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A crucial parameter in determining the prognosis of oral cavity cancer is depth of invasion (DOI). This research aimed to correlate pathological DOI at different intra-oral anatomical sites for oral squamous cell carcinoma (OSCC) with the risk of regional lymph node metastasis (LNM). This study also investigated the correlation of 3-year overall survival (OS) and disease-specific survival (DSS) with tumor depth. DOI measurement of the primary tumor at different intra-oral anatomic sites of clinically node negative patients who underwent curative surgery with elective neck dissection (END) was carried out as per AJCC 8th Edition staging guidelines in 3 DOI groups of ≤5 mm(A), >5 to ≤10 mm(B) and >10 mm(C). Association of groupwise DOI values with histopathological parameters including LNM and 3 years survival was evaluated. Univariate and multivariate logistic regression analysis (Odds ratio (OR) = 1.1 95 % CI: 1.0-1.2, p < 0.05) showed DOI to be a significant predictor for sub-clinical nodal metastasis observed in 136/382 OSCC patients. Receiver operating curve suggested that at 5 mm DOI (4 mm for early-stage OSCC), the risk of occult LNM was >20 % for all intra-oral sites combined. DOI <5 mm group demonstrated a superior 3-year OS (OR = 19.8 % CI: 7.8-49.9) and DSS (OR = 14.7 % CI: 5.9-37.0). Thus, DOI is an independent predictor of nodal metastasis and has significant association with LNM, OS and DSS. Our findings suggest that a DOI of ≥4 mm is an accurate cut-off value for performing END in early-stage OSCC and > 5 mm for advanced cases across all evaluated oral anatomic sites.

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OBJECTIVES: This study investigates the relationship between the total volume of oral tongue cancer pre-operatively and the RFFF volume post-operatively. MATERIALS AND METHODS: A total of 52 DICOM imaging datasets (CT or MRI) of 26 patients were included in this study. The volume of the desired structure was quantified using semi-automatic segmentation using the software ITK-SNAP. All extracted measurements were validated by two further clinicians at separate instances. RESULTS: The variation of MeanVolTu can be predicted by MeanVolFlap moderately reliable with 59.1% confidence (R-Qua: 0.591). ANOVA Testing to represent how well the regression line fits the data, resulted in the overall regression model being statistically significant in predicting the MeanVolTu (p < 0.001). The flap volume may be predicted using the following algorithm: MeanVolFlap0 = 3241,633 + 1, 322 * MeanVolTu. CONCLUSION: The results of this study show positive correlation between tumor volume and flap volume, highlighting the significance of efficient flap planning with increasing tumor volume. A larger extraction volume of the radial forearm free flap from the donor site compromises the forearm more, thus increasing the probability of post-operative complications. CLINICAL RELEVANCE: Radial forearm free flap design in accordance with its corresponding 3D tumor volume.

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OBJECTIVE: Cervical lymph node metastasis (CLNM) is one of the most relevant influencing factors for the oncological outcome of patients with oral squamous cell carcinoma (OSCC). Several studies showed that the tumors depth of invasion (DOI) influences the risk for CLNM, however varying across the oral subsites. The aim of this study is to investigate the role of DOI and other risk factors in OSCC of the tongue in relation to the occurrence of occult CLNM. MATERIALS AND METHODS: In this retrospective study, n = 139 patients with primary OSCC of the tongue, treated by complete surgical resection (R0) with curative intention between 2013 and 2021, were included. For data analysis, epidemiologic data as well as preoperative tumor staging, surgical therapy including neck management, histopathological tumor data and follow-up were considered. Uni- and multivariate logistic regression were used to determine association between histopathological risk factors and the occurrence of occult CLNM. RESULTS: The rate of occult cervical metastasis was 19.4%. T-staging, cervical nodal disease (pN+) and lymphatic invasion were significantly associated with reduced OS and RFS. While DOI had no relevant influence on the OS and RFS (p = 0.88 and p = 0.91 respectively), there was significant correlation between DOI and the occurrence of occult CLNM (OR: 1.17, 95%CI: 1.05-1.30; p < 0.01). The optimal cutoff in predicting occult CLNM was 6 mm (Sensitivity: 84.2%, Specificity: 73.5%, AUC: 0.75). CONCLUSIONS: The DOI is a helpful risk parameter to predict the occurrence of occult nodal disease in OSCC of the tongue. Given the critical decision cutoff between 2 and 4 mm DOI for performing elective neck dissection in the current guidelines, our data suggests that in these cases, surgical de-escalation could be feasible with close follow-up. CLINICAL RELEVANCE: This study highlights the relevance of DOI as a risk parameter in the prediction of CLNM with the aim to specify the individual patient risk and to deescalate surgical therapy in order to decrease comorbidities while improving the oncological prognosis.

