Depth Of Tumor Invasion Research Articles

The clinical and pathological significance of tertiary lymphoid structure in extramammary Paget's disease

BackgroundTumor-associated tertiary lymphoid structures (TLSs) are functional immune-responsive aggregates, which have been reported to be associated with better prognosis in various tumors. However, their exact characteristics and prognostic value in extramammary Paget’s disease (EMPD) remain unknown.ObjectiveTo explore the features of TLSs in EMPD and their association with clinicopathological characteristics.MethodsIn total, 171 EMPD patients from 2015 to 2023, retrospective, single center cohort were collected to assess the presence, maturation status, and location of TLSs by immunohistochemistry. Then, their clinicopathologic association and prognostic significance were further examined.ResultsTLSs were detected in 97 cases (57%) of 171 EMPD patients, including high-density TLSs in 88 cases (91%), peritumoral TLSs (pTLSs) in 89 cases (92%), TLSs around appendages (aTLSs) in 23 cases (24%), and mature TLSs in 16 cases (16%). Secondary EMPD was more likely to produce TLS (Secondary: 16/21 [76%]; Primary: 81/150 [54%]; P = 0.06), and more likely to produce Mature TLS (Secondary: 5/10 [50%]; Primary: 11/80 [14%]; P = 0.02). The subjective symptoms of EMPD patients did not seem to correlate with the presence of TLS. EMPD patients with tumor invasion were more likely to form mature TLS (Invasion: 8/32 [25%]; In situ: 8/65 [12%]; P = 0.06), recurrent EMPD patients were more likely to form TLS (Recurrent: 34/50 [68%]; Initial: 63/121 [52%]; P = 0.06) especially mature TLS (Recurrent: 8/34 [24%]; Initial: 8/63 [13%]; P = 0.04). The depth of tumor invasion in EMPD patients with mature TLS was mostly less than or equal to 4mm (mature TLS+: 7/8 [88%]; TLS-: 6/17 [35%]; P = 0.05), aTLS were less common in EMPD patients with skin appendage invasion (aTLS+: 4/23 [17%]; aTLS-: 32/74 [43%]; P = 0.03). The same EMPD patients relapse after, the existence of TLS increased [TLS+ (initial): 9/17 (53%); TLS+ (recurrence):14/17 (82%); P =.07].LimitationsRetrospective study design.ConclusionsMature TLS is a positive prognostic factor for invasive EMPD and may serve as a new biomarker and therapeutic target for EMPD.

Peritoneal recurrence in gastric cancer after curative gastrectomy: risk factors and predictive score model

Peritoneal recurrence (PR) remains the most common pattern of relapse in gastric cancer (GC), even after curative resection. Given its dismal prognosis, the identification of risk factors for PR is essential for developing new treatment modalities and selecting a more appropriate subgroup of patients. This study aimed to evaluate the risk factors and survival outcomes of patients with GC who had PR and to develop a risk score to predict PR. All patients with GC who underwent curative gastrectomy were included. For analysis, patients were divided into no recurrence (NR), recurrence in other sites (ROS), and PR. Risk factors for PR were analyzed to build a risk score. Among 622 patients with GC, 460 (74.0%) had NR, 98 (15.7%) had ROS, and 64 (10.3%) had PR. Female patients, linitis on computed tomography, depth of tumor invasion, and diffuse/mixed type were associated with PR. Patients with PR had worse overall survival than those with ROS (22.0 vs 29.8 months, respectively; P=.008). The median survival estimates after recurrence were 5.0 months in the PR group and 9.9 months in the ROS group (P<.001). The scoring system developed with 8 variables had an accuracy of 81% in predicting PR. Accordingly, 385 patients (61.9%) were classified as low risk, and 237 patients (38.1%) were classified as high risk. Among the 64 patients with PR, 53 (82.8%) were correctly classified as high risk (P<.001). Patients with PR had distinct clinicopathologic characteristics and extremely restricted survival compared with patients with recurrence in other sites. The risk-scoring model was able to identify patients at higher risk of PR.

