Clinicopathological Outcomes Research Articles

Prognostic Significance of DSCC1, a Biomarker Associated with Aggressive Features of Breast Cancer

Background and Objectives: Invasive breast cancer (BC) was traditionally investigated visually, and no technique could identify the key molecular drivers of patient survival. However, essential molecular drivers of invasive BC have now been discovered using innovative genomic, transcriptomic, and proteomic methodologies. Nevertheless, few evaluations of the prognostic factors of BC in Saudi Arabia have been performed. Evaluating the biomarkers associated with the development of early-stage BC could help determine the risk of metastasis and guide treatment decisions. In a previous study, using large BC cohorts and artificial neural network techniques, DNA replication and sister chromatid cohesion 1 (DSCC1) was found to be one of the principal genes in invasive BC samples. To date, no studies have addressed the prognostic significance of DSCC1 in invasive BC and its association with aggressive tumor behavior. This research aimed to address this gap. Materials and Methods: The association of clinicopathological features and patient outcomes with DSCC1 expression at the mRNA level was assessed using the Molecular Taxonomy Breast Cancer International Consortium (METABRIC; n = 1980) and The Cancer Genome Atlas (TCGA; n = 854) cohorts. DSCC1 was also evaluated at the protein level using immunohistochemistry on samples from invasive BC patients (n = 100) presenting to King Abdul Aziz Specialist Hospital in Saudi Arabia. The association of clinicopathological parameters (including patient age, tumor grade, tumor size, and patient outcome) with protein level was also evaluated. Results: In both METABRIC and TCGA cohorts, high expression of DSCC1 was significantly associated with high histological grade, large tumor size, lymphovascular invasion positivity, and hormone receptor negativity (all p < 0.001). A high DSCC1 mRNA level was associated with poor outcomes (p < 0.001 for METABRIC, p = 0.23 for TCGA). At the protein level, high DSCC1 expression was associated with high histological grade (p = 0.001), lymph node presence (p = 0.008), hormone receptor negativity (p = 0.005), high Ki67 expression (p = 0.036), and shorter survival (p = 0.008). Conclusions: This study confirmed the prognostic significance of DSCC1 in invasive BC patients. DSCC1 could be a therapeutic target in BC cases with poor outcomes.

Clinicopathological features and outcomes of rare lung adenocarcinoma metastasis to the thyroid gland: A single-center, 11-year experience.

Metastasis to the thyroid gland from lung adenocarcinoma is rare and challenging to diagnose due to similar histopathological features. This study aimed to analyze the clinicopathological characteristics of and treatment strategies for lung adenocarcinoma metastasis to the thyroid based on 11 years of institutional experience. A retrospective study included patients with lung adenocarcinoma metastasis to the thyroid at our center from 2010 to 2023. Clinicopathological features and clinical outcomes were analyzed. Among 9714 lung adenocarcinoma patients, nine patients (five females, 55.6%) were diagnosed with thyroid metastasis, presenting primarily with cough symptoms. Most patients (88.9%) had synchronous tumors, whereas a minority (11.1%) had metachronous tumors. The median time from primary tumor diagnosis to metastasis was 4.8 months. Most patients developed bilateral thyroid metastases (88.9%). Diagnosis of thyroid metastasis was primarily through fine-needle aspiration (FNA), with one case misdiagnosed as papillary thyroid carcinoma. Immunohistochemical staining revealed thyroid transcription factor-1 (TTF-1) and novel aspartic proteinase of pepsin family A (Napsin-A) positivity and paired box 8 (PAX8) negativity. Genetic testing found epidermal growth factor receptor mutations in 71.4% of patients. The individualized comprehensive therapy included surgery, chemotherapy, immunotherapy, and targeted and supportive therapy. The median overall survival was 56.0 months, with a progression-free survival of 12.7 months. Kaplan-Meier (K-M) analysis suggested improved survival with no advanced symptoms (p = 0.03) and targeted therapies (p = 0.05). Lung adenocarcinoma metastasis to the thyroid is a rare disease, with an incidence of 0.1% among lung adenocarcinoma patients. Early treatment after symptom onset and personalized targeted therapies may improve prognosis. Despite rapid disease progression, favorable outcomes can be achieved with comprehensive treatment.

Characterization of Breast Cancer Intra-Tumor Heterogeneity Using Artificial Intelligence.

