Fluorescence imaging for real-time detection of breast cancer tumors using IV injection of indocyanine green with non-conventional imaging: a systematic review of preclinical and clinical studies of perioperative imaging technologies.

BACKGROUND: This review summarizes the available data on the effectiveness of indocyanine green fluorescence imaging (ICG-FI) for real-time detection of breast cancer (BC) tumors with perioperative imaging technologies. METHODS: PubMed and Scopus databases were exhaustively searched for publications on the use of the real-time ICG-FI evaluation of BC tumors with non-conventional breast imaging technologies. RESULTS: Twenty-three studies were included in this review. ICG-FI has been used for BC tumor identification in 12 orthotopic animal tumor experiences, 4 studies on animal assessment, and for 7 human clinical applications. The BC tumor-to-background ratio (TBR) was 1.1-8.5 in orthotopic tumor models and 1.4-3.9 in animal experiences. The detection of primary human BC tumors varied from 40% to 100%. The mean TBR reported for human BC varied from 2.1 to 3.7. In two studies evaluating BC surgical margins, good sensitivity (93.3% and 100%) and specificity (60% and 96%) have been reported, with a negative predictive value of ICG-FI to predict margin involvement intraoperatively of 100% in one study. CONCLUSIONS: The use of ICG-FI as a guiding tool for the real-time identification of BC tumors and for the assessment of tumor boundaries is promising. There is great variability between the studies with regard to timing and dose. Further evidence is needed to assess whether ICG-guided BC surgery may be implemented as a standard of care.

Artificial Intelligence Improves the Ability of Physicians to Identify Prostate Cancer Extent.

PURPOSE: Defining prostate cancer contours is a complex task, undermining the efficacy of interventions such as focal therapy. A multireader multicase study compared physicians' performance using artificial intelligence (AI) vs standard-of-care methods for tumor delineation. MATERIALS AND METHODS: Cases were interpreted by 7 urologists and 3 radiologists from 5 institutions with 2 to 23 years of experience. Each reader evaluated 50 prostatectomy cases retrospectively eligible for focal therapy. Each case included a T2-weighted MRI, contours of the prostate and region(s) of interest suspicious for cancer, and a biopsy report. First, readers defined cancer contours cognitively, manually delineating tumor boundaries to encapsulate all clinically significant disease. Then, after ≥ 4 weeks, readers contoured the same cases using AI software. Using tumor boundaries on whole-mount histopathology slides as ground truth, AI-assisted, cognitively-defined, and hemigland cancer contours were evaluated. Primary outcome measures were the accuracy and negative margin rate of cancer contours. All statistical analyses were performed using generalized estimating equations. RESULTS: The balanced accuracy (mean of voxel-wise sensitivity and specificity) of AI-assisted cancer contours (84.7%) was superior to cognitively-defined (67.2%) and hemigland contours (75.9%; P < .0001). Cognitively-defined cancer contours systematically underestimated cancer extent, with a negative margin rate of 1.6% compared to 72.8% for AI-assisted cancer contours (P < .0001). CONCLUSIONS: AI-assisted cancer contours reduce underestimation of prostate cancer extent, significantly improving contouring accuracy and negative margin rate achieved by physicians. This technology can potentially improve outcomes, as accurate contouring informs patient management strategy and underpins the oncologic efficacy of treatment.

To Revise or Not Revise? Isolated Margin Positivity in Localized Pancreatic Ductal Adenocarcinoma.

