High-grade Tumors Research Articles

Oncological outcomes of organ-sparing cystectomy versus standard radical cystectomy in male patients diagnosed with bladder cancer.

To compare the oncological outcomes between standard radical cystectomy (SRC) and organ-sparing cystectomy (OSC) in male patients diagnosed with bladder cancer. Patients with stage Ta-T3 bladder cancer who underwent OSC or SRC were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The association between preoperative factors and the implementation of OSC was analyzed using logistic regression. Propensity score matching (PSM) was employed to balance baseline characteristics between the two groups. Patients' overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Subgroup analyses based on the T stage were also conducted. A total of 7264 patients were included, with 96.8% (7033 patients) receiving SRC and 3.2% (231 patients) receiving OSC. Patients with higher T stages and high-grade tumors were less likely to undergo OSC. After PSM, OSC was associated with significantly worse OS and CSS than SRC. Subgroup analysis revealed that OSC did not lead to worse OS and CSS in non-muscle invasive bladder cancer and T2 stage patients, but it resulted in significantly worse outcomes in T3 stage patients. Our study indicates that OSC is associated with poorer oncological outcomes compared to SRC, particularly in patients with advanced-stage tumors. These findings suggest the need for stringent selection criteria for OSC in bladder cancer patients. Given the negative impact on prognosis, stage T3 should potentially be considered a contraindication for OSC. Further evidence is required to confirm these assertions.

Growth velocity of fetal sacrococcygeal teratoma as predictor of perinatal morbidity and mortality: multicenter study.

To identify prenatal predictors of poor perinatal outcome in fetuses with isolated sacrococcygeal teratoma (SCT). This was a retrospective study of fetuses with isolated (non-syndromic) SCT managed at one of five pediatric surgery and/or fetal medicine centers between January 2007 and December 2017. The primary outcome was the occurrence of poor perinatal outcome, defined as prenatal death (including termination), or neonatal death or severe compromise (hemorrhagic shock). Data regarding prenatal diagnosis (sonographic features both at referral and at the last ultrasound examination before pregnancy outcome, assessment of SCT growth velocity), perinatal complications and outcome, and neonatal course were analyzed to determine prenatal SCT characteristics associated with adverse perinatal outcome. Fifty-five fetuses were included, diagnosed with isolated SCT at a median gestational age of 22 (interquartile range, 18-23) weeks. There was a poor perinatal outcome in 31% (n = 17) of these cases, including intrauterine fetal demise (4%, n = 2), pregnancy termination (13%, n = 7) and neonatal severe compromise (15%, n = 8), leading to neonatal death in five cases. The overall survival rate after prenatal diagnosis of isolated SCT was 75% (n = 41 of 55). Earlier gestational age at diagnosis (P = 0.02), large tumor volume at referral (P < 0.001), presence of one or more hemodynamic complications (P = 0.02), fast tumor growth velocity (P < 0.001) and high tumor grade (highest tumor grade ≥ 3) (P = 0.049) were associated with poor perinatal outcome on univariate analysis. On stepwise logistic regression analysis, tumor growth velocity was the only remaining independent factor associated with poor perinatal outcome (odds ratio (OR) (per 1-mm/week increase), 1.48 (95%CI, 1.22-1.97), P = 0.001). The best predictive cut-off of tumor growth velocity for poor perinatal outcome was 7 mm/week (OR, 25.7 (95%CI, 5.6-191.3), P < 0.001), yielding a sensitivity of 88% and a specificity of 77%. Approximately 30% of fetuses with a diagnosis of isolated SCT have poor perinatal outcome. Tumor growth velocity ≥ 7 mm/week appears to be an appropriate discriminative cut-off for poor perinatal outcome. These results could help to inform prenatal management and counseling of parents with an affected pregnancy. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The association between non-HDL cholesterol and high-grade pancreatic neuroendocrine neoplasms.

