Fluorescein-stained confocal laser endomicroscopy versus conventional frozen section for intraoperative histopathological assessment of intracranial tumors.

BACKGROUND: The aim of this clinical trial was to compare Fluorescein-stained intraoperative confocal laser endomicroscopy (CLE) of intracranial lesions and evaluation by a neuropathologist with routine intraoperative frozen section (FS) assessment by neuropathology. METHODS: In this phase II noninferiority, prospective, multicenter, nonrandomized, off-label clinical trial (EudraCT: 2019-004512-58), patients above the age of 18 years with any intracranial lesion scheduled for elective resection were included. The diagnostic accuracies of both CLE and FS referenced with the final histopathological diagnosis were statistically compared in a noninferiority analysis, representing the primary endpoint. Secondary endpoints included the safety of the technique and time expedited for CLE and FS. RESULTS: A total of 210 patients were included by 3 participating sites between November 2020 and June 2022. Most common entities were high-grade gliomas (37.9%), metastases (24.1%), and meningiomas (22.7%). A total of 6 serious adverse events in 4 (2%) patients were recorded. For the primary endpoint, the diagnostic accuracy for CLE was inferior with 0.87 versus 0.91 for FS, resulting in a difference of 0.04 (95% confidence interval -0.10; 0.02; P = .367). The median time expedited until intraoperative diagnosis was 3 minutes for CLE and 27 minutes for FS, with a mean difference of 27.5 minutes (standard deviation 14.5; P < .001). CONCLUSIONS: CLE allowed for a safe and time-effective intraoperative histological diagnosis with a diagnostic accuracy of 87% across all intracranial entities included. The technique achieved histological assessments in real time with a 10-fold reduction of processing time compared to FS, which may invariably impact surgical strategy on the fly.

Assessment of large droplet fat in frozen sections of donor liver biopsies: utility and interobserver variability of the newly described Banff method compared to a simplified Average of Fields method.

AIMS: There is great variability in the assessment and reporting of fat in frozen sections of donor liver biopsies. The Banff Working Group has proposed a novel method and definition for scoring large droplet fat (LDF) in donor liver biopsies. This study compares the Banff method with a simpler Average of Fields (AF) method and evaluates the impact of different LDF definitions. METHODS: Three pathologists assessed percentage of LDF (LDF%) in 10 donor liver biopsies using Banff and AF methods, applying the Banff LDF definition (cell distention with a single droplet larger than adjacent hepatocytes). Additionally, LDF% by the AF method was compared using two LDF definitions: Banff definition versus LDF definition 2 (single fat droplet occupying greater than half of a hepatocyte with nuclear displacement). RESULTS: Intraobserver concordance between the Banff and AF methods was similar for all three pathologists (kappa 0.76-1). Both methods exhibited 70% interobserver concordance, and there was substantial agreement (kappa 0.68) in the LDF% among the three pathologists for both methods. Comparing the two LDF definitions, results were significantly lower with the Banff definition; LDF >50% was observed in four cases with LDF definition 2 but none of the cases with the Banff definition. CONCLUSIONS: There is high interobserver and intraobserver concordance of LDF% between the Banff and AF methods. LDF% determined by the Banff definition was lower than with LDF definition 2, and needs to be validated based on graft outcome before it can be recommended for clinical use.

Paradigm Change for Intraoperative Surgical Margin Assessment for Oral Squamous Cell Carcinoma.

