Superficial Margin Research Articles

What’s behind Margin Status in Oral Cancer?

In the 2nd century AD, Galen argued that the failure to remove any single ‘root’ of a malignant tumor could result in a local relapse. After nearly 2 millennia, this problem appears to be even more challenging due to our increased understanding of the complexity of tumor formation and spread. Pathological analysis of tumor margins under a microscope remains the primary and only accepted method for confirming the complete tumor removal. However, this method is not an all-or-nothing test, and it can be compromised by various intrinsic and extrinsic limitations. Among the intrinsic limitations of pathological analysis we recall the pathologist handling, tissue shrinkage, the detection of minimal residual disease and the persistence of a precancerous field. Extrinsic limitations relate to surgical tools and their thermal damage, the different kinds of surgical resections and frozen sections collection. Surgeons, as well as oncologists and radiotherapists, should be well aware of and deeply understand these limitations to avoid misinterpretation of margin status, which can have serious consequences. Meanwhile, new technologies such as Narrow band imaging have shown promising results in assisting with the achievement of clear superficial resection margins. More recently, emerging techniques like Raman spectroscopy and near-infrared fluorescence have shown potential as real-time guides for surgical resection.The aim of this narrative review is to provide valuable insights into the complex process of margin analysis and underscore the importance of interdisciplinary collaboration between pathologists, surgeons, oncologists, and radiotherapists to optimize patient outcomes in oral cancer surgery.

Pathology and resection margins following mastectomy prior to immediate breast reconstruction.

Risk of local recurrence (LR) (and even distant disease-free survival) after mastectomy is associated with margin status. Furthermore, the vast majority of LR are located at the anterior (superficial) margin. Margins in mastectomy are considered anatomical borders and not true resection margins; such a conception may erroneously lead to underestimation of the risk of LR after mastectomy. If dissection is accurate along the fascia, only skin, subcutaneous tissue and minimal residual breast gland tissue (rBGT) are expected to remain in the patient. However, the subcutaneous fascia is an inconsistent anatomical structure that may be absent in almost half of patients. Studies and routine clinical practice suggest that resection may frequently, though often focally, be within the breast glandular tissue leaving various amounts of rBGT. Such areas may be nidus for subsequent de novo or recurrent premalignant or malignant disease. There is no consensus on handling of close/positive margins and intervention is extrapolated from studies on breast conserving surgery with subsequent radiotherapy. Handling of a close/positive margin is complicated by poor correlation between the ex vivo findings on the specimen and the attempt to relocate the area of concern in a patient with reconstructed breasts. In this clinical practice review, we strongly advocate for reporting of the lesion-to-margin distance in mastectomies to collect further evidence on the association between LR and margin status.

292 Intraoperative Confocal Laser Endomicroscopy During 5-ALA Guided Glioma Surgery: Significant Considerations for Resection at the Tumor Margins

INTRODUCTION: Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) has proven effective in aiding the detection of glioma marginal zones and enhancing maximal safe resection. FDA-cleared confocal laser endomicroscopy is another imaging modality for intraoperative brain tissue discrimination on cellular level that could improve visualization at the glioma margin. METHODS: 5-ALA wide-field imaging and CLE were used in 9 patients with gliomas (6 enhancing, 3 non-enhancing). CLE imaging was enhanced by the use of a telesurgical pathology software platform to enable real-time conversation between neurosurgeons and pathologists located remotely. CLE was used for imaging tumor regions subjectively regarded as tumor margins under normal visualization with the operative microscope. After CLE imaging, 5-ALA wide-field imaging was performed in the same regions. A tissue was harvested at imaging locations, and interpretations of CLE and 5-ALA wide-field imaging were compared to permanent histological sections. RESULTS: Overall, 20 deep and superficial margin regions of interest (ROI) were imaged with CLE and 5-ALA imaging. Most of the ROIs interpreted by the neuropathologist as infiltrative glioma based on CLE imaging lacked 5-ALA-induced fluorescence. Permanent histological sections from the corresponding regions were concordant with the interpretation of CLE images in 15 of 20 (75%) ROIs and with the interpretation of 5-ALA imaging in 11 of 20 (55%) ROIs. Sensitivity/specificity of CLE and 5-ALA for interpretation of tumor margins were 79%/67%, and 50%/67%, respectively. Positive/negative predictive values for CLE and 5-ALA were 85%/57%, and 78%/37%, respectively. CONCLUSIONS: Conventional intraoperative understanding of tumor margins based on wide-field fluorescence could underestimate the invasiveness of gliomas. The ongoing study demonstrates that CLE shows higher accuracy in detecting regions with infiltrating tumor than intraoperative 5-ALA imaging.

