Rapid diagnosis and tumor margin assessment during pancreatic cancer surgery with the MasSpec Pen technology.
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ABSTRACT:
SUBMITTER: King ME
PROVIDER: S-EPMC8285949 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A method of rapidly differentiating lung tumor from healthy tissue is extraordinarily needed for both the diagnosis and the intraoperative margin assessment. We assessed the ability of fluorescence lifetime imaging microscopy (FLIM) for differentiating human lung cancer and normal tissues with the autofluorescence, and also elucidated the mechanism in tissue studies and cell studies. A 15-patient testing group was used to compare FLIM results with traditional histopathology diagnosis. Based on the endogenous fluorescence lifetimes of the testing group, a criterion line was proposed to distinguish normal and cancerous tissues. Then by blinded examined 41 sections from the validation group of other 16 patients, the sensitivity and specificity of FLIM were determined. The cellular metabolism was studied with specific perturbations of oxidative phosphorylation and glycolysis in cell studies. The fluorescence lifetime of cancerous lung tissues is consistently lower than normal tissues, and this is due to the both decrease of reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) lifetimes. A criterion line of lifetime at 1920 ps can be given for differentiating human lung cancer and normal tissues.The sensitivity and specificity of FLIM for lung cancer diagnosis were determined as 92.9% and 92.3%. These findings suggest that NADH and FAD can be used to rapidly diagnose lung cancer. FLIM is a rapid, accurate and highly sensitive technique in the judgment during lung cancer surgery and it can be potential in earlier cancer detection.
| S-EPMC5447569 | biostudies-literature
Project description:BackgroundRoughly 23% of breast conserving surgery (BCS) patients undergo a second re-excision procedure due to pathologically positive surgical margins. We investigated the feasibility and potential value of micro-Computed Tomography (micro-CT) as a surgical margin guidance tool during BCS.MethodsA cohort of 32 BCS specimens was prospectively imaged with a pre-clinical micro-CT system upon arrival in the surgical pathology laboratory. Reconstructed micro-CT scans were evaluated retrospectively by an experienced breast radiologist, who provided binary determinations whether lesions extended to the specimen margin. These readings were then compared to the final pathological diagnosis and to 2D specimen radiography readings.ResultsOf the 32 specimens imaged, 28 had malignant and four had benign pathological diagnoses. Overall five (four malignant, one benign) of the 32 specimens had lesion tissue extending to the margin. For all 32 specimens, micro-CT reconstructions were calculated (< 4 min. acquisition + reconstruction time) and each specimen was volumetrically analyzed by a radiologist. Of the 28 malignant specimen readings, 18 matched the final pathological diagnosis [64%, 95 CI (47%-81%)], with a negative predictive value of 89% [95 CI (74%-96%)]. Micro-CT readings revealed changes in the tumor location and margin status as compared to single-projection radiography readings.ConclusionsMicro-CT scanning of BCS specimens enabled margin status assessment over the entirety of the surgical surface in a clinically relevant time frame, provided additional spatial information over single-projection radiography, and may be a potentially useful BCS guidance tool.
| S-EPMC6245085 | biostudies-literature
Project description:BackgroundAccurate tissue diagnosis during ovarian cancer surgery is critical to maximize cancer excision and define treatment options. Yet, current methods for intraoperative tissue evaluation can be time intensive and subjective. We have developed a handheld and biocompatible device coupled to a mass spectrometer, the MasSpec Pen, which uses a discrete water droplet for molecular extraction and rapid tissue diagnosis. Here we evaluated the performance of this technology for ovarian cancer diagnosis across different sample sets, tissue types, and mass spectrometry systems.MethodsMasSpec Pen analyses were performed on 192 ovarian, fallopian tube, and peritoneum tissue samples. Samples were evaluated by expert pathologists to confirm diagnosis. Performance using an Orbitrap and a linear ion trap mass spectrometer was tested. Statistical models were generated using machine learning and evaluated using validation and test sets.ResultsHigh performance for high-grade serous carcinoma (n = 131; clinical sensitivity, 96.7%; specificity, 95.7%) and overall cancer (n = 138; clinical sensitivity, 94.0%; specificity, 94.4%) diagnoses was achieved using Orbitrap data. Variations in the mass spectra from normal tissue, low-grade, and high-grade serous ovarian cancers were observed. Discrimination between cancer and fallopian tube or peritoneum tissues was also achieved with accuracies of 92.6% and 87.9%, respectively, and 100% clinical specificity for both. Using ion trap data, excellent results for high-grade serous cancer vs normal ovarian differentiation (n = 40; clinical sensitivity, 100%; specificity, 100%) were obtained.ConclusionsThe MasSpec Pen, together with machine learning, provides robust molecular models for ovarian serous cancer prediction and thus has potential for clinical use for rapid and accurate ovarian cancer diagnosis.
