Tumor Size Research Articles

Association Between Phosphorylated AXL Expression and Survival in Patients with Gastric Cancer

Background: Gastric cancer (GC) is a leading cause of cancer-related mortality, particularly in East Asia. Despite treatment advances, the prognosis remains poor owing to late diagnosis and high metastatic potential. Phosphorylated AXL (pAXL), a receptor tyrosine kinase, promotes cancer progression, including epithelial–mesenchymal transition (EMT), tumor growth, and metastasis. In this study, we aimed to investigate the relationship between pAXL expression and prognosis in patients with GC, focusing on survival outcomes and other biomarkers such as fibronectin and phosphorylated AKT (pAkt). Methods: Immunohistochemistry was performed to assess the expression of pAXL, fibronectin, and pAkt in 188 GC specimens collected between 2000 and 2013. H-scores were calculated based on staining intensity and percentage. The association between pAXL expression and patient outcomes was assessed using Kaplan–Meier survival analysis and multivariate logistic regression. Results: Higher pAXL expression was significantly associated with improved survival, particularly in male patients. pAXL expression positively correlated with fibronectin and pAkt upregulation, suggesting its role in promoting tumor invasion and EMT. Multivariate analysis identified pAXL, fibronectin, and pAkt as significant prognostic indicators, whereas other factors such as age, tumor grade, and tumor size were not statistically significant. Conclusions: This study identified pAXL as a valuable prognostic marker in GC, with higher expression levels associated with better survival outcomes, particularly in male patients. pAXL enhanced the invasive potential of GC cells through fibronectin and pAkt regulation, making it a promising therapeutic target. Further research is needed to explore the potential of pAXL-targeted therapies and better understand their role in cancer progression and treatment response.

Quantitative Assessment of Collagen Architecture to Determine Role of Tumor Stroma During Vestibular Schwannoma Progression.

The primary objective was to characterize the abundance and architecture of collagen in the extracellular matrix in vestibular schwannoma (VS). The secondary objective was to investigate the association between collagen architecture and tumor size. Retrospective cohort study. Academic referral center. Tumor samples were obtained from patients with sporadic VS undergoing microsurgical resection. Histological analyses were performed including picrosirius red (PSR) staining under polarized light. Collagen architecture was quantified using an automated fiber detection software. Second Harmonic Generation (SHG) microscopy and immunofluorescence (IF) were utilized to characterize collagen architecture. Eleven tumor specimens were included (mean tumor diameter = 2.80 cm, range 1.5-4.0 cm), and were divided into large (mean diameter = 3.5 ± 0.4 cm) and small (mean tumor diameter = 2.0 ± 0.4 cm) cohorts based on size. The large VS cohort showed significantly higher collagen density (27.65% vs 12.73%, P = .0043), with more thick fibers (mature Type I, 24.54% vs 12.97%, P = .0022) and thin fibers (immature Type I or mature Type III, 23.55% vs 12.27%, P = .026). Tumor volume correlated with greater degree of collagen fiber disorganization (P = .0413, r2 = 0.298). Specifically, collagen type I intensity was significantly higher in large VS compared to small tumors (P < .001) and peripheral nerve (P = .028). Larger VS exhibit increased collagen abundance in the tumor stroma, and a more disorganized collagen architecture compared to smaller VS and normal peripheral nerve tissue. This finding indicates that collagen organization may play a significant role in extracellular matrix remodeling and the progression of VS.

Diagnostic value of the flare sign in predicting extracapsular extension in metastatic axillary lymph nodes and nodal status on breast magnetic resonance imaging.

