Advanced Stage Research Articles

Intratumoral microbiota: an emerging force in diagnosing and treating hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) ranks among the most prevalent types of cancer in the world and its incidence and mortality are increasing year by year, frequently diagnosed at an advanced stage. Traditional treatments such as surgery, chemotherapy, and radiotherapy have limited efficacy, so new diagnostic and treatment strategies are urgently needed. Recent research has discovered that intratumoral microbiota significantly influences the development, progression, and metastasis of HCC by modulating inflammation, immune responses, and cellular signaling pathways. Intratumoral microbiota contributes to the pathologic process of HCC by influencing the tumor microenvironment and altering the function of immune system. This article reviews the mechanism of intratumoral microbiota in HCC and anticipates the future possibilities of intratumoral microbiota-based therapeutic strategies for HCC management. This emerging field provides fresh insights into early diagnosis and personalized approaches for HCC while holding substantial clinical application potential to improve patient outcomes and tailor interventions to individual tumor profiles.

Epidemiological profile and clinical characteristics of ocular and periocular tumors in North and Central India.

To describe the epidemiological profile and clinical characteristics of ocular and periocular tumors in patients presenting to three tertiary care referral centers in North and Central India. Hospital-based consortium study. Retrospective, descriptive, observational study. A total of 3184 patients were diagnosed with 3557 ocular and periocular tumors over 11 years from 2010 to 2021. Of these, 2395 (67.33%) were benign, 84 (2.36%) were premalignant, and 1078 (30.30%) were malignant. The most common location was the ocular surface (n = 1294, 37.09%), followed by the eyelid (n = 1185, 33.97%), intraocular (n = 624, 17.88%), and orbit (n = 454, 13.01%). The most common tumors were retinoblastoma (n = 483, 13.57%), ocular surface squamous neoplasia (OSSN) (n = 301, 8.46%), and dermoid cyst (n = 167, 4.69%). In the pediatric age group, retinoblastoma was the most common tumor (n = 483, 13.57%), while in adults, it was OSSN (n = 301, 8.46%). The stage at presentation for malignant tumors was divided into in-situ (57.14%), local spread (8.16%), and metastasis (32.83%). For specific tumor locations, the stages were 78.83%, 17.51%, and 2.18%, respectively, for eyelid tumors; 51.76%, 27.05%, and 17.64%, respectively, for orbital tumors; 88.37%, 5.81%, and 5.19%, respectively for ocular surface tumors; and 35.71%, 14.15%, and 50.28%, respectively, for intraocular tumors. Identifying the epidemiological characteristics of ocular and periocular tumors will aid in early diagnosis and timely intervention. Intraocular tumors showed delayed diagnosis, advanced stages at presentation, and required patients to travel longer distances for treatment, indicating the need for strengthened diagnostic and treatment facilities to improve access to care.

RNF2 promotes chondrosarcoma progression by regulating ubiquitination and degradation of CBX7

ObjectiveChondrosarcoma (CHS) is resistant to conventional chemotherapy and radiotherapy and currently lacks effective treatment options when in advanced stages. Accordingly, this research investigated the mechanism of RNF2/CBX7 in CHS to drive the development of molecularly targeted drugs for CHS.MethodsRNF2 and CBX7 levels were detected in CHS cells and tissues. RNF2 and CBX7 expression was modulated through cell transfection to examine their effects on cell proliferation, apoptosis, migration, and angiogenesis. The correlation between RNF2 and CBX7 levels was determined, and the ubiquitination level of CBX7 was tested. Protein synthesis was blocked in RNF2-knockdown/overexpressing cells with CHX to assess the effect of RNF2 on CBX7 stability. JJ012 cells transfected with LV-sh-RNF2 were subcutaneously injected into nu/nu nude mice to ascertain the action of RNF2 in the growth and metastasis of CHS.ResultsRNF2 was highly expressed in CHS cells and tissues. RNF2 knockdown curbed CHS cell proliferation, migration, and angiogenesis while promoting apoptosis. RNF2 knockdown in JJ012 cells upregulated CBX7 protein levels and reduced CBX7 ubiquitination, whilst RNF2 had no effect on CBX7 mRNA expression. CBX7 knockdown partially nullified the repressing effects of RNF2 knockdown on CHS cell proliferation, migration, and angiogenesis, and CBX7 overexpression partially abolished the promotional effects of RNF2 overexpression. LV-sh-RNF2 prominently restricted tumor growth and weight and declined lung metastatic nodules and Ki-67-positive cells in mice.ConclusionRNF2 fosters CHS progression by elevating CBX7 degradation via the ubiquitination pathway.

