Tumor Resection Research Articles

Cystoscopy and Transurethral Resection of Bladder Tumors with Stent and Foley Catheter Placement

Cystoscopy and Transurethral Resection of Bladder Tumors with Stent and Foley Catheter Placement

Appendiceal neurofibroma after resection of multiple gastrointestinal stromal tumors of the small intestine in a patient with neurofibromatosis type 1: a case report

BackgroundNeurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is an autosomal dominant disorder that can affect multiple organs. Although gastrointestinal manifestations, such as neurofibromas and gastrointestinal stromal tumors (GISTs), can occur, appendiceal neurofibromas are extremely rare, with no documented cases of their occurrence following other gastrointestinal lesions. Herein, we report a case of an appendiceal neurofibroma following the resection of multiple small intestinal GISTs.Case presentationA 68-year-old man with NF1 presented with melena and was diagnosed with anemia due to bleeding from multiple small intestinal GISTs. Laparoscopic three partial resection of the small intestine was performed to control the bleeding. Histopathologic examination revealed the proliferation of spindle cells that are positive for c-kit and Discovered on GIST-1, confirming the diagnosis of GIST. Two years later, a follow-up computed tomography (CT) scan revealed a progressively enlarging mass in the appendix with suspected invasion into the small intestine. Positron emission tomography/CT showed fludeoxyglucose accumulation in the tumor. Therefore, considering the possibility of malignancy, laparoscopic ileocecal resection with lymph node dissection was performed. Postoperatively, melena was observed, but the anemia did not progress and improved with fasting and hemostatic therapy. The patient was eventually discharged on postoperative day 8. Histopathologic examination revealed spindle cell proliferation with positivity for S-100, confirming the diagnosis of neurofibroma.ConclusionsPatients with NF1 can develop a variety of gastrointestinal lesions. Appendiceal neurofibroma can be difficult to diagnose preoperatively and differentiate from malignancy. Hence, surgical resection should be considered.

Wrist arthrodesis following resection of recurrent giant cell tumor of distal end of radius: A case report

The recurrence rate of giant cell tumor (GCT) of bone is 20%. GCT of bone is an aggressive and potentially malignant lesion, and variable clinical behaviour. The distal femur and proximal tibia are the most common sites, accounting for 50% of all GCT of bone, followed by the distal radius (10%). The prevalence of GCT peaks during the 3rd decade, with 80% of cases occurring between 20 and 50 years of age. Local recurrence and loss of joint function are still major problems following surgery The goals of treatment are to achieve satisfactory removal of the tumor, to decrease the chance of local recurrence, and to preserve as much wrist function as possible. Here we present a case of 32-year-old female patient presented with painful lump over right wrist joint since 2 months. Previously patient was surgically treated with intralesional curettage and illiac crest bone graft and bone cement for GCT of distal end of Radius 2 years back. Xray and Magnetic resonance imaging (MRI) showed a well-defined u expansile lytic soft tissue lesion which is homogenously enhanced involving medullary cavity with cortical erosion and extending into soft tissue plane. We performed wide resection of distal third radius and ulna using dorsal approach with radial strut graft and wrist arthrodesis. Functional outcome was evaluated using the modified Musculoskeletal Tumor Society scoring system. Grip strength was assessed using a dynamometer, and range of motion of the metacarpophalangeal joint was assessed using a goniometer.

The normalization trend of ventricular morphology after lateral ventricular tumor resection without additional diversion

Intraventricular tumors frequently provoke alterations in ventricular morphology. This study aims to quantificational assess perioperative dynamic fluctuations in the cerebrospinal fluid (CSF) volume within the lateral ventricles of patients harboring lateral ventricular tumors. A retrospective review encompassing 90 patients who underwent surgical intervention for lateral ventricular tumors at our institution was undertaken. Comprehensive observations at multiple perioperative time points were conducted, and LVCV analyses were performed to delineate the longitudinal dynamic alterations in ventricular morphology. Additionally, LVCV measurements were juxtaposed with data from 19 healthy subjects to stratify patients into two cohorts: those exhibiting preoperative increased LVCV and those without such changes. After surgical excision of intraventricular tumors, alterations in LVCV were compared between these cohorts, with a factor analysis undertaken specifically among patients demonstrating increased LVCV to elucidate potential influencing variables. 40 patients (44.4%) diagnosed with intraventricular tumors presenting with enlarged preoperative LVCV [74.6 (49.3–101.8) cm3] compared with the normal subject group, and the LVCV demonstrated a significant postoperative [41.3 (27.6–67.5) cm3] reduction in 3 months (p < 0.001). Meanwhile, 50 patients (55.6%) without LVCV enlargement [14.5 (8.1–21.0) cm3] experienced a notable increase following surgery in 3 months [20.2 (14.1–33.3) cm3, p = 0.002]. Preoperative increased LVCV is an important factor leading to the increased LVCV postoperatively (p = 0.022, OR = 26.239), however, compared to healthy subjects, both groups exhibited a trend toward normalization of LVCV value postoperatively (p = 0.165, p = 0.072, respectively). Following appropriate surgical excision of the tumor, the preoperative increased LVCV associated with intraventricular tumors does not hinder the normalization trend of ventricular morphology. Not all ventricular dilation requires preventive long-term external ventricular drainage and aggressive ventriculoperitoneal shunt treatment.

