Histological Stage Research Articles

Comparison of Breast Cancer Characteristics in Women below and above 50 at Mankweng Hospital in Limpopo Province, South Africa

Background: Breast cancer normally occurs in elderly women, although it also affects young women. In the Limpopo province, South Africa over 38% of breast cancer occurred in younger women under 50 years of age. The main objectives of the study were to identify the characteristics of breast cancer in women >50 years and <50 years and to categorise any differences (histological type, stage, grading and molecular subtype) exist between these two groups of breast cancer patients. Methods: This is a cross-sectional design study to analyse the profile of women >50 and <50 years with breast cancer who attended Mankweng Breast Oncology Clinic from July 2020 to December 2021. Patient demographics were summarised using descriptive statistics. Categorical variables were expressed as proportions and frequency. Association between categorical variables was done using a Chi-square test. Results: Total 222 patients. Age: >50 years-old: 131(59%); <50 years old: 91(41%). Age: >50 years group: Early stage: 49(37.4%), late stage: 82(62.6%). Molecular subtype: luminal A: 23(17.6%); luminal B: 67(51.2%); HER-2 overexpression: 21(16%); triple negative: 20(15.3%). Histological type: invasive ductal carcinoma: 126(96.2%). Age: <50 years group: Early stage: 31(34.1%), late stage: 60(65.9%). Molecular subtype: luminal A: 28(30.8%); luminal B: 40(44%); HER-2 overexpression: 5(5.5%); triple negative: 18(19.8%). Histological type: invasive ductal carcinoma: 89(98%). Conclusion: Majority of patients presented at an advanced stage in both groups. HER2 overexpression molecular subtype was higher in the >50-year patient group in compared to <50 years group (p-value 0.016). Health education and breast cancer awareness campaigns are essential for all women, young and elderly in the Limpopo province.

Significance of N-terminal pro-B-type natriuretic peptide levels in lung cancer

High blood levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) have been shown in various malignancies. In lung cancer, the importance of NT-proBNP is not clear. In this study, we aimed to investigate the significance of the correlation of NT-proBNP levels in lung cancer with tumor stage, tumor diameter, histopathology, and specific sites of mediastinal metastasis: lymphadenopathy; pericardial, cardiac, major vessel, other mediastinal organ or lymphatic involvement/invasion. A total of 105 lung cancer and 120 control patients (chronic obstructive lung disease, interstitial lung disease, pulmonary thromboembolism, and pneumonia; 30/subgroup) with measured NT-proBNP levels were included retrospectively. Demographics, comorbidities, and echocardiographic findings in all patients, as well as histologic subtype, diameter, stage, and radiologic and/or pathologic mediastinal involvement/invasion of the tumor to the mediastinum in patients with lung cancer, were studied with regards to blood NT-proBNP levels. When lung cancer and control groups were compared globally or as subgroups with comorbidities, NT-proBNP levels did not show meaningful differences. However, NT-proBNP levels were determined to be 249 pg/mL and 88 pg/mL in lung cancer (n=68) and control subgroups (n=58) without comorbidities, respectively (p=0.001). Among lung cancer patients without comorbidities and those with cardiac, pericardial, major vascular, or other mediastinal involvement/invasion (lymphadenopathy, lymphatic, or other organ invasion) (n=27), the NT-proBNP level was 303 pg/mL, whereas it was 166 pg/mL in those without these mediastinal invasions (n=41) (p=0.031). There is a need for much larger, randomized studies to obtain evidence for the potential role of NT-proBNP as a helpful diagnostic biomarker for lung cancer. Clinical suspicion of malignancy may be posed if high NT-proBNP levels cannot be explained by all other risk factors and disorders or diseases. Furthermore, pericardial, cardiac, major vessel, or other mediastinal invasion/involvement should be sought when high NT-proBNP levels are determined in lung cancer patients without any comorbidities or risk factors for high NT-proBNP levels.