Exploring the complexity, treatment challenges, and outcomes in pediatric nodular lymphocyte predominant Hodgkin lymphoma: a perspective from a low–middle-income country

BackgroundIn children, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma. Given the lack of data on the best chemotherapy regimen, there is a knowledge gap in best management.MethodsThis retrospective study included all pediatric patients with NLPHL diagnosed and treated at the Children’s Cancer Hospital, Egypt (2007–2018). We analyzed the clinical characteristics, and treatment outcome according to disease stage (early and advanced), treatment strategy (doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD] or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] and explored the prognostic factors for progression-free survival.ResultsThe median age at diagnosis was 12 years; 40 (68%) patients had early-stage disease, and 19 (32%) had advanced-stage disease. The median follow-up was 70 months; the 5-year EFS and OS were 75% and 97%, respectively. The 5-year EFS was 78% for early-stage disease and 60% for advanced-stage disease; the 5-year OS was 100% for early-stage disease and 88% for advanced-stage disease. The patients who underwent R-CHOP had a better 3-year EFS (100%) compared with those who underwent ABVD (65%) regimen (P = 0.01). Seventeen (25%) patients relapsed: 9/40 (22%) had early-stage disease, and 8/19 (42%) had advanced-stage disease. Splenic involvement, mediastinal disease, extranodal disease, and slow early response were independent predictors of relapse risk.ConclusionPediatric patients with early-stage NLPHL have an excellent prognosis, with a 5-year OS of 100%. However, those with advanced stages had a high relapse rate. R-CHOP was associated with a better response and relapse-free rate than ABVD.

Cholangiocarcinoma: A Comprehensive Review and Update Guideline

Cholangiocarcinoma is a rare cancer of the gastrointestinal system. However, the prognosis for people with this disease has not improved in the last decade. CCA has a poor prognosis because most cases are diagnosed at an advanced stage and the availability of treatment options is limited. This literature review aims to provide information regarding the current understanding and guidelines for cholangiocarcinoma. In this literature review, we searched the National Center for Biotechnology Information (NCBI) and Google Scholar using the search keywords "Cholangiocarcinoma", "cholangiocarcinoma management", "cholangiocarcinoma guidelines" taken ScienceDirect, Researchgate, National Comprehensive Cancer Network, and PubMed published in the last 10 years. From various databases, the literature used and according to the selection criteria amounted to 50 articles In the latest articles and the Cancers NCCN Guidelines for Biliary Tract Cancer in 2023, CCA treatment is carried out based on the patient's profile. Targeted therapy is an additional treatment option today by targeting the molecular profile involved in the pathogenesis of CCA. The diagnosis of cholangiocarcinoma is made through histology, radiography, and laboratory examination. Based on the Cancers NCCN Guidelines for Biliary Tract Cancer in 2023, the treatment carried out consists of determining cancer staging, surgery, radiation therapy, and systemic therapy.

Decitabine Enhances Sorafenib Sensitivity in Renal Cell Carcinoma by Promoting BIN1 and SYNE1 Expressions.

