Stage T1 Research Articles

Necrosis area, Tumor Size, and Lymph Node of Breast Cancer

Background: Breast cancer is the leading cause of cancer deaths in women worldwide in 2020. The high mortality rate is often influenced by various reasons, one of which is patients's prognosis. One of the prognostic factors is necrosis area, caused by hypoxic tumor tissue that can affect tumor growth and metastasis. Therefore, this study aims to determine the relationship between necrosis area with tumor size and lymph node metastasis in breast cancer patients. Methods: This study was an observational analytic with a cross-sectional approach. This research was conducted at the Anatomical Pathology Laboratory of Dr Soedarso Pontianak General Hospital and the Microscopy Laboratory of the Faculty of Medicine Tanjungpura University from September until November 2022. The study sample was 55 slides of Formalin-Fixed Paraffin-Embedded (FFPE). The study was conducted by observing the preparations under a microscope and then analyzed using ImageJ and SPSS software. The independent variable in this study was the necrosis area in the tumor microenvironment, and the dependent variables were tumor size and lymph node metastasis in breast tissue. Results: All study samples were female patients with invasive ductal carcinoma. Breast cancer tends to occur in patients aged 48-55 years. The highest percentage of necrosis area was 21% and the most diagnosed breast tumor size and lymph node metastasis were stage T4 and stage N2. Spearman's rho correlation test showed that there was no relationship between necrosis area and tumor size (p = 0.122; r = 0.16) and lymph node metastasis (p = 0.637; r = 0.18). Conclusions: There is no correlation between necrosis area with tumor size and lymph node metastasis of breast cancer patients in the Anatomical Pathology Laboratory at Dr Soedarso Pontianak General Hospital.

Assessment of clinical and pathological response to neoadjuvant chemotherapy in breast cancer according to molecular subtypes

Background. Breast cancer (BC) is the commonest tumor in women. It is the leading malignancy in world, and representing an emerging oncologic issue in all countries. In Iraq, BC cases reached 7246 in 2021by Iraqi Cancer Registry reports. Objectives. The study conducted for assessment the clinical and pathological responses to neoadjuvant chemotherapy in BC among molecular subtypes and for description the clinico-pathologic features, and patterns of BC according to molecular subtypes. Methods. A prospective study of 60 females with breast cancer histologically confirmed were enrolled. All women received neoadjuvant chemotherapy. Then all patients underwent definitive surgery including MRM+AC or BCS+AC. The patients’ demographic, the pathologic and molecular subtypes date of the primary tumor were recorded. Results. The mostly distributed age group was belong to group 46-55 yrs in 22, 36.7%. The mean age was 49.7±10.8 yrs. The IDC represented the most common histopathological types of BC. The most of cases seen in upper-outer quadrant (UOQ). The results post-chemotherapy as followed: ypTx stage reported in 32 (53.3%), ypT1 in 15 (25.0%), ypT2 in 10 (16.7%) and ypT3 in 3 (5.0%). ypN0 stage in 40 patients (66.7%), ypN1 in 11 (18.3%), ypN2 in 6 (10.0%), and ypN3 in 3 (5.0%). There was a high statistical difference between cT and ypT in pre and post-chemotherapy (P<0.0001), between cN and ypN in pre and post-chemotherapy (P=0.001) and between M and ypM in pre and post-chemotherapy (P=0.002). The mass location (P=0.005) and tumor size (P = 0.011) had significantly impacted on BC responses post NACT. 18(30.0%) had clinical complete response (cCR), 32 women (53.3%) had partial response (cPR), six cases (10.0%) had stable disease, and four cases (6.7%) had progressive disease. The cCR was better seen in T1 (77.8%) than T2 (22.2%), with statistical significant difference (P=0.002). The cCR was better seen in N0 (61.1%) than N1 (38.9%), with a high statistical significant difference (P<0.0001). Conclusions. The commonest age breast cancer is four to five decade. The IDC and mass situated at UOQ are the most common features of BC. Approximately, 30.0% of women have clinical complete response (cCR), 53.3% have partial response (cPR), 10.0% have stable disease, and 6.7% have progressive disease post NACT. The ER positive, PR positive, and HER2neu negative are the mostly frequent subtype recorded in this study. The cCR is better seen in T1 and N0 stages. ER+ and PR+ are more reported after NACT whereas HER2neu- is more post NACT.