Intra-tumor heterogeneity (ITH) is a fundamental characteristic of breast cancer (BC), influencing tumor progression, prognosis, and therapeutic responses. However, the complexity of ITH in BC makes its accurate characterization challenging. This study leverages deep learning (DL) techniques to comprehensively evaluate ITH in early-stage luminal BC and provide a nuanced understanding of its impact on tumor behavior and patient outcomes. A large cohort (n = 2561) of early-stage luminal BC was evaluated using whole slide images (WSIs) of hematoxylin and eosin-stained slides of excision specimens. Morphological features of both the tumor and stromal components were meticulously annotated by a panel of pathologists in a subset of cases. A DL model was applied to develop an algorithm to assess the degree of heterogeneity of various morphological features per individual case utilizing defined patches. The results of extracted features were used to generate an overall heterogeneity score that was correlated with the clinicopathological features and outcome. Overall, 162 features were quantified and a significant positive correlation between these features was identified. Specifically, there was a significant association between a high degree of intra-tumor heterogeneity and larger tumor size, poorly differentiated tumors, highly proliferative tumors, tumors of no special type (NST), and those with low estrogen receptor (ER) expression. When all features are considered in combination, a high overall heterogeneity score was significantly associated with parameters characteristic of aggressive tumor behavior, and it was an independent predictor of poor patient outcome. In conclusion, DL models can be used to accurately decipher the complexity of ITH and provide extra information for outcome prediction.

Comparison of clinical features of patients with or without severe gastrointestinal complications in aggressive gastrointestinal lymphomas.

Aggressive primary gastrointestinal non-Hodgkin lymphoma (PGINHL) is an uncommon and heterogeneous group of lymphoid malignancies, that differs from indolent lymphoma and has a high incidence of severe gastrointestinal complications (GICs). To investigate and compare the clinicopathological characteristics, treatments and outcomes in the GICs and No-GICs group with aggressive PGINHL. This retrospective analysis was performed on aggressive PGINHL patients between January 2013 and December 2021 at our hospital. The independent influence factors of GICs were obtained by univariate and multivariate Logistic regression analysis, the selected variables significantly related to GICs were selected as the final predictors to construct nomogram. Kaplan-Meier curves further analyzed the survival of patients in GICs and No-GICs groups. Survival analysis of GICs group was performed using Cox regression. We focused on 124 aggressive PGINHL cases, which had a relatively high incidence 48.4% (60/124 cases) of GICs, the most common histological type in GICs group was diffuse large B-cell lymphoma (DLBCL) (n = 49, 81.7%). In the GICs group, small intestine was the most common anatomic site of lesion (43.3%), followed by large intestine (31.7%), and then stomach and esophagus (25.0%). Multivariate Logistic regression analysis showed that the independent risk factors for GICs were the small intestine [odd ratio (OR) = 3.33; 95% confidence interval (CI): 1.47-9.41; P = 0.009), aggressive B-cell (OR = 0.09; 95%CI: 0.01-0.83; P = 0.033), maximum tumor diameter (OR = 1.25; 95%CI: 1.07-1.47; P = 0.005), invaded deep serous layer (OR = 3.38; 95%CI: 1.24-9.19; P = 0.017). We developed a nomogram to predict risk of GICs in aggressive PGINHL patients based on independent risk factors. The value of area under curve calculated by receiver operating characteristic curve was 0.815, and calibration curve and decision curve analysis further indicated that the prediction effect was superior. The majority of patients with GICs were given combination therapy (chemotherapy combined with surgery or radiation). Event-free survival and overall survival in GICs group were no worse than those in the No-GICs group. The complication rate of GICs in patients with aggressive PGINHL was relatively high, particularly in PGI-DLBCL. The independent risk factors for GICs were the small intestine, PGI-TNKL, bulky tumor, and depth of invasion. A combination treatment, involving surgery, improved survival in the GICs group.

Prognostic value of lncRNA CBR3-AS1 for patients with cancer: A meta-analysis.