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Objectives: The primary aim is to determine the accuracy of contrast-enhanced computed tomography (CT) in evaluation of depth of invasion (DOI) and detection of cervical node metastasis. We also analysed the relation between radiographic DOI (rDOI) and cervical lymph node metastasis. Materials and Methods: We have retrospectively reviewed 201 oral squamous cell carcinoma (SCC) patients. The rDOI was compared with histological DOI. Sensitivity, specificity, accuracy, and negative (NPV) and positive (PPV) predictive values were evaluated for CT scan in predicting nodal metastasis. The relation between rDOI and lymph node metastasis was analysed using ROC curve. Results: rDOI correlated significantly with histologic DOI for oral tongue, buccal mucosa, gingiva, and mucosal lip SCC (P < 0.05) and for tumours with rDOI > 5 mm. The sensitivity, specificity, PPV, NPV and accuracy rate of CT scan were found to be 84.71%, 50.86%, 55.81%, 81.94% and 65.17%, respectively. Tumours with rDOI > 16 mm had significant (P < 0.001) chance of having neck node metastasis. Conclusion: CT-derived DOI correlates significantly with pathological DOI although both are not similar. CT scan can predict nodal metastasis in fairly accurate manner using the four radiographic criteria used in this study. Radiographic depth of invasion can be used as predictor of cervical node metastasis.

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In 1977, the American Joint Committee on Cancer (AJCC) introduced the inaugural Cancer Staging Manual, which implemented the T (tumor extent), N (regional lymph node status), and M (presence or absence of distant metastasis) staging system. This systematic approach aimed to convey the extent of disease across various cancer types, providing clinicians with a practical framework to plan treatment strategies, predict prognosis, and assess outcomes. The AJCC 8th edition, effective from January 1, 2018, continues this tradition. However, certain shortcomings persist in the AJCC 8th edition, as identified through clinical experience. Specifically, challenges arise in accurately assessing depth of invasion in unique histological variants of oral squamous cell carcinoma (e.g., Oral verrucous carcinoma, Carcinoma cuniculatum, and Papillary squamous cell carcinoma) and minor salivary gland tumors. Additionally, discrepancies exist in the perception of bone invasion patterns and in reporting practices. There is also a need for staging guidelines for malignant odontogenic tumors and multifocal tumors of the oral cavity, supplemented by diagrammatic representations. Lastly, there is a call for comprehensive staging criteria for carcinomas of the ear, external auditory canal, and temporal bone. We advocate for the inclusion of these considerations in future editions of the AJCC Cancer Staging Manual.

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Background: Magnetic resonance imaging (MRI) is a routinely used imaging modality for pre-treatment radiologic evaluation of tongue carcinoma, providing accurate information regarding the extent of the disease. Aims and objectives: To investigate the role of MRI-derived depth of invasion and tumor thickness evaluation in squamous cell carcinoma of the tongue, and to assess if any correlation exists between depth of invasion, tumor thickness, nodal metastasis, muscles, and space involved. Materials and methods: Thirty-three patients with oral squamous cell carcinoma of the tongue who had undergone pre-treatment MRI and excisional biopsy were included. The tumor thickness (TT) and depth of invasion (DOI) were evaluated on MRI and histopathologic images. Result: The relation between different methodologies for assessing showed a very high correlation for the tumor tissue thickness (r = 0.99, p < 0.05) and depth of invasion (r = 0.82, p < 0.05). The tumor thickness and the depth of invasion increased with the loss of differentiation in the carcinoma histopathologically. As the depth of invasion increases, the extent of the spread of the carcinoma to tongue musculature, lingual septum, and spaces also increases. Conclusion: The present study has depicted a high correlation between the tumor thickness and the depth of invasion between MRI and histopathological findings and is the first of its kind to correlate DOI to the invasiveness of the disease.

