Tumors Of Origin Research Articles

A unique presentation of pericardial epithelioid angiosarcoma with multifaceted complications

Introduction and importance: Angiosarcomas are rare tumors of endothelial origin and may arise in any organ. Epithelioid angiosarcomas are a subtype of angiosarcoma that are rapidly progressive and typically fatal. Case presentation: We report a case of a 25-year-old previously healthy female who presented initially for dyspnea and palpitations, on further evaluation she was found to have large bilateral pleural effusions and cardiac tamponade. Clinical Discussion: Pericardiocentesis and thoracentesis were performed alongside biopsies that revealed atypical cellular proliferation. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed avid uptake in the anterior mediastinum, perivascular, paratracheal, subcarinal and pleural lymph nodes with large FDG uptake in the bilateral pleural effusion. Mediastinoscopy was done and biopsies showed an overtly malignant, epithelioid neoplasm with foci of vaso-formation; Keeping with high grade epithelioid angiosarcoma of the pericardium. She received six cycles of weekly paclitaxel, but imaging for abdominal pain incidentally showed evidence of metastasis to the liver and spine so she was switched to Adriamycin-Ifosfamide for which she received one cycle so far. Her hospital course was complicated by high output pleural effusions, chylothorax, left atrial thrombus formation and an intensive care unit stay for septic shock. Conclusion: Pericardial epithelioid angiosarcoma has been reported rarely in the literature. We aim to report a case of extensive metastatic pericardial epithelioid angiosarcoma in a young patient; which we believe can be an addition to the literature of a malignancy associated with poor prognosis and no definitive proven treatment regimen.

Microchip Based Isolation and Drug Delivery of Patient-Derived Extracellular Vesicles Against Their Homologous Tumor.

Extracellular vesicles (EVs) have demonstrated significant potential in drug delivery and anti-tumor therapy. Despite this promising strategy, challenges such as specific targeting, EVs purification persist. In this study, a personalized nanodrug delivery platform using patient-derived tumor EVs (PT-EVs) based on a microchip is presented. The microchip integrates multiple functions, including capture, enrichment, drug loading, and elution of PT-EVs. The isolation and drug-carrying procedures are completed within a 12 h timeframe, achieving a recovery rate of 65%, significantly surpassing the conventional ultracentrifuge (UC) method. Furthermore, PT-EVs derived from patient tumor models are first utilized as natural drug carriers, capitalizing on their inherent homing ability to precisely target homologous tumors. Lenvatinib and doxorubicin (DOX), two commonly utilized drugs in the clinical treatment of hepatocellular carcinoma (HCC), are loaded into PT-EVs and delivered to a matched in vitro tumor model that recapitulates original tumors for drug susceptibility testing. As is proven, PT-EVs exhibit robust tumor cell targeting and efficient receptor-mediated cellular uptake, and the efficacy of chemotherapeutic drugs is improved significantly. These results suggest that this platform could be a valuable tool for efficient isolation of PT-EVs and personalized drug customization, particularly when working with limited clinical samples, thus supporting personalized and precision medicine.

Real-World Study of Lanreotide Autogel in Routine Practice in Patients with Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Hong Kong and Taiwan.

There is a lack of data on the efficacy, effectiveness, and safety of lanreotide autogel in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) of Chinese ethnicity. This non-interventional, retrospective study evaluated the effectiveness and safety of lanreotide autogel in patients of Chinese ethnicity with GEP-NETs in clinical practice. Patient charts were abstracted from five hospitals in Hong Kong and Taiwan (July-September 2021), where lanreotide autogel is approved for treating GEP-NETs. Included patients were adults with unresectable, metastatic, or locally advanced GEP-NETs who received a first injection (index) of lanreotide autogel 120mg between 01 January 2017 and 30 June 2020 (planned sample size: N = 30). Follow-up ran from index to a maximum of 48 (± 4) weeks or until disease progression, start of new antitumor treatment, or death. The primary endpoint was progression-free survival (PFS) rate at week 48 (±4), and secondary endpoints included PFS rate at week 24 (±4), estimated using Kaplan-Meier analyses. All analyses were descriptive. Of 27 patients enrolled, 22 (81.5%) had 48weeks of follow-up. Tumors of pancreatic origin were the most common (73.9%). PFS rate was 0.96 (95% confidence interval: 0.72 - 0.99) at 24weeks and 0.82 (0.53-0.94) at 48weeks. Overall, 74.1% patients experienced ≥1 treatment-emergent adverse event; none were serious. No deaths were reported. Lanreotide autogel was well tolerated and showed good tumor control rate in a real-world setting. These findings align with results from previous studies in Caucasian, Japanese, and Korean patients, thus supporting lanreotide autogel for treating patients with GEP-NETs of Chinese ethnicity.

