Stage T1 Research Articles

Comparative analysis of the oncologic outcomes and risk factors for open conversion in laparoscopic surgery for non-metastatic colorectal cancer: A retrospective multicenter study

PurposeLaparoscopic colon surgery is now commonly used for colorectal cancer (CRC) resection. The objective of this study was to compare the oncologic outcomes between open conversion and laparoscopic surgery, and to identify risk factors for open conversion. MethodsWe retrospectively reviewed the medical records of patients who underwent curative resection for stage 0–III CRC at five Hallym University-affiliated hospitals between January 2011 and June 2021. The patients were divided into the conversion and laparoscopic groups according to whether laparoscopic surgery was completed. ResultsOut of 2231 patients, laparoscopic surgery was completed in 2131 patients and 100 (4.5 %) converted to open surgery. The operation time (P = 0.028) and postoperative hospital stay (P = 0.036) were longer in the conversion group than in the laparoscopic group. Overall (P = 0.022) and severe (Clavien–Dindo classification grade ≥3) (P = 0.048) complications were more frequent in the conversion group than in the laparoscopic group. The 5-year recurrence-free survival (RFS) rate was worse in the conversion group than in the laparoscopic group (P = 0.002). In the multivariable analysis, open conversion was not a prognostic factor for RFS (P = 0.082). Abdominal surgery history (P = 0.021), obstruction (P < 0.001), and T4 stage (P < 0.001) were independently associated with open conversion. ConclusionThe conversion group had worse perioperative and oncologic outcomes. History of abdominal surgery, obstruction, and T4 stage were associated with open conversion. However, conversion itself was not associated with RFS.

Construction and Validation of a Prognostic Prediction Model for Gastric Mucinous Adenocarcinoma Based on the SEER Database

This study focused on the development and validation of a prognostic model to predict overall survival (OS) in patients with gastric mucinous adenocarcinoma (GMA), utilizing data from the SEER database. A cohort of 537 GMA patients was analyzed to identify factors affecting survival, using both univariate and multivariate Cox regression analyses on demographic and clinicopathological variables. The analysis led to the creation of a nomogram model. Findings revealed that TNM staging and the administration of radiotherapy or chemotherapy were significant factors impacting survival outcomes. Specifically, patients at stages T4, N3, and M1 faced a notably higher mortality risk, while those who received radiotherapy and chemotherapy experienced a significant reduction in mortality risk. The model's performance, as indicated by C-indices of 0.73 in the training set and 0.66 in the validation set, suggests robust predictive capability. The area under the curve (AUC) analysis confirmed high accuracy in predicting 1-year, 3-year, and 5-year survival rates, and calibration curves displayed strong agreement between predicted and actual outcomes. Decision curve analysis (DCA) demonstrated that the model exhibited significant clinical utility across various thresholds. Overall, this study presents a reliable prognostic tool for individualized risk stratification and clinical treatment in GMA patients. Future work should focus on enhancing the model by incorporating molecular biological data to increase its predictive accuracy and applicability.

Neoadjuvant chemotherapy followed by definitive local treatment in locally advanced sinonasal squamous cell carcinoma.

Sinonasal squamous cell carcinoma (SCC) is a rare disease entity, comprising less than 5% of malignancies of the head and neck. While surgery is the primary treatment approach, neoadjuvant and adjuvant therapies play crucial roles in enhancing the prognosis of patients undergoing treatment with the goal of cure. In this study, we aimed to explore the treatment outcomes of neoadjuvant chemotherapy (NAC) in patients with locally advanced sinonasal SCC. Medical records of patients diagnosed of locally advanced (cT3-4b, N0-3) sinonasal SCC treated with a definitive aim between January 2005 and March 2023 were retrospectively reviewed. Patients were categorized into the following groups based on the initial treatment: NAC followed by surgery, NAC followed by concurrent chemoradiotherapy (CCRT), definitive CCRT, or upfront surgery. Initial treatment plan was decided by a multidisciplinary team. Primary endpoint was overall survival (OS) and objective response rate, and secondary endpoints were progression free survival (PFS), cumulative incidence of local and distant failures, and treatment-related toxicity. The treatment response was assessed according to the RECIST criteria. Total 126 patients were included, and the median follow-up period was 25.6 months. The objective response rate to NAC was 48.2%. The subsequent resection rate was 70%, 42.9%, and 16.7% for patients with stage T3, T4a, and T4b disease, respectively. Two-year progression-free survival did not differ significantly between the NAC followed by surgery and upfront surgery groups (53.6% vs. 60.6%, P = 0.615) or between the NAC followed by CCRT and definitive CCRT groups (26.7% vs. 37.4%, P = 0.506). NAC may be a valuable treatment option for patients with locally advanced sinonasal SCC, as it provides an opportunity for curative surgery and exhibits non-inferior oncological outcomes compared with upfront definitive local treatments.

A Single-Center Analysis of Patient Characteristics and Overall Survival in Patients with Resectable Gallbladder Cancer.