OBJECTIVE: Achieving clear surgical margins is one of the primary surgical goals in treating oral squamous cell carcinoma (OSCC) and thus aiming to improve overall and disease-specific survival. Therefore, we developed the Goal-Oriented Assessment for Intraoperative Margin ('GAIM') protocol, a novel intraoperative approach for margin assessment, and present here our 5-year experience and outcomes. METHODS: 'GAIM' is a 7-step procedure comprising systematic ruler-aided resection of labeled tumor-bed margins, frozen section (FS) co-produced by both pathologists and operating surgeons, and immediate extension of resection according to FS findings. Data from all patients operated using the 'GAIM' protocol at a single tertiary center between 2018 to 2022 were analyzed, including margin status on FS and final pathology (FP) records, recurrence, and mortality. RESULTS: A total of 196 patients were included, 56.6% (n = 111) stages I-II, and 43.4% (n = 85) stages III-IV. Using the 'GAIM' protocol, we achieved an overall 94.4% of clean and revised clean surgical margins. Patients with a 2-year and longer follow-up (n = 141) had local recurrence in 3.5% when both FS and final margins were clean, 8.1% when FP margins were clean, and 16.7% with close/positive final margins. CONCLUSIONS: The proposed 'GAIM' protocol is a novel, effective, reproducible, and safe approach for margin evaluation that can be systematically applied. It can increase the rate of final clean surgical margins and potentially improve patients' outcomes. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1725-1732, 2024.

A deep learning algorithm to detect cutaneous squamous cell carcinoma on frozen sections in Mohs micrographic surgery: A retrospective assessment.

Intraoperative margin analysis is crucial for the successful removal of cutaneous squamous cell carcinomas (cSCC). Artificial intelligence technologies (AI) have previously demonstrated potential for facilitating rapid and complete tumour removal using intraoperative margin assessment for basal cell carcinoma. However, the varied morphologies of cSCC present challenges for AI margin assessment. The aim of this study was to develop and evaluate the accuracy of an AI algorithm for real-time histologic margin analysis of cSCC. To do this, a retrospective cohort study was conducted using frozen cSCC section slides. These slides were scanned and annotated, delineating benign tissue structures, inflammation and tumour to develop an AI algorithm for real-time margin analysis. A convolutional neural network workflow was used to extract histomorphological features predictive of cSCC. This algorithm demonstrated proof of concept for identifying cSCC with high accuracy, highlighting the potential for integration of AI into the surgical workflow. Incorporation of AI algorithms may improve efficiency and completeness of real-time margin assessment for cSCC removal, particularly in cases of moderately and poorly differentiated tumours/neoplasms. Further algorithmic improvement incorporating surrounding tissue context is necessary to remain sensitive to the unique epidermal landscape of well-differentiated tumours, and to map tumours to their original anatomical position/orientation.

A biosensor for D-2-hydroxyglutarate in frozen sections and intraoperative assessment of IDH mutation status.

The oncometabolite D-2-hydroxyglutarate (D-2-HG) has emerged as a valuable biomarker in tumors with isocitrate dehydrogenase (IDH) mutations. Efficient detection methods are required and rapid intraoperative determination of D-2-HG remains a huge challenge. Herein, D-2-HG dehydrogenase from Achromobacter xylosoxidans (AX-D2HGDH) was found to have high substrate specificity. AX-D2HGDH dehydrogenizes D-2-HG and reduces flavin adenine dinucleotide (FAD) bound to the enzyme. Interestingly, the dye resazurin can be taken as another substrate to restore FAD. AX-D2HGDH thus catalyzes a bisubstrate and biproduct reaction: the dehydrogenation of D-2-HG to 2-ketoglutarate and simultaneous reduction of non-fluorescent resazurin to highly fluorescent resorufin. According to steady-state analysis, a ping-pong bi-bi mechanism has been concluded. The Km values for resazurin and D-2-HG were determined as 0.56 µM and 10.93 µM, respectively, suggesting high affinity to both substrates. On the basis, taking AX-D2HGDH and resazurin as recognition and fluorescence transducing element, a D-2-HG biosensor (HGAXR) has been constructed. HGAXR exhibits high sensitivity, accuracy and specificity for D-2-HG in different biological samples. With the aid of HGAXR and the matched low-cost palm-size detecting device, D-2-HG levels in frozen sections of resected brain tumor tissues can be measured in a direct, simple and accurate manner with a fast detection (1-3 min). As the technique of frozen section is familiar to surgeons and pathologists, HGAXR and the portable device can be easily integrated into the current workflow, having potential to provide rapid intraoperative pathology for IDH mutation status and guide decision-making during surgery.