The seven-day cumulative post-esophagectomy inflammatory response predicts cancer recurrence

BackgroundThe relationship between postoperative cumulative systemic inflammation and cancer survival needs to be investigated. We developed an approach to the prognostication of postoperative esophageal cancer by establishing low and high cut-off values for the C-reactive protein (CRP) area under the curve (AUC) at 7 and 14 days after esophagectomy.MethodsOne hundred and twenty-five consecutive patients with biopsy-proven invasive esophageal squamous cell carcinoma (SCC) who underwent esophagectomies were evaluated. Postoperative CRP levels were analyzed for the first 14 days after surgery. The AUC on days 7 and 14 were calculated and compared with clinicopathological features and survival. The cut-off values for CRP at 7 days (CRP 7 d) and 14 days (CRP 14 d) were 599 mg/L and 1153 mg/L, respectively.ResultsThe patients in the low CRP 7 d group had significantly better recurrence-free survival (RFS) and overall survival (OS), not that in the low CRP 14d group. The OS rates in the high CRP groups at PODs 1, 3, 10, and 14 were significantly lower than those in the low CRP groups. Postoperative complications were more common in the high CRP groups on PODs 3, 10, and 14. Univariate analyses revealed that pTNM stage, depth of tumor invasion, tumor location, lymph node involvement, and CRP 7 d were significant prognostic factors for both OS and RFS. The Cox proportional hazards model identified pTNM, tumor location, and CRP 7d as independent prognostic factors for the RFS and OS.ConclusionsEarly prediction of patients with postoperative complications, and adequate management will suppress the elevation of CRP 7 d and further suppress the CRP value in the late postoperative period, which may improve the prognosis of esophageal cancer patients after esophagectomy.

Training program for radiologists for improving the multidisciplinary approach for the treatment of rectal cancer

BACKGROUND: Diagnosis and treatment of patients with colorectal cancer is a multidisciplinary task. The transition to a new edition of clinical guidelines for the treatment of colorectal cancer in 2024, while maintaining the routine approach to MR staging of malignant neoplasms of this localization, reduces the level of continuity between medical specialists. AIM: To improve the quality and completeness of MR diagnostics of malignant neoplasms of the rectum to ensure continuity and improve the multidisciplinary approach. MATERIALS AND METHODS: A retrospective analysis of the completeness of compliance with the parameters of TNM 8 (2017) and the MRI subclassification T3 of rectal cancer was carried out on 137 MRI scans of the pelvic organs and protocols with conclusions to them. Based on the results of the analysis, educational training and a conclusion template for radiologists were developed and conducted, after which the MR images were re-evaluated. Before and after the training, the most fully evaluated MRI scans by radiologists were provided to medical experts to form a “second opinion”. The results obtained made it possible to calculate the absolute and relative number of consensuses (coinciding in all parameters of the conclusions) and to identify cases of rectal cancer restaging that require changes in treatment tactics. RESULTS: Before the educational training, only 11% of MRI scans and their reports met the requirements of the modern protocol. After the training, 78% of the images were completed in compliance with all requirements. Particular difficulties and the majority of “discrepancies” in conclusions arose when determining the depth of tumor invasion into the mesorectal tissue; measuring the distance from the tumor and/or affected lymph node to the mesorectal fascia or edge of the levator ani muscle and identifying signs of extramural vascular invasion. It was not possible to achieve complete consensus in all cases on these parameters. CONCLUSION: The analysis of MRI scans of the pelvic organs, the development and implementation of educational training to improve the interpretation of medical images, made it possible to significantly improve the staging of rectal cancer and ensure proper continuity in the implementation of a multidisciplinary approach.

High dose rate brachytherapy for lip cancer with interstitial, surface, or a combination of interstitial and surface mold technique

High-dose-rate brachytherapy (HDR-BT) is now becoming more common than low-dose-rate and pulsed-dose-rate BT in the treatment of lip cancer. However, due to the limited history of HDR-BT, relatively few studies have been published. Two institutions (in Ukraine and the USA) reviewed their clinical outcomes of lip cancer patients treated with HDR-BT as monotherapy or in combination with external beam radiotherapy (EBRT). An interstitial (IS), surface custom mold (SC), or a combination of IS and SC (IS+SC) was used for treatments based on the depth of tumor invasion. Prescription doses were 24 Gy in 6 BID fractions when combined with 46-50 Gy of EBRT, 45-55 Gy in 9-10 BID fractions for IS and IS+SC monotherapy or 3 Gy × 16 daily fractions for SC monotherapy. A total of 33 cases of lip cancer were treated from 2015 to 2021. By using TNM staging classification, there were 14 stage I (42.4%), 15 stage II (45.5%), and 4 stage III (12.1%) lip cancers. Thirty-one patients (93.9%) had a complete response to the treatment. Only 2 patients (6.1%) displayed local recurrence. Grade 1, 2, and 3 acute toxicities were observed in 30.3%, 51.5%, and 18.2% of patients, respectively. Grade 1, 2, and 3 late toxicities were observed in 39.4%, 21.2%, and 0.0% of cases. Cosmetic results were excellent in 21.2%, good in 54.5%, fair in 18.2%, and poor in 6.1% of patients. HDR-BT is an effective and safe treatment for lip carcinomas with excellent local control, functional, and cosmetic outcomes and should be considered as a standard treatment.