This study aimed to evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in predicting extracapsular extension (ECE) and axillary nodal status in the axillary metastatic lymph nodes of patients with breast cancer. The preoperative MRI scans of 92 patients with breast cancer and axillary metastases who did not receive neoadjuvant treatment between January 2018 and January 2024 were retrospectively examined. The presence of an increased signal in the axillary fatty tissue surrounding the lymph node (flare sign) on T2-weighted images, irregular nodal contour (shaggy margin), axillary asymmetry (difference in the number and size of lymph nodes compared with the unaffected axilla), loss of the fatty hilum in the most suspicious lymph node, and morphological features on T1-weighted images were assessed. Each dissected axillary lymph node was examined for ECE, and the histopathological results were recorded. Axillary flare sign was significantly associated with the presence of ECE (P < 0.001), number of lymph nodes with ECE (P < 0.001), the presence of ≥4 axillary metastatic lymph nodes (P < 0.001), size of the primary tumor (P = 0.033), lymphovascular invasion in the primary tumor (P < 0.001), and presence of perineural invasion (P = 0.001). The flare sign exhibited 65.7% sensitivity, 96% specificity, 97.8% positive predictive value, 51.1% negative predictive value, and 73.9% accuracy in predicting ECE. Additionally, the receiver operating characteristic curve analysis revealed an area under the curve of 0.808 (95% confidence interval: 0.719-0.898). The flare sign has high performance in predicting ECE and axillary nodal status and is associated with primary tumor aggressiveness, indicating its potential utility in preoperative evaluation. The flare sign on breast MRI may play a crucial role in preoperative planning, surgical decision-making, and axillary status assessment by accurately predicting ECE.

An integrated quantitative systems pharmacology virtual population approach for calibration with oncology efficacy endpoints.

In drug development, quantitative systems pharmacology (QSP) models are becoming an increasingly important mathematical tool for understanding response variability and for generating predictions to inform development decisions. Virtual populations are essential for sampling uncertainty and potential variability in QSP model predictions, but many clinical efficacy endpoints can be difficult to capture with QSP models that typically rely on mechanistic biomarkers. In oncology, challenges are particularly significant when connecting tumor size with time-to-event endpoints like progression-free survival while also accounting for censoring due to consent withdrawal, loss in follow-up, or safety criteria. Here, we expand on our prior work and propose an extended virtual population selection algorithm that can jointly match tumor burden dynamics and progression-free survival times in the presence of censoring. We illustrate the core components of our algorithm through simulation and calibration of a signaling pathway model that was fitted to clinical data for a small molecule targeted inhibitor. This methodology provides an approach that can be tailored to other virtual population simulations aiming to match survival endpoints for solid-tumor clinical datasets.

Neuroendocrine tumours and pregnancy: Real-world data from an European Neuroendocrine Tumour Centre of Excellence.

Neuroendocrine neoplasms (NENs) arise from the diffuse endocrine system and have been considered to be rare. However, the incidence and prevalence of these tumours have increased in recent years, and they are being seen in younger patients including women in the reproductive age group. Due to the paucity of data, diagnostic and therapeutic strategies in managing such tumours during pregnancy can be challenging to both treating physicians and patients. This article describes the experience and outcomes of managing pregnant women with NEN at a European Neuroendocrine Tumour Society (ENETS) Centre of Excellence. In this retrospective analysis, we evaluated a total of 22 pregnancies in 18 pregnant women with concurrent diagnoses of NENs who were managed at Royal Free Hospital ENETS Centre of Excellence throughout their pregnancy. These were identified from our tumour registry of 3500 NEN patients between 2015 and 2023. Cross-sectional imaging (computed tomography (CT)/magnetic resonance imaging (MRI)), pre- and post-pregnancy, for each patient was reviewed by an experienced radiologist. Tumour growth rate (TGR) was calculated using the formula: TGR = 100 × [exp (TG) - 1]; TG. [3 × log (D2/D1)]/time (months), where D1 is the tumour size at date 1; D2 is the tumour size at date 2; and time (months) = (Date 2 - Date 1 + 1)/30.44. Tumour growth rate pre-conception (TGRpc) and tumour growth rate post-partum (TGRpp) were calculated for each patient. In a sub-group of patients, positivity for oestrogen and progesterone receptors were analysed on the tumour tissue to evaluate whether the presence of these receptors affected tumour progression during the pregnancy. We also reviewed the pregnancy outcome in patients treated with somatostatin analogues during pregnancy. We analysed the data of a total 22 pregnancy encounters in 18 women: 15 pregnancies (68%) preceded the diagnosis of the NEN, whereas the diagnosis of NEN was made during pregnancy or in the post-partum period in 5 (23%) and 2 (9%) pregnancies respectively. Eight patients (44%) had a diagnosis of a pancreatic NEN, whereas 5 (28%) were diagnosed with mid-gut NENs, and a further 5 at other sites. The majority of the patients (n = 12, 67%) had evidence of metastatic disease at the time of diagnosis. Most pregnancies had a successful outcome (n = 19, 86%), whereas 3 patients (14%) had miscarriages in the 1st trimester. Five patients in total of 6 pregnancies were treated with somatostatin analogues as monotherapy during the pregnancy, and all of them had stable disease after pregnancy. All of them delivered healthy babies without any side effects or complications due to therapy. The average TGRpc was -0.8% (n = 5) and the average TGRpp was +0.96% (n = 6); 2 patients who did not have suitable targets for calculation of TGRpc developed new lesions suggesting disease progression. Moreover, 2 of the 4 patients who have had both pre-conception and post-pregnancy scans showed an increase in TGRpp compared to TGRpc. The management of NENs during pregnancy should be multidisciplinary with an individualised approach to each patient. Somatostatin analogues appear to be safe during pregnancy, though further robust studies are needed. Pregnancy per se may accelerate tumour progression, and patients should be counselled regarding this possibility.

