy (HAIP-SYS) for liver-only colorectal liver metastases (CRLMs) has shown promising results but has not been adopted worldwide. This study evaluated the feasibility of HAIP-SYS in the Netherlands. METHODS: This was a single-arm phase II study of patients with CRLMs who received HAIP-SYS consisting of floxuridine with concomitant systemic FOLFOX or FOLFIRI. Main inclusion and exclusion criteria were borderline resectable or unresectable liver-only metastases, suitable arterial anatomy and no previous local treatment. Patients underwent laparotomy for pump implantation and primary tumour resection if in situ. Primary end point was feasibility, defined as ≥70% of patients completing two cycles of HAIP-SYS. Sample size calculations led to 31 patients. Secondary outcomes included safety and tumour response. RESULTS: Thirty-one patients with median 13 CRLMs (i.q.r. 6-23) were included. Twenty-eight patients (90%) received two HAIP-SYS cycles. Three patients did not get two cycles due to extrahepatic disease at pump placement, definitive pathology of a recto-sigmoidal squamous cell carcinoma, and progressive disease. Five patients experienced grade 3 surgical or pump device-related complications (16%) and 11 patients experienced grade ≥3 chemotherapy toxicity (38%). At first radiological evaluation, disease control rate was 83% (24/29 patients) and hepatic disease control rate 93% (27/29 patients). At 6 months, 19 patients (66%) had experienced grade ≥3 chemotherapy toxicity and the disease control rate was 79%. CONCLUSION: HAIP-SYS for borderline resectable and unresectable CRLMs was feasible and safe in the Netherlands. This has led to a successive multicentre phase III randomized trial investigating oncological benefit (EUDRA-CT 2023-506194-35-00). Current trial registration number: clinicaltrials.gov (NCT04552093).

Spatial and Spectral Reconstruction of Breast Lumpectomy Hyperspectral Images.

(1) Background: Hyperspectral imaging has emerged as a promising margin assessment technique for breast-conserving surgery. However, to be implicated intraoperatively, it should be both fast and capable of yielding high-quality images to provide accurate guidance and decision-making throughout the surgery. As there exists a trade-off between image quality and data acquisition time, higher resolution images come at the cost of longer acquisition times and vice versa. (2) Methods: Therefore, in this study, we introduce a deep learning spatial-spectral reconstruction framework to obtain a high-resolution hyperspectral image from a low-resolution hyperspectral image combined with a high-resolution RGB image as input. (3) Results: Using the framework, we demonstrate the ability to perform a fast data acquisition during surgery while maintaining a high image quality, even in complex scenarios where challenges arise, such as blur due to motion artifacts, dead pixels on the camera sensor, noise from the sensor's reduced sensitivity at spectral extremities, and specular reflections caused by smooth surface areas of the tissue. (4) Conclusion: This gives the opportunity to facilitate an accurate margin assessment through intraoperative hyperspectral imaging.

Initial Impact of National CRC Screening on Incidence and Advanced Colorectal Cancer.

BACKGROUND AND AIMS: Screening for colorectal cancer (CRC) aims to decrease CRC incidence and mortality. Biennial fecal immunochemical test screening started in the Netherlands in 2014 for individuals 55-75 years of age. This study investigated the effect of screening on stage-specific incidence, with focus on stage III and IV CRC. METHODS: Inhabitants diagnosed with CRC in 2009-2018 were included. CRC incidence per stage, year, and detection method (ie, screen-detected vs clinically detected) was evaluated. Patient, tumor, and treatment characteristics, and survival of patients with stage III and IV CRC, were compared according to the detection method. RESULTS: Included were 140,649 CRCs in 136,882 patients. An initial peak of stage I-III CRC diagnoses after initiation of screening was followed by a continuous decrease within screening-eligible ages. Total CRC incidence remained higher than before screening, although stage II and IV CRC incidence decreased below prescreening levels. Screen-detected CRCs were significantly more frequently located in the left-sided colon (stage III; 43.7% vs 30.9%; stage IV: 45.1% vs 36.1%), and the primary tumor resection rate was higher (stage III colon: 99.8% vs 99.0%, rectum: 97.3% vs 89.7%; stage IV colon: 65.4% vs 56.6%, rectum: 47.3% vs 33.5%). Patients with screen-detected stage IV CRC had significantly more often single-organ metastases (74.5% vs 57.0%; P < .001) and more frequently received treatment with curative intent (colon: 41.3% vs 27.4%; rectum: 33.8% vs 24.6%). Overall survival significantly improved for patients with screen-detected CRCs (stage III: P < .001; stage IV: P < .001). CONCLUSIONS: Five years after the start of a nationwide CRC screening program, a decrease in stage II and IV CRC incidence was observed. Patients with screen-detected stage III and stage IV CRC had less extensive disease and improved survival compared with those with clinically detected CRC.