Helicobacter Pylori Infection as the Predominant High-Risk Factor for Gastric Cancer Recurrence Post-Gastrectomy: An 8-Year Multicenter Retrospective Study.

The reappearance of gastric cancer, a frequent postoperative complication following radical gastric cancer surgery, substantially impacts the near-term and far-reaching medical outlook of patients. The objective of this research was to create a machine learning algorithm that could recognize high-risk factors for gastric cancer recurrence and anticipate the correlation between gastric cancer recurrence and Helicobacter pylori (H. pylori) infection. This investigation comprised 1234 patients diagnosed with gastric cancer, and 37 characteristic variables were obtained. Four machine learning algorithms, namely, extreme gradient boosting (XGBoost), random forest (RF), k-nearest neighbor algorithm (KNN), and multilayer perceptron (MLP), were implemented to develop the models. The k-fold cross-validation technique was utilized to perform internal validation of the four models, while independent datasets were employed for external validation of the models. In contrast to the other machine learning models, the XGBoost algorithm demonstrated superior predictive ability regarding high-risk factors for gastric cancer recurrence. The outcomes of Shapley additive explanation (SHAP) analysis revealed that tumor invasion depth, tumor lymph node metastasis, H. pylori infection, postoperative carcinoembryonic antigen (CEA), tumor size, and tumor number were risk elements for gastric cancer recurrence in patients, with H. pylori infection being the primary high-risk factor. Out of the four machine learning models, the XGBoost algorithm exhibited superior performance in predicting the recurrence of gastric cancer. In addition, machine learning models can help clinicians identify key prognostic factors that are clinically meaningful for the application of personalized patient monitoring and immunotherapy.

Intratumoral T cells are associated with prognosis and chemotherapy benefit in gastric cancer.

Tumor-infiltrating lymphocytes (TILs) have been described in various malignancies and viewed as a sign of anti-tumor immunity, so they are frequently thought to be implicated in the prognosis of cancers. However, little information is available on the association of the distribution pattern of TILs with clinical outcomes in gastric cancer (GC). TIL densities at different regions were assessed immunohistochemically in 59 GC patients to analyze their relationship with clinicopathological characteristics. We found that GC patients in the high-density TIL group were significantly associated with reduced tumor invasion depth, absence of lymph node metastasis, earlier TNM stage, and improved progression-free survival (PFS). Both intratumoral CD3+ TILs and pathological T stage were identified as having an independent prognostic value. Additionally, GC patients with a high density of intratumoral CD3+ TILs were found to gain more benefit from chemotherapy. Overall, these results underscored the predictive power of intratumoral TILs in survival prognosis and chemotherapy benefit for GC.

Possibilities and limitations of magnetic resonance imaging in the diagnostics of endocervical adenocarcinomas

