Tumor Depth Research Articles

Correlation Between Serum and Tissue SIRT1 Levels in Patients With Esophageal Squamous Cell Carcinoma.

Identifying prognostic and molecular markers as therapeutic targets for esophageal squamous cell carcinoma (ESCC) could enhance the efficacy of multidisciplinary treatments. While tissue expression of sirtuin 1 (SIRT1) has been linked to tumor progression in ESCC, prognostic significance of serum SIRT1 levels and their correlation with tissue SIRT1 remains unexplored. This study aimed to investigate the correlation between serum and tissue SIRT1 levels in patients with ESCC. A total of 38 patients diagnosed with ESCC who were untreated preoperatively were recruited for this study. SIRT1 expression in the surgical specimens was assessed through immunostaining, while serum SIRT1 levels were measured using an enzyme-linked immunosorbent assay. We analyzed the association between tissue and serum SIRT1 levels, clinicopathological features, and patient prognosis. Positive SIRT1 expression in tissue was significantly associated with deeper tumor depth (p=0.020). It was also significantly associated with poorer overall survival (OS) and relapse-free survival (RFS) (p=0.041 and p=0.012, respectively). Elevated serum SIRT1 levels were significantly correlated with increased tumor depth and weight loss (p=0.012 and p=0.030). While higher serum SIRT1 levels tended to be associated with poorer OS (p=0.069), no significant correlation was found between SIRT1 expression in tissue and its concentration in serum. SIRT1 tissue expression may be a valuable prognostic marker in ESCC. However, the clinical significance of serum SIRT1 levels appears to differ from that of its tissue expression. Future research is required to clarify the role of serum SIRT1 in ESCC.

Long-term outcomes of nodal surveillance practices in sentinel node positive melanoma: An early post MSLT-II cohort

BackgroundThe Second Multicenter Selective Lymphadenectomy Trial (MSLT-II), published in 2017, demonstrated equivalent melanoma-specific survival between nodal surveillance and completion lymph node dissection (CLND) for sentinel lymph node (SLN) positive melanoma. This study evaluated outcomes of nodal surveillance in an early post-MSLT-II institutional cohort. MethodsIncluded patients received nodal surveillance from 2017 to 2023. Primary outcomes were nodal basin and any site recurrence. Kaplan Meier curves and Cox proportional hazard models were used to evaluate recurrence-free survial and associated factors. ResultsThis 212 patient cohort (median age 61 years, 57.7 ​% male, 96.7 ​% white) had median primary tumor depth of 1.9 ​mm and one positive SLN. Sixty-three patients (29.7 ​%) recurred at 23 month median follow-up. Sixty percent received adjuvant therapy. Any site and nodal basin recurrence-free survival were 58.3 ​% and 80.9 ​% at 3 years. On adjusted analysis, older age and head/neck primary site were associated with worse recurrence-free survival. ConclusionLong-term outcomes at a single institution were comparable to clinical trial findings. Nodal surveillance remains a feasible management strategy for SLN ​+ ​melanoma.

Molecular Genetic Factors of Risk Stratification of Lymph Node Metastasis in Endometrial Carcinoma.

According to epidemiological studies, endometrial carcinoma is one of the most frequently diagnosed malignancies of the female reproductive system, with an increasing incidence. Currently, the risk stratification of this neoplasm takes into account the stage, degree of tumor differentiation, histological type and depth of myometrial invasion. Since the publication of the last International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer in 2009, numerous reports have appeared on the molecular characteristics of different types of endometrial carcinoma. Taking this into account, the FIGO Committee determined in 2023 that changes and updates to the staging system are justified to reflect new information about this tumor. Due to the high prevalence of the disease and mortality from endometrial cancer, an in-depth study of the molecular genetic characteristics of tumor cells is relevant; the results of such studies can be used to improve the efficiency of diagnosis, assess the risk of metastasis and prognosis of the disease. Lymph node assessment is crucial for the choice of treatment strategy for endometrial cancer, since metastatic lymph node involvement is one of the main factors affecting prognosis. At the same time, the criteria for the appropriateness of lymphadenectomy in low-differentiated malignant tumors are not clearly defined. Various molecular methods have been proposed to assess the status of lymph nodes; candidate genes are being studied as potential diagnostic biomarkers, as well as microRNA. The aim of the study was to analyze the literature data on numerous studies of molecular risk factors for progression in endometrioid carcinoma, as well as to preserve the most important marker changes in relation to the prognostic development of this disease. A literature review was conducted using data from the electronic databases PubMed, Google Scholar, and Wiley Cochrane Library for the period from 2018 to 2023 using the specific keywords. The current scientific genetic studies on metastasis and prognostic factors in uterine cancer were analyzed, and a systematization of the reviewed data from the modern literature was done. To select the most effective treatment - intraoperative, adjuvant or combination therapy, minimize postoperative risks of lymphadenectomy and clearly predict the results - further study of the molecular genetic features of endometrial cancer is necessary.