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Tongue is a complex, principally muscular structure extending from oral cavity to oropharynx. Hypopharynx extends from the level of hyoid bone and to the level of inferior margin of cricoid cartilage and is divided into pyriform sinus, posterior cricoid region and posterior pharyngeal wall. Lesions that can affect the tongue and hypopharynx include neoplastic, congenital, vascular and infectious etiologies. Imaging provides crucial details for diagnosis and the appropriate management of these lesions. To evaluate the role of MRI in characterisation of benign and malignant lesions of tongue, malignant lesions of hypopharynx and staging the neoplastic lesions. The study was performed on 60 patients suspected of tongue and hypopharyngeal lesions in Dr Ram Manohar Lohia Hospital, New Delhi from 1st January 2021 to 31st May 2022. The study was done on SEIMENS skyra MRI scanner. Radiological characteristics, clinical features were studied and statistical inference was interrogated. Out of 60 patients, 32 were of tongue cancer, 10 of base of tongue cancer, 8 of hypopharyngeal cancer, 8 of hemangioma tongue and 2 of thyroglossal cyst. The mean age of our study population was 42.87 years. The qualitative analysis between diffusion restriction and histopathological examination shows a strong and substantial agreement between the two variables and a p value of 0.0014. The overall diagnostic accuracy of MRI was 85.5% and for CT was 82.5%. MRI plays an important role in differentiation of benign from malignant lesions of tongue and hypopharynx and staging of the malignant lesions. The correlation between MRI and CT findings of malignant lesions of tongue and hypopharynx indicated that both CECT and MRI have high diagnostic accuracy in diagnosing and staging but MRI is better for T and N staging of the malignant lesions with a diagnostic accuracy of 85.5% which was higher than the diagnostic accuracy of CT (82.5%). Thus, in conclusion MRI has a remarkable role in characterization and staging of benign and malignant lesions of tongue and hypopharynx. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04532-y.

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Aim: The current study aimed to assess the frequency of CDH1 promoter gene hypermethylation in gastric cancer and chronic gastritis and its correlation with clinicopathological aspects. Methods: Methylation-specific PCR was used to detect CDH1 promoter gene hypermethylation in 53 chronic gastritis patients and 40 gastric cancer patients along with normal adjacent tissues. Results: The chronic gastritis group comprised 29 males and 24 females with a mean age of 51.8 ± 12.96 years, and 49.1 % of them were positive for H. pylori infection. The frequency of CDH1 hypermethylation in gastritis lesions was 18.8 %. CDH1 hypermethylation showed a significant correlation with H. pylori infection (p = 0.039), but no significant association was observed with other clinical features. The gastric cancer group consisted of individuals with a mean age of 65.4 ± 10.6, among them, 77.5 % were male and 22.5 % were female, 62.5 % had PT3 tumors, 40 % had PN1 lymph node involvement, and the majority (47.5 %) of samples were obtained from body segment. CDH1 hypermethylation was significantly associated with depth of invasion (p = 0.017) and nodal invasion (p = 0.041) in this group. In both groups, normal adjacent specimens lacked CDH1 hypermethylation, and there was no statistically significant correlation between CDH1 hypermethylation and age at which the tumor was diagnosed, gender, activity level, or tumor location. Conclusion: This study demonstrates that E-cadherin methylation is associated with some characteristics of chronic gastritis and gastric cancer. These findings support previous research indicating that CDH1 hypermethylation may play a significant role in the development of gastric cancer.

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BACKGROUND: The accurate indication for level IV dissection is crucial for preventing complications such as phrenic nerve damage and chylous fistulas in clinically N0 tongue cancer. Although the depth of invasion is an established independent risk factor for occult lymph node metastasis in tongue cancer, its relationship with level IV metastasis has not been evaluated. This study investigated the relationship between the depth of invasion and level IV nodal metastasis in clinically N0 tongue cancer. METHODS: We retrospectively investigated clinical N0 patients who underwent glossectomy and level I-IV neck dissection. We examined lymph node metastasis, risk factors, and the relationship between depth of invasion and metastasis. RESULTS: Our study included 58 patients, and no patient had isolated level IV metastasis. Additionally, there was no level IV metastasis in well-differentiated tumors. Tumor size, depth of invasion, differentiation, and perineural invasion were significantly associated with level IV neck metastasis. We found a critical tumor size of 2.5 cm and depth of invasion of 8 mm for level IV neck metastasis. CONCLUSION: Based on our findings, we recommend that level IV dissection should be considered for poorly differentiated tumors, tumors greater than 2.5 cm in size, and those deeper than 8 mm. This study highlights the importance of depth of invasion as a prognostic factor for predicting level IV metastasis and suggests that our findings can be used to prevent unnecessary level IV dissections that may lead to complications in tongue cancer surgery.