Tolerability and Safety Assessment of Adjuvant Chemoradiotherapy with S-1 after Limited Surgery for T1 or T2 Lower Rectal Cancer

Background: The short-term outcomes of chemoradiotherapy (CRT) with S-1 (a combination of tegafur, gimeracil, and oteracil) following limited surgery for patients with T1 or T2 lower rectal cancer have shown encouraging results. Objectives: This study was designed to delve deeper into the long-term outcomes of CRT with S-1 after limited surgery, with the goal of evaluating both the long-term efficacy and potential risks associated with this treatment approach in patients diagnosed with T1 or T2 lower rectal cancer. Methods: This was conducted as a multicenter, single-arm, prospective phase II trial. The patient population consisted of individuals clinically diagnosed with either T1 or T2 lower rectal or anal canal cancer, with a maximum tumor diameter of 30 mm and classified as N0 or M0. Patients underwent local excision or endoscopic resection. After surgery, CRT with S-1 was administered to patients meeting several criteria, including the confirmation of well-differentiated or moderately differentiated adenocarcinoma, negative surgical margins, submucosal invasion depth of ≥1000 µm, and high tumor-budding grade (2/3). The primary endpoint of this study was relapse-free survival, while secondary endpoints included local recurrence-free survival, overall survival, anal sphincter preservation rate, and safety. Results: A total of 52 patients were included, with pathological diagnoses revealing T1 in 36 patients and T2 in 16 patients. The 3-year and 5-year relapse-free survival rates were 90.17% and 85.87%, respectively. The 3-year and 5-year local recurrence-free survival rates were 90.17% and 88.07%, respectively, while the 3-year and 5-year overall survival rates were 94.03% and 91.94%, respectively. Conclusions: CRT with S-1 after limited surgery for T1 lower rectal cancer demonstrated favorable outcomes in terms of recurrence, survival, and local control rates while effectively maintaining anal function in patients. However, further treatment approaches may be necessary to improve outcomes for patients diagnosed with stage T2 lower rectal cancer

Early recurrence as a pivotal event in nasopharyngeal carcinoma: identifying predictors and key molecular signals for survivors

PurposeThe duration of response to treatment is a significant prognostic indicator, with early recurrence (ER) often predicting poorer survival outcomes in nasopharyngeal carcinoma (NPC) survivors. This study seeks to elucidate the factors contributing to the onset of ER following radiotherapy in NPC survivors.MethodsThis investigation encompassed 2,789 newly diagnosed NPC patients who underwent radical intensity-modulated radiotherapy. Ordinal logistic regression analysis was employed to evaluate the independent predictors of earlier recurrence. A machine learning-based prediction model of NPC recurrence patterns was developed. Tumorous RNA-sequencing (in-house cohort: N = 192) and biological tipping point analysis were utilized to infer potential molecular mechanisms associated with ER.ResultsOur results demonstrated that ER within 24 months post-initial treatment was the optimal time frame for identifying early malignant progression in NPC survivors. The ER cohort (150 of 2,789, 5.38%) exhibited a notably short median overall survival of 48.6 months. Multivariate analyses revealed that male gender, T4 stage, local or regional residual disease, detectable pre- and post-radiotherapy EBV DNA, and the absence of induction chemotherapy were significant predictors of earlier recurrence. The machine learning-based predictive model further underscored the importance of tumor-related factors in NPC recurrence. Moreover, ER emerged as a pivotal stage in NPC progression, with 15 critical transition signals identified potentially associated with the negative modulation of the immune response.ConclusionsOur comprehensive analysis of NPC recurrence patterns has unveiled insights into the key factors driving ER and provided novel insights into potential early warning biomarkers and the mechanisms underlying NPC progression.

Investigating the impact of clinical and genetic factors on the post-surgery prognosis of sinonasal squamous cell carcinoma