Oral T-cell-rich large B-cell lymphoma in a horse.

Lymphoma is the most common tumor of hematopoietic origin in horses. The course of the disease and clinical signs vary greatly, depending on tumor location and extent. The aim of this report is to describe the occurrence of T-cell-rich oral large B-cell lymphoma with marked local infiltration in a 25-year-old Crioula mare. The mare showed an increase in volume on the right side of its face, dyspnea, anorexia, and progressive weight loss. The clinical assessment showed that the lesion was located in the rostral and caudal sinuses and was markedly invasive to adjacent structures. The autopsy revealed a yellow mass with a soft to firm consistency, infiltrating multiple bones in the skull, and extensively invading the hard palate and masseter muscle. Histologically the mass comprised an undifferentiated malignant neoplasm characterized by a densely cellular neoplasm composed of large CD20 + neoplastic B-lymphocytes admixed with sheets of small, CD3 + reactive T-lymphocytes supported by delicate fibrovascular stroma leading to the diagnosis of oral T-cell-rich large B-cell lymphoma.

Construction and drug screening of Co-culture system using extrahepatic cholangiocarcinoma organoids and tumor-associated macrophages

Patient-derived organoids (PDOs) have been proposed as a novel in vitro tumor model that can be applied to tumor research and drug screening. However, current tumor organoid models lack components of the tumor microenvironment, particularly tumor-associated macrophages(TAMs).We collected peripheral blood and tumor samples from 6 patients with extrahepatic cholangiocarcinoma(eCCA). Monocytes were induced into TAMs by cytokine and conditioned medium, and then co-cultured with tumor organoids. Our comprehensive analysis and comparison of histopathology and genomics results confirmed that this co-culture model can better capture intra- and inter-tumor heterogeneity retain the specific mutations of the original tumor. Drug sensitivity data in vitro revealed that gemcitabine and cisplatin are effective drugs for cholangiocarcinoma, but TAMs in the tumor microenvironment promote organoids growth and chemotherapy resistance. In conclusion, our organoid model of cholangiocarcinoma co-cultured with TAMs can not only shorten the model construction cycle, but also preserve the heterogeneity of original tumors to improve the accuracy of drug screening, and can also be applied to the researches of TAMs and tumors.

Itinerary: Clinical and Therapeutic Profile of Brain Tumors

Introduction Brain tumors, defined by the abnormal proliferation of anaplastic cells within the brain meninges or cranial nerves, remain significant contributors to morbidity and mortality despite advances in imaging techniques like MRI, PET, and SPECT, and neuro-oncological therapies. Histological types of these tumors vary by age. This study aims to outline the epidemiological and histological profiles of central nervous system (CNS) tumors at the National Institute of Oncology in Rabat, Morocco.  Materials and Methods A retrospective descriptive study was conducted on patients treated at the radiotherapy department from November 2018 to October 2021. Parameters such as age, sex, primary clinical signs, tumor origin for secondary lesions, tumor location, and histological types were analyzed.  Results 182 cases of CNS tumors were recorded, with a median patient age of 43 years (range 8-73 years). Women represented 73.2% of the cases, and children made up 8.5% of the study population. The most common symptoms at diagnosis were headaches (68.3%), decreased visual acuity (28%), and nausea/vomiting (24.4%). Tumors were mostly located above the tentorium (80%). Of the tumors, 49% were secondary, primarily originating from the breast (58.6%) and lungs (46%). Glioblastoma was the most common primary tumor (39.1%), with a mortality rate of 55%. Multidisciplinary care is crucial for addressing the challenges posed by this serious prognosis.  Conclusion CNS tumors are uncommon in Morocco and are generally observed in adults, mainly secondary to breast cancer. Glioblastoma is the most frequent primary tumor. Effective multidisciplinary approaches are necessary to manage these complex cases.