Cost-Efficacy Analysis of Use of Frozen Section Histology for Margin Assessment During Breast Conservation Surgery in Breast Cancer Patients.

BACKGROUND: Margin assessment is an essential component of breast conservation surgery (BCS). Re-excision of infiltrated margin(s) detected on paraffin section histology (PSH) needs reoperation, adding time, inconvenience and cost. Intra-operative assessment of margins using frozen section histology (IFSH) can potentially obviate need for re-operation, thus facilitating one-step oncologically complete BCS. METHODS: IFSH and PSH reports of consecutive patients undergoing BCS (2010-2020) were reviewed. Accuracy and cost-efficacy of IFSH were assessed, considering PSH as gold standard. Cost of achieving oncologically complete BCS in whole cohort with IFSH (Scenario-A) was calculated and compared using appropriate statistical tests, with hospital costs for the cohort in a hypothetical Scenario-B, where IFSH was presumed not to have been used and all patients with infiltrated margin(s) on PSH would have been re-operated. RESULTS: Of the 367 patients screened, 39 were excluded due to incomplete IFSH data. Of 328 patients analyzed, 59 (18%) had one or more margins were reported infiltrated on IFSH, managed by re-excision or mastectomy in the same sitting, thus avoiding a reoperation. Additional 8 (2.4%) had involved margins on PSH (False negative IFSH). Significantly higher number of reoperations (p < 0.001) would have been needed in scenario-B. Average cost of the first operation with use of IFSH was Indian Rupees (INR) 25791 which included INR660 as IFSH cost. The average cost of reoperation was INR23724 which could be avoided in 59 (18%) by use of IFSH. The average cost per patient to achieve oncologically complete surgery in scenario A utilizing IFSH was significantly lower (p = 0.001) by INR3101 (11.7%), c.w. that in scenario B. Significant cost-saving with IFSH was maintained in cost-efficacy analysis undertaken with various higher and lower costs assumptions. CONCLUSIONS: Use of IFSH facilitates one-step oncologically complete BCS in majority of patients and results in considerable cost saving, resulting in avoidance of reoperations, besides preventing patient anxiety and delay in adjuvant treatment. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI/2021/08/035896).

NRAS-mutated oncocytic benign liver lesion in an organ donor: Pitfalls and troubles in frozen section diagnosis and risk assessment.

BACKGROUND: In the transplant setting, the definition of the risk of neoplastic transmission from donor to recipient often requires intraoperative pathological evaluation on frozen sections. Although most lesions can be easily classified into acceptable or unacceptable risk according to the Italian National Guidelines, there are cases in which unusual histologic features cannot be further investigated because of the lack of ancillary techniques on frozen sections. CASE PRESENTATION: Here we present a case of a liver lesion in a 51-year-old male donor, subjected to histopathological on-call examination. The frozen sections showed a well-demarcated lesion consisting of epithelioid cells disposed in laminar structures and intermingled with a dense lymphocytic population: this led to organ discard with interruption of the donation process. The definitive histological analysis required an extensive immunohistochemical (IHC) investigation: the final diagnosis was "bile duct adenoma with oncocytic features", eventually confirmed by a strongly positive anti-mitochondrial IHC. Finally, an NGS panel analysis was performed, which revealed NRAS mutation. DISCUSSION: To the best of our knowledge, this is the first case of oncocytic bile duct adenoma confirmed by anti-mitochondrial IHC and with NRAS mutation. The most challenging aspect of this case was represented by the transplant setting. In fact, the oncocytic features and the dense lymphocytic infiltrate represented concomitant unusual histological features that led to the halt of the organ donation procedures.

Diagnostic accuracy of intraoperative margin assessment techniques in surgery for head and neck squamous cell carcinoma: A meta-analysis.