Gallbladder cancer (GBC) is a rare and aggressive hepatobiliary malignancy with poor prognosis. The symptoms of GBC are insidious and non-specific in its early stages, and most patients are diagnosed at advanced or late stages. Surgical resection is the only potentially curative treatment for GBC for select patients. There is a lack of robust data for patients with GBC, leading to heterogenous practices in management strategies and outcomes. In this study, we aimed to identify patient characteristics and cumulative overall survival (OS) in patients with GBC who underwent surgical resection with curative intent. All adult patients (age ≥18 years) with localized or locoregionally advanced GBC who underwent definitive surgery with curative intent at our tertiary institution between 1/2013 and 12/2023 were retrospectively identified. Clinical, laboratory, radiology, histopathology, treatment, and survival data were collected from electronic medical records. Postoperative data included the use of adjuvant chemotherapy or radiotherapy, and patient survival mortality at a cut-off date of 1 February, 2024, calculated from the date of curative surgery. Continuous variables are reported as median and quartile 1 (Q1) and quartile 3 (Q3), while categorical variables are reported as counts and percentages. A total of 94 patients with GBC were included in the study. Median age was 71 (62-77) years and 58 (61.7%) patients were female. Median tumor size was 3.3 (1.9-5.0) cm. Perineural invasion was seen in 48.9% and vascular invasion in 38.3% of patients. A positive surgical margin was present in 50% of the patients, and incidental GBC (IGBC) was seen in 48.9% of patients. Tumor grade was well differentiated in 7.6%, moderately differentiated in 53.3%, and poorly differentiated in 39.1% of the patients. Patients with stage T1a (2.1%) and T1b (11.7%) tumors comprised the minority, and the majority of the tumors were stage T2 (55.3%), followed by T3 (31.9%). A total of 60.6% of patients with GBC underwent adjuvant chemotherapy, and 17% underwent adjuvant radiotherapy after surgical resection. Overall, 62 (66.0%) patients died, and the median OS was 1.88 years. The 1-year OS was 68.7%, 3-year OS was 37.4%, and 5-year OS was 32.2%. A higher absolute median OS was seen in patients who had adjuvant chemotherapy (2.1 years) compared to no chemotherapy (1.9 years); however, this finding was not statistically significant (p = 0.36). The median survival was 2.3 years in IGBC compared to 1.6 years in non-IGBC (p = 0.63). GBC is an aggressive hepatobiliary malignancy that is often diagnosed at advanced stages. Our study showed high rates of local and systemic involvement and high mortality, and the need for prospective and randomized studies on adjuvant therapies to assess their survival benefit. Real-world patient data remain important to identify patients at risk of worse outcomes and to stratify risks prior to surgery.

VALUE OF REPEATED TRANSURETHRAL RESECTION IN SUPERFICIAL BLADDER CANCER

Background: Bladder cancer is a prevalent malignancy of the urinary system, with superficial tumors representing the majority of cases. Despite initial treatment with transurethral resection (TUR), these tumors have high recurrence rates (70-80%) and can progress to muscle-invasive disease in 20-30% of cases. Repeat transurethral resection (re-TUR) has been proposed as a method to improve staging accuracy and reduce the likelihood of recurrence by detecting residual tumor tissue. Methods: This prospective study included 100 patients with superficial bladder cancer (Ta and T1 stages) treated at the Urology Clinic of Istanbul Fatih Sultan Mehmet Training and Research Hospital between January 2005 and December 2006. Following the initial TUR, all patients underwent re-TUR within 4 to 6 weeks. Pathological findings from both procedures were analyzed to identify residual tumor presence and changes in tumor stage. Patients were followed up for 24 months to monitor recurrence rates and progression to muscle-invasive disease. Results: Re-TUR revealed residual tumor tissue in 40% of patients, with higher detection rates in T1 and Grade II tumors. Patients with residual tumors had a significantly higher recurrence rate (40%) compared to those without residual tumors (15%). Additionally, 20% of patients with residual tumors progressed to muscle-invasive bladder cancer, while no progression was observed in patients without residual tumors. Conclusion: Re-TUR plays a vital role in improving staging accuracy and reducing recurrence in patients with superficial bladder cancer. The presence of residual tumors significantly increases the risk of recurrence and progression, highlighting the importance of re-TUR, especially in high-risk patients. These findings support the routine use of re-TUR in managing superficial bladder cancer.

Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer

BackgroundWhether stereotactic body radiotherapy (SBRT) is noninferior to conventionally or moderately hypofractionated regimens with respect to biochemical or clinical failure in patients with localized prostate cancer is unclear.MethodsWe conducted a phase 3, international, open-label, randomized, controlled trial. Men with stage T1 or T2 prostate cancer, a Gleason score of 3+4 or less, and a prostate-specific antigen (PSA) level of no more than 20 ng per milliliter were randomly assigned (in a 1:1 ratio) to receive SBRT (36.25 Gy in 5 fractions over a period of 1 or 2 weeks) or control radiotherapy (78 Gy in 39 fractions over a period of 7.5 weeks or 62 Gy in 20 fractions over a period of 4 weeks). Androgen-deprivation therapy was not permitted. The primary end point was freedom from biochemical or clinical failure, with a critical hazard ratio for noninferiority of 1.45. The analysis was performed in the intention-to-treat population.ResultsA total of 874 patients underwent randomization at 38 centers (433 patients in the SBRT group and 441 in the control radiotherapy group) between August 2012 and January 2018. The median age of the patients was 69.8 years, and the median PSA level was 8.0 ng per milliliter; the National Comprehensive Cancer Network risk category was low for 8.4% of the patients and intermediate for 91.6%. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% (95% confidence interval [CI], 93.3 to 97.4) in the SBRT group and 94.6% (95% CI, 91.9 to 96.4) in the control radiotherapy group (unadjusted hazard ratio for biochemical or clinical failure, 0.73; 90% CI, 0.48 to 1.12; P=0.004 for noninferiority), which indicated the noninferiority of SBRT. At 5 years, the cumulative incidence of late Radiation Therapy Oncology Group (RTOG) grade 2 or higher genitourinary toxic effects was 26.9% (95% CI, 22.8 to 31.5) with SBRT and 18.3% (95% CI, 14.8 to 22.5) with control radiotherapy (P<0.001), and the cumulative incidence of late RTOG grade 2 or higher gastrointestinal toxic effects was 10.7% (95% CI, 8.1 to 14.2) and 10.2% (95% CI, 7.7 to 13.5), respectively (P=0.94).ConclusionsFive-fraction SBRT was noninferior to control radiotherapy with respect to biochemical or clinical failure and may be an efficacious treatment option for patients with low-to-intermediate-risk localized prostate cancer as defined in this trial. (Funded by Accuray and others; PACE-B ClinicalTrials.gov number, NCT01584258.)

Exploring Molecular Signatures in Early-Stage Pancreatic Ductal Adenocarcinoma: Implications for Patient Management and Therapeutic Strategies

Abstract Introduction/Objective Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges to patient survival, predominantly due to its tendency for late-stage diagnosis and high rates of post-surgical cancer recurrence. Therefore, a comprehensive understanding of the molecular characteristics associated with the early stages of PDAC is imperative. This understanding holds the potential to improve patient treatment strategies by enabling targeted interventions and personalized therapies. Methods/Case Report Initially, RNA-seq datasets of early-stage PDAC cases (stages IA, IB, IIA, and IIB, all without distant metastasis; M0) were extracted from the GEO database. Subsequently, the datasets were analyzed in four distinct groups, and differentially expressed genes were identified within each group. Group 1 compared T1T2 cases with T3 cases (T: primary tumor), irrespective of N status (N: regional lymph nodes), while group 2 compared N0 cases with N1 cases, regardless of T status. Group 3 included comparisons between T1T2N0 cases and T3N0 cases, and group 4 compared T1T2N1 cases with T3N1 cases. Utilizing a Venn diagram, commonalities between gene expression profiles were isolated. Afterward, gene ontology and signaling pathways were determined using KEGG and Enrichr. Finally, a protein network was constructed, and the proteins were evaluated using the GEPIA and TCGA clinical databases. Results (if a Case Study enter NA) The study encompassed a total of 43 cases, with 25 (58.1%) being male and 18 (41.9%) female. The mean age of the participants was 64.4 years. In group 1, the expression levels of MUC5AC, AKAP13, and SPG7 were significantly upregulated in T3 cases. In group 2, STAB1, PDLIM1, and MTUS1 emerged as the top upregulated genes in N1 cases. Group 3 exhibited notable upregulation of CCNL2, CEACAM6, and TSPAN3 in T3N0 cases, while group 4 demonstrated marked upregulation of LTBR, AKAP12, and BOP1 in T3N1 cases. These genes exhibited diverse functions in PDAC progression. They contributed to the regulation of gene expression and cell cycle progression, modulating cell proliferation, inhibiting tumor growth, regulating cell signaling, and were involved in cytoskeletal organization. Conclusion The upregulated genes in cases with the T3 and/or N1 staging components may shed light on the potential mechanisms of progression from stage IA/B to stage IIA/B in PDAC cases. Furthermore, the identified genetic alterations may hold potential therapeutic and prognostic applications for future use in the early stages of PDAC.

Value of narcotrend anesthesia depth monitoring in predicting POCD in gastrointestinal tumor anesthesia block patients

BackgroundThe purpose of this research was to evaluate the efficacy of Narcotrend (NT) monitoring on cognitive dysfunction in patients undergoing anesthesia blockade for gastrointestinal tumors and its effect on cerebral oxygen metabolism and inflammatory response.MethodsPatients preparing to undergo resection of gastrointestinal tumor resection were included and randomly divided into a control group (depth of anesthesia assessed by physician experience) and a research group (depth of anesthesia monitored by NT). HR and MAP were monitored at the preoperatively (T0), 12 h postoperative (T1), 24 h postoperative (T2), and 48 h postoperative (T3) stages. MMSE score was recorded to assess changes in cognitive function. Intracerebral oxygenation indicators (CjvO2, CERO2, and rSO2) were assessed by a blood gas analyzer. ELISA assay was conducted to explore the serum inflammatory indexes (CRP, IL-1β, and TNF-α) and neurological function indicators (NSE and MBP).ResultsMAP was higher in the research group than in the control group at T1 and T2 (P < 0.05). MMSE scores at T1, T2, and T3 stages were higher in the research group than in the control (P < 0.05). The incidence of POCD was also lower in the research group compared with the control (P < 0.05). CjvO2, CERO2, and rSO2 were significantly higher (P < 0.05) and were positively correlated with the MMSE scores. Postoperative serum inflammatory indexes were significantly elevated in both groups, but more significantly in the control group (P < 0.05). Both neurological function indicators were usually reduced after surgery, but the reduction was more significant in the research group (P < 0.05).ConclusionNT monitoring of anesthetic depth has a less physical impact on patients with gastrointestinal tumor anesthetic block, reduces the degree of postoperative POCD, and has significant clinical value.

