Does the use of intraoperative frozen section of bone marrow from the cut end of the mandible help assess the adequacy of bone margins following mandibulectomy for oral cancer?

BACKGROUND: The adequacy of the cut end of the mandible following a segmental mandibulectomy done for oral cancer intraoperatively is at times assessed using a frozen section (FS) of the bone marrow (BM) at the cut ends. The study aimed to assess its utility to guide the intraoperative decision on the adequacy of bony margins. MATERIALS AND METHODS: All patients with oral squamous cell carcinoma (OSCC) who underwent segmental mandibulectomy from January 2012 to December 2021 at our institute and for whom intraoperative FS of BM was utilized were included. We analyzed the sensitivity, specificity, and positive and negative predictive value (PPV, NPV) of this in predicting positive bone margins. RESULTS: A total of 457 patients were included in the study. The majority of the cases were per premium cases (n = 372, 81.4%). The median age of the cohort was 52 years (range: 22-80 years). Most patients had T4 disease (n = 406, 88.8%). On FS, BM was positive in only 18 patients (3.9%) for whom the bone margin was revised. BM biopsy report in the final histopathology was positive in 12 patients (2.2%). The sensitivity, specificity PPV, and NPV were 52.3%, 98.65%, 64.7%, and 97.7% respectively. No factors predicting BM positivity on FS could be identified in this cohort. CONCLUSIONS: The BM FS was positive in only a small percentage of patients, and it helped in reducing the bone margin positivity rate from 3.9% to 2.2% only. Hence the intraoperative BM FS seems to have limited utility as seen from our study.

Frequency and accuracy of intraoperative bone margin sampling for T4a cancers of the head and neck at the QEII Health Sciences Centre: a retrospective chart review.

BACKGROUND: Stage T4a cancers are associated with a 5-year survival of 21.6-59.0%. Adequate resection of these tumors is a critical factor in maximizing survival. Tumors invading bone pose a unique challenge to intraoperative bone margin assessment. Due to processing limitations, there had been no formal standardized protocol for intraoperative bone sampling at the QEII Health Sciences Centre. These resections often involve extensive reconstruction, making salvage surgery difficult if positive margins are detected post-surgically. The purpose of this study was to assess the accuracy and frequency of intraoperative bone margin assessment during the study period and to determine survival and recurrence rates associated with positive final bone margins. METHODS: A retrospective chart review was conducted including patients with stage T4a head and neck cancer involving bone that underwent primary surgical resection in Nova Scotia between 2009 and 2019. Eligible patients were identified through the Cancer Care Nova Scotia registry. Exclusion criteria included patients with stage T4a tumors involving bone that did not receive primary surgical treatment with curative intent and patients with stage T4a tumors that did not invade bone. RESULTS: Of 67 patients included, 50 were amenable to intraoperative bone margin sampling while 18 had intraoperative sampling. Four patients had positive intraoperative margins and one had final positive bone margins. The incidence of final bone margin positivity was 7.5%. Median survival following surgery was 4.56 years for patients with final negative bone margins (n = 62) and 3.98 years for patients with positive final bone margins (n = 5). All patients with final positive bone margins received adjuvant radiation therapy. Of patients with negative final bone margins, 16.1% received no adjuvant therapy, 61.3% received adjuvant radiation therapy and 21.0% received adjuvant chemoradiation therapy. CONCLUSION: Intraoperative bone margin sampling occurred in 26.8% of all cases and 36.0% of amenable cases. Median survival of patients with positive final bone margins was 0.58 years lower than those with negative final bone margins, although this difference did not reach statistical significance. This will provide baseline data for comparison of the standardized intraoperative bone margin sampling protocol implemented at the QEII Health Sciences Centre.

Controversial Issues Regarding Positive Bone Margins in Surgery for Diabetic Foot Osteomyelitis: A Pilot Study.

Obtaining clean margins in patients who undergo surgical treatment for diabetic foot osteomyelitis (DFO) is recommended. We hypothesize that the rate of recurrence of the infection is not associated with positive margins, even when using a short-term duration of postoperative antibiotic treatment. We conducted a retrospective pilot study of patients who underwent surgery for DFO confirmed by histopathological analysis of the resected bone from August 1, 2020, to December 1, 2020. Bone samples were taken from the proximal margins to be studied by microbiology and histopathology. Twenty-five (89.3%) patients underwent conservative surgery, and 3 (10.7%) patients underwent a minor amputation. After surgery, the antibiotics were stopped in 19 (67.9%) patients and continued in 9 (32.1%) patients for a median period of 4 days. The microbiology of the bone margins was positive in 20 (71.4%) cases, but the histopathology of the bone margins was positive in just 7 (25%) cases. Recurrence of the infection was detected in 3 (10.7%) patients. Seventeen (68%) patients with microbiological-positive margins did not have a recurrence of infection, while 3 (100%) patients had a recurrence of infection (P = .53). Six (24%) patients among those with histopathological-positive margins did not have a recurrence of infection, and1 (33.3%) patient had a recurrence of infection (P = 1). The recurrence of infection was low and always detected in soft tissues, including the cases with a histopathological-positive bone margin. Postoperative antibiotics were administered for a short period of time and not based on the analysis of bone margins.