BACKGROUND: The study determined the proportion of patients with pancreatic adenocarcinoma (PDAC) who had margin-positive disease and no other adverse pathologic findings (APF) using institutional and administrative datasets. METHODS: Patients with clinical stage I or II PDAC in the National Cancer Database (NCDB 2010-2020) and those who underwent pancreatectomy at the authors' institution (2010-2021) were identified. Isolated margin positivity (IMP) was defined as a positive surgical margin with no APF (negative nodes, no lymphovascular/perineural invasion). RESULTS: The study included 225 patients from the authors' institution and 23,598 patients from the NCDB. The margin-positive rates were 21.8% and 20.3%, and the IMP rates were 0.4% and 0.5%, respectively. In the institutional cohort, 68.4% of the patients had recurrence, and most of the patients (65.6%) had distant recurrences. The median recurrence-free survival (RFS) was 63.3 months for no APF, not reached for IMP, 14.8 months for negative margins & 1 APF, 20.3 months for positive margins & 2 APFs, and 12.9 months with all APF positive. The patients in the NCDB with IMP had a lower median OS than the patients with no APF (20.5 vs 390 months), but a higher median OS than those with margin positivity plus 1 APF (20.5 vs 18.0 months) or all those with APF positivity (20.5 vs 15.4 months). Based on institutional rates of IMP, any margin positivity, neck margin positivity (NMP), and no APF, the fraction of patients who might benefit from neck margin revision was 1 in 100,000, and those likely to benefit from any margin revision was 1 in 18,500. In the NCDB, those estimated to derive potential benefit from margin revision was 1 in 25,000. CONCLUSIONS: Isolated margin positivity in resected PDAC is rare, and most patients experience distant recurrence. Revision of IMP appears unlikely to confer benefit to most patients.

A New Nephrometry Score for Predicting Positive Surgical Margin After Laparoscopic Partial Nephrectomy.

PURPOSE: To introduce the KESKIN ratio as a novel predictor of positive surgical margin (PSM) after laparoscopic partial nephrectomy (PN) and to evaluate other clinical characteristics and nephrometry scores (including RENAL, PADUA, and C-index) for predicting PSM. METHODS: We retrospectively analyzed 95 patients who underwent laparoscopic PN between June 2020 and April 2023. The KESKIN ratio was defined for all patients. The KESKIN ratio, tumor and patient-related paramaters, and nephrometry scores were analyzed to predict PSM. RESULTS: Positive surgical margin was found in 12 of 95 patients (12.6%). There was no statistical difference between the PSM and negative surgical margin (NSM) groups in RENAL, PADUA, and C-index scores. Only the KESKIN ratio was found to be a statistically significant predictor of PSM in both univariate and multivariate regression analysis (p = 0.007 and p = 0.043, respectively). Mean endophytic diameter and endophytic percentage were found to be statistically significant predictors of PSM in only univariate analysis (p = 0.005 and p = 0.01, respectively). The value of 0.5 was determined as the cut-off value for the KESKIN ratio. Values higher than 0.5 indicate an increase in PSM. CONCLUSIONS: The KESKIN ratio is a novel, easily measurable, and calculable image-based parameter that can be used to predict PSM after laparascopic PN. If externally validated in a larger patient population, the KESKIN ratio may be used in future versions of the current nephrometry scoring systems for predicting the PSM.

3D Specimen Scanning and Mapping in Musculoskeletal Oncology: A Feasibility Study.

BACKGROUND: Surgical resection is the primary treatment for bone and soft tissue tumors. Negative margin status is a key factor in prognosis. Given the three-dimensional (3D) anatomic complexity of musculoskeletal tumor specimens, communication of margin results between surgeons and pathologists is challenging. We sought to perform ex vivo 3D scanning of musculoskeletal oncology specimens to enhance communication between surgeons and pathologists. METHODS: Immediately after surgical resection, 3D scanning of the fresh specimen is performed prior to frozen section analysis. During pathologic grossing, whether frozen or permanent, margin sampling sites are annotated on the virtual 3D model using computer-aided design (CAD) software. RESULTS: 3D scanning was performed in seven cases (six soft tissue, one bone), with specimen mapping on six cases. Intraoperative 3D scanning and mapping was performed in one case in which the location of margin sampling was shown virtually in real-time to the operating surgeon to help achieve a negative margin. In six cases, the 3D model was used to communicate final permanent section analysis. Soft tissue, cartilage, and bone (including lytic lesions within bone) showed acceptable resolution. CONCLUSIONS: Virtual 3D scanning and specimen mapping is feasible and may allow for enhanced documentation and communication. This protocol provides useful information for anatomically complex musculoskeletal tumor specimens. Future studies will evaluate the effect of the protocol on positive margin rates, likelihood that a re-resection contains additional malignancy, and exploration of targeted adjuvant radiation protocols using a patient-specific 3D specimen map.

