Tumors Of Origin Research Articles

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.

AB091. Establishment and application of brainstem glioma organoids.

Traditional preclinical experiments on brainstem gliomas mainly rely on patient-derived primary cell lines, but there are problems such as low success rate in establishment and inability to preserve tumor heterogeneity, which limit the clinical transformation. As a new type of in vitro tumor model, organoids have similar structure and function to the original tumor, requiring less tissue for cultivation, with short cycle and high success rate, which is particularly suitable for brainstem glioma biopsy. There is currently no precedent for the successful construction of brainstem glioma organoid models. This new established organoid provides us a more robust preclinical tool for comprehending the pathogenesis and conducting drug screening for this kind of disease. Cultivate patient-derived brainstem glioma organoids in vitro, verify the genetic fidelity and consistency of the organoids through morphological experiments as well as sequencing technology. Then explore the evolutionary direction of multiple types of brainstem gliomas through pseudo-time series analysis. Complete drug screening, natural killer (NK) cell co-culture, oncolytic virus therapy, and other treatments based on organoids in vitro, and evaluate the efficacy. Complete co-culture of organoids and Institute of Cancer Research (ICR) mouse brain slices in vitro. Establish patient-derived organoid xenograft (PDOX) mouse models derived from organoids in vivo. The establishment of organoids of all types of brainstem gliomas was completed for the first time in the world, with a total of 41/48 organoid models derived from patients, with a success rate of 85.4%, covering all segments and pathological types. The results of morphological experiments and sequencing showed that the genetic characteristics of organoids were highly consistent with those of tumor tissues. Drug screening tests for temozolomide and panobinostat were completed in vitro, and NK cell co-culture and oncolytic virus therapy testing were achieved. Co-culture of brainstem glioma organoids and mouse brain slices was achieved in vitro. Furthermore, a PDOX model of brainstem glioma was established. Brainstem glioma organoids can be established maturely, stably, and reliably, and can be used for preclinical drug testing for patients. Animal models derived from brainstem glioma organoids have broad preclinical experimental value.

Trends in the treatment of human papillomavirus-associated oropharyngeal carcinoma in Slovakia.

The optimal treatment of oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) is currently a subject of clinical research. This questionnaire study investigated current trends in the treatment of HPV-associated (HPV+) OPC in Slovakia with the incorporation of deintensification of oncological treatment into routine clinical practice outside of clinical trials. The Slovak Cooperative Head and Neck Cancer Group (SCHNCG) developed a questionnaire aimed at identifying trends in the oncological treatment of HPV+ OPC intended for all radiation oncology (RO) facilities in Slovakia. Specialists in the field of RO responded to general questions about the character of their individual institutions as well as to 4 theoretical clinical scenarios (case reports) regarding the treatment of HPV+ OPC, focusing primarily on the applied dose of radiotherapy (RT), the extent of target volumes, and the type of concurrent chemotherapy (CHT). The questionnaire study involved 35 RO specialists from 14 institutions in Slovakia. Regarding primary chemoradiotherapy (CRT) in T1N1M0 HPV+ OPC, 16 respondents (45.7%) would consider de-escalation of the RT dose to <70 Gy. In the case of postoperative RT in pT1pN1M0 HPV+ OPC with negative resection margins (R0) and absent extracapsular extension (ECE), 4 physicians (11.4%) would consider de-escalation of the RT dose to <60 Gy in the tumor bed area, while the majority of the treating specialists (n=19, 54.3%) would omit concurrent CHT. In the case of primary RT in elderly patient with T2N1M0 HPV+ OPC, the same number of physicians (n=16, 45.7%) would consider de-escalation of the RT dose to <70 Gy, and 14 respondents (40.0%) would completely omit CHT. In a high-risk patient with T2N3M0 HPV+ OPC with a complete response after 3 cycles of induction chemotherapy (iCHT), none of the respondents would indicate a reduction in the RT dose to the area of the original tumor and lymphadenopathy to <60 Gy. The doses and extent of irradiated volumes in the treatment of HPV+ OPC in Slovakia vary among different institutions. The tendency to de-escalate RT doses and reduce doses of concurrent systemic therapy in Slovakia is high and there was also an observed trend to reduce the extent of radiation treatment fields.