Several studies have shown that the long noncoding RNA (lncRNA) CBR3-AS1 is overexpressed in various cancers and is playing an oncogene role. This meta-analysis aims to elucidate the relationship between lncRNA CBR3-AS1 expression and the prognosis and clinicopathological features of cancer patients. A comprehensive and systematic search was conducted in PubMed, Web of Science, Cochrane Library, and EMBASE database. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were employed to evaluate the association between lncRNA CBR3-AS1 expression and clinical outcomes and clinicopathological features in cancer patients. This meta-analysis finally enrolled 9 studies comprising 800 cancer patients. The combined results indicated that lncRNA CBR3-AS1 overexpression was significantly associated with shorter overall survival (pooled hazard ratios = 1.69, 95% CI 1.28-2.21, P < .001). Furthermore, elevated lncRNA CBR3-AS1 expression was closely correlated with larger tumor size (large vs small OR = 2.17, 95% CI: 1.50-3.14, P < .0001), lymph node metastasis (yes vs no OR = 2.75, 95% CI: 1.67-4.51, P < .0001), distant metastasis (yes vs no OR = 3.08, 95% CI: 1.82-5.23, P < .0001), and advanced tumour, node, metastasis stage (III/IV vs I/II OR = 2.82, 95% CI: 1.68-4.75, P < .0001). Upregulated expression of lncRNA CBR3-AS1 showed significant association with unfavorable survival and indicated worse clinicopathological outcomes in multiple kinds of human cancer, and therefore might serve as a promising prognosis biomarker and therapeutic target for cancers.

Association of BRAF V600E allele frequency with clinicopathologic outcomes in papillary thyroid cancer.

BRAF V600E mutation is the most common genetic driver of papillary thyroid cancer (PTC), where it is found with various allele frequency (AF), reflecting the proportion of cells carrying the mutant and wild-type gene alleles. To determine whether BRAF V600E AF can improve prognostication and inform initial surgical management of PTC. Retrospective cohort study (2016-2019). UCLA health. Consecutive patients with Bethesda V/VI nodules and isolated BRAF V600E mutation who underwent surgery with histopathology showing PTC. Blinded ThyroSeq v3 molecular analysis after completion of initial management and follow-up. Aggressive histopathology and cancer persistence/recurrence. Of 73 patients, the median BRAF V600E AF was 25.5% (IQR, 16.7-34.3%). Higher median AF was seen in patients classified as American Thyroid Association (ATA) high-risk (37%) vs. intermediate-risk (25.3%, p<0.01) and low-risk (24.7%, p<0.01), largely attributed to higher AF in patients with gross extrathyroidal extension (ETE) (40.1% vs. 25.2% without gross ETE, p=0.02). No differences in AF were observed on the basis of lymph node positivity or presence of aggressive variants of PTC. A higher BRAF V600E AF was also found in patients with tumors ≥2cm vs. <2cm (median 32.0% vs. 24.4%, p<0.01). Over 4.1 years of follow-up, disease persistence/recurrence was found in 7 patients (9.4%) and was associated with higher median AF than those without recurrence (35.3% vs. 25.2%, p=0.02). Higher AF was associated with poorer recurrence-free survival (AF≥35%, HR 7.40, CI 1.4-38.1). Higher AF was associated with gross ETE and increased recurrence risk. This may inform initial management in patients with PTC harboring an isolated BRAF V600E mutation.

Abstract 4135447: Demographics, Clinicopathological Outcomes and Comparative Survival Analysis of Pleural and Pericardial Mesothelioma; A Retrospective Population-Based Study

Background: Malignant mesothelioma (MM) is an aggressive and rare tumor of mesothelial cells that is strongly correlated with asbestos exposure. Due to its long latency period, MM is characterized by its poor prognosis. In this study, we primarily analyzed data for the clinicopathological analysis of malignant pleural mesothelioma with comparative overall survival (OS) and cancer-specific survival (CSS) with primary pericardial mesothelioma. Method: The data was collected from the Epidemiology and End Results (SEER) database, comprising 12,991 mesothelioma patients from 2000 to 2020. Results: A total of 12,991 cases of MM were extracted from the database, of which 99.55% were pleural and only 0.177% were pericardial. The median age was 74 years. Regarding gender, 80% of the patients were male. MM was found to be more common in older age (&gt;65, 77%). 52% of the patients had a tumor size greater than 5 cm. The common histologic type was mesothelioma NOS (45%), followed by the epithelioid type (36%). The most common treatment modality was chemotherapy. Multivariate analysis showed better survival outcomes in younger, female patients undergoing combination therapies. Moreover, the histologic subtype, especially epithelioid mesothelioma, showed the overall best prognosis. Regarding comparative OS and CSS between pleural and pericardial mesothelioma, the 3-year OS of pleural mesothelioma was 11.2% (95% CI: 0.107 - 0.118) and for pericardial mesothelioma, the 3-year OS was 4.7% (95% CI: 0.007 - 0.317). Pleural mesothelioma had a 1-year CSS of 37.1% (95% CI: 0.343 - 0.401), and for pericardial mesothelioma, the CSS at 9 months was 28.6% (95% CI: 0.089 - 0.922), and all patients survived &lt; 1 year in the cohort. Conclusion: Malignant mesothelioma is a rare and aggressive tumor. Pericardial mesothelioma has lower survival in comparison to pleural mesothelioma. Genomic analysis and including all ethnicities in future clinical trials will help in future personalized therapeutic approaches.