The Impact of Radioactive Iodine on Disease-Specific Survival in Low-to-Intermediate Risk N1b Papillary Thyroid Carcinoma.

The association of radioactive iodine (RAI) with disease-specific survival (DSS) is controversial in N1b papillary thyroid carcinoma (PTC). We aimed to evaluate whether RAI is associated with DSS in low-to-intermediate-risk N1b PTC. The Surveillance, Epidemiology, and End Results database was queried for pT1-3, N1b, M0/Mx classic PTC treated with total thyroidectomy. Multivariable Cox regression was performed to identify predictors of DSS. Subanalyses were conducted for age, intermediate-risk versus otherwise low-risk features, and positive lymph node ratio (LNR) > 0.17. Radioactive iodine recipients were younger (43.0 vs. 44.0 years, p = 0.036) with increased capsular or local invasion (49.2% vs. 41.9%, p < 0.001) and median LNR (0.37 vs. 0.33, p = 0.001). Worse DSS was associated with age (adjusted-HR = 1.09, p < 0.001), tumor size (adjusted-HR = 1.02, p < 0.001), and local invasion (adjusted-HR = 1.86, p = 0.003). Radioactive iodine was associated with improved DSS in the whole cohort (adjusted-HR = 0.61, p = 0.014), in patients ≥ 55 years (adjusted-HR = 0.48, p = 0.001) and in patients ≥55 years with LNR > 0.17 (adjusted-HR = 0.45, p = 0.001) but not LNR ≤ 0.17. Radioactive iodine was not associated with a DSS benefit in patients < 55 years even when stratified by LNR 0.17. Radioactive iodine administered to patients with at least one intermediate-risk feature (> 5 pathologic LNs or any local invasion) was associated with improved DSS (adjusted-HR = 0.60, p = 0.019) but not those with otherwise low-risk features (adjusted-HR = 0.71, p = 0.502). Radioactive iodine is associated with improved DSS in N1b PTC patients with intermediate-risk features, age ≥ 55 years, and LNR > 0.17 in older patients, but not in patients with otherwise low-risk features. These factors could help guide RAI utilization in N1b PTC.

Vestibular Schwannoma Koos Grade I International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS-K1 Study.

This investigation evaluates the safety and efficacy of stereotactic radiosurgery (SRS) vs observation for Koos grade I vestibular schwannomas (VS). In a multicenter study, we retrospectively analyzed data of patients with Koos grade I VS who underwent SRS (SRS group) or were observed (observation group). Propensity score matching was used to equilibrate demographics, tumor size, and audiometric data across groups. The outcome analyzed included tumor control, preservation of serviceable hearing, and neurological function. The study matched 142 patients, providing a median follow-up period of 36 months. SRS significantly enhanced tumor control compared with observation, with a 100% control rate at both 5- and 8-year marks in the SRS group vs 48.6% and 29.5% in the observation group at the same time intervals, respectively (P < .001). Preservation of serviceable hearing outcomes between groups showed no significant difference at 5 and 8 years, ensuring a comparable quality of auditory function (SRS 70.1% vs observation 53.4% at 5 years; P = .33). Furthermore, SRS was associated with a reduced likelihood of tinnitus (odds ratio [OR] = 0.46, P = .04), vestibular dysfunction (OR = 0.17, P = .002), and overall cranial nerve dysfunction (OR = 0.49, P = .03) at last follow-up. SRS management of patients with Koos grade I VS was associated with superior tumor control and reduced odds for cranial nerve dysfunction, while not compromising hearing preservation compared with observation. These findings support the safety and efficacy of SRS as a primary care approach for this patient population.