Renal cell carcinoma (RCC), especially clear cell RCC (ccRCC), significantly impacts health, and results in particularly poor outcomes in patients at the advanced stage. Resistance to vascular endothelial growth factor (VEGF) pathway-targeting tyrosine kinase inhibitors (TKIs) is a major barrier in effective ccRCC treatment. Herein, we aim to explore how decitabine mediates bridging integrator 1 (BIN1) and spectrin repeat containing nuclear envelope protein 1 (SYNE1) to impact resistance of ccRCC to sorafenib. Employing bioinformatics on datasets GSE64052 and CancerSea, we identified genes linked to TKI resistance, ultimately focusing on SYNE1. We assessed influences of SYNE1 overexpression and BIN1 knockdown via quantitative real-time PCR (qRT-PCR) and Western blot. Assessment of cell viability and apoptosis was accomplished using cell counting kit-8 (CCK-8) assays and flow cytometry. The investigation into the potential interactions between SYNE1 and BIN1, as well as their impacts on sorafenib sensitivity was accomplished by Co-Immunoprecipitation (Co-IP) and Glutathione-S-transferase (GST) Pull-down. SYNE1 was substantially down-regulated in sorafenib-resistant ccRCC cells, and its overexpression increased sorafenib sensitivity, decreased viability and enhanced apoptosis. Interaction between BIN1 and SYNE1 was confirmed, with BIN1 level lower in resistant cells. BIN1 knockdown reduced the beneficial effects of SYNE1 overexpression on sorafenib sensitivity. Decitabine treatment elevated both SYNE1 and BIN1, while boosting apoptosis and reducing sorafenib resistance. SYNE1 contributes to the modulation of sorafenib resistance in ccRCC cells through interacting with BIN1. Decitabine treatment enhances expressions of these two proteins to improve TKI response, suggesting a potential strategy for counteracting resistance and bettering patient outcomes.

“I Pink I Can” Breast Cancer Intervention Program: Its Effectiveness in Raising Knowledge among Junior High School Students of San Pablo City Integrated High School

As incidence rates rise from one in ten women to one in eight by 2023, breast cancer continues to be a serious worldwide health concern. Regardless of its rarity in men, this study included men in addition to women who frequently get breast cancer. Both sexes are affected by breast cancer, and its effects frequently get worse when discovered in advanced stages. This study highlights the importance of breast cancer education for people of all genders, in order to improve early detection and treatment outcomes. It aims to support the Sustainable Development Goal of "Good Health and Well-Being" by increasing Junior High Students' knowledge about breast cancer through an intervention program. Using a quasi- experimental design, 156 students' knowledge was assessed via a pre-test and post-test after exposure to leaflets, posters, and health teaching. A rigorously tested questionnaire focused on: breast cancer, signs and symptoms, risk factors, risk populations, and breast cancer screening showed that while students had basic knowledge initially, misconceptions were common. Post-intervention results demonstrated a significant increase in correct responses, indicating that the program effectively improved knowledge and corrected misconceptions. This underscores the value of targeted health education in promoting breast health and encouraging preventive measures.

Stemness in solid malignancies: coping with immune attack.

Immunotherapy has become a key new pillar of cancer treatment, and this has sparked interest in understanding mechanisms of cancer immune evasion. It has long been appreciated that cancers are constituted by heterogeneous populations of tumour cells. This feature is often fuelled by specialized cells that have molecular programs resembling tissue stem cells. Although these cancer stem cells (CSCs) have capacity for unlimited self-renewal and differentiation, it is increasingly evident that some CSCs are capable of achieving remarkable immune resistance. Given that most immunotherapy regiments have overlooked CSC-specific immune-evasive mechanisms, many current treatment strategies often lead to cancer relapse. This Review focuses on advancements in understanding how CSCs in solid tumours achieve their unique immune-evasive properties, enabling them to drive tumour regrowth. Moreover, as cancers often arise from tissue stem cells that acquired oncogenic mutations, we discuss how tissue stem cells undergoing malignant transformation activate intrinsic immune-evasive mechanisms and establish close interactions with suppressive immune cells to escape immune surveillance. In addition, we summarize how in advanced disease stages, CSCs often hijack features of normal stem cells to resist antitumour immunity. Finally, we provide insights in how to design a new generation of cancer immunotherapies to ensure elimination of CSCs.