Modified Textbook Outcome was a Predictor for Early Mortality After Oral Cancer Surgery.

To explore prognostic factors for early mortality among patients undergoing surgery for oral cavity cancer (OCC) and identify valuable strategies to improve patient outcomes. A total of 397 patients treated by primary tumor resection and neck dissection between 2017 and 2021 were retrospectively analyzed. Univariate and multivariate Cox regression analysis were used to explore the relationships between the study factors and early death (within 12months). Predictors were further incorporated into a nomogram for estimation of 1-year overall survival (OS). The mean age was 57.2 (SD, 9.8)years and 92.9% patients were male. The early death rate was 12.6% overall, 35.6% in patients with pN2-3, 22.3% in patients with tumor size > 3 cm, and 36.2% in patients with lymphovascular invasion. A non-modified textbook outcome (mTO), pN2-3, tumor size > 3 cm, and lymphovascular permeation were independent prognosticators for early mortality. A nomogram with the above-mentioned four factors were created with good discrimination and calibration. Among the pN2-3 or tumor size > 3 cm subgroup, a non-mTO, cancer resource center (CRC) visits, perineural invasion, and lymphovascular permeation were independent prognostic factors for early death. In addition to traditional clinicopathological features, a non-mTO and CRC visits could serve as prognostic factors for early death in OCC. A novel nomogram had good discrimination and calibration. Quality improvements in terms of mTO and patients demanding resource support could improve survival outcomes in OCC.

NEW TECHNOLOGIES AVAILABLE FOR MICRONEUROSURGICAL REMOVAL OF ACOUSTIC NEUROMAS

Introduction The aim of this study was to analyze the results of microsurgery removal of acoustic neuromas (AN) using new technologies: flexible hand-held laser fiber, Sonopet Ultrasound Aspirator, Facial Nerve “detector” monopolar stimulation (for localize position and course of facial nerve), BAER’s with level specific (LS) CE-Chirp stimulus for hearing preservation, endoscope for IAC final check, and injectable bone substitute for closure. We report a retrospective nonrandomized clinical study on 300 cases consecutively operated on. Material and Methods From July, 2010 to December, 2023, 350 consecutive patients suffering from AN have been operated on with microneurosurgical technique by key-hole retrosigmoid approach. In majority of cases tumor resection was performed with the aid of a handheld flexible laser fiber. In the same period, Sonopet Ultrasound aspirator was used for tumor debulking and/or opening of the internal auditory meatus and canal. From May 2015, hearing preservation by means LS CE-Chirp BAER was attempted in patients with preoperative socially useful hearing (AAO-HNS class A and B). In addition, we check the removal of tumor inside the internal auditory canal (IAC) by using the flexible and/or rigid endoscope, for completing tumor removal near the fundus. Results Overall time from incision to skin suture changed in relation to size of tumor (from 165 to 575 minutes) and was not affected by the use of hand-held laser. Facial nerve function was clinically assessed with the House-Brackmann (HB) scale preoperatively, in the early postoperative period (after 1 week), and at 6-month follow-up. In 3 cases a preoperative facial nerve palsy was observed (HB III and HB IV, respectively). In the remaining cases, 6 months after surgery facial nerve preservation rate (HB I) was 92%, Hearing preservation rate (AAO-HNS A and B, pre- and postoperatively) was 52% in eligible cases. Total and “nearly total” removal of tumor was possible in about 80% of cases. Dura closure was performed with underlaying autologous pericranium. Injectable bone substitute in the gaps after bone flap repositioning minimized postoperative CSF leakage and improved the aesthetic result. Conclusions The use of new technologies (handheld flexible laser fibers, Sonopet Ultrasound Aspirator, fluoreceine, Nimbus facial nerve continuous monitoring, LS CE-Chirp BAER, endoscope for IAC final check) in AN microsurgery seems to be safe and efficacious and facilitates tumor resection, especially in ‘‘difficult’’ conditions (e.g., large size, highly vascularized, or hard tumors). The good functional outcome following conventional microsurgery seems to be further improved and the extent of tumor removal could be increased with the proper use of the new technologies available in the neurosurgical armamentarium.