Imaging assessment of tumor densities and sizes following pazopanib treatment for central nervous system solitary fibrous tumors with multiple extracranial metastases: A case series

Imaging assessment of tumor densities and sizes following pazopanib treatment for central nervous system solitary fibrous tumors with multiple extracranial metastases: A case series

A novel reopenable clip with sharp claw for complete closure of mucosal defects after colorectal endoscopic submucosal dissection.

The MANTIS Closure Device (MCD; Boston Scientific, Marlborough, Massachusetts, USA) is a reopenable clip with a sharp claw used for closure after endoscopic submucosal dissection (ESD). We evaluated the effectiveness of the MCD for fast and complete closure after colorectal ESD. Cases involving closure with the MCD after ESD of 20-60-mm colorectal lesions between April 2023 and January 2024 were reviewed. The primary end point was complete closure of the ESD defect with the MCD. Secondary end points included closure time, delayed bleeding, delayed perforation, and post-ESD coagulation syndrome (PECS). MCD application involved: 1) grasping the mucosa on the anal-side of the defect; 2) pushing the clip toward the oral-side mucosa and deploying it; 3) adding other reopenable clips for complete closure. 61 cases involving MCD were analyzed. Mean tumor size was 32.3 (SD 9.2) mm. Complete closure rate was 98.4% and mean closure time was 6.9 (SD 2.6) minutes. The mean number of MCDs and other clips used was 1.0 (SD 0.1) and 4.7 (SD 1.4), respectively. Rates of delayed bleeding, delayed perforation, and PECS were 0%, 0%, and 9.8%, respectively. Fast and complete closure after colorectal ESD was successfully achieved using the MCD.

Development and validation of the competing risk nomogram and risk classification system for predicting cancer-specific mortality in patients with cervical adenosquamous carcinoma treated via radical hysterectomy

In this study, we established and validated a competing risk nomogram for predicting the cumulative incidence of cervical adenosquamous carcinoma (ASC)-specific death in patients undergoing radical hysterectomy. Patients diagnosed with ASC between 2010 and 2019 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence function (CIF) for various variables influencing ASC-specific mortality was computed. A Fine-Gray competing risk model was used to identify independent predictors, formulating a competing risk nomogram. A multivariate Cox proportional hazards model was also applied for comparative analysis. The performance of the nomogram was assessed using metrics such as the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). A corresponding risk classification system was constructed based on nomogram-derived scores. Factors such as advanced age, racial background (Black race), higher tumor grade, increased tumor size, advanced TNM stage, and receipt of radiotherapy without chemotherapy were found to be positively associated with elevated ASC-specific mortality. Additionally, age, T stage, M stage, and chemotherapy were identified as independent predictors correlated with ASC-specific mortality. The established nomogram exhibited accurate discriminatory capabilities and superior net benefits compared to the traditional TNM staging system. Additionally, the high-risk group consistently demonstrated higher probabilities of ASC-specific death in both the training and validation sets. The developed nomogram proficiently quantified the incidence of ASC-specific death in patients subjected to radical hysterectomy for ASC. This tool could help clinicians in formulating personalized treatment strategies and devising follow-up protocols.

Distinct Impacts of Clinicopathological and Mutational Profiles on Long-Term Survival and Recurrence in Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors. Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, longterm clinical outcomes, and prognostic factors for recurrence and mortality were analyzed. The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980-2009 and 2010-2020 (P=0.995); however, the 1980-2009 group had significantly lower RFS rates (P=0.031). The 2010-2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group. Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.

The Effect of After-Hours Resection on the Outcomes in Patients with High-Grade Gliomas.