Identification of lncRNA dual targeting PD-L1 and PD-L2 as a novel prognostic predictor for gastric cancer

BackgroundAlthough breakthroughs have been achieved in gastric cancer (GC) therapy with immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), the acquisition of high response rate remains a huge challenge for clinicians. It is imperative to identify novel biomarkers for predicting response to immunotherapy and explore alternative therapeutic strategy for GC.MethodsThe transcriptomic profiles and clinical information of GC patients from The Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD) database was used to screen differentially expressed lncRNAs between the tumor specimens and the paracancerous tissues. The TargetScan, miRDB and miRcode database were then utilized to construct competing endogenous RNA (ceRNA) networks and identify pivotal lncRNAs. An independent dataset from GEO (GSE70880) and 23 pairs of GC specimens of our cohort were subsequently performed for external validity. The relationship between clinical variables and gene expression were evaluated by Kruskal–wallis test and Wilcoxon signed-rank. The prognostic value of the candidate genes was assessed using Kaplan-Meier analysis and Cox regression models. CIBERSORT and Gene set enrichment analysis (GSEA) were used to determine immune cell infiltration. Gastric adenocarcinoma AGS cells and human embryonic kidney 293T (HEK293T) cells with knockdown of LINC01094 were generated by siRNA transfection, followed by detecting the alteration of the target miRNA and PD-L1/PD-L2 by RT-qPCR. Besides, the interaction between lncRNA and the miRNA–PD-L1/PD-L2 axis were verified by dual luciferase reporter assay.ResultsTwenty-two intersecting lncRNAs were identified to be PD-L1/PD-L2-related lncRNAs and LINC01094–miR-17-5p–PD-L1/PD-L2 was constructed as a potential ceRNA network. LINC01094 was increased in tumor specimens than adjacent normal samples and was positively associated with advanced tumor stages and EBV and MSI status. Furthermore, LINC01094 expression was an independent risk factor for poor overall survival (OS) in GC patients. CD8+ T cell exhaustion-related genes were enriched in high-LINC01094 tissues and high-PD-L2 group. A strong positive association of LINC01094 expression was established with M2 macrophages, IL-10+ TAM, as well as PD-L1 and PD-L2 levels, therefore a LINC01094–miR-17-5p–IL-10 network was proposed in macrophages. Using the exoRBase database, LINC01094 was assumed in blood exosomes of GC patients The results of knockdown experiments and luciferase reporter assays revealed that LINC01094 interacted with miR-17-5p and served as a miRNA sponge to regulate the expression of PD-L1 and PD-L2.ConclusionLINC01094 dually regulates the expression of PD-L1 and PD-L2 and shapes the immunosuppressive tumor microenvironment via sponging miR-17-5p. LINC01094 may serve as a potential prognostic predictor and therapeutic target in GC.

Proportion and characteristics of Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: A systematic review and meta-analysis.

While Helicobacter pylori (H. pylori) infection is common in patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, there are still individuals who test negative for it. The proportion and characteristics of these patients remain unclear. We conducted a systematic search of the PubMed, Embase, and Cochrane Library databases for relevant articles. Using a random effects model, we performed a meta-analysis to assess the pooled proportion of gastric MALT lymphoma patients with negative H. pylori tests. Additionally, we compared characteristics between gastric MALT lymphoma patients with and without H. pylori infection to examine clinical features in H. pylori-negative cases. A total of 50 studies involving 6033 patients were included. The overall proportion of gastric MALT lymphoma patients with negative H. pylori tests was 20.5% (95% confidence interval: 17.0%-24.6%). This rate exhibited an increasing trend over the years, particularly in non-Asian countries and in studies published after 2013, as well as in cases with sample sizes exceeding 100 participants, in male individuals, and among those with proximal or multiple lesions, non-superficial type morphology, submucosal invasion, and advanced clinical staging. Compared to H. pylori-positive patients, those who tested negative were more likely to be male, have proximal lesions, exhibit submucosal invasion, and present with an advanced clinical stage. This study provides comprehensive information on the proportion and characteristics of H. pylori-negative gastric MALT lymphoma cases, highlighting the need for future clinical attention to treatment and surveillance in this patient population.