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This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography (EUS) in the context of small rectal neuroendocrine neoplasms (NENs). A total of 108 patients with rectal subepithelial lesions (SELs) with a diameter of < 20 mm were included in the analysis. The diagnosis and depth assessment of EUS was compared to the histology findings. The prevalence of NENs in rectal SELs was 78.7% (85/108). The sensitivity of EUS in detecting rectal NENs was 98.9% (84/85), while the specificity was 52.2% (12/23). Overall, the diagnostic accuracy of EUS in identifying rectal NENs was 88.9% (96/108). The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9% (78/84). Therefore, EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs, with good sensitivity but inferior specificity. EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.

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PURPOSE: To determine the significance of depth of invasion as a predictor of recurrence and mortality in tongue and non-tongue early-stage oral cavity squamous cell carcinoma patients treated with surgery and no postoperative radiotherapy. MATERIALS AND METHODS: 344 patients with oral cavity squamous cell carcinoma from 2005 to 2022 at a tertiary academic medical center were reviewed. Patients were included if they had newly diagnosed, previously untreated T1-T2N0 disease treated with surgery alone that was observed within a follow-up of 5 years. For each patient, anatomic site of oral cavity squamous cell carcinoma was categorized as either tongue or non-tongue. Cox proportional hazards regression analyses were performed to determine the association of depth of invasion with recurrence and mortality, with anatomic site, smoking status, and age at biopsy as covariates. Model assumptions were tested by statistical and graphical evaluation using Schoenfeld residuals. RESULTS: Of 108 patients with T1-T2N0 disease, 78 (72.2 %) had tongue disease, and 30 (27.8 %) had non-tongue disease. Median follow-up was 18.2 months (range, 0.01-58.2 months). In the Cox proportional hazards models, with adjustment for anatomic site and other covariates, depth of invasion positively predicted recurrence (HR 1.16, 95 % CI: 1.01-1.32, p = 0.034) and death (HR 1.42, 95 % CI: 1.11-1.83, p = 0.006). CONCLUSIONS: Depth of invasion is an independent predictor of recurrence and death across early-stage tongue and non-tongue squamous cell carcinoma. Therefore, depth of invasion may indicate a need for more aggressive treatment than surgery alone, such as postoperative radiotherapy, even in the absence of other adverse features on pathology within the early-stage population.

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PURPOSE: The 8th edition of the American Joint Committee on Cancer staging system included the depth of invasion (DOI) for the T classification of oral cancer. However, no standardized method has been established to clinically measure the DOI. This study aimed to investigate the accuracy of MRI-based DOI for oral tongue squamous cell carcinoma (OTSCC) in each MRI sequence. METHODS: We enrolled 49 patients with histologically proven OTSCC, treated surgically between April 2017 and February 2021. We divided the DOI into three groups using 5 and 10 mm, the thresholds for determining the T stage, and retrospectively evaluated the agreement between MRI-based DOI and pathological DOI (pDOI) for each MRI sequence, axial T1-weighted imaging (T1WI), T2-weighted imaging with fat suppression (FS-T2WI), contrast-enhanced T1WI with fat suppression (CE-T1WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) maps. We also divided the DOI into two groups using 3 mm, the threshold for considering elective neck dissection, and evaluated the overestimation rate of MRI-based DOI in lesions with pDOI ≤ 3 mm. RESULTS: With 5-mm and 10-mm divisions, the accuracy of the DOI assessment was highest on DWI (0.82, weighted kappa = 0.85). With a 3-mm division, the accuracy was also highest on DWI (0.87, kappa = 0.73). The overestimation rate of the MRI-based DOI in lesions with pDOI ≤ 3 mm was lowest on DWI (27.8%). CONCLUSION: DOI on DWI exhibits a comparatively higher rate of concordance with pDOI. DWI may be more useful than other MRI sequences in evaluating the DOI of OTSCC.