Is Immunohistochemical Galectin-3 Expression Associated with the Epithelial-Mesenchymal Transition in High- and Low-Grade Invasive Urothelial Carcinomas of the Bladder?

Background/Objectives: Bladder cancer, predominantly urothelial carcinoma, is an important malignancy of the urinary system. Despite the same histologic grade and stage, some patients seem to have a worse prognosis. In this context, the epithelial-mesenchymal transition (EMT), characterized by the loss of E-cadherin and gain of vimentin expression, is an important process in tumor progression. Galectin-3, a lactose-binding protein involved in various cellular processes, has been associated with increased tumor cell migration, invasion, and treatment resistance. Methods: In this study, 223 bladder cancer cases were examined, and E-cadherin, vimentin, and galectin-3 expression was evaluated by immunohistochemical staining in tumor budding areas and invasive components. These markers were also correlated with clinicopathological parameters, including tumor grade and stage. Results: The results indicated a significant decrease in E-cadherin expression and an increase in vimentin staining in higher-grade and higher-stage tumors, supporting EMT involvement. Galectin-3 expression was notably higher in T1 high-grade tumors but decreased in T2 stage tumors. Despite this, no significant correlation was found between galectin-3 and E-cadherin or vimentin, suggesting a complex role of galectin-3 in EMT. Conclusions: High galectin-3 expression in T1 high-grade tumors highlights its potential role in early tumor progression and as a therapeutic target. However, the decrease in its expression in advanced stages underscores the need for further research to understand its multifaceted involvement in bladder cancer. These findings suggest that while galectin-3 may contribute to the EMT and early tumor progression, its exact role and potential as a therapeutic target require more detailed investigation.

Habitat-based CT radiomics enhances the ability to predict spread through air spaces in stage T1 invasive lung adenocarcinoma.

Spread through air spaces (STAS) represents a novel invasive pattern in lung adenocarcinoma (LUAD) and is a risk factor for poor prognosis in stage T1 LUAD. This study aims to develop and validate a CT habitat imaging analysis model for predicting STAS in stage T1 invasive LUAD. We retrospectively analyzed 217 patients with preoperative stage T1 invasive LUAD (115 STAS-positive and 102 STAS-negative cases, including 151 in the train set and 66 in the test set). Semi-automatic segmentation was performed on the regions of interest (ROIs) in all CT images, with an automatic 3mm expansion around the tumor, considering the intratumoral and peritumoral 3mm area. This area was divided into three sub-regions via K-means clustering, and 1197 radiomic features were extracted from each sub-region and the overall combined region. After dimension reduction through the Mann-Whitney U test, Pearson correlation analysis, and least absolute shrinkage and selection operator(LASSO), the best features for each sub-region and overall were selected. Models were then built using the selected radiomic features through the Adaptive Boosting (AdaBoost) and Multilayer Perceptron (MLP) classifiers. Four different models were established based on different sub-regions and the overall features. The performance of these models was evaluated through receiver operating characteristic curves (AUC) under the DeLong test, calibration curves via the Hosmer-Lemeshow test, and decision curve analysis to assess the performance of these features. In this study, we evaluated the predictive performance of AdaBoost and MLP classifiers on rad feature models across various subregions and the overall dataset. In the test set, the AdaBoost classifier achieved a maximum AUC of 0.871 in Habitat 3, whereas the MLP classifier demonstrated slightly superior performance with an AUC of 0.879. Both classifiers exhibited high efficiency in habitat 3, with the MLP algorithm showing enhanced model performance. CT habitat imaging analysis for the preoperative prediction of STAS in stage T1 invasive LUAD shows satisfactory diagnostic performance, with the habitat3 model exhibiting the highest efficacy, reflecting tumor heterogeneity.

