Clinical Pathological Features Research Articles

Effect of endometriosis on prognosis of ovarian clear cell carcinoma: a 10-year retrospective study

IntroductionEndometriosis is considered as a precancerous lesion for OCCC; however its prognostic significance remains controversial. This study aims to evaluate the prognostic significance of endometriosis in patients with ovarian clear cell carcinoma (OCCC) and analyze the impact of other clinical pathological features on prognosis. Additionally, we also assess the role of laparoscopic surgery and chemotherapy in OCCC, hoping to provide evidence for improving the clinical diagnosis and treatment of OCCC.MethodsA retrospective analysis was conducted on medical records of 105 OCCC patients diagnosed and treated at the Gynecologic Cancer Center of Hubei Cancer Hospital in China from 2013 to 2022. Based on the presence or absence of endometriosis, OCCC patients were divided into two groups: a group with ovarian endometriosis consisting of 44 cases (41.9%) (EC-positive group) and a group without ovarian endometriosis consisting of 61 cases (58.1%)(EC-negative group). Clinical pathological characteristics, progression-free survival (PFS), and overall survival (OS) were compared between the two groups.ResultsThere were no statistically significant differences between the two groups in terms of age, CA125, tumor size, FIGO stage, adjuvant chemotherapy regimen, or chemotherapy efficacy (P>0.05). Residual tumor after surgery, staging, site invasion involvement, presence of ascites, positive cytology in ascitic fluid, lymph node metastasis, and chemotherapy efficacy were predictive factors for recurrence among patients with statistical significance (P<0.10); chemotherapy efficacy remained as independent predictors for recurrence (P<0.05); staging and chemotherapy efficacy remained as independent predictors for survival (P<0.05). There was no statistically significant difference observed between both groups regarding OS or PFS.ConclusionIn this study, co-existing endometriosis was not a prognostic factor for survival in patients with OCCC. The most important predictors of OS and PFS were FIGO stage and chemotherapy sensitivity. The intrinsic link between endometriosis and OCCC requires larger, better-designed prospective studies to draw more definitive conclusions.

Prediction of lateral lymph node metastasis with short diameter less than 8mm in papillary thyroid carcinoma based on radiomics.

The aim of this study was to establish an ensemble learning model based on clinicopathological parameter and ultrasound radomics for assessing the risk of lateral cervical lymph node with short diameter less than 8mm (small lymph nodes were used instead) metastasis in patients with papillary thyroid cancer (PTC), thereby guiding the selection of surgical methods. This retrospective analysis was conducted on 454 patients diagnosed with papillary thyroid carcinoma who underwent total thyroidectomy and lateral neck lymph node dissection or lymph node intraoperative frozen section biopsy at the First Hospital of China Medical University between January 2015 and April 2022. In a ratio of 8:2, 362(80%) patients were assigned to the training set and 92(20%) patients were assigned to the test set. Clinical pathological features and radomics features related to ultrasound imaging were extracted, followed by feature selection using recursive feature elimination (RFE). Based on distinct feature sets, we constructed ensemble learning models comprising random forest (RF), extreme gradient boosting (XGBoost), categorical boosting (CatBoost), gradient boosting decision tree (GBDT), and light gradient boosting machine (Lightgbm) to develop clinical models, radiomics models, and clinical-radiomic models. Through the comparison of performance metrics such as area under curve (AUC), accuracy (ACC), specificity (SPE), precision (PRE), recall rate, F1 score, mean squared error (MSE) etc., we identified the optimal model and visualized its results using shapley additive exPlanations (SHAP). In this study, a total of 454 patients were included, among whom 342 PTC patients had small lymph node metastasis in the lateral neck region, while 112 did not have any metastasis. A total of 1035 features were initially considered for inclusion in this study, which were then narrowed down to 10 clinical features, 8 radiomics features, and 17 combined clinical-omics features. Based on these three feature sets, a total of fifteen ensemble learning models were established. In the test set, RF model in the clinical model is outperforms other models (AUC = 0.72, F1 = 0.75, Jaccard = 0.60 and Recall = 0.84), while CatBoost model in the radiomics model is superior to other models (AUC = 0.91, BA = 0.83 and SPE = 0.76). Among the clinical-radiomic models, Catboost exhibits optimal performance (AUC = 0.93, ACC = 0.88, BA = 0.87, F1 = 0.91, SPE = 0.83, PRE = 0.88, Jaccard = 0.83 and Recall = 0.92). Using the SHAP algorithm to visualize the operation process of the clinical-omics CatBoost model, we found that clinical omics features such as central lymph node metastasis (CLNM), Origin_Shape_Sphericity (o_shap_sphericity), LoG-sigma3_first order_ Skewness (log-3_fo_skewness), wavelet-HH_first order_Skewness (w-HH_fo_skewness) and wavelet-HH_first order_Skewness (sqr_gldm_DNUN) had the greatest impact on predicting the presence of lateral cervical small lymph node metastasis in PTC patients. (1) In this study, among the ensemble learning models established based on clinicopathological features and radiomics features for predicting PTC lateral small lymph node metastasis, the clinical-radiomic CatBoost model has the best performance. (2) SHAP can visualize how the clinical and radiomics features affect the results and realize the interpretation of the model. (3) The combined CatBoost model can improve the diagnostic accuracy of suspicious lymph nodes with short diameter < 8mm that are difficult to obtain accurate puncture results. The combined application of radiomics features is more accurate and reasonable than the prediction of clinical data alone, which helps to accurately evaluate the surgical scope and provide support for individual clinical decision making.