Using Copy Number Variation Data and Neural Networks to Predict Cancer Metastasis Origin Achieves High Area under the Curve Value with a Trade-Off in Precision.

The accurate identification of the primary tumor origin in metastatic cancer cases is crucial for guiding treatment decisions and improving patient outcomes. Copy number alterations (CNAs) and copy number variation (CNV) have emerged as valuable genomic markers for predicting the origin of metastases. However, current models that predict cancer type based on CNV or CNA suffer from low AUC values. To address this challenge, we employed a cutting-edge neural network approach utilizing a dataset comprising CNA profiles from twenty different cancer types. We developed two workflows: the first evaluated the performance of two deep neural networks-one ReLU-based and the other a 2D convolutional network. In the second workflow, we stratified cancer types based on anatomical and physiological classifications, constructing shallow neural networks to differentiate between cancer types within the same cluster. Both approaches demonstrated high AUC values, with deep neural networks achieving a precision of 60%, suggesting a mathematical relationship between CNV type, location, and cancer type. Our findings highlight the potential of using CNA/CNV to aid pathologists in accurately identifying cancer origins with accessible clinical tests.

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 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.

Pyrimidine-Dependent UV-Mediated Cross-Linking Magnifies Minor Genetic or Epigenetic Changes in Clinical Samples.

Detection of minor DNA allele alterations is becoming increasingly important for early detection and monitoring of cancer. We describe a new method that uses ultraviolet light to eliminate wild-type DNA alleles and enables improved detection of minor genetic or epigenetic changes. Pyrimidine-dependent UV-based minor-allele enrichment (PD-UVME) employed oligonucleotide probes that incorporated a UVA-sensitive 3-cyanovinylcarbazole (CNVK), placed directly opposite interrogated pyrimidines, such as thymine (T) or cytosine (C) in wild-type (WT) DNA. Upon UVA-illumination, CNVK cross-linked with T/C, preventing subsequent amplification. Mutations that removed the T/C escaped cross-linking and were amplified and detected. Similarly, CNVK discriminated between methylated and unmethylated cytosine in CpG dinucleotides, enabling direct enrichment of unmethylated DNA targets. PD-UVME was combined with digital droplet PCR (ddPCR) to detect serine/threonine-protein kinase B-Raf (BRAF) V600E mutations in model systems, thyroid patient cancer tissue samples, and circulating DNA of tumor origin (ctDNA) from melanoma patients. One thyroid cancer sample out of 9, and 6 circulating-DNA samples out of 7 were found to be BRAF V600E-positive via PD-UVME while classified as negative by conventional ddPCR. Positive samples via conventional ddPCR were also found positive via PD-UVME. All 10 circulating cell-free DNA (cfDNA) samples obtained from normal volunteers were negative via both approaches. Furthermore, preferential enrichment of unmethylated alleles in MAGEA1 promoters using PD-UVME was demonstrated. PD-UVME mutation/methylation enrichment performed prior to ddPCR magnifies low-level mutations or epigenetic changes and increases sensitivity and confidence in the results. It can assist with clinical decisions that hinge on the presence of trace alterations like BRAF V600E.

PCSK2 can be Useful in a Panel Approach to Distinguish Foregut and Midgut Neuroendocrine Tumors.