Neuroendocrine differentiation and serotonin expression in oesophageal adenocarcinomas after neoadjuvant therapy: correlation with clinicopathological features and outcome.

Oesophageal adenocarcinoma (EAC) is a glandular or mucinous epithelial malignancy that can show immunohistochemical evidence of neuroendocrine differentiation (NED) and express the hormone serotonin. The objective of this study was to correlate the presence of NED and serotonin with clinicopathological characteristics and patient outcome after neoadjuvant chemoradiation. A retrospective cohort of patients treated between 2002 and 2021 was established and included 218 oesophagectomy specimens with residual tumour. Representative full-face sections of tumour were stained for synaptophysin, chromogranin-A and serotonin by immunohistochemistry, and staining results were correlated with disease-free survival (DFS) and overall survival (OS). In total, 129 (59%) tumours showed evidence of NED, defined as immunohistochemical expression of synaptophysin or chromogranin-A, while 40 (18%) showed evidence of NED and expressed serotonin. Patients with neuroendocrine-positive tumours had significantly shorter median OS compared to those with neuroendocrine-negative tumours (22.5 versus 48.8 months, P = 0.006), but similar median DFS (13.3 versus 17.8 months, P = 0.34). Using Cox regression, the association between NED and OS was significant in univariate [hazard ratio (HR) = 1.68, 95% confidence interval (CI) = 1.16-2.45] and multivariate (HR = 1.65, 95% CI = 1.08-2.52) analysis. Patients with serotonin-expressing tumours had similar median OS (21.7 versus 25.9 months, P = 0.24) and DFS (7.3 versus 15.6 months, P = 0.12) compared to those with NED but lacking serotonin. Using Cox regression, serotonin expression was associated with reduced OS in univariate (HR = 1.62, 95% CI = 1.06-2.47) but not multivariate (HR = 1.03, 95% CI = 0.64-1.65) analysis. Our findings support NED as independent predictor of OS in EAC after neoadjuvant chemoradiation. While a subset of tumours with NED expressed serotonin, this did not provide additional prognostic information.

Clinicopathological features of epithelioid hemangioma of 43 patients with long-term follow-up: A two-center retrospective study.

Epithelioid hemangioma (EH) is a rare angioproliferative disorder for which histopathology is the main approach to diagnosis. The tendency to recur is of concern to clinicians and patients. The factors associated with recurrence have been sporadically reported and a large-scale cohort study has been lacking. This study aims to investigate the clinicopathological characteristics and long-term clinical outcomes of EH patients from two tertiary care hospitals. A two-center retrospective cohort study of 43 patients with a diagnosis of EH between 2013 and 2023 was evaluated at follow-up. A comprehensive and detailed review of clinical and pathological data with long-term follow-up was performed. Information on prognosis was available for 43, and 8 (8/43, 18.6%) experienced local recurrence. Facial (Cramer's V = 0.405, P = 0.029) and multiple (relative risk [RR] 4.306, 95% confidence interval [CI] 1.213, 15.282, Phi = 0.369, P = 0.016) lesions, subcutaneous involvement (RR 5.063, 95% CI 1.157, 22.151, Phi = 0.374, P = 0.014), and the presence of lymphoid follicles (RR 9.750, 95% CI 3.853, 24.671, Phi = 0.670, P < 0.001) were associated with higher recurrence rates. According to the presence or absence of well-differentiated angiogenesis, EH can be pathologically classified into vascular, cellular, and intermediate types, while the depth, degree, and pattern of inflammation, tissue eosinophilia, eosinophilic microabscesses, and hobnail endothelial cells differed significantly between cellular and vascular types. The characteristics of EH are distinguished by different pathological subtypes. This study provides insight into the clinicopathological features and outcome of EH to assist clinicians in the diagnosis and management of this rare condition.