PREDICTORS OF POSTOPERATIVE COMPLICATIONS AND FUNCTIONAL OUTCOMES IN PEDIATRIC PATIENTS WITH SURGICALLY TREATED FOURTH VENTRICLE TUMOR

Background Tumors of fourth ventricle are frequently treated pathologies in pediatric neurosurgery. Data regarding predictors for permanent neurological deficits, long-term functional outcomes, cerebellar mutism (CM), the extent of resection (EOR), and oncological outcomes are scarce. We attempt to contribute to this topic with analysis of our institutional cohort. Methods A retrospective single-center study of patients aged ? 19 years who underwent primary surgical resection of fourth ventricular tumor over a 15-year period (2006–2021). Predictors analyzed included: age, gender, surgical approach, anatomical pattern, tumor grade, EOR, tumor volume, and others as appropriate. Results 106 patients were included (64 males, mean age 7.3 years). Rate of permanent neurological deficit was 24.2%; lateral tumor extension (p = 0.036) and tumor volume greater than 38 cm3 (p = 0.020) were significant predictors. Presence of deficit was the only significant predictor of reduced (less than 90) Lansky score (p = 0.005). CM occurred in 20.8% of patients and was influenced by medulloblastoma histology (p = 0.011), lateral tumor extension (p = 0.017), and male gender (p = 0.021). No significant difference between transvermian and telovelar approach in development of CM was detected (p = 0.478). No significant predictor was found for EOR. EOR was not found to be significant predictor of overall survival for both low-grade and high-grade tumors, however, gross total resection (GTR) was protective against tumor recurrence compared to near-total or subtotal resection (p &lt; 0.001). Survival was found to be better in older patients (? 7.0 years, p = 0.019). Conclusion The overall rate of postoperative complications remains high due to the eloquent localization. Older patients (&gt;7 years) have been found to have better outcomes and prognosis. Achieving GTR whenever feasible and safe has been shown to be critical for tumor recurrence. CM was more common in patients with medulloblastoma, and in patients with tumors extending through the foramen of Luschka. The telovelar approach uses a safe and anatomically sparing corridor, however, it has not been associated with a lower incidence of CM and neurological sequelae in our series, showing that each case should be assessed on an individual basis.

Abstract B013: Investigation of a novel lncRNA, TROLL-9, in breast cancer formation and progression

Abstract Breast cancer (BC) is the most diagnosed cancer and the second leading cancer-related cause of mortality among women in the US. Despite advances in treatment, BC remains a challenge due to its metastatic potential. The most aggressive BC subtype, triple negative (TN), often harbors mutations in the tumor suppressor gene, p53. One of the effects of mutant p53 involves the inhibition of the tumor and metastatic suppressive functions of TAp63, a p53 family member. Loss of TAp63 leads to the formation of metastatic mammary adenocarcinomas in mice, in part through the regulation of a group of nine long non-coding RNAs (lncRNAs), that we identified and named TAp63 regulated oncogenic lncRNAs (TROLLs). We previously characterized two TROLLs, TROLL-2 and TROLL-3, as markers of tumor progression in multiple cancer types via the activation of the AKT pathway. Currently we are investigating the role of another member, TROLL-9. To investigate the biological role of TROLL-9, we performed in vivo experiments using preclinical mouse models. Specifically, MCF-DCIS, MCF-CA1D, and MDA-MB-231 triple negative breast cancer (TNBC) cells constitutively expressing TROLL-9 were generated and utilized for two mouse models: orthotopic xenografts for primary tumor growth and spontaneous metastasis. The former was designed to identify the potential role of TROLL-9 in tumor formation, whereas the latter involved the resection of a primary tumor and monitoring for metastases via bioluminescence imaging. Notably, TROLL-9 overexpression led to increased formation of lung and livers metastases in all these models, suggesting a role for TROLL-9 in the metastatic cascade. In order to elucidate the mechanism of function of TROLL-9, two complementary approaches were used. Firstly, pulldown using MS2-TRAP followed by mass spectrometry (MS) was performed and led to the identification of putative protein interactors. In parallel, Laser Capture Microscopy (LCM) of the lung metastases followed by RNA-sequencing was used to assess for any gene expression changes due to TROLL-9 overexpression. Integration of the two datasets is currently being performed to unveil the network of genes and proteins perturbed by TROLL-9. Furthermore, to understand the relevance in BC patients, TROLL-9 expression levels were analyzed in the TCGA BC dataset. Interestingly, differences in TROLL-9 levels across BC subtypes were observed, thus supporting its putative role in TNBC. Overall, our data suggest a role for TROLL-9 in BC progression. Our findings provide evidence for further characterizing its mechanism of function as a potential therapeutic target for the treatment of invasive BC, particularly TNBC harboring TP53 mutations. Citation Format: Avani A Deshpande, Marco Napoli, John H Lockhart, Christina L Carr, Jaden R Baldwin, Elsa R Flores. Investigation of a novel lncRNA, TROLL-9, in breast cancer formation and progression [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B013.