BACKGROUND: Positive margins following head and neck squamous cell carcinoma (HNSCC) surgery lead to significant morbidity and mortality. Existing Intraoperative Margin Assessment (IMA) techniques are not widely used due to limitations in sampling technique, time constraints and resource requirements. We performed a meta-analysis of the diagnostic performance of existing IMA techniques in HNSCC, providing a benchmark against which emerging techniques may be judged. METHODS: The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Studies were included if they reported diagnostic metrics of techniques used during HNSCC surgery, compared with permanent histopathology. Screening, manuscript review and data extraction was performed by multiple independent observers. Pooled sensitivity and specificity were estimated using the bivariate random effects model. RESULTS: From an initial 2344 references, 35 studies were included for meta-analysis. Sensitivity (Sens), specificity (Spec), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC) were calculated for each group (n, Sens, Spec, DOR, AUROC): frozen section = 13, 0.798, 0.991, 309.8, 0.976; tumour-targeted fluorescence (TTF) = 5, 0.957, 0.827, 66.4, 0.944; optical techniques = 10, 0.919, 0.855, 58.9, 0.925; touch imprint cytology = 3, 0.925, 0.988, 51.1, 0.919; topical staining = 4, 0.918, 0.759, 16.4, 0.833. CONCLUSIONS: Frozen section and TTF had the best diagnostic performance. Frozen section is limited by sampling error. TTF shows promise but involves administration of a systemic agent. Neither is currently in widespread clinical use. Emerging techniques must demonstrate competitive diagnostic accuracy whilst allowing rapid, reliable, cost-effective results.

Invasiveness assessment by artificial intelligence against intraoperative frozen section for pulmonary nodules ≤ 3 cm.

PURPOSE: To investigate the performance of an artificial intelligence (AI) algorithm for assessing the malignancy and invasiveness of pulmonary nodules in a multicenter cohort. METHODS: A previously developed deep learning system based on a 3D convolutional neural network was used to predict tumor malignancy and invasiveness. Dataset of pulmonary nodules no more than 3 cm was integrated with CT images and pathologic information. Receiver operating characteristic curve analysis was used to evaluate the performance of the system. RESULTS: A total of 466 resected pulmonary nodules were included in this study. The areas under the curves (AUCs) of the deep learning system in the prediction of malignancy as compared with pathological reports were 0.80, 0.80, and 0.75 for all, subcentimeter, and solid nodules, respectively. Additionally, the AUC in the AI-assisted prediction of invasive adenocarcinoma (IA) among subsolid lesions (n = 184) was 0.88. Most malignancies that were misdiagnosed by the AI system as benign diseases with a diameter measuring greater than 1 cm (26/250, 10.4%) presented as solid nodules (19/26, 73.1%) on CT. In an exploratory analysis involving nodules underwent intraoperative pathologic examination, the concordance rate in identifying IA between the AI model and frozen section examination was 0.69, with a sensitivity of 0.50 and specificity of 0.97. CONCLUSION: The deep learning system can discriminate malignant diseases for pulmonary nodules measuring no more than 3 cm. The AI model has a high positive predictive value for invasive adenocarcinoma with respect to intraoperative frozen section examination, which might help determine the individualized surgical strategy.

A Quantitative and Qualitative Assessment of Frozen Section Diagnosis Accuracy and Deferral Rate Across Organ Systems.

OBJECTIVES: Monitoring of frozen section diagnostic performance provides an important quality improvement measure. METHODS: Surgical specimens involving a frozen section diagnosis over a 3-year period were retrospectively reviewed. Glass slides were reviewed on cases with discordance. Discordance and deferral rates were calculated. RESULTS: Of 3,675 frozen section diagnoses included, 96 (2.7%) were discordant with the final diagnosis. Additionally, 114 frozen section diagnoses (3.1%) were deferred. The organ-specific discordance rates were lowest in breast and genitourinary specimens and highest for pancreas, lymph node, and gynecologic specimens. Deferral rates were highest in musculoskeletal, breast, and hepatobiliary cases and lowest in thyroid, parathyroid, and neuropathology cases. Discordance was explained by block-sampling error (45%), specimen-sampling error (27%), or interpretation error (27%). Discordant frozen section diagnoses from gynecologic specimens were responsible for 81% of specimen-sampling errors; frozen section diagnoses of lymph nodes, head and neck, and pancreas were responsible for 54% of interpretation errors; 51% of block-sampling errors involved lymph node evaluation for metastatic carcinoma. CONCLUSIONS: Careful gross evaluation and microscopic examination of multiple levels should minimize specimen-sampling error and block-sampling error, respectively. Periodic review of accuracy and deferral rates may help reduce errors and improve the overall performance of this essential procedure.

