Intraoperative Pathological Assessment Research Articles

Sentinel lymph node pathological ultrastaging: Final outcome of the Sentix prospective international study in patients with early-stage cervical cancer

ObjectiveTo report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs. MethodsEligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-μm intervals/levels). SLNs from each site were submitted for central quality control. ResultsIn the SENTIX SLN study, 647 out of 733 enrolled patients underwent SLN ultrastaging, identifying 12.5% (81/647) with node positive, N1 cases. Intraoperative detection revealed metastases in 56.8% (46/81) of these cases, categorized into macrometastases (83.7%), micrometastases (26.3%), and isolated tumor cells (9.1%). Ultrastaging identified additional metastatic involvement in 43.2% (35/81) of patients, with detailed sectioning revealing metastases (MAC/MIC) at first level in 20 cases (24.7%), at levels 2–4 in 9 cases (11.1%), and at level ≥5 in 6 cases (7.4%). ConclusionSLN ultrastaging detects additional 43% of N1 (MAC/MIC) in patients with negative LNs by imaging and intraoperative pathological assessment. The detection rate of positive SLN correlates with the intensity (number of levels) of ultrastaging. Examination of four levels from paraffin blocks, which detects >90% of patients with N1, is a reasonable compromise for an international standard for ultrastaging.Study registration:NCT02494063 (ClinicalTrials.gov).

ASO Visual Abstract: Intraoperative Pathology Assessment May Lead to Overtreatment of the Axilla in Clinically Node-Negative Breast Cancer Patients Undergoing Upfront Mastectomy.

ASO Visual Abstract: Intraoperative Pathology Assessment May Lead to Overtreatment of the Axilla in Clinically Node-Negative Breast Cancer Patients Undergoing Upfront Mastectomy.

Intraoperative Pathology Assessment May Lead to Overtreatment of the Axilla in Clinically Node-Negative Breast Cancer Patients Undergoing Upfront Mastectomy.

Randomized trials have established the safety of observation or axillary radiation (AxRT) as an alternative to axillary lymph node dissection (ALND) in patients with limited nodal disease who undergo upfront surgery. Variability remains in axillary management strategies in cN0 patients undergoing mastectomy found to have one to two positive sentinel lymph nodes (SLNs). We examined the impact of intraoperative pathology assessment in axillary management in a national cohort of AMAROS-eligible mastectomy patients. The National Cancer Database was used to identify AMAROS-eligible cT1-2N0 breast cancer patients undergoing upfront mastectomy and SLN biopsy (SLNB) and found to have one to two positive SLNs, from 2018 to 2019. We constructed a variable defining intraoperative pathology as 'not performed/not acted on' if ALND was either not performed or performed at a later date than SLNB, or 'performed/acted on' if SLNB and ALND were completed on the same day. Adjusted multivariable analysis examined predictors of treatment with both ALND and AxRT. Overall, 8222 patients with cT1-2N0 disease underwent upfront mastectomy and had one to two positive SLNs. Intraoperative pathology was performed/acted on in 3057 (37.2%) patients. These patients were significantly more likely to have both ALND and AxRT than those without intraoperative pathology (41.0% vs. 4.9%; p<0.001). On multivariate analysis, the strongest predictor of receiving both ALND and AxRT was use of intraoperative pathology (odds ratio 8.99, 95% confidence interval 7.70-10.5; p<0.001). We advocate that consideration should be made for omission of routine intraoperative pathology in mastectomy patients likely to be recommended postmastectomy radiation to minimize axillary overtreatment with both ALND and AxRT in appropriate patients.

Intraoperative surgical margin evaluation using macroscopic pathological examination in breast cancer patients undergoing primary breast-conserving surgery

Background: Worldwide, nearly 20% of breast cancer (BC) women treated by breast-conserving surgery (BCS) need reoperation because of positive margins at final pathology. Intraoperative margin assessment techniques have been developed to improve the real-time assessment of tumor margins during BCS. In our hospital practice, the intraoperative pathologic assessment with macroscopic (gross) pathologic margin evaluation of all lumpectomy specimens is a routine. The study aims were to evaluate the accuracy of intraoperative macroscopic pathological margin evaluation (IMPME) in BC patients treated by BCS and to evaluate the rate of perioperative and secondary margin re-excision.