Primary orbital mesenchymal chondrosarcoma: clinicopathological characteristics and prognostic prediction

PurposeThis study aimed to analyze the clinicopathological characteristics of a rare malignant tumour, primary orbital mesenchymal chondrosarcoma (MCS), and identify the risk factors influencing its prognosis. MethodsA total of 15 patients with histologically confirmed primary orbital MCS were enrolled between April 2013 and October 2022. The relationships between clinicopathological features and outcomes, including recurrence and survival were analyzed. ResultsDuring the follow-up period, 9 patients (60%) experienced disease relapse, and 7 patients (46.7%) succumbed to the disease. Immunohistochemical analysis showed positive rates for SMA, CD-99, S-100, vimentin, and Bcl-2 at 60%, 60%, 53.3%, 100%, and 93.3%, respectively. The Ki67 index was positively associated with the recurrence and mortality rates. ConclusionOur study suggested that the Ki67 index could be a vital prognostic factor for MCS. Further follow-up studies are required to assess the efficacy of chemotherapy and radiotherapy in improving patient outcomes.

Clinicopathologic features and outcomes of hepatic inflammatory pseudotumour (IPT) and hepatic IPT-like lesions.

Hepatic inflammatory pseudotumours (IPTs) are nonneoplastic hepatic masses characterized by variably fibroblastic stroma and inflammatory infiltrate, hypothesized to arise as part of a response to infection or prior surgery. The aim of this study was to evaluate the clinicopathologic features and outcomes of biopsy-proven hepatic IPT as well as other cases with IPT-like histologic features. A database search at our institution identified cases with a pathologic diagnosis of hepatic IPT (n = 80) between 2000 and 2023. Histologic features (stromal quality, inflammatory cell components, granulomas, and necrosis) were evaluated. Past medical and surgical history, microbiologic studies, and outcomes were reviewed retrospectively. Patients frequently had a past medical history of malignancy (34%), biliary disease (15%), or prior intraabdominal surgery (24%), and often presented with multifocal hepatic lesions (36%). Variable inflammatory backgrounds were present, including histiocytic (36%), lymphoplasmacytic (34%), or neutrophilic (24%). Specific organisms were identified in 15% of cases, most commonly Klebsiella and Staphylococcus species. Most patients with available clinical follow-up demonstrated radiologic resolution and/or had repeat negative biopsy; a minority of patients (8%) were subsequently diagnosed with neoplastic hepatic lesions. No significant association was seen between histologic features and the subsequent clinical or pathologic diagnosis of hepatic neoplastic lesions. Hepatic IPT is a heterogeneous entity that can present in a variety of clinical scenarios and show a wide morphologic spectrum. These lesions often regress spontaneously or with antibiotics. A subset of cases with hepatic IPT-like histologic features were subsequently diagnosed with malignancy, emphasizing the need for continued follow-up and repeat biopsy depending on clinical and radiologic features.

The prognostic role of activation of the complement pathways in the progression of advanced IgA nephropathy to end-stage renal disease

IntroductionThe role of complement system in late stage of IgA nephropathy (IgAN) remains unknown. We therefore investigated the effects of complement system on worsening kidney function in advanced (stage 4 CKD) IgAN.MethodsRenal specimens of 69 IgAN patients who underwent renal biopsy during stage 4 CKD between 2010 and 2021, were stained using immunofluorescence (IF) and immunohistochemistry (IHC) for glomerular complement components. The primary outcome was progression to end-stage renal disease (ESRD). Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses.ResultsDuring a median follow-up of 18.0 months, 26 (37.7%) patients progressed to ESRD and none died. C1q and C3 deposition were detected in 12 and 66 patients, respectively. Higher eGFR [hazards ratio (HR), 0.852, 95% confidence interval (CI), 0.756–0.959; P = 0.008], higher C3 intensity (HR, 2.955, 95%CI, 1.063–8.220; P = 0.038) and T1-2 score (HR, 2.576, 95%CI, 1.205–5.576, P = 0.015) were predictive of time to ESRD in CKD 4 stage IgAN. Significant expressions of C1q (P = 0.005), C4d (P < 0.001), factor B (P < 0.001), C3 (P = 0.042) and C5b-9 (P = 0.004) were identified in ESRD group than in non-ESRD group by IHC, while MBL expression was low. Although they were not associated with baseline 24 h-UP, higher factor B and C1q expressions were both correlated with a lower baseline eGFR (P < 0.001 and = 0.04, respectively) and the deterioration of kidney function during follow-up (P = 0.046 and 0.015, respectively).ConclusionComplement deposition in IgAN patients with stage 4 CKD portends a faster deterioration of kidney function. Activation of classical and alternative complement pathways plays a major role in this stage.