P0243 Evaluation of liver fibrosis and steatohepatitis associated with metabolic dysfunction (MASH) in patients with inflammatory bowel disease (IBD) and steatotic liver disease associated with metabolic dysfunction (MASLD)

Abstract Background Inflammatory bowel disease (IBD) is associated with a systemic inflammatory state and dysbiosis, which may increase the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). This occurs through intestinal bacterial translocation and the increased entry of lipopolysaccharides, free fatty acids, and other toxins into the liver via the portal circulation. One significant complication of MASLD is metabolic dysfunction-associated steatohepatitis (MASH), which can progress to cirrhosis. This study aimed to evaluate the prevalence of MASLD in IBD patients and assess the frequency of complications, such as MASH and liver fibrosis. Methods The presence of MASLD was based on the presence of NAFLD associated with the metabolic criterion in outpatients with IBD. The presence of NAFLD was confirmed using liver ultrasound. Noninvasive estimate of liver fibrosis (FIB-4) Index and NAFLD Fibrosis Score (NFS) were used as indirect scores of liver fibrosis. Patients with scores greater than NFS > 0.675 and/or FIB-4 > 2.67; and patients with indeterminate or discordant scores were indicated for liver biopsy to quantify liver fibrosis and evaluate MASH. Liver elastography was not performed due to unavailability in our center. Results A total of 179 patients underwent liver ultrasound, with 72 (40.2%) diagnosed with MASLD, including 33 with Crohn’s disease (CD) and 39 with ulcerative colitis (UC). Regarding disease activity, 36.11% were clinically active and 50% were endoscopically active. Biological therapy was used by 54.2% of patients. The degree of steatosis was mild (41.67%), moderate (44.4%) and intense (13.89%). According to the FIB-4 Index, patients were classified as low risk of fibrosis (72.22%), intermediate risk (26.32%) and high risk (1.39%). According to the NFS, the risks for fibrosis were low (53.52%), undetermined (38.08%) and high (8.45%). Sixteen (22.22%) patients underwent liver biopsy, and the presence of fibrosis was observed in 11 (68.75%) patients. The histological stage of fibrosis was F1 (n=6, 54.5%), F2 (n=3, 27,3%), F3 (n=1, 9.1%) and F4 (n=1, 9.1%) according to Kleiner's classification. 4 patients (25%) met criteria for MASH. Conclusion A high prevalence of MASLD was observed in patients with IBD. Among patients with MASLD, we must be aware of the risk of liver fibrosis and MASH. Routine monitoring of liver function and fibrosis, including liver biopsy or elastography when appropriate, is crucial for early detection and management of complications. Due to the lack of routine elastography in our center in Brazil, liver biopsy remains essential for accurate assessment in those patients.

Recurrence Patterns and Management after Pleurectomy Decortication for Pleural Mesothelioma.

We hypothesize that recurrence following pleurectomy decortication (PD) is primarily local. We explored factors associated with tumor recurrence patterns, disease-free interval (DFI), and post-recurrence survival (PRS). Tumor recurrence is a major barrier for long-term survival after pleural mesothelioma (PM) surgery. All patients who underwent PD between 1998 and 2022 were identified. Patients with diffuse PM who achieved macroscopic complete resection and had sufficient information on tumor relapse were included. Postoperative scans were reviewed to determine the timing and sites of the first recurrence. A total of 436 patients had tumor recurrence during follow-up. Local recurrences occurred most frequently (N=370, 85%) and represented the only recurrence site in 29% (N=129) of cases. Patients with sarcomatoid tumors relapsed earlier than other subtypes (P=0.003) with more frequent distant spread compared to other subtypes (P<0.001). Multivariable analysis revealed that age (P=0.015), preoperative tumor volume (P<0.001), epithelioid histology (P<0.001), intraoperative chemotherapy (P<0.001), and TNM stage IV (P=0.003) were associated with DFI. Similarly, age (P=0.042), performance status (P<0.001), epithelioid histology (P<0.001), intraoperative chemotherapy (P<0.001), TNM stages III and IV (P=0.003 and 0.010 respectively), type of surgery (P=0.019), and number of recurrent lesions (P=0.024) were associated with PRS. Recurrence surgery (HR 0.46, 95% CI 0.29-0.74) and chemotherapy (HR 0.69, 95% CI 0.54-0.92) were independently associated with PRS in patients with distant with or without local recurrences. PM is frequently associated with local recurrence. Repeat surgical resection is feasible and can achieve good local control in selected cases.

Incidence, characteristics, and comorbidities of a complete unselected Danish cohort of patients with thymic epithelial tumors.