Application of cell blocks to assist in precise cytological diagnosis of serous effusion

Objective: To investigate the importance of cell block and immunohistochemistry in the accurate diagnosis of serous effusion. Methods: A retrospective study was conducted on 3 124 cases of serous effusion from the Department of Pathology, Beijing Hospital from 2018 to 2022, include 2 213 cases of pleural effusion, 768 cases of peritoneal effusion, 143 cases of pericardial effusion. There were 1 699 males (54.4%) and 1 425 females (45.6%), average age 69 years old. Of which 1 292 cases were prepared with cell blocks and examined with immunohistochemical stain. Results: The percentage of malignant diagnosis increased from 64.9% (839/1 292) to 84.0% (1 086/1 292) after cell block preparation, and 1 086 cases were accurately diagnosed with histological type and/or origin of primary tumor. The undetermined diagnosis of suspected malignancy decreased from 13.3% (172/1 292) to 0.1% (1/1 292) and that of atypical hyperplasia from 18.8% (243/1 292) to 0.4% (5/1 292). The negative result for malignancy rate increased from 3.0% (38/1 292) to 15.5% (200/1 292). The differences highlighted above were statistically significant (Pearson's chi-squared test=12.739, P<0.01). Conclusion: Application of immunohistochemistry based on cell block can significantly improve malignant diagnosis in serous effusion, identify tumor origin and histological type as well as decrease the uncertain diagnosis.

The effects of carbon-ion beam irradiation on three-dimensional in vitro models of normal oral mucosa and oral cancer: development of a novel tool to evaluate cancer therapy.

Given that the original tumor microenvironment of oral cancer cannot be reproduced, predicting the therapeutic effects of irradiation using monolayer cultures and animal models of ectopic tumors is challenging. Unique properties of carbon-ion irradiation (CIR) characterized by the Bragg peak exert therapeutic effects on tumors and prevent adverse events in surrounding normal tissues. However, the underlying mechanism remains unclear. The biological effects of CIR were evaluated on three-dimensional (3D) in vitro models of normal oral mucosa (NOMM) and oral cancer (OCM3 and OCM4) consisting of HSC-3 and HSC-4 cells. A single 10- or 20-Gy dose of CIR was delivered to NOMM, OCM3, and OCM4 models. Histopathological and histomorphometric analyses and labeling indices for Ki-67, γH2AX, and TUNEL were examined after CIR. The concentrations of high mobility group box 1 (HMGB1) were measured. NOMM exhibited epithelial thinning after CIR, which could be caused by the decreased presence of Ki-67-labeled basal cells. The relative proportion of the thickness of cancer cells to the underlying stroma in cancer models decreased after CIR. This finding appeared to be supported by changes in the three labeling indices, indicating CIR-induced cancer cell death, mostly via apoptosis. Furthermore, the three indices and the HMGB1 release levels significantly differed among the OCM4 that received different doses and with different incubation times after CIR while those of the OCM3 models did not, suggesting more radiosensitivity in the OCM4. The three 3D in vitro models can be a feasible and novel tool to elucidate radiation biology.

PAX8 expression in cancerous and non-neoplastic tissue: a tissue microarray study on more than 17,000 tumors from 149 different tumor entities.

