PSAT1 enhances the efficacy of the prognosis estimation nomogram model in stage-based clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is associated with a high prevalence of cancer-related deaths. The survival rates of patients are significantly lower in late-stage ccRCC than in early-stage ccRCC, due to the spread and metastasis of late-stage ccRCC, surgery has not reached the goal of radical cure, and the effect of traditional radiotherapy and chemotherapy is poor. Thus, it is crucial to accurately assess the prognosis and provide personalized treatment at an early stage in ccRCC. This study aims to develop an efficient nomogram model for stratifying and predicting the survival of ccRCC patients based on tumor stage. METHODS: We first analyzed the microarray expression data of ccRCC patients from the Gene Expression Omnibus (GEO) database and categorized them into two groups based on the disease stage (early and late stage). Subsequently, the GEO2R tool was applied to screen out the genes that were highly expressed in all GEO datasets. Finally, the clinicopathological data of the two patient groups were obtained from The Cancer Genome Atlas (TCGA) database, and the differences were compared between groups. Survival analysis was performed to evaluate the prognostic value of candidate genes (PSAT1, PRAME, and KDELR3) in ccRCC patients. Based on the screened gene PSAT1 and clinical parameters that were significantly associated with patient prognosis, we established a new nomogram model, which was further optimized to a single clinical variable-based model. The expression level of PSAT1 in ccRCC tissues was further verified by qRT-PCR, Western blotting, and immunohistochemical analysis. RESULTS: The datasets GSE73731, GSE89563, and GSE150404 identified a total of 22, 89, and 120 over-expressed differentially expressed genes (DEGs), respectively. Among these profiles, there were three genes that appeared in all three datasets based on different stage groups. The overall survival (OS) of late-stage patients was significantly shorter than that of early-stage patients. Among the three candidate genes (PSAT1, PRAME, and KDELR3), PSAT1 was shown to be associated with the OS of patients with late-stage ccRCC. Multivariate Cox regression analysis showed that age, tumor grade, neoadjuvant therapy, and PSAT1 level were significantly associated with patient prognosis. The concordance indices were 0.758 and 0.725 for the 3-year and 5-year OS, respectively. The new model demonstrated superior discrimination and calibration compared with the single clinical variable model. The enhancer PSAT1 used in the new model was shown to be significantly overexpressed in tissues from patients with late-stage ccRCC, as demonstrated by the mRNA level, protein level, and pathological evaluation. CONCLUSION: The new prognostic prediction nomogram model of PSAT1 and clinicopathological variables combined was thus established, which may provide a new direction for individualized treatment for different-stage ccRCC patients.

MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.

X-ray-guided self-expandable metal stent (SEMS) implantation in oesophageal malignancy as an alternative treatment.

<b><br>Indroduction:</b> Significant dysphagia, aspiration pneumonia, and impossible oral nutrition in patients with unresectable or recurrent gastroesophageal malignancy or bronchial cancer invading the oesophagus with a tracheoesophageal fistula lead to cachexia. Dehiscence of the esophago-jejunal or gastroesophageal anastomosis may cause severe oesophageal haemorrhage. We believe that X-ray-guided oesophageal stent implantation (SEMS) is an alternative palliative method for microjejunostomy or full parenteral nutrition.</br> <b><br>Aim:</b> The aim of this paper was to assess the safety and efficacy of a novel X-ray-guided oesophageal stent implantation technique.</br> <b><br>Materials and methods:</b> This retrospective analysis included 54 patients (35 men and 19 women) treated for malignant dysphagia, gastroesophageal/gastrointestinal anastomotic fistula or bronchoesophageal fistula in two Surgical Units between 2010 and 2019, using a modified intravascular approach to oesophageal stent implantation.</br> <b><br>Results:</b> The presented modified intravascular method of oesophageal stent implantation was successfully performed in all described patients requiring oral nutrition restoration immediately following oesophageal stent implantation. Two patients with oesophageal anastomotic dehiscence died on postoperative days 7 and 9 due to circulatory and respiratory failure. One patient was reimplanted due to a recurrent fistula. Two patients with ruptured thoracic aneurysm and thoracic stent graft implantation due to oesophageal haemorrhage, who were implanted with an oesophageal stent, died on postoperative days 4 and 14.</br> <b><br>Conclusions:</b> The modified intravascular X-ray-guided SEMS technique may be a palliative treatment for patients with unresectable oesophageal malignancies.</br>.