High-resolution intraoperative infrared thermography for the functional imaging and tumor resection maximization of a low-grade glioma: Technical case report

Currently, it is widely recognized the role of the extent of resection on overall and progression-free survival for gliomas surgery. Brain mapping and intraoperative image guidance are generally required to attain such an objective. Infrared Thermography (IRT) has a potential role in the identification of surgical margins, but it has not been consistently assessed in the literature. We aim to demonstrate the use of intraoperative IRT to detect superficial and deep tumoral margins of low-grade glioma, to identify adjacent functional motor cortex, and to maximize surgical resection in a 45-year-old lady with a long history of partial and secondary generalization seizures.

Radial resection margin distinguishes between superficial versus deep resection in colorectal cancer: a retrospective study.

Randomized studies showed that robotic surgery was short-term useful and safe for cancer patients. We investigated whether robots improve deep resection margins or superficial resection margins for radial resection margins in terms of short-term results. From an institutional database, we selected all superficial groups (≤ 3mm) and deeper groups (≥ 4mm) with rectal cancer treated with resection for a year. We evaluated the short-term post-operative 90-day outcomes on a radial resection size-based margin differentiation, including the first bowel movement, length of hospital stay, sepsis, and harvested lymph node. The main results were grades III-IV on the Clavien-Dindo scale and complications. We found 120 patients who had oncologic resection of rectal cancer; 42 patients with a superficial radial resection margin of ≤ 3 mm, all the following outcomes improved: the harvested lymph node, proximal resection margin, TME, flatus time, liquid diet duration, anastomotic leakage, and sepsis. Among these advantages were a reduced risk of metastasis and an overall reduction in local recurrence.

Intraoperative ultrasound margin evaluation as a tool to reduce positive superficial margins in nipple and skin sparing mastectomy in breast cancer patients

BackgroundIntraoperative ultrasound (IOUS) guided conservative surgery has been shown to reduce rates of positive margins in breast cancer. The aim of the study is to evaluate the feasibility of using IOUS to assess superficial/anterior margins in nipple and skin sparing mastectomy (NSM/SSM) and its impact on reducing rates of positive margins. MethodsThis prospective study includes all breast cancer patients who had an indication for NSM/SSM at our Institution. Superficial margin width was measured by IOUS before surgery and the area marked on the skin. Same measurement was performed afterwards in the mastectomy specimen. Any superficial margin < 5 mm was re-excised intraoperatively following the mark on the skin. ResultsFifty-nine patients were included, 47 patients (79.7%) underwent NSM, and 12 patients (20.3%) a SSM. Of the 59 patients, 23 (38.98%) had margins ≥5 mm and 36 patients (61.02%) had margins of ≤5 mm. Of the 36 patients with superficial margins ≤5 mm, 20 had margins <2 mm, and 6 of them had intraoperative involved superficial margins in final pathology. However, after IOUS-guided re-excision, final pathology showed no involved margins. A 2 mm margin was set as the cut-off point for performing an intraoperative re-excision. IOUS guided re-excisions for intraoperative margins ≤2 mm significantly reduced the risk of close/positive margins in final pathology, p < 0.0001. ConclusionThe results showed that IOUS margin evaluation significantly reduced the rate of superficial positive margins in NSM/SSM. It is feasible and effective and may avoid challenging reoperations and/or additional radiation therapy for positive margins.

Risk of Tract Seeding Following Laser Interstitial Thermal Therapy for Brain Tumors.