MANAGEMENT OF EXTRAMEDULLARY INTRADURAL SPINAL TUMORS

Spinal tumors are relatively uncommon, accounting for approximately 5%–10% of all central nervous system tumors, with an estimated 70%–80% being located in the intradural extramedullary space. The most common intradural extramedullary tumors are schwannomas, followed by meningiomas. Other less common intradural extramedullary tumors include myxopapillary ependymomas. The clinical presentation of these tumors is often rather nonspecific, and clinicians must maintain a high index of suspicion when evaluating patients with chronic back pain. Approximately 50% of affected individuals experience nonspecific back pain, whereas radiating pain, motor deficits, and sensory loss often progress gradually. This study examines the surgical management of intradural spinal tumors treated in our department, focusing on surgical techniques Some of these benign lesions can pose a surgical challenge due to their location to spinal cord, tumor consistency (densely mineralized / calcified). Posterior approaches involving laminectomy while preserving facet joints are typically sufficient for the surgical resection of dorsal and dorsolateral tumors. In conclusion the total surgical removal of these tumors while preserving neurological function remains can pose a surgical challenge especially for those that are densely calcifed and situated anterolateral to spinal cord, but employing standard microsurgical techniques often makes these resections possible.

Rational Design of a Tandem Activatable Fluorescent Probe for Differential Diagnosis and Therapeutic Assessment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a formidable disease, distinguished by its high aggressiveness and dismal outcomes. Although leucine aminopeptidase (LAP) has been widely employed as a biomarker in biological imaging of HCC, it is still susceptible to interference from false-positive signals activated in injured liver tissues. In this study, based on the significant difference of GSH levels in alcohol-damaged liver tissues and tumor tissues, a dual-tandem activatable probe (PCLT) was designed for differential diagnosis and treatment guidance of HCC by near-infrared fluorescence (NIRF) imaging. This probe comprised a dual-locked hemicyanine dye decorated with a tetraethylene glycol chain and dual-recognition unit of glutathione (GSH) and LAP, which could be sequentially cleaved by GSH and LAP to restore its NIRF signal. PCLT excellently discriminated orthotopic HCC from ALI far earlier (7 days) than histological analysis (28 days) and exhibited higher specificity toward early orthotopic HCC than the single-locked probe (PCL). In addition, PCLT is capable of accurately delineating the tumor contour, assisting in surgical resection of HCC tumors under fluorescence visualization, and noninvasively assessing the antitumor effect of HCC chemotherapy during ferroptosis, thereby presenting promising clinical implications for clinical diagnosis and therapy of HCC.

The effective duration of systemic therapy and the neutrophil-to-lymphocyte ratio predict the surgical advantage of primary tumor resection in patients with de novo stage IV breast cancer: a retrospective study

BackgroundThe primary tumor resection (PTR) of de novo stage IV breast cancer (DnIV BC) is controversial, and previous studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) could be a poor-prognosis factor for BC. We investigated PTR’s surgical advantage related to clinical outcomes, the surgery timing in responders to systemic therapy, and whether the NLR can predict the benefit of surgery for DnIV BC.Patients and methodsWe retrospectively analyzed the cases of the DnIV BC patients who received systemic therapies and/or underwent PTR at our institution between January 2004 and December 2022. Blood tests and NLR measurement were performed before and after each systematic therapy and/or surgery.ResultsSixty patients had undergone PTR local surgery (Surgery group); 81 patients had not undergone surgical treatment (Non-surgery group). In both groups, systemic treatment was performed as chemotherapy (95%) and/or endocrine therapy (92.5%) (p < 0.0001). The groups’ respective median progression-free survival (PFS) durations were 88 and 30.3 months (p = 0.004); their overall survival (OS) durations were 100.1 and 31.8 months (p = 0.0002). The Surgery-group responders to systemic therapy lasting > 8.1-months showed significantly longer OS (p = 0.044). The PFS and OS were significantly associated with the use of postoperative systemic therapy (p = 0.0012) and the NLR (p = 0.018). A low NLR (≤ 3) was associated with significantly better prognoses (PFS and OS; p < 0.0001).ConclusionsA longer effective duration of systemic therapy (> 8.1 months) and a low pre-surgery NLR (≤ 3.0) could predict PTR’s surgical advantage for DnIV BC. These variables may help guide decisions regarding the timing of surgery for DnIV BC.

Abstract B008: Evaluating ctDNA as a risk-stratifying biomarker in non-metastatic triple-negative breast cancer treated with neoadjuvant chemotherapy