Lectin-Based Immunophenotyping and Whole Proteomic Profiling of CT-26 Colon Carcinoma Murine Model.

A murine colorectal carcinoma (CRC) model was established. CT26 colon carcinoma cells were injected into BALB/c mice's spleen to study the primary tumor and the mechanisms of cell spread of colon cancer to the liver. The CRC was verified by the immunohistochemistry of Pan Cytokeratin and Vimentin expression. Immunophenotyping of leukocytes isolated from CRC-bearing BALB/c mice or healthy controls, such as CD19+ B cells, CD11+ myeloid cells, and CD3+ T cells, was carried out using fluorochrome-labeled lectins. The binding of six lectins to white blood cells, such as galectin-1 (Gal1), siglec-1 (Sig1), Sambucus nigra lectin (SNA), Aleuria aurantia lectin (AAL), Phytolacca americana lectin (PWM), and galectin-3 (Gal3), was assayed. Flow cytometric analysis of the splenocytes revealed the increased binding of SNA, and AAL to CD3 + T cells and CD11b myeloid cells; and increased siglec-1 and AAL binding to CD19 B cells of the tumor-bearing mice. The whole proteomic analysis of the established CRC-bearing liver and spleen versus healthy tissues identified differentially expressed proteins, characteristic of the primary or secondary CRC tissues. KEGG Gene Ontology bioinformatic analysis delineated the established murine CRC characteristic protein interaction networks, biological pathways, and cellular processes involved in CRC. Galectin-1 and S100A4 were identified as upregulated proteins in the primary and secondary CT26 tumor tissues, and these were previously reported to contribute to the poor prognosis of CRC patients. Modelling the development of liver colonization of CRC by the injection of CT26 cells into the spleen may facilitate the understanding of carcinogenesis in human CRC and contribute to the development of novel therapeutic strategies.

Cellular senescence and metabolic reprogramming model based on bulk/single-cell RNA sequencing reveals PTGER4 as a therapeutic target for ccRCC.

Clear cell renal cell carcinoma (ccRCC) is the prevailing histological subtype of renal cell carcinoma and has unique metabolic reprogramming during its occurrence and development. Cell senescence is one of the newly identified tumor characteristics. However, there is a dearth of methodical and all-encompassing investigations regarding the correlation between the broad-ranging alterations in metabolic processes associated with aging and ccRCC. We utilized a range of analytical methodologies, such as protein‒protein interaction network analysis and least absolute shrinkage and selection operator (LASSO) regression analysis, to form and validate a risk score model known as the senescence-metabolism-related risk model (SeMRM). Our study demonstrated that SeMRM could more precisely predict the OS of ccRCC patients than the clinical prognostic markers in use. By utilizing two distinct datasets of ccRCC, ICGC-KIRC (the International Cancer Genome Consortium) and GSE29609, as well as a single-cell dataset (GSE156632) and real patient clinical information, and further confirmed the relationship between the senescence-metabolism-related risk score (SeMRS) and ccRCC patient progression. It is worth noting that patients who were classified into different subgroups based on the SeMRS exhibited notable variations in metabolic activity, immune microenvironment, immune cell type transformation, mutant landscape, and drug responsiveness. We also demonstrated that PTGER4, a key gene in SeMRM, regulated ccRCC cell proliferation, lipid levels and the cell cycle in vivo and in vitro. Together, the utilization of SeMRM has the potential to function as a dependable clinical characteristic to increase the accuracy of prognostic assessment for patients diagnosed with ccRCC, thereby facilitating the selection of suitable treatment strategies.