We report the incidence, characteristics, and comorbidities of the complete unselected Danish cohort of patients with thymic epitheliums (TETs), which may serve as evidence for guiding treatment, surveillance, and counselling of TET patients. All patients diagnosed with TETs from January 1st, 2015, to December 31st, 2020, were identified using the Danish Pathology Data Registry. Data on patient characteristics, comorbidities, and tumor histology were collected from electronic medical records available for all patients. The cohort consisted of 283 patients with a mean age of 64 years (SD: 12). The crude rate was 8.2/1,000,000 TETs annually, thus higher than the age-standardized rates of 4.8/1,000,000 in the WHO World Standard Population and 6.1/1,000,000 in the European Standard Population. Thymomas were diagnosed in 240 patients (85%) (9% type A, 31% AB, 18% B1, 26% B2, 6% B3, 5% micronodular, 0.4% metaplastic, and 5% of unspecified subtype), thymic carcinomas in 39 patients (14%), and thymic neuroendocrine tumors in 4 patients (1.4%). Tumors in Tumour, Node, Metastasis (TNM) stage I were diagnosed in 181 patients (64%) and were mostly thymomas (72%). Prior to TET diagnosis, 91 (32%) patients presented with autoimmune disorders (19% myasthenia gravis) and 82 patients (29%) had at least one cancer diagnosis. We found a higher incidence of TETs in Denmark than in previous European population-based studies, while reporting a similar distribution of histological types and tumor stages. Furthermore, we found an increased prevalence of autoimmune disorders and cancers in the cohort before TET diagnosis compared to the general population.

Development, validation, and prognostic evaluation of LiverPRO for the prediction of significant liver fibrosis in primary care: a prospective cohort study.

Clinically significant liver fibrosis is associated with future adverse events in patients with steatotic liver disease. We designed a software tool for detection of clinically significant liver fibrosis in primary care. In this prospective cohort study, we developed and validated LiverPRO using six independent cohorts from Denmark, Germany, and England that included patients from primary and secondary care with steatotic liver disease related to alcohol or metabolic dysfunction. We used clinically significant fibrosis (histology stage ≥F2) and advanced fibrosis (≥F3) as outcomes for variable selection in the development cohort and built the model with fractional polynomial regression. In all cohorts, we independently validated the tool for prediction of elevated liver stiffness by transient elastography (≥8 kPa and ≥12 kPa) and for the 2-year and 5-year risk of liver-related events. Diagnostic performance was assessed using the area under the receiver operating curve (AUC), with clinical performance evaluated through sensitivity, specificity, and Harrell's C-statistic for prognostic purposes. In the development cohort (n=462), we derived 466 multivariable models consisting of age in combination with three to nine variables from a list of nine blood tests (aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, international normalised ratio, albumin, sodium, bilirubin, platelet count, and cholesterol). In the development cohort, LiverPRO diagnosed clinically significant fibrosis with good accuracy (transient elastography ≥8 kPa area under the receiver operating characteristic curve [AUC] 0·86 [95% CI 0·83-0·90]). In the DECIDE validation cohort (n=6468), LiverPRO detected participants with a transient elastography of 8 kPa or higher with good accuracy (AUC 0·80 [95% CI 0·78-0·82]), comparable to enhanced liver fibrosis testing (0·78 [0·75-0·80]) and the LiverRisk score (0·81 [0·79-0·84]), but superior to the Fibrosis-4 index (0·69 [0·66-0·72]) and NAFLD Fibrosis Score (0·74 [0·72-0·77]). Findings were consistent in three other validation cohorts (n=2554), albeit accuracy was slightly lower. Using a rule-out cutoff of less than 25% (indicating no further examinations required), LiverPRO had a rule-out sensitivity of 80·6% (95% CI 76·4-84·3) and a rule-out negative predictive value of 98·0% (95% CI 97·5-98·4) in the DECIDE cohort. Similarly, with a rule-out cutoff of less than 1·3, FIB-4 had a rule-out sensitivity of 53·8% (48·5-58·9) and a rule-out negative predictive value of 95·8% (95·1-96·4). For rule-in thresholds, using a cutoff of more than 65% (indicating referral to a hepatologist required) LiverPRO had a rule-in specificity of 95·5% (95% CI 94·9-96·0) and a rule-in positive predictive value of 33·0% (95% CI 28·5-37·8) in the DECIDE cohort whereas FIB-4, with a rule-in threshold of 2·67, had a rule-in specificity of 98·7% (94·9-96·0) and a rule-in positive predictive value 35·6% (27·0-44·9). Using UK Biobank data, LiverPRO predicted liver-related events with a C-statistic of 0·80 (0·77-0·84) at 2 years. LiverPRO reliably identifies clinically significant liver fibrosis and elevated liver stiffness, predicts the risk of liver-related events in primary care, and is adaptable to the availability of different liver blood test analytes. On the basis of these results LiverPRO was certified according to IVDR class b, obtaining European CE approval in 2024. EU Horizon 2020 research and innovation programme and Novo Nordisk Foundation.