Magnitude of anemia and associated factors among HIV infected children on antiretroviral therapy in Awi zone health facilities, Northwest Ethiopia, 2023

BackgroundAnemia is a common complication of HIV infected children and it is enabling HIV disease progression, and decreasing survival. In Ethiopia, there is limited evidence on the prevalence of anemia and its associated factors among HIV infected children particularly in the Awi Zone. Therefore, this study aimed to assess the magnitude and associated factors of anemia among HIV infected children on ART aged from 6 months to 15 year-old in ART Clinic, Awi-Zone, Ethiopia.ObjectiveTo assess the magnitude and associated factors of anemia among HIV infected children on antiretroviral therapy in Awi zone health facilities, Northwest, Ethiopia, 2022.MethodsA facility based cross-sectional study design was conducted from October to December 2022. A simple random sampling method was used to select the study participants. Descriptive statistics, including frequencies and proportions was used to summarize the study variables and data had been entered in to Epi data 4.2 and exported to SPSS version 25. Bivariable logistic regression followed by multivariable logistic regression was performed. Degree of association between dependent and independent variables had been assessed using adjusted odds ratio with 95% CI at p value of ≤ 0.05.ResultFrom 346 participants in the selected sample 339 (97.9%) of them responded. Prevalence of anemia was 13.3% (n = 45) among which, majority (44.4%) of them had mild anemia, while about (42.2%,) had moderate anemia and around 13.3%, of them were severely anemic. Baseline CD4 count (AOR = 6.58, 95% CI: 2.85–15.22), WHO clinical stage III or IV (AOR = 8.42, 95% CI = 3.47, 20.45), hookworm infection (AOR = 5.06, 95% CI = 2.04, 12) and malaria infection (AOR = 4.92, 95% CI (2.19–11.02) were significantly associated with anemia among children on HAART.ConclusionThe prevalence of anemia among participants was relatively low in this study. However, a considerable proportion of participants had moderate to severe anemia. Lower CD4 count at enrolment, advanced HIV clinical stage, malaria and hookworm infection were significantly linked with anemia. Thus, it requires regular monitoring of anemia status in these patients for better clinical outcomes and quality of life improvements.

Relative burden of cancer and noncancer mortality among long-term survivors of differentiated thyroid cancer in the US

BackgroundLimited information is available regarding the relative risks of cancer-specific mortality and noncancer-specific mortality among long-term survivors with differentiated thyroid cancer (DTC).MethodsIn this retrospective study, nationwide data from the Surveillance, Epidemiology, and End Results database (1992-2020) were utilized. The Accelerated Failure Time Model was applied to calculate Survival Time Ratios (TR), with the primary focus on mortality resulting from DTC. The competing risks model was employed to investigate the relative risks of various outcomes in DTC patients with a survival duration of 5 years or more.ResultsIn our cohort, 279 patients succumbed to DTC, while 748 died from other diseases. Notably, in DTC cohorts, noncancer-specific mortality rates were consistently higher than DTC-specific mortality rates across different age groups and genders. The risk of DTC and noncancer-specific mortality varied based on the TNM stage. With more advanced disease stages, the risk of DTC and other cancer-specific mortality gradually increased. The cumulative mortality from other cancer-specific causes was consistently the lowest.ConclusionsIn long-term surviving DTC patients, noncancer-specific mortality outweighed DTC-specific mortality irrespective of age and gender. For stage I and II patients, increased attention should be directed toward noncancer-specific mortality in postoperative follow-ups. Conversely, for stage III and IV patients, greater consideration should be given to DTC-related causes of death. In addition, for stage III and IV DTC patients, the risk of death from other cancers was significantly higher than for stages I and II.