Advanced ultrasound diagnosis of extrahepatic bile duct lesions.

Ultrasound (US) has high specificity and sensitivity, and it should be performed first for patients with suspicion of biliary tract cancer. However, the complicated anatomy in addition to the gas images makes it difficult to delineate the entire extrahepatic bile duct (EHBD). The keys to depiction of EHBD are the "J" shape manipulation in the left lateral decubitus position and the use of magnified images with high-frequency transducers. Furthermore, indirect findings such as gallbladder (GB) distension, BD dilatation, and debris echo in the GB and BD are also important for detecting occult lesions, particularly in the ampullary region of Vater. For the differential diagnosis of BD wall thickening, the spreading pattern in the long and short axial directions should be assessed first. Then, the characteristics of the innermost hyperechoic layer (IHL) and outermost hyperechoic layer (OHL) should be evaluated. Asymmetrical wall thickening, absence of IHL, and presence of irregularity or discontinuity in OHL are characteristic patterns of cholangiocarcinoma (CCA). Because CCA is the most common BD polypoid lesion, it is important to diagnose tumor extension and depth invasion in addition to differential diagnosis. Nodular-type CCA is usually hypoechoic and more likely to invade vertically. In contrast, papillary-type CCA is often hyperechoic and extends laterally. Contrast‑enhanced US may be useful for evaluating these findings. However, if the possibility of CCA cannot be ruled out or a definitive diagnosis is needed, a transpapillary biopsy or endoscopic US-guided tissue acquisition should be considered.

Analysis of clinical features, treatment methods, and prognostic influence factors in patients with malignant peripheral nerve sheath tumor

To investigate the clinical features, treatment methods, and prognostic influence factors of patients with malignant peripheral nerve sheath tumor (MPNST). A retrospective analysis was conducted on 96 MPNST patients treated between January 1, 2015 and December 31, 2021. There were 46 males and 50 females, aged between 15 and 87 years (mean, 48.2 years). The tumors were located in the trunk in 50 cases, extremities in 39 cases, and head and neck in 7 cases. The maximum tumor diameter was <5 cm in 49 cases, ≥5 cm in 32 cases, with 15 cases missing data. Tumor depth was deep in 77 cases and superficial in 19 cases. The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) histological grading was G1 in 9 cases, G2 in 12 cases, and G3 in 34 cases, with 41 cases missing data. There were 37 recurrent MPNST cases, 32 cases with neurofibromatosis type 1 (NF1), and 26 cases in stage Ⅳ. Postoperative adjuvant radiotherapy was administered to 25 patients, perioperative chemotherapy to 45 patients, and anlotinib-targeted therapy to 30 patients. R 0 resection was achieved in 73 cases. Patients were divided into groups based on the presence or absence of NF1, and baseline data between the two groups were compared. Kaplan-Meier curves were generated to assess disease-free survival (DFS) and overall survival (OS) based on various factors (age, gender, presence of NF1, recurrent MPNST, stage Ⅳ MPNST, FNCLCC grade, R 0 resection, tumor location, tumor size, tumor depth, perioperative chemotherapy, postoperative adjuvant radiotherapy, and anlotinib-targeted therapy), and differences between survival curves were analyzed using the Log-Rank test. Multivariate COX proportional hazards regression was used to identify independent prognostic factors for MPNST. Patients with NF1 had a significantly higher proportion of superficial tumors and lower FNCLCC grade compared to those without NF1 ( P<0.05); no significant difference was found for other variables ( P<0.05). Kaplan-Meier analysis showed that recurrent MPNST, stage Ⅳ MPNST, FNCLCC grade, R 0 resection, perioperative chemotherapy, and anlotinib-targeted therapy were factors influencing 1-year DFS ( P<0.05), while stage Ⅳ MPNST, FNCLCC grade, and perioperative chemotherapy were factors affecting 3-year OS ( P<0.05). Multivariate COX proportional hazards regression analysis revealed that recurrent MPNST and high-grade FNCLCC (G3) were independent prognostic factors for 1-year DFS ( P<0.05), while stage Ⅳ MPNST, superficial tumor depth, age over 60 years, postoperative adjuvant radiotherapy, and anlotinib-targeted therapy were independent prognostic factors for 3-year OS ( P<0.05). MPNST patients with NF1 tend to have more superficial tumors and lower FNCLCC grades. FNCLCC grade, R 0 resection, and adjuvant therapies, including radiotherapy and anlotinib-targeted therapy, are closely associated with MPNST prognosis. Complete surgical resection should be prioritized in clinical management, along with adjuvant treatments such as radiotherapy and targeted therapy of anlotinib to improve patient outcomes.