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Oral squamous cell carcinoma (OSCC) of the tongue is the most common type of oral cavity cancer, and tumor depth of invasion (DOI) is an important prognostic factor. In this study, we investigated the accuracy of intraoral ultrasound and magnetic resonance imaging (MRI) for assessing DOI in patients with OSCC. Histopathological measurement of DOI was used as a reference standard. We conducted a prospective study including patients planned for surgical treatment of OSCC in the tongue. The DOI was measured in an outpatient setting by intraoral ultrasound and MRI, and was compared to the histopathological DOI measurements. Bland-Altman analysis compared the mean difference and 95% limits of agreement (LOA) for ultrasound and MRI, and the Wilcoxon signed-rank test was used to test for significance. The correlation was evaluated using Pearson's correlation coefficient. We included 30 patients: 26 with T1 or T2 tumors, and 4 with T3 tumors. The mean difference from histopathology DOI was significantly lower for ultrasound compared to MRI (0.95 mm [95% LOA -4.15 mm to 6.06 mm] vs. 1.90 mm [95% LOA -9.02 mm and 12.81 mm], p = 0.023). Ultrasound also led to significantly more correct T-stage classifications in 86.7% (26) of patients compared to 56.7% (17) for MRI, p = 0.015. The Pearson correlation between MRI and histopathology was 0.57 (p < 0.001) and the correlation between ultrasound and histopathology was 0.86 (p < 0.001). This prospective study found that intraoral ultrasound is more accurate than MRI in assessing DOI and for the T-staging of oral tongue cancers. Clinical practice and guidelines should implement intraoral ultrasound accordingly.

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OBJECTIVES: In early-stage oral squamous cell carcinoma (OSCC) patients, whether the margin-to-depth-of-invasion ratio (MDR) can assist in stratifying the prognosis remains unclear. METHODS: Patients diagnosed with early stage OSCC at National Taiwan University Hospital between January 2007 and December 2021 were reviewed. Patients with margin > 1 mm were classified into two groups: MDR < 0.5 and MDR ≥ 0.5. RESULTS: We analyzed 911 pT1-2N0M0 OSCC patients, 723 (79.36 %) with MDR ≥ 0.5 and 188 (20.64 %) with MDR < 0.5. Patients in the MDR < 0.5 group displayed a significantly higher local recurrence rate (odds ratio 2.81, p = 0.002) compared with MDR ≥ 0.5 group. The 5-year disease-free survival were 80.8 % for clear margin, 76.3 % for close margin (MDR ≥ 0.5), and 65.2 % for close margin (MDR < 0.5). The overall survival displayed a similar pattern, with 5-year rates of 88.3 % for clear margin, 86.8 % for close margin (MDR ≥ 0.5), and 75.0 % for close margin (MDR < 0.5). There were no significant overall survival differences between the two MDR ≥ 0.5 groups, but both were significantly superior to patients with MDR < 0.5 (p = 0.001; p = 0.01). After multivariant cox analysis, MDR < 0.5 was a significant risk factor for disease-free survival (p < 0.001). CONCLUSION: For early stage OSCC patients without positive margin (≦1mm), the survival outcome between MDR ≥ 0.5 group and MDR < 0.5 group was significantly different. The MDR < 0.5 group had significantly higher risk of local recurrence that may warrant adjuvant treatment.

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BACKGROUND: Tongue cancer is associated with debilitating diseases and poor prognostic outcomes. The use of imaging techniques like ultrasonography to assist in the clinical management of affected patients is desirable, but its reliability remains debatable. Therefore, the aim of this study is to investigate the importance of ultrasound use for the clinicopathological management of tongue cancer. METHODS: A scoping review was carried out using specific search strategies in the following electronic databases: PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Collected data included bibliographical information, study design, ultrasound equipment, the aim of the ultrasonography use, the timing of ultrasound use during oncological treatment (pre-, trans-, and/or post-operatively), and the advantages and disadvantages of the use of the ultrasound. RESULTS: A total of 47 studies were included in this review after following the selection process. The majority of the studies investigated the use of ultrasound pre-operatively for the investigation of lymph node metastases or to determine the tumor thickness and depth of invasion. The sensitivity, specificity, and accuracy of ultrasound to determine clinical lymph node metastases ranged from 47% to 87.2%, from 84.3% to 95.8%, and from 70% to 86.2%, respectively. The sensitivity and specificity to determine the microscopic depth of invasion were 92.3% and from 70.6% to 82.1%, respectively. CONCLUSION: Ultrasonography seems to be a reliable imaging technique for the investigation of important prognostic parameters for tongue cancer, including depth of invasion and lymph node metastases.