The management of intracranial oncological disease remains a significant challenge despite advances in systemic cancer therapy. Laser interstitial thermal therapy (LITT) represents a novel treatment for local control of brain tumors through photocoagulation with a stereotactically implanted laser fiber. Because the use of laser interstitial thermal therapy continues to increase within neurosurgery, characterization of LITT is necessary to improve outcomes. To quantify the risk of tumor seeding along the laser fiber tract in patients receiving LITT for primary or metastatic brain tumors at a high-volume treatment center. We retrospectively reviewed all patients receiving LITT from 2015 to 2021 at our medical center. Patients with biopsy-confirmed tumors were included in this study. Tract seeding was identified as discontinuous, newly enhancing tumor along the LITT tract. Fifty-six patients received LITT for biopsy-confirmed tumors from 2015 to 2021, with tract seeding identified in 3 (5.4%). Twenty-nine (51.8%) patients had gliomas, while the remainder had metastases, of which lung was the most common histology (20 patients, 74%). Tract seeding was associated with ablation proceeding inward from superficial tumor margin closest to the cranial entry point ( P = .03). Patients with tract seeding had a shorter median time to progression of 1.1 (0.1-1.3) months vs 4.2 (2.2-8.6) months ( P = .03). Although the risk of tract seeding after LITT is reassuringly low, it is associated with decreased progression-free survival. This risk may be related to surgical technique or experience. Follow-up radiosurgery to the LITT tract has the potential to prevent this complication.

The use of intraoperative ultrasound reduces the risk of positive superficial margin in nipple and skin sparing mastectomy in breast cancer patients

The use of intraoperative ultrasound reduces the risk of positive superficial margin in nipple and skin sparing mastectomy in breast cancer patients

PERIOPERATIVE SMALL LUNG NODULE LOCALIZATION FOR MINIMALLY INVASIVE THORACIC SURGERY WITH AN ELECTROMAGNETIC NAVIGATIONAL SYSTEM

PERIOPERATIVE SMALL LUNG NODULE LOCALIZATION FOR MINIMALLY INVASIVE THORACIC SURGERY WITH AN ELECTROMAGNETIC NAVIGATIONAL SYSTEM

Image-guided surgery in oral cancer: toward improved margin control.

The aim of this review is to discuss recent studies on the assessment of tumor extension and resection margins by different intraoperative techniques allowing for image-guided surgery of oral cancer. There are different in-vivo and ex-vivo intraoperative techniques to improve margin control of which intraoperative ultrasound and targeted fluorescence-guided resections have high potential clinical value and are closest to clinical implementation. In oral cancer surgery, resection margins, particularly deep margins, are often inadequate. Intraoperative frozen section does not improve resection margin control sufficiently. Specimen-driven intraoperative assessment for gross analysis of suspected margins reduces the amount of positive resection margins substantially but leaves still room for improvement. Mucosal staining methods, optical coherence tomography and narrow band imaging can only be used for superficial (mucosal) resection margin control. Spectroscopy is under investigation, but clinical data are scarce. Intraoperative ex-vivo imaging of the resection specimen by magnetic resonance and PET/computed tomography may be used to assess resection margins but needs more research. Intraoperative in-vivo ad ex-vivo ultrasound and targeted fluorescence imaging have high potential clinical value to guide oral cancer resections and are closest to clinical implementation for improved margin control.

Intraoperative ultrasound to assess superficial margin in nipple and skin sparing mastectomy.

Background: Local recurrence after mastectomy is significantly based in biology and other features, including margin status. Patients with positive margins after nipple (NSM) or skin paring mastectomy (SSM) have an increased risk of local and/or distant recurrence. Identifying this positive superficial margin postoperatively can be challenging. Intraoperative ultrasound (IOUS) has been found to be an effective tool to evaluate margins intraoperatively in breast conserving surgery. The aim of this study is to evaluate the feasibility of IOUS in assessing superficial margins in NSM and SSM and its correlation with pathology.

Clinical Implication of the Regional Thickness of the Lower Facial Skin, Superficial Fat, and Superficial Musculoaponeurotic System on High-Intensity Focused Ultrasound Treatment.