MDM2 Testing In Lipomatous Tumors: An Institutional Experience with 1,161 Neoplasms

Abstract Introduction/Objective Amplifications of the MDM2 gene is a well-recognized central molecular event in atypical lipomatous tumors, well-differentiated liposarcomas, and dedifferentiated liposarcomas. However, given the fact that most adipocytic neoplasms are benign, the specific testing approaches that will maximize the detection of MDM2 amplified tumors in an accurate and cost-efficient manner remains unclear. The purpose of this study is to present our experience with MDM2 testing by FISH in a large cohort of lipomatous neoplasms. Methods/Case Report The pathologic database of an academic medical center was queried for all lipomatous tumors as well as all tumors for which MDM2 testing was performed during a three-year period. At our center, MDM2 testing for well differentiated adipocytic neoplasms is triggered by the so-called “traditional criteria”: a deep tumor and/or tumor size &amp;gt;10 cm and/or recurrence. We also take an expanded approach for a variety of indications that may include equivocal atypia or clinical/imaging concern, among others. Testing is also performed on overt malignancies for which dedifferentiated liposarcoma is a plausible consideration after review of morphologic features. Clinicopathologic data, including patient age of diagnosis, tumor size, depth of tumor, results from MDM2 testing [when performed], anatomic location(s) and recurrence [where applicable], were collected for each patient. Results (if a Case Study enter NA) 1161 cases were assessed, 456 of whom underwent MDM2 testing, and 108 of which were ultimately classified as MDM2 amplified. Standardized bivariable comparisons found that a deep tumor location (p=0.0014) and older age (p=0.0002), but not tumor size at the &amp;gt;10 cm cut off were associated with MDM2 positivity. However, a logistic regression model showed that neither size, depth or age were significantly associated with MDM2 positivity. Among the MDM2-positive cohort, 91% had tumor sizes &amp;lt;10 cm, 14% were superficial, 23% were non-recurrent and 15% were less than the median cohort patient age of 58 years. If the aforementioned “traditional criteria” were used as the sole basis for MDM2 testing, 50 (46.29%) of the 108 cases that were ultimately classified as MDM2 positive would not have been tested. Conclusion Our findings suggest that a strict adherence to “traditional criteria” may result in a significant subset of MDM2 positive tumors not being tested in lipomatous tumors. A more expansive approach that incorporates additional indications for testing, should be evaluated.