Multiple carcinomas in a woman with HIV infection: a case report and literature review.

Non-acquired immunodeficiency syndrome-defining cancers (NADCs) are malignancies in persons living with human immunodeficiency virus (PLWHIV) and are not primarily due to the host's immunodeficiency. There is renewed clinical interest in long-term morbidities in PLWHIV as well as malignancies that occur in this population. We herein describe a 36-year-old woman with a 2-year history of an anal wound and right breast mass. She had been diagnosed with HIV infection prior to the development of these lesions. Clinical and laboratory evaluations led to diagnoses of breast and anal cancers. Chemotherapy and antiretroviral therapy were begun, but the patient discontinued these treatments early and was lost to follow-up. NADCs will continue to be a major clinical issue as the global population ages. This presentation of two NADCs (breast and anal cancers) in a PLWHIV further highlights the burden of multiple malignancies on the depleted health of HIV-infected patients. Early identification and treatment of HIV upon patients' presentation to cancer care sites and screening for NADCs at HIV/AIDS care sites are recommended for improved outcomes.

Peritumor Mucosa in Advanced Laryngeal Carcinoma Exhibits an Aberrant Proangiogenic Signature Distinctive from the Expression Pattern in Adjacent Tumor Tissue.

The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the "classical" borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer-the process of tumor neoangiogenesis.

Dual-loss of PBRM1 and RAD51 identifies hyper-sensitive subset patients to immunotherapy in clear cell renal cell carcinoma.

BACKGROUND: Homologous recombination deficiency (HRD), though largely uncharacterized in clear cell renal cell carcinoma (ccRCC), was found associated with RAD51 loss of expression. PBRM1 is the second most common mutated genes in ccRCC. Here, we introduce a HRD function-based PBRM1-RAD51 ccRCC classification endowed with diverse immune checkpoint blockade (ICB) responses. METHODS: Totally 1542 patients from four independent cohorts were enrolled, including our localized Zhongshan hospital (ZSHS) cohort and Zhongshan hospital metastatic RCC (ZSHS-mRCC) cohort, The Cancer Genome Atlas (TCGA) cohort and CheckMate cohort. The genomic profile and immune microenvironment were depicted by genomic, transcriptome data and immunohistochemistry. RESULTS: We observed that PBRM1-loss ccRCC harbored enriched HRD-associated mutational signature 3 and loss of RAD51. Dual-loss of PBRM1 and RAD51 identified patients hyper-sensitive to immunotherapy. This dual-loss subtype was featured by M1 macrophage infiltration. Dual-loss was, albeit homologous recombination defective, with high chromosomal stability. CONCLUSIONS: PBRM1 and RAD51 dual-loss ccRCC indicates superior responses to immunotherapy. Dual-loss ccRCC harbors an immune-desert microenvironment but enriched with M1 macrophages. Dual-loss ccRCC is susceptible to defective homologous recombination but possesses high chromosomal stability.

Myoepithelial Carcinoma of Soft Tissue: Report of Two Cases.

CASE: A 40-year-old man was evaluated for a painful mass on his right calf, and a 36-year-old woman presented with a painless mass on her right foot. Final pathology revealed marked nuclear atypia and positivity for S100/SOX10 and AE1/AE3 confirming diagnoses of myoepithelial carcinoma. Both patients underwent surgical resection and are without evidence of local recurrence or metastatic disease at 1-year follow-up. CONCLUSION: Soft-tissue tumors presenting in the extremities warrant careful evaluation and timely histopathologic diagnosis. Myoepithelial carcinomas are rare, aggressive tumors with a propensity for local recurrence and metastasis. Treatment of these tumors should be discussed by a multidisciplinary tumor team.