The relationship between micronutrients and cognitive ability in an elderly population with mild cognitive impairment and Alzheimer’s disease: a cross-sectional study

BackgroundMild cognitive impairment (MCI) and Alzheimer’s disease (AD) are significant neurodegenerative disorders with increasing prevalence worldwide. Lifestyle and dietary factors, including micronutrients, have been suggested as modifiable risk factors for disease development. This study aims to investigate the association between micronutrients and cognitive ability in these diseases.MethodsA cross-sectional study involving 105 participants with MCI and AD was conducted. Dietary assessments were performed using a validated food frequency questionnaire (FFQ), and micronutrient intake was calculated based on nutrient content. Disease severity was evaluated using the Functional Assessment Staging Tool (FAST). Statistical analyses, including correlation coefficients and multiple regression models, were employed to examine the association between micronutrients and disease progression.ResultsThe results revealed significant correlations between disease severity and several micronutrients, including omega-3 fatty acids (B = -0.2, P = 0.01), carotenoids (B = -0.19, P = 0.02), dietary antioxidant compounds, including vitamins A, C, D, E (B = -0.19, P = 0.02), selenium (B = -0.17, P = 0.03), alpha-carotene (B = -0.16, P = 0.04), beta-carotene (B = -0.17, P = 0.03), and lycopene (B = -0.16, P = 0.04). Multivariate regression analysis showed that higher intake of omega-3 fatty acids was associated with slower disease progression. Furthermore, the levels of these micronutrients declined in advanced stages of the disease.ConclusionOmega-3 fatty acids and carotenoids may affect the cognitive ability and disease progression. Further longitudinal studies are warranted to establish causality and explore the therapeutic implications of these findings for the prevention and management of MCI and AD.

A Study on Lymph Node Distribution in the Main Lymph Node Area for Left-sided Colon Cancer.

In advanced left-sided colorectal cancer, cutting the root of the inferior mesenteric artery (IMA) branching from the aorta is recommended for complete lymph node dissection. However, this procedure sometimes causes severe complications. This study aimed to elucidate the lymph nodes' distribution around the IMA and identify the most critical sites for lymph node dissection. This study included 30 consecutive patients with left-sided colorectal cancer who underwent curative resection with main lymph node dissection in a single institution between January and June of 2022. The mesenteric sections (main lymph nodes, IMA, left colic artery [LCA], and inferior mesenteric vein) were removed from the surgically excised specimen. Subsequently, whole-tissue sections were prepared and stained with hematoxylin and eosin. The positional relationships between each blood vessel and respective lymph nodes were then assessed using the pathological findings. The main lymph nodes were identified in 26 out of 30 patients. The total number of dissected lymph nodes per patient was 0-30 (average: 5.3), and the median distance from the IMA to the main lymph node was 7.61 mm (1.87-43.26 mm). Dividing the lymph nodes into segments, we found 18%, 46%, and 36% of the lymph nodes in the proximal, middle, and distal segments, respectively. Additionally, all lymph nodes were found outside of the IMA sheath surrounding each arterial wall. In left-sided colorectal cancer, the main lymph nodes are mostly located around the LCA bifurcation, which may be essential to ensure main lymph node dissection for advanced stage cases.

Management and evaluation of osteoarthritis knee, stage III and IV by total knee arthroplasty in an institution at rural set-up: a cases series

The management of advanced knee osteoarthritis remains a subject of discussion. The use of total knee prosthesis is a solution to improve the quality of life’s patients. The end of this work was to describe the epidemiology and estimate the results of a series of 60 cases advanced knee osteoarthritis, treated with total knee prostheses in the department. This was a retrospective study conducted from August 2023 to June 2024 at Dr. PMR Institute of medical Sciences and Teaching Hospital, Chevella, Telangana. The study concerned the analysis of the patients operated on for advanced stage III and IV knee osteoarthritis by total knee prostheses. We collected 15 patients which includes 9-female and 6 male. The average age of the patients was 55 years. All patients were operated on under indigenous anesthesia in the supine position with a pneumatic tourniquet. The surgical site was approached antero-medially. The functional results evaluated according to the International Knee Society (IKS) score were favorable in 96.7%. In conclusion, knee osteoarthritis is a condition of elderly females. Its treatment, using total knee arthroplasty, evaluated according to the IKS score, gave satisfactory results.