Surgical techniques for Bone Biopsy in Diabetic Foot Infection, and association between results and treatment duration.

Surgery is an important part of the management of patients diagnosed with DFO. It consists in some selected patients, to remove all or part of the infected bone(s) or even to amputate all or part of the foot. Despite the use of sophisticated imaging techniques, it is however difficult to remove all the infected tissue while respecting the principles of an economical surgery. Bone biopsy performed at the margins of the resection permits to identify residual osteomyelitis and to adjust the post-surgical antibiotic treatment. Some recent studies have reported the way to perform bone margin biopsies and have assessed the impact of the bone results on the patient's outcome. However, the real impact of a residual osteomyelitis on the risk of recurrent DFO is still debated and questions regarding the interpretation of the results remain to be solved. Similarly, the consequences in terms of choice and duration of the antimicrobial treatment to use in case of positive bone margin are not clearly established.

Diagnostic value of intraoperative bone marrow assessment for bone margins in patients with head and neck squamous cell carcinoma: a systematic review and meta-analysis.

A clear bone margin is essential for complete resection of the bone-involved tumour, but the evaluation of hard tissue takes time and is impractical intraoperatively. Bone marrow assessment remains controversial. The aim of this study was to investigate the diagnostic value of intraoperative bone marrow assessment for bone margins. PubMed and Web of Science were searched for studies published between 1990 and 2017. A systematic review was conducted. After quality assessment, 10 articles with 11 cohorts and 404 patients were identified. Sensitivity, specificity, and other measures were pooled for meta-analysis; the estimates for intraoperative bone marrow assessment were as follows: sensitivity 0.82 (95% confidence interval (CI) 0.62-0.93), specificity 0.99 (95% CI 0.96-1.00), positive likelihood ratio 109.79 (95% CI 22.99-524.34), negative likelihood ratio 0.18 (95% CI 0.08-0.42), and diagnostic odds ratio 241.82 (95% CI 90.33-647.38). Furthermore, sensitivity and specificity at the summary operating point of the summary receiver operating characteristic curve were 0.82 and 0.99, respectively, and the area under the curve was 0.99. Intraoperative bone marrow assessment was investigated by meta-analysis and shown to have a high level of overall accuracy for the diagnosis of bone margins.

Defining secure surgical bone margins in head and neck squamous cell carcinomas: The diagnostic impact of intraoperative cytological assessment of bone resection margins compared with preoperative imaging.

BACKGROUND: Imaging provides crucial staging information for treatment planning of head and neck squamous cell carcinomas (HNSCCs). Despite technical progress in imaging techniques, defining the extent of bone involvement preoperatively remains challenging and requires intraoperative information to control for adequate resection. The intraoperative cytological assessment of the bone resection margins (ICAB) provides information whether bone is infiltrated by carcinoma. The aim of this study was to assess the diagnostic value of preoperative imaging compared with ICAB in order to achieve carcinoma-free bone margins. MATERIALS AND METHODS: 108 HNSCC patients underwent preoperative computed tomography (CT), magnetic resonance imaging (MRI) and orthopantomogram (OPG) for staging and surgical planning. Curative resection was planned based on imaging. Intraoperatively, the resection margins were controlled by ICAB. The diagnostic value of preoperative imaging and ICAB was assessed with reference to the histological findings. RESULTS: CT showed a sensitivity of 89.7%, specificity of 63.0%, positive predictive value (PPV) of 85.9%, and negative predictive value (NPV) of 70.8%. MRI revealed a sensitivity of 45.5%, specificity of 66.7%, PPV of 71.4% and NPV of 40.0%. OPG-imaging had a sensitivity of 64.7%, specificity of 76.2%, PPV of 81.5%, NPV 57.1%. In comparison, ICAB provided a sensitivity of 78.6%, specificity of 95.7%, PPV 73.3%, and NPV 96.7%. The accuracy was 82.1%, 52.9%, 69.0%, and 93.5% for CT, MRI, OPG, and ICAB, respectively. CONCLUSION: Preoperative imaging lacks accuracy in defining adequate bone resection margins, compared with ICAB. ICAB supports preoperative imaging and intraoperative frozen sections to improve bone margin control.

Incidence, predictors and impact of positive bony margins in surgically treated T4 stage cancers of the oral cavity.