Treatment Strategy for Breast Benign Intraductal Papilloma: A Meta-Analysis.

Currently, the optimal treatment approach for breast benign intraductal papilloma (IDP) diagnosed via biopsy remains uncertain. There is ongoing debate regarding the feasibility of clinical follow-up and the criteria for selective surgical excision. This study aims to conduct a meta-analysis to determine the rate of upgrade from breast benign IDP and identify predictive factors associated with the conversion of benign IDP to high-risk lesions or carcinoma, which could guide healthcare practitioners in selecting the appropriate clinical treatment strategy. We conducted a comprehensive search across multiple databases (PubMed, Web Of Science, Cochrane Library, and Embase) for studies published between 2012 and 2023 that evaluated upgrade rates and predictive factors of breast benign IDP diagnosed via biopsy. In addition, we included studies that reported on the clinical follow-up of patients with breast benign IDP. In total, 32 studies comprising 7371 cases of biopsy-diagnosed breast benign IDP were included. Among these cases, 720 demonstrated an upgrade to high-risk lesions or carcinoma, resulting in an upgrade rate of 6.94% [95% confidence interval (CI): 3.0-8.0%]. A subgroup of 1713 patients was clinically followed up, demonstrating an average follow-up duration of 30.95 months. Among them, 26 cases experienced an upgrade to high-risk lesions or carcinoma, yielding an upgrade rate of 1.51% (95% CI 0.00-2.00). Furthermore, we identified nine predictive factors associated with the upgrading of breast benign IDP, which included age at diagnosis, personal history of breast cancer, family history of breast cancer, multiple IDPs, lesion size ≥ 10 mm, palpable mass, calcification, and the presence of mass and asymmetry in mammographic findings. Although the conversion rate of breast benign IDP to high-risk lesions or carcinoma is relatively low, timely identification of predictive factors associated with benign IDP upgrades may help selecting the optimal clinical treatment strategy, such as surgery for patients with benign IDP presenting one or more predictive factors, while clinical follow-up for those without specific risk factors.

Effect of CHST11, a novel biomarker, on the biological functionalities of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor, and the role of carbohydrate sulfotransferase 11 (CHST11) in this cancer remains unclear. Here, by using bioinformatics methods, we comprehensively analyzed the relationship between CHST11 and clinical significance, immune infiltration, functional enrichment, m6A methylation, and protein-protein interaction networks. We found that CHST11 expression was significantly higher in ccRCC samples than in normal tissues. Additionally, CHST11 levels correlated with the clinicopathological features of ccRCC patients and functioned as a prognostic factor for patient survival. Functional analysis revealed the involvement of CHST11 in metabolic pathways. Immune infiltration and m6A methylation analysis suggested the association of CHST11 with immune cell abundance in the tumor microenvironment and specific methylation patterns in ccRCC. The in vitro analysis of the clinical samples and ccRCC cell lines demonstrated that the overexpression of CHST11 promotes ccRCC cell proliferation, migration, and invasion, while its suppression has the opposite effect. Thus, CHST11 may play a remarkable role in the occurrence and progression of ccRCC. Functionally, CHST11 promotes the aggressiveness of ccRCC cells. These findings provide insights into the role of CHST11 in ccRCC progression.Registry and the Registration No. of the study/trial: No. 2021K034.

A paradigm shift in cancer research based on integrative multi-omics approaches: glutaminase serves as a pioneering cuproptosis-related gene in pan-cancer.