Assessment of Quality of Frozen Section Services at a Large Academic Hospital Before and After Relocation.

OBJECTIVES: To determine outcomes following relocation of frozen section services (FSS) and the implementation of a dedicated gastrointestinal frozen service. METHODS: We reviewed our FSS 6 months prior to and following FSS relocation. Satisfaction surveys were sent to surgeons and pathologists. Survey feedback resulted in a pilot of gastrointestinal subspecialist frozen section coverage. RESULTS: There were 1,607 and 1,472 specimens from 667 and 602 patients pre- and post-FSS relocation, respectively. There was a decline in median specimen delivery time to pathology (12 vs 10 minutes, P < .001) and an increase in median time from receipt in pathology to intraoperative diagnosis (20 vs 22 minutes, P = .008) in cases with intrapathology consultation but no change without consultation (median, 19 minutes). Intrapathology consultation decreased from 19.7% (317/1,607) to 11.5% (169/1,472) (P < .001). Discordance rates between frozen section and permanent section remained low and similar (2.0% [33/1,607] vs 2.7% [40/1,472], P = .24). There was no significant change in discordance with dedicated gastrointestinal subspecialty frozen section interpretation. CONCLUSIONS: Relocation of FSS and dedicated subspecialty interpretation may improve surgeon satisfaction but can also create workflow challenges. Pathology departments need to achieve a balance between satisfaction and adequacy to establish best frozen section coverage models.

Association of Intraoperative Frozen Section Controls With Improved Margin Assessment During Transoral Robotic Surgery for Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma.

Importance: Intraoperative margin assessment is an important technique for ensuring complete tumor resection in malignant cancers. However, in patients undergoing transoral robotic surgery (TORS) for oropharyngeal carcinomas, tissue artifact may provide pathologic uncertainty. Objective: To assess the benefit of providing frozen section control samples ("positive tumor biopsies") for use during intraoperative margin assessment for patients undergoing TORS for human papillomavirus (HPV)-16-positive oropharyngeal squamous cell carcinoma (OPSCC). Design, Setting, and Participants: In this cohort study, patients receiving curative-intent TORS for biopsy-proven HPV-16-positive OPSCC performed by a single attending surgeon (A.H.M.) at Ronald Reagan UCLA Medical Center from 2017 to 2021 were included in a retrospective data analysis. Exclusion criteria included HPV-negative status, participation in clinical trials, and tumors of unknown primary origin. Main Outcomes and Measures: Survival outcomes investigated included overall and disease-free survival. Adverse pathologic outcomes measured included occurrence of nondiagnostic margins and margin reversal from frozen to fixed pathology. Results: Of the 170 patients included (mean [SD] age, 61.8 [9.9] years; 140 [82%] male), 50% of patients (n = 85) received a frozen section control. Use of a frozen section control was associated with statistically significantly improved sensitivity of intraoperative margin assessment, from 82.8% to 88.9% (difference, 6.1%; 95% CI, 3.9%-8.3%). Eleven percent (n = 18) of all tumors evaluated exhibited at least 1 nondiagnostic intraoperative margin, and 11% (n = 18) experienced margin reversal from frozen to fixed pathology. In patients with nondiagnostic margins, use of frozen section controls was associated with statistically significantly reduced time spent in the operating room (Cohen d, 1.14; 95% CI, 0.12-2.14). Conclusions and Relevance: In this cohort study, frozen intraoperative margins assessed during TORS resections of HPV-16-positive OPSCC were diagnostically challenging. Adverse pathologic outcomes, such as margin status reversal from positive on frozen pathology to negative on formal analysis, were common. Providing intraoperative frozen section control biopsies may offer clarity in cases with nondiagnostic margins, reducing the need for additional sampling and time spent in the operating room.