Dedifferentiated liposarcoma of the extremities: a Korean multi-center study of 107 cases

BackgroundDedifferentiated liposarcoma of the extremities (DDL-E) is rare in comparison to that of the retroperitoneum. Its clinical features and surgical principle for resection margins at the dedifferentiated and the well-differentiated components are yet to be elucidated.MethodsThis retrospective multi-center study examined patients diagnosed with DDL-E from August 2004 to May 2023 at 5 sarcoma centers. Clinical features, oncologic outcomes, and prognostic factors were analyzed.ResultsA total of 107 patients were reviewed. The 5-year local recurrence free survival (LRFS), metastasis-free survival (MFS) and disease specific survival (DSS) were 84.7%, 78.6%, and 87.8%, respectively. Other primary malignancies and extrapulmonary metastasis were observed in 27 and 4 patients, respectively. The independent risk factor for local recurrence was R1/2 margin at the dedifferentiated component of the tumor. Metastasis was associated with tumor size in univariate analysis. The independent risk factor for DSS was tumor grade. Previous unplanned excision, de novo presentation, tumor depth, absence of the well-differentiated component, infiltrative border, R1/2 margin at the well-differentiated component were not associated with oncologic outcomes.ConclusionsThis is the largest study examining DDL-E to-date. Localized DDL-E has low potential for metastasis and carries an excellent prognosis. Other primary malignancy and extrapulmonary metastasis are more frequent in DDL-E, thus close monitoring of other sites during follow-up is recommended. While wide resection margin is the standard surgical approach for DDL-E, further investigation into moderated wide resection margin at the well-differentiated component is warranted.

Development and Validation of a Computed Tomography-Based Model for Noninvasive Prediction of the T Stage in Gastric Cancer: Multicenter Retrospective Study.

As part of the TNM (tumor-node-metastasis) staging system, T staging based on tumor depth is crucial for developing treatment plans. Previous studies have constructed a deep learning model based on computed tomographic (CT) radiomic signatures to predict the numberoflymphnodemetastases and survival in patients with resected gastric cancer (GC). However, few studies have reported the combination of deep learning and radiomics in predicting T staging in GC. This study aimed to develop a CT-based model for automatic prediction of the T stage of GC via radiomics and deep learning. A total of 771 GC patients from 3 centers were retrospectively enrolled and divided into training, validation, and testing cohorts. Patients with GC were classified into mild (stage T1 and T2), moderate (stage T3), and severe (stage T4) groups. Three predictive models based on the labeled CT images were constructed using the radiomics features (radiomics model), deep features (deep learning model), and a combination of both (hybrid model). The overall classification accuracy of the radiomics model was 64.3% in the internal testing data set. The deep learning model and hybrid model showed better performance than the radiomics model, with overall classification accuracies of 75.7% (P=.04) and 81.4% (P=.001), respectively. On the subtasks of binary classification of tumor severity, the areas under the curve of the radiomics, deep learning, and hybrid models were 0.875, 0.866, and 0.886 in the internal testing data set and 0.820, 0.818, and 0.972 in the external testing data set, respectively, for differentiating mild (stage T1~T2) from nonmild (stage T3~T4) patients, and were 0.815, 0.892, and 0.894 in the internal testing data set and 0.685, 0.808, and 0.897 in the external testing data set, respectively, for differentiating nonsevere (stage T1~T3) from severe (stage T4) patients. The hybrid model integrating radiomics features and deep features showed favorable performance in diagnosing the pathological stage of GC.

Treatment strategy for cervical lymph node metastases from early-stage tongue and floor of the mouth squamous cell carcinoma using tumour budding and depth of invasion as predictors.

This study aimed to determine whether elective neck dissection can help improve outcomes in early-stage tongue and floor squamous cell carcinoma (SCC) by statistically analysing the relationship between information obtained from biopsy specimens and the incidence and prognosis of cervical lymph node metastasis (CLM). Biopsy specimens of 103 patients diagnosed with early cT1-T2 cancer of the tongue and floor of the mouth were included. Multivariate analysis showed that the three parameters significantly correlated with CLM, and univariate analyses showed that budding score (BS) ≥ 5 and pathological depth of invasion (pDOI) ≥ 5mm were independent risk factors for CLM. There were significant differences in the 5-year cumulative disease-specific survival between the BS < 5 and BS ≥ 5 groups, the pDOI < 5mm and pDOI ≥ 5mm groups, and the positive and negative budding and depth of invasion (BD) score groups. In early-stage tongue and floor of the mouth cancers with maximum tumour diameter ≤ 20mm, it may be necessary to treat occult CLM during initial surgery based on the following preoperative criteria: pDOI ≥ 5mm or BS ≥ 5 in biopsy specimens and DOI ≥ 8mm on imaging. The BD model exhibited the highest specificity and proved helpful for CLM prediction. pDOI ≥ 5mm and BS ≥ 5 were independent predictors of CLM and prognosis in early-stage tongue and floor of the mouth cancers with a maximum tumour diameter of 20mm.