Abstract Introduction: Patients with triple-negative breast cancer (TNBC) who respond well to neoadjuvant chemotherapy (NACT) generally experience favorable outcomes. However, those with residual disease after NACT face a higher risk of relapse and exhibit varying outcomes. Therefore, additional tools for assessing relapse risk are critical for guiding personalized treatment strategies. We aim to investigate the role of circulating tumor DNA (ctDNA) in conjunction with homologous recombination deficiency (HRD) as a risk-stratifying biomarker in TNBC patients with residual disease. Methods: TNBC were classified as HRD-Hereditary or Sporadic using multi-gene genetic testing. Comprehensive Genomic Profiling (CGP) was performed and tumor acquired small variants were tracked in plasma samples by a personalized-amplicontarget-sequencing (PATS) approach. Plasma samples were collected at six key time points: before treatment (BT), after the first block of NACT (ab1Neo), post-completion of NACT (aNeo), after tumor resection (aSur), and at two monitoring intervals every three months (M3m and M6m). Results: Of 105 TNBC patients tested for germline variants, 26% were classified as HRD-Hereditary, primarily due to BRCA1 mutations. CGP was performed on 73 tumors, with 12.5% displaying high tumor mutation burden (TMB), not associated with HRD- Hereditary status. Tumor-specific variants were identified in 95% (69/73) of cases, with TP53 variants being the most frequent (84%). Regarding response to NACT, 55% (58/105) achieved pathological complete response (RCB=0), while 11% (12/105) had RCB=I, 16% (17/105) RCB=II, 10% (11/105) RCB=III and 7% (7/105) unavailable RCB score. ctDNA analysis was feasible for 62% (65/105) of cases. Positive ctDNA (ctDNApos) was detected in 66.2% (43/65) at BT, 48.4% (30/62) at ab1Neo, 25.4% (15/59) at aNeo, 32.8% (20/61) at aSur, 18.6% (11/59) at M3m and 28.6% (14/49) at M6m. Interestingly, sporadic tumor patients exhibited significantly higher ctDNApos rates compared with HRD-Hereditary tumors at BT, aNeo, and aSur. No significant association was found between ctDNApos at any timepoint and RCB scores. Strong negative predictive value of RCB=0/1 and ctDNAneg aSur for progression was observed (94.2% - 65/69 and 85.4% - 35/41, respectively; mean follow-up 39.7 months, median 36.9 months). In contrast, the positive predictive value for both RCB=2/3 and ctDNApos aSur was relatively low (50% - 14/28; 50% - 10/20, respectively). However, when ctDNApos at aSur were combined with RCB=2/3, the PPV improved to 77.8%. Moreover, ctDNApos was significantly associated with clinical progression at BT (p=0.0359) and aSur (p=0.0053) and consistently anticipated progression detected by standard imaging, with a mean lead-time of 4.7 months. Patients with ctDNApos also demonstrated worse progression-free survival, strongly suggesting its potential as a prognostic marker. Conclusions: ctDNA appears to be a promising risk-stratifying biomarker for TNBC patients with residual cancer, offering valuable insights for tailoring patient management and improving outcomes. Citation Format: Rafael Canfield Brianese, Karina Miranda Santiago, Nathalia de Angelis de Carvalho, Marina de Brot Andrade, Giovana Tardin Torrezan, Vladmir Claudio Cordeiro de Lima, Solange Moraes Sanches, Maria Nirvana da Cruz Formiga, Fabiana Baroni Alves Makdissi, Dirce Maria Carraro. Evaluating ctDNA as a risk-stratifying biomarker in non-metastatic triple-negative breast cancer treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B008.

Abstract A043: Tumor-informed whole genome sequencing of ctDNA from lymph and plasma detects molecular residual disease in HPV-negative head and neck cancer patients

Abstract Introduction: Recurrence after tumor resection is a major cause of failure in HPV-negative head and neck squamous cell carcinoma (HNSCC), with up to 50% of patients recurring within 2 years. There is unmet need for an accurate diagnostic test that can predict risk of recurrence prior to adjuvant therapy selection. We previously demonstrated that ctDNA in lymphatic exudate collected via surgical drains (“lymph”) accurately identifies molecular residual disease (MRD) and outperforms plasma in HNSCC patients using a targeted sequencing (TS) approach. While TS assays are robust and sensitive, they have key limitations, namely limited ctDNA features, higher cost, longer turnaround times, and lower throughput. Here we evaluate whole genome sequencing (WGS) for detection of MRD in both lymph and plasma sampled 24 hours after surgery. Methods: Lymph, plasma, and whole blood were collected 24 hours postoperatively from 30 HPV-negative HNSCC patients (stages I – IV) along with resected tumor. To detect ctDNA, we utilized WGS analyses of patient matched tumor, germline (blood), and cfDNA from lymph or plasma samples at approximately 150x, 30x, and 30x depth, respectively. Tumor- specific single nucleotide variants were identified from tumor and germline datasets, from which a candidate variant set was used to determine the presence of ctDNA within lymph or plasma DNA through a random forest machine learning model. ctDNA status was determined based on the level of signal compared to a reference population of noncancerous donor plasma samples (n=80). 5 tumors and 1 lymph sample failed QC; in total, 24 patients remained, yielding 10 patients with disease recurrence and 14 with no evidence of disease with &amp;gt;1 year of follow-up. The Kaplan-Meier (KM) estimator with log-rank test and Cox proportional-hazards model were used for survival analyses. Results: KM survival analyses indicated that WGS of lymph ctDNA accurately predicts recurrence (sensitivity (SN) = 50%, specificity (SP) = 93%; p = 0.003, Hazard ratio (HR) = 6.0), consistent with previously published results using a TS MRD approach in this cohort (SN = 80%, SP = 64%, p = 0.02, HR = 5.3). WGS of lymph ctDNA outperformed plasma at this timepoint (SN = 30%, SP = 93%, p = 0.03, HR = 4.2). WGS of lymph ctDNA also showed enhanced performance in locoregional relapse (n=21, SN = 57%, SP = 93%; p = 0.006, HR = 6.7). Finally, the ctDNA fraction of proximal lymph was higher than paired plasma in all locoregional recurrences (n=7), while peripheral plasma had a higher ctDNA fraction in 2 out of 3 distant recurrences. Conclusions: Tumor-informed WGS analysis of lymph ctDNA represents a robust MRD approach in HPV-negative HNSCC. Lymph outperforms time-matched plasma for prediction of recurrence, particularly in patients with locoregional relapse. Accurate MRD identification in the immediate post-surgical timeframe suggests that lymph analysis has potential to augment pathology and longitudinal plasma testing to provide more personalized adjuvant treatment decision-making in patients with HPV-negative HNSCC. Citation Format: Zhuosheng Gu, Seka Lazare, Noah Earland, Marra S Francis, Adam Harmon, Megan Long, Amy Greer, Ellen Verner, Andrew Georgiadis, Mark Sausen, Shakti Ramkissoon, Jose P Zevallos, Aadel A Chaudhuri, Taylor J Jensen, Wendy Winckler. Tumor-informed whole genome sequencing of ctDNA from lymph and plasma detects molecular residual disease in HPV-negative head and neck cancer patients [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A043.