Imaging Photoplethysmography for Noninvasive Anastomotic Perfusion Assessment in Intestinal Surgery.

INTRODUCTION: Anastomotic leakage after gastrointestinal surgery has a high impact on patient's quality of life and its origin is associated with inadequate perfusion. Imaging photoplethysmography (iPPG) is a noninvasive imaging technique that measures blood-volume changes in the microvascular tissue bed and detects changes in tissue perfusion. MATERIALS AND METHODS: Intraoperative iPPG imaging was performed in 29 patients undergoing an open segment resection of the small intestine or colon. During each surgery, imaging was performed on fully perfused (true positives) and ischemic intestines (true negatives) and the anastomosis (unknowns). Imaging consisted of a 30-s video from which perfusion maps were extracted, providing detailed information about blood flow within the intestine microvasculature. To detect the predictive capabilities of iPPG, true positive and true negative perfusion conditions were used to develop two different perfusion classification methods. RESULTS: iPPG-derived perfusion parameters were highly correlated with perfusion-perfused or ischemic-in intestinal tissues. A perfusion confidence map distinguished perfused and ischemic intestinal tissues with 96% sensitivity and 86% specificity. Anastomosis images were scored as adequately perfused in 86% of cases and 14% inconclusive. The cubic-Support Vector Machine achieved 90.9% accuracy and an area under the curve of 96%. No anastomosis-related postoperative complications were encountered in this study. CONCLUSIONS: This study shows that noninvasive intraoperative iPPG is suitable for the objective assessment of small intestine and colon anastomotic perfusion. In addition, two perfusion classification methods were developed, providing the first step in an intestinal perfusion prediction model.

Optical tissue measurements of invasive carcinoma and ductal carcinoma in situ for surgical guidance.

BACKGROUND: Although the incidence of positive resection margins in breast-conserving surgery has decreased, both incomplete resection and unnecessary large resections still occur. This is especially the case in the surgical treatment of ductal carcinoma in situ (DCIS). Diffuse reflectance spectroscopy (DRS), an optical technology based on light tissue interactions, can potentially characterize tissue during surgery thereby guiding the surgeon intraoperatively. DRS has shown to be able to discriminate pure healthy breast tissue from pure invasive carcinoma (IC) but limited research has been done on (1) the actual optical characteristics of DCIS and (2) the ability of DRS to characterize measurements that are a mixture of tissue types. METHODS: In this study, DRS spectra were acquired from 107 breast specimens from 107 patients with proven IC and/or DCIS (1488 measurement locations). With a generalized estimating equation model, the differences between the DRS spectra of locations with DCIS and IC and only healthy tissue were compared to see if there were significant differences between these spectra. Subsequently, different classification models were developed to be able to predict if the DRS spectrum of a measurement location represented a measurement location with "healthy" or "malignant" tissue. In the development and testing of the models, different definitions for "healthy" and "malignant" were used. This allowed varying the level of homogeneity in the train and test data. RESULTS: It was found that the optical characteristics of IC and DCIS were similar. Regarding the classification of tissue with a mixture of tissue types, it was found that using mixed measurement locations in the development of the classification models did not tremendously improve the accuracy of the classification of other measurement locations with a mixture of tissue types. The evaluated classification models were able to classify measurement locations with > 5% malignant cells with a Matthews correlation coefficient of 0.41 or 0.40. Some models showed better sensitivity whereas others had better specificity. CONCLUSION: The results suggest that DRS has the potential to detect malignant tissue, including DCIS, in healthy breast tissue and could thus be helpful for surgical guidance.

Nationwide registry study on trends in localization techniques and reoperation rates in non-palpable ductal carcinoma in situ and invasive breast cancer.