Intraoperative margin assessment during radical prostatectomy: is microscopy frozen in time or ready for digital defrost?

Intraoperative frozen section (IFS) is used with the intention to improve functional and oncological outcomes for patients undergoing radical prostatectomy (RP). High resource requirements of IFS techniques such as NeuroSAFE may preclude widespread adoption, even if there are benefits to patients. Recent advances in fresh-tissue microscopic digital imaging technologies may offer an attractive alternative, and there is a growing body of evidence regarding these technologies. In this narrative review, we discuss some of the familiar limitations of IFS and compare these to the attractive counterpoints of modern digital imaging technologies such as the speed and ease of image generation, the locality of equipment within (or near) the operating room, the ability to maintain tissue integrity, and digital transfer of images. Confocal laser microscopy (CLM) is the modality most frequently reported in the literature for margin assessment during RP. We discuss several imitations and obstacles to widespread dissemination of digital imaging technologies. Among these, we consider how the 'en-face' margin perspective will challenge urologists and pathologists to understand afresh the meaning of positive margin significance. As a part of this, discussions on how to describe, categorize, react to, and evaluate these technologies are needed to improve patient outcomes. Limitations of this review include its narrative structure and that the evidence base in this field is relatively immature but developing at pace.

Margin status impact on recurrence of phyllodes tumors in high-risk groups: a retrospective observational study.

BACKGROUND: Phyllodes tumor (PT) is an fibroepithelial tumor with potential for local recurrence. The optimal margin for surgical resection of PT is still debated, particularly in cases of positive margins. This study aimed to identify the risk factors for phyllodes tumor recurrence and the effect of a free margin on tumor recurrence by considering these risk factors. MATERIALS AND METHODS: This is a retrospective observational study of patients diagnosed with PT who had undergone surgical management. The data were collected from medical records from 2001 to 2020 in the breast clinic of Shahid Motahhari Clinic of Shiraz. Patients were followed up for at least 3 years after the operation to be checked for local recurrence or distant metastasis at regular intervals. RESULTS: This retrospective study included 319 patients with PT who underwent surgical management. Of these patients, 83.9% (n = 267), 7.6% (n = 24), and 8.5% (n = 27) were classified as benign, borderline, and malignant, respectively. 8.8% of all patients and 7.6% of non-malignant cases experienced local recurrence, and risk factors for recurrence included oral contraceptive use, smoking, size > 4 cm, stromal overgrowth, and stromal cell atypia. A negative surgical margin decreased the prevalence of recurrence in tumors > 4 cm and with stromal overgrowth significantly. CONCLUSION: The study found that a negative margin in all patients did not reduce the recurrence rate in benign and borderline phyllodes tumors, suggesting close follow up as a reasonable alternative. However, a negative margin may be effective in reducing recurrence in certain high-risk groups.

Bicenter validation of a risk model for the preoperative prediction of extraprostatic extension of localized prostate cancer combining clinical and multiparametric MRI parameters.

BACKGROUND: This study aimed to validate a previously published risk model (RM) which combines clinical and multiparametric MRI (mpMRI) parameters to predict extraprostatic extension (EPE) of prostate cancer (PC) prior to radical prostatectomy (RP). MATERIALS AND METHODS: A previously published RM combining clinical with mpMRI parameters including European Society of Urogenital Radiology (ESUR) classification for EPE was retrospectively evaluated in a cohort of two urological university hospitals in Germany. Consecutive patients (n = 205, January 2015 -June 2021) with available preoperative MRI images, clinical information including PSA, prostate volume, ESUR classification for EPE, histopathological results of MRI-fusion biopsy and RP specimen were included. Validation was performed by receiver operating characteristic analysis and calibration plots. The RM's performance was compared to ESUR criteria. RESULTS: Histopathological T3 stage was detected in 43% of the patients (n = 89); 45% at Essen and 42% at Düsseldorf. Discrimination performance between pT2 and pT3 of the RM in the entire cohort was AUC = 0.86 (AUC = 0.88 at site 1 and AUC = 0.85 at site 2). Calibration was good over the entire probability range. The discrimination performance of ESUR classification alone was comparable (AUC = 0.87). CONCLUSIONS: The RM showed good discriminative performance to predict EPE for decision-making for RP as a patient-tailored risk stratification. However, when experienced MRI reading is available, standardized MRI reading with ESUR scoring is comparable regarding information outcome. A main limitation is the potentially limited transferability to other populations because of the high prevalence of EPE in our subgroups.