Comprehensive Clinicopathological and Immunohistochemical Analysis of Human Papillomavirus-independent Squamous Cell Carcinoma and Adenosquamous Carcinoma of the Uterine Cervix.

Human papillomavirus-independent (HPVI) squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC) of the uterine cervix are extremely rare. The aim of this study was to comprehensively describe the clinicopathological features, patient outcomes, and immunophenotypes of HPVI SCC and ASC. We found four and two patients with HPVI SCC and ASC, respectively, and reviewed their electronic medical records and pathology slides. We also performed immunostaining for p16 and p53. All except one patient underwent surgery. Two, one, and one patients with HPVI SCC were diagnosed as having IIIC1, IVA, and IVB diseases, respectively. Two patients with HPVI SCC experienced recurrences, and died of disease within nine months after treatment initiation. Both patients with HPVI ASC developed lung metastasis at four months post-operatively. HPVI SCCs and the squamous component of HPVI ASCs showed keratinizing, condylomatous, or poorly differentiated morphology. The glandular component of HPVI ASCs was gastric-type endocervical adenocarcinoma. None of the six tumors exhibited block positivity for p16. Two HPVI SCCs and one HPVI ASC displayed aberrant p53 expression. HPVI SCC is a rare and aggressive cervical malignancy that presents initially as advanced-stage disease with poor prognosis. Although the patients with initial stage I and II HPVI ASC were treated with curative intent, distant metastases appeared in the lungs during the early course of treatment. Further investigations are necessary to clarify the association between histological features and clinical behavior of HPVI ASC.

Hormone Receptor Positive Breast Cancer in Young Women: A Review.

The global incidence of hormone-positive breast cancer (HR+ BC) in young women is rising, though the underlying reasons remain unclear. HR+ disease in younger women appears to represent a distinct clinical entity compared to that in older women, exhibiting distinct clinicopathological characteristics, outcomes and responses to treatment. Despite these differences, there is a paucity of large-volume data focusing on young women with HR+ in contemporary literature. Hormone receptor positive breast cancer in young women is associated with poorer prognoses compared to older women. Additionally, early age onset breast cancer presents unique challenges, including concerns related to fertility, the toxic effects of therapeutic agents, and specific surgical considerations. The purpose of this review is to report the existing literature on HR+ disease in young women.

Treatment approaches and survival outcomes in elderly colorectal cancer patients: a single-center comparative study.

Geriatric patients account for nearly half of new colorectal cancer (CRC) cases. This study compares clinicopathological features, treatments, outcomes, and frailty in elderly (≥ 70) and younger (< 70) CRC patients at our center. Patients diagnosed with non-metastatic or de novo metastatic CRC between January 2015 and April 2024 were included. Demographic, pathological, and survival data were retrospectively collected. Analyses were performed using SPSS version 25, with statistical significance set at P < 0.05. Of the 414 non-metastatic CRC patients, 26.6% were aged ≥ 70. Elderly patients received less perioperative chemotherapy (60% vs. 81.6%, P < 0.001) and had more dose reductions (41.6% vs. 19.2%, P < 0.001). Frailty reduced perioperative chemotherapy in elderly non-metastatic patients (54.5% vs. 92.1%, P < 0.001) but did not affect dose reduction (37.9% vs. 33.3%, P = 0.764) or treatment duration (median 24weeks for both groups, P = 0.909). In metastatic patients, frailty shortened chemotherapy duration (9.5 vs. 15.5weeks, P = 0.129). Elderly patients had lower 5- and 8-year overall survival (OS) rates (64.7%, 60.1% vs. 83.0%, 78.8%, P = 0.004). In the de novo metastatic cohort (135 patients), age did not affect OS (19.4 vs. 17.3months, P = 0.590) or PFS (9.8 vs. 7.5months, P = 0.209). Rectal cancer (HR: 2.751, P = 0.005) and early chemotherapy termination (HR: 4.138, P < 0.001) worsened OS in non-metastatic CRC, while absence of RAS (HR: 2.043, P = 0.047), BRAF mutations (HR: 8.263, P = 0.010), and metastasectomy (HR: 3.650, P = 0.036) improved OS in metastatic CRC. Age does not independently worsen CRC survival, though early chemotherapy discontinuation impacts outcomes. Reduced-dose chemotherapy or monotherapy can help minimize adverse effects in elderly patients.