PAX8 plays a role in development of the thyroid, kidney, and the Wolffian and Mullerian tract. In surgical pathology, PAX8 immunohistochemistry is used to determine tumors of renal and ovarian origin, but data on its expression in other tumors are conflicting. To evaluate PAX8 expression in normal and tumor tissues, a tissue microarray containing 17,386 samples from 149 different tumor types and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. PAX8 results were compared with previously collected data on cadherin 16 (CDH16). PAX8 positivity was found in 40 different tumor types. The highest rate of PAX8 positivity was found in thyroidal neoplasms of follicular origin (98.6-100%), gynecological carcinomas (up to 100%), renal tumors (82.6-97.8%), and urothelial neoplasms (2.3-23.7%). Important tumors with near complete absence of PAX8 staining (< 1%) included all subtypes of breast cancers, hepatocellular carcinomas, gastric, prostatic, pancreatic, and pulmonary adenocarcinomas, neuroendocrine neoplasms, small cell carcinomas of various sites, and lymphomas. High PAX8 expression was associated with low tumor grade in 365 non-invasive papillary urothelial carcinomas (p < 0.0001) but unrelated to patient outcome and/or tumor phenotype in clear cell renal cell carcinoma, high-grade serous ovarian cancer, and endometrioid endometrial carcinoma. For determining a renal tumor origin, sensitivity was 88.1% and specificity 87.2% for PAX8, while sensitivity was 85.3% and specificity 95.7% for CDH16. The combination of PAX8 and CDH16 increased specificity to 96.8%. In conclusion, PAX8 immunohistochemistry is a suitable diagnostic tool. The combination of PAX8 and CDH16 positivity has high specificity for renal cell carcinoma.

Reprogramming the tumor immune microenvironment using engineered dual-drug loaded Salmonella

Synergistic combinations of immunotherapeutic agents can improve the performance of anti-cancer therapies but may lead to immune-mediated adverse effects. These side-effects can be overcome by using a tumor-specific delivery system. Here, we report a method of targeted immunotherapy using an attenuated Salmonella typhimurium (SAM-FC) engineered to release dual payloads: cytolysin A (ClyA), a cytolytic anti-cancer agent, and Vibrio vulnificus flagellin B (FlaB), a potent inducer of anti-tumor innate immunity. Localized secretion of ClyA from SAM-FC induces immunogenic cancer cell death and promotes release of tumor-specific antigens and damage-associated molecular patterns, which establish long-term antitumor memory. Localized secretion of FlaB promotes phenotypic and functional remodeling of intratumoral macrophages that markedly inhibits tumor metastasis in mice bearing tumors of mouse and human origin. Both primary and metastatic tumors from bacteria-treated female mice are characterized by massive infiltration of anti-tumorigenic innate immune cells and activated tumor-specific effector/memory T cells; however, the percentage of immunosuppressive cells is low. Here, we show that SAM-FC induces functional reprogramming of the tumor immune microenvironment by activating both the innate and adaptive arms of the immune system and can be used for targeted delivery of multiple immunotherapeutic payloads for the establishment of potent and long-lasting antitumor immunity.

Pelvic Exenteration in Advanced, Recurrent or Synchronous Cancers-Last Resort or Therapeutic Option?

First described some 80 years ago, pelvic exenteration remain controversial interventions with variable results and ever-changing indications. The previous studies are not homogenous and have different inclusion criteria (different populations and different disease characteristics) and methodologies (including evaluation of results), making it extremely difficult to properly assess the role of pelvic exenteration in cancer treatment. This study aims to describe the indications of pelvic exenterations, the main prognostic factors of oncologic results, and the possible complications of the intervention. Methods: For this purpose, we conducted a retrospective study of 132 patients who underwent various forms of pelvic exenterations in the Institute of Oncology "Prof. Dr. Al. Trestioreanu" in Bucharest, Romania, between 2013 and 2022, collecting sociodemographic data, characteristics of patients, information on the disease treated, data about the surgical procedure, complications, additional cancer treatments, and oncologic results. Results: The study cohort consists of gynecological, colorectal, and urinary bladder malignancies (one hundred twenty-seven patients) and five patients with complex fistulas between pelvic organs. An R0 resection was possible in 76.38% of cases, while on the rest, positive margins on resection specimens were observed. The early morbidity was 40.63% and the mortality was 2.72%. Long-term outcomes included an overall survival of 43.7 months and a median recurrence-free survival of 24.3 months. The most important determinants of OS are completeness of resection, the colorectal origin of tumor, and the presence/absence of lymphovascular invasion. Conclusions: Although still associated with high morbidity rates, pelvic exenterations can deliver important improvements in oncological outcomes in the long-term and should be considered on a case-by-case basis. A good selection of patients and an experienced surgical team can facilitate optimal risks/benefits.

Development of 3D-iNET ORION: a novel, pre-clinical, three-dimensional in vitro cell model for modeling human metastatic neuroendocrine tumor of the pancreas.