Transoral Laser or Robotic Surgery Outcomes for Oropharyngeal Carcinoma

Transoral robotic surgery (TORS) or transoral laser microsurgery (TLM) offer excellent oncological outcomes for oropharyngeal squamous cell carcinoma caused by human papillomavirus (HPV) infection. TORS may offer greater margin clearance around tumors than TLM. To determine whether the differing energy sources used and surgical technique of TORS or TLM is associated with postoperative early swallowing function, feeding tube use, and specific factors related to quality of life. This prespecified cohort study was performed within the Postoperative Adjuvant Treatment for HPV-Positive Tumours (PATHOS) randomized clinical trial at 40 centers in the UK, Germany, France, the US, and Australia between November 1, 2015, and August 31, 2023. PATHOS trial participants with HPV-positive oropharyngeal carcinoma of stages T1 to T3 and N0 to N2b M0 (TNM7) who underwent TLM or TORS were eligible. Of 989 consecutively recruited patients on the PATHOS trial, 508 were eligible for this substudy. The exposure of interest was TORS or TLM. Preplanned outcome measures included nasogastric tube insertion rates within 4 weeks after surgery, length of in-hospital stay following surgery, specific scales from the MD Anderson Dysphagia Inventory (MDADI), 35-item European Organization for Research and Treatment of Cancer Head and Neck Questionnaire (H&N35), and 30-item Quality of Life Questionnaire (QLQ C30), water swallow test results, and videofluoroscopy scores. Of the 508 patients included in the analysis (390 [76.8%] male; median age, 58.3 [IQR, 52.8-63.6] years), 195 had TLM and 313 had TORS. Nasogastric tube insertion rates were higher after TORS than TLM (85 of 189 [45.0%] vs 10 of 126 [7.9%]; adjusted odds ratio [OR], 4.41 [95% CI, 1.01-19.32]). Mean scores favored TLM with small effect sizes in all MDADI domains and the H&N35 swallowing item at 4 weeks after surgery; between-group difference for the MDADI composite score was -4.89 (95% CI, -8.27 to -1.50); for the MDADI physical functioning score, -6.37 (95% CI, -10.15 to -2.59); for the MDADI global score, -10.02 (95% CI, -16.50 to -3.54); and for H&N35 swallowing score, 7.24 (95% CI, 2.17-12.30). No other measures showed evidence of clinically meaningful differences. In this cohort study, functional outcomes were moderately less impaired 4 weeks following TLM compared with TORS. Once the longer-term outcomes for these patients are known, these findings could aid the design and use of future head and neck-specific surgical robots. ClinicalTrials.gov Identifier: NCT02215265.

Cancer of the paranasal sinuses in Germany: Data on incidence and survival from a population-based cancer registry

PurposeThis study aims to provide a broad overview of the epidemiology of cancer of the paranasal sinuses (PSC) in Germany. The data include information on incidence, staging, clinicopathological features and survival from one of the largest cancer registries in Europe. MethodsPopulation-based data on PSC diagnosed from January 1st, 2009 until December 31st, 2019 were retrieved from the German Centre for Cancer Registry Data (ZfKD). Age standardized incidence was calculated and relative survival estimates were computed by sex, histological subtype, age group and T-, N-, and M-Stage. ResultsIn total, 3975 cases were included in this study. The age-adjusted incidence rate (ASR) for PSC was 0.3/100,000 which remained stable during the observation period. The most frequent tumor localization was the maxillary sinus (41.9 %) and the most common histological subtype was keratinizing squamous cell carcinoma (kSCC) (44.3 %). All subtypes were predominantly found in the maxillary sinus except for adenocarcinoma and neuroendocrine carcinomas (SNEC), which were most frequently located in the ethmoidal sinus. The majority of the patients with a known T stage was diagnosed in tumor stage T4 (60.8 %). The overall 5-year relative survival (RS) for all patients with PSC was 52 %. RS dropped from 93 % for T1 stage tumors to 39 % for T4 tumors. RS was 58 % for N0 and 31 % for N+ cases, 54 % for M0 and 27 % for M1 cases. ConclusionAge-adjusted incidence for PSC is low and has been stable for the observed 11-year period. RS decreases continuously with increasing T-, N- and M-stage.

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.

The First Comprehensive Evaluation of Immuno-Inflammatory Markers for Prognosis in Esophageal Cancer Patients: A South Asian Perspective.

Background: Esophageal cancer (EC) remains a significant health challenge in South Asia, with poor prognosis despite advancements in diagnostics and treatment. Identifying and validating prognostic factors is essential for improving patient outcomes. Methods: A prospective study was conducted with 146 biopsy-confirmed EC patients at the Dr. Ruth K.M. Pfau Civil Hospital, Karachi, Pakistan. Clinical and laboratory data were collected and analyzed using descriptive statistics, receiver operating characteristic (ROC) analysis, and the Chi-square test. Survival outcomes were assessed using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models for univariate and multivariate regression analyses, with statistical significance set at p ≤ 0.05. Results: Bivariate analysis showed significant associations of the neutrophil lymphocyte ratio (NLR) (p = 0.017), C-reactive protein to albumin ratio (CAR) (p = 0.033), red cell distribution width to platelet ratio (RPR) (p = 0.020), and systemic immune-Inflammation index (SII) (p = 0.009) with patient survival. Univariate analysis identified tumor length >10 cm (p = 0.016), T4 stage (p = 0.015), metastasis (p < 0.001), surgery not performed (p < 0.001), and SII (p = 0.022) as significant factors for survival, with higher SII linked to poorer overall survival (p = 0.020). Interestingly, in the multivariate model, only metastasis (p < 0.001) and surgery not performed (p = 0.011) remained significant. Conclusions: Immuno-inflammatory markers may be less pertinent prognostic factors for EC in the South Asian population.

Nomogram to Predict Nodal Recurrence-Free Survival in Early Oral Squamous Cell Carcinoma.