A number of immunohistochemical stains have been examined for utility in establishing the site of origin for metastatic well-differentiated neuroendocrine tumors (NETs). In the gastrointestinal (GI) tract, distinguishing metastatic duodenal NETs from jejunoileal and other GI NETs is important for clinical work-up, prognosis, and therapy. A recent study indicated that prohormone convertase 2 (PCSK2 or PC2) had broad expression in small intestine and appendiceal NETs. Because the study did not include duodenal NETs, we examined PCSK2 expression in duodenal and other GI NETs. GI NETs (n = 69) and 13 corresponding lymph node metastases from stomach, duodenum, pancreas, ileum, appendix, and rectum were evaluated for the expression of PCSK2, along with ISL1, NKX2.2, CDX2, SATB2, and PAX8. Expression of each stain was evaluated using the H-score system, and differences in expression by site were evaluated by the chi square test. PCSK2 was expressed at similar frequency in duodenal (50%), pancreatic (59%), and ileal NETs (40%). PCSK2 was infrequently expressed in stomach (0%), appendiceal (8%), and rectal (25%) NETs. However, incorporating PCSK2 into a panel including ISL1, NKX2.2, CDX2, and SATB2 allowed development of an algorithm which had 87% sensitivity and 93% specificity for classification of ileal NETs; and 68% sensitivity and 98% specificity for pancreaticoduodenal NETs. In contrast to previous findings, PCSK2 does not show specificity for any particular GI site. An algorithmic approach incorporating the expression of PCSK2 with that of ISL1, NKX2.2, CDX2, and SATB2 is useful in discriminating pancreatic, duodenal, ileal, appendiceal, and rectal NETs.

Non-small Cell Lung Cancer with Metachronous Mutations of EGFR and ALK Genes: A Case Report and Literature Review

Multiple primary lung cancer (MPLC) refers to patients with two or more primary lesions of lung cancer. It can be divided into synchronous MPLC (sMPLC) and metachronous MPLC (mMPLC) based on the timing of occurrence. In recent years, the detection rate of MPLC has gradually increased. However, considerable controversy exists in distinguishing MPLC from intrapulmonary metastasis (IM), especially when the histopathological types are identical. Given the significant differences in treatment strategies and prognosis in clinical practice currently, accurate diagnosis of MPLC is crucial for personalized precision therapy. Molecular genetics and sequencing technologies offer effective strategies for assessing the clonal origin of tumors. There have been reports of coexisting mutations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) fusion genes in non-small cell lung cancer, but case of EGFR mutation following an ALK mutation has not been mentioned. This article accurately diagnoses and retrospectively analyzes the clinical data of a case of ALK mutant adenocarcinoma in a male patient who developed an EGFR mutation with multiple metastases four years after surgery, and reviews the relevant literature. This paper aims to deepen the understanding of mMPLC and provide clinical references for the diagnosis and treatment of such patients. .

Efficacy and safety of office-based diode laser ablation for recurrent low-grade non-muscle-invasive bladder cancer under local anaesthesia: A pilot study

ABSTRACT Introduction Low-grade tumors account for approximately 50% of non-muscle invasive bladder cancer (NMIBC) with recurrence rates between 46% and 62%. Management of NMIBC recurrence typically involves transurethral resection of bladder tumor (TURBT) under general or regional anesthesia, which carries perioperative risks and considerable healthcare costs due to repeated procedures. Therefore, less invasive treatments such as office-based laser ablation, which aim to manage recurrences and reduce inpatient procedures without compromising oncological control, are needed. Objectives This study aims to assess the efficacy and safety of office-based diode laser ablation for treating recurrent NMIBC under local anesthesia and to evaluate the influence of tumor size on treatment outcomes. Methods A retrospective analysis was conducted on patients with recurrent low-grade NMIBC who underwent office-based diode transurethral laser ablation (TULA) under local anesthesia between 2021 and 2022. Results A total of 30 patients were included, with a mean age of 55 (±12) years. The mean original tumor size was 2.82 (±2.59) cm The mean recurrent tumor size was 1.15 (±0.88) cm, with a median of two recurrent tumors (range 1–20). The recurrence rate post-ablation for the entire cohort was 70%, with a median post-ablation recurrence duration of 5 months. The recurrence rate post-TULA was significantly higher in patients with an ablated tumor size of more than 1 cm compared to those with a tumor size of less than 1 cm (86.6% vs. 53.3%, p = 0.046). None of the patients experienced tumor progression, with a median follow-up duration of 12 months. Patients tolerated the procedure well, reporting only mild pain, and there were no complications greater than grade 1 on the Clavien-Dindo classification. Conclusion Office-based diode laser ablation is a safe, effective, and well-tolerated alternative for treating recurrent low-grade NMIBC with a low volume, less than 1 cm, under local anesthesia.