Neuroendocrine tumors (NETs) of the pancreas are rare neoplasms that present complex challenges to diagnosis and treatment due to their indolent course. The incidence of pancreatic neuroendocrine tumors has increased significantly over the past two decades. A limited number of pancreatic neuroendocrine cell lines are currently available for the research. Here, we present 3D-iNET ORION, a novel 3-dimensional (spheroid) cell line, isolated from human pancreatic neuroendocrine tumor liver metastasis. Three-dimensionally grown (3D) cancer cell lines have gained interest over the past years as 3D cancer cell lines better recapitulate the in vivo structure of tumors, and are more suitable for in vitro and in vivo experiments. 3D-iNET ORION cancer cell line showed high potential to form tumorspheres when embedded in Matrigel matrix and expresses synaptophysin and EpCAM. Electron microscopy analysis of cancer cell line proved the presence of dense neurosecretory granules. When xenografted into athymic mice, 3D-iNET ORION cells produce slow-growing tumors, positive for chromogranin and synaptophysin. Human Core Exome Panel Analysis has shown that 3DiNET ORION cell line retains the genetic aberration profile detected in the original tumor. In conclusion, our newly developed neuroendocrine cancer cell line can be considered as a new research tool for in vitro and in vivo experiments.

Melanoma Brain Metastases Patient-Derived Organoids: An In Vitro Platform for Drug Screening.

Brain metastases are prevalent in the late stages of malignant melanoma. Multimodal therapy remains challenging. Patient-derived organoids (PDOs) represent a valuable pre-clinical model, faithfully recapitulating key aspects of the original tumor, including the heterogeneity and the mutational status. This study aimed to establish PDOs from melanoma brain metastases (MBM-PDOs) and to test the feasibility of using them as a model for in vitro targeted-therapy drug testing. Surgical resection samples from eight patients with melanoma brain metastases were used to establish MBM-PDOs. The samples were enzymatically dissociated followed by seeding into low-attachment plates to generate floating organoids. The MBM-PDOs were characterized genetically, histologically, and immunohistologically and compared with the parental tissue. The MBM-PDO cultures were exposed to dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) followed by a cell viability assessment. Seven out of eight cases were successfully cultivated, maintaining the histological, immunohistological phenotype, and the mutational status of the parental tumors. Five out of seven cases harbored BRAF V600E mutations and were responsive to BRAF and MEK inhibitors in vitro. Two out of seven cases were BRAF wild type: one case harboring an NRAS mutation and the other harboring a KIT mutation, and both were resistant to BRAF and MEK inhibitor therapy. We successfully established PDOs from melanoma brain metastases surgical specimens, which exhibited a consistent histological and mutational profile with the parental tissue. Using FDA-approved BRAF and MEK inhibitors, our data demonstrate the feasibility of employing MBM-PDOs for targeted-therapy in vitro testing.

Dose-Response Relationship in Patients with Liver Metastases from Neuroendocrine Neoplasms Undergoing Radioembolization with 90Y Glass Microspheres.

The benefit of multicompartment dosimetry in the radioembolization of neuroendocrine neoplasms is not firmly established. We retrospectively assessed its potential with patient outcome. Methods: Forty-three patients were eligible. The association of mean absorbed dose (MAD) for tumors and treatment response was tested per lesion with a receiver operating characteristic curve analysis, and the association of MAD with progression-free survival (PFS) and overall survival was tested per patient using uni- and multivariate Cox regression analyses. Results: The area under the curve for treatment response based on MAD was 0.79 (cutoff, 196.6 Gy; P < 0.0001). For global PFS, grade (grade 2 vs. 1: hazard ratio [HR], 2.51; P = 0.042; grade 3 vs. 1: HR, 62.44; P < 0.001), tumor origin (HR, 6.58; P < 0.001), and MAD (HR, 0.998; P = 0.003) were significant. For overall survival, no prognostic parameters were significant. Conclusion: In line with prior publications, a MAD of more than 200 Gy seemed to favor treatment response. MAD was also associated with PFS and may be of interest for radioembolization planning for neuroendocrine neoplasm patients.