This study aimed to develop and internally validate a prognostic nomogram for predicting nodal recurrence-free survival (NRFS) in patients with early-stage oral squamous cell carcinoma (OSCC) with clinically negative neck lymph nodes. The management of early-stage oral cancer patients with clinically negative neck lymph nodes (cN0) remains controversial, especially concerning the need for elective neck dissection. Data from a single institution spanning 2010 to 2020 were utilized to develop and evaluate the nomogram. The nomogram was constructed using multivariable Cox regression and LASSO regression analyses to identify independent risk factors for lymph node metastasis. Internal validation was performed using bootstrap resampling to assess the nomogram's predictive accuracy. A total of 930 cN0 patients with T1 and T2 stage OSCC were randomly divided into training and validation cohorts (8:2 ratio). Independent risk factors for lymph node metastasis included tumor pathological grade (well: reference, moderate/poor: OR 1.69), cT (cT1: reference, cT2: OR 2.01), history of drinking (never: reference, current/former: OR 1.72), and depth of invasion (0 mm < DOI ≤ 5 mm: reference, 5 mm < DOI ≤ 10 mm: OR 1.31). The nomogram, incorporating these variables, demonstrated good predictive accuracy with a C-index of 0.67 (95% CI: 0.58-0.76) in the validation set. In both training and validation groups, the nomogram effectively stratified patients into low-risk and high-risk groups for occult cervical nodal metastases (p < 0.05). The nomogram enables risk stratification and improved identification of occult cervical nodal metastases in clinically node-negative OSCC patients by incorporating tumor-specific and patient-specific risk factors.

Mood State in Patients with Post-traumatic Stress Disorder due to Lung Cancer: A Clinical Application Study of Intensive Cognitive Management.

Post-traumatic stress disorder (PTSD) due to lung cancer seriously affects the mood state of patients. Intensive cognitive management is a structured management method based on cognitive behavioral therapy, which can correct cognitive distortions and regulate adverse emotions. This study mainly explored the effect of intensive cognitive management on the mood state of patients with PTSD due to lung cancer. A retrospective analysis was conducted on the clinical data of 169 patients with PTSD due to lung cancer admitted to our hospital from June 2020 to June 2021. Based on different clinical management schemes, these patients were divided into the reference group (RG, n = 87, routine management) and the study group (SG, n = 82, routine management+intensive cognitive management). The sleep status and degree of depression and anxiety were evaluated using the Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Scale (SAS), Depression Scale (D), and Post-traumatic Stress Disorder Check List (PCL). After 2 weeks (T1) and 4 weeks (T2) of nursing, the scores on the PSQI (p < 0.001), SAS (T0-T1: p < 0.001; T0-T2: p < 0.001) and D (T0-T1: p = 0.026, p < 0.001; T0-T2: p < 0.001), as well as three PCL factors (p < 0.001) of the two groups were significantly lower than those before nursing (T0). At the T1 and T2 stages, difference scores for the PSQI (difference score 1: p = 0.003; difference score 2: p = 0.006), SAS (difference score 1: p = 0.002; difference score 2: p = 0.007), and D (difference score 1: p < 0.001; difference score 2: p = 0.002) were higher in the SG compared with the RG. At the T1 stage, the difference score of the PCL high-alert factor (p = 0.008) was higher in the SG compared with the RG, with no significant difference in difference scores of other two factors (p > 0.05). At the T2 stage, the SG had higher difference scores for the three PCL factors compared with the RG (p < 0.001, p = 0.011, p < 0.001). Intensive cognitive management can effectively improve sleep quality and adverse emotions and has potential for clinical management of PTSD in patients with lung cancer.

8080 Factors Affecting Survival of Lymph Node Positive Medullary Thyroid Cancer: A Population-Based Study From Surveillance, Epidemiology, and End Results (SEER) Program

Abstract Disclosure: M. Mortagy: None. A. Abdelhameed: None. M. Hegazy: None. Introduction: 50-70% of patients with MTC have positive lymph nodes. The Aim is to identify factors affecting survival of the lymph node positive MTC sub-population. Understanding these factors is important in treating these patients. Methods 1359 patients with lymph node positive MTC who were diagnosed with positive histology or cytology from 1975 to 2020 were extracted from SEER after removing duplicates. Survival analysis was performed, and Kaplan-Meier graph was produced. Univariate and multivariable Cox regression were performed, and respective hazard ratios (HR) were generated. Results: The cohort were 54% males with a median age of 55 years. Median survival: for the cohort was 163 months with survival of 91%, 80% and 74% at 1, 3, and 5 years respectively. Univariate Cox regression was statistically significant for age (HR 1.04), female sex (HR 0.64), T4 stage (HR 2.48), M1 stage (HR 5.43), bone metastasis (HR 4.74), brain metastasis (HR 17.1), liver metastasis (HR 5.41), lung metastasis (HR 5.97), distant lymph node metastasis (HR 6.00), number of positive lymph nodes (HR 1.008), lymph node ratio (HR 4.50), tumor size (HR 1.02), multifocal tumor (HR 0.69), total number of malignant tumors (HR 1.21), not performing total thyroidectomy (HR 6.35), chemotherapy (HR 3.85), radiotherapy after surgery (HR 1.67), beam radiotherapy (HR 2.20), systemic therapy after surgery (HR 0.67). Univariate Cox regression was not statistically significant for grade, treatment delay, total number of benign tumors, race/ethnicity, income, and living in rural areas. Multivariable cox regression was done after inclusion of all significant variables from univariate Cox regression. It was only significant for number of positive lymph nodes (HR 1.03), bone metastasis (HR 0.18), liver metastasis (HR 14.57), multifocal tumor (HR 3.49), total number of malignant tumors (HR 2.66), T4 stage (HR 3.57), M1 stage (HR 3.65), not performing total thyroidectomy (HR 352.43), tumor size (HR 1.03). Conclusion: Number of positive lymph nodes, T4 stage, M1 stage, presence of liver metastasis, presence of multifocal tumor, not performing total thyroidectomy and large tumor size lead to worse prognosis. Age, gender, chemotherapy, and lymph node ratio don’t affect survival. Future research is required to study this group of patients. Presentation: 6/2/2024