Prostate size ≥ 100 g and its association with long-term outcomes of Retzius-sparing robot-assisted radical prostatectomy.

BACKGROUND: It is unknown whether perioperative and functional outcomes of Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) may be affected by large prostate sizes (PS). METHODS: All patients treated with RS-RARP were identified and compared according to PS. The definition of PS relied on the prostatic weight at final pathology (PS < 100 g vs ≥ 100 g). Multivariable logistic regression models tested immediate and 12-month urinary continence recovery (UCR, namely, 0-1 safety pad per-day), and positive surgical margins (PSM). Multivariable Poisson log-linear regression analyses tested operative time (OT), estimated blood loss (EBL), and length of stay (LOS). The analyses relied on the database of a high-volume European institution (2010-2022). RESULTS: Of 1,555 overall patients, 1503 (96.7%) had a PS < 100 g and 52 (3.3%) had a PS ≥ 100 g. No differences were recorded in LOS (3 days), and intraoperative (1.9 vs 2.3%) as well as postoperative complications (13 vs 12%; all p values > 0.05). No significant difference was recorded in PSM (25 vs 23%, p = 0.6). In patients with PS ≥ 100 g vs < 100 g, immediate UCR rate was 42 vs 64% (p = 0.002), and 12-month UCR rate was 87 vs 88% (p = 0.3). PV ≥ 100 g independently predicted worse immediate UCR (odds ratio 0.55, 95% CI 0.30-0.98, p = 0.044), but not worse 12-month UCR (p = 0.3) or higher PSM (p = 0.7). PV ≥ 100 g independently predicted longer OT (incidence rate ratio [IRR] 1.12, 95% CI 1.10-1.15, p < 0.001) and higher EBL (IRR 1.26, 95% CI 1.24-1.28, p < 0.001), but not longer LOS (p = 0.3). CONCLUSIONS: RS-RARP is a valid option for prostate cancer treatment, even in case of very large prostates. Specifically, no significant association was recognized between PS ≥ 100 g and PSM or 12-month UCR.

Prognostic factors among patients with pathological Grade Group 5 prostate cancer based on robot-associated radical prostatectomy specimens from a large Japanese cohort (MSUG94).

PURPOSE: There are no definitive prognostic factors for patients with pathological Grade Group 5 (pGG 5) prostate cancer (PCa) undergoing robot-associated radical prostatectomy (RARP). This study aimed to explore the prognostic factors among patients with pGG 5 PCa in a large Japanese cohort (MSUG94). METHODS: This retrospective, multi-institutional cohort study was conducted between 2012 and 2021 at ten centers in Japan and included 3195 patients. Patients with clinically metastatic PCa (cN1 or cM1) and those receiving neoadjuvant and/or adjuvant therapy were excluded. Finally, 217 patients with pGG5 PCa were analyzed. RESULTS: The median follow-up period was 28.0 months. The 3- and 5-year biochemical recurrence-free survival (BCRFS) rates of the overall population were 66.1% and 57.7%, respectively. The optimal threshold value (47.2%) for the percentage of positive cancer cores (PPCC) with any GG by systematic biopsy was chosen based on receiver operating characteristic curve analysis. Univariate analysis revealed that the prostate-specific antigen level at diagnosis, pT, pN, positive surgical margins (PSMs), lymphovascular invasion, and PPCC were independent prognostic factors for BCRFS. A multivariate analysis revealed that PSMs and PPCC were independent prognostic factors for BCRFS. Using these two predictors, we stratified BCRFS, metastasis-free survival (MFS), and castration-resistant PCa-free survival (CRPC-FS) among patients with pGG 5 PCa. CONCLUSION: The combination of PSMs and PPCC may be an important predictor of BCRFS, MFS, and CRPC-FS in patients with pGG 5 PCa undergoing RARP.