The immunomodulatory role of paracrine signalling factor VSIG4 in peritoneal metastases

Peritoneal metastasis (PM), the regional progression of intra-abdominal malignancies, is a common sequelae of colorectal cancer (CRC). Immunotherapy is slated to be effective in generating long-lasting anti-tumour response as it utilizes the specificity and memory of the immune system. In the tumour microenvironment, tumour associated macrophages (TAMs) are posited to create an anti-inflammatory pro-tumorigenic environment. In this paper, we aimed to identify immunomodulatory factors associated with colorectal PM (CPM). A publicly available colorectal single cell database (GSE183916) was analysed to identify possible immunological markers that are associated with the activation of macrophages in cancers. Immunohistochemical analysis for V-set and immunoglobin containing domain 4 (VSIG4) expression was performed on tumour microarrays (TMAs) of tumours of colorectal origin (n = 211). Expression of VSIG4 in cell-free ascites obtained from CPM patients (n = 39) was determined using enzyme-linked immunosorbent assay (ELISA). CD163-positive TAMs cluster expression was extracted from a publicly available single cell database and evaluated for the top 100 genes. From these macrophage-expressed genes, VSIG4, a membrane protein produced by the M2 macrophages, mediates the up-regulation of anti-inflammatory and down-regulation of pro-inflammatory macrophages, contributing to an overall anti-inflammatory state. CRC TMA IHC staining showed that low expression of VSIG4 in stromal tissues of primary CRC are associated with poor prognosis (p = 0.0226). CPM ascites also contained varying concentrations of VSIG4, which points to a possible role of VSIG4 in the ascites. The contribution of VSIG4 to CPM development can be further evaluated for its potential as an immunotherapeutic agent.

Development and interpretation of a multimodal predictive model for prognosis of gastrointestinal stromal tumor

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal original tumor in gastrointestinal (GI) tract and is considered to have varying malignant potential. With the advancement of computer science, radiomics technology and deep learning had been applied in medical researches. It’s vital to construct a more accurate and reliable multimodal predictive model for recurrence-free survival (RFS) aiding for clinical decision-making. A total of 254 patients underwent surgery and pathologically diagnosed with GIST in The First Hospital of China Medical University from 2019 to 2022 were included in the study. Preoperative contrast enhanced computerized tomography (CE-CT) and hematoxylin/eosin (H&E) stained whole slide images (WSI) were acquired for analysis. In the present study, we constructed a sum of 11 models while the multimodal model (average C-index of 0.917 on validation set in 10-fold cross validation) performed the best on external validation cohort with an average C-index of 0.864. The multimodal model also reached statistical significance when validated in the external validation cohort (n = 42) with a p-value of 0.0088 which pertained to the recurrence-free survival (RFS) comparison between the high and low groups using the optimal threshold on the predictive score. We also explored the biological significance of radiomics and pathomics features by visualization and quantitative analysis. In the present study, we constructed a multimodal model predicting RFS of GIST which was prior over unimodal models. We also proposed hypothesis on the correlation between morphology of tumor cell and prognosis.

The clinical prognostic significance of miR-140–5p expression in patients with cancer: A Meta and Bioinformatic analysis