BACKGROUND: In recent decades, the incidence of cervical adenocarcinomas has increased from 5% to 20%. Endocervical adenocarcinomas are characterized by a more aggressive course and early metastasis. Owing to the difficulties in the cytological diagnosis of cervical adenocarcinoma, early radiation diagnostics and staging subsequently play a key role. Very few studies have examined the use of magnetic resonance imaging in diagnosing cervical adenocarcinomas. AIM: To determine the diagnostic informativeness of magnetic resonance imaging in the staging of cervical adenocarcinomas according to the T-criterion and assessing the depth of tumor invasion into the stroma of the cervix and clarify the semiotic signs of adenocarcinoma and features of tumor growth in the uterus. MATERIALS AND METHODS: In total, 123 patients diagnosed with cervical cancer (C53), who underwent diagnosis and treatment between 2020 and 2023, were examined. The examination results of 22 (18%) patients with cervical adenocarcinoma were analyzed. The average patient age was 56 years. A multiparametric magnetic resonance examination of the pelvic organs was performed on 22 patients using tomographs with a magnetic field strength of 1.5 T. Moreover, 14 (64%) patients underwent surgery including extirpation of the uterus and appendages with pelvic lymphadenectomy. The information value of magnetic resonance imaging was evaluated in 11 patients, whose first stage was surgical treatment. RESULTS: In this study, cervical adenocarcinoma was detected in 18% among all cases of cervical cancer. The information value of magnetic resonance imaging in assessing the local prevalence of endocervical adenocarcinoma according to the T-criterion was as follows (main value with the corresponding 95% confidence interval): sensitivity, 77.78% (39.99%–97.19%); specificity, 50.00% (1.26%–98.74%); positive predictive value, 87.50% (62.64%–96.69%); negative predictive value, 33.33% (7.30%–76.04%); and accuracy, 72.73% (39.03%–93.98%). The information value of magnetic resonance imaging in assessing the depth of tumor invasion into the cervical stroma was as follows: odds ratio, 3.500 (0.145%–84.694%); sensitivity, 85.7% (0.757%–0.993%); specificity, 33.3% (0.018%–0.0648%); positive predictive value, 75% (0.673%–0.883%); negative predictive value, 50% (0.027%–0.972%). CONCLUSIONS: The results of this study showed that magnetic resonance imaging is a good tool with high diagnostic informativeness in detecting endocervical cervical adenocarcinoma. The four macrostructures of tumor growth in endocervical adenocarcinoma identified during magnetic resonance imaging data analysis indicate locally aggressive tumor growth and a high frequency of endometrial dropouts. This finding will allow radiologists to structure a descriptive picture, including the verified cervical adenocarcinoma, to enhance methods of developing a treatment plan for the patient.

EP392 - Different modalities used in the investigation of anorectal lesions: a case report and discussion

Abstract Introduction Endoanal ultrasound scan (EAUS) /MRI rectum followed by early open/endoscopic, resection/biopsy for histology are important to plan management of all anorectal lesions. Here, we report an incidentally found inter-sphincteric lesion investigated with both EAUS and MRI scans, followed by excision. Case report A 55-year-old patient presented with post-menopausal bleeding and was investigated with an MRI pelvis which confirmed the causative subserosal fibroid. An incidental 15x12 mm focal soft tissue lesion at 2 o’clock between the internal and external anal canal sphincters was also picked up by the consultant GI radiologist. Her colonoscopy was normal but her digital rectal examination revealed a palpable submucosal elongated pea shaped lump at 2 o’clock. A lower GI specialist nurse performed an EAUS which suggested the lesion to be at 10 o’clock. At examination under anaesthetic (EUA), the mass in the inter-sphincter anal canal was confirmed at 2 o’clock, and excised after careful dissection from its intersphincteric location; histology confirmed a leiomyoma. The patient recovered well from the procedure. Discussion MRI and endoanal ultrasound are key imaging modalities in the diagnosis of rectal masses. EAUS provides more accurate assessment of depth of tumour invasion compared to MRI, and its relation to the anal sphincters; however, the scans are highly operator-dependent, as we found, and need to be interpreted with the benefit of clinical examination. Conclusion MRI and EAUS are complimentary in investigating rectal masses; however clinical examination, (especially under anaesthetic), as well as histology, gives the best information to plan subsequent management of common and unusual lesions (such as this) in the anorectum.

392. MACHINE LEARNING TO PREDICT LYMPH NODE METASTASIS IN T1 ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A MULTICENTER STUDY

Abstract Background Lymph node metastases (LNM) is a relatively uncommon but possible complication of T1 esophageal squamous cell carcinoma (ESCC). Existing models do poorly when it comes to quantifying this risk. As a branch of artificial intelligence, machine learning (ML) algorithms have developed and become more prominent. Up to now, no individualized ML prediction model aimed at predicting LNM in T1 esophageal squamous cell carcinoma patients is available. This study aimed to develop a machine learning model for LNM in patients with T1 esophageal squamous cell carcinoma. Methods Patients with T1 squamous cell carcinoma treated with surgery between January 2010 and September 2021 from 3 institutions were included. Machine-learning models were developed using data on patients’ age and sex, depth of tumor invasion, tumor size, tumor location, macroscopic tumor type, lymphatic and vascular invasion, and histologic grade. Elastic net regression (ELR), random forest (RF), extreme gradient boosting (XGB), and a combined (ensemble) model of these was generated. Use Area Under Curve (AUC) to evaluate the predictive ability of models. The contribution of each factor was calculated. To meet clinical needs, we designed the model as a user-friendly website. Results 926 and 341 patients were included in the derivation and validation cohorts. The lymph node metastasis rate was 14.8%. The models all exhibited potent discriminating power. The elastic net regression model performed best with externally validated AUC of 0.803 (AUC 0.773 for RF, 0.791 for XGB, 0.799 for ensemble) whereas the NCCN guidelines identified patients with LNM with an AUC of 0.576 and logistic model with an AUC of 0. 670. The most important features were lymphatic and vascular invasion as well as depth of tumor invasion. Conclusions The model created utilizing machine learning approaches had excellent performance estimating the likelihood of LNM in T1 ESCC, which can help patients achieve personalized treatment options.