9233 Sperm-carried IGF2: a Spark Contributing To Embryo Growth And Development

Abstract Disclosure: R. Cannarella: None. O.J. Rando: None. R.A. Condorelli: None. C. Sandrine: None. S. Romano: None. A. Guglielmino: None. Q. Yin: None. H. Gustafsson: None. F. Mancuso: None. C. Bellucci: None. G. Luca: None. S. La Vignera: None. A.E. Calogero: None. Background: Sperm RNAs can regulate early embryo development. A potential key regulator of growth is insulin-like growth factor 2 (IGF2), a highly conserved paternally-imprinted gene involved in cell growth and proliferation that is expressed in human spermatozoa. Animal research supports the positive impact of IGF2-supplemented cultures on embryo quality. However, the role of sperm-carried IGF2 in the early development of the human embryo is unknown. Objective: To study whether sperm-carried IGF2 mRNA influences the morphokinetics of the human embryo. Design: Prospective, uncontrolled, observational pilot study. Setting: University-affiliated fertility center. Subjects: We enrolled 16 patients undergoing assisted reproductive techniques (ART) for idiopathic or male factor infertility and 10 healthy fertile controls with proven paternity. Couples with female factor infertility due to reduced oocyte reserve were excluded, while those with tubal factor or anovulation were included. Main Outcome Measure(s): After clinical use, an aliquot of the sperm samples employed for ART was used to evaluate IGF2 mRNA levels. Embryo kinetics were recorded and correlated with the amount of IGF2 mRNA, correcting for female age, body mass index (BMI), anti-Müllerian hormone (AMH) levels, and oocyte quality. To provide mechanistic insights into the human data, a transcriptome analysis was performed of parthenotes obtained from twelve-week-old superovulated mice injected with Igf2 mRNA plus Gfp mRNA (experimental group, n=20) or Gfp mRNAs (control group, n=20). Pathway enrichment analysis was then performed using g:Profiler g:GOSt and EnrichR. Results: Sperm IGF2 mRNA negatively correlated with time to 2-cell stage (t2), t3, t4, t5, and time to expanded blastocyst (tEB), independently of maternal age, BMI, AMH, and oocyte quality. IGF2 mRNA index &amp;gt;4.9 predicted the ability of the embryo to reach the blastocyst stage at day 5, with a sensitivity of 100% and specificity of 71.6% (AUC 0.845; p&amp;lt;0.001). The distribution of sperm IGF2 levels differs significantly between morphologically good or poor embryos, with the lowest levels more frequently associated with morphologically poor embryos (61.9%) than with good ones (38.1%) (p=0.0091). Furthermore, sperm-derived IGF2 levels were significantly lower in subfertile men compared to fertile controls with proven paternity. Transcriptome analysis of Igf2-injected embryos demonstrated differential expression of 101 genes activating pathways regulating early embryo development. Conclusion: Sperm-carried IGF2 mRNA can support early embryo development, independently of female factors. Larger studies are needed to confirm this finding and to investigate its role as a clinical marker to predict the chances of obtaining blastocysts that can be implanted in infertile couples undergoing ART. Presentation: 6/1/2024