The "weekend effect" is the finding that patients presenting for medical care outside of regular working hours tend to have worse outcomes. There is a paucity of literature in the neuro-oncology space exploring this effect. We investigated the extent of resection and complication rates in patients undergoing after-hours high-grade glioma resection. A retrospective review was conducted on patients with high-grade glioma requiring emergent surgery between January 1, 2021, and March 31, 2023. After hours was defined as surgical resection on the weekend and/or evening (>50% of surgical time between 1630 and 0659). These patients were matched to patients undergoing resection during regular working hours. Groups were compared on the basis of the extent of resection, postoperative complications and 6-month mortality rate. A total of 38 patients were included in this study (19 after hours, 19 regular hours). There was no significant difference in age, sex, tumor grade and tumor size between the two groups (all p > 0.05). There was no significant difference in the extent of resection between the groups (p = 0.7442). There was no significant difference in the rate of intraoperative complications, postoperative complications, reoperation and death at 6 months between the groups (all p > 0.05). Estimated blood loss was significantly higher in the regular hours group (p = 0.0278). There was no significant difference in the total operative time (p = 0.0643) and length of stay (p = 0.0601). After-hours high-grade glioma surgery has similar outcomes to regular-hours surgery for lesions not requiring specialized functional mapping.

British Skull Base Society Consensus on Vestibular Schwannoma Surveillance

Abstract Objective Surveillance plays a crucial role in managing patients with vestibular schwannomas (VSs). Consensus is lacking on the optimal duration, frequency, and modality of imaging. Standardizing this approach would ensure safe and effective care, reduce patient distress, and promote consistency in management decisions among clinicians. Methods In July 2022, a multi-disciplinary Delphi consensus was conducted at the British Skull Base Society Meeting. Expert United Kingdom-based skull-base surgeons and neuroradiologists were presented semi-systematic literature reviews summarizing current evidence on VS management. Anonymized opinions were collated and discussed to reach a majority vote, which was deemed the final consensus opinion. Results Recommendations for VS managed by surveillance are: (1) surveillance frequency should decrease over time; (2) surveillance may be discontinued when the remaining lifetime risk of VS growth is &lt;0.5% (∼8.5 years); (3) factors such as age, VS size, VS location, and cystic components should be considered. Surveillance after surgery or radiotherapy has limited evidence but recommendations are: (4) surveillance should be adjusted based on residual tumor size or nodular enhancement. Imaging modality and sequences are recommended to be (5) high-resolution magnetic resonance imaging with T1, T2, FIESTA/CISS multiplanar sequences, contrast is not required in untreated cases, and linear reporting of measurements is pragmatically sufficient. Conclusion This consensus and literature review provides an evidence and expert opinion–based guide to help clinicians with the surveillance of patients with VS. Further research should focus on better understanding the dynamic nature of growth risks and the growth characteristics of postintervention VS to enable personalized growth risk stratification.

An Unusual Case of Alarming Lactic Acidosis: Brain Metabolic Cross-Talk

AbstractA 39-year-old male with a BMI of 30.8 kg/m2 and a normal medical history underwent excision of a left orbito-cavernal hemangioma (4 × 2 × 2 cm) under general anesthesia. Balanced anesthesia and fluid management guided by pulse pressure variation (kept below 12%) were employed. Despite stable hemodynamics and normal blood sugar levels, arterial blood gas (ABG) analysis revealed a progressive rise in lactate levels, reaching 10.6 mmol/L, accompanied by acidemia. Systemic hypoperfusion was ruled out by maintaining mean arterial pressure between 70-80 mm Hg, ensuring a capillary refill time of less than 3 seconds, and confirming a central venous oxygen saturation of 72%. With a total blood loss of 800 mL, one unit of packed red blood cells was transfused due to concerns about decreased microcirculation and tissue hypoxia. After 10 hours of surgery, sodium bicarbonate (NaHCO3) was administered to mitigate metabolic acidosis and its potential impact on intracranial pressure. Postoperatively, lactate levels remained elevated (8-9 mmol/L), but with continued NaHCO3 infusion, lactate reduced to 6.4 mmol/L, allowing extubation. The patient's lactate normalized by the evening, and recovery was uneventful. This case highlights the significant metabolic disturbances, particularly lactic acidosis, that can arise during brain tumor surgery due to prolonged operative times, large tumor size, higher BMI, and stress-induced metabolic derangements. Awareness and prompt management of these disturbances are crucial for successful patient outcomes.

Development and validation of a tumor size-stratified prognostic nomogram for patients with gastric signet ring cell carcinoma.