Radiofrequency spectroscopy with intraoperative pathological assessment for breast carcinoma: synergistic or redundant?

ABSTRACT Background Published MarginProbe (Dune Medical Devices Ltd., Israel) data reports ≥50% reduction in positive lumpectomy margins. We sought to determine whether adjunctive use of MarginProbe would provide value over intraoperative pathologic assessment alone. Methods This is a retrospective chart review of 86 consecutive lumpectomies with MarginProbe from December 2018 to November 2019. Margins were considered positive using ‘no ink on tumor’ guideline for invasive cancer, and 2 mm or greater for ductal carcinoma in-situ. Significance was measured using Fisher’s exact test. Results Seventy-six patients yielded 86 lumpectomies for inclusion. Mean age was 69.8 and mean tumor size was 1.09 cm. Sixty-eight invasive cancers were assessed using adjunct MarginProbe and gross assessment, while 18 ductal carcinoma in-situ cases utilized MarginProbe only. Among all cases, gross assessment alone reduced positive margins(29.2% relative reduction, p = 0.28). Utilizing both modalities, positive margins decreased from 27.9% to 9.3% (66.7% relative reduction, p < 0.01) representing a 46.9% relative reduction versus gross assessment alone. After gross assessment and MarginProbe evaluation, additional excised volume averaged 2.9 cc. Conclusions Synergistic use of MarginProbe and gross assessment reduces positive margins during breast conserving surgery. Surgeons can weigh its cost against it benefit with the succinct analysis we provide.

A Descriptive Analysis of Occult Gynecologic Malignancy in a Large Series of Supracervical Hysterectomy with Sacrocolpopexy

<h3>Study Objective</h3> The incidence of occult malignancy in patients with pelvic organ prolapse (POP) undergoing a supracervical hysterectomy (SCH) at the time of robotic-assisted laparoscopic sacrocolpopexy (RA-SCP) is not well documented in the medical literature. This has clinical implications as discovery would entail further operative management to perform staging, remove oncologic burden, and possibly revise the approach to pelvic reconstructive surgery. This study aims to detect the prevalence of oncologic pathology and ability of diagnostic preoperative work-up to detect such disease. <h3>Design</h3> Retrospective descriptive analysis. <h3>Setting</h3> University-affiliated community hospital. <h3>Patients or Participants</h3> All women undergoing a RA-SCP with SCH by one surgeon between March 2017 and March 2020 without symptoms of abnormal or postmenopausal bleeding. <h3>Interventions</h3> N/A. <h3>Measurements and Main Results</h3> A total of 425 women were included in this study. Of these, 19 (4.2%) patients were found to have uterine pathology of either pre-malignancy (n=14, 3.5%) or malignancy (n=5, 1.2%). Transvaginal ultrasonography (TVUS) had lower cases of missing pathology compared to EMB in the case of endometrial cancer (EC) (0% vs. 1.2%), endometrial hyperplasia +/- atypia (EH) (2.4% vs. 3%), or in combination EC and EH (2.4% vs 4.2%). EC and EH collectively were undiagnosed by either TVUS or EMB until final pathology in 4.2% of cases. <h3>Conclusion</h3> A small subset of asymptomatic postmenopausal women who undergo a SCH at the time of RA-SCP for POP will have underlying gynecologic malignancy or premalignant conditions. EMB or TVUS in these patients have inadequate sensitivity to rule out endometrial pathology and patients should be counseled appropriately regarding the small but possible necessity to remove the cervix in its entirety. Patients may be offered an intraoperative pathology assessment of the SCH prior to attachment of SCP mesh material to the cervix when appropriate.

A pre-screening strategy to assess resected tumor margins by imaging cytoplasmic viscosity and hypoxia.