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OBJECTIVE: The prognostic value of depth of invasion (DOI) in oral squamous cell cancer carcinoma and cutaneous melanoma is well established, while there is a lack of reports investigating the role of DOI in laryngeal cancer. This study aims to explore the association of glottic cancer DOI with other established pathological risk factors and nodal metastasis and evaluate the feasibility of measuring DOI preoperatively using tomographic imaging. METHODS: The medical records of glottic cancer patients treated between 2015 and 2020 in a single tertiary referral center were screened retrospectively. Pathologically measured DOI (pDOI) value was also reviewed and registered. Preoperative computer tomography (CT) was used to obtain the radiological DOI (rDOI) measured by two dedicated radiologists. Their inter-rated agreement was assessed and the correlation between pDOI and rDOI was calculated. pDOI association with the main pathology report features was assessed with univariable analysis. Cox univariable and multivariable models were used to explore the role of pDOI on survival. RESULTS: Ninety-one patients had pDOI data available, of which 59 also had rDOI data. A strong concordance between the two radiologists was found (concordance correlation coefficient = 0.96); rDOI and pDOI were highly and significantly correlated (R = 0.85; p < 0.001). pDOI was significantly higher in patients with perineural invasion (PNI; p < 0.001), lymphovascular invasion (LVI; p < 0.001), and nodal metastasis (p < 0.001). pDOI was associated with disease-free survival at univariable analysis (p = 0.04) while it did not show a significant impact (p = 0.10) at multivariable analysis. CONCLUSION: Glottic carcinoma DOI correlates with PNI, LVI, and nodal metastasis and it can be reliably assessed in a preoperative setting using CT imaging. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3230-3237, 2024.

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OBJECTIVE: The prognostic stratification for oral tongue squamous cell carcinoma (OTSCC) is heavily based on postoperative pathological depth of invasion (pDOI). This study aims to propose a preoperative MR T-staging system based on tumor size for non-pT4 OTSCC. METHODS: Retrospectively, 280 patients with biopsy-confirmed, non-metastatic, pT1-3 OTSCC, treated between January 2010 and December 2017, were evaluated. Multiple MR sequences, including axial T2-weighted imaging (WI), unenhanced T1WI, and axial, fat-suppressed coronal, and sagittal contrast-enhanced (CE) T1WI, were utilized to measure radiological depth of invasion (rDOI), tumor thickness, and largest diameter. Intra-class correlation (ICC) and univariate and multivariate analyses were used to evaluate measurement reproducibility, and factors' significance, respectively. Cutoff values were established using an exhaustive method. RESULTS: Intra-observer (ICC = 0.81-0.94) and inter-observer (ICC = 0.79-0.90) reliability were excellent for rDOI measurements, and all measurements were significantly associated with overall survival (OS) (all p < .001). Measuring the rDOI on axial CE-T1WI with cutoffs of 8 mm and 12 mm yielded an optimal MR T-staging system for rT1-3 disease (5-year OS of rT1 vs rT2 vs rT3: 94.0% vs 72.8% vs 57.5%). Using multivariate analyses, the proposed T-staging exhibited increasingly worse OS (hazard ratio of rT2 and rT3 versus rT1, 3.56 [1.35-9.6], p = .011; 4.33 [1.59-11.74], p = .004; respectively), which outperformed pathological T-staging based on nonoverlapping Kaplan-Meier curves and improved C-index (0.682 vs. 0.639, p < .001). CONCLUSIONS: rDOI is a critical predictor of OTSCC mortality and facilitates preoperative prognostic stratification, which should be considered in future oral subsite MR T-staging. CLINICAL RELEVANCE STATEMENT: Utilizing axial CE-T1WI, an MR T-staging system for non-pT4 OTSCC was developed by employing rDOI measurement with optimal thresholds of 8 mm and 12 mm, which is comparable with pathological staging and merits consideration in future preoperative oral subsite planning. KEY POINTS: • Tumor morphology, measuring sequences, and observers could impact MR-derived measurements and compromise the consistency with histology. • MR-derived measurements, including radiological depth of invasion (rDOI), tumor thickness, and largest diameter, have a prognostic impact on OS (all p < .001). • rDOI with cutoffs of 8 mm and 12 mm on axial CE-T1WI is an optimal predictor of OS and could facilitate risk stratification in non-pT4 OTSCC disease.