Establishment of advanced tumor organoids with emerging innovative technologies

Tumor organoids have emerged as a crucial preclinical model for multiple cancer research. Their high establishment rates, stability, and ability to replicate key biological features of original tumor cells in vivo render them invaluable for exploring tumor molecular mechanisms, discovering potential anti-tumor drugs, and predicting clinical drug efficacy. Here, we review the establishment of tumor organoid models and provide an extensive overview of organoid culturing strategies. We also emphasize the significance of integrating cellular components of the tumor microenvironment and physicochemical factors in the organoid culturing system, highlighting the importance of artificial intelligence technology in advancing organoid construction. Moreover, we summarize recent advancements in utilizing organoid systems for novel anti-cancer drug screening and discuss promising trends for enhancing advanced organoids in next-generation disease modeling.

Immunohistochemical expression of SATB2 and PAX8 in differentiating primary from metastatic ovarian mucinous neoplasms.

Accurate stratification of an ovarian mucinous neoplasm as primary or secondary is always challenging as they show overlapping histomorphological and immunohistochemical features. Immunohistochemical staining for SATB2 and PAX8 was performed on 80 cases of mucinous ovarian neoplasms subdivided into 53 primary [25 primary ovarian mucinous carcinomas (POMCs) and 28 mucinous borderline tumors (MBTs)] and 27 secondary (12 of colonic origin, 7 of appendiceal origin, and 8 of gastric origin). Expression was correlated with different clinicopathologic parameters. PAX8-positive immunostaining was detected in 38 out of 53 cases (71.69%) of primary ovarian mucinous neoplasms (POMNs) with null positivity in the secondary ovarian mucinous tumors (0/27). SATB2-positive expression was detected in 16 out of 27 cases (59.26%) of the secondary ovarian mucinous tumors. None of the studied POMNs showed any positive immunostaining for SATB2 (0/53). A profile of SATB2-/PAX8+ and SATB2+/PAX8- can be used to differentiate POMNCs from secondary ovarian mucinous tumors of GI origin, respectively, with 100% specificity. PAX8 expression is associated with some clinicopathologic parameters providing the basis for the possible usage of PAX8 as prognostic marker.

Metastatic GIST with a TWIST of RCC: A case report

Gastrointestinal Stromal Tumors (GIST) is a tumor of mesenchymal origin in the digestive tract, arising from Interstitial cells of Cajal. Majorly, they are an incidental finding in people of older age group (&amp;#62;60 years) with very rare bone metastasis. Our aim is to understand the role of genetic mutations in metastasis of GIST and coexistence of other malignancy in the same patient. We present an unusual case of a 75-year-old male with jejunal GIST, managed with resection of the tumor and imatinib, who 15 years later presented with subsequent liver, rare femoral head metastases and coexisting Renal Cell Carcinoma in left kidney. GIST cases can be associated with different syndromes and malignancies. This necessitates additional work up and long term follow up.

Composite hemangioendothelioma of breast: A case report with review of literature

Composite hemangioendothelioma (CHE) is an intermediate grade neoplastic tumor of vascular origin. It consists of a varied mixture of benign, intermediate and malignantvascular components. Only few cases of CHE occurring in different soft tissue areas of the body and rarely in internal organs have been reported in literature till now. We report a case of CHE presenting as lump in the breast in a 42 year old female. A review of literature is also presented to create awareness of this entity which can be misleading in breast where angiosarcoma is also known to occur.

TOTEM: a multi-cancer detection and localization approach using circulating tumor DNA methylation markers