Tumor thickness is associated with metastasis in patients with submucosal invasive adenocarcinoma of the esophagogastric junction.

In submucosal invasive adenocarcinoma of the esophagogastric junction (pT1b-SM AEG), the extent of tumor submucosal (SM) invasion is measured using the vertical depth of SM invasion with the muscularis mucosa. This study aimed to investigate whether tumor thickness and depth of invasion without accounting for muscularis mucosa were superior to the vertical depth of SM invasion as metastasis predictors. We enrolled patients with pT1b-SM AEG who underwent endoscopic resection or surgical resection (SR) at our institution between January 2011 and September 2019 and were followed up for ≥2years. The relationship between metastasis and clinicopathological factors was examined. Metastasis was defined as pathologically confirmed lymph node metastasis in the surgical specimen or recurrence during follow-up. This study included 57 patients (44 men; median age, 72years). Endoscopic resection and SR were performed in 16 and 41 patients, respectively. Nine patients were diagnosed with metastasis: five who underwent SR showed pathologically confirmed lymph node metastasis in the surgical specimens, and four experienced recurrences during a median follow-up of 48months. Univariate analyses showed that tumor thickness was significantly associated with metastasis (P = 0.021), and the vertical depth of SM invasion (P = 0.48) and depth of invasion (P = 0.38) were not. Furthermore, in multivariate analysis, tumor thickness ≥2800μm (odds ratio, 38.70; P = 0.013) was a significant predictor for metastasis. Tumor thickness may be a more convenient and useful predictor of metastasis in patients with pT1b-SM AEG than the vertical depth of SM invasion.

Validation of clinical tumor depth of invasion measure in patients with oral cavity cancer

ObjectivesThe 8th edition of the American Joint Committee on Cancer (AJCC) for head and neck malignancies incorporated depth of invasion (DOI) for oral cavity squamous cell carcinoma (OCSCC). Currently, there is no standardized method to determine clinical DOI (cDOI). We aim to validate radiologic DOI (rDOI) utilizing contrast-enhanced computed tomography (CECT) imaging. Materials and MethodsRadiographic DOI was defined as the coronal measurement of the deepest margin parallel to the expected normal mucosal plane. To establish a valid, accurate and repeatable rDOI, a retrospective cohort at a single institution tertiary hospital underwent preoperative CECT. Radiographic DOI was independently assessed by 2 neuroradiologists. Correlation was determined between rDOI and pDOI. A prospective pilot study of 49 patients with newly diagnosed OCSCC underwent rDOI assessment compared to final pDOI to assess our rDOI method clinical applicability. ResultsNeuroradiologists demonstrated a high degree of predictability between rDOI and pDOI with as great as 90.91% accuracy for readable CECTs. Inter-observer correlations were strong in the retrospective (Session 1: ICC= 0.956; Session 2: ICC= 0.932) and prospective cohorts (Session 1: ICC= 0.859; Session 2: ICC=0.913) illustrating reliability. Intraobserver correlations were also strong (Retrospective Reader 1 ICC=0.968, Reader 2 ICC=0.941; prospective Reader 1 ICC=0.965, Reader 2 ICC=0.800, p<0.001). T1 lesions were immeasurable 25-62.5% of the time. ConclusionsUsing CECT, the coronal measurement of the deepest margin parallel to the expected normal mucosal plane can enhance determination of a reliable cDOI in OCSCC corresponding to pDOI without change in staging for T2 and greater lesions.