BACKGROUND: There is a transition from wire-guided localization (WGL) of non-palpable breast cancer to other localization techniques. Multiple prospective studies have sought to establish superior clinical outcomes for radioactive-seed localization (RSL), but consistent and congruent evidence is missing. METHODS: In this study, female patients with breast cancer operated with breast-conserving surgery after tumour localization of a non-palpable breast cancer or ductal carcinoma in situ (DCIS) were included. The cohort was identified from the nationwide Netherlands Breast Cancer Audit conducted between 2013 and 2018. Trends in localization techniques were analysed. Univariable and multivariable analyses were performed to assess the association between the localization technique and the probability of a reoperation. RESULTS: A total of 28 370 patients were included in the study cohort. The use of RSL increased from 15.7 to 61.1 per cent during the study years, while WGL decreased from 75.4 to 31.6 per cent. The localization technique used (RSL versus WGL) was not significantly associated with the odds of a reoperation, regardless of whether the lesion was DCIS (odds ratio 0.96 (95 per cent c.i. 0.89 to 1.03; P = 0.281)) or invasive breast cancer (OR 1.02 (95 per cent c.i. 0.96 to 1.10; P = 0.518)). CONCLUSION: RSL is rapidly replacing WGL as the preoperative localization technique in breast surgery. This large nationwide registry study found no association between the type of localization technique and the odds of having a reoperation, thus confirming the results of previous prospective cohort studies.

Surgical navigation for challenging recurrent or pretreated intra-abdominal and pelvic soft tissue sarcomas.

BACKGROUND: This study assessed whether electromagnetic navigation can be of added value during resection of recurrent or post-therapy intra-abdominal/pelvic soft tissue sarcomas (STS) in challenging locations. MATERIALS AND METHODS: Patients were included in a prospective navigation study. A pre-operatively 3D roadmap was made and tracked using electromagnetic reference markers. During the operation, an electromagnetic pointer was used for the localization of the tumor/critical anatomical structures. The primary endpoint was feasibility, secondary outcomes were safety and usability. RESULTS: Nine patients with a total of 12 tumors were included, 7 patients with locally recurrent sarcoma. Three patients received neoadjuvant radiotherapy and three other patients received neoadjuvant systemic treatment. The median tumor size was 4.6 cm (2.4-10.4). The majority of distances from tumor to critical anatomical structures was <0.5 cm. The tumors were localized using the navigation system without technical or safety issues. Despite the challenging nature of these resections, 89% were R0 resections, with a median blood loss of 100 ml (20-1050) and one incident of vascular damage. Based on the survey, surgeons stated navigation resulted in shorter surgery time and made the resections easier. CONCLUSION: Electromagnetic navigation facilitates resections of challenging lower intra-abdominal/pelvic STS and might be of added value.

Randomized controlled trial comparing magnetic marker localization (MaMaLoc) with wire-guided localization in the treatment of early-stage breast cancer.

Wire-guided localization (WGL) is the standard of care in the surgical treatment of nonpalpable breast tumors. In this study, we compare the use of a new magnetic marker localization (MaMaLoc) technique to WGL in the treatment of early-stage breast cancer patients. Open-label, single-center, randomized controlled trial comparing MaMaLoc (intervention) to WGL (control) in women with early-stage breast cancer. Primary outcome was surgical usability measured using the System Usability Scale (SUS, 0-100 score). Secondary outcomes were patient reported, clinical, and pathological outcomes such as retrieval rate, operative time, resected specimen weight, margin status, and reoperation rate. Thirty-two patients were analyzed in the MaMaLoc group and 35 in the WGL group. Patient and tumor characteristics were comparable between groups. No in situ complications occurred. Retrieval rate was 100% in both groups. Surgical usability was higher for MaMaLoc: 70.2 ± 8.9 vs. 58.1 ± 9.1, p < 0.001. Patients reported higher overall satisfaction with MaMaLoc (median score 5/5) versus WGL (score 4/5), p < 0.001. The use of magnetic marker localization (MaMaLoc) for early-stage breast cancer is effective and has higher surgical usability than standard WGL.

Using Diffuse Reflectance Spectroscopy to Distinguish Tumor Tissue From Fibrosis in Rectal Cancer Patients as a Guide to Surgery.