Endoscopic resection for esophageal granular cell tumors: report of 62 cases.

To analyze the clinical manifestations, endoscopic features, pathological features, endoscopic resection, and prognosis of esophageal granular cell tumors (GCTs). The present study retrospectively analyzed and followed up the clinical data of 62 patients diagnosed with esophageal GCTs who underwent endoscopic resection at Zhongshan Hospital of Fudan University between July 2007 and March 2022. The clinicopathological features, endoscopic diagnosis, and treatment experience of esophageal GCT patients were summarized. Among the 62 patients with esophageal GCT, there were 34 males and 28 females, with an average age of 49.3 ± 11.7 years. Only 11 patients had symptoms, such as epigastric discomfort, regurgitation or dysphagia. One patient had multiple lesions, and the rest had single lesions, totaling 63 lesions. Most lesions (53/63) were located in the median and lower esophagus, the diameters ranged from 3 to 22mm. The endoscopic morphology of the GCTs was molar, flat, hemispherical, or irregular submucosal protuberance. Endoscopic ultrasound (EUS) was performed in 38 cases, most cases (31/38) were hypoechoic, and 32 cases were appeared as homogeneous lesions. There were no complications during or after the endoscopic operations, and the en bloc resection rate was 100%. The negative rate of microscopic incisional margin was 63.5% (40/63). No patients developed recurrence during the follow-up period. The follow-up duration was 21-197 months (100.5 months for average). Esophageal GCT is a rare disease with no obvious symptoms and a good prognosis. Endoscopic resection is a safe and effective method of diagnosis and treatment for esophageal GCTs. A microscopic positive tumor margin may not increase the rate of recurrence.

Clinical pathological features and progress of Fumarate hydratase-deficient renal cell carcinoma

Clinical pathological features and progress of Fumarate hydratase-deficient renal cell carcinoma

CYSTS OF THE CENTRAL NERVOUS SYSTEM: A REVIEW OF 35 CASES WITH OUTCOMES

Objective: Non-neoplastic, non-inflammatory cysts of the central nervous system (CNS) may cause symptoms as a result of changes in pressure, rupture or secondary inflammation. The cyst-related details, such as its age, site, cyst wall, and its contents, also provide an insight into their embryology and histogenesis. This paper reviews the clinic-pathological features of cysts of CNS. Methods: In this study, a prospective analysis of the cysts of CNS diagnosed between November 2019 and October 2023 who presented to our outpatient department and managed at Command Hospital Lucknow and Base Hospital Delhi Cantt were reviewed. Written informed consent was taken from all patients. Cystic degeneration in tumors or inflammatory lesions was excluded from the study. Results: There were 35 cysts in the study period of 04 years. Majority of intracranial cysts presented with signs of raised intracranial pressure. Patients with epidermoid cysts had additional cerebellar signs, visual disturbances and deafness. Cord compression is the main presentation of all spinal cysts. Conclusion: Cysts of CNS are usually maldevelopment in nature. A few are acquired. The radiological identification of these cysts and pathological confirmation is necessary for prognostic purposes.