Comprehensive analysis of single-cell and bulk RNA sequencing reveals postoperative progression markers for non-muscle invasive bladder cancer and predicts responses to immunotherapy

BackgroundNon-muscle-invasive bladder cancer (NMIBC) is renowned for its high recurrence, invasiveness, and poor prognosis. Consequently, developing new biomarkers for risk assessment and investigating innovative therapeutic targets postoperative in NMIBC patients are crucial to aid in treatment planning.ApproachesDifferential gene expression analysis was performed using multiple Gene Expression Omnibus (GEO) datasets to identify differentially expressed genes (DEGs) between NMIBC and normal tissue, as well as between NMIBC and muscle-invasive bladder cancer (MIBC). Functional enrichment analysis was conducted based on the DEGs identified. Subsequently, prognosis-related genes were selected using Kaplan–Meier (KM) analysis and Cox regression analysis. The Boruta algorithm was utilized to further screen for core DEGs related to postoperative progression in NMIBC based on the aforementioned prognosis-related genes. Single-cell and clinical correlation studies were performed to verify their expression across various stages of bladder cancer. To investigate the link between core genes and the immune microenvironment, single-sample gene set enrichment analysis (ssGSEA) was utilized, and Receiver Operating Characteristic (ROC) and KM analyses were performed to confirm predictive power for immune therapy outcomes. Machine learning (ML) models were constructed using the DepMap dataset to predict the efficacy of core gene inhibitors in treating bladder cancers. The prognostic performance of the core genes was evaluated using ROC curve analysis. An online prediction tool was developed based on the core genes to provide prognostic predictions. Finally, RT-qPCR, CCK-8, and Transwell assays were used to verify the pro-tumor effects of the GINS2 in bladder cancer.ResultsA total of 70 DEGs were identified, among which 11 prognostic genes were obtained through KM analysis, and an additional 8 prognostic genes were obtained through COX analysis. The Boruta algorithm selected AURKB, GINS2, and UHRF1 as the three core DEGs. Single-cell and clinical variable correlation analyses indicated that the core genes promoted the progression of bladder cancer. The analysis of immune infiltration revealed a strong positive association between the core genes and both activated CD4 T cells and Type 2 helper T cells. Two random forest (RF) models were constructed to effectively predict the treatment effect of bladder cancer after targeted inhibition of AURKB and GINS2. In addition, an online nomogram tool was developed to effectively predict the risk of postoperative progression in NMIBC patients undergoing TURBT. Finally, RT-qPCR, CCK8, and Transwell assays showed that GINS2 promoted the growth and progression of bladder cancer.ConclusionAURKB, GINS2, and UHRF1 have the potential to enhance postoperative management of NMIBC patients undergoing transurethral resection of bladder tumor (TURBT) and can predict immunotherapy response, establishing them as promising therapeutic targets.

Basic Study on Gene Biology of Bladder Cancer Metastasis

Bladder cancer is a complex disease with distinct treatment approaches based on its progression. For non-muscle invasive bladder cancer, the primary treatment method involves complete tumor resection, followed by immunotherapy, intravesical chemotherapy, and regular monitoring. In cases of muscle-invasive bladder cancer, a multimodal approach-including radical cystectomy and neoadjuvant chemotherapy offers the best chance of cure; though some tumors still progress to metastatic disease, which is associated with high mortality rate. Metastasis remains the primary cause of bladder cancer mortality. Since research on tumor metastasis began in 1889, discoveries like the seed and soil hypothesis and the role of host factors have shaped the treatment strategies and contributed to our understanding of metastatic behavior. Advancing our knowledge of tumor biology, particulary in relation to metastasis, remains essential, and summarizing current findings in this area will support further progress in bladder cancer metastasis research.