Intraoperative assessment of surgical margins using "en face" frozen sections in the management of cutaneous carcinomas.

BACKGROUND: Basal cell and squamous cell carcinomas (BCC and SCC) are the most common types of cancer worldwide. Intraoperative assessment of surgical margins by frozen section has been widely used to ensure disease-free margins. The intraoperative "en face" freezing technique evaluates all peripheral and deep margins. OBJECTIVE: To report the results of the "en face" freezing technique in relation to tumor recurrence and agreement with paraffin-embedded tissue examination. METHODS: Retrospective analysis of patients undergoing surgical excision of BCC and SCC at the A. C. Camargo Cancer Center, Brazil. RESULTS: This study included 542 skin carcinomas, which were excised from 397 patients. A total of 201 male patients (50.6%), and 196 female patients (49.4%) were assessed, whose mean age was 64 years. The tumors were mostly located on the head and neck region (87.8%). BCC corresponded to 79.7% of the cases. The mean follow-up was 38 months. Tumor relapse occurred in 0.86% of the primary tumors and 3.7% of recurrent tumors. The result of the intraoperative "en face" frozen section evaluation was in agreement with the final result of the anatomopathological examination (paraffin test) in 98% of the lesions. STUDY LIMITATIONS: Not having a minimum follow-up time of 5 years for all patients. CONCLUSION: The "en face" freezing technique shows low tumor relapse, being reliable and safe to guarantee negative surgical margins of the tumor.

Cost-Effectiveness Analysis of Intraoperative Frozen Section in Women with Breast Cancer: Evidence from South of Iran.

Background: Breast cancer is one of the most prevalent malignancies in women worldwide, and the rate of breast cancer is increasing among Iranian women. The purpose of this study is to determine the cost-effectiveness of intraoperative frozen section analysis in women with breast cancer. Methods: This study was a cost-effectiveness analysis, which was implemented as a cross-sectional study from a societal perspective. In this case, total direct and indirect costs were calculated, and the study outcome was involved in preventing reoperation. A data collection form has been used to collect the cost and effectiveness data. The sample size was comprised of all the patients referred to the hospitals of Shiraz University of Medical Sciences for breast cancer surgery in 2019. The patients were studied in two different groups, including individuals who received frozen counseling during surgery, and individuals who did not receive it. A one-way sensitivity analysis was performed for this case. Moreover, the Tree Age and Microsoft Excel Software were employed for analyzing processes. Results: The results demonstrated that the mean costs of frozen and non-frozen patients were 4168$ and 3843$ purchasing power parity (PPP), respectively. In addition, the effectivenesses were 0.996 for the former and 0.8 for the latter. Furthermore, the incremental cost-effectiveness ratio (ICER) was 1658.2 PPP$. This issue revealed that the frozen section procedure during surgery was more cost-effective than the other case. Because, the cost-effectiveness of this option was below the threshold. Besides, the one-way sensitivity analysis confirmed the robustness of the study results. Conclusion: The results showed that performing frozen sections during surgery in women with breast cancer was more cost-effective than ignoring them. Indeed, the frozen section can prevent the costs of subsequent reoperations.

Upper Tract Urinary Cancer Recurrence after Radical Cystectomy: Risk Assessment of Intraoperative Frozen Section.