203. THE NUMBER OF RESECTED LYMPH NODES FROM THE UPPER MEDIASTINAL AREA PREDICTS LONG-TERM OUTCOMES OF ESOPHAGEAL CANCER AFTER MIE

Abstract Background The total number of resected lymph nodes (LNs) is an important determinant of longer survival after esophagectomy for esophageal squamous cell carcinoma (ESCC). However, resected LN counts from which areas affect long-term outcomes remain unclear. Methods: This study comprised 406 patients who underwent minimally invasive esophagectomy (MIE) at Kobe University Hospital. Resected LN counts were evaluated in the following areas: upper mediastinal (UM), middle mediastinal (MM), lower mediastinal (LM), and abdominal (Abd). Cut-off values for LN counts from each area were determined using receiver operating characteristics analysis to the survival status. Cox proportional hazards regression analyses were performed to identify prognostic factors. Results: The cut-off values for large or small numbers of resected LN counts in the UM, MM, LM, and Abd areas were 4, 8, 5, and 18 in patients with upper and middle thoracic (Ut/Mt) ESCC, respectively, and 7, 6, 5, and 24 in patients with lower thoracic (Lt) ESCC, respectively. Multivariate analysis in patients with Ut/Mt ESCC revealed that tumor invasion depth, lymph node metastasis and the resected LN count from the UM area were independent risk factors for overall survival (hazard ratio = 7.04; 95% confidence interval = 4.47-11.1, hazard ratio = 4.01; 95% confidence interval = 1.96-8.21, hazard ratio = 2.18; 95% confidence interval = 1.24-3.82, respectively). In patients with Lt ESCC, tumor invasion depth, lymph node metastasis and pulmonary complication were independent risk factors for overall survival (hazard ratio = 4.23; 95% confidence interval = 2.14-8.35, hazard ratio = 3.83; 95% confidence interval = 1.75-8.38, hazard ratio = 2.80; 95% confidence interval = 1.38-5.65, respectively). Resected LN counts from no areas were prognostic factors. Conclusions: The number of resected LNs from the UM area influenced survival outcomes of patients with Ut/Mt ESCC after MIE.

NFS1 as a Candidate Prognostic Biomarker for Gastric Cancer Correlated with Immune Infiltrates.

Cysteine desulfurase (NFS1) is closely associated with the occurrence and development of human tumors, but its relationship with the prognosis and immunity of gastric cancer (GC) patients remains unclear. To study the relationship between NFS1 and GC, GC-related data of TCGA were downloaded and analyzed. At the same time, Tumor Immune Estimation Resource (TIMER) and Kaplan‒Meier Plotter were used for relevant online analysis. Clinical samples were collected for immunohistochemical testing to validate the results. The mRNA and protein levels of NFS1 in GC tissues were significantly higher than those in normal tissues. In terms of the operating characteristic curve (ROC), the area under the curve (AUC) was 0.793, indicating that NFS1 had a high diagnostic value for GC. Further analysis showed that NFS1 expression was highly correlated with the depth of tumor invasion, lymph node metastasis, and tumor stage. Survival analysis showed that patients with high expression of NFS1 had a poorer prognosis, and NFS1 was an independent risk factor. Enrichment analysis by GO, KEGG, and GSEA showed that NFS1 was enriched in immune-related pathways. The expression of NFS1 was significantly positively correlated with the proportion of macrophages M0 and plasma cells but negatively correlated with the proportion of B cells memory, monocytes, and mast cells resting. In addition, NFS1 expression was significantly correlated with TMB levels and responses to immunotherapy. Our results suggest that NFS1 may be a potential biomarker for the diagnosis and prediction of prognosis and immunotherapy efficacy in GC.