Assessment of secondary cancer risks within non-target organs during proton therapy for lung cancer: A Monte Carlo study

Proton therapy is a rapidly progressing modality with a significant impact on lung cancer treatment. However, there are concerns about the subsequent effects of secondary radiation in out-of-field organs. Thus, the present study aimed to evaluate the risk of subsequent secondary cancers within non-target organs during proton therapy for lung cancer. A Monte Carlo model of the International Commission on Radiological Protection (ICRP) 110 male phantom was employed to calculate the absorbed dose associated with secondary photons and neutrons within out-of-field organs for different tumor locations. The risk of induced secondary cancers was then estimated using the Biological Effects of Ionizing Radiation Committee (BEIR) VII and National Council on Radiation Protection and Measurements (NCRP) 116 risk models. Organs close to the tumor, such as the heart, esophagus, thymus, and liver, received the highest equivalent doses. The calculated equivalent doses increased as the tumor depth increased from 4–8 cm to 12–16 cm. The contribution of neutrons to the total equivalent dose was dominant (up to 90%) in most of the organs studied. The calculated risks of secondary cancers were higher in the liver and esophagus compared with other organs when using the BEIR risk model. The maximum risk value was obtained for the left lung when the NCRP 116 risk model was used. Furthermore, the estimated risks of secondary malignancies increased with the tumor depth using both risk models. The calculated risks of radiation-induced secondary cancers were relatively lower than the baseline cancer risks. However, extra attention is warranted to minimize subsequent secondary cancers after proton therapy for lung cancer.

Deep learning-enabled fluorescence imaging for surgical guidance: in silico training for oral cancer depth quantification.

Oral cancer surgery requires accurate margin delineation to balance complete resection with post-operative functionality. Current in vivo fluorescence imaging systems provide two-dimensional margin assessment yet fail to quantify tumor depth prior to resection. Harnessing structured light in combination with deep learning (DL) may provide near real-time three-dimensional margin detection. A DL-enabled fluorescence spatial frequency domain imaging (SFDI) system trained with in silico tumor models was developed to quantify the depth of oral tumors. A convolutional neural network was designed to produce tumor depth and concentration maps from SFDI images. Three in silico representations of oral cancer lesions were developed to train the DL architecture: cylinders, spherical harmonics, and composite spherical harmonics (CSHs). Each model was validated with in silico SFDI images of patient-derived tongue tumors, and the CSH model was further validated with optical phantoms. The performance of the CSH model was superior when presented with patient-derived tumors ( ). The CSH model could predict depth and concentration within 0.4mm and , respectively, for in silico tumors with depths less than 10mm. A DL-enabled SFDI system trained with in silico CSH demonstrates promise in defining the deep margins of oral tumors.

Preoperative prognostic stratification and prediction of long-term outcomes after pancreatoduodenectomy for distal cholangiocarcinoma

BackgroundPatients with distal cholangiocarcinoma (DCC) frequently receive adjuvant chemotherapy in preoperative and postoperative settings, but prediction of prognostic risk at the time of treatment selection remains challenging. MethodsThis single-center retrospective study enrolled DCC patients who underwent initial pancreatoduodenectomy (PD) between 2009 and 2022. Preoperative clinical parameters were collected, and Cox regression analysis was used to identify risk factors for overall survival (OS). ResultsAmong 170 patients examined, the median tumor depth was 10 mm, and 37 % of the patients were diagnosed with pT3. Overall, 46 % of patients had lymph node metastasis. The median and 5-year OS was 58.2 months and 50 %, respectively. Multivariate analysis revealed tumor size on computed tomography (CT) ≥15 mm and main pancreatic duct (MPD) dilatation (≥3 mm) as independent risk factors for OS among various preoperative parameters; the prognosis was stratified based on these two parameters. Patients with one risk factor had similar outcomes (5-year OS: 39 %) to pStage IIB DCC (pT2N1 or pT3), while those with two risk factors had a prognosis akin to pStage IIIA (pN2), with a high early recurrence rate of 64 % (5-year OS: 8 %). Among non-risk group patients with low carbohydrate antigen (CA)19-9 levels (<37 U/mL), the prognosis was comparable (5-year OS: 72 %) to those with pStage I DCC. ConclusionA simple stratification approach was developed to predict long-term postoperative outcomes. To improve poor prognosis, intensive therapy, including neoadjuvant chemotherapy, should be considered for patients with two risk factors.