BACKGROUND: Cuproptosis is a newly identified form of unprogrammed cell death. As a pivotal metabolic regulator, glutaminase (GLS) has recently been discovered to be linked to cuproptosis. Despite this discovery, the oncogenic functions and mechanisms of GLS in various cancers are still not fully understood. METHODS: In this study, a comprehensive omics analysis was performed to investigate the differential expression levels, diagnostic and prognostic potential, correlation with tumor immune infiltration, genetic alterations, and drug sensitivity of GLS across multiple malignancies. RESULTS: Our findings revealed unique expression patterns of GLS across various cancer types and molecular subtypes of carcinomas, underscoring its pivotal role primarily in energy and nutrition metabolism. Additionally, GLS showed remarkable diagnostic and prognostic performance in specific cancers, suggesting its potential as a promising biomarker for cancer detection and prognosis. Furthermore, we focused on uterine corpus endometrial carcinoma (UCEC) and developed a novel prognostic model associated with GLS, indicating a close correlation between GLS and UCEC. Moreover, our exploration into immune infiltration, genetic heterogeneity, tumor stemness, and drug sensitivity provided novel insights and directions for future research and laid the foundation for high-quality verification. CONCLUSION: Collectively, our study is the first comprehensive investigation of the biological and clinical significance of GLS in pan-cancer. In our study, GLS was identified as a promising biomarker for UCEC, providing valuable evidence and a potential target for anti-tumor therapy. Overall, our findings shed light on the multifaceted functions of GLS in cancer and offer new avenues for further research.

[Non-primary solid malignancies of breast in needle core biopsy: a clinicopathological analysis of 23 cases].

Objective: To investigate the accurate diagnosis and differential diagnosis of non-primary solid malignant tumors in breast needle core biopsy. Methods: Twenty-three cases of breast, axilla or neck lymph nodes pathologically diagnosed as non-primary solid malignant tumors were collected at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from January 2013 to March 2023. The differential diagnoses and diagnostic features were analyzed, based on combining clinical data, histology, and expression characteristics of biomarkers. Results: All patients were female, with age ranging from 29 to 75 years (average 56 years). The average time from the diagnosis of primary tumor to the current diagnosis was 21 months (0 to 204 months).The primary sites included the ovary (9 cases), the lung (5 cases), the gastrointestinal tract (4 cases), the pancreas, intrahepatic bile duct, thyroid gland, nasal cavity and forearm skin (1 case each). No carcinoma in situ was found in any of the cases. The morphological differences were significant among the tumors, but similar to the primary tumors. The tumors of neuroendocrine and female reproductive tract had great morphological and immunophenotypic overlaps with breast cancer. Metastatic lung cancer cells showed obvious atypia and tumor giant cells. The morphology and immunophenotype of metastatic serous carcinoma of female reproductive system might resemble invasive micropapillary carcinoma of the breast. Metastatic adenocarcinoma of the gastrointestinal tract often had features of mucous secretion. Metastatic neuroendocrine tumors were bland in appearance and morphologically similar to solid papillary carcinoma of breast, but negative for ER. TRPS1 was mostly negative (18/23) and variably positive in ovarian (4/9) and intrahepatic bile duct (1/1) tumors. Conclusions: The diagnosis of breast needle core biopsy specimen should be combined with clinical history, imaging study, and careful examination of histological features, such as presence of in situ component, morphological similarity between the primary and metastatic tumors, and using appropriate markers to differentiate the primary from metastatic tumors.

Tubulin alpha-1b chain was identified as a prognosis and immune biomarker in pan-cancer combing with experimental validation in breast cancer.