Recent advances in the diagnosis of rectal cancer and evaluation of clinical treatment efficacy using magnetic resonance imaging

Accurate preoperative tumor staging is essential for precise treatment of rectal cancer, and magnetic resonance imaging (MRI) is the preferred method. In addition to accurately determining tumor (T) and stages node (N), MRI can also be used to evaluate factors related to the prognosis of rectal cancer, such as depth of tumor invasion into the muscular layer, extramural vascular invasion of the tumor, and distance to the circumferential resection margin. MRI is also an important method for evaluating tumor regression after neoadjuvant therapy, and quantitative biomarkers of functional MRI can objectively reflect treatment efficacy. Moreover, MRI can predict response after neoadjuvant therapy, local recurrence rate, and disease-free survival before treatment. The present article reviews recent advances in the preoperative diagnosis and staging of rectal cancer, reassessment after neoadjuvant therapy, and evaluation of clinical treatment efficacy using MRI.

The comparison of clinicopathological characteristics of two distinct manifestations of gastric signet ring cell carcinoma under EUS

ABSTRACT Background and Objectives There are two different endoscopic ultrasonographic manifestations of gastric signet ring cell carcinoma (GSRCC). No studies have been reported on the differences in the clinical profiles of patients based on EUS examination. We aim to study the variations in clinicopathological characteristics between two distinct endoscopic ultrasonographic manifestations of GSRCC. Methods A total of 302 patients with GSRCC confirmed by pathological examination who underwent EUS were enrolled in the study. Based on the endoscopic ultrasonographic features, patients were categorized into two groups: type 1, where the entire layer structure disappeared, and type 2, where the layer structure was still present and appeared lymphomatoid. Clinicopathologic features were collected retrospectively and analyzed. Results Compared with type 2 patients, type 1 patients tended to develop GSRCC at an older age (P = 0.033) and had higher serum levels of tumor markers and were more likely to experience anemia (P &lt; 0.001) and weight loss (P &lt; 0.001) during the disease progression. Significant increases in the tumor size (P &lt; 0.001), thickness of the affected gastric wall (P &lt; 0.001), and depth of tumor invasion (P &lt; 0.001) were observed in type 1 patients. Furthermore, type 1 patients had higher prevalence of affected blood vessels (P &lt; 0.001), nerves (P &lt; 0.001), lymph nodes (P &lt; 0.001), and peritoneal metastasis (P &lt; 0.001). However, no difference was found in the duration of disease between the two groups, and all deficient mismatch repairs were observed in type 1 patients. Conclusions The two distinct endoscopic ultrasonographic manifestations of GSRCC exhibited different clinicopathological characteristics, suggesting that they may represent different subtypes of the disease that require special attention in management strategies.

Association between tumor size and prognosis in patients with small bowel adenocarcinoma-a SEER-based study

BackgroundThe association between small-bowel adenocarcinoma (SBA) tumor size and prognosis is unclear, and we used the Surveillance, Epidemiology, and End Results (SEER) database to assess the prognostic value of SBA tumor size. MethodsPatients with postoperative SBA were selected from the SEER database, and overall survival (OS) and cancer-specific survival (CSS) were used as outcome variables. Tumor size was used as a categorical and continuous variable, respectively, to adjust for confounders and analyze the association between SBA tumor size and prognosis using Cox proportional hazard regression, and the results were visualized using restricted cubic splines (RCS). Spearman correlation coefficient was used to evaluate the statistical correlation between tumor size and tumor invasion depth (T-stage). Kaplan-Meier survival curves were used to estimate OS at different T stages. ResultsWhen the tumor size was analyzed as a quantitative variable, the adjusted covariate model showed that the HR was 1.008 (P = 0.04) for OS and 1.021 (P = 0.03) for CSS. And regardless of OS or CSS, when the tumor size < 3–4 cm, there was a close linear relationship between tumor size and HR. What's more, in the SEER database, the 5-year survival rates of T1, T2, T3 and T4 patients were 81.8 %, 81.1 %, 66.0 % and 50.9 % (P < 0.001) according to AJCC T-stage. However, in the modified T-stage (mT), these rates were 82.8 %, 70.6 %, 60.7 % and 39.8 % (P < 0.001). When patients within each of the AJCC T stages were stratified by mT stages, significant survival heterogeneity was observed within each of the AJCC T1 to T4 stages(P < 0.001). ConclusionWhen tumor size is used in a quantitative way, tumor size is an independent predictor of poor outcome in patients with SBA. Furthermore, we established a modified T-stage based on tumor size and depth of invasion.