Sinonasal squamous cell carcinoma (SNSCC) is an aggressive cancer affecting the nasal and sinus regions, with its progression factors, particularly genetic ones, not yet fully understood. Here, we first conducted a retrospective study with 219 SNSCC patients to identify clinical factors affecting SNSCC prognosis. Additionally, we mined a vast literature dataset to uncover genetic factors associated with SNSCC progression. Based on this data, we constructed SNSCC prognosis pathways and performed a gene set enrichment analysis (GSEA). Clear operative margins were linked to a 73.5–86.3% improvement in overall survival and a 73.5–88.9% lower risk of recurrence. Nasal cavity-originated cases exhibited a 67.6–97.4% decrease in mortality and an 80.7–96.7% lower recurrence rate. Patients at T1-2 staging had a 65.0–80.6% reduced risk of death and recurrence compared to those at T3 stage. Additionally, we identified 53 genes associated with SNSCC, with 14 also implicated in primary tumor site, T stage, and operative margin. These genes, including EGFR, PIK3CA, ERBB2, PTEN, BCL2, BRAF, KRAS, and PRL, form a complex SNSCC-prognosis pathway and were significantly enriched in 42 KEGG pathways and Gene Ontology (GO) terms (FDR-corrected p-value < 0.001), influencing cell growth, apoptosis, and oncogenic signaling pathways. Our study suggests that three clinical parameters (operative margin type, primary tumor site, and T-stage) and 14 genetic factors may influence SNSCC prognosis post-surgery. These findings deepen our understanding of SNSCC and offer potential avenues to enhance its treatment and outcomes.

Risk factors and distribution pattern of lateral lymph node recurrence after central neck dissection for cN1a papillary thyroid carcinoma

BackgroundThe indication and extent of selective lateral neck dissection (LND) for cN1a papillary thyroid carcinoma (PTC) remain uncertain. The present study aimed to identify potential predictors and distribution pattern of lateral lymph node recurrence (LLNR) after central neck dissection in cN1a PTC patients.MethodsThe cN1a PTC patients who underwent initial central neck dissection at our centre were retrospectively reviewed, and the median follow-up period was 6.8 years. Reoperation with LND was performed when LLNR was confirmed. Risk factors for LLNR were identified, and the metastatic status of each lateral level was recorded.ResultsOf the 310 patients enrolled in the present study, fifty-eight patients (18.7%) presented with LLNR. Six independent factors, including tumour diameter, pathological T4 stage, number of involved central lymph nodes, pTNM stage, extrathyroidal extension, and I131 treatment (P values < 0.05) were identified via multivariate analysis. LLNR was found at level II in 26 patients (44.8%), level III in 38 patients (65.5%), level IV in 30 patients (51.7%), and level V in 8 patients (13.8%). The number of positive lateral lymph nodes at levels II, III, IV and V was 44 (22.9%), 76 (39.6%), 63 (32.8%), and 9 (4.9%), respectively.ConclusionsFor cN1a PTC patients who underwent central neck dissection, tumour diameter ≥ 2 cm, pathological T4 stage, number of involved central lymph nodes ≥ 3, pTNM stage III-IV, extrathyroidal extension, and failure to receive I131 treatment were independent predictors of LLNR, which was more likely to occur at levels III and IV.

Oncological long-term outcomes of laparoscopic versus open gastrectomy for cT3-4 gastric cancer at surgical staging: a propensity-score matched cohort study.

The oncological efficacy of laparoscopic surgery for advanced gastric cancer (AGC) has been evaluated by several randomized trials. However, the inclusion of earlier-stage disease was a limitation in previous studies. Patients with cT3-4 gastric cancer, determined by surgical staging to minimize migration of earlier stages, treated at a tertiary cancer center from 2009 to 2018 were included. Based on the surgical approach, the patients were divided into two groups: the laparoscopic gastrectomy (LG) and the open gastrectomy (OG) and matched for age, sex, macroscopic appearance (type 4 or non-type 4), body mass index, estimated tumor size, clinical stage T3'T4, clinical N stage, pathologic T stage (T3 or T4), and type of surgery (total or distal gastrectomy). 588 patients (221 LG, 367 OG) were included in the analysis. After 1:1 propensity-score matching, 386 patients (193 LG, 193 OG) were assigned for analysis. In the LG group, operation time was longer with lower blood loss. The incidence of postoperative complications (≥ grade III) did not differ significantly between the groups (OG: 8.3%, vs. LG: 9.3%). Overall survival (OS) was longer in the LG group (5-year OS: 79.3 vs. 73% HR 0.66, 95% CI 0.44-0.99, P = 0.0497). Relapse-free survival (RFS) did not show a statistical difference (5-year RFS: 69.5 vs. 68.7 HR 0.88, 95% CI 0.62-1.26, P = 0.487). Subgroup analysis for OS also demonstrated equivalent outcomes. LG demonstrates comparable safety and efficacy to OG for advanced gastric cancer at surgical staging, with similar rates of severe complications and long-term oncological outcomes. Further research is needed to validate these findings, particularly for total gastrectomy and for patients from Western populations.