BACKGROUND AND OBJECTIVES: In patients with rectal cancer who received neoadjuvant (chemo)radiotherapy, fibrosis is induced in and around the tumor area. As tumors and fibrosis have similar visual and tactile feedback, they are hard to distinguish during surgery. To prevent positive resection margins during surgery and spare healthy tissue, it would be of great benefit to have a real-time tissue classification technology that can be used in vivo. STUDY DESIGN/MATERIALS AND METHODS: In this study diffuse reflectance spectroscopy (DRS) was evaluated for real-time tissue classification of tumor and fibrosis. DRS spectra of fibrosis and tumor were obtained on excised rectal specimens. After normalization using the area under the curve, a support vector machine was trained using a 10-fold cross-validation. RESULTS: Using spectra of pure tumor tissue and pure fibrosis tissue, we obtained a mean accuracy of 0.88. This decreased to a mean accuracy of 0.61 when tumor measurements were used in which a layer of healthy tissue, mainly fibrosis, was present between the tumor and the measurement surface. CONCLUSION: It is possible to distinguish pure fibrosis from pure tumor. However, when the measurements on tumor also involve fibrotic tissue, the classification accuracy decreases. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Toward assessment of resection margins using hyperspectral diffuse reflection imaging (400-1,700 nm) during tongue cancer surgery.

BACKGROUND AND OBJECTIVES: There is a clinical need to assess the resection margins of tongue cancer specimens, intraoperatively. In the current ex vivo study, we evaluated the feasibility of hyperspectral diffuse reflectance imaging (HSI) for distinguishing tumor from the healthy tongue tissue. STUDY DESIGN/MATERIALS AND METHODS: Fresh surgical specimens (n = 14) of squamous cell carcinoma of the tongue were scanned with two hyperspectral cameras that cover the visible and near-infrared spectrum (400-1,700 nm). Each pixel of the hyperspectral image represents a measure of the diffuse optical reflectance. A neural network was used for tissue-type prediction of the hyperspectral images of the visual and near-infrared data sets separately as well as both data sets combined. RESULTS: HSI was able to distinguish tumor from muscle with a good accuracy. The diagnostic performance of both wavelength ranges (sensitivity/specificity of visual and near-infrared were 84%/80% and 77%/77%, respectively) appears to be comparable and there is no additional benefit of combining the two wavelength ranges (sensitivity and specificity were 83%/76%). CONCLUSIONS: HSI has a strong potential for intra-operative assessment of tumor resection margins of squamous cell carcinoma of the tongue. This may optimize surgery, as the entire resection surface can be scanned in a single run and the results can be readily available. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Clinical Implementation of In-House Developed MR-Based Patient-Specific 3D Models of Liver Anatomy.

Knowledge of patient-specific liver anatomy is key to patient safety during major hepatobiliary surgery. Three-dimensional (3D) models of patient-specific liver anatomy based on diagnostic MRI images can provide essential vascular and biliary anatomical insight during surgery. However, a method for generating these is not yet publicly available. This paper describes how these 3D models of the liver can be generated using open source software, and then subsequently integrated into a sterile surgical environment. The most common image quality aspects that degrade the quality of the 3D models as well possible ways of eliminating these are also discussed. Per patient, a single diagnostic multiphase MRI scan with hepatospecific contrast agent was used for automated segmentation of liver contour, arterial, portal, and venous anatomy, and the biliary tree. Subsequently, lesions were delineated manually. The resulting interactive 3D model could be accessed during surgery on a sterile covered tablet. Up to now, such models have been used in 335 surgical procedures. Their use simplified the surgical treatment of patients with a high number of liver metastases and contributed to the localization of vanished lesions in cases of a radiological complete response to neoadjuvant treatment. They facilitated perioperative verification of the relationship of tumors and the surrounding vascular and biliary anatomy, and eased decision-making before and during surgery.

Prospective study on image-guided navigation surgery for pelvic malignancies.