To assure complete tumor removal, frozen section analysis is the most common procedure for intraoperative pathological assessment of resected tumor margins. However, during one operation, multiple biopsies may be sent for examination, but only few of them are made into cryosections because of the complex preparation protocols and time-consuming pathological analysis, which potentially increases the risk of overlooking tumor involvement. Here, we propose a fluorescence-based pre-screening strategy that allows high-throughput, convenient, and fast gross assessment of resected tumor margins. A dual-activatable cationic fluorescent molecular rotor was developed to specifically illuminate live tumor cells' cytoplasm by emitting two different fluorescence signals in response to elevations in hypoxia-induced nitroreductase (a biochemical marker) and cytoplasmic viscosity (a biophysical marker), two characteristics of cancer cells. The ability of the fluorescent molecular rotor in detecting tumor cells was evaluated in mouse and human specimens of multiple tissues by comparing with hematoxylin and eosin staining. Importantly, the fluorescent molecular rotor achieved 100 % specificity in discriminating lung and liver cancers from normal tissue, allowing pre-screening of the tumor-free surgical margins and promoting clinical decision. Altogether, this type of fluorescent molecular rotor and the proposed strategy may serve as a new option to facilitate intraoperative assessment of resected tumor margins.

Deep learning enables ultraviolet photoacoustic microscopy based histological imaging with near real-time virtual staining

Histological images can reveal rich cellular information of tissue sections, which are widely used by pathologists in disease diagnosis. However, the gold standard for histopathological examination is based on thin sections on slides, which involves inevitable time-consuming and labor-intensive tissue processing steps, hindering the possibility of intraoperative pathological assessment of the precious patient specimens. Here, by incorporating ultraviolet photoacoustic microscopy (UV-PAM) with deep learning, we show a rapid and label-free histological imaging method that can generate virtually stained histological images (termed Deep-PAM) for both thin sections and thick fresh tissue specimens. With the tissue non-destructive nature of UV-PAM, the imaged intact specimens can be reused for other ancillary tests. We demonstrated Deep-PAM on various tissue preparation protocols, including formalin-fixation and paraffin-embedding sections (7-µm thick) and frozen sections (7-µm thick) in traditional histology, and rapid assessment of intact fresh tissue (~ 2-mm thick, within 15 min for a tissue with a surface area of 5 mm × 5 mm). Deep-PAM potentially serves as a comprehensive histological imaging method that can be simultaneously applied in preoperative, intraoperative, and postoperative disease diagnosis.

Unplanned excision of soft tissue sarcoma: does it impact the accuracy of intra-operative pathologic assessment at time of re-excision?

An "unplanned excision" refers to soft tissue sarcomas excised without planning imaging studies and a diagnostic biopsy, resulting in the presence of residual disease and usually necessitating a re-excision procedure.We aimed to assess the impact of previous unplanned excisions on the intra-operative pathologic assessment at the time of re-excision, in terms of need to perform repeat assessments and the accuracy to predict margin status of the final pathologic specimen. Data was collected for all patients with extremity soft tissue sarcoma who had undergone wide local excision limb salvage surgery or amputation between 2012 and 2017. Intra-operative pathologic assessment with frozen sections was performed in all cases and was classified as negative, negative but close (< 1mm), and positive. A total of 173 patients with extremity soft tissue sarcoma were included, 54 in the unplanned excision group and 119 in the planned excision group. The accuracy of intra-operative pathologic assessment to predict the margin status on final pathology was similar between groups (87% unplanned vs. 90.7% planned excisions). However, the need for repeat intra-operative pathologic assessment and subsequent resection due to microscopically positive margins was found to be higher within the unplanned excision group ((p = 0.04), OR = 3.2 (95% CI: 1.1-9.1, p = 0.048)). Intra-operative pathologic assessment of resection margins had a similar accuracy in planned and unplanned excisions; however, unplanned excisions showed a higher risk of re-resection during the same surgical setting.