High-density lipoprotein cholesterol (HDL-c) plays an important role in tumorigenesis in several endocrine-related cancers. Few studies have shown the effect of non-HDL-c in malignant tumors. The present study aimed to identify the association between non-HDL-c and high-grade pancreatic neuroendocrine neoplasms (PNENs). A total of 197 PNEN patients who underwent surgery were analyzed retrospectively. Clinical and histopathological features, such as patients' age and sex, tumor location and size, tumor grade, the level of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and fasting plasma-glucose levels were obtained. Non-HDL-c was calculated as total cholesterol - HDL-c. The relationships between those features and high-grade PNENs were identified using logistic regression analysis. Among the 197 patients with PNENs, a lower HDL-c level was more common seen in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.05). The non-HDL-c/HDL-c ratio was greater in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.01). Similarly, a greater proportion of patients with a non-HDL-c/HDL-c ratio larger than 5 was found in patients with poorly differentiated PNENs than in those with well-differentiation PNENs (P < 0.01). Multivariate logistic analysis showed that the non-HDL-c/HDL-c ratio was positively associated with poorly differentiated PNENs (odds ratio (OR) = 1.45, 95% conference interval (CI):1.13-1.87). Similarly, the risk of poorly differentiated PNENs increased significantly in patients with a non-HDL-c/HDL-c greater than 5 (OR = 14.13, 95%CI: 2.98-66.89). The risk of high-grade PNENs increased in patients with a high non-HDL-c/HDL-c ratio (OR = 1.27, 95% CI: 1.04-1.55), and the risk also increased markedly when the ratio was greater than 5 (OR = 5.00, 95%CI: 1.28-19.49). A high ratio of non-HDL-c/HDL-c was associated with high-grade PNENs or poorly differentiated PNENs.

ZNF143-mediated upregulation of MEX3C promotes hepatocellular carcinoma progression.

Microvascular invasion is strongly associated with aggressive tumor behavior and recurrence in hepatocellular carcinoma (HCC) patients. Zinc finger protein 143(ZNF143) is a transcription factor involved in a wide variety of physiological and developmental processes. This study primarily focuses on the exact biological role and mechanism of ZNF143 in HCC migration and invasion. The expression and prognosis of ZNF143 in HCC patients were analyzed. The levels of ZNF143, mex-3 RNA binding family member C (MEX3C) were quantified by western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell migration ability was detected by wound- healing assay. Matrigel transwell assay was conducted to evaluate the invasion of HCC cells. The differential expression genes of ZNF143 overexpression and knockdown were screened by mRNA profiling analysis. Dual luciferase assay was performed to determine the promoter activity of MEX3C. The enrichment of ZNF143 at MEX3C promoter was determined by chromatin immunoprecipitation (ChIP). ZNF143 is overexpressed in HCC tissues and that its overexpression is correlated with poorer prognosis, especially in HCC patients with higher tumor grades and microvascular invasion. Gain- and loss-of function experiments showed that ZNF143 promotes migration and invasion in HCC cells. mRNA profiling showed that ZNF143 significantly upregulates MEX3C. ZNF143 was positively correlated with MEX3C expression in HCC tissue. ZNF143 activates MEX3C transcription by directly binding to its promoter. MEX3C knockdown inhibited migration and invasion induced by ZNF143 overexpression in HCC cells. ZNF143 promotes HCC cell migration and invasion by binding to MEX3C promoter and activating its expression.