The prognostic value of microRNA-140–5p (miR-140–5p) expression in cancer patients has been investigated, but with inconsistent results. This meta-analysis aims to determine the prognostic significance of miR-140–5p expression in patients with various malignancies. A comprehensive literature search was conducted using PubMed, Web of Science, ProQuest, Cochrane, and Google Scholar to identify relevant studies published before June 2023. Pooled hazard ratios (HR) and odds ratios (OR) with 95 % confidence intervals (CI) were calculated to assess the prognostic importance and clinicopathological features of miR-140–5p in overall survival (OS) and disease-free survival (DFS) of cancer patients, respectively. The CancerMIRNome database and other OS analysis webservers were utilized to explore the prognostic value and expression profile of miR-140–5p. A total of 17 studies were included in the final analysis. The results demonstrated that decreased miR-140–5p expression was significantly associated with inferior OS (pooled HR 0.63; 95 % CI, 0.51–0.79; p < 0.001) and DFS (pooled HR 0.40; 95 % CI, 0.25–0.64; p < 0.001). Pooled ORs indicated a significant correlation between reduced miR-140–5p expression and positive lymph node metastasis (LNM; OR = 3.42; 95 % CI, 2.36–4.94; p < 0.001), advanced tumor stage (OR = 2.80; 95 % CI, 2.07–3.78; p < 0.001), and positive distant metastasis (DM; OR = 10.81; 95 % CI, 3.31–35.30; p < 0.001). No significant associations were observed between miR-140–5p expression and gender (OR = 0.94; 95 % CI, 0.70–1.28; p = 0.70), age (OR = 1.31; 95 % CI, 0.99–1.74; p = 0.06), tumor size (OR = 1.55; 95 % CI, 0.77–3.10; p = 0.22), and histological grade (OR = 1.20; 95 % CI, 0.46–3.10; p = 0.71). Subgroup analyses revealed that decreased miR-140–5p expression was associated with shorter OS in subgroups based on sample size (<100 or >100), tumor origin (GI or non-GI), and cancer type (GC/CRC). Bioinformatic analysis supported the finding that miR-140–5p was downregulated in most tumor tissues, and its reduced expression was linked to poor prognosis in patients with multiple malignancies. The prognostic significance of miR-140–5p in predicting reduced OS and DFS suggests that measuring miR-140–5p expression levels before treatment could serve as a valuable biomarker for identifying cancer patients with an unfavorable prognosis and improving clinical management.

Site-specific therapy guided by a 90-gene expression assay versus empirical chemotherapy in patients with cancer of unknown primary (Fudan CUP-001): a randomised controlled trial

Empirical chemotherapy remains the standard of care in patients with unfavourable cancer of unknown primary (CUP). Gene-expression profiling assays have been developed to identify the tissue of origin in patients with CUP; however, their clinical benefit has not yet been demonstrated. We aimed to evaluate the efficacy and safety of site-specific therapy directed by a 90-gene expression assay compared with empirical chemotherapy in patients with CUP. This randomised controlled trial was conducted at Fudan University Shanghai Cancer Center (Shanghai, China). We enrolled patients aged 18-75 years, with previously untreated CUP (histologically confirmed metastatic adenocarcinoma, squamous cell carcinoma, poorly differentiated carcinoma, or poorly differentiated neoplasms) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, who were not amenable to local radical treatment. Patients were randomly assigned (1:1) by the Pocock and Simon minimisation method to receive either site-specific therapy or empirical chemotherapy (taxane [175 mg/m2 by intravenous infusion on day 1] plus platinum [cisplatin 75 mg/m2 or carboplatin area under the curve 5 by intravenous infusion on day 1], or gemcitabine [1000 mg/m2 by intravenous infusion on days 1 and 8] plus platinum [same as above]). The minimisation factors were ECOG performance status and the extent of the disease. Clinicians and patients were not masked to interventions. The tumour origin in the site-specific therapy group was predicted by the 90-gene expression assay and treatments were administered accordingly. The primary endpoint was progression-free survival in the intention-to-treat population. The trial has been completed and the analysis is final. This study is registered with ClinicalTrials.gov (NCT03278600). Between Sept 18, 2017, and March 18, 2021, 182 patients (105 [58%] male, 77 [42%] female) were randomly assigned to receive site-specific therapy (n=91) or empirical chemotherapy (n=91). The five most commonly predicted tissues of origin in the site-specific therapy group were gastro-oesophagus (14 [15%]), lung (12 [13%]), ovary (11 [12%]), cervix (11 [12%]), and breast (nine [10%]). At the data cutoff date (April 30, 2023), median follow-up was 33·3 months (IQR 30·4-51·0) for the site-specific therapy group and 30·9 months (27·6-35·5) for the empirical chemotherapy group. Median progression-free survival was significantly longer with site-specific therapy than with empirical chemotherapy (9·6 months [95% CI 8·4-11·9] vs 6·6 months [5·5-7·9]; unadjusted hazard ratio 0·68 [95% CI 0·49-0·93]; p=0·017). Among the 167 patients who started planned treatment, 46 (56%) of 82 patients in the site-specific therapy group and 52 (61%) of 85 patients in the empirical chemotherapy group had grade 3 or worse treatment-related adverse events; the most frequent of these in the site-specific therapy and empirical chemotherapy groups were decreased neutrophil count (36 [44%] vs 42 [49%]), decreased white blood cell count (17 [21%] vs 26 [31%]), and anaemia (ten [12%] vs nine [11%]). Treatment-related serious adverse events were reported in five (6%) patients in the site-specific therapy group and two (2%) in the empirical chemotherapy group. No treatment-related deaths were observed. This single-centre randomised trial showed that site-specific therapy guided by the 90-gene expression assay could improve progression-free survival compared with empirical chemotherapy among patients with previously untreated CUP. Site-specific prediction by the 90-gene expression assay might provide more disease information and expand the therapeutic armamentarium in these patients. Clinical Research Plan of Shanghai Hospital Development Center, Program for Shanghai Outstanding Academic Leader, and Shanghai Anticancer Association SOAR PROJECT. For the Chinese translation of the abstract see Supplementary Materials section.