The Impact of Preoperative Flexible Fiberoptic Laryngoscopy on Anesthesia's Intubation Plans.

Purpose: To assess the value of conducting a preairway management review of flexible fiberoptic laryngoscopy examinations (FFL) by the anesthesia team for patients with head and neck cancer and to examine its impact on intubation strategies and overall patient safety. Methods: Prospective study at a single tertiary referral center including patients with stage T2 and greater cancers of the oropharynx, hypopharynx, or larynx who underwent intubation by the anesthesia team between May 2022 and April 2023. Pre- and postoperative surveys gathered data on the intubation plan, including details such as method, sedation, patient respiration, laryngoscope, tube size, and use of paralysis. Postoperative surveys gauged the FFL's subjective utility and documented intubation details and complications. Results: Thirty-four patients (49-87 years of age) were included in the study. Eleven intubation plans were changed after reviewing the FFL, while 23 were not. Although this was a pilot study, there was no significant correlation between location of the tumor and change in intubation plan. Of the 34 intubations, 9 were executed based on the plan after reviewing FFL. The majority of the attending anesthesiologists agreed or strongly agreed that seeing the FFL was more helpful than reading the findings in clinic notes and that reviewing the FFL was helpful in creating the intubation plan, 77% and 88%, respectively. Conclusion: Reviewing the FFL led to changes in the anesthesia team's intubation plan in 32% of the cases in our pilot study. While these findings are promising, they highlight the need for further research with larger sample sizes and across multiple centers to validate the impact of FFL on intubation strategies for patients with stage T2 and greater cancers of the oropharynx, hypopharynx, or larynx.

Bicenter validation of a risk model for the preoperative prediction of extraprostatic extension of localized prostate cancer combining clinical and multiparametric MRI parameters

BackgroundThis study aimed to validate a previously published risk model (RM) which combines clinical and multiparametric MRI (mpMRI) parameters to predict extraprostatic extension (EPE) of prostate cancer (PC) prior to radical prostatectomy (RP).Materials and methodsA previously published RM combining clinical with mpMRI parameters including European Society of Urogenital Radiology (ESUR) classification for EPE was retrospectively evaluated in a cohort of two urological university hospitals in Germany. Consecutive patients (n = 205, January 2015 –June 2021) with available preoperative MRI images, clinical information including PSA, prostate volume, ESUR classification for EPE, histopathological results of MRI-fusion biopsy and RP specimen were included. Validation was performed by receiver operating characteristic analysis and calibration plots. The RM‘s performance was compared to ESUR criteria.ResultsHistopathological T3 stage was detected in 43% of the patients (n = 89); 45% at Essen and 42% at Düsseldorf. Discrimination performance between pT2 and pT3 of the RM in the entire cohort was AUC = 0.86 (AUC = 0.88 at site 1 and AUC = 0.85 at site 2). Calibration was good over the entire probability range. The discrimination performance of ESUR classification alone was comparable (AUC = 0.87).ConclusionsThe RM showed good discriminative performance to predict EPE for decision-making for RP as a patient-tailored risk stratification. However, when experienced MRI reading is available, standardized MRI reading with ESUR scoring is comparable regarding information outcome. A main limitation is the potentially limited transferability to other populations because of the high prevalence of EPE in our subgroups.

Collagen fiber arrangement in the normal bladder lamina propria and their potential impact on the pathological substaging of bladder cancer stage T1.

The lamina propria (LP) of the urinary bladder lies between the urothelial mucosa and the muscularis propria. This complex stratum is composed of extracellular matrix, several cell types, and collagen types I and III fibers. LP invasion by urothelial carcinoma (progression from stage Ta to T1) is a determinant of bladder cancer advancement. We attempted to characterize collagen fiber arrangement in the LP. This could enrich our understanding of this important layer and potentially provide clues for sub-staging of the T1 bladder cancer. A total of 24 Masson trichrome-stained images of normal bladder, including 12,530 collagen fibers were quantitatively analyzed using the Dragonfly software. The LP was divided according to fiber orientation into superficial LP (SLP, 15% of the thickness) and the deep LP (DLP, 85% of the thickness). Collagen fiber geometry analysis demonstrated that the SLP fibers are more parallel to the urothelium with an average angle of 260±230 compared to 400±260 in the DLP (p=3.4X10-144), more packed (average distance to the closest fiber of 0.61±0.67 compared to 0.66±0.77, p=0.0001), and their aspect ratio is considerably longer (average of 1.93±0.12 compared to 0.20±0.11, p=2.84x10-8). No difference was found in fiber perimeter or Feret diameter. Thus, we conclude that bladder collagen fibers are arranged in two distinct layers: a dense-ordered SLP and a loose disorder DLP. This indicates that the physical barrier to cancer cell invasion probably lies in the SLP, immediately underneath the urothelium. Once this barrier is breached, the looser and disorganized DLP poses no remarkable obstacle. Thus, we believe that histology-based subdivisions of stage T1 are expected to fail in providing clinically meaningful prognostic information.