Preliminary evaluation of FAPI-04-PET/CT for differentiating recurrence and post-treatment changes in high-grade gliomas

Fibroblast-activated protein (FAP) expression in glial cells is attributed to FAP-positive foci on tumor vessels and neoplastic cells. Preclinical and pilot studies have shown FAP expression in high-grade gliomas. We aimed at comparing PET imaging with FAP-inhibitor (FAPI-PET) with current standard, i.e., fluoro-ethyl tyrosine (FET) PET in post-treatment setting to differentiate recurrence and post-treatment changes. 6 patients with WHO Grade III and IV glioma who received standard treatment underwent Ga-68-FAPI-04 PET/CT (FAPI-PET/CT). Tracer uptake greater than background was considered positive. FET PET was performed and interpreted as per institutional standards, which formed the basis of treatment decision. There was concordance between FAPI expression and FET uptake in 5 patients suggestive of disease recurrence. There was no FAPI expression seen in 1 patient, in whom FET PET was suggestive of post-treatment changes. FAPI PET uptake correlated with amino acid expression to differentiate post treatment changes from recurrence in high-grade glial tumors; further validation with prospective study and histopathological confirmation is needed.

Long-term trends analysis of the incidence and mortality in patients with ovarian cancer: a large sample study based on SEER database.

To analyze long-term trends of the incidence and mortality of ovarian cancer in the United States. Patients diagnosed with ovarian cancer were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2017. Joinpoint regression analysis was used to analyze the incidence and mortality trend, and the changes were reported as average annual percentage change (AAPC) with a 95% confidence interval (CI). Kaplan-Meier survival curve and Cox regression analyses were utilized for survival analysis. A total of 74 682 patients were included, among whom 49 491 (66.27%) died and 44 487 (59.57%) died from ovarian cancer. The mean age was 61.95 ± 15.23years. The incidence of ovarian cancer showed a decreased trend from 2000 to 2017 with an AAPC of -1.9 (95%CI: -2.0, -1.7). Both the overall mortality and cancer-specific mortality for ovarian cancer decreased from 2000 to 2017, with AAPCs of -5.0 (95%CI: -5.7, -4.2) and -4.6 (95%CI: -5.4, -3.8), respectively. There was a significant decrease in the incidence and mortality of patients with the distant SEER stage, histological subtypes of serous and malignant Brenner carcinoma, and grades II and III from 2000 to 2017. Older age, Black race, histological subtypes of carcinosarcoma, higher tumor grade, and radiotherapy were associated with poorer overall survival and cancer-specific survival, whereas higher income, histological subtype of endometrioid, and surgery were associated with better survival. This study provided evidence of a statistically significant decrease in the incidence and mortality of ovarian cancer from 2000 to 2017. Key message What is already known on this topic? Ovarian cancer is one of the most common tumors in women, with high morbidity and mortality. However, trends in long-term morbidity and mortality of patients with ovarian cancer have not been reported. What this study adds Overall incidence and mortality for ovarian cancer showed a decreased trend from 2000 to 2017, and trends in incidence and mortality varied by stage, histological subtype, and tumor grade. Factors associated with overall survival and cancer-specific survival also differ. How this study might affect research, practice, or police This study provides evidence of long-term trends in ovarian cancer incidence and mortality from 2000 to 2017.

Utility and Safety of 5-ALA Guided Surgery in Pediatric Brain Tumors: A Systematic Review

Background: 5-Aminolevulinic acid-guided surgery for adult gliomas has been approved by the European Medicines Agency and the US Food and Drug Administration, becoming a reliable tool for improving gross total resection rates and patient outcomes. This has led several medical centers to explore the off-label use of 5-ALA in the resection of pediatric brain tumors, assessing its efficacy and safety across various tumor types. However, given the differences between children and adults, the appropriateness of 5-ALA use in pediatric populations has not yet been fully established. Methods: We collected eligible publications from Embase, Scopus, PubMed, and Proquest, ultimately selecting 27 studies. Data extraction and retrospective analysis of 249 surgical cases were conducted to determine the current efficacy and safety of 5-ALA in pediatric brain tumors. The fluorescence rate and utility stratified by several clinical features, including WHO grade, tumor classification, and tumor location, were analyzed. Results: Most studies suggest that 5-ALA can enhance tumor identification in high-grade tumors, including glioblastomas and anaplastic astrocytomas. Changes in survival or recurrence rates associated with 5-ALA-guided resection have not been reported. None of the cases reported significant postoperative complications related to the use of 5-ALA. Conclusions: 5-ALA can aid in the resection of high-grade gliomas in pediatric patients. The efficacy of 5-ALA in low-grade gliomas and other tumors may require enhancement with additional tools or modified administration protocols. The safety of 5-ALA has reached a preliminary consensus, although further randomized controlled trials and data on survival and molecular characteristics are needed.