Abstract A007: Transient elevation of ctHPVDNA in human papilloma virus-mediated oropharynx squamous cell carcinoma patients following diagnostic surgical procedures

Abstract Background: Circulating tumor DNA (ctDNA) is now widely used across a variety of malignancies as a viable “liquid biopsy” method, with applications in early detection, treatment response evaluation, prognostication, and recurrence monitoring. Recently, ctDNA derived from the tumor-integrated HPV (ctHPVDNA) has borne promising results in HPV-associated cancers, including HPV+ oropharyngeal squamous cell carcinoma (OPSCC). Studies indicate that undetectable ctHPVDNA after complete surgical excision in HPV+ OPSCC corresponds with improved prognosis. However, ctHPVDNA kinetics after diagnostic procedures such as transoral robotic surgery (TORS) in head neck squamous cell carcinoma from an unknown primary (HNSCCUP) or unknown primary has not been extensively studied. The purpose of this study is to show an unexpected trend in NavDx levels following these procedures. Methods: Patients undergoing TORS at Stanford University (September 2023 and August 2024) were prospectively screened and enrolled. A commercially available ctHPVDNA assay (NavDx) was collected at baseline, immediate postoperative (24-48 hours), 7-14 days following surgery, 3 months post- treatment and every 3 months thereafter up to 12 months. Results: Eight patients presented with HNSCCUP, 87.5% (7/8) had detectable baseline ctHPVDNA levels ranging from 2 to 1237. 75% (6/8) of the patients were confirmed p16+ by immunohistochemistry (IHC), while 25% (2/8) tested HPV+ by in situ hybridization (ISH). Diagnostic TORS was performed in 75% (6/8), while 25% (2/8) underwent direct laryngoscopy, with all primary tumors found in the oropharynx, 100% (8/8). Notably, 85.7% (6/7) of patients showed an unexpected elevation in total tumor mutational volume (TTMV) scores post-diagnostic procedure compared to baseline, with ctHPVDNA levels ranging from 30 to 2466, including one case where levels nearly quintupled. One patient had no post-diagnostic procedure TTMV score due to a negative baseline. However, in one other case, there was a negative post-procedure level. Among those with elevated post ctHPVDNA, 71.4% (5/7) underwent complete TORS excision, resulting in decreased postoperative ctHPVDNA levels in all patients, consistent with recent studies. Conclusion: This study provides insight that diagnostic procedures, such as TORS or direct laryngoscopy, in patients with p16+ HPV-mediated oropharyngeal cancer may lead to transient and unexpected elevations in ctHPVDNA levels, measured by TTMV scores. Although most patients showed a subsequent decrease in ctHPVDNA levels following a complete tumor resection, the observed post-diagnostic elevation emphasizes the importance of considering the timing of ctHPVDNA measurements. These findings suggest surgical manipulation may temporarily influence ctHPVDNA kinetics that could impact clinical decision-making and postoperative monitoring. Further research is needed to understand the implications of these transient elevations and optimizing the timing of ctHPVDNA assessments in clinical practice. Citation Format: Hlu Vang, Joanne Soo, Nikita Bedi, Andrea Garofalo, Michelle M Chen, Andrey Finegersh, Floyd Christopher Holsinger. Transient elevation of ctHPVDNA in human papilloma virus-mediated oropharynx squamous cell carcinoma patients following diagnostic surgical procedures [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A007.

Advances in Bioceramics for Bone Regeneration: A Narrative Review.

Large osseous defects resulting from trauma, tumor resection, or fracture render the inherent ability of the body to repair inadequate and necessitate the use of bone grafts to facilitate the recovery of both form and function of the bony defect sites. In the United States alone, a large number of bone graft procedures are performed yearly, making it an essential area of investigation and research. Synthetic grafts represent a potential alterative to autografts due to their patient-specific customizability, but currently lack widespread acceptance in the clinical space. Early in their development, non-autologous bone grafts composed of metals such as stainless steel and titanium alloys were favorable due to their biocompatibility, resistance to corrosion, mechanical strength, and durability. However, since their inception, bioceramics have also evolved as viable alternatives. This review aims to present an overview of the fundamental prerequisites for tissue engineering devices using bioceramics as well as to provide a comprehensive account of their historical usage and significant advancements over time. This review includes a summary of commonly used manufacturing techniques and an evaluation of their use as drug carriers and bioactive coatings-for therapeutic ion/drug release, and potential avenues to further enhance hard tissue regeneration.