Monte Carlo simulation of spatial frequency domain imaging for breast tumors during compression.

Near-infrared optical imaging methods have shown promise for monitoring response to neoadjuvant chemotherapy (NAC) for breast cancer, with endogenous contrast coming from oxy- and deoxyhemoglobin. Spatial frequency domain imaging (SFDI) could be used to detect this contrast in a low-cost and portable format, but it has limited imaging depth. It is possible that local tissue compression could be used to reduce the effective tumor depth. To evaluate the potential of SFDI for therapy response prediction, we aim to predict how changes to tumor size, stiffness, and hemoglobin concentration would be reflected in contrast measured by SFDI under tissue compression. Finite element analysis of compression on an inclusion-containing soft material is combined with Monte Carlo simulation to predict the measured optical contrast. When the effect of compression on blood volume is not considered, contrast gain from compression increases with the size and stiffness of the inclusion and decreases with the inclusion depth. With a model of reduction of blood volume from compression, compression reduces imaging contrast, an effect that is greater for larger inclusions and stiffer inclusions at shallower depths. This computational modeling study represents a first step toward tracking tumor changes induced by NAC using SFDI and local compression.

A case controlled study of risk factors for metastatic squamous cell carcinoma in organ transplant recipients: single academic medical center.

Solid organ transplant recipients (SOTRs) are at high risk of cutaneous squamous cell carcinoma (cSCC) metastasis. Despite prior studies identifying risk factors, mortality remains high. Understanding additional risk factors may aid in reducing mortality in this population. This study aimed to investigate risk factors and predictive variables for metastatic cSCC in SOTRs. The primary goal was to accurately identify transplant patients at increased risk of metastatic cSCC. A retrospective case-control study in a single institution of 3576 cases of organ transplants were identified from January 1991 to July 2022. A cohort of metastatic cancer patients and two randomly generated age and organ matched control cohorts were identified. 16 SOTR patients developed metastatic cSCC. The majority were male, with high-risk tumor sites. Tumor depth varied and half exhibited perineural invasion. Cylex® (p = 0.05) and white blood cell counts (p = 0.04) were significantly lower in these patients compared to control. Lung transplants were at highest risk relative to other solid organ transplants. Voriconazole exposure was also associated with increased metastatic risk (p = 0.04). Small sample size at a single institution. Close monitoring of SOTR, especially those with lung transplants given their increased risk, reducing immunosuppression, and limiting exposure to voriconazole can improve outcomes in SOTRs with metastatic cSCC.

Prognostic significance of anatomic site-specific depth of invasion in oral squamous cell carcinoma - An eastern Indian multi-center study

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.

Prevalence and Risk Factors for Malignant Nodal Involvement in Early esophago-gastric Adenocarcinoma: Results from the Multicenter Retrospective Congress Study (endosCopic resectiON, esophaGectomy or Gastrectomy For Early Esophagogastric Cancers).

The aim of this study was to quantify LNM risk and outcomes following treatment of early esophago-gastric (EG) adenocarcinoma. The standard of care for early T1N0 EG cancer is endoscopic resection (ER). Radical surgical resection is recommended for patients perceived to be at risk of lymph node metastasis (LNM). Current models to select organ-preserving vs. surgical treatment are inconsistent. CONGRESS is a UK-based multicentre retrospective cohort study. Patients diagnosed with clinical or pathological T1N0 EG adenocarcinoma from 2015-2022 were included. Outcomes and rates of LNM were assessed. Cox regression was performed to assess the impact of prognostic and treatment factors on overall survival. 1,601 patients from 26 centres were included, with median follow-up 32 months(IQR 14-53). 1285/1612(80.3%) underwent ER, 497/1601(31.0%) underwent surgery. Overall rate of LNM was 13.5%. On ER staging, tumour depth (T1bsm2-3 17.6% vs. T1a 7.1%), lymphovascular invasion (17.2% vs. 12.6%), or signet cells (28.6% vs. 13.0%) were associated with LNM. In multivariable regression analysis, these were not significantly associated with LNM rates or survival. Adjusting for demographic and tumour variables, surgery after ER was associated with significant survival benefit, HR 0.33(0.15-0.77),P=0.010. This large multicentre dataset suggests that early EG adenocarcinoma is associated with significant risk of LNM. This data is representative of current real clinical practice with ER-based staging, and suggests previously held beliefs regarding reliability of predictive factors for LNM may need to be reconsidered. Further research to identify patients who may benefit from organ-preserving vs. surgical treatment is urgently required.