Changes in clinical features and seasonal variations of Crohn’s disease at diagnosis: a 10-year observational study in China

Background and aimsThe clinical aspects of Crohn’s disease (CD) at diagnosis determine its therapy and management. The onset of CD follows a seasonal pattern. We aimed to analyze changes in the clinical features and seasonal variations of newly CD patients over the last decade.MethodsCD patients were divided into cohort 1 (2012–2016) and cohort 2 (2017–2021). The clinical characteristics were collected and the trends according to the year and season of diagnosis were analyzed.ResultsA total of 2038 patients were included. Cohort 1 had a considerably greater proportion of diarrhea, fever, hematochezia, weight loss and extraintestinal manifestations. The levels of platelet and C-reactive protein were higher in cohort 2 patients, but the opposite was true for albumin levels (p&amp;lt;0.05). The rate of increased eosinophils, increased gangliocyte and abundant lymphoplasmacytic infiltrate significantly decreased over the years. Patients with granulomas were diagnosed with CD at an earlier age (p = 0.006). Cohort 1 patients used more conventional drugs, while cohort 2 patients apply more biologics (p&amp;lt;0.05). The diagnosis occurred more frequently in summer and less frequently in winter. Patients diagnosed in winter had notably higher BMI, lower frequency of perianal disease and lowest incidence of asthenia and weight loss.ConclusionThe clinical phenotype, laboratory and pathological characteristics of CD has changed over time in China. The diagnosis of CD tends to have a seasonal trend with the highest incidence in summer. CD patients diagnosed in winter appear to have a milder form of the disease.

HIF-1Α IN SALIVA: A PROMISING BIOMARKER FOR EARLY DIAGNOSIS OF ORAL SUBMUCOUS FIBROSIS AND ITS MALIGNANT POTENTIAL

Oral submucous fibrosis (OSF) is a chronic condition with a high risk of transforming into oral squamous cell carcinoma (OSCC). Identifying reliable biomarkers for early diagnosis and monitoring of OSF is crucial for malignancy prevention. Objective: This study evaluates the expression of Hypoxia Inducible Factor-1α (HIF-1α) in saliva as a potential biomarker for OSF. Methods: Study was a cross-sectional study conducted in Karachi. The study was completed in 6 months from July 2023 to December 2023 and Sixty-five OSF patients participated in the study, providing saliva samples analyzed for HIF-1α expression using immunohistochemically (IHC). Clinic pathological features, including age, gender, body mass index (BMI), and etiological factors (tobacco, smoking, areca nut), were documented. Relationships between clinical symptoms (burning sensation, pain, ulceration, and dry mouth), fibrosis severity, and HIF-1α staining intensity in blood vessels and fibroblasts were assessed. Results: The study population included 68.3% males and 31.7% females, with a mean age of 32.56±4.12 years. Tobacco use (47.7%) was the most common etiology. HIF-1α expression was significantly elevated in fibroblasts compared to blood vessels, with mild staining in 54.2% of blood vessels and 49.8% of fibroblasts. Increased HIF-1α expression correlated with more severe OSF symptoms, indicating a higher risk of malignant transformation. Conclusion: HIF-1α is a promising biomarker for early diagnosis and assessment of malignant potential in OSF. Early detection and monitoring could improve clinical management and reduce OSCC risk, warranting further research for validation and therapeutic targeting.

Prior antibiotics, proton pump inhibitors, and probiotics in patients with extensive stage small cell lung cancer treated with immune checkpoint blockade: A post-hoc analysis of the phase I/III IMpower 133 trial.

The potential impact of concomitant medications such as systemic antibiotics, proton pump inhibitors (PPIs), and probiotics in patients with extensive-stage small cell lung cancer (ES-SCLC) receiving first-line chemo-immunotherapy combinations remains unclear. We ran a post hoc analysis of the IMpower133 phase I/III trial, which randomized patients with ES-SCLC to receive carboplatin/etoposide with either atezolizumab or placebo for 4 cycles, followed by maintenance therapy. We included any systemic antibiotic/probiotic exposure within 42 days prior to treatment initiation and any PPIs treatment within 30 days prior to treatment initiation. We explored the potential prognostic impact of antibiotics, PPIs and probiotics across the atezolizumab/chemotherapy and placebo/chemotherapy arms including the multivariable interaction term between the treatment modality and antibiotics/PPIs/probiotics. The analysis included 198 patients in the atezolizumab/chemotherapy arm and 195 in the placebo/chemotherapy arm. Baseline clinic-pathologic features were well balanced between the two cohorts, with 17 (8.6%) and 14 (7.2%) patients on antibiotics, 43 (21.7%) and 55 (28.2%) on PPIs, and 3 (1.5%) and 5 (2.6%) on probiotics among the atezolizumab/chemotherapy and placebo/chemotherapy cohorts, respectively. Exposure to antibiotics, PPIs, or probiotics was not associated with overall survival or progression free survival in either cohort. Furthermore, interaction terms between these medications and treatment modalities were not statistically significant. Baseline use of antibiotics, PPIs or probiotics did not influence clinical outcomes in patients with ES-SCLC treated with first-line atezolizumab/placebo plus chemotherapy, suggesting that they may not have a notable impact on clinical outcomes and could be considered for use in this patient population when necessary.