Downregulation of malic enzyme 3 facilitates progression of gastric carcinoma via regulating intracellular oxidative stress and hypoxia-inducible factor-1α stabilization

BackgroundGastric cancer (GC) is one of the most malignant cancers worldwide. Metabolism disorder is a critical characteristic of malignant tumors related to tumor progression and metastasis. However, the expression and molecular mechanism of malic enzyme 3 (ME3) in GC are rarely reported. In this study, we aim to investigate the molecular mechanism of ME3 in the development of GC and to explore its potential value as a prognostic and therapeutic target in GC.MethodME3 mRNA and protein expression were evaluated in patients with GC using RT-qPCR, WB, and immunohistochemistry, as well as their correlation with clinicopathological indicators. The effect of ME3 on proliferation and metastasis was evaluated using Cell Counting Kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU) assay, transwell assay, wound healing assay, and subcutaneous injection or tail vein injection of tumor cells in mice model. The effects of ME3 knockdown on the level of metabolites and hypoxia-inducible factor-1α (HIF-1α) protein were determined in GC cells. Oxidative phosphorylation was measured to evaluate adenosine triphosphate (ATP) production.ResultsME3 was downregulated in human GC tissues (P < 0.001). The decreased ME3 mRNA expression was associated with younger age (P = 0.02), pathological staging (P = 0.049), and lymph node metastasis (P = 0.001), while low ME3 expression was associated with tumor size (P = 0.048), tumor invasion depth (P < 0.001), lymph node metastasis (P = 0.018), TNM staging (P < 0.001), and poor prognosis (OS, P = 0.0206; PFS P = 0.0453). ME3 knockdown promoted GC cell malignancy phenotypes. Moreover, α-ketoglutarate (α-KG) and NADPH/NADP+ ratios were reduced while malate was increased in the ME3 knockdown group under normoxia. When cells were incubated under hypoxia, the NADPH/NADP+ ratio and α-KG decreased while intracellular reactive oxygen species (ROS) increased significantly. The ME3 knockdown group exhibited an increase in ATP production and while ME3 overexpression group exhibited oppositely. We discovered that ME3 and HIF-1α expression were negatively correlated in GC cells and tissues, and proposed the hypothesis: downregulation of ME3 promotes GC progression via regulating intracellular oxidative stress and HIF-1α.ConclusionWe provide evidence that ME3 downregulation is associated with poor prognosis in GC patients and propose a hypothesis for the ME3 regulatory mechanism in GC progression. The present study is of great scientific significance and clinical value for exploring the prognostic and therapeutic targets of GC, evaluating and improving the clinical efficacy of patients, reducing recurrence and metastasis, and improving the prognosis and quality of life of patients.

Value of surgical lymph node assessment for patients with vulvar melanoma

ObjectiveInvestigate the utilization and outcomes of lymphadenectomy/ sampling (LND) for patients with vulvar melanoma. Materials and methodsPatients diagnosed between 2004–2015 with vulvar melanoma with known depth of tumor invasion and no distant metastases were identified in the National Cancer Database. Based on pathology report patients who underwent inguinal lymph node sampling/dissection were identified. Clinico-pathological characteristics and overall survival were compared between the two groups. ResultsA total of 1286 patients were identified; 62.8 % (n = 808) underwent lymphadenectomy/ sampling. Patients who underwent lymphadenectomy/ sampling were younger (median 66 vs 76 years, p < 0.001), more likely to have private insurance (42.9 % vs 27.8 %, p < 0.001), present with tumor ulceration (65.9 % vs 58.6 %, p = 0.01), have deeper tumor invasion (p < 0.001) and undergo radical vulvectomy (26.4 % vs 12.1 %, p < 0.001). Patients who underwent lymphadenectomy/ sampling had better overall survival compared to those who did not (median 49.08 vs 35.91 months respectively, p < 0.001). After controlling for patient age, race, insurance status, comorbidities, presence of tumor ulceration and Breslow depth of invasion performance of lymphadenectomy/ sampling was associated with better survival (hazard ratio: 0.78, 95 % confidence intervals: 0.67, 0.92). ConclusionFor patients with vulvar melanoma with at least 1 mm invasion lymphadenectomy/ sampling was associated with better overall survival likely secondary to stage migration.