BACKGROUND AND OBJECTIVES: Surgery of advanced tumors and lymph nodes in the pelvis can be challenging due to the narrow pelvic space and vital surrounding structures. This study explores the application of a novel electromagnetic navigation system to guide pelvic surgery. METHODS: This was a prospective study on surgery for malignancies in the pelvis. Preoperatively obtained imaging was used to create a patient-specific three-dimensional (3D) roadmap. In the operating room, the 3D roadmap was registered to an intraoperative computed tomography scan. A tracked pointer was used during surgery for guidance. Primary endpoint was safety and feasibility, secondary endpoints were accuracy and usability. RESULTS: Twenty-eight colorectal, four liposarcomas, and one gynecological patient were included. There were no safety issues. Navigation was feasible in 31 patients. The mean target registration errors of 4.0 and 6.3 mm were achieved for straight and French position, respectively. In seven of seven patients with a locally advanced rectal tumor and in seven of eight patients with recurrences, negative margins were achieved. Thirty-three of 36 target lymph nodes were successfully removed. Surgeons using the system indicated faster localization of the tumor and improved decisiveness. CONCLUSION: This novel surgical navigation system was safe and feasible during pelvic surgery and can facilitate its users.

Towards the use of diffuse reflectance spectroscopy for real-time in vivo detection of breast cancer during surgery.

BACKGROUND: Breast cancer surgeons struggle with differentiating healthy tissue from cancer at the resection margin during surgery. We report on the feasibility of using diffuse reflectance spectroscopy (DRS) for real-time in vivo tissue characterization. METHODS: Evaluating feasibility of the technology requires a setting in which measurements, imaging and pathology have the best possible correlation. For this purpose an optical biopsy needle was used that had integrated optical fibers at the tip of the needle. This approach enabled the best possible correlation between optical measurement volume and tissue histology. With this optical biopsy needle we acquired real-time DRS data of normal tissue and tumor tissue in 27 patients that underwent an ultrasound guided breast biopsy procedure. Five additional patients were measured in continuous mode in which we obtained DRS measurements along the entire biopsy needle trajectory. We developed and compared three different support vector machine based classification models to classify the DRS measurements. RESULTS: With DRS malignant tissue could be discriminated from healthy tissue. The classification model that was based on eight selected wavelengths had the highest accuracy and Matthews Correlation Coefficient (MCC) of 0.93 and 0.87, respectively. In three patients that were measured in continuous mode and had malignant tissue in their biopsy specimen, a clear transition was seen in the classified DRS measurements going from healthy tissue to tumor tissue. This transition was not seen in the other two continuously measured patients that had benign tissue in their biopsy specimen. CONCLUSIONS: It was concluded that DRS is feasible for integration in a surgical tool that could assist the breast surgeon in detecting positive resection margins during breast surgery. Trail registration NIH US National Library of Medicine-clinicaltrails.gov, NCT01730365. Registered: 10/04/2012 https://clinicaltrials.gov/ct2/show/study/NCT01730365.

Nerve detection using optical spectroscopy, an evaluation in four different models: In human and swine, in-vivo, and post mortem.

OBJECTIVE: Identification of peripheral nerve tissue is crucial in both surgery and regional anesthesia. Recently, optical tissue identification methods are presented to facilitate nerve identification in transcutaneous procedures and surgery. Optimization and validation of such techniques require large datasets. The use of alternative models to human in vivo, like human post mortem, or swine may be suitable to test, optimize and validate new optical techniques. However, differences in tissue characteristics and thus optical properties, like oxygen saturation and tissue perfusion are to be expected. This requires a structured comparison between the models. STUDY DESIGN: Comparative observational study. METHODS: Nerve and surrounding tissues in human (in vivo and post mortem) and swine (in vivo and post mortem) were structurally compared macroscopically, histologically, and spectroscopically. Diffuse reflective spectra were acquired (400-1,600 nm) after illumination with a broad band halogen light. An analytical model was used to quantify optical parameters including concentrations of optical absorbers. RESULTS: Several differences were found histologically and in the optical parameters. Histologically nerve and adipose tissue (subcutaneous fat and sliding fat) showed clear similarities between human and swine while human muscle enclosed more adipocytes and endomysial collagen. Optical parameters revealed model dependent differences in concentrations of ß-carotene, water, fat, and oxygen saturation. The similarity between optical parameters is, however, sufficient to yield a strong positive correlation after cross model classification. CONCLUSION: This study shows and discusses similarities and differences in nerve and surrounding tissues between human in vivo and post mortem, and swine in vivo and post mortem; this could support the discussion to use an alternative model to optimize and validate optical techniques for clinical nerve identification. Lasers Surg. Med. 50:253-261, 2018. © 2017 Wiley Periodicals, Inc.