Knowledge of the topographic thickness of the skin and soft tissues is necessary when performing a high-intensity focused ultrasound (HIFU) procedure. Thermal tissue injury to the superficial musculoaponeurotic system (SMAS) or deeper can injure the facial nerve and its branches. To demonstrate the topographic thickness of the lower facial skin, superficial fat, and SMAS. The ultrasound data of 200 healthy patients who underwent lower facial rejuvenation were retrospectively reviewed. The mean age was 41.1 ± 13.7 years (range, 19-76 years). The jowl had thinner skin, thicker superficial fat, and deeper superficial and deep margins of the SMAS than the preauricle or lower cheek. The thickness of the superficial fat decreased with age, especially on the preauricle, lower cheek, and jowl. Women had thicker superficial fat than men on the preauricle and lower cheek. The superficial and deep margins of the SMAS were located more superficially in old and male patients with a slim facial figure than in young and female patients with a chubby facial figure. The present findings provide anatomical information regarding the superficial fat and SMAS, which is useful in determining the focal penetration depth of HIFU treatment for lower face rejuvenation.

Comparison of Recurrence Rate Between Re-Excision With Radiotherapy and Radiotherapy-Only Groups in Surgical Margin Involvement of In Situ Carcinoma.

PurposeSurgical margin status is a surrogate marker for residual tumors after breast-conserving surgery (BCS). A comparison of ipsilateral breast tumor recurrence (IBTR) rates between re-excision combined with radiotherapy (excision with RTx) and RTx alone, following the confirmation of ductal carcinoma in situ (DCIS) in the resection margin after BCS, has not been reported previously. Therefore, in the present study, the clinical characteristics of DCIS involvement in the surgical resection margin between excision with RTx and RTx alone were investigated, and the IBTR rate was compared.MethodsWe analyzed 8,473 patients treated with BCS followed by RTx between January 2013 and December 2019. Patients were divided into 2 groups based on surgical resection margin status in permanent pathology, and superficial and deep margins were excluded. Patients who underwent re-excision with DCIS confirmed in the resection margin were identified and the IBTR rate was examined.ResultsAmong 8,473 patients treated with BCS, 494 (5.8%) had positive surgical resection margins. The median follow-up period was 47 months. Among the 494 patients with a positive resection margin, 368 (74.5%) had residual DCIS at the surgical resection margin in the final pathology. Among those with confirmed DCIS at the resection margin, 24 patients (6.5%) were re-excised, and 344 patients (93.5%) underwent RTx after observation. The IBTR rates were 4.2% and 1.2% in the re-excision and observation groups, respectively. IBTR-free survival analysis revealed no significant difference between the excision with RTx and RTx-only groups (p = 0.262).ConclusionThe IBTR rate did not differ between the excision with RTx and RTx-only groups when DCIS was confirmed at the resection margins. This suggests that RTx and close observation without re-excision could be an option, even in cases where minimal involvement of DCIS is confirmed on surgical resection.

Superficial margins in skin sparing and nipple sparing mastectomies for DCIS: A margin of potential concern

Skin-sparing and nipple-sparing mastectomies with immediate reconstruction for breast cancer are increasing. The superficial fascia is considered a natural border and the superficial margin may not be evaluated. We emphasize the need for reporting of the superficial margin status in these procedures to obtain valid information on its association with local recurrence risks.

Introduction of a New Pathology Workup Protocol for Glottic Cancer Treated With Transoral Laser Microsurgery (TLM): Prospective Analysis of Oncological Outcomes and Matched Case-Control Study.

Background/PurposeThe value of margin status after TLM for glottic cancer is debatable, due to difficulties in specimen orientation and margin analysis. To reduce these difficulties, we recently introduced a standardized protocol of oriented fixation of TLM specimens. This proved feasible and resulted in high margin evaluability rates and a decreased rate of false positive deep margins, when compared to a historical TLM cohort. For the patients whose specimens were processed according to this protocol, we prospectively analyzed oncological outcomes, identified prognostic factors and assessed the influence of the protocol introduction on outcomes compared with a historical TLM cohort.MethodsNinety-six patients with glottic malignancies treated with TLM were included. Resection specimens were processed according to the new protocol. Descriptive statistics and survival analyses were used to determine oncological outcomes. To assess the effect of the protocol introduction on outcomes, a matched-case-control analysis was performed, using a historical TLM-cohort as controls. The Cox proportional hazards model was used to analyze prognostic effects of patient and treatment characteristics, including the pathology protocol introduction, on overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and local recurrence-free survival (LRFS).ResultsTwo-year outcomes were favorable: 88.5% OS, 97.0% DSS, and 87.6% LRFS. At multivariable analysis, the presence of multiple positive superficial margins was a negative prognosticator for OS (HR 4.102) and increasing cT classification proved a negative prognosticator for DFS (HR 2.828) and LRFS (HR 2.676). Matched case-control analysis did not reveal a significant difference in oncological outcomes between cohorts. Deep margin status had a strong differential effect for DFS (p-value for interaction = 0.0205) and for LRFS (p-value for interaction = 0.0176) between cohorts, indicating a prognostic effect of deep margin status on both outcomes in the current cohort, but not in the historical cohort.Discussion/ConclusionThe introduction of a new standardized technique of oriented fixation of TLM specimens did not affect oncological outcomes when compared to a historical TLM cohort, but assigned a significant prognostic effect to deep margin status for DFS and LRFS, facilitating the decision making process with regards to planning of second-look procedures, administration of adjuvant radiotherapy or determination of follow-up intensity.