OBJECTIVES: A sea of literature addressing the adequacy of mucosal/soft tissue surgical margins in oral cavity cancers is available, but no mention exists regarding bony margins. We aim to study the predictors and impact on survival of positive bony margins and propose a safe margin distance. METHODS: This is a retrospective study of 400 consecutive surgically treated pT4 oral cavity squamous cell carcinoma patients between January 2012 and December 2015. The factors predicting positive bony margins were determined using chi-square test. Kaplan Meier and Cox regression hazard models were used for survival analysis. The median follow up was 36 months. RESULTS: The only factor that significantly predicted positive bony margins was lymphovascular emboli. The 3-year OS with bony margin positivity was 36.9%, compared to 67.5% for patients with adequate margins. When the tumor infiltrated the bone beyond mucosa (20.25%) the survival outcomes were significantly worse than the other patterns. Microscopic spread was seen in 10% cases, at a distance of 8 mm, the presence of which significantly impacted survival outcomes. Analysis of the receiver operating curve identified a cutoff of more than 15 mm as appropriate for classifying adequate bony margins. When the margins were taken above this, a significant positive impact on survival outcomes was present. CONCLUSION: The presence of lymphovascular emboli may impact the status of bony margins. Based on our results, to achieve an "adequate margin in bone" we propose taking the bony cut at least 15 mm away from the clinically discernible tumor when treating advanced oral cancers.

Bone Margin Analysis for Osteonecrosis and Osteomyelitis of the Jaws.

Bone margin analysis in cases of osteomyelitis, osteoradionecrosis, and medication-related osteonecrosis of the jaw is a controversial topic. There is little evidence to guide treatment and the interpretation of bone margin results. This article examines the significance of margin status and any possible effect on progression of the disease process. A review of various treatment adjuncts used for intraoperative margin analysis during removal of affected tissue is provided. Literature on the role of imaging is also discussed with regards to treatment planning for surgical resection. The histology of the three separate entities including the approach to surgical and pathologic evaluation of margins is also discussed.

Intraoperative cell isolation for a cytological assessment of bone resection margins in patients with head and neck cancer.

The intraoperative cytological assessment of bony resection margins (ICAB) is a feasible diagnostic approach to support frozen section for assessment of invasion of margins of soft and hard tissue. However, complex resection margins could challenge both diagnostic approaches. Our objective here was to identify the limitations of intraoperative diagnostic methods for assessing margins. We present an advanced cytological approach to assess complex margins that may solve the problem. Data from 119 patients in whom frozen section was supported by ICAB, were reviewed and the reasons for false results analysed. In 35 patients with squamous cell carcinoma infiltrating bone, specimens (n=100) from the resection margin went through an intraoperative cell isolation process for the cytological assessment of bony margins (ICAB). The results were compared with the histological results of the corresponding margins of bone as a reference. Limitations to the assessment of operative bony margins intraoperatively included an infiltrative histological pattern of growth of the carcinoma, with carcinoma cells disseminated within the cancellous bone, complex and uneven resection margins with soft and bony tissue, inflammation, and signs of previous radiotherapy. Intraoperative cell isolation plus (ICICAB) allowed the microscopic assessment of up to 1cm3 of bony tissue to detect disseminated carcinoma cells within the cancellous bone with a sensitivity of 92.3% (95% CI 74.9% to 99.1%), and a specificity of 100% (95% CI 95.1% to 100%), and positive and negative predictive values of 100% (95% CI 85.8% to 100%) and 97.4% (95%CI 90.8% to 99.7%), respectively. Intraoperative cell isolation is a feasible new technique to support ICAB and frozen section in the assessment of bony and soft tissue margins.

Evaluation of intraoperative cytological assessment of bone resection margins in patients with oral squamous cell carcinoma.

BACKGROUND: Frozen sections are routinely applied to control for adequate resection margins. In cases in which carcinoma infiltrates bone, the intraoperative microscopic assessment of bone margins remains challenging due to technical difficulties to section native bone. The objective of the current study was to evaluate an intraoperative cytological approach to control bone resection margins in patients with bone-infiltrating oral squamous cell carcinomas. METHODS: A total of 174 cytological preparations obtained from bone margins of bone-infiltrating oral squamous cell carcinomas (28 patients) were assessed intraoperatively and compared with the corresponding histological findings. In a validation cohort (45 patients) the intraoperative cytological assessment of bone resection margins (ICAB) (104 margins) was evaluated as a diagnostic tool for routine clinical application. RESULTS: In the first patient cohort, the ICAB revealed 95.3% sensitivity and 96% specificity. The results provided an accuracy of 95.7% with a significant correlation noted between cytological and histological results (κ, 0.91; P < .001), and a positive predictive value and negative predictive value of 93.8% and 96.9%, respectively. In the validation cohort, ICAB revealed 80% sensitivity and 98.9% specificity with 98% accuracy. There was a significant correlation found between cytological and histological results (κ, 0.91; P < .001), providing a positive predictive value and negative predictive value of 80% and 98%, respectively. ICAB could predict final resection status at bone margins with 80% sensitivity and 97.5% specificity. A significant correlation was found between the cytological and histological resection status at bone margins (κ, 0,75; P < .001). CONCLUSIONS: ICAB could supplement intraoperative frozen sections of soft tissue margins as a standard procedure to control for adequate resection at bone margins.