Gastric signet ring cell carcinoma (GSRC) is a rare malignancy without a commonly acknowledged prognostic assessment and treatment system. This study aimed to determine the optimal cut-off value of tumor size (TS), and construct a prognostic nomogram in combination with other independent prognostic factors (PFs) to predict 3year and 5year overall survival (OS) in GSRC patients. From the Surveillance, Epidemiology, and End Results (SEER) database, this study collected 4744 patients diagnosed with GSRC. These patients were randomized into a training cohort (n = 2320,) and a validation cohort (n = 1142). A restricted cubic spline (RCS) was used to determine the cut-off value for TS, and univariate and multivariate Cox regression analyses were performed in the training cohort to identified significant predictors. A prognostic nomogram was constructed to predict OS at 3 and 5years. Concordance index (C index), receiver operating characteristics curve (ROC curve), area under curve (AUC), and calibration curve were used to test the predictive accuracy of the model. A non-linear relationship was observed between TS and the risk of OS in GSRC, with TS thresholds at 4.4cm and 9.6cm. Survival was significantly lower in GSRC patients with TS > 4.4cm. Age, marriage, chemotherapy, surgery, TS, SEER stage, regional lymph node status, and total number were independent predictors of OS. The C index in the training cohort was 0.748, and the AUC values for both 3- and 5-year OS were higher than 0.80. Similar results were observed in the validation cohort. In addition, the calibration curves showed good agreement between the predicted 3year and 5year OS and the actual OS. TS is a key prognostic factor for patients with GSRC, and patients with a TS of 4.4-9.6cm and > 9.6cm may have a poorer prognosis than those with a TS of < 4.4cm. The TS-stratified nomogram we constructed and validated has favorable accuracy and calibration precision, and may be helpful in predicting the survival rate of patients.

ZNF281 Facilitates the Invasion of Cervical Cancer Cell Both In Vivo and In Vitro †

Background: Cervical cancer is the fourth most common cancer among women worldwide. The zinc finger transcription factor 281 (ZNF281)/ZBP-99 protein specifically binds to GC-rich DNA sequences and regulates gene expression, and it has been shown to promote tumor progression. In this study, we aim to investigate the function and molecular mechanism of ZNF281 in uterine cervical carcinoma. Methods: We conducted immunohistochemistry and Western blot assays to determine the expression of ZNF281 in eight human cervical cancer tissues. And, xenograft experiments involving the injection of HeLa cells into nude mice was used to determine the function of ZNF281 on proliferation. Transwell assays were used to detect the migration and invasion of HeLa cells after indicated that ZNF281 overexpression. Results: Our results indicated that ZNF281 protein levels were higher in cervical cancer tissues compared to normal cervical tissues. Additionally, ZNF281 was expressed in human cervical carcinoma cell lines, including HeLa, SiHa, C-33 A, CaSki, and HT-3, and is localized in both the cell nucleus and cytoplasm. ZNF281 overexpression did not influence HeLa cell proliferation or tumor size in situ. Moreover, nude mice injected with ZNF281-overexpressing cell lines developed more tumor lesions in the lungs compared to those injected with control cell lines. Conclusions: These findings suggest that ZNF281 is associated with tumor metastasis without affecting cell proliferation, both in vivo and in vitro.

Case report: Efficacy of later-line fam-trastuzumab deruxtecan in a patient with triple-positive breast cancer with brain metastases

Fam-trastuzumab deruxtecan (T-DXd) has demonstrated substantial antitumor activity and durable responses in patients with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer. We report here the treatment outcomes of T-DXd in a patient with HER2+ breast cancer with brain metastases that repeatedly recurred and progressed after two lines of salvage therapy. In 2016, a 23-year-old G0P0 female with risk factors including menarche at age 9 years, Li-Fraumeni syndrome, and a strong family history of cancer was diagnosed with bilateral, triple-positive breast cancer. She received chemotherapy, HER2-targeted therapies, total mastectomy, and locoregional radiotherapy, but a brain metastasis in the left parieto-occipital lobe was detected in 2020. After receiving capecitabine, lapatinib, gonadotropin-releasing hormone (GnRH) agonist, and tamoxifen, multiple new lesions appeared in the brain after 14 months. The patient then received capecitabine, neratinib, GnRH agonist, and letrozole; however, her brain metastases still progressed after 7 months. In 2022, she started T-DXd treatment. Good response to treatment was observed 4 months later, including a continuous decrease in the cancer antigen 15-3 level, a reduction in the size of the major brain tumor, and the absence of new lesions. Now aged 30, the patient is continuing to receive T-DXd treatment to prevent recurrence. We conclude that T-DXd was effective for the treatment of brain metastases in this young patient with triple-positive metastatic breast cancer who had multiple risk factors and had received several anti-HER2 therapies prior to T-DXd.