| S-EPMC7433751 | biostudies-literature
Project description:BACKGROUND:The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is poor and selection of patients for surgery is challenging. This study examined the impact of a positive resection margin (R1) on locoregional recurrence (LRR) and overall survival (OS); and also aimed to identified tumour characteristics and/or technical factors associated with a positive resection margin in patients with PDAC. METHODS:Patients scheduled for pancreatic resection for PDAC between 2006 and 2016 were identified from an institutional database. The effect of resection margin status, patient characteristics and tumour characteristics on LRR, distant metastasis and OS was assessed. RESULTS:A total of 322 patients underwent pancreatectomy for PDAC. A positive resection (R1) margin was found in 129 patients (40·1 per cent); this was associated with decreased OS compared with that in patients with an R0 margin (median 15 (95 per cent c.i. 13 to 17) versus 22 months; P < 0·001). R1 status was associated with reduced time to LRR (median 16 versus 36 (not estimated, n.e.) months; P = 0·002). Disease recurrence patterns were similar in the R1 and R0 groups. Risk factors for early recurrence were tumour stage, positive lymph nodes (N1) and perineural invasion. Among 100 patients with N0 disease, R1 status was associated with shorter OS compared with R0 resection (median 17 (10 to 24) versus 45 (n.e.) months; P = 0·002), whereas R status was not related to OS in 222 patients with N1 disease (median 14 (12 to 16) versus 17 (15 to 19) months after R1 and R0 resection respectively; P = 0·068). CONCLUSION:Although pancreatic resection with a positive margin was associated with poor survival and early recurrence, particularly in patients with N1 disease, disease recurrence patterns were similar between R1 and R0 groups.
| S-EPMC6617755 | biostudies-literature
Project description:RationalePositive margin status due to incomplete removal of tumor tissue during breast conserving surgery (BCS) is a prevalent diagnosis usually requiring a second surgical procedure. These follow-up procedures increase the risk of morbidity and delay the use of adjuvant therapy; thus, significant efforts are underway to develop new intraoperative strategies for margin assessment to eliminate re-excision procedures. One strategy under development uses topical application of dual probe staining and a fluorescence imaging strategy termed dual probe difference specimen imaging (DDSI). DDSI uses a receptor-targeted fluorescent probe and an untargeted, spectrally-distinct fluorescent companion imaging agent topically applied to fresh resected specimens, where the fluorescence from each probe is imaged and a normalized difference image is computed to identify tumor-target distribution in the specimen margins. While previous reports suggested this approach is a promising new tool for surgical guidance, advancing the approach into the clinic requires methodical protocol optimization and further validation.MethodsIn the present study, we used breast cancer xenografts and receiver operator characteristic (ROC) curve analysis to evaluate a wide range of staining and imaging parameters, and completed a prospective validation study on multiple tumor phenotypes with different target expression. Imaging fluorophore-probe pair, concentration, and incubation times were systematically optimized using n=6 tissue specimen replicates per staining condition. Resulting tumor vs. normal adipose tissue diagnostic performance were reported and staining patterns were validated via receptor specific immunohistochemistry colocalization. Optimal staining conditions were tested in receptor positive and receptor negative cohorts to confirm specificity.ResultsThe optimal staining conditions were found to be a one minute stain in a 200 nM probe solution (area under the curve (AUC) = 0.97), where the choice of fluorescent label combination did not significantly affect the diagnostic performance. Using an optimal threshold value determined from ROC curve analysis on a training data set, a prospective study on xenografts resulted in an AUC=0.95 for receptor positive tumors and an AUC = 0.50 for receptor negative (control) tumors, confirming the diagnostic performance of this novel imaging technique.ConclusionsDDSI provides a robust, molecularly specific imaging methodology for identifying tumor tissue over benign mammary adipose tissue. Using a dual probe imaging strategy, nonspecific accumulation of targeted probe was corrected for and tumor vs. normal tissue diagnostic potential was improved, circumventing difficulties with ex vivo tissue specimen staining and allowing for rapid clinical translation of this promising technology for tumor margin detection during BCS procedures.