The α-tubulin subtype, Tubulin α-1b chain (TUBA1B), has been shown to influence immune cell infiltration, cancer growth, and survival across various malignancies. However, a comprehensive study has not yet been undertaken examining the immunological and predictive effects of TUBA1B in a pan-carcinoma context. Using data from TCGA, GEO, and other databases, we analyzed TUBA1B expression across various carcinoma types using transcriptional profiling, prognostic implications, genetic and epigenetic alterations, methylation patterns, and immunological significance. To validate our findings, we conducted Western blot analysis to assess TUBA1B protein levels in matched breast cancer tissue samples and performed CCK-8 proliferation assay, flow cytometry, transwell invasion, and migration assays to comprehensively examine the functional impact of TUBA1B on breast cancer cells. Our pan-cancer analysis found TUBA1B upregulation across most tumor types, with varying expression patterns in distinct immune and molecular subtypes. High TUBA1B expression was an independent risk factor and associated with poor prognoses in several cancers, including BRCA, KICH, LGG, LUAD, and MESO. TUBA1B also demonstrates moderate to high diagnostic accuracy in most tumor types. Increased m6A methylation levels were observed in the TUBA1B gene, while its promoter region displayed low methylation levels. TUBA1B's expression impacted some cancers by elevating tumor mutation burden, microsatellite instability, neoantigen formation, immune cell infiltration, and the modulation of immune checkpoints. Functional enrichment analysis highlights TUBA1B's involvement in important cellular processes such as the cell cycle, p53 signaling, cell senescence, programmed cell death, and the regulation of immune-related pathways. Moreover, our study reveals higher TUBA1B protein expression in breast cancer tissues compared to adjacent tissues. In vitro experiments confirm that TUBA1B deletion reduces breast cancer cell proliferation, invasion, and migration while increasing apoptosis. In conclusion, our study suggests that TUBA1B could potentially serve as a diagnostic marker for predicting cancer immunological profiles and survival outcomes and shed light on the expression and role of TUBA1B in breast cancer, providing a solid foundation for considering it as a promising therapeutic target for breast cancer patient treatment.

NRSN2 promotes the malignant behavior of HPV-transfected laryngeal carcinoma cells through AMPK/ULK1 pathway mediated autophagy activation.

Neurensin-2 (NRSN2) performs a pro-carcinogenic function in multiple cancers. However, the function of NRSN2 in HPV-infected laryngeal carcinoma (LC) remains unclear. HPV transfection was performed in LC cells. The mRNA and protein levels were monitored using RT-qPCR, immunoblotting, and IF. Cell viability and proliferation were found using the CCK-8 assay and Edu staining. Cell invasion, migration, and apoptosis were probed using the Transwell, wound healing, and flow cytometry, respectively. The autophagosome was observed using TEM. NRSN2 was overexpressed in HPV-transfected LC cells. Inhibition of NRSN2 restrained the autophagy and malignant behavior of HPV-transfected LC cells. Meanwhile, the inhibition of AMPK/ULK1 pathway limited the increased autophagy of HPV-transfected LC cells caused by NRSN2 overexpression. Furthermore, NRSN2 knockdown inhibits autophagy by suppressing AMPK/ULK1 pathway, thereby restraining the malignant behavior of HPV-transfected LC cells. Our research confirmed that HPV transfection increased the autophagy and malignant behavior of LC cells by regulating the NRSN2-mediated activation of the AMPK/ULK1 pathway, offering a new target for cure of LC.

Placental metastasis from maternal NUT carcinoma: diagnostic pitfalls and challenges.

We report a young pregnant woman with large midline thoracic mass and markedly elevated serum alpha-fetoprotein (AFP) levels. Initially suspected as a germ cell tumour (GCT) due to age, site, and high AFP levels, a biopsy unveiled a high-grade malignant tumour characterised by undifferentiated monotonous cells. Although tumour cells exhibited positive AFP, the overall immunoprofile did not provide additional evidence to support GCT. Further work-up showed positive for NUT (nuclear protein in testis) immunostaining and the presence of BRD4-NUT1 fusion, confirming the diagnosis of NUT carcinoma. On radiology, there were extensive metastases to lungs, liver, vertebrae, and placenta. Despite aggressive chemotherapy, radiotherapy and immunotherapy, she did not respond to the therapies. Fortunately, her child was not affected by the carcinoma. This is the first case highlighting that thoracic lung primary NUT carcinoma can spread to the placenta and manifest with elevated serum AFP levels, potentially leading to misdiagnosis as GCT both clinically and pathologically.