Excision of a supergiant spinal schwannoma: illustrative case.

The authors report on a patient who presented with an extremely large presacral schwannoma and subsequent mass effect-induced hydronephrosis and kidney failure. To the authors' knowledge, this case represents the largest radiographically verified spinal schwannoma in the medical literature. The tumor presented here was more than three times as large as a typical giant schwannoma. While smaller presacral schwannomas are usually uncomplicated surgical cases, the supergiant schwannomas described here create significant surgical challenges. The extremely large size of this nerve sheath tumor introduced a level of surgical complexity not seen in most spinal schwannoma cases. The authors hope that this case informs surgeons regarding the approach to excision of giant spinal schwannomas. The resection of giant spinal schwannomas is likely to involve one or more lengthy surgeries, and the resection volume can be limited by excessive bleeding. Physicians approaching these large, benign spinal tumors should be aware of the challenges of surgery duration and hemostasis before approaching a tumor of this kind. https://thejns.org/doi/10.3171/CASE24224.

Are background breast parenchymal features on preoperative breast MRI associated with disease-free survival in patients with invasive breast cancer?

To evaluate whether breast parenchymal features of the contralateral breast on preoperative MRI are associated with primary breast cancer characteristics and disease-free survival (DFS) in women with invasive breast cancer. Women with newly diagnosed invasive breast cancer who underwent preoperative breast MRI followed by surgery were retrospectively evaluated. Background parenchymal enhancement (BPE) on dynamic contrast-enhanced MRI and background diffusion signal (BDS) on diffusion-weighted MRI of the contralateral breast were qualitatively assessed using a four-category scale: minimal, mild, moderate, or marked. Primary breast cancer characteristics were compared based on the degree of BPE or BDS. Cox proportional hazards models were used to evaluate the association between MRI parenchymal features and DFS after adjusting for clinicopathologic features. A total of 515 women (mean age, 54years) were included. Of whom, 46 (8.9%) patients who developed disease recurrence at a median follow-up of 60months were observed. A high level (moderate/marked) of BPE or BDS was associated with younger age (≤ 45) and premenopausal status (all P < 0.05) compared to a low level (minimal/mild), but it was not associated with primary cancer characteristics such as tumor stage, grade, or subtype. Multivariable Cox proportional hazards analysis demonstrated that larger tumor size (> 2cm) (hazard ratio [HR], 3.877; P < . 001), triple-negative subtype (HR, 2.440; P = .013), and axillary node metastasis (HR, 1.823; P = .049) were associated with worse DFS. No associations were observed between background parenchymal features and disease outcomes. MRI parenchymal features, including BPE and BDS, of the contralateral breast showed no associations with primary breast cancer characteristics or DFS in women with invasive breast cancer.

Tumor Spread Through Air Spaces Predicts Survival in Resected Pulmonary Lymphoepithelial Carcinoma.

Tumor spread through air spaces (STAS) has been recognized as a prognostic factor for several types of lung cancers. However, information regarding its clinical significance in pulmonary lymphoepithelial carcinoma is limited. Therefore, this study investigated effects of STAS on the clinical outcomes for patients with pulmonary lymphoepithelial carcinoma. This study retrospectively reviewed 56 surgically resected pulmonary lymphoepithelial carcinomas. The study defined STAS as the presence of tumor cells within air spaces in lung parenchyma beyond the tumor edge. Artifacts were excluded. Recurrence-free survival (RFS) was analyzed using the log-rank test and Cox proportional hazards model. In 18 patients (32.1%), STAS was observed and found to be associated with larger tumor size (>3 cm) (p = 0.009), higher pathologic stage (p = 0.026), and tumor necrosis (p = 0.046). Patients with STAS had a significantly lower 5-year RFS rate (p = 0.025). Multivariate analysis showed that STAS was an independent predictor of worse RFS (hazard ratio, 3.395; p = 0.038). Patients with STAS had a significantly increased risk of locoregional recurrence (p = 0.049). The study findings suggest that STAS is an independent predictor of poor RFS. Based on these findings, a new three-tier grading system based on the patterns of tumor border and STAS was proposed for effective prediction of 5-year RFS in pulmonary lymphoepithelial carcinoma.