18F]FDG and [68Ga]Ga-FAPI-04-Directed Imaging for Outcome Prediction in Patients with High-Grade Neuroendocrine Neoplasms.

We aimed to quantitatively investigate the prognostic value of PET-based biomarkers on [18F]FDG and [68Ga]Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in patients with highly aggressive neuroendocrine neoplasms (NENs) and to compare the visually assessed differences in uptake on both examinations with progression-free survival (PFS). Methods: In this single-center retrospective analysis, 20 patients with high-grade NENs had undergone [18F]FDG and [68Ga]Ga-FAPI-04 PET. Both PET scans were visually compared, and the presence of [18F]FDG-positive, [68Ga]Ga-FAPI-04-negative (FDG+/FAPI-) lesions was noted. In addition, we assessed maximum, peak, and mean SUV; tumor volume (TV); and total lesion uptake (TLU = TV × SUVmean) for both radiotracers using a 40% lesion-based threshold. The results of quantitative and visual analysis were correlated with PFS using log-rank analysis or univariate Cox regression. PFS was defined radiographically using RECIST 1.1., clinically using signs of disease progression, or as death. Results: Most primary tumors were located in the gastrointestinal tract (13/20 patients, 65%) or were cancer of unknown primary (5/20 patients, 25%). FDG+/FAPI- lesions were found in 9 of 20 patients (45%). Patients with FDG+/FAPI- lesions had a significantly decreased PFS of 4 mo, compared with 9 mo for patients without FDG+/FAPI- metastases (P = 0.0063 [log-rank test]; hazard ratio [HR], 5.637; 95% CI 1.619-26.16; P = 0.0110 [univariate Cox regression]). On univariate analysis, a significant correlation was also found between PFS and TV for both radiotracers ([18F]FDG: mean TV, 258 ± 588 cm3; HR, 1.024 [per 10 cm3]; 95% CI, 1.007-1.046; P = 0.0204) ([68Ga]Ga-FAPI-04: mean TV, 130 ± 192 cm3; HR, 1.032 [per 10 cm3]; 95% CI, 1.001-1.062; P = 0.0277) and TLU on [18F]FDG PET (mean TLU, 1,931 ± 4,248 cm3; HR, 1.004 [per 10 cm3]; 95% CI, 1.001-1.007; P = 0.0135). Conclusion: The presence of discordant FDG+/FAPI- lesions is associated with a significantly shorter PFS, which might indicate more aggressive disease prone to early progression. Dual-tracer PET/CT of patients with highly aggressive NENs could help guide treatment decisions or identify high-risk lesions for additional local therapeutic approaches.

Bilateral Somatically Derived Germ Cell Tumors With 12p Gains Arising in High-grade Serous Carcinomas of the Ovary: A Case Report and Review of the Literature.

Epithelial ovarian neoplasms are commonly observed in older patients, while germ cell tumors (GCTs) typically present in young individuals. When GCTs are detected in patients over 35yrs old, they often have an associated epithelial component, a phenomenon known as somatically derived GCTs. We report a unique case of mixed GCT involving bilateral ovaries with a background of high-grade serous carcinoma, including a yolk sac tumor and choriocarcinoma in the mixed GCT component. Somatically derived GCTs are rare with only 45 cases of ovarian carcinoma with somatic yolk sac tumor reported to date. Pathologists face diagnostic challenges in identifying somatically derived GCTs, as they can mimic high-grade epithelial neoplasms. Somatically derived GCTs have poor outcomes, therefore, precise diagnosis is crucial for prognostic and therapeutic considerations.