Utilization of breast magnetic resonance imaging in the pre-operative setting and its ability to better predict local staging in non-metastatic breast cancer patients

Background: Breast cancer can be difficult to stage using ultrasound (USS) and mammography (MMG) alone. The use of MRI in the pre-operative setting has been increasingly incorporated to aid in treatment planning. However, the indications for breast magnetic resonance imaging (MRI) are not universally agreed upon, and its direct impact on patient care requires further research. This paper aims to assess pre-operative non-metastatic breast cancer patients to determine whether breast MRI led to changes in management and to evaluate its accuracy in predicting tissue staging when compared to ultrasound and mammography. Method: This is a retrospective study of 44 patients diagnosed with non-metastatic breast cancer who underwent upfront surgery and received pre-operative breast MRI between March 1, 2022, and March 1, 2024. Patient demographics, pre-operative imaging (including USS, MMG, and MRI), and final tissue histology were reviewed. The findings from breast MRI and its impact on pre-operative planning, as well as its concordance with final tissue histological staging, were assessed. Results: Of the 44 patients who underwent pre-operative breast MRI, 12 experienced a change in management, and 11 required additional investigations. This was largely due to an upstaging of the disease, leading to mastectomy instead of the previously planned breast-conserving surgery. Furthermore, breast MRI demonstrated better concordance with final histological staging at 69.4% compared to USS/MMG alone at 52.7%. Conclusion: Breast MRI is a valuable tool in pre-operative planning for newly diagnosed breast cancer patients. It can significantly affect surgical management in a substantial proportion of patients and has been shown to be more accurate in estimating disease burden.

Surgical indications for pleurectomy/decortication in pleural mesothelioma based on the newly revised 9th edition of the tumour-node-metastasis classification.

The MARS2 trial questioned the efficacy of curative intent surgery for pleural mesothelioma (PM), while real-world clinical data from Japan suggest a favourable prognosis in surgical cases, indicating survival benefits in selected patients. The newly revised 9th edition of the tumour-node-metastasis (TNM) classification introduces a novel indicator based on pleural thickness. We conducted a retrospective evaluation of patients with PM who underwent pleurectomy/decortication between 2012 and 2022. Patient characteristics, complications and treatment outcomes were assessed. Additionally, outcomes were analysed based on the 9th edition of the TNM classification. A total of 62 patients were included in the analysis. The median overall survival (OS) was 37.3 months, with a median relapse-free survival (RFS) of 15.5 months. Patients with the epithelioid subtype (OS: 61.6 months; RFS: 26.0 months) and pStage IA (OS: not reached; RFS: 69.1 months) had significantly better outcomes. The 9th edition of the TNM classification showed a stronger prognostic correlation than the 8th edition, with a median OS of 77.0, 31.9, 20.4 and 25.3 months for stages I, II, IIIA and IIIB (P = 0.0016) and median RFS of 34.3, 12.3, 13.7 and 6.9 months for stages I, II, IIIA and IIIB (P = 0.013), respectively. Surgical intervention remains crucial in the treatment of PM, particularly for patients with epithelioid histology and early stages of the disease. This study evaluates surgical indications for PM using the newly revised 9th edition of the TNM classification, indicating that it enhances the precision of surgical candidate selection and potentially improves patient outcomes.

Precise vesical wall staging of bladder cancer in the era of precision medicine: has it been fulfilled?

Urinary bladder cancer is a global disease that poses medical and socioeconomic challenges to patients and healthcare systems. Predicting detrusor invasiveness and pathological grade of bladder cancer by the radiologist is imperative for informed decision-making and effective patient-tailored therapy. Cystoscopy and TURBT are the current gold standard for preoperative histologic diagnosis and local pathological staging but are compromised by their intrusiveness, under-sampling, and staging inaccuracies. Over the last few decades, incredible imaging technology advancements have enabled radiologists to progress in these grading and staging tasks. MRI has become widely accepted as a noninvasive alternative. It supplements morphologic data with functional insights into the tumor microenvironment, enhancing tumor characterization and predicting the detrusor's histologic grade and invasiveness status. Radiomics is a promising field that helps radiologists achieve higher accuracies in bladder cancer staging, re-staging, and direct treating teams to potential management readjustments. Such knowledge leaps hold promise for personalized management of bladder cancer in a precision medicine era.

The Impact of Tumor Stage and Histopathology on Survival Outcomes in Esophageal Cancer Patients over the Past Decade.