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BACKGROUND: "Depth of invasion" is an additional index incorporated in 8th AJCC staging system for oral cavity squamous cell carcinoma based on its prognostic significance. Pre-operative assessment by clinical palpation and imaging modalities has been used with limitations. The aim of the study is to compare different techniques including clinical palpation, ultrasound, and magnetic resonance imaging with histopathology for assessment of depth of tumor invasion. MATERIALS: Fifty patients of carcinoma tongue (T1-T3) were enrolled. Clinical palpation, Ultrasound tongue, and Magnetic resonance imaging were used to assess depth of tumor invasion. Microscopic depth of invasion was considered as reference. Statistical analysis was done to assess the level of agreement, reliability, and internal consistency. ROC analysis was done to find the "Area Under Curve" for microscopic depth versus ultrasound, MRI, and gross histopathological "depth of invasion". RESULTS: Ultrasound tongue showed highest "area under curve", Intra class correlation (ICC:0.786) with a good consistency (Cronbach's Alpha:0.880) with histological reference compared to MRI(ICC:0.689;CA:0.816). Clinical palpation showed weak agreement (Kappa:0.43) for assessing depth. To observe the concordance between ultrasound and microscopic depth, Lin's Concordance Correlation Coefficient (CCC = 0.782) was calculated with 95% limits of agreement. Lin's concordance correlation between ultrasound and microscopic depth showed a good agreement. CONCLUSIONS: Ultrasound tongue is a reliable imaging modality for pre-operative T staging by assessing tumor "depth of invasion" in carcinoma tongue patients with good internal consistency as per 8th AJCC staging system. LEVEL OF EVIDENCE: 2 (CEBM-Level of Evidence-2.1) Laryngoscope, 134:215-221, 2024.

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The American Joint Committee on Cancer (AJCC) 8th edition T-staging system for distal cholangiocarcinoma (DCC) proposes classification according to the depth of invasion (DOI); nevertheless, DOI measurement is complex and irreproducible. This study focused on the fibromuscular layer and evaluated whether the presence or absence of penetrating fibromuscular invasion of DCC contributes to recurrence and prognosis. In total, 55 patients pathologically diagnosed with DCC who underwent surgical resection from 2002 to 2022 were clinicopathologically examined. Subserosal layer and/or pancreatic (SS/Panc) invasion, defined as penetration of the fibromuscular layer and invasion of the subserosal layer or pancreas by the cancer, was assessed with other clinicopathological prognostic factors to investigate recurrence and prognostic factors. According to the AJCC 8th edition, there were 11 T1, 28 T2, and 16 T3 cases, with 44 (80%) cases of SS/Panc invasion. The DOI was not significantly different for both recurrence and prognostic factors. In the multivariate analysis, only SS/Panc was identified as an independent factor for prognosis (hazard ratio: 16.1; 95% confidence interval: 2.1-118.8, p = 0.006). In conclusion, while the determination of DOI in DCC does not accurately reflect recurrence and prognosis, the presence of SS/Panc invasion may contribute to the T-staging system.

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Background: Radical cystectomy (RC) is the standard surgical treatment for patients with muscle-invasive bladder cancer, but the prognosis is not favorable, and new prognostic factors need to be discovered. We investigated the potential of depth of invasion (DOI) as a prognostic factor in patients with muscle-invasive bladder cancer who underwent RC. Furthermore, we examined the association between preoperative levels of circulating cell-free DNA and DOI. Materials and methods: We retrospectively reviewed patients who underwent RC between January 2007 and December 2017; those who received neoadjuvant chemotherapy were excluded. Depth of invasion was measured using hematoxylin-eosin-stained RC specimens. Results: Of the 121 patients selected, 41 (33.9%) were eligible for analysis. The median follow-up period was 14 months and mean DOI was 17 mm (range, 2-75 mm). Long DOI (>17 mm) was significantly associated with shorter progression-free survival (hazard ratio, 14.5; 95% confidence interval, 3.9-53.97, p < 0.0001) and cancer-specific survival (hazard ratio, 18.97; 95% confidence interval, 4.04-88.99, p = 0.0002) compared with short DOI. Multivariate analysis revealed that DOI was an independent risk factor for cancer-specific survival. The levels of circulating cell-free DNA were significantly higher in patients with a longer DOI than in those with short DOI (65 vs. 20 ng/mL, respectively; p = 0.028). Conclusions: Depth of invasion predicted with levels of circulating cell-free DNA and thus could be a useful prognostic factor.