Utility of photodynamic diagnosis plus reflectance confocal microscopy in detecting the margins of extramammary Paget disease.

Due to the clinically poorly delineated unclear margin of extramammary Paget disease, the recurrence rate after surgical resection is high. To compare photodynamic diagnosis and photodynamic plus reflectance confocal microscopy diagnosis in determining the tumor margins in patients with extramammary Paget disease. Thirty-six patients with histopathologically confirmed primary extramammary Paget disease between January 2017 to June 2018 were included in the study. The skin lesion margins were preoperatively observed by the naked eye and with photodynamic diagnosis and photodynamic diagnosis plus reflectance confocal microscopy and they were compared to the postoperative histopathological examination results. Among the 130 sections taken from 36 patients, 83 sections (63.8%, 83/130) had tumor margins beyond the macroscopic line with a distance of 3.5 ± 3.1mm and a median of 2.7mm. Forty-six sections (35.4%, 46/130) exceeded the photodynamic diagnosis marker line with a distance of 2.1 ± 1.7mm and a median of 1.5mm. Twenty seven sections (20.8%, 27/130) were obtained beyond the photodynamic diagnosis plus reflectance confocal microscopy marker line with a distance of 1.4 ± 1.2mm and a median of 0.9mm. Photodynamic diagnosis and reflectance confocal microscopy detection can be used to observe only the superficial margin of the tumor and not the deep part. Moreover, reflectance confocal microscopy was not used alone as a control. In terms of determining the extramammary Paget disease margin invasively, photodynamic diagnosis and photodynamic diagnosis plus reflectance confocal microscopy were found superior to observations made with the naked eye, while photodynamic diagnosis plus reflectance confocal microscopy was superior to photodynamic diagnosis alone.

Current indications for adjuvant treatment following transoral laser microsurgery of early and intermediate laryngeal cancer.

This review summarizes the information in the literature on the indications for adjuvant therapy after transoral laser microsurgery (TLM) for early/intermediate stage laryngeal cancer. A high rate of 'nonevaluable' margins after TLM significantly complicates decision-making concerning adjuvant therapy. However, consensus grows that second-look TLM in patients with multiple superficial and deep positive margins is more sensible than sending these patients systematically for adjuvant radiotherapy (RT). The classical adagium: 'Failure to achieve negative margins indicates need for adjuvant RT' does not translate automatically to patients with glottic cancer treated by TLM. Rather, specifically patients with multiple superficial positive margins and positive deep margins after TLM need careful judging what constitutes the best additional adjuvant treatment. Second-look resection is nowadays regarded as the preferred adjuvant treatment for many of these patients whereas RT is reserved for those in whom a second look TLM is judged unlikely to result in 'true negative margins.' Additionally, when the pathology of the re-resection reveals multiple foci of residual disease or suggests again a resection with positive margins, adjuvant postoperative RT is likely to result in a better local control. If this strict selection of patients for adjuvant RT is adhered to carefully, oncological and functional results will be optimal.

Shrinkage of specimens after CO2 laser cordectomy: an objective intraoperative evaluation.