Nerve detection during surgery: optical spectroscopy for peripheral nerve localization.

Precise nerve localization is of major importance in both surgery and regional anesthesia. Optically based techniques can identify tissue through differences in optical properties, like absorption and scattering. The aim of this study was to evaluate the potential of optical spectroscopy (diffuse reflectance spectroscopy) for clinical nerve identification in vivo. Eighteen patients (8 male, 10 female, age 53 ± 13 years) undergoing inguinal lymph node resection or resection or a soft tissue tumor in the groin were included to measure the femoral or sciatic nerve and the surrounding tissues. In vivo optical measurements were performed using Diffuse Reflectance Spectroscopy (400-1600 nm) on nerve, near nerve adipose tissue, muscle, and subcutaneous fat using a needle-shaped probe. Model-based analyses were used to derive verified quantitative parameters as concentrations of optical absorbers and several parameters describing scattering. A total of 628 optical spectra were recorded. Measured spectra reveal noticeable tissue specific characteristics. Optical absorption of water, fat, and oxy- and deoxyhemoglobin was manifested in the measured spectra. The parameters water and fat content showed significant differences (P < 0.005) between nerve and all surrounding tissues. Classification using k-Nearest Neighbor based on the derived parameters revealed a sensitivity of 85% and a specificity of 79%, for identifying nerve from surrounding tissues. Diffuse Reflectance Spectroscopy identifies peripheral nerve bundles. The differences found between tissue groups are assignable to the tissue composition and structure.

Review: in vivo optical spectral tissue sensing-how to go from research to routine clinical application?

Innovations in optical spectroscopy have helped the technology reach a point where performance previously seen only in laboratory settings can be translated and tested in real-world applications. In the field of oncology, spectral tissue sensing (STS) by means of optical spectroscopy is considered to have major potential for improving diagnostics and optimizing treatment outcome. The concept has been investigated for more than two decades and yet spectral tissue sensing is not commonly employed in routine medical practice. It is therefore important to understand what is needed to translate technological advances and insights generated through basic scientific research in this field into clinical practice. The aim of the discussion presented here is not to provide a comprehensive review of all work published over the last decades but rather to highlight some of the challenges found in literature and encountered by our group in the quest to translate optical technologies into useful clinical tools. Furthermore, an outlook is proposed on how translational researchers could proceed to eventually have STS incorporated in the process of clinical decision-making.

In vivo tumor identification of colorectal liver metastases with diffuse reflectance and fluorescence spectroscopy.

BACKGROUND AND OBJECTIVE: Over the last decade, an increasing effort has been put towards the implementation of optical guidance techniques to aid surgeons during cancer surgery. Diffuse reflectance spectroscopy (DRS) and fluorescence spectroscopy (FS) are two of these new techniques. The objective of this study is to investigate whether in vivo optical spectroscopy is able to accurately discriminate colorectal liver metastases (CRLM) from normal liver tissue in vivo. MATERIALS AND METHODS: DRS and FS were incorporated at the tip of a needle and were used for in vivo tissue differentiation during resection of CRLM. Measurements were taken in and around the tumor lesions and measurement sites were marked and correlated to histology (i.e., normal liver tissue or tumor tissue). Patients with and without neoadjuvant systemic chemotherapy were included into the study. RESULTS: Four hundred and eighty-four measurements were taken in and near 19 liver lesions prior to resection. Overall sensitivity and specificity for DRS was 95% and 92%, respectively. Bile was the most discriminative parameter. The addition of FS did not improve the overall accuracy. Sensitivity and specificity was not hampered by neo-adjuvant chemotherapy; sensitivity and specificity after neo-adjuvant chemotherapy were 92% and 100%, respectively. CONCLUSION: We have successfully integrated spectroscopy technology into a disposable 15 Gauge optical needle and we have shown that DRS and FS can accurately discriminate CRLM from normal liver tissue in the in vivo setting regardless of whether the patient was pre-treated with systemic therapy. This technique makes in vivo guidance accessible for common surgical practice. Lasers Surg. Med. 48:820-827, 2016. © 2016 Wiley Periodicals, Inc.

Diffuse reflectance spectroscopy: toward real-time quantification of steatosis in liver.