Biological and clinical characteristics of non-small cell lung cancer non-specific subtype

BackgroundNon-small cell lung cancer-not otherwise specified (NSCLC-NOS) is a rare subtype of NSCLC that cannot be classified specifically based on morphology and/or special staining. This study aimed to explore the clinical features, biological and pathological characteristics, treatment, and prognosis of NSCLC-NOS. MethodsThis retrospective study included NSCLC-NOS patients diagnosed and treated between 2010 and 2022. Clinical features, gene expression, first-line treatment, and prognosis were analyzed. Kaplan-Meier methods were calculated and log-rank tests and univariable and multivariable Cox regression analyses were performed to determine the relationship between prognostic factors and survival. ResultsOf 105 NSCLC-NOS patients, most were male (92.4%), smokers (78.1%), with a median age of 64 years, and advanced stage (IIIc-IV, 72.4%). Immunohistochemical analysis showed minimal expression of p40, NapsinA, and TTF-1, whereas cytokeratin (CK) was expressed in 100% of cases. 20.5% of 39 patients who underwent genetic testing had driver gene mutations, including EGFR, KRAS, and ROS1. Among 69 patients with complete treatment information, 58 received platinum-based chemotherapy, with paclitaxel being the most commonly used combination chemotherapy drug (n=25), followed by pemetrexed (n=21). The objective response rate (ORR) of paclitaxel was found to be higher compared to pemetrexed (83.3% vs. 54.5%, P=0.296). Furthermore, the combination of paclitaxel with immunotherapy demonstrated superior benefits in comparison to pemetrexed (76.9% vs. 50.0%, P=0.367). The median progression-free survival (PFS) for patients treated with monotherapy paclitaxel, the paclitaxel-immunotherapy combination, and the pemetrexed-immunotherapy combination were 6.6 months (95% CI: 1.508-11.692; P=0.017), 15.7 months (95% CI: 14.071-17.329; P=0.017), and 11.8 months (95% CI: 10.279-13.321; P=0.324), respectively. The median overall survival (OS) was 13.6 months. Anatomic location (P=0.026) and immunotherapy use (P=0.003) were associated with OS. Multivariate analysis confirmed that anatomical location and immunotherapy use were factors influencing the prognosis. ConclusionNSCLC-NOS is common in male smokers and often diagnosed at an advanced stage with low mutation rate. Paclitaxel with immunotherapy may have better benefits as a first-line treatment. Anatomic location and immunotherapy use are prognostic factors.

Occult endometrial cancer in atypical endometrial hyperplasia: Assessment of clinical-pathologic characteristics and oncologic outcomes

Occult endometrial cancer in atypical endometrial hyperplasia: Assessment of clinical-pathologic characteristics and oncologic outcomes

Clinicopathological Features of Membranous Nephropathy Complicated by IgA Nephropathy: A Retrospective Analysis of Seven Cases.

Aims/Background Both membranous nephropathy (MN) and immunoglobulin A nephropathy (IgAN) are immune complex-mediated glomerular diseases, but the concurrent occurrence of these two conditions in the same patient is not common, a phenomenon that is currently not supported by clinical data in terms of treatment and prognosis. This study explores the clinical and pathological characteristics, as well as the treatment outcomes, of patients affected by MN and IgAN simultaneously. Methods The clinical data, pathological features, and diagnostic and therapeutic information of seven cases of MN complicated by IgAN, treated between December 2015 and December 2022, were retrospectively analyzed. Results Among the seven cases, there were two male and five female patients, with an average age of 57.3 ± 9.2 years. All patients presented with clinical manifestations of proteinuria and edema upon admission, with an average 24-hour urine protein of 3716.6 ± 1519.4 mg/24 h. Phospholipase A2 receptor (PLA2R) expression was detected in all seven cases, and nephrotic syndrome was clinically diagnosed in five cases. Additionally, all seven cases showed microscopic hematuria, with intermittent gross hematuria in two cases. All seven patients included in this study underwent renal biopsy. After disease staging, the patients had MN stages I-III and IgAN stages II-III. Pathological findings revealed abnormal glomerular basement membrane (GBM) and diffuse immunoglobulin G (IgG) deposition in the subepithelial space, predominantly of the IgG4 subtype. Simultaneously, there was diffuse mesangial zone deposition of immunoglobulin A (IgA) to varying degrees, co-localization of complement component C3 and IgA, and mesangial cell proliferation. Treatment strategies included angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in combination with steroids or immunosuppressive therapies such as tacrolimus, cyclophosphamide, and rituximab. After 2-6 months of treatment, all patients achieved complete remission with a favourable prognosis. Conclusion MN accompanied by IgAN tends to occur more frequently in middle-aged and elderly individuals, with a relatively low incidence. The latent feature of the comorbidities manifests as a form of IgAN superimposed on the background of MN. Utilizing ACEI or ARB in combination with steroids or various immunosuppressive therapies represents a potentially effective treatment strategy.