Esophageal cancer (EC) is the sixth leading cause of cancer-related mortality worldwide, continuing to be a significant public health concern. The purpose of this study is to assess the impact of staging and histopathology of EC on associated mortality. The study also aims to further investigate clinical characteristics, prognostic factors, and survival outcomes in patients diagnosed with EC between 2010 and 2017. Furthermore, we analyzed the interaction between tumor histology and staging and the risk of mortality. A total of 24,011 patients diagnosed with EC between 2010 and 2017 in the United States were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Demographic parameters, tumor stage, and histologic subtypes were analyzed and associated overall mortality (OM) and cancer-specific mortality (CSM) were measured across all subgroups. Covariates reaching the level of statistical significance, demonstrable by a p-value equal to or less than 0.01, were incorporated into a multivariate Cox proportional hazards model. A hazard ratio greater than 1 was indicative of an increased risk of mortality in the presence of the variable under discussion. Additionally, the study explores the interaction between histology and tumor stage on outcomes. The majority of patients were male (80.13%) and non-Hispanic white (77.87%), with a predominant age at diagnosis of between 60 and 79 years (59.86%). Adenocarcinoma was the most common tumor subtype (68.17%), and most patients were diagnosed at a distant stage (41.29%). Multivariate analysis revealed higher mortality risks for males, older patients, unmarried individuals, and those with advanced-stage tumors. Higher income, receiving radiation or chemotherapy, and undergoing surgery were associated with lower mortality. Tumor subtype significantly influenced mortality, with squamous cell carcinoma and neuroendocrine tumors showing higher hazard ratios compared to adenocarcinoma. Adenocarcinoma is linked to a poorer prognosis at advanced stages, whereas the opposite trend is observed for SCC. The study identifies significant demographic and clinicopathologic factors influencing mortality in esophageal cancer patients, highlighting the importance of early diagnosis and treatment intervention. Future research should focus on tailored treatment strategies to improve survival outcomes in high-risk groups and to understand the interaction between tumor histology and tumor stage.

TRIB3 overexpression predicts malignant progression and poor prognosis in human solid tumors: bioinformatics validation and clinical significance

ABSTRACT Introduction Overexpression of tribbles homolog 3 (TRIB3) has been reported in various cancers, yet its clinical significance remains contentious. This study aims to elucidate the association between TRIB3 overexpression and the progression and prognosis of solid tumors. Methods A comprehensive analysis was conducted using data from published studies and The Cancer Genome Atlas (TCGA) up to May 2023. We evaluated the impact of high TRIB3 expression on tumor malignancy and survival outcomes across different cancer types. Results Seventeen studies met the inclusion criteria. Our findings revealed that TRIB3 overexpression is significantly associated with increased distant metastasis (OR = 4.01, 95% CI: 2.36–6.74, p < 0.001) and advanced histological stage (OR = 2.68, 95% CI: 1.50–4.78, p < 0.001). Additionally, high TRIB3 expression significantly elevated the risk of reduced overall survival (OS) in cancer patients (HR = 1.52, 95% CI: 1.05–2.20, p < 0.001), indicating a poor prognosis. Analyses of TCGA data among various prognostic indicators corroborated these findings. Conclusions TRIB3 overexpression is significantly linked to malignant progression and unfavorable prognosis in diverse solid tumors. These results suggest that TRIB3 holds promise as a biomarker and therapeutic target in human cancers.

Is There Anything New in Canine AGASACA?

Apocrine gland anal sac adenocarcinoma (AGASACA) is a locally invasive tumor with a high potential for early metastasis. The most recent studies indicate that 23.4-83% of dogs have metastases to the iliosacral lymph nodes (LNs), and 2.1-31% have distant metastases to other organs at the time of first presentation. Usually, only one anal sac is affected, but bilateral involvement has been reported in 4-20% of dogs. About 16-53% of dogs present with paraneoplastic hypercalcemia. The most recent studies show an overall improvement in median survival time (MST) (15-28 months) for dogs with different stages of AGASACA treated with surgery and adjuvant therapy compared to those treated with chemotherapy alone (6.9 to 8.7 months). The highest MST (22-32 months) was reported when radiation therapy (RT) was selected as a sole or adjunctive treatment. Several studies have been published to identify the subset of tumors with more aggressive behavior and higher metastatic potential. The main negative prognostic factors are the size of the primary tumor, metastatic regional lymphadenopathy at first presentation, the size and the number of the metastatic lymph nodes, distant metastases at the time of diagnosis, and the histological characteristics of the primary tumor. In this critical review, the latest advancements in histological diagnosis, staging, treatment, and prognosis of AGASACA are described. The aim is to provide a full overview of this neoplasm, focusing on the latest advancements on prognostic variables and treatments.