Real-world data of poly (ADP-ribose) polymerase inhibitor response in Japanese patients with ovarian cancer.

BACKGROUND: Poly (ADP-ribose) polymerase (PARP) inhibitors have been increasingly used in the treatment of ovarian cancer, with BRCA positivity and homologous recombination deficiency (HRD) being common biomarkers used for predicting their efficacy. However, given the limitations of these biomarkers, new ones need to be explored. METHODS: This retrospective study included 181 ovarian cancer patients who received olaparib or niraparib at two independent hospitals in Japan between May 2018 and December 2022. Clinical information and blood sampling data were collected. Patient characteristics, treatment history, and predictability of treatment duration based on blood data before treatment initiation were examined. RESULTS: High-grade serous carcinoma, BRCA positivity, HRD, and maintenance therapy after recurrence treatment were observed more frequently in the olaparib group than in the niraparib group. The most common reasons for treatment interruption were anemia, fatigue, and nausea in the olaparib group and thrombocytopenia in the niraparib group. Regarding response to olaparib treatment, complete response to the most recent treatment, maintenance therapy after the first chemotherapy, high-grade serous carcinoma, and germline BRCA positivity were observed significantly more frequently among responders than among non-responders. Furthermore, neutrophil counts were significantly higher among responders than among non-responders. CONCLUSIONS: Inflammation-related blood data, such as neutrophil count, obtained at the initial pre-treatment visit might serve as potential predictors for prolonged olaparib treatment. While this study offers valuable insights into potential indicators for prolonged olaparib treatment, it underscores the need for more expansive research to strengthen our understanding of PARP inhibitors and optimize treatment strategies in ovarian cancer.

Olaparib Addition to Maintenance Bevacizumab Therapy in Ovarian Carcinoma With BRCA-Like Genomic Aberrations.

Importance: Testing for homologous recombination deficiency is required for the optimal treatment of high-grade epithelial ovarian cancer. The search for accurate biomarkers is ongoing. Objective: To investigate whether progression-free survival (PFS) and overall survival (OS) of patients with high-grade epithelial ovarian cancer treated with maintenance olaparib or placebo differed between patients with a tumor BRCA-like genomic profile and patients without a tumor BRCA-like profile. Design, Setting, and Participants: This cohort study was a secondary analysis of the PAOLA-1 randomized clinical trial that compared olaparib plus bevacizumab with placebo plus bevacizumab as maintenance treatment in patients with advanced high-grade ovarian cancer after a good response to first-line platinum with taxane chemotherapy plus bevacizumab, irrespective of germline or tumor BRCA1/2 mutation status. All patients with available tumor DNA were included in the analysis. The current analysis tested for an interaction between BRCA-like status and olaparib treatment on survival outcomes. The original trial was conducted between July 2015 and September 2017; at the time of data extraction for analysis in March 2022, a median follow-up of 54.1 months (IQR, 28.5-62.2 months) and a total follow-up time of 21 711 months was available, with 336 PFS and 245 OS events. Exposures: Tumor homologous recombination deficiency was assessed using the BRCA-like copy number aberration profile classifier. Myriad MyChoice CDx was previously measured. The trial was randomized between the olaparib and bevacizumab and placebo plus bevacizumab groups. Main Outcomes and Measures: This secondary analysis assessed hazard ratios (HRs) of olaparib vs placebo among biomarker strata and tested for interaction between BRCA-like status and olaparib treatment on PFS and OS, using Cox proportional hazards regression. Results: A total of 469 patients (median age, 60 [range 26-80] years) were included in this study. The patient cohort consisted of women with International Federation of Gynaecology and Obstetrics stage III (76%) high-grade serous (95%) ovarian cancer who had no evaluable disease or complete remission at initial or interval debulking surgery (76%). Thirty-one percent of the tumor samples (n = 138) harbored a pathogenic BRCA mutation, and BRCA-like classification was performed for 442 patients. Patients with a BRCA-like tumor had a longer PFS after olaparib treatment than after placebo (36.4 vs 18.6 months; HR, 0.49; 95% CI, 0.37-0.65; P < .001). No association of olaparib with PFS was found in patients with a non-BRCA-like tumor (17.6 vs 16.6 months; HR, 1.02; 95% CI, 0.68-1.51; P = .93). The interaction was significant (P = .004), and HRs and P values (for interaction) were similar in the relevant subgroups, OS, and multivariable analyses. Conclusions and Relevance: In this secondary analysis of the PAOLA-1 randomized clinical trial, patients with a BRCA-like tumor, but not those with a non-BRCA-like tumor, had a significantly longer survival after olaparib plus bevacizumab treatment than placebo plus bevacizumab treatment. Thus, the BRCA1-like classifier could be used as a biomarker for olaparib plus bevacizumab as a maintenance treatment.