Clinicopathological characteristics and outcomes of patients with unexplained renal impairment: a single center study

Background: Chronic kidney disease (CKD) is a growing health problem. About 20% of CKD patients have undetermined causes. Data describing histopathological patterns of unexplained impaired kidney functions in Egypt are lacking. We aimed to identify the clinicopathological characteristics and short-term outcomes of adult cases with unexplained impaired kidney functions.Methods: We conducted a prospective study in Assiut University Hospital from August 2018 to May 2022. It included patients with unexplained elevated serum creatinine (serum creatinine > 115 µmol/L) who underwent renal biopsies. Descriptive statistics were used to summarize data on patient demographics, histopathological patterns, and outcomes after three months. Clinical trial registration number: NCT03586531.Results: Overall, 210 native renal biopsies were included in the analysis. Glomerular diseases were the most common pathological finding (n=88, 44.9 %), amyloidosis and FSGS were the most prevalent glomerular pathology (15.2%, 14.3%, respectively). Chronic kidney disease of unknown etiology (CKDu) was diagnosed in 8.1% of the cases; histology suggestive of genetic origin was found in 2.5%, and LECT amyloidosis was found in 3.8% of the cases. Poor outcomes were observed in 43.6% of the patients i.e., renal replacement therapy or death. Treatment strategies were changed based on the biopsy findings in 86 patients (40%).Conclusion: Amyloidosis and FSGS were the most common causes of unexplained renal impairment. CKDu is not uncommon in Egypt, and more preventive measures are needed. This study supports the irreplaceable role of renal biopsy in disease diagnosis, treatment decisions, and predicting prognosis even in advanced stages.

Histone modifications and Sp1 promote GPR160 expression in bone cancer pain within rodent models.

Bone cancer pain (BCP) affects ~70% of patients in advanced stages, primarily due to bone metastasis, presenting a substantial therapeutic challenge. Here, we profile orphan G protein-coupled receptors in the dorsal root ganglia (DRG) following tumor infiltration, and observe a notable increase in GPR160 expression. Elevated Gpr160 mRNA and protein levels persist from postoperative day 6 for over 18 days in the affected DRG, predominantly in small-diameter C-fiber type neurons specific to the tibia. Targeted interventions, including DRG microinjection of siRNA or AAV delivery, mitigate mechanical allodynia, cold, and heat hyperalgesia induced by the tumor. Tumor infiltration increases DRG neuron excitability in wild-type mice, but not in Gpr160 gene knockout mice. Tumor infiltration results in reduced H3K27me3 and increased H3K27ac modifications, enhanced binding of the transcription activator Sp1 to the Gpr160 gene promoter region, and induction of GPR160 expression. Modulating histone-modifying enzymes effectively alleviated pain behavior. Our study delineates a novel mechanism wherein elevated Sp1 levels facilitate Gpr160 gene transcription in nociceptive DRG neurons during BCP in rodents.

PALB2 analysis in the diagnostic process of breast cancer: An Italian monocentric experience.

The clinical utility of germline BRCA1 and BRCA2 testing is well established in patients with family history suggestive for hereditary breast and ovarian cancer syndrome. Recently, germline PALB2 pathogenic variants were also associated with an increased risk of breast and other cancers and, in the Italian population, it has been described in few studies without a systematic germline analysis of BRCA1, BRCA2 and PALB2. In this study, we described ASST Sette Laghi cancer genetic counselling services' experience in the analysis of 402 patients with suspected breast and ovarian cancer syndrome, by using BRCA1, BRCA2 and PALB2 germline genetic test. The frequency of PALB2 pathogenic variants was 1.2% compared to 3.5% and 3.2% for BRCA1 and BRCA2, respectively, whereas class 3 variants were detected in 0.3% and 0.5% of the BRCA1 and BRCA2 investigated patients, respectively. PALB2 pathogenic variants were identified in patients with a strong family history for breast cancer. Moreover, PALB2 variants were significantly associated with a younger age of breast cancer onset (mean age, 40.25 years) compared to wild-type patients (mean age 51.2 years, p-value = 0.0331). Similar to BRCA-associated breast cancer, the majority of PALB2 breast cancers were identified at an advanced clinical stage. Pedigree analysis revealed a family history of breast and ovarian cancer syndrome in all PALB2 pathogenic variants carriers (early breast cancer onset, bilateral breast cancer and ovarian cancer). In conclusion, the germline analysis of BRCA1, BRCA2 and PALB2 should be included in breast cancer clinical practice as a not negligible number of PALB2 carriers could be identified and referred to specific surveillance protocols.