Effects of the Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls score on postoperative clinical outcomes following colorectal cancer surgery: a retrospective study.

Sarcopenia has known negative effects on clinical and oncological outcomes in patients with colorectal cancer (CRC). The use of the Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls (SARC-F) questionnaire to determine the effects of sarcopenia on postoperative complications of CRC has not been reported to date. Therefore, this study aimed to investigate the relationship of SARC-F score with clinicopathologic outcomes after CRC surgery. We retrospectively included 285 patients who completed SARC-F questionnaires before CRC surgery between July 2019 and March 2022. Patients with an SARC-F score ≥4 (total score: 10) were classified in the high SARC-F group. Overall, 34 (11.9%) patients had high SARC-F scores. These patients were older (76.9 ± 8.5 vs. 64.5 ± 11.4 years, p < 0.001) and had a higher preoperative CRP (2.5 ± 3.9 vs. 0.8 ± 1.6 mg/L, p = 0.019), lower body mass index (21.7 ± 3.4 vs. 24.0 ± 3.8 kg/m2, p = 0.001), and higher pan-immune-inflammation value (632.3 ± 615.5 vs. 388.9 ± 413.8, p = 0.031). More postoperative complications were noted in the high SARC-F group than in the low SARC-F group (58.8% vs. 35.6%, p = 0.009). High SARC-F scores were significantly associated with higher nodal stage, higher number of harvested lymph nodes, and larger tumor size. Univariate and multivariate analyses revealed high SARC-F score and operation time as independent risk factors associated with postoperative complications (odds ratio, 2.212/1.922; 95% confidence interval, 1.021-4.792/1.163-3.175; p = 0.044/0.011, respectively). Preoperative SARC-F score was an independent risk factor associated with postoperative complications following colorectal cancer surgery.

Overexpression of a disintegrin and metalloproteinase 9 (ADAM9) in relation to poor prognosis of patients with oral squamous cell carcinoma

This study investigates the expressions of ADAM9, CDCP1 and t-PA in OSCC and their impacts on patient prognosis. Previous research has demonstrated the overexpression of ADAM9 and activation of plasminogen activator in OSCC, but CDCP1's role remains unexplored. While these biomolecules are known to contribute to lung cancer metastasis, their concurrent expressions in OSCC have not been thoroughly examined. Our aim is to assess the expressions of ADAM9, CDCP1, and t-PA in OSCC specimens, compare them with normal oral tissues, and explore their correlation with OSCC's clinicopathological features and patient survival outcomes.

SH3 domain‑binding glutamic acid‑rich protein‑like 3 is associated with hyperglycemia and a poor outcome in Epstein‑Barr virus‑negative gastric carcinoma.

SH3 domain-binding glutamic acid-rich protein-like 3 (SH3BGRL3) is involved in several human cancers. However, its relationship with gastric cancer (GC) remains elusive. Multiple online bioinformatic tools were used to evaluate the messenger (m)RNA expression levels of SH3BGRL3 in GC using data from The Cancer Genome Atlas and Gene Expression Omnibus databases. Reverse transcription-quantitative PCR and tissue microarray-based immunohistochemistry were performed to assess SH3BGRL3 expression in relation to clinicopathological parameters and outcomes in patients with GC. Significant differentially expressed genes (DEGs) of SH3BGRL3 were enriched and visualized. Furthermore, associations between the expression of SH3BGRL3 and the infiltration of immune cells were explored. SH3BGRL3 exhibited aberrant expression in tumor tissues compared with adjacent normal tissues at the mRNA and protein expression levels, especially in Epstein-Barr virus-negative GC (EBVnGC). Higher SH3BGRL3 expression was significantly associated with increasing tumor-node-metastasis staging, tumor budding, perineural invasion, EGFR expression, and a notably higher preoperative blood glucose concentration in clinical specimens. Multivariate analysis revealed that higher SH3BGRL3 expression was an independent adverse prognostic factor for the overall survival of patients with EBVnGC (hazard ratio, 1.666; P=0.018). Furthermore, the stratified analysis revealed that the SH3BGRL3 phenotype could help to refine prognosis in patients. The C-index of the nomogram was 0.740 when combining SH3BGRL3 with other clinicopathological parameters, which indicated a good model for clinical follow-up decisions. Gene functional enrichment analysis also revealed that the DEGs of SH3BGRL3 were mainly enriched in regulating ATP metabolism, ATP synthesis, oxidative phosphorylation and the electron transport chain in GC. Moreover, a higher SH3BGRL3 expression was significantly positively correlated with the infiltrating macrophages in GC. In conclusion, SH3BGRL3 is upregulated in GC, particularly in EBVnGC. Higher SH3BGRL3 expression is closely associated with hyperglycemia and poor outcomes in patients with EBVnGC, suggesting its potential as a biomarker and prognostic predictor.