The margin status after CO2 laser cordectomy for glottic carcinoma may influence prognosis. There are no studies assessing the possible bias due to anatomic changes of the specimens for shrinkage. The authors evaluated the intraoperative shrinkage of specimens immediately after transoral CO2 laser microsurgery (CO2 TOLMS) to improve the understanding and the interpretation of surgical margins. This is a prospective study involving a consecutive cohort of 23 patients (19 males, 4 females, mean age 69.9years, range 42-83years) with early glottic carcinoma treated by CO2 TOLMS from February 2017 to April 2019. The anteroposterior shrinkage of the specimen, of the tumor, and of the anterior and posterior margins was measured intraoperatively with a cross table reticle glass micrometer ruler, inserted into the eyepiece of the surgical microscope. The mean shrinkage of the mucosal specimen from intralaryngeal measurement to post-resection measurement was 3.8 ± 0.3mm, resulting in an average loss of 29% of the anteroposterior length (p < 0.01). The anteroposterior length of both the tumor and the margins after resection significantly decreased, but the shrinkage of the anterior and posterior margins was significantly greater than the shrinkage of the tumor (49% versus 20% and 45% versus 20%, p < 0.01). The present study demonstrates significant shrinkage of specimens after CO2 TOLMS, especially in the anteroposterior length of the vocal cords, and justifies the good oncological results for specimens with close and single positive superficial margins. Follow-up versus a second surgical look policy could be safely suggested in cases of close superficial and single positive superficial margins.

Transoral laser microsurgery: feasibility of a new exoscopic HD-3D system coupled with free beam or fiber laser.

In the last decades, new technological devices and instruments have been developed to overcome the technical limits of transoral laser microsurgery. The recent introduction of 3D endoscopy seems to be a promising tool in the field of diagnostic and operative laryngology as an alternative to the traditional microlaryngoscopy. Our work aims to present a novel transoral microsurgical setting that expands the use of exoscopic systems (in this case the VITOM® 3D-HD) as an alternative to the standard operating microscope. A customized support arm and an adaptor to firmly connect the VITOM® 3D-HD camera to the laser micromanipulator were specially designed. This setup was used as an alternative to the standard operating microscope in a cohort of 17 patients affected by suspicious early to intermediate pharyngo-laryngeal neoplasms. A historical cohort of patients treated with the traditional setting and matching the same inclusion criteria was used as a reference for the duration of surgical procedures. The surgical procedures comprised 7 cordectomies, 2 endoscopic partial supraglottic laryngectomies, 4 tongue base resections, and 4 lateral oropharyngectomies or hypopharyngectomies. In 6 cases (35%), a simultaneous neck dissection was performed. The low rate of positive deep (6%) or superficial (12%) margins reinforced the safety of this platform, and the results obtained in terms of operating time were comparable to the control group (p > 0.05), which confirms the feasibility of the system. Our surgical setting setup is a convincing alternative to traditional transoral laser microsurgery for early to intermediate pharyngo-laryngeal neoplasms. The main advantages of this system are comfortable ergonomics for the first surgeon and a potential benefit in terms of teaching if applied in university hospitals, since the entire surgical team can view the same surgical 3D-HD view of the first operator. Further work is still needed to objectively compare the traditional and new technique, and to validate our preliminary clinical findings.

MR imaging findings for differentiating cutaneous malignant melanoma from squamous cell carcinoma

PurposeThis study aimed to assess the efficacy of using MR imaging findings for differentiating cutaneous malignant melanoma (cMM) from cutaneous squamous cell carcinoma (cSCC). MethodsPreoperative MR images of patients with histopathologically proven primary cMM and primary cSCC were retrospectively reviewed and compared between the two pathologies. ResultsA total of 16 patients with primary cMM (7 men and 9 women; age range, 45–97 years; median age, 75 years) and 49 with primary cSCC (37 men and 12 women; age range, 46–90 years; median age, 76 years) were enrolled in this study. Intratumoral T1 hyperintensity compared to that of the dermis was more frequently observed in cMM than in cSCC (50 % vs. 4 %; p < 0.01). Superficial depression (51 % vs. 19 %; p < 0.05), superficial irregular margins (55 % vs. 25 %; p < 0.05), and reticular or linear T2 hyperintensity (27 % vs. 0 %; p < 0.05) were more frequently observed in cSCC than in cMM, respectively. ConclusionscMM predominantly exhibited intratumoral T1 hyperintensity, whereas cSCC predominantly exhibited superficial depression, superficial irregular margins, reticular or linear T2 hyperintensity.