Giant Appendiceal Mucocele with High Grade Mucinous Neoplasm—Case Report and Review of the Literature

Appendiceal mucocele is a rare entity first described by Carl von Rokitansky, characterized by cystic dilatation of the appendiceal lumen due to obstruction, epithelial proliferation or inflammation and accumulation of mucoid material. The cause can be either neoplastic or non-neoplastic. Patients with appendiceal mucocele can be asymptomatic or present with right lower quadrant pain which may mimic acute appendicitis. We present the case of a 68-year-old male, who presented to the Emergency Room with a two-day history of right lower quadrant pain, nausea, vomiting and loss of appetite. Abdominal examination revealed tenderness over the Mc Burney point with localized guarding and laboratory results showed leukocytosis with neutrophilia. The abdominal computed tomography revealed a cystic dilated appendix, with a length of 130 mm and a diameter of 75 mm, situated ascending retrocecal and associating peri-appendicular inflammatory changes. The patient underwent right hemicolectomy with side-to-side ileo-colonic anastomosis, due to a wide intraluminal communication between the appendix and the cecum and the inflammation of both structures. Histopathological examination showed both high-grade and low-grade appendiceal mucinous neoplasm.

Oncogenic role of lncRNA SBF2-AS1 in bladder cancer.

Bladder cancer is a malignant neoplasm with increasing incidence rates. LncRNAs play an important role in cancer, including development, prognosis, and response to therapies. It is known that lncRNA SBF2-AS1 was associated with cell proliferation and worse prognosis in various tumor types, but its role remains incompletely understood in bladder cancer. In this context, our objective was to evaluate the effect of lncRNA SBF2-AS1 silencing on bladder cancer cells. J82 and UM-UC-3 high-grade bladder tumor cells were treated with two siRNAs specific for SBF2-AS1 to evaluate cytotoxicity, clonogenic survival, morphology, cell migration, and cell cycle progression. Expression inhibition of SBF2-AS1 resulted in cytotoxicity, morphological changes, and decreased clone formation and cell migration. Cell cycle alterations were not observed. Our study revealed that SBF2-AS1 plays an oncogenic role and holds promise as a potential target for the treatment of bladder cancer.

Long-term recurrence risk, metastatic potential and length of cystoscopic surveillance of low-grade non-muscle invasive bladder cancer.

Patients with Ta low-grade (LG) non-muscle invasive bladder cancer (NMIBC) rarely develop metastases or die from it. Long-term data are scant and length of follow-up poorly defined. This retrospective study included 521 patients diagnosed with primary TaLG (n=491) or papillary urothelial neoplasm of low malignant potential (PUNLMP, n=30) from 1989-2019 at an Academic center. Patient data was acquired using patient records chart review and a bladder cancer informatics registry at the center. Risk of recurrence, progression in stage, to muscle invasion, metastases and death due to BC were analyzed. RNAseq assessed the transcriptomic profiles of four TaLG that metastasized. Interobserver variability in pathological grading (WHO 2004/2022 and 1973, n=80) was blindly assessed by three expert pathologists. Median follow-up was 9.6 (95%CI: 8.6-10.2) years. Among 521 patients (73% men, median age 67.0 years), 350 recurred, 57 progressed in stage, 20 developed metastases, and 15 died from BC (median of 9.6 years after diagnosis). Cancer-specific survival probabilities were 0.99, 0.98 and 0.96 at 5-, 10- and 15- years, respectively. Fifty patients who were recurrence-free for the first 5 years developed late recurrences and 2 of them died of BC. Metastatic TaLG had more adverse transcriptomic findings in keeping with higher grade tumors despite phenotypically similar to indolent tumors. Grading concordance for the 2004/2022 system and WHO 1973 was 0.78 (95%CI: 0.65-0.90) and 0.41 (95%CI: 0.32-0.50), respectively. This study with long-term data challenges the assumption that primary TaLG NMIBC nearly never progresses to lethal disease if followed long enough. However, the risk of BC-related mortality is extremely low in patients who are recurrence-free for the first 5 years. Minimizing variability in pathological grading remains an unmet need.