MAOA uVNTR Polymorphism in a Sample of Patients Diagnosed with Papillary Thyroid Cancer

Thyroid gland carcinoma (TGC), though only 1% of all carcinomas, is the most common endocrine neoplasm with an increasing incidence since the 1990s. Of the TGC types, papillary thyroid carcinoma (PTC) is the most common and has the best overall prognosis. Although primarily studied in various neural spectrum disorders, monoamine oxidase A (MAOA) may also contribute to cancer occurrence. This case control study assessed the prevalence of MAOA uVNTR polymorphism in PTC patients, compared its frequency with a healthy control, and assessed the variant’s impact on clinical features. The research participants consisted of 30 PTC patients (20 female, 10 male) over 18 years old who underwent thyroidectomy and radioiodine therapy at a Federal District private clinic and 30 paired and unrelated healthy volunteers (18 female, 12 male). The most frequent MAOA uVNTR alleles were 3R and 4R. Although no significant difference was detected in the genotypic distribution nor the PTC patients’ thyroglobulin, thyroid-stimulating hormone, and antithyroglobulin levels; body mass indexes; administered radiopharmaceutical (131I) doses; or biological sex, the presence of at least one 3R allele was associated with a larger tumor size (T3 + T4 staging). Thus, the 3R allele seems to be associated with PTC pathogenesis severity.

Frequency of KRAS and BRAF mutations in colorectal carcinoma and their association with clinical-pathological characteristics in a tertiary hospital in Kenya.

Colorectal carcinoma is a leading cause of cancer morbidity and mortality globally. Its management includes the use of targeted therapy which require assessment for biomarkers to choose eligible patients. KRAS and BRAF mutations are biomarkers predictive of response to anti-EGFR therapy. This study aimed at determining the frequency of BRAF V600E and KRAS exon 2,3,4 mutations in colorectal carcinoma patients at the Aga Khan University Hospital Nairobi, Kenya. Study participants were patients who had colectomy for colorectal carcinoma. They were identified from the laboratory information system. The patients age, gender and tumor location were determined from the medical records. The histological diagnosis, pathological tumor and nodal stage were confirmed by examining hematoxylin and eosin-stained slides prepared from the colectomy specimen. DNA was extracted from the specimens using Qiagen QIAamp DNA FFPE Tissue Kit and PCR performed using EntroGen KRAS/BRAF mutation analysis kit following manufacturer's protocol. One hundred fourteen patients were enrolled. Colorectal carcinoma was significantly more common in males than females. The mean age at diagnosis was 58 years. Majority of the tumors were in the right colon, were of pathological tumor stage T3 and had nodal involvement. Forty six percent (46%) of the cases had KRAS mutations while 5.3% had BRAF V600E mutation. KRAS mutation was associated with a high pathological tumor stage and nodal involvement. Colorectal carcinoma in our patients is more common in males and tend to occur at a younger age. The patients tend to have a high tumor pathological stage and nodal involvement at diagnosis. The high frequency of KRAS exon 2,3,4 mutation and low frequency of BRAF V600E mutations is similar to what has been reported in literature.

Abstract C049: Computational Methods for Central and Lipid Metabolism Networks Analysis to Reveals Flux Change in PDAC