Assessment of fatty liver grafts during orthotopic liver transplantation is a challenge due to the lack of real-time analysis options during surgery. Diffuse reflectance spectroscopy (DRS) could be a new diagnostic tool to quickly assess steatosis. Eight hundred and seventy-eight optical measurements were performed in vivo in 17 patients in liver tissue during surgery and ex vivo on liver resection specimens from 41 patients. Liver steatosis was quantified from the collected optical spectra and compared with the histology analysis from the measurement location by three independent pathologists. Twenty two patients were diagnosed with <5% steatosis, 15 patients had mild steatosis, and four had moderate steatosis. Severe steatosis was not identified. Intraclass correlation between the pathologists analysis was 0.949. A correlation of 0.854 was found between the histology and DRS analyses of liver steatosis ex vivo. For the same liver tissue, a correlation of 0.925 was demonstrated between in vivo and ex vivo DRS analysis for steatosis quantification. DRS can quantify steatosis in liver tissue both in vivo and ex vivo with good agreement compared to histopathology analysis. This analysis can be performed real time and may therefore be useful for fast objective assessment of liver steatosis in liver surgery.

The value of optical coherence tomography in determining surgical margins in squamous cell carcinoma of the vulva: a single-center prospective study.

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) is treated with wide local excision. The challenge is to remove as much skin as necessary to prevent recurrence, but meanwhile preserve genital skin to diminish morbidity. Optical coherence tomography (OCT) is a noninvasive imaging tool that produces cross-sectional images. Optical coherence tomography could be helpful in determining appropriate surgical margins during excision of VSCC. OBJECTIVE: This study aimed to assess the value of OCT in determining appropriate surgical margins in patients operated for VSCC. We hypothesize that benign tissue will differ qualitatively (presence of clear epidermal layers) and quantitatively (epidermal layer thickness and attenuation coefficient) from (pre)malignant tissue. MATERIALS AND METHODS: In 18 patients with a pretreatment biopsy of VSCC, before excision, areas within the center (tumor), at the margin (skin next to the center), and in normal vulvar skin outside the area of resection were imaged by OCT. Optical coherence tomography data were assessed on the presence of a clear epidermal layer, thickness of the epidermal layer, and values of µOCT. Results were grouped according to histopathological report in a benign group and a (pre)malignant group. RESULTS: A clear epidermal layer was observed in all OCT images of benign tissue and only in 6 of 23 premalignant lesions (P < 0.001). The epidermal layer thickness as well as the µOCT was significantly smaller for benign vulvar tissue than for (pre)malignant tissue (0.29 vs 1.03 mm, and 2.4 vs 4.1 mm(-1), respectively; P < 0.001). The diagnostic accuracy of OCT, as calculated by receiver operating characteristic curve analysis, showed at defined thresholds a sensitivity of 100% and specificity of 80% when considering layer thickness, and a sensitivity of 100% and specificity of 70% when considering the attenuation coefficient. CONCLUSIONS: We show that qualitative and quantitative OCT imaging can distinguish between benign and (pre)malignant vulvar tissue, enabling appropriate surgical margin detection with noninvasive in vivo OCT imaging.

Deformable multi-modal image registration for the correlation between optical measurements and histology images.

Significance: The accurate correlation between optical measurements and pathology relies on precise image registration, often hindered by deformations in histology images. We investigate an automated multi-modal image registration method using deep learning to align breast specimen images with corresponding histology images. Aim: We aim to explore the effectiveness of an automated image registration technique based on deep learning principles for aligning breast specimen images with histology images acquired through different modalities, addressing challenges posed by intensity variations and structural differences. Approach: Unsupervised and supervised learning approaches, employing the VoxelMorph model, were examined using a dataset featuring manually registered images as ground truth. Results: Evaluation metrics, including Dice scores and mutual information, demonstrate that the unsupervised model exceeds the supervised (and manual) approaches significantly, achieving superior image alignment. The findings highlight the efficacy of automated registration in enhancing the validation of optical technologies by reducing human errors associated with manual registration processes. Conclusions: This automated registration technique offers promising potential to enhance the validation of optical technologies by minimizing human-induced errors and inconsistencies associated with manual image registration processes, thereby improving the accuracy of correlating optical measurements with pathology labels.