Survival benefit added by adjuvant chemotherapy in adenoid cystic carcinoma of salivary gland

The aim of this study was to investigate the potential survival advantages associated with chemoradiotherapy (CRT) compared to radiotherapy (RT) as standalone modalities in the treatment of adenoid cystic carcinoma (ACC) of the salivary glands. Patients diagnosed with resected salivary gland ACC were retrospectively enrolled and categorized into two groups based on the type of adjuvant therapy received. The overall survival outcomes between the CRT and RT cohorts were evaluated using a multivariable Cox model. Post propensity score-matching, a total of 114 patients (57 in each treatment group) were included in the analysis. In the general patient population, CRT did not confer an additional survival benefit compared to RT alone. High-grade tumors, positive surgical margins, and the presence of five or more positive lymph nodes were identified as independent prognostic factors associated with poorer overall survival. Specifically, for patients with positive surgical margins, CRT was significantly associated with improved overall survival relative to RT, displaying a hazard ratio of 0.93 (95% CI: 0.81–0.99). Furthermore, in patients with more than four metastatic lymph nodes, CRT significantly reduced the risk of mortality by 6% (95% CI: 1-24%) when compared to RT alone. Conversely, in patients with high-grade tumors, the addition of adjuvant chemotherapy to RT did not yield significant alterations in survival outcomes compared to RT alone (p = 0.437, HR: 0.95, 95% CI: 0.75–2.07). CRT may offer an overall survival benefit for patients with salivary gland ACC, particularly those characterized by positive margin or the presence of five or more metastatic lymph nodes.

Clinical and Pathological Characteristics of Bladder Cancer in Patients Aged 18–45 Undergoing Transurethral Resection of Bladder Tumor

Background and Objectives: Bladder cancer in patients under 45 is poorly characterized and rarely described, with variabilities in clinical outcomes and tumor properties. Our study aimed to elucidate the clinical and pathological features and outcomes of bladder cancer in this younger demographic to better inform management strategies. Materials and Methods: We conducted a retrospective analysis at the Urology Department of “Pius Brînzeu” County Emergency Clinical Hospital in Timișoara, Romania, on 60 patients aged 18–45 who underwent transurethral resection of bladder tumor (TURBT) during a 9-year period. Results: The cohort had a mean age of 38.5 ± 5.6 years with a male predominance (70%). Most tumors were non-muscle-invasive (NMIBC; 80%), with 16.7% being papillary urothelial neoplasms of low malignant potential (PUNLMP), 50% stage pTa, and 30% stage pT1. High-grade tumors were present in 43.3% of the patients. Recurrence occurred in 40% of the patients, while progression was observed in 16.7%. The 3-year overall survival rate was 93.3%, and the progression-free survival rate was 83.3%. Patients with high-grade tumors had a significantly higher recurrence rate (61.5% vs. 23.5%, p = 0.003) and lower survival rates compared to those with low-grade tumors. Conclusions: Young patients predominantly present with low-to-intermediate-stage tumors, yet a significant portion exhibit high-grade tumors associated with poorer outcomes. These findings suggest that while bladder cancer in younger patients tends to be less invasive, aggressive follow-up and treatment are crucial in those with high-grade tumors.

Giant intracranial tuberculomas in children: An unexpected diagnosis and difficult management – About two cases and review of the literature