Nanoparticle-Mediated Gene Delivery for Bone Tissue Engineering.

Critical-sized bone defects represent an urgent clinical problem, necessitating innovative treatment approaches. Gene-activated grafts for bone tissue engineering have emerged as a promising solution. However, traditional gene delivery methods are constrained by limited osteogenic efficacy and safety concerns. Recently, organic and inorganic nanoparticle (NP)vectors have attracted significant attention in bone tissue engineering for their safe, stable, and controllable gene delivery. Targeted gene delivery guided by insights into bone healing mechanisms, coupled with the multifunctional design of NPs, is crucial for enhancing therapeutic outcomes. Here, the theoretical foundations underlying NP-mediated gene therapy for enhancing bone healing across different histological stages are elucidated. Furthermore, the distinct attributes of functionalized NP vectors are discussed, and cutting-edge strategies aimed at optimizing gene delivery efficiency throughout the therapeutic process are highlighted. Additionally, the review addresses the unresolved challenges and prospects of this technology. This review may contribute to the continued development and clinical application of NP-mediated gene delivery for treating critical-sized bone defects.

Endoscopic submucosal dissection of colorectal pedunculated polyps.

Background and study aims For pedunculated colon polyps, en bloc resection with inclusion of the polyp stalk is necessary to yield an accurate histologic staging. This can be challenging in cases of a large polyp and/or broad stalk using conventional snare resection. We evaluated the feasibility of endoscopic submucosal dissection (ESD) for large pedunculated polyps with broad stalks. Patients and methods Between February 2019 and November 2021 all patients with large pedunculated polyps defined as polyp diameter ≥ 20 mm and or a broad stalk > 5 mm were enrolled in the study. All polyps were resected in ESD technique with dissection of the polyp stalk at the base after injection. Results Twenty-five patients (male = 18, age mean: 67 years) were included. En bloc resection was achieved in 100% of the patients (25/25 polyps). Polyps were mainly located in the sigmoid (n = 19) and rectum (n = 3). Median polyp size was 30×25×17 mm. Histologic examination revealed the following results: adenoma low-grade intraepithelial neoplasia (LG-IEN): nine; high-grade intraepithelial neoplasia (HG-IEN): seven; pTis: three; adenoarcinoma: five (G1, pT1, L0, V0, Haggitt 3: 2/G2, pT1, L0, V0, Haggitt 3:2/G3, pT1, Bd3, V1, Haggitt 4: 1); other: 1. R0 resection rate was 100% and the curative resection rate yielded 96% (24/25) without severe adverse events. Conclusions ESD achieved high en bloc and R0 resection rates for large pedunculated polyps. In our collective, up to 32% of polyps already had adenocarcinoma, resulting in a high curative resection rate due to complete resection and subsequently accurate risk classification.

Meniere's disease: Structural considerations in early cochlea hydrops.

Structural features of the human cochlea may control early lesion formation in endolymphatic hydrops. This process may hinge on three structural features: the flattened spiral shape of the human cochlea, the toroidal configuration of the distended cochlea duct, and the distensibility characteristics of Reissner's membrane. An analytical method is presented to assess the variation in hydropic distention that may occur in the several turns of the cochlea due to these structural features. A normal human cochlea is used to illustrate the method of analysis. Structural dimensions were taken from a mid-modiolar section. Reissner's membrane was projected to assume a spiral toroid shape as it distends. Peak membrane stress proclivities in each cochlea turn were calculated analytically. Membrane strain was assessed from a collagen model of Reissner's membrane. Sagittal membrane displacements were quantified geometrically. Stress levels in Reissner's membrane were projected to be the lowest in the lower basal turn and to increase progressively to a peak value in the apex. Strain in Reissner's membrane in the apical turn was projected to be substantially higher than in the lower turns. Sagittal displacement of Reissner's membrane was projected to be most pronounced in the apical turn in all the stages of early cochlea hydrops. Structural features appear to underlie a differential susceptibility to hydrops in the human cochlea. The flattened spiral shape of the human cochlea coupled with the anticlastic configuration and the distensile characteristics of Reissner's membrane are projected to result in distinct histological stages as hydropic disease in the cochlea progresses.