Predicting tumor invasion depth in gastric cancer: developing and validating multivariate models incorporating preoperative IVIM-DWI parameters and MRI morphological characteristics

IntroductionAccurate assessment of the depth of tumor invasion in gastric cancer (GC) is vital for the selection of suitable patients for neoadjuvant chemotherapy (NAC). Current problem is that preoperative differentiation between T1-2 and T3-4 stage cases in GC is always highly challenging for radiologists.MethodsA total of 129 GC patients were divided into training (91 cases) and validation (38 cases) cohorts. Pathology from surgical specimens categorized patients into T1-2 and T3-4 stages. IVIM-DWI and MRI morphological characteristics were evaluated, and a multimodal nomogram was developed. The MRI morphological model, IVIM-DWI model, and combined model were constructed using logistic regression. Their effectiveness was assessed using receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC).ResultsThe combined nomogram, integrating preoperative IVIM-DWI parameters (D value) and MRI morphological characteristics (maximum tumor thickness, extra-serosal invasion), achieved the highest area under the curve (AUC) values of 0.901 and 0.883 in the training and validation cohorts, respectively. No significant difference was observed between the AUCs of the IVIM-DWI and MRI morphological models in either cohort (training: 0.796 vs. 0.835, p = 0.593; validation: 0.794 vs. 0.766, p = 0.79).ConclusionThe multimodal nomogram, combining IVIM-DWI parameters and MRI morphological characteristics, emerges as a promising tool for assessing tumor invasion depth in GC, potentially guiding the selection of suitable candidates for neoadjuvant chemotherapy (NAC) treatment.

A comparison of whole-mount and conventional sections for pathological mesorectal extension and circumferential resection margin assessment after total mesorectal excision

IntroductionThe objective of the study is to compare 2 techniques for histological handling of rectal cancer specimens, namely whole-mount in a large block vs conventional sampling using small blocks, for mesorectal pathological assessment of circumferential resection margin status and depth of tumor invasion into the mesorectal fat. MethodsThis is a prospective study including 27 total mesorectal excision specimens of rectal cancer from patients treated for primary rectal carcinoma between 2020 and 2022 in a specialized multidisciplinary Colorectal Unit. For each total mesorectal excision specimen, 2 contiguous representative tumoral slices were selected and comparatively analyzed with whole-mount and small blocks macroscopic dissection techniques, enabling comparison between them in the same surgical specimen. The agreement between the 2 techniques to assess the distance of the tumor from the circumferential resection margin as well as the depth of tumor invasion was evaluated with the Student’s t-test for paired samples, Pearson’s correlation coefficient, and the Bland-Altman method comparison analysis. ResultsComplete mesorectal excision was observed in 8% of cases. Circumferential resection margin involvement was observed in only one case (4 %). The whole-mount and small block techniques obtained similar results when we assessed the distance to the circumferential resection margin (t-test P = 0.8, r = 0.92) and the depth of mesorectal infiltration (t-test P = 0.6, r = 0.95). ConclusionsBoth gross dissection techniques (whole-mount vs multiple small cassettes) are equivalent and reliable to assess the distance to circumferential resection margin and the depth of mesorectal infiltration in the mesorectal fat in rectal cancer staging.

Cathepsin V is a useful prognostic factor for colorectal cancer

Molecular studies have identified various treatment-related prognostic molecules to enhance the effectiveness of colorectal cancer (CRC) treatment and improve survival rates. The expression of cathepsin V in gastrointestinal cancer cells prompted an investigation into its potential as a prognostic indicator for CRC. The evaluation of cathepsin V expression and its clinicopathological significance was conducted through immunohistochemistry in a tissue microarray, encompassing 142 CRC and normal colorectal tissues. Overall and disease-free survival rates, based on cathepsin V expression levels, were assessed using the Kaplan–Meier method and compared utilizing the log-rank test. Univariate and multivariate analyses, employing a Cox proportional hazards model, were performed to identify prognostic factors. Cathepsin V expression exhibited no correlation with age, sex, tumor location, tumor size, or histological grade. However, it was significantly correlated with depth of tumor invasion, regional lymph node (LN) metastasis, distant metastasis, and lymphovascular involvement (all p<0.001). Overall and disease-free survival rates were significantly better with low cathepsin V expression than with high expression (p<0.001). Univariate analysis identified several prognostic factors, including histological grade (low vs. high), tumor size (≤ vs. >5 cm), tumor depth (T1 vs. ≥T2), regional LN metastasis, distant metastasis, tumor-node-metastasis (TNM) stage (Stage I vs ≥II), lymphovascular involvement, and cathepsin V expression. Multivariate analysis revealed that tumor depth, distant metastasis, and cathepsin V expression are independent predictors of poor survival. Cathepsin V is frequently expressed in CRC, and its high expression is associated with poor prognosis. Therefore, cathepsin V is a useful prognostic marker for CRC.