7110 Sperm-carried IGF2: a Spark Contributing To Embryo Growth And Development

Abstract Disclosure: R. Cannarella: None. O.J. Rando: None. R.A. Condorelli: None. C. Sandrine: None. S. Romano: None. A. Guglielmino: None. Q. Yin: None. H. Gustafsson: None. F. Mancuso: None. C. Bellucci: None. G. Luca: None. S. La Vignera: None. A.E. Calogero: None. Background: Sperm RNAs can regulate early embryo development. A potential key regulator of growth is insulin-like growth factor 2 (IGF2), a highly conserved paternally-imprinted gene involved in cell growth and proliferation that is expressed in human spermatozoa. Animal research supports the positive impact of IGF2-supplemented cultures on embryo quality. However, the role of sperm-carried IGF2 in the early development of the human embryo is unknown. Objective: To study whether sperm-carried IGF2 mRNA influences the morphokinetics of the human embryo. Design: Prospective, uncontrolled, observational pilot study. Setting: University-affiliated fertility center. Subjects: We enrolled 16 patients undergoing assisted reproductive techniques (ART) for idiopathic or male factor infertility and 10 healthy fertile controls with proven paternity. Couples with female factor infertility due to reduced oocyte reserve were excluded, while those with tubal factor or anovulation were included. Main Outcome Measure(s): After clinical use, an aliquot of the sperm samples employed for ART was used to evaluate IGF2 mRNA levels. Embryo kinetics were recorded and correlated with the amount of IGF2 mRNA, correcting for female age, body mass index (BMI), anti-Müllerian hormone (AMH) levels, and oocyte quality. To provide mechanistic insights into the human data, a transcriptome analysis was performed of parthenotes obtained from twelve-week-old superovulated mice injected with Igf2 mRNA plus Gfp mRNA (experimental group, n=20) or Gfp mRNAs (control group, n=20). Pathway enrichment analysis was then performed using g:Profiler g:GOSt and EnrichR. Results: Sperm IGF2 mRNA negatively correlated with time to 2-cell stage (t2), t3, t4, t5, and time to expanded blastocyst (tEB), independently of maternal age, BMI, AMH, and oocyte quality. IGF2 mRNA index &amp;gt;4.9 predicted the ability of the embryo to reach the blastocyst stage at day 5, with a sensitivity of 100% and specificity of 71.6% (AUC 0.845; p&amp;lt;0.001). The distribution of sperm IGF2 levels differs significantly between morphologically good or poor embryos, with the lowest levels more frequently associated with morphologically poor embryos (61.9%) than with good ones (38.1%) (p=0.0091). Furthermore, sperm-derived IGF2 levels were significantly lower in subfertile men compared to fertile controls with proven paternity. Transcriptome analysis of Igf2-injected embryos demonstrated differential expression of 101 genes activating pathways regulating early embryo development. Conclusion: Sperm-carried IGF2 mRNA can support early embryo development, independently of female factors. Larger studies are needed to confirm this finding and to investigate its role as a clinical marker to predict the chances of obtaining blastocysts that can be implanted in infertile couples undergoing ART. Presentation: 6/1/2024

7110 Sperm-carried IGF2: a Spark Contributing To Embryo Growth And Development

Abstract Disclosure: R. Cannarella: None. O.J. Rando: None. R.A. Condorelli: None. C. Sandrine: None. S. Romano: None. A. Guglielmino: None. Q. Yin: None. H. Gustafsson: None. F. Mancuso: None. C. Bellucci: None. G. Luca: None. S. La Vignera: None. A.E. Calogero: None. Background: Sperm RNAs can regulate early embryo development. A potential key regulator of growth is insulin-like growth factor 2 (IGF2), a highly conserved paternally-imprinted gene involved in cell growth and proliferation that is expressed in human spermatozoa. Animal research supports the positive impact of IGF2-supplemented cultures on embryo quality. However, the role of sperm-carried IGF2 in the early development of the human embryo is unknown. Objective: To study whether sperm-carried IGF2 mRNA influences the morphokinetics of the human embryo. Design: Prospective, uncontrolled, observational pilot study. Setting: University-affiliated fertility center. Subjects: We enrolled 16 patients undergoing assisted reproductive techniques (ART) for idiopathic or male factor infertility and 10 healthy fertile controls with proven paternity. Couples with female factor infertility due to reduced oocyte reserve were excluded, while those with tubal factor or anovulation were included. Main Outcome Measure(s): After clinical use, an aliquot of the sperm samples employed for ART was used to evaluate IGF2 mRNA levels. Embryo kinetics were recorded and correlated with the amount of IGF2 mRNA, correcting for female age, body mass index (BMI), anti-Müllerian hormone (AMH) levels, and oocyte quality. To provide mechanistic insights into the human data, a transcriptome analysis was performed of parthenotes obtained from twelve-week-old superovulated mice injected with Igf2 mRNA plus Gfp mRNA (experimental group, n=20) or Gfp mRNAs (control group, n=20). Pathway enrichment analysis was then performed using g:Profiler g:GOSt and EnrichR. Results: Sperm IGF2 mRNA negatively correlated with time to 2-cell stage (t2), t3, t4, t5, and time to expanded blastocyst (tEB), independently of maternal age, BMI, AMH, and oocyte quality. IGF2 mRNA index &amp;gt;4.9 predicted the ability of the embryo to reach the blastocyst stage at day 5, with a sensitivity of 100% and specificity of 71.6% (AUC 0.845; p&amp;lt;0.001). The distribution of sperm IGF2 levels differs significantly between morphologically good or poor embryos, with the lowest levels more frequently associated with morphologically poor embryos (61.9%) than with good ones (38.1%) (p=0.0091). Furthermore, sperm-derived IGF2 levels were significantly lower in subfertile men compared to fertile controls with proven paternity. Transcriptome analysis of Igf2-injected embryos demonstrated differential expression of 101 genes activating pathways regulating early embryo development. Conclusion: Sperm-carried IGF2 mRNA can support early embryo development, independently of female factors. Larger studies are needed to confirm this finding and to investigate its role as a clinical marker to predict the chances of obtaining blastocysts that can be implanted in infertile couples undergoing ART. Presentation: 6/1/2024