Evaluation of Clinicopathologic Characteristics and Survival Rates of Patients with Renal Cell Carcinoma in Northeast of Iran

Background: Renal cell carcinoma (RCC) is the 9th most common cancer in men and the 14th most common in women. To date, there remains considerable uncertainty regarding factors that influence the survival of RCC patients. Objectives: This study aimed to determine the clinicopathologic characteristics and outcomes of RCC over a 15-year period in northeast Iran. Methods: Data were collected from RCC patient records at Omid and Imam Reza Hospitals and Reza Radiation Oncology Center from 2001 to 2016. Demographic and clinicopathological data were extracted from patient records, and the current status of participants was assessed through telephone follow-ups. Overall and disease-free survival were analyzed using SPSS version 20. Results: A total of 230 RCC patients were enrolled in this study. The majority of patients were male, with a mean age of 56.78 years. Overweight status was common among patients, and pain was the most frequently reported symptom. The most common histologic subtype was clear cell carcinoma. The median follow-up period was 10.50 months, with overall survival rates at 1, 3, 5, and 10 years being 74.8%, 52.2%, 44.8%, and 39.6%, respectively. The mean overall and disease-free survival rates were approximately 24 and 25 months, respectively. Survival was significantly associated with RCC histologic subtype, disease stage, hemoglobin level, and underweight status. In contrast, sex, type of surgery, and chemotherapy regimen did not significantly impact survival. Conclusions: Renal cell carcinoma patient survival was influenced by histologic subtype, disease stage, low hemoglobin levels, and underweight status.

Comparative diagnostic efficacy of two-dimensional shear wave and transient elastography in predicting the risk of esophagogastric varices and histological staging in patients with primary biliary cholangitis

BackgroundThis study aimed to compare the diagnostic efficacy of Two-dimensional shear wave elastography (2D-SWE) with that of transient elastography (TE) in predicting the risk of esophagogastric varices and histological staging in patients with primary biliary cholangitis (PBC).MethodsThis single-center prospective study enrolled the patients with PBC diagnosed by liver biopsy following 2D-SWE and TE. Receiver operating characteristic (ROC) curves were constructed for SWE-liver stiffness measurement (LSM) and TE-LSM to assess their diagnostic efficacy for histological staging ≥ stage 2, ≥ stage 3, and = stage 4. The diagnostic efficacy and accuracy of SWE-LSM were compared with those of the Baveno VI criteria for detecting esophagogastric varices. Additionally, the impact of different laboratory parameters on SWE-LSM was analyzed.ResultsWe evaluated 77 patients (median age, 52 years (range: 16 − 75 years), 66 females). ROC curves constructed using TE-LSM and SWE-LSM demonstrated similar diagnostic efficacy for histological staging ≥ stage 2 (area under the curve [AUC]: 0.824 vs. 0.823 for TE-LSM and SWE-LSM, respectively, p = 0.9764), ≥ stage 3 (AUC: 0.918 vs. 0.907 for TE-LSM and SWE-LSM, respectively, p = 0.6443), and = stage 4 (AUC: 0.907 vs. 0.902 for TE-LSM and SWE-LSM, respectively, p = 0.8763). Additionally, while there was no significant difference in the diagnostic efficacy between the two methods for detecting esophagogastric varices (Z = 1.516, p = 0.1296), 2D-SWE had a slightly higher diagnostic accuracy than TE (61.8% vs. 76.4%). Transaminases and bilirubin levels had little influence on SWE-LSM.Conclusion2D-SWE exhibited comparable performance to TE in predicting the risk of esophagogastric varices and histological staging.

Enhanced NSCLC subtyping and staging through attention-augmented multi-task deep learning: A novel diagnostic tool

ObjectivesThe objective of this study is to develop a novel multi-task learning approach with attention encoders for classifying histologic subtypes and clinical stages of non-small cell lung cancer (NSCLC), with superior performance compared to currently popular deep-learning models. Material and methodsData were collected from six publicly available datasets in The Cancer Imaging Archive (TCIA). Following the inclusion and exclusion criteria, a total of 4548 CT slices from 758 cases were allocated. We evaluated multiple multi-task learning models that integrate attention mechanisms to resolve challenges in NSCLC subtype classification and clinical staging. These models utilized convolution-based modules in their shared layers for feature extraction, while the task layers were dedicated to histological subtype classification and staging. Each branch sequentially processed features through convolution-based and attention-based modules prior to classification. ResultsOur study evaluated 758 NSCLC patients (mean age, 66.2 years ± 10.3; 473 men), spanning ADC and SCC cases. In the classification of histological subtypes and clinical staging of NSCLC, the MobileNet-based multi-task learning model enhanced with attention mechanisms (MN-MTL-A) demonstrated superior performance, achieving Area Under the Curve (AUC) scores of 0.963 (95 % CI: 0.943, 0.981) and 0.966 (95 % CI: 0.945, 0.982) for each task, respectively. The model significantly surpassed its counterparts lacking attention mechanisms and those configured for single-task learning, as evidenced by P-values of 0.01 or less for both tasks, according to DeLong’s test. ConclusionsThe integration of attention encoder blocks into our multi-task learning network significantly enhanced the accuracy of NSCLC histological subtyping and clinical staging. Given the reduced reliance on precise radiologist annotation, our proposed model shows promising potential for clinical application.