Is subareolar intraoperative biopsy still necessary to predict nipple involvement

To predict the occult tumor involvement of nipple-areola complex (NAC) using preoperative MR imaging and to investigate whether the intraoperative histopathological examination of the subareolar tissue is still necessary. Out of 712 patients submitted to nipple-sparing mastectomy (NSM) between 2014 and 2019, we selected 188 patients who underwent preoperative breast MRI. Breast MRI and intraoperative histopathological examination of the subareolar tissue were performed to predict NAC involvement at permanent pathology. All parameters were correlated with final pathological NAC assessment by univariate and multivariate analysis. Forty-three patients (22.9%) had tumor involvement of the NAC. At univariate analysis, non-mass enhancement type (p = 0.009), multifocality/multicentricity (p = 0.002), median tumor size (p < 0.001), median tumor-NAC distance measured by MRI (p < 0.001), tumor-NAC distance ≤ 10 mm (p < 0.001) and tumor-NAC distance ≤ 20 mm (p < 0.001), and lymphovascular invasion (p = 0.001) were significantly correlated with NAC involvement. At multivariate analysis, only tumor-NAC distance ≤ 10 mm retained statistical significance. The sensitivity and specificity of MRI tumor-NAC distance ≤ 10 mm were 79.1% and 97.2% and those of intraoperative pathologic assessment were 74,4% and 100%, respectively. Tumor-NAC distance is the only reliable MRI characteristic that can predict NAC involvement in breast cancer patients. Although several cut-offs showed promising performances, intraoperative pathologic assessment is still mandatory.

Selective sentinel lymph node biopsy in squamous vulvar cancer. Ten-year follow-up analysis

AimApplication of sentinel lymph node biopsy (SLNB) procedure in early-stage vulvar cancer and analysis of results, recurrences and complications. Material and methods40 patients with vulvar cancer and SLNB between 2008 and 2018 were retrospectively reviewed. During the surgical procedure the inguinofemoral lymph nodes were checked with a gamma probe to identify the sentinel nodes that were removed and referred for intraoperative pathological assessment. Subsequently, long-term patient follow-up was performed with analysis of complications, relapse and mortality. Results40 patients (mean age: 72 years [47–86]), the overall detection rate per patient was 95% and a total of 129 sentinel lymph nodes (SLNs) were removed (3.22SLN/patient). In 3 out of 25 patients with lateral tumor lesions drainage was bilateral and in 2 out of 15 with midline lesions drainage was unilateral. On lymphoscintigraphy, 16 out of 40 had bilateral drainage and 24 unilateral. A total of 119 SLN− and 10 SLN+ were obtained, in 8 out of 10 an inguinofemoral lymphadenectomy was performed. In the SLN− group, one case of lymphatic blockage and one false negative were included. In 12 out of 40 patients there were post-surgical complications, 4 of them lymphoedemas. In the median follow-up (40 months), 6 out of 10 with SLN+ (40% mortality) and 7 out of 30 SLN− (16% mortality) had recurrences. ConclusionsSLNB in vulvar cancer is the technique of choice for correct staging and locoregional therapy. Correct clinical lymph node staging is important before surgery in order to avoid potential blockage drainages which could induce a false negative SLN.

Biopsia selectiva de ganglio centinela en el carcinoma escamoso de vulva. Análisis de seguimiento a 10 años

AimApplication of sentinel lymph node biopsy (SLNB) procedure in early-stage vulvar cancer and analysis of results, recurrences and complications. Material and methods40 patients with vulvar cancer and SLNB between 2008 and 2018 were retrospectively reviewed. During the surgical procedure the inguinofemoral lymph nodes were checked with a gamma probe to identify the sentinel nodes that were removed and referred for intraoperative pathological assessment. Subsequently, long-term patient follow-up was performed with analysis of complications, relapse and mortality. Results40 patients (mean age: 72 years [47-86], the overall detection rate per patient was 95% and a total of 129 Sentinel Lymph Nodes (SLNs) were removed (3.22 SLN/patient). In 3 out of 25 patients with lateral tumour lesions drainage was bilateral and in 2 out of 15 with midline lesions drainage was unilateral. On lymphoscintigraphy, 16 out of 40 had bilateral drainage and 24 unilateral. A total of 119 SLN- and 10 SLN+ were obtained, in 8 out of 10 an inguinofemoral lymphadenectomy was performed. In the SLN- group, one case of lymphatic blockage and one false negative were included. In 12 out of 40 patients there were post-surgical complications, 4 of them lymphoedemas. In the median follow-up (40 months), 6 out of 10 with SLN+ (40% mortality) and 7 out of 30 SLN- (16% mortality) had recurrences. ConclusionsSLNB in vulvar cancer is the technique of choice for correct staging and locoregional therapy. Correct clinical lymph node staging is important before surgery in order to avoid potential blockage drainages which could induce a false negative SLN.