Fibrinogen to pre-albumin ratio is an independent prognostic index for patients with pancreatic ductal adenocarcinoma after radical resection

BackgroundThis study aims to elucidate the significance of the preoperative fibrinogen to pre-albumin ratio (FPR) in predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC), a correlation not extensively explored previously.MethodsA cohort of 563 patients diagnosed with PDAC and subjected to radical surgical resection was examined. We meticulously documented a range of inflammatory markers, clinical-pathological features, and oncological outcomes. The prognostic value of preoperative FPR was assessed using Kaplan–Meier survival analysis and Cox proportional hazards regression modeling. Furthermore, the predictive accuracy of FPR was evaluated through time-dependent receiver operating characteristic (ROC) curves and decision curve analyses (DCA).ResultsThe determined optimal threshold for FPR was 14.77, which facilitated the stratification of patients into groups with low and high FPR levels. Notably, patients in the high FPR cohort exhibited significantly reduced recurrence-free survival (RFS) and overall survival (OS) rates compared to their low FPR counterparts. Multivariate Cox regression analysis underscored FPR as an independent prognostic indicator for both RFS and OS. In comparison to the neutrophil-to-lymphocyte ratio (NLR), FPR demonstrated superior prognostic accuracy and clinical utility.ConclusionThe preoperative fibrinogen to pre-albumin ratio serves as an independent prognostic marker for RFS and OS among PDAC patients undergoing radical resection. Our findings suggest that FPR could be a valuable addition to the current prognostic models, potentially guiding therapeutic decision-making and patient management strategies in PDAC.

Metastatic Melanoma to the Small Bowel and Colon: A Systematic Review of the Global Experience and Institutional Cohort Analysis Detailing a Rare Clinical Entity.

Cutaneous melanoma is among the most common solid tumors to metastasize to the gastrointestinal (GI) tract. Literature summarizing the clinical experience and features of this unique pathology is lacking. A systematic review of the available literature reporting clinically salient features of melanoma metastases to the small and large intestines was conducted. Additionally, we surveyed our institutional experience of surgically treated melanoma metastasis to the small bowel and colon. A descriptive analysis was performed. Kaplan-Meier curves with log-rank tests were used to analyze time-to-event intervals. Univariable and multivariable Cox logistic regression models were generated to identify predictors of survival. Over 100 studies including 1153 patients were included. GI metastases predominantly affected males, were in the small bowel/jejunum, equally presented as solitary and multiple lesions, and were generally not the first site of distant metastatic disease. The median time from primary lesion diagnosis to GI metastasis was 48 months. Analysis of our institutional cohort suggested that survival in patients receiving complete GI-specific surgical resection and immune checkpoint inhibitors (ICIs) was prolonged compared to palliative resection and without ICI therapy. Positive prognostic factors for survival following GI metastasis included fewer GI metastatic lesions, complete resection, and longer duration between primary tumor diagnosis and GI metastasis. GI metastases are a sign of advanced metastatic melanoma. Clinical suspicion of metastatic involvement in patients with a history of melanoma who develop any abdominal symptoms or anemia should remain high. Receipt of complete surgical resection and ICIs may prolong survival in disseminated melanoma.