Abstract Pancreatic ductal adenocarcinoma (PDAC) is among the most challenging cancers to treat due to its aggressive nature and the difficulties in early detection. The disease progresses rapidly from stage T1 to T4, leaving a narrow window for effective intervention. This swift progression is closely tied to significant metabolic alterations, and current studies have highlighted specific metabolic changes. This includes elevated glutamine metabolism and altered aspartate and alpha-ketoglutarate production to support uncontrolled tumor growth; and elevated lysophosphatidylcholines secretion by cancer-associated fibroblasts to support tumor progression. These insights underscore the need for a holistic understanding of PDAC metabolism. Hence, there is an urgent need for a comprehensive and high-resolution analysis of PDAC's metabolic landscape remains unexplored. To computationally characterize the PDAC metabolism and fully leverage the large-scale transcriptomics with matched or unmatched metabolomics data, we developed an algorithm based on the Michaelis-Menten equation to estimate distribution-wise variations in mass-carrying metabolic networks using gene expression and metabolomics data. We start by manually curating a PDAC-specific metabolic network that focuses on central metabolism, glutamine-glutamate metabolism, and lipid metabolism. We then gathered comprehensive kinetic parameters, predicted enzyme activity from transcriptomics data, and conducted metabolomic profiling to determine metabolic compound concentrations. By applying Monte Carlo sampling methods, we achieved an overall balance of metabolic flux, enabling us to model reaction rates accurately and predict metabolic shifts. This approach holds potential to provide a comprehensive perspective on the rewired metabolism in PDAC, inspiring the development of metabolic targets or diet interventions for therapeutic treatment. Citation Format: Sha Cao, Haiqi Zhu, Yijie Wang, Melissa Fishel, Chi Zhang. Computational Methods for Central and Lipid Metabolism Networks Analysis to Reveals Flux Change in PDAC [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C049.

Prognostic analysis of appendectomy versus right hemicolectomy for T1 appendiceal adenocarcinoma: a multicenter retrospective analysis

Background and aimAppendiceal adenocarcinoma, an exceedingly rare malignancy, sparks debate on the optimal surgical approach—appendectomy or right hemicolectomy—for early-stage cases. This study aims to investigate the impact of these two surgical methods on the survival prognosis of patients with early appendiceal adenocarcinoma.MethodUtilizing a multicenter medical database, we gathered data from 168 patients diagnosed with T1 stage appendiceal adenocarcinoma admitted between January 2008 and January 2015. This study aims to compare the impact of different treatment modalities on the prognosis of appendiceal adenocarcinoma in these two groups.ResultIn patients diagnosed with T1 appendiceal adenocarcinoma, the survival prognosis was not significantly improved with right hemicolectomy compared to appendectomy. Out of one hundred twenty-seven patients undergoing right colon resection, only three exhibited lymphatic metastasis, resulting in a rate of 2.3%.ConclusionSimple appendectomy can fulfill the objective of achieving radical tumor resection, rendering right hemicolectomy unnecessary.

The significance of risk stratification through nomogram-based assessment in determining postmastectomy radiotherapy for patients diagnosed with pT1 − 2N1M0 breast cancer

ObjectiveTo explore the high-risk factors affecting the prognosis of pT1 − 2N1M0 patients after mastectomy, establish a nomogram prediction model, and screen the radiotherapy benefit population.MethodThe clinical data of 936 patients with pT1 − 2N1M0 who underwent mastectomy in the fourth hospital of Hebei Medical University from 2010 to 2016 were retrospectively analyzed. There were 583 patients received postmastectomy radiotherapy(PMRT), and 325 patients without PMRT. Group imbalances were mitigated using the propensity score matching (PSM) method, and the log-rank test was employed to compare overall survival (OS) and disease-free survival (DFS) between the cohorts. The efficacy of PMRT across various risk groups was evaluated using a nomogram model.ResultThe median follow-up period was 98 months, Patients who received PMRT demonstrated significantly improved 5-year and 8-year OS and DFS compared to those who did not (P < 0.001). Multivariate analysis revealed that age, primary tumor site, positive lymph node, stage, and Ki-67 level independently influenced OS, while age, primary tumor site, and stage independently affected DFS. PMRT drastically enhanced OS in the high-risk group (P = 0.001), but did not confer benefits in the low-risk and intermediate risk groups (P = 0.057, P = 0.099). PMRT led to a significant improvement in disease-free survival (DFS) among patients in the intermediate and high-risk groups (P = 0.036, P = 0.001), whereas the low-risk group did not experience a significant benefit (P = 0.475).ConclusionAge ≤ 40 years, tumor located in the inner quadrant or central area, T2 stage, 2–3 lymph nodes metastasis, and Ki67 > 30% were the high-risk factors affecting the prognosis of this cohort of patients. In OS nomogram, patients with a risk score of 149 or higher who received PMRT exhibited improved OS. Similarly, in DFS nomogram, patients with a risk score of 123 or higher who received PMRT demonstrated enhanced DFS.