Background: Giant intracranial tuberculomas are rare space-occupying lesions in the brain parenchyma, with a diameter &gt;2.5 cm. They can mimic gliomas, meningiomas, and metastases. Diagnosis of this disease can be difficult without histological evidence. Tuberculosis (TB) affects people of all ages but is a major health problem among children. Misdiagnosis is common, as many clinical and radiological features are non-specific. Case Description: Case 1: A 4-year-old child presented with intracranial hypertensive syndrome and Brave– Jackson seizures. Imaging showed a left temporoparietal lesion with intense peripheral ring enhancement after gadolinium injection, and attaching to the dura mater. Total surgical excision was performed, and histological analysis confirmed granulomatous TB. A month later, he presented to the emergency department with neurological deterioration. Magnetic resonance imaging revealed disseminated TB of the central nervous system, with tuberculomas in the brain stem. The child died after a month in intensive care. Case 2: An 11-year-old boy presented with a headache that had been progressively worsening for 7 months. Imaging revealed a right frontal process mimicking a high-grade glial tumor. The child underwent surgery with total excision of the tumor. After a few days, he developed tubercular miliaria and was put on anti-bacillary treatment. Conclusion: Treatment includes antituberculosis therapy combined with surgery. This article describes the value of surgery for giant intracranial tuberculomas in two children under our care, with a review of the literature. We believe that the results of surgery for giant intracranial tuberculomas in children are favorable.

Transmanubrial osteomuscular sparing approach: different indications for non-pulmonary malignancies.

The transmanubrial osteomuscular sparing approach (TMA) is recommended for surgeries involving or originating from the thoracic outlet structures. We present a series of consecutive patients treated from 2014 to 2024 who underwent oncological thoracic outlet surgery for primary or metastatic (non-pulmonary) malignancies. Overall, 33 patients were included. Our procedures resulted in no mortality, seven complications (21.2%) and all surgeries achieved radical (R0) status. In the hands of experienced professionals, the TMA approach proves to be safe and conservative, enabling radical surgery for tumors of the thoracic outlet. For low-grade tumors, it avoids the need for additional combined surgical access, while for high-grade tumors, it allows for more extensive en bloc resection.

WRAD core perturbation impairs DNA replication fidelity promoting immunoediting in pancreatic cancer.

It is unclear how cells counteract the potentially harmful effects of uncoordinated DNA replication in the context of oncogenic stress. Here, we identify the WRAD (WDR5/RBBP5/ASH2L/DPY30) core as a modulator of DNA replication in pancreatic ductal adenocarcinoma (PDAC) models. Molecular analyses demonstrated that the WRAD core interacts with the replisome complex, with disruption of DPY30 resulting in DNA re-replication, DNA damage, and chromosomal instability (CIN) without affecting cancer cell proliferation. Consequently, in immunocompetent models, DPY30 loss induced T cell infiltration and immune-mediated clearance of highly proliferating cancer cells with complex karyotypes, thus improving anti-tumor efficacy upon anti-PD-1 treatment. In PDAC patients, DPY30 expression was associated with high tumor grade, worse prognosis, and limited response to immune checkpoint blockade. Together, our findings indicate that the WRAD core sustains genome stability and suggest that low intratumor DPY30 levels may identify PDAC patients who will benefit from immune checkpoint inhibitors.

Osteopontin is a therapeutic target that drives breast cancer recurrence

Recurrent breast cancers often develop resistance to standard-of-care therapies. Identifying targetable factors contributing to cancer recurrence remains the rate-limiting step in improving long-term outcomes. In this study, we identify tumor cell-derived osteopontin as an autocrine and paracrine driver of tumor recurrence. Osteopontin promotes tumor cell proliferation, recruits macrophages, and synergizes with IL-4 to further polarize them into a pro-tumorigenic state. Macrophage depletion and osteopontin inhibition decrease recurrent tumor growth. Furthermore, targeting osteopontin in primary tumor-bearing female mice prevents metastasis, permits T cell infiltration and activation, and improves anti-PD-1 immunotherapy response. Clinically, osteopontin expression is higher in recurrent metastatic tumors versus female patient-matched primary breast tumors. Osteopontin positively correlates with macrophage infiltration, increases with higher tumor grade, and its elevated pathway activity is associated with poor prognosis and long-term recurrence. Our findings suggest clinical implications and an alternative therapeutic strategy based on osteopontin’s multiaxial role in breast cancer progression and recurrence.