BackgroundDetection of cancer and identification of tumor origin at an early stage improve the survival and prognosis of patients. Herein, we proposed a plasma cfDNA-based approach called TOTEM to detect and trace the cancer signal origin (CSO) through methylation markers.MethodsWe performed enzymatic conversion-based targeted methylation sequencing on plasma cfDNA samples collected from a clinical cohort of 500 healthy controls and 733 cancer patients with seven types of cancer (breast, colorectum, esophagus, stomach, liver, lung, and pancreas) and randomly divided these samples into a training cohort and a testing cohort. An independent validation cohort of 143 healthy controls, 79 liver cancer patients and 100 stomach cancer patients were recruited to validate the generalizability of our approach.ResultsA total of 57 multi-cancer diagnostic markers and 873 CSO markers were selected for model development. The binary diagnostic model achieved an area under the curve (AUC) of 0.907, 0.908 and 0.868 in the training, testing and independent validation cohorts, respectively. With a training specificity of 98%, the specificities in the testing and independent validation cohorts were 100% and 98.6%, respectively. Overall sensitivity across all cancer stages was 65.5%, 67.3% and 55.9% in the training, testing and independent validation cohorts, respectively. Early-stage (I and II) sensitivity was 50.3% and 45.7% in the training and testing cohorts, respectively. For cancer patients correctly identified by the binary classifier, the top 1 and top 2 CSO accuracies were 77.7% and 86.5% in the testing cohort (n = 148) and 76.0% and 84.0% in the independent validation cohort (n = 100). Notably, performance was maintained with only 21 diagnostic and 214 CSO markers, achieving a training AUC of 0.865, a testing AUC of 0.866, and an integrated top 2 accuracy of 83.1% in the testing cohort.ConclusionsTOTEM demonstrates promising potential for accurate multi-cancer detection and localization by profiling plasma methylation markers. The real-world clinical performance of our approach needs to be investigated in a much larger prospective cohort.

Clinical features and prognosis of conjunctival melanoma in Japanese patients.

To evaluate the clinical features and prognosis of conjunctival melanoma in Japanese patients. Retrospective observational case series. Twenty patients (8 men and 12 women) diagnosed with conjunctival melanoma at a singlehospital between 2003 and 2017 were analyzed. Data on clinical presentation, sex, age, the affected eye, tumor location, tumor origin, tumor stage according to the American Joint Committee on Cancer staging system (eighth edition), treatment, outcomes, local recurrence, metastasis, and survival were extracted from the patients' medical records and reviewed. The mean age at diagnosis was 64.2 ± 14.8 years. Tumor locations at the first examination included the bulbar conjunctiva (n = 19), plica (n = 13), and fornix (n = 12). The tumor stage was T1 in 5 cases (25%), T2 in 12 cases (60%), T3 in 3 cases (15%), and T4 in none. The mean follow-up duration was 91.7 ± 46.0 months. The local recurrence rates at 1, 5, and 10 years were 5.0%, 18.8%, and 31.5%, respectively, whilst the metastasis rates were 5.0%, 25.6%, and 32.4%, respectively. Four of the 6 patients who experienced metastasis died; duration from metastasis to death was 17.5 months (range, 7-25). The 5-year survival rate for conjunctival melanoma was 78.8%. Tumor thickness was significantly associated with survival duration on univariate Cox regression analyses. The mortality rate for conjunctival melanoma in the Japanese population was lower and higher than that reported in the Chinese and United States populations, respectively. Tumor thickness was a prognostic factor for survival in patients with conjunctival melanoma.

In Vivo Mouse Models for Adult Brain Tumors: Exploring Tumorigenesis and Advancing Immunotherapy Development.

Brain tumors, particularly glioblastoma (GBM), are devastating and challenging to treat, with a low 5-year survival rate of only 6.6%. Mouse models are established to understand tumorigenesis and develop new therapeutic strategies. Large-scale genomic studies have facilitated the identification of genetic alterations driving human brain tumor development and progression. Genetically engineered mouse models (GEMMs) with clinically relevant genetic alterations are widely used to investigate tumor origin. Additionally, syngeneic implantation models, utilizing cell lines derived from GEMMs or other sources, are popular for their consistent and relatively short latency period, addressing various brain cancer research questions. In recent years, the success of immunotherapy in specific cancer types has led to a surge in cancer immunology-related research which specifically necessitates the utilization of immunocompetent mouse models. In this review, we provide a comprehensive summary of GEMMs and syngeneic mouse models for adult brain tumors, emphasizing key features such as model origin, genetic alteration background, oncogenic mechanisms, and immune-related characteristics. Our review serves as a valuable resource for the brain tumor research community, aiding in the selection of appropriate models to study cancer immunology.