| S-EPMC5706095 | biostudies-literature
Project description:Background and objectiveA positive surgical margin (PSM) occurs in up to 32% of patients undergoing robot-assisted radical prostatectomy (RARP). Diffuse reflectance spectroscopy (DRS), which measures tissue composition according to its optical properties, can potentially be used for real-time PSM detection during RARP. Our objective was to assess the feasibility of DRS in distinguishing prostate cancer from benign tissue in RARP specimens.MethodsIn a single-center prospective study, DRS measurements were taken ex vivo for RARP specimens from 59 patients with biopsy-proven prostate carcinoma. Discriminating features from the DRS spectra were used to create a machine learning-based classification algorithm. The data were split patient-wise into training (70%) and testing (30%) sets, with ten iterations to ensure algorithm robustness. The average sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) from ten classification iterations were calculated.Key findings and limitationsWe collected 542 DRS measurements, of which 53% were tumor and 47% were healthy-tissue measurements. Twenty discriminating features from the DRS spectra were used as the input for a support vector machine model. This model achieved average sensitivity of 89%, specificity of 82%, accuracy of 85%, and AUC of 0.91 for the test set. Limitations include the binary label input for classification.Conclusions and clinical implicationsDRS can potentially discriminate prostate cancer from benign tissue. Before implementing the technique in clinical practice, further research is needed to assess its performance on heterogeneous tissue volumes and measurements from the prostate surface.Patient summaryWe looked at the ability of a technique called diffuse reflectance spectroscopy to guide surgeons in discriminating prostate cancer tissue from benign prostate tissue in real time during prostate cancer surgery. Our study showed promising results in an experimental setting. Future research will focus on bringing this technique to clinical practice.
| S-EPMC11369370 | biostudies-literature
Project description:BackgroundWith the advent of intensive combination regimens, an increasing number of patients with unresectable pancreatic cancer (UPC) have regained the opportunity for surgery. We investigated the clinical benefits and prognostic factors of conversion surgery (CS) in UPC patients.MethodsWe retrospectively enrolled patients with UPC who had received CS following first-line systemic treatment in our center between 2014 to 2022. Treatment response, safety of the surgical procedure and clinicopathological data were collected. We analyzed the prognostic factors for postoperative survival among UPC patients who had CS.ResultsSixty-seven patients with UPC were enrolled (53 with locally advanced pancreatic cancer (LAPC) and 14 with metastatic pancreatic cancer (MPC)). The duration of preoperative systemic treatment was 4.17 months for LAPC patients and 6.52 months for MPC patients. All patients experienced a partial response (PR) or had stable disease (SD) preoperatively according to imaging. Tumor resection was unsuccessful in four patients and, finally, R0 resection was obtained in 81% of cases. Downstaging was determined pathologically in 87% of cases; four patients achieved a complete pathological response. Median postoperative-progression-free survival (PO-PFS) was 9.77 months and postoperative overall survival (PO-OS) was 31.2 months. Multivariate logistic regression analyses revealed that the resection margin and postoperative changes in levels of tumor markers were significant prognostic factors for PO-PFS. No factors were associated significantly with PO-OS according to multivariate analyses.ConclusionsCS is a promising strategy for improving the prognosis of UPC patients. The resection margin and postoperative change in levels of tumor markers are the most important prognostic factors for prolonged PFS. Multidisciplinary treatment in high-volume centers is strongly recommended. Prospective studies must be undertaken to resolve the various problems regarding optimal regimens, the duration of treatment, and detailed criteria for CS.