Impact of sentinel lymph node frozen section evaluation to avoid combined treatment in early-stage cervical cancer

BackgroundThe need for radical surgery followed by adjuvant chemoradiation may be reduced by abandoning radical surgery in patients in whom lymph node involvement is detected intra-operatively.ObjectivesTo analyze, in a retrospective...

Direct intraoperative assessment of total mesorectal excision specimens by expert pathologists in patients with very low rectal cancer prevents unnecessary abdominoperineal resections

In patients with low rectal cancer, the intraoperative assessment of sufficient distal resection margins can be challenging. The assessment determines whether reconstruction can be performed or whether permanent colostomy is required. The goal of the present study was to evaluate intraoperative assessment of the total mesorectal excision (TME) specimen during an interruption of the operation. The intraoperative strategy of eight patients with low rectal cancer was evaluated. In all cases, intraoperative pathological assessment of the TME specimen by an expert pathologist together with the surgeon was performed. Assessment of the distance of the tumor to the resection margin was measured macroscopically as well as microscopically. All patients underwent neoadjuvant chemoradiation. The tumor was located at an average 4.8 ± 1.4cm from the anal verge. In all cases, preoperative MRI revealed mrT3 tumors. The intraoperative assessment showed a median distal resection margin of 10mm (2-15mm). In six patients, sufficient margins allowed for reconstruction while in two patients APR was needed. In three patients (37.5%), the pathological assessment changed the operative strategy: In one patient APR could be avoided while two patients required APR instead of the anticipated TME. The intraoperative assessment of the TME specimen by an expert pathologist together with the surgeon is a valuable tool to avoid unnecessary APR or R1 resections. We therefore suggest routine intraoperative pathological assessment in all operations for borderline low rectal cancers.

Evaluation of Role of Intraoperative Cytology Technique in Diagnosis and Management of Cancer.

Context:Intraoperative pathological assessment provides valuable information in a patient's diagnosis and management. Touch imprint/crush cytology is simple, rapid, and cost-effective. Also, imprint smears give excellent cytomorphology.Aims:To assess the utility and feasibility of intraoperative cytology technique as a rapid and reliable method for diagnosis and to compare sensitivity, specificity and diagnostic accuracy with histopathology.Materials and Methods:Cytology smears were collected intraoperatively from 52 cases of suspected/proven malignancy. From tumors, surgical margins, lymph nodes; crush, imprint, and scrape smears were prepared. Smears were taken from specimens before formalin fixation and stained with rapid ultrafast Papanicolaou stain. The slides were compared with the histopathology report which is the gold standard.Statistical Analysis:Sensitivity, specificity, and diagnostic accuracy were used for statistical analysis.Results:Intraoperative cytology report could be given in time for the surgeon to modify margins of resection and the extent of lymph node dissection. It helps the surgeon to modify surgery. The diagnostic test evaluation showed satisfactory results.Conclusion:Intraoperative imprint/crush cytology is a simple, inexpensive, rapid, accurate cytodiagnostic technique in the diagnosis of cancer where frozen section facilities are not available. It can also be used to assess the clearance of surgical margins.

Perioperative assessment of myometrial invasion in patients with endometrial cancer – comparison of the accuracy of magnetic resonance imaging and intraoperative pathological assessment

Perioperative assessment of myometrial invasion in patients with endometrial cancer – comparison of the accuracy of magnetic resonance imaging and intraoperative pathological assessment

Oncologic outcome after completing or abandoning (radical) hysterectomy in patients with cervical cancer and intraoperative detection of lymph node positivity; ABRAX (ABandoning RAd hyst in cerviX cancer)

BackgroundThe management of patients with intraoperative detection of lymph node involvement remains controversial. The most significant aspect is the decision regarding the completion of the cervical procedure, such as hysterectomy,...