Disulfidptosis-related subtype and prognostic signature in prostate cancer

BackgroundDisulfidptosis refers to cell death caused by the accumulation and bonding of disulfide in the cytoskeleton protein of SLC7A11-high level cells under glucose deprivation. However, the role of disulfidptosis-related genes (DRGs) in prostate cancer (PCa) classification and regulation of the tumor microenvironment remains unclear.MethodsFirstly, we analyzed the expression and mutation landscape of DRGs in PCa. We observed the expression levels of SLC7A11 in PCa cells through in vitro experiments and assessed the inhibitory effect of the glucose transporter inhibitor BAY-876 on SLC7A11-high cells using CCK-8 assay. Subsequently, we performed unsupervised clustering of the PCa population and analyzed the differentially expressed genes (DEGs) between clusters. Using machine learning techniques to select a minimal gene set and developed disulfidoptosis-related risk signatures for PCa. We analyzed the tumor immune microenvironment and the sensitivity to immunotherapy in different risk groups. Finally, we validated the accuracy of the prognostic signatures genes using single-cell sequencing, qPCR, and western blot.ResultsAlthough SLC7A11 can increase the migration ability of tumor cells, BAY-876 effectively suppressed the viability of prostate cancer cells, particularly those with high SLC7A11 expression. Based on the DRGs, PCa patients were categorized into two clusters (A and B). The risk label, consisting of a minimal gene set derived from DEGs, included four genes. The expression levels of these genes in PCa were initially validated through in vitro experiments, and the accuracy of the risk label was confirmed in an external dataset. Cluster-B exhibited higher expression levels of DRG, representing lower risk, better prognosis, higher immune cell infiltration, and greater sensitivity to immune checkpoint blockade, whereas Cluster A showed the opposite results. These findings suggest that DRGs may serve as targets for PCa classification and treatment. Additionally, we constructed a nomogram that incorporates DRGs and clinical pathological features, providing clinicians with a quantitative method to assess the prognosis of PCa patients.ConclusionThis study analyzed the potential connection between disulfidptosis and PCa, and established a prognostic model related to disulfidptosis, which holds promise as a valuable tool for the management and treatment of PCa patients.

MiR-559 rs58450758 polymorphism is associated with colorectal cancer risk and prognosis in Chinese Han population.

Aim: This research examined the correlation between miR-559 rs58450758 and the clinical pathological characteristics and prognosis of CRC.Materials & methods: RT-qPCR was utilized to assess the miR-559 expression levels. Chi-square test was used to investigate the relationship between miR-559 and clinical features. The association between rs58450758 different genotypes and CRC risk, as well as clinical pathological parameters, was explored, utilizing logistic regression analysis and chi-square tests. The Cox regression model and Kaplan-Meier analysis evaluated overall survival in individuals with CRC.Results: The miR-559 was down-regulated in CRC patients' serum. The expressions of miR-559 were significantly associated with tumor size, differentiation, TNM stage and lymph node metastasis. The rs58450758 TT genotype and T allele carriers were more prevalent among CRC patients. The rs58450758 polymorphism was notably linked to tumor size, differentiation, TNM stage and lymph node metastasis in CRC patients. Furthermore, CC genotype carriers exhibited a longer survival period than CT/TT genotypes within the CRC population.Conclusion: The miR-559 rs58450758 polymorphism exhibits promise as a potential biomarker for prognosticating the outcomes of CRC.

Clinical characteristics of ABCB4 gene variant-associated cholestatic liver disease in adults

Objective: To investigate the clinical manifestations, pathological, and gene mutation characteristics of ABCB4 gene variant-associated cholestatic liver disease in adults. Methods: Eight adult cases of ABCB4 gene variant-associated cholestatic liver disease who were hospitalized in the Department of Hepatology, Fifth Medical Center of the People's Liberation Army General Hospital from May 2010 to December 2022 were enrolled in this study. The clinical manifestations, pathological features, gene variant features, and prognostic conditions were analyzed. Patient gene testing and biological information analysis were performed using whole-exome next-generation sequencing. SPSS 19.0 software was used to conduct descriptive analysis. Results: Among the eight adult cases of the ABCB4 gene variant, there were three males and five females, with a median age of onset of 24 (20, 37) years. There were three cases with a compound heterozygous variant in ABCB4, and the clinical phenotypes included two cases of progressive familial intrahepatic cholestasis type 3 and one case of intrahepatic cholestasis of pregnancy overlapping with low-phospholipid-associated cholelithiasis syndrome. There were five cases with a single heterozygous variant in ABCB4, and the clinical phenotypes included two cases of intrahepatic cholestasis of pregnancy overlapping with drug-induced liver injury and three cases of low-phospholipid-associated cholelithiasis syndrome. Imaging of all eight cases showed liver fibrosis, and six cases already had cirrhosis. All patients underwent liver histopathological examination, which mainly showed cholestasis and portal fibrosis in eight cases, small bile duct hyperplasia in seven cases, copper deposition in three cases, and cirrhosis in five cases. ABCB4 screening revealed 11 different mutations, including eight new mutations. The pathogenicity assessment showed that c.2394+82C>T (intron) was a benign mutation, and the rest were deleterious mutations. Ursodeoxycholic acid was the treatment for all patients, with a follow-up time of 7.5 (0.5, 12.7) years. One case died of end-stage liver disease, two cases developed cholestatic cirrhosis, and five cases were in stable condition. Conclusion: The adult ABCB4 gene variant-associated cholestatic liver disease are mostly single heterozygous mutations, the clinical phenotypes are diverse and overlapping, the disease is more severe in those who carried non-functional mutations.