[Clinical characteristics and prognosis analysis of pulmonary sarcomatoid carcinoma].

Objective: To summarize the clinical characteristics, treatment, and outcomes of patients with pulmonary sarcomatoid carcinoma (PSC) in order to improve clinicians' understanding of this disease. Methods: The clinical data of patients diagnosed with PSC in our hospital from January 1, 2015 to November 30, 2023 were retrospectively analyzed. According to whether radical resection was performed, the patients were divided into resectable group and unresectable group. The characteristics and treatments of PSC in different groups were compared. The survival curves were drawn by Kaplan-Meier method to compare the prognosis of different groups of patients. Results: A total of 43 PSC patients were included, including 32 males, with an average age of (62.79±9.59) years, and 31 smokers. Peripheral-type tumors were more common, with imaging showing predominantly solid soft tissue masses, and the maximum diameter of the tumor was more than 5 cm in 14 patients. Among the 23 patients who underwent NGS gene testing, the KRAS mutation rate was 43.5%, the TP53 mutation rate was 30.4%, and the MET mutation rate was 8.7%, all of which were MET-14 exon skipping mutations. PD-L1 expression was detected in 13 patients, 10 of whom showed high expression. The median overall survival (mOS) of the 43 patients with PSC was 24.6 months (13.0-52.7 months). Among them, 22 patients underwent radical lobectomy plus mediastinal lymph node dissection, 13 patients had postoperative recurrence, and 7 patients died during follow-up. The median disease-free survival (mDFS) was 12.3 months, the mOS was not achieved and the 1-year OS rate was 77.3 %. Twenty-one patients had unresectable locally advanced or advanced stage, and 15 patients died. The mDFS was 2.5 months, the mOS was 6.2 months, and the 1-year OS rate was 42.9 %. Seventeen patients received immunotherapy, and 1 patient received targeted therapy with the MET inhibitor glumetinib. Conclusions: PSC has a higher incidence in the elderly, smokers, and males, is highly malignant and has a poor prognosis. Based on its molecular biological characteristics, PD-L1 expression and tumor molecular detection can be performed to guide treatment options.

Bowel perforation with generalised peritonitis secondary to recurrent primary fallopian tube carcinoma after 17 years.

We describe a case of bowel perforation secondary to a recurrence of primary fallopian tube carcinoma treated more than a decade ago. A woman in her 70s presented to a rural centre with an acute abdomen. An abdominal CT showed a perforated ileum secondary to a pelvic mass. Emergency laparotomy identified the pelvic mass that was adherent to the side wall and invading the ileum at the site of perforation. Its adherence to the external iliac vessels posed a challenge to achieve en-bloc resection; therefore, a defunctioning loop ileostomy was created. Final histopathology and immunopathology were consistent with the recurrence of her primary fallopian tube carcinoma. The patient was further discussed in a multidisciplinary team meeting at a tertiary referral hospital. This case highlighted the importance of having a high index of suspicion for cancer recurrence, the utility of rapid source control laparotomy and multidisciplinary team patient management.