| S-EPMC9840266 | biostudies-literature
Project description:Purpose: Surgery is an essential part of the curative plan for most patients affected with solid tumors. The outcome of such surgery, e.g., recurrence rates and ultimately patient survival, depends on several factors where the resection margin is of key importance. Presently, the resection margin is assessed by classical histology, which is time-consuming (several days), destructive, and basically only gives two-dimensional information. Clearly, it would be advantageous if immediate feedback on tumor extension in all three dimensions were available to the surgeon intraoperatively. Approach: We investigate a laboratory propagation-based phase-contrast x-ray computed tomography system that provides the resolution, the contrast, and, potentially, the speed for this purpose. The system relies on a liquid-metal jet microfocus source and a scintillator-coated CMOS detector. Our study is performed on paraffin-embedded non-stained samples of human pancreatic neuroendocrine tumors, liver intrahepatic cholangiocarcinoma, and pancreatic serous cystic neoplasm (benign). Results: We observe tumors with distinct and sharp edges having cellular resolution ( ∼10 μm ) as well as many assisting histological landmarks, allowing for resection margin assessment. All x-ray data are compared with classical histology. The agreement is excellent. Conclusion: We conclude that the method has potential for intraoperative three-dimensional virtual histology.
| S-EPMC8820384 | biostudies-literature
Project description:BACKGROUND:Wearable technology is finding its way into clinical practice. Physical activity describes patients' functional status after cardiac surgery and can be monitored remotely by using dedicated trackers. OBJECTIVE:The aim of this study was to compare the progress of physical activity in cardiac rehabilitation by using wearable fitness trackers in patients undergoing coronary artery bypass surgery by either the conventional off-pump coronary artery bypass (OPCAB) or the robotically assisted minimally invasive coronary artery bypass (RA-MIDCAB). We hypothesized faster recovery of physical activity after RA-MIDCAB in the first weeks after discharge as compared to OPCAB. METHODS:Patients undergoing RA-MIDCAB or OPCAB were included in the study. Each patient received a Fitbit Charge HR (Fitbit Inc, San Francisco, CA) physical activity tracker following discharge. Rehabilitation progress was assessed by measuring the number of steps and physical activity level daily. The physical activity level was calculated as energy expenditure divided by the basic metabolic rate. RESULTS:A total of 10 RA-MIDCAB patients with a median age of 68 (min, 55; max, 83) years and 12 OPCAB patients with a median age of 69 (min, 50; max, 82) years were included. Baseline characteristics were comparable except for body mass index (RA-MIDCAB: 26 kg/m²; min, 22; max, 28 versus OPCAB: 29 kg/m²; min, 27; max, 33; P<.001). Intubation time (P<.05) was significantly lower in the RA-MIDCAB group. A clear trend, although not statistically significant, was observed towards a higher number of steps in RA-MIDCAB patients in the first week following discharge. CONCLUSIONS:RA-MIDCAB patients have an advantage in recovery in the first weeks of revalidation, which is reflected by the number of steps and physical activity level measured by the Fitbit Charge HR, as compared to OPCAB patients. However, unsupervised assessment of daily physical activity varied widely and could have consequences with regard to the use of these trackers as research tools.
| S-EPMC6374731 | biostudies-literature
Project description:Aim: We aim to study clinically and pathologically whether narrow resection margin (<1 cm) is acceptable in hepatoblastoma surgery. Methods: A total of 42 patients who underwent surgery for hepatoblastoma were selected, and these patients were divided into two groups according to whether or not they underwent preoperative chemotherapy (CHT). The general characteristics of the patients were summarized, the resection margin distance was recorded, and the event-free survival rates were followed up. Pathologically, H&E staining and immunochemical staining were used to study the invasion distance outside the tumor capsule in the tumor border. Results: Clinically, the event-free survival rates were not significantly different between the patients with wide resection margin (>1 cm) and narrow resection margin (<1 cm) of the two groups. Pathologically, the tumor of all 42 patients had capsules surrounding the tumor. Of the patients in Group 1 (without preoperative CHT), 9% (2/22) had micrometastatic cancer nests outside the capsule, and the farthest distance from the cancer nests to the capsule was 4.6 mm. Of the patients in Group 2 (with preoperative CHT), 75% (15/20) showed residual cancer nests in the paratumor liver tissue, and the farthest distance was 9.6 mm; three and two cases, respectively, showed extracapsular intravascular microtumorous thrombi. Conclusion: Clinically and pathologically, narrow resection margin is acceptable in hepatoblastoma surgery.
| S-EPMC7064447 | biostudies-literature