Early Onset Pancreatic Adenocarcinoma (EOPAC): presentation, clinical course and treatment outcomes in comparison to Average Onset Pancreatic Adenocarcinoma (AOPAC): a retrospective cohort study

BackgroundPancreatic adenocarcinoma (PAC) is a disease of decimal prognosis, with around 50% of patients presenting with metastatic disease. Previous trials reported a high incidence of early onset pancreatic cancer (EOPAC) in Egypt, presenting about 25% of patients with PAC. The clinic-pathological features and prognosis of EOPAC needs more study.Patients and methodsA retrospective analysis of patients’ records at Shefa Al-Orman comprehensive cancer center database. Patients with histo-pathologically confirmed diagnosis of PAC. We categorized patients according to the age at diagnosis into EOPAC (≤ 50 years) and average onset PAC (AOPAC). Data on risk factors, family history, presenting symptoms, clinic-pathological features, treatment, and prognosis were extracted. Patients with histopathologically confirmed diagnosis of pancreatic cancer diagnosed between December 2016-December 2022 were included.ResultsThe study cohort consisted of 412 patients. EOPAC represented 20.3% of patients, with no significant differences in risk factors and family history compared to AOPAC. Duration of symptoms before diagnosis is longer in EOPAC, with the majority of EOPAC presenting with localized disease (23.8%) and locally advanced tumors (28.5%) compared to AOPAC. AOPAC presented more with metastatic disease (64% vs. 45.2%, p = 0.003). EOPAC are usually submitted to more aggressive treatment including radical surgery, neoadjuvant therapy, and aggressive chemotherapy regimens in metastatic disease. Disease free survival (DFS) of EOPAC was shorter than AOPAC (11 months vs. 17 months, p = 0.889), but overall survival OS was significantly longer in EOPAC (10 months vs. 6 months, p = 0.013).ConclusionPatients with EOPAC in Egypt represent around 25% of cases. EOPAC tend to have a shorter disease free survival (DFS) in patients presenting with localized disease. The overall survival (OS) is longer in EOPAC compared to AOPAC. Further studies are mandatory to identify the epidemiological and risk factors of EOPAC in Egypt.

Single-Stage Image-Guided Percutaneous Ablation with Thoracoscopic Resection for Multiple Pulmonary Lesions in a Hybrid Operating Room: A Retrospective Study.

Different approaches are required in treating patients with multiple pulmonary lesions. A multistage procedure may increase the risk of complications and patient discomfort. This study reports an initial experience with single-stage management of multiple lung lesions using percutaneous ablation with thoracoscopic resection in a hybrid operating room (HOR). We retrospectively evaluated patients who underwent combined ablation and resection in an HOR between May 2022 and July 2024. All patients received a single anesthesia via endotracheal tube intubation. The clinical data, operative findings, and pathological characteristics of the lung nodules were recorded. A total of 22 patients were enrolled in this study. Twenty patients underwent unilateral procedures, while the other two patients underwent bilateral procedures. Ablations were performed before lung resection in 21 patients; only 1 patient underwent surgery first. The median global operating room time was 227.0 min. The median total radiation dose (dose area product) was 14,076 μGym2. The median hospital postoperative length of stay was 2 days. The single-stage procedure of percutaneous ablation with thoracoscopic resection under general anesthesia in an HOR is feasible and safe. This procedure is an alternative method for managing multiple pulmonary lesions.

Discordance of human epidermal growth factor receptor 2-low status between breast primary and distant metastases with clinical-pathological correlation.