Clinical impact of pancreatic invasion in T1-stage distal bile duct cancer and prognostic factors associated with long-term survival: A multicenter study.

The eighth edition of the AJCC staging system introduced a shift in the staging of distal bile duct cancer (DBC), emphasizing the depth of invasion over adjacent organ invasion. This study aimed to evaluate the clinical impact of pancreatic invasion in pT1-stage DBC and identify prognostic factors for long-term survival. This multicenter retrospective analysis encompassed DBC patients who underwent pancreaticoduodenectomy between 2009 and 2019 in six Korean tertiary centers, specifically those with final pathology confirming AJCC eighth edition T1 stage and intrapancreatic bile duct tumor origin. Primary endpoints were five-year recurrence-free survival (RFS) and overall survival (OS). Secondary objectives included the identification of prognostic determinants. This study involved 287 patients, comprising 190 without and 97 with pancreatic invasion. Pancreatic invasion did not significantly influence five-year OS and RFS rates (OS: without pancreatic invasion 69.9% vs. with pancreatic invasion 54.1%, p = .25; RFS: 56.3% vs. 55.4%, p = .97). Multivariate analysis highlighted male gender, age, lymphovascular invasion, and N stage as significant OS determinants. Notably, male gender, ampulla of Vater invasion, lymphovascular invasion, and N1 stage were also associated with RFS. In pT1 DBC, pancreatic invasion demonstrates no substantial impact on long-term prognosis, in accordance with the depth-based paradigm of the eighth edition AJCC staging system. The prognostic factors influencing OS were identified as male gender, age, lymphovascular invasion, and nodal metastasis.

Clinical features and treatment of apoplectic intratumoral hemorrhage of glioma

ObjectiveThe primary objective of this study was to explore the clinical characteristics of apoplectic intratumoral hemorrhage in gliomas and offer insights for improving the diagnosis and treatment of this disease.MethodsWe analyzed the clinical data of 35 patients with glioma and hemorrhage. There were eight cases of multiple cerebral lobe involvement, and 22 cases involved a single lobe. Twenty-one patients had a preoperative Glasgow Coma Scale (GCS) score of ≥ 9 and had a craniotomy with tumor resection and hematoma evacuation after undergoing preoperative preparation. A total of 14 patients with GCS < 9, including one with thalamic hemorrhage breaking into the ventricles and acute obstructive hydrocephalus, underwent craniotomy for tumor resection after external ventricular drainage (EVD). One patient had combined thrombocytopenia, which was surgically treated after platelet levels were normalized through transfusion. The remaining 12 patients received immediate intervention in the form of craniotomy hematoma evacuation and tumor resection.ResultsWe performed subtotal resection on three tumors of thalamic origin and two tumors of corpus callosum origin, but we were able to successfully resect all the tumors in other locations that were gross total resection Pathology results showed that 71.43% of cases accounted for WHO-grade 4 tumors. Among the 21 patients with a GCS score of ≥ 9, two died perioperatively. Fourteen patients had a GCS score < 9, of which eight patients died perioperatively.ConclusionsPatients with a preoperative GCS score ≥ 9 who underwent subemergency surgery and received aggressive treatment showed a reasonable prognosis. We found their long-term outcomes to be correlated with the pathology findings. On the other hand, patients with a preoperative GCS score < 9 required emergency treatment and had a high perioperative mortality rate.