Lymph Node Metastasis and Its Risk Factors for Early Gastritis Individuals Who Underwent Noncurative Endoscopic Resection: A Systematic Review and Meta-Analysis.

In the present review, we carried out a systematic review and meta-analysis to analyze possible lymph node metastasis (LNM) hazards in individuals with endoscopic resection of gastric cancer. Relevant literature was selected by evaluating the PubMed, Cochrane Library, and Google Scholar electronic databases since from inception to March 2022. Corresponding clinicopathological outcomes were summarized, and pooled log odds ratios and 95% confidence intervals were assessed. The random effect model was preferred if variations among studies is high otherwise fixed effect model was preferred. Overall, 12 associated papers, including 4808 early gastric cancer individuals who endured more surgery after noncurative endoscopic resection, were entered into this analysis. The outcomes showed that submucosal invasion (log odd ratio 1.75, 95% (CI): 0.77-3.95, I2 = 80.0%); vertical margin (log odd ratio 6.53, 95% (CI): 2.81-15.17, I2 = 65%); horizontal margin (log Odd ratio 0.69 95% (CI): 0.22-2.14, I2 = 52%), lymphatic invasion (Odd ratio 6.33 95% (CI): 1.98-20.24, I2 = 91%), and vascular invasion (Odd ratio 3.55, 95% (CI): 1.31-9.58, I2 = 92%) was significantly related to metastasis of lymph node for these patients. There was a significant association of LNM hazards in individuals with endoscopic resection of gastric cancer. Therefore, invasion to lymph, vascular, submucosa and positive vertical margin should be strongly noticed when selecting surgical treatment factors.

Clonal Bronchopulmonary B-Cell Proliferations of Indeterminate Malignant Potential in Patients with Common Variable Immune Deficiency (CVID) associated Granulomatous Lymphocytic Interstitial Lung Disease (GLILD)

Abstract Introduction/Objective Pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is often challenging to distinguish from reactive nodular lymphoid hyperplasia, and assessing B-cell clonality in such cases is crucial in making the distinction. However, patients with common variable immune deficiency (CVID) can harbor clonal or oligoclonal lymphoid populations in their tissues, particularly in association with granulomatous lymphocytic interstitial lung disease (GLILD), making the distinction from MALT lymphoma extremely challenging. We report six cases of GLILD with clonal or oligoclonal B cell infiltrates in lung wedge resection specimens and describe their clinicopathologic characteristics, management, and outcomes. Methods/Case Report A retrospective review was performed to collect lung wedge resection specimens from patients with CVID showing atypical B-cell infiltrates associated with GLILD between 01/2015 and 08/2023. The clinicopathologic findings, management, and response to treatment were studied. Results (if a Case Study enter NA) A total of six GLILD cases were identified with variable degrees of architectural and cytologic lymphoid atypia. Clonality of the lymphoid infiltrate was assessed by kappa/lambda in situ hybridization staining in all six, flow cytometry in 3/6, and IGH gene rearrangement in 4/6 cases. The infiltrate showed frank lambda restriction in 1/6, lambda predominance in 1/6, polytypic expression in 1/6, and no significant plasmacytic component in 3/6 cases. Flow cytometry detected atypical light chain skewed B-cell populations in 3/3 of cases. IGH was positive for clonality in 3/4 and oligoclonal in 1/4 cases. Four patients received therapeutic intervention for GLILD, including one with Rituximab monotherapy, two with Rituximab+Azathioprine, and one with Rituximab+Mycophenolate leading to marked symptomatic and radiologic improvement in all four patients. The remaining two patients were observed to have stable disease. Conclusion Patients with CVID can harbor clonal B-cell populations due to their underlying immune dysfunction. Studies have shown that these can be transient and may not always progress to overt lymphoma. In the setting of GLILD, detecting these populations makes the distinction from MALT lymphoma very challenging. Given that the first- line therapy for both GLILD and MALT is anti-CD20 therapy, the malignant potential of these clones remains uncertain and can only be determined with long-term clinical follow-up.