INTRODUCTION: Upper tract urinary cancer recurrence (UTUCR) after radical cystectomy (RC) is outcome-limiting. Surgical recommendations on intraoperative performance of frozen section analysis (FSA) and management of positive ureteral margin (PUM) are lacking. METHODS: 634 RC cases were identified (2010-2018). In patients with PUM, sequential ureteral resections up to a negative margin were performed. We investigated the accuracy of FSA, significance of PUM, and identified risk factors (RFs) to stratify patients for UTUCR. RESULTS: FSA was performed in 355 patients, including a total of 693 ureters. FSA sensitivity was 0.93 and specificity 0.99. PUM conversion was possible in 52 (91.2%) cases. UTUCR occurred in 17 (4.8%) patients. Identified UTUCR RFs are non-muscle invasive bladder carcinoma (NMIBC) (OR 3.8, 95% confidence intervals [CI] 1.4-10.2, p = 0.008), multifocal bladder cancer in cystectomy specimen (OR 4.7, CI 1.1-20.8, p = 0.042), and recurrent NMIBC (OR 4.1, CI 1.5-10.9, p = 0.006). Risk-group stratification showed a six-fold increase in UTUCR risk (low-to high-risk). CONCLUSION: FSA is a sensitive and specific method to identify PUM. UTUCR occurs significantly more often in patients with recurrent, multifocal NMIBC at the time of RC. Patients can be risk stratified for UTUCR. In case of NMIBC-PUM, surgeons can safely opt for a kidney preserving strategy.

Assessment of the feasibility of frozen sections for the detection of spread through air spaces (STAS) in pulmonary adenocarcinoma.

Spread through air spaces (STAS) is reportedly associated with worse prognosis in sublobar resections of lung adenocarcinoma. Recently, it was proposed that STAS detected on frozen sections can be an indication for lobectomy instead of sublobar resection. We undertook this study to evaluate the reliability of STAS assessment on frozen sections compared to permanent sections, as well as the associations among STAS, tumor grade, and recurrence-free survival (RFS) after sublobar resection. A total of 163 stage I lung adenocarcinoma resections with frozen sections were identified retrospectively. For each case, and for frozen and permanent sections separately, the presence or absence of STAS, as well as the tumor grade, were recorded. Compared to permanent sections, STAS detection on frozen sections had low sensitivity (55%), low positive predictive value (48%), and fair agreement (K = 0.34), whereas there was higher specificity (80%) and negative predictive value (85%). Accuracy was 74%. Tumor grade assessment on frozen sections showed higher sensitivity (77%), positive predictive value (90%), agreement (K = 0.72), specificity (94%), and accuracy (87%), and the same negative predictive value (85%). High-grade histology on frozen sections was associated with shorter RFS (p = 0.02), whereas STAS on frozen sections was not (p = 0.47). Our results suggest that the intraoperative detection of STAS has low sensitivity and positive predictive value. False-positive results may lead to overtreatment of patients with lung cancer. The determination of tumor grade on frozen sections offers better sensitivity and specificity, plus it is associated with RFS, whereas STAS on frozen sections is not. Further study is needed to explore the utility of assessing tumor grade on frozen sections.

Performance and survival outcomes of defect-driven versus specimen-driven method of frozen section intraoperative margin assessment in oral cancers.

Margin status is one of the most important prognostic factors in oral cancers. Intraoperative frozen section (FS) can be performed to ensure a margin-negative resection, however the method of FS assessment is debatable. The aim of this study was to compare the defect-driven (DDA) versus specimen-driven (SDA) approach for intraoperative assessment of tumour margins in oral cancer resections and their impact on loco-regional recurrence and survival. The primary study endpoint was margin status determined from the final histopathological examination report. Secondary endpoints were disease recurrence and survival. This retrospective cohort study compared the two methods of FS in terms of their performance and survival outcomes. All oral squamous cell carcinoma patients who underwent surgery as the primary treatment from January 2018 to February 2019 were included. The involved margin rate was slightly lower with SDA than DDA (7.5% vs 11.8%), however the difference was not statistically significant. The recurrence rate was higher with DDA (19/51, 37.2%) than SDA (14/53, 26.4%), although this was not statistically significant. Local recurrence-free survival (DDA 62% vs SDA 75%; P = 0.653) and overall survival (DDA 76% vs SDA 78%; P = 0.300) at 18 months of follow-up were comparable. There was no significant difference in sensitivity or specificity of intraoperative FS for margin assessment between SDA and DDA. The type of intraoperative FS technique used did not affect loco-regional recurrence or overall survival.