Management of the Uninvolved Uterus and Adnexa During Routine Pelvic Peritonectomy in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Varies by Histology and Menopausal Status: An International Survey of Peritoneal Surface Malignancy Surgeons.

No guidelines exist regarding the management of the uninvolved uterus or adnexa (fallopian tubes and/or ovaries) in patients with peritoneal metastases (PM) from non-gynecologic malignancies. It is unclear whether salpingo-oophorectomy, hysterectomy, or both should be performed when a complete pelvic peritonectomy is otherwise warranted. A 25-item electronic survey was sent to 225 surgeons worldwide who routinely perform cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). Participants were recruited through listservs of expert groups. Individual surgeon approaches to the management of the grossly uninvolved uterus and adnexa in pre- and post-menopausal women with PM from low- and high-grade appendiceal neoplasms, colorectal cancer, and peritoneal mesothelioma were collected using a 5-point Likert scale. A total of 135 complete responses (60% response rate) were obtained from surgeons practicing in 27 countries. Respondents reported a median practice of 10 years (interquartile range [IQR] 6-15 years) and a median performance of 20 (IQR 12-30) CRS/HIPEC operations per year. Rates of salpingo-oophorectomy differed by histology and a woman's menopausal status, ranging from 29 to 42% in pre-menopausal women to 71-77% in post-menopausal women (P < 0.001). Notably, the number of surgeons who would perform a hysterectomy was lower, ranging from 12 to 27% for pre-menopausal women and from 32 to 44% for post-menopausal women, dependent on histology (P < 0.001). Surgeons are overall more aggressive with adnexal resection than with hysterectomy in both pre- and post-menopausal women with PM from non-gynecologic malignancies. Further prospective studies are required to determine the best approach to optimize surgical and oncologic outcomes while also accounting for the fertility and hormonal impact.

CIC/ATXN1-rearranged tumors in the central nervous system are mainly represented by sarcomas: A comprehensive clinicopathological and epigenetic series.

CIC fusions have been described in two different central nervous system (CNS) tumor entities. On one hand, fusions of CIC or ATXN1 genes belonging to the same complex of transcriptional repressors, were reported in the CIC-rearranged, sarcoma (SARC-CIC). The diagnosis of this tumor type, which was recently added to the World Health Organization (WHO) Classification of CNS tumors, is difficult mainly because the data concerning its histopathology (as compared to its soft tissue counterpart), immunoprofile, and clinical as well as radiological characteristics are scarce in the literature. On the other hand, a recent study, based on DNA-methylation profiling, has identified a novel high-grade neuroepithelial tumor characterized by recurrent CIC fusions (HGNET-CIC). The aim of this multicentric study was to characterize a cohort of 15 primary CNS tumors harboring a CIC or ATXN1 fusion in terms of clinical, radiological, histopathological, immunophenotypical, and epigenetic characteristics. According to the integrated diagnoses, 14/15 tumors corresponded to SARC-CIC, and only one to HGNET-CIC. The tumors showed similar clinical (mainly pediatric), radiological (mostly supratentorial, cystic, and contrast enhancing), immunophenotypical (common expression of glioneuronal markers), and genetic (similar spectrum of fusions) profiles but their histopathological appearance was clearly distinct. Moreover, we found a novel fusion transcript (CIC::EWSR1) in a SARC-CIC. Most DNA methylation profiles using the Heidelberg Brain Tumor Classifier (v12.8) annotated the samples to the methylation class "SARC-CIC" (9/14 tumors with available data). By using uniform manifold approximation and projection analysis, four other samples were classified as SARC-CIC and another clustered within the methylation class of HGNET-CIC. Our findings confirm that CNS CIC-fused tumors do not represent a single molecular tumor entity. Further analyses are needed to characterize HGNET-CIC in more detail. These results may help to refine the essential diagnostic criteria for SARC-CIC and their terminology (with a suggested consensual name of sarcoma, CIC/ATXN1-complex rearranged).