739. SIGNIFICANCE OF COX2 INHIBITOR FOR ESOPHAGEAL CANCER FROM THE CLINICAL AND EXPERIMENTAL ESTIMATE

Abstract (Aims) We report experimental and clinical evidence that COX2 represent a potential molecular target for the treatment and prevention of esophageal cancer. (Methods) (A)Experiment: Thirty 8-week male wistar rats were exposed to duodenal content esophageal reflux. All animal underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. In ten rats the sham (Control). They were sacrified at 40th week. Their esophagi were examined for HE, COX2,PGE2, PCNA and total bile acids in the esophageal lumen was measured. (B)Clinical: The expression of COX2 was examined for 68 specimens of esophageal squamous cell carcinoma (SCC) and the correlation of COX2 expression with clinicopatholigic features was examined. (Results) (A) After 40 weeks of reflux, columnar dysplasia, squamous cell carcinoma and adenocarcinoma were found. Total bile acid in the esophageal lumen was significantly increased in the EDA group compared with the sham operated rats. PCNA LI and esophageal tissue PGE2 were higher in dysplastic and cancer tissue than that of control. Overexpression of COX2 was shown in dysplastic and cancer tissue. COX2 may play an important role in esophageal cancer by duodenal content reflux.(B) COX2 immunoreactivity was weak in 27(40%) and strong in 41(60%) of the carcinomas. The proportion of poorly differentiated SCC among tumors with a strong expression of COX2 (34%) was significantly higher than among tumors with a weak expression of COX2 (19%, p=0.02). The depth of tumors (p=0.004), lymph node metastasis (p=0.0009) and the stage of the tumors (p=0.001) were advanced significantly more progressively in ECCS with a strong COX2 expression. Moreover, survival was significantly reduced (p=0.02) among patients with strong COX2 expression when compared with the COX2 weak group. This study showed that strong expression of COX2 was correlated with tumor progression and poor differentiation in ESCC. (Conclusion) In this experimental study, we demonstrate that bile reflux of duodenal contents induce COX2 and increase prostaglandin synthesis in dysplastic and cancer tissue. Our study suggests that COX2 may play a role in esophageal carcinoma development and progression, COX2 inhibitors may be potential targets for the prevention or treatment of esophageal carcinoma.

Prognostic value of tumor-infiltrating lymphocytes and PD-L1 expression in esophageal squamous cell carcinoma.

Tumor cells (TC) participate in tumor progression by altering the immune responses in the tumor microenvironment. However, the clinical relevance and prognostic effect of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in esophageal squamous cell carcinoma (ESCC) are unknown. The purpose of this study was to investigate the interactions and clinical significance of PD-L1 expression and TILs in ESCC. Tissue specimens were collected from 126 patients with ESCC who underwent curative esophagectomy. Immunohistochemical analysis and multiplex immunofluorescence for CD4, CD8, CD25, FOXP3, and PD-L1 in the tumor were used to identify multiple tumor-infiltrating immune cells (TIIC), Tregs, and TC. PD-L1 was expressed in tumor cells (PD-L1 TC). PD-L1 TIIC and PD-L1 TC affected the biological behavior of TC. The positive expression rate of PD-L1 TC and CD8+ TILs was 27.8% (35/126) and 31.7% (40/126), respectively. Kaplan-Meier analysis showed that overall survival (OS) was significantly associated with decreased CD8+ TILs and PD-L1 TC-positive expression, which promote ESCC progression and metastasis. Tumor depth, CD8, and PD-L1 TC were independent prognostic factors in ESCC, and a predictive nomogram with these three risk factors improved the accuracy of predicting OS in patients with ESCC after surgical resection. The conjoint analysis of multiple immune-related factors is beneficial for stratifying patient survival risk.