Downstaging Effect Rather than the Full Intended Cycles of Perioperative Chemotherapy Determines the Value of Adjuvant Chemotherapy in Gastric Cancer.

Perioperative chemotherapy is the standard treatment modality for locally advanced gastric cancer. However, the efficacy and indication of adjuvant chemotherapy in patients who have already received neoadjuvant chemotherapy remain unclear. This study aims to explore the association between adjuvant chemotherapy with patient prognosis in those who have received neoadjuvant chemotherapy plus D2 gastrectomy in a real-world setting, and whether this association is affected by the duration of neoadjuvant treatment. A total of 174 patients with cT3-4N+ gastric cancer who had received neoadjuvant chemotherapy plus D2 radical gastrectomy were included in the study. Kaplan-Meier curves and log-rank tests were used to assess and compare the survival outcomes between patients who received adjuvant therapy and those who did not. Patients who were younger age, had a lower American Society of Anesthesiologists (ASA) grade, did not experience postoperative complication, and received fewer than six cycles of neoadjuvant chemotherapy were more likely to receive adjuvant chemotherapy, rather than those with advanced ypTNM stage or poor tumor regression grade. Patients who received adjuvant therapy had a better overall survival (OS) (2-year OS rate 86.2% versus 64.1%, p=0.002). Adjuvant therapy was associated with longer survival in patients who remained ypTNM stage III despite receiving at least six cycles of neoadjuvant chemotherapy. However, there was no significant longer survival observed in patients with ypTNM stages 0-II receiving adjuvant chemotherapy, even when they received less than six cycles of neoadjuvant chemotherapy. Patients with locally advanced gastric cancer may still need adjuvant chemotherapy, even after receiving neoadjuvant chemotherapy. The value of adjuvant chemotherapy after neoadjuvant chemotherapy depends more on the actual downstaging effect achieved after neoadjuvant chemotherapy, rather than the completion of "full intended" cycles of perioperative treatment.

Gastric metastasis of small cell lung carcinoma: A rare but noteworthy entity to consider.

Small cell lung carcinoma (SCLC) is an aggressive malignancy known for its propensity for early and extensive metastatic spread. Gastric metastasis, where cancer cells disseminate from the lung to the stomach, is a rare but increasingly recognized complication of SCLC. This review provides a comprehensive overview of gastric metastasis in SCLC, addressing its clinical significance, diagnostic challenges, management strategies, and prognosis. Additionally, it examines the broader metastatic patterns of SCLC and compares them with other malignancies known for gastric metastasis. Gastric metastasis in SCLC, though infrequent, is clinically significant and often indicates advanced disease with a poor prognosis. SCLC typically metastasizes to the liver, brain, bones, and adrenal glands, with the stomach being an unusual site. The incidence of gastric metastasis ranges from 1% to 5% in autopsy studies, although this may be underestimated due to diagnostic difficulties and asymptomatic early lesions. Diagnosing gastric metastasis presents several challenges, including the asymptomatic nature of many cases, limitations of conventional imaging techniques, and difficulties in distinguishing metastatic lesions from primary gastric cancer via endoscopy. Histopathological diagnosis requires careful examination to identify SCLC cells through their characteristic small cell morphology and neuroendocrine markers. Management of gastric metastasis in SCLC typically involves a multidisciplinary approach. Systemic therapy, primarily chemotherapy, remains the cornerstone of treatment, with palliative care addressing symptoms and complications. Surgical intervention is usually reserved for specific cases requiring symptomatic relief. The prognosis for patients with gastric metastasis from SCLC is generally poor, reflecting the advanced stage of the disease. Median survival is significantly reduced compared to patients without gastric metastasis. This review emphasizes the need for enhanced awareness and early detection to improve patient outcomes and highlights the importance of ongoing research into better diagnostic and therapeutic strategies.