Sperm-carried IGF2: towards the discovery of a spark contributing to embryo growth and development.

Spermatozoa have been shown to carry key RNAs which, according to animal evidence, seem to play a role in early embryo development. In this context, a potential key growth regulator is insulin-like growth factor 2 (IGF2), a highly conserved paternally expressed imprinted gene involved in cell growth and proliferation which, recent observations indicate, is expressed in human spermatozoa. We herein hypothesized that sperm IGF2 gene expression and transmission at fertilization is required to support early embryo development. To test this hypothesis, we analyzed sperm IGF2 mRNA levels in the same semen aliquot used for homologous assisted reproductive technique (ART) in infertile couples and correlated these levels with embryo morphokinetics. To find a mechanistic explanation for the observed results, the transcriptomes of blastocysts obtained after injection of Igf2 mRNA in mouse parthenotes were analyzed. Sperm IGF2 mRNA negatively correlated with time of 2-cell stage (t2), t3, t4, t5, and time of expanded blastocyst (tEB), independently of maternal age, body mass index, anti-Müllerian hormone levels, and oocyte quality. An IGF2 mRNA index >4.9 predicted the ability of the embryos to reach the blastocyst stage on Day 5, with a sensitivity of 100% and a specificity of 71.6% (AUC 0.845; P < 0.001). In the animal study, transcriptome analysis demonstrated that 65 and 36 genes were, respectively, up- and down-regulated in the experimental group compared to the control group. These genes belong to pathways that regulate early embryo development, thus supporting the findings found in humans. This study has the potential to challenge the longstanding tenet that spermatozoa are simply vehicles carrying paternal DNA. Instead, it suggests that IGF2 mRNA in healthy spermatozoa provides critical support for early embryo development. Pre-ART sperm-carried IGF2 mRNA levels may be used as a marker to predict the chances of obtaining blastocysts to be transferred for infertile couples undergoing ART.

Efficacy of neoadjuvant chemotherapy combined with prophylactic intraperitoneal hyperthermic chemotherapy for patients diagnosed with clinical T4 gastric cancer who underwent laparoscopic radical gastrectomy: a retrospective cohort study based on propensity score matching

BackgroundClinical T4 (cT4) stage gastric cancer presents with frequent postoperative recurrence and poor prognosis. This study is to evaluate the oncological efficacy of laparoscopic radical total gastrectomy combined with postoperative prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with cT4N + M0 gastric cancer who received neoadjuvant chemotherapy.MethodsWe reviewed the clinicopathological data of 174 patients with clinical T4 gastric cancer who underwent neoadjuvant chemotherapy followed by laparoscopic radical total gastrectomy between June 2017 and December 2021. Among them, 142 were included in the non-HIPEC group, and 32 in the HIPEC group. Patients in both groups were paired based on propensity score in a 2:1 ratio to assess disparities in tumor recurrence and long-term survival.ResultsAfter matching, there were no significant differences in the clinicopathological data between the two groups. The peritoneum (16.1%) and distant organs (10.9%) were the most frequent locations for recurrence. Prior to matching, the recurrence rates were similar at all sites for both groups. Compared with those in the non-HIPEC cohort, the recurrence rates at all sites, the lung, and the peritoneum were notably lower in the HIPEC cohort. Prior to matching, the 3-year overall survival and disease-free survival rates were similar between the two groups; following matching, the HIPEC group exhibited notably greater survival rates than did the non-HIPEC group. The disparities in survival rates between the groups became even more pronounced after conducting a stratified analysis among patients with stage III disease.ConclusionsNeoadjuvant chemotherapy combined with prophylactic HIPEC after laparoscopic radical gastrectomy can effectively reduce the rate of peritoneal metastasis in patients with cT4N + M0 advanced gastric cancer and significantly improve the prognosis of such patients, which is of great clinical value.