Factors Associated with Reoperation in Breast-Conserving Surgery for Cancer: A Prospective Study of American Society of Breast Surgeon Members

BackgroundMore than 20% of patients undergoing initial breast-conserving surgery (BCS) for cancer require reoperation. To address this concern, the American Society of Breast Surgeons (ASBrS) endorsed 10 processes of care (tools) in 2015 to be considered by surgeons to de-escalate reoperations. In a planned follow-up, we sought to determine which tools were associated with fewer reoperations.MethodsA cohort of ASBrS member surgeons prospectively entered data into the ASBrS Mastery® registry on consecutive patients undergoing BCS in 2017. The association between tools and reoperations was estimated via multivariate and hierarchical ranking analyses.ResultsSeventy-one surgeons reported reoperations in 486 (12.3%) of 3954 cases (mean 12.7% [standard deviation (SD) 7.7%], median 11.5% [range 0–32%]). There was an eightfold difference between surgeons in the 10th and 90th percentile performance groups. Actionable factors associated with fewer reoperations included routine planned cavity side-wall shaves, surgeon use of ultrasound (US), neoadjuvant chemotherapy, intra-operative pathologic margin assessment, and use of a pre-operative diagnostic imaging modality beyond conventional 2D mammography. For patients with invasive cancer, ≥ 24% of those who underwent reexcision did so for reported margins of < 1 or 2 mm, representing noncompliance with the SSO-ASTRO margin guideline.ConclusionsAlthough ASBrS member surgeons had some of the lowest rates of reoperation reported in any registry, significant intersurgeon variability persisted. Further efforts to lower rates are therefore warranted. Opportunities to do so were identified by adopting those processes of care, including improved compliance with the SSO-ASTRO margin guideline, which were associated with fewer reoperations.

Intraoperative palpation of sentinel lymph nodes can accurately predict axilla in early breast cancer.

Recent randomized trials have shown that completion axillary lymph node dissection (ALND) is not required in all patients with a positive sentinel lymph node (SLN) who will receive radiation therapy. Although routine intraoperative pathologic assessment (IPA) becomes unnecessary and less indicated by breast surgeons in the United States and some European countries, it is still widely used all around the world. In this prospective study, the feasibility of intraoperative nodal palpation (INP) as opposed to IPA of the SLN has been analyzed. Between March 2014 and June 2015, 305 patients with clinical T1-2/N0 breast cancer from two different breast clinics (cohort A; [n=225] and cohort B; [n=80]) who underwent any breast surgery with sentinel lymph node biopsy (SLNB) were included in this study. Surgeons evaluated the SLNs by manual palpation before sending for IPA, and findings compared with the final pathology. The positive predictive values (PPV) of INP and IPA were 81.8% and 97.9%, respectively, whereas the negative predictive values (NPV) of INP and IPA were 83% and 92.4%. The accuracies of INP and IPA were 82.6% and 94.1%, respectively. If patients with SLNB including micrometastasis were also considered in the final pathologic assessment (FPA) (-) group that would not require a further axillary dissection, the revised NPV of INP and FPA were found to be 92.6% and 98.1%, respectively. The revised accuracy of INP also found to be increase to 86.9%. Our study, which is the only prospective one about palpation of dissected SLNs in the literature, suggests that INP can help to identify patients who do not need ALND, which encourages omitting IPA in cT1-2N0 breast cancer.

Preoperative Sonographic Evaluation and Sampling of Axillary Lymph Nodes in Breast Cancer Patients: A Local Experience

Axillary ultrasound (US) is useful in the preoperative assessment of breast cancer patients. US-guided fine-needle aspiration (FNA) biopsy of pathological nodes avoids the need for a sentinel lymph node biopsy (SLNB). SLNB is more extensive, requiring nuclear medicine and intraoperative pathological assessment. We performed a retrospective chart audit to assess (1) the accuracy of local preoperative axillary node US interpretation and (2) the performance of US-guided axillary node FNA biopsies in the work-up of patients with breast cancer. Axillary metastases were detected preoperatively in 33 out of 81 patients (sensitivity = 40.7%). On pathology, 113 out of 124 patients with negative interpretations were truly negative (specificity = 91.1%). Sensitivity and specificity of FNA at our site is 89.7% and 55.6%, respectively. The results of this audit emphasize the continued need for adequate training in axillary node US interpretation.