Breast cancer with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 1+ or 2+ with negative in-situ hybridisation (ISH) (HER2-low) can now be targeted by HER2 antibody drug conjugates. We set out to compare HER2 status between matched primary invasive breast carcinoma (IBC) and distant metastases (DM) with clinical-pathological correlation, with specific interest in HER2-low. Biomarker studies and clinical-pathological features of primary IBC with matched DM diagnosed between 2021 and 2022 were retrospectively analysed. HER2 status was assessed per 2023 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines for IHC (4B5) and ISH (IQFISH pharmDX). Bilateral breast primaries were excluded. HER2 IHC 0 to 1+ were reassessed. One hundred and forty-seven cases of primary IBC with matched DM were identified. Biomarkers were performed on core biopsy (n = 74) and resection (n = 73). One hundred and twenty-six (86%) were initially classified as 'HER2-negative'; of these, 67 (46%) were reclassified as HER2-low. Patients with HER2-positive primaries were younger (P = 0.01) and had an increased incidence of micropapillary carcinoma (P = 0.02). HER2-low primaries also had an increased incidence of micropapillary carcinoma (P = 0.02) and oestrogen receptor (ER) positivity (P = 0.02) compared to HER2 0. One hundred and sixty-nine matched DM cases excluding bone metastasis were identified (range = one to seven metastases per IBC). The most common sites of metastases were liver (50 of 169, 30%), lung (36 of 169; 21%), distant lymph node (26 of 169, 15%); 138 DM cases (82%) were previously classified as 'HER2-negative', and 62 (37%) were reclassified as HER2-low. Like HER2-low primaries, HER2-low metastases were frequently ER-positive (52 of 62; 84%) (P = 0.02). Brain metastases were more frequently HER2-positive (five of 32; 16%) (P = 0.04). Comparing HER2 status in matched primaries and DM, HER2 status was discordant in 62 cases (37%). Most changes occurred from HER2-low to HER2 0 (33 of 169, 20%), HER2 0 to HER2-low (17 of 169, 10%) and HER2-low to positive (10 of 169, 6%). All HER2-low to HER2 0 changes were HER2 1+ to 0. In 30 patients with multiple DM sites (47 cases), HER2 status among different DM samples was discordant in 16 patients (53%), mainly from HER2-low to HER2 0 (16 of 47, 34%). A significant proportion of previous 'HER2-negative' primaries and DM cases were reclassified as HER2-low. Discordant HER2 status between IBC primary and metastasis and between different DM sites demonstrated tumour heterogeneity and highlights the need for HER2 retesting in distant metastasis.

Clinicopathological analysis of small intestinal metastasis from extra-abdominal/extra-pelvic malignancy.

The metastatic tumors in the small intestine secondary to extra-abdominal/extra-pelvic malignancy are extremely rare. However, the small intestine metastases are extremely prone to misdiagnosis and missed diagnosis due to the lack of specific clinical manifestations and examination methods, thus delaying its treatment. Therefore, in order to improve clinical diagnosis and treatment capabilities, it is necessary to summarize its clinical pathological characteristics and prognosis. To summarize the clinicopathological characteristics of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy, and to improve the clinical capability of diagnosis and treatment for rare metastatic tumors in the small intestine. The clinical data of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy were retrieved and summarized, who admitted to and treated in the Air Force Medical Center, Chinese People's Liberation Army. Then descriptive statistics were performed on the general conditions, primary tumors, secondary tumors in the small intestine, diagnosis and treatment processes, and prognosis. Totally 11 patients (9 males and 2 females) were enrolled in this study, including 8 cases (72.3%) of primary lung cancer, 1 case (9.1%) of malignant lymphoma of the thyroid, 1 case (9.1%) of cutaneous malignant melanoma, and 1 case (9.1%) of testicular cancer. The median age at the diagnosis of primary tumors was 57.9 years old, the median age at the diagnosis of metastatic tumors in the small intestine was 58.81 years old, and the average duration from initial diagnosis of primary tumors to definite diagnosis of small intestinal metastases was 9 months (0-36 months). Moreover, small intestinal metastases was identified at the diagnosis of primary tumors in 4 cases. The small intestinal metastases were distributed in the jejunum and ileum, with such clinical manifestations as hematochezia (5, 45.4%) and abdominal pain, vomiting and other obstruction (4, 36.4%). In addition, 2 patients had no obvious symptoms at the diagnosis of small intestinal metastases, and 5 patients underwent radical resection of small intestinal malignancies and recovered well after surgery. A total of 3 patients did not receive subsequent treatment due to advanced conditions. Small intestinal metastases of extra-abdominal/extra-pelvic malignancy is rare with high malignancy and great difficulty in diagnosis and treatment. Clinically, patients with extra-abdominal/extra-pelvic malignancy should be alert to the occurrence of this disease, and their prognosis may be improved through active surgery combined with standard targeted therapy.