Identification of Candidates for MASLD Treatment with Indeterminate Vibration-Controlled Transient Elastography

A noteworthy proportion of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) have an indeterminate vibration-controlled transient elastography (VCTE). Among these patients, we aimed to identify candidates for MASLD treatment by diagnosing significant fibrosis. This was a real-world prospective study including a large dataset of MASLD patients with paired VCTE and liver biopsy from 6 centers. A total of 1196 patients were recruited and divided in training (3 centers, Spain), internal validation (2 centers, Spain), and external validation (1 center, United States) cohorts. In patients with indeterminate liver stiffness measurement (LSM) (8-12 kPa), a diagnostic algorithm was developed to identify significant fibrosis, defined as histological stage ≥F2. Statistical analysis was performed using Gaussian mixture model (GMM) and k-means unsupervised clusterization. From the eligible population, 33%, 29%, and 31% had indeterminate VCTE in the training, internal and external validation samples, respectively. The controlled attenuation parameter allowed the differentiation of GMM clusters with a cutoff of 280 dB/m (area under the curve, 0.89; 95% confidence interval, 0.86-0.97). Within patients with <280 dB/m, a LSM between 8.0-9.0 kPa showed a 93% sensitivity and a 91% negative predictive value to exclude significant fibrosis. Among patients with ≥280 dB/m, a LSM between 10.3 and 12.0 kPa diagnosed significant fibrosis with a 91% specificity. Applying this algorithm to the validation cohorts, 36% of the indeterminate VCTE were reallocated. The reallocated high-risk group showed a prevalence of 86% significant fibrosis, opening the therapeutic window for MASLD patients. To identify candidates for MASLD treatment among indeterminate VCTE, an algorithm-based on the sequential combination of LSM and controlled attenuation parameter thresholds can optimize the diagnosis of moderate-to-advanced fibrosis.

Surgery for Patients With cT3/4N2M0, Stage IIIB NSCLC. Is It Time to Redefine Resectability?

IntroductionChemoradiation followed by durvalumab is considered a standard approach for patients with locally advanced NSCLC. With improvements in perioperative and neoadjuvant approaches, there is renewed interest in offering surgery to carefully selected patients with cT3/4N2 stage IIIB cancer. We sought to assess survival outcomes after surgery as part of a multimodality treatment regimen for these patients. MethodsPatients with cT3/T4N2M0 NSCLC who received surgery (S) as part of a multimodality approach and patients receiving multimodality treatment without surgery (chemoradiation [CRT] or systemic therapy only) were identified in the National Cancer Database (2010–2019). We evaluated factors associated with the receipt of S (logistic regression). After propensity matching, we estimated the overall survival (OS) of patients who received S and compared with those who received CRT (Kaplan-Meier and Cox regression). ResultsA total of 44,756 patients were identified, of whom 3928 (8.8%) underwent S, 29,798 (66.6%) CRT, and 11,030 (24.6%) systemic therapy only. Fewer comorbidities (Charlson-Deyo index 0 or 1, adjusted OR [aOR]: 1.22, 95% confidence interval [CI]: 1.05–1.42), treatment at an academic facility (aOR: 1.70, 95% CI: 1.52–1.89), private insurance (aOR: 2.44, 95% CI: 1.61–3.69), adenocarcinoma histology (aOR: 1.48, 95% CI: 1.22–1.79), and clinical T3 stage (<7 cm, aOR: 1.70, 95% CI: 1.53–1.89) were associated with S. In well-balanced, propensity-matched cohorts, patients selected for S had better OS compared with those who underwent CRT (hazard ratio 0.59, 95% CI: 0.56–0.63, p < 0.001) (median OS 49.7 versus 25.0 mo). ConclusionsIn this retrospective cohort analysis, patients with cT3/4N2, stage IIIB NSCLC who underwent surgical resection had better OS compared with those patients treated with CRT. Careful patient selection is undoubtedly critical, but stage IIIB designation alone should not exclude patients from surgical consideration.