A new surgical strategy for T4 stage posterior buccal carcinoma: anatomical unit resection

Objective: To investigate the effect of anatomical unit resection on the overall survival rate of patients with T4 stage posterior buccal carcinoma. Methods: We conducted a retrospective study on 79 patients with T4 stage posterior buccal squamous cell carcinoma underwent radical surgery for buccal mucosa cancer and reconstruction with free anterolateral thigh flap in the Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital, Central South University from March 2014 to December 2019. The 74 patients were males and the 5 patients were females, aged from 28 to 72 years old. The 40 patients in control group underwent traditional extended resection (1.5-2.0 cm safe margin), and 39 patients in the experimental group underwent anatomical unit resection. The clinicopathological parameters of patients were collected and followed up regularly. The overall survival rate was assessed by Log-rank and Cox proportional risk regression model. Multivariate analysis was performed by linear regression model. Results: There were significant differences between experimental group and control group in overall survival rates (61.53% vs 27.50%, χ2=6.624, P=0.010) and local disease control rates (74.36% vs 27.50%, χ2=17.350, P<0.001). Multiple linear regression analysis showed that local disease control rate was significantly correlated with anatomical unit resection (t=3.880, P<0.001) and lymph node metastasis (t=2.619, P=0.011), and also Cox proportional hazards regression model analysis identified that overall survival rate was significantly correlated with anatomical unit resection (Z=2.421, P=0.016) and lymph node metastasis (Z=2.793, P=0.005). Conclusion: For posterior buccal carcinoma with multiple anatomical units involved, anatomical unit resection can significantly reduce local recurrence and improve overall survival rate of patients.

Intracorporeal urinary diversion offers the advantage of delaying postoperative renal function injury in patients undergoing robot-assisted radical cystectomy.

To analyze changes in renal function and associated risk factors in patients with bladder cancer undergoing robot-assisted radical cystectomy (RARC) with intracorporeal or extracorporeal urinary diversion (ICUD or ECUD). Clinical-pathological data was extracted from electronic medical records of 266 patients with bladder cancer who underwent RARC at our institution between August 2015 and August 2022. Postoperative renal function was assessed using the estimated glomerular filtration rate (eGFR). Patients were classified into ECUD and ICUD groups based on the surgical approach. Significant differences in eGFR were observed between the two groups at 1, 2, and 3 years postoperatively. Moreover, 112 patients (42.1%) experienced long-term renal function injury. Independent risk factors for long-term renal function injury included the type of surgical approach, ureteroenteric anastomotic strictures, and pathological stage T3 or above. In terms of short-term renal function, 30 cases of acute kidney injury (AKI) were observed, with an incidence rate of 11.3%. No difference in AKI incidence was found between the groups. Postoperative AKI and chronic kidney injury are prevalent complications following RC. This study highlights that pathological stage, ureteroenteric anastomotic strictures, and ECUD significantly impact long-term renal function, but the type of urinary diversion (ileal conduit or orthotopic neobladder) had no effect on renal function, and ICUD was superior in terms of long-term renal injury rate. Therefore, precise preoperative assessment and the selection of appropriate surgical approach are crucial for preserving renal function in patients with bladder cancer.

Apelin (APLN) is a biomarker contributing to the diagnosis and prognosis of hepatocellular carcinoma

Liver cancer, classified as a malignant hepatic tumor, can be divided into two categories: primary, originating within the liver, and secondary, resulting from metastasis to the liver from other organs. Hepatocellular carcinoma (HCC) is the main form of primary liver cancer and the third leading cause of cancer-related deaths. The diagnosis and prognosis of HCC using current methods still face numerous challenges. This study aims to develop novel diagnostic and prognostic models while identifying new biomarkers for improved HCC treatment. Diagnostic and prognostic models for HCC were constructed using traditional binary classification methods and machine learning algorithms based on the TCGA database (Downloaded in August 2023). The mechanisms by which APLN (Apelin) affects HCC were investigated using single-cell sequencing data sourced from the GEO database (GSE149614). The diagnostic models yielded by various algorithms could effectively distinguished HCC samples from normal ones. The prognostic model, composed of four genes, was constructed using LASSO and Cox regression algorithms, demonstrating good performance in predicting the three-year survival rate of HCC patients. The HCC biomarker Apelin (APLN) was identified in this study. APLN in liver cancer tissues mainly comes from endothelial cells and is associated with the carcinogenesis of these cells. APLN expression is significantly upregulated in liver cancer tissues, marking it as a viable indicator of endothelial cell malignancy in HCC. Furthermore, APLN expression was determined to be an independent predictor of tumor endothelial cell carcinogenesis, unaffected by its modifications such as single nucleotide variation, copy number variation, and methylation. Additionally, liver cancers characterized by high APLN expression are likely to progress rapidly after T2 stage. Our study presents diagnostic and prognostic models for HCC with appreciably improved accuracy and reliability compared to previous reports. APLN is a reliable HCC biomarker and contributes to the establishment of our models.