Abstract 4134712: Pheochromocytoma-Induced Cardiomyopathy Requiring Mechanical Support with Ejection Fracture Recovery Following Surgical Resection

Introduction: Pheochromocytomas are catecholamine-secreting tumors that arise from chromaffin cells of the adrenal medulla. The annual incidence is approximately 0.8 per 100,000 persons, though this is an underestimate given a high percentage diagnosed at autopsy. Classically, patients present with episodic headache, sweating, and tachycardia, however, pheochromocytomas can be associated with cardiomyopathy secondary to the catecholamine excess. We present an unusual case of pheochromocytoma-induced cardiogenic shock highlighting an excellent use of mechanical circulatory support with Impella and Extracorporeal Membrane Oxygenation (ECMO) bridging to surgical intervention resulting in left ventricular ejection fraction (LVEF) recovery. Case Description: A 49-year-old female with past medical history of asthma initially presented to an outside hospital for palpitations, chest pain, and hypertension. Transthoracic echo (TTE) showed preserved left ventricle ejection fraction (LVEF) while cardiac MRI showed a LVEF of 43% with dilated left ventricle and diffuse global hypokinesis consistent with a dilated cardiomyopathy. She underwent a coronary angiogram demonstrating nonobstructive CAD. She was then discharged with readmission a month later at our hospital for chest tightness, palpitations, vomiting, weakness, and dizziness. Repeat TTE showed a drop in LVEF to 10-15%. She progressed to cardiogenic shock requiring BiPAP and inotrope initiation, with progressive shock and hypotension ultimately requiring Impella 5.5 and venoartrial ECMO. Abdominal imaging was notable for 4.7 x 4.2 cm right adrenal nodule and further workup with serum and urine metanephrines confirmed pheochromocytoma. While supported, the patient underwent right adrenalectomy with subsequent wean of mechanical circulatory support and biventricular recovery on TTE. Discussion: Pheochromocytoma-induced heart failure is a rare but potentially life-threatening complication from excess catecholamine effects on the myocardium. Pheochromocytomas should be considered in the evaluation of idiopathic heart failure even in the absence of symptoms related to catecholamine excess. Early detection, pharmacological management, and surgical resection may prevent progression of myocardial remodeling. Mechanical circulatory support can be a valuable adjunct in managing refractory heart failure in these patients by providing temporary hemodynamic stabilization while awaiting definitive tumor resection.

The epidemiological and histopathological factors for delayed local recurrence in oral squamous cell carcinoma

BackgroundOral squamous cell carcinoma (OSCC) is a prevalent malignancy in oral cancer. Approximately 26% of OSCC cases recur after initial curative treatment, with over 80% of these recurrences occurring within the first 2 years. Delayed local recurrence (DLR) occurring beyond the 2-year period in cases of OSCC is infrequent. The aim of this study is to investigate the histopathological characteristics associated with DLR.MethodsThis study included 197 patients diagnosed with OSCC who underwent primary surgery from 2006 to 2022. Epidemiological features, such as age and gender, and histopathological features, including primary tumor sites, TNM staging, histopathological grading, depth of invasion, the presence of lymphovascular or perineural invasion, and the utilization of radiation therapy (RT) and neck dissection (ND) were analyzed.ResultsThe mean interval until local recurrence was 22 ± 27 months. There were 10 cases of DLR (20.83%) among 51 patients with local recurrence. The epidemiological and histopathological analysis of these cases is as follows: 10 patients (3 males and 7 females) aged 51–80 years (median, 56.5 years). Primary tumor sites were tongue (n = 3), maxillary gingiva (n = 1), mandibular gingiva (n = 3), retromolar trigone (n = 1), and buccal mucosa (n = 2). Tumor size was advanced (T3/T4) in 5 cases, while a smaller size (T1/T2) was observed in 5 cases. No lymph node metastasis was 80.0%. Histopathological grading was well differentiated in 9 cases and moderately differentiated in 1 case, with no cases of poorly differentiated tumors. Depth of invasion > 5 mm was 70.0% of the cases (n = 7). Lymphovascular invasion and perineural invasion were not present. Three patients received RT, and 8 patients underwent ND. There were 2 patients who consumed alcohol, and 2 patients who smoked tobacco. The results showed that histological differentiation had a significant relationship with the interval (p = 0.031).ConclusionsDLR, occurring more than 2 years after the initial tumor resection surgery, is infrequent. Histological differentiation is associated with tumor recurrence intervals. Patients with a higher histological grading require more precise follow-up observation during the initial 2 years after surgery.

Left-sided portal hypertension caused by a solid pseudopapillary neoplasm of pancreas tail: a pediatric case report

BackgroundSolid pseudopapillary neoplasm (SPN) is a low-grade malignant tumor that occurs in 60% of all pediatric pancreas tumors. Radical tumor resection is essential; however, spleen preservation is also crucial to prevent overwhelming post-splenectomy infection. In contrast, spleen preservation is not always possible, because left-sided portal hypertension (LSPH) can cause splenic vein stenosis or occlusion induced by pancreatic tumor. We herein report on a pediatric patient of LSPH due to SPN in the pancreatic tail.Case presentationA 12-year-old girl was admitted to our hospital with left upper quadrant abdominal pain. A solid mass was palpated in the left costal region. The patient showed slight anemia (Hb: 11.8 g/dL) and elevation of inflammatory reaction (CRP: 5.98 mg/dL) without positive tumor markers. A radiological examination revealed that a 9 cm-sized mass with hemorrhagic necrosis in the pancreatic tail. Splenic venous flow was not detected and collateral draining into the left gastric vein and left renal veins were developed with splenomegaly. LSPH was involved at the time of diagnosis. The tumor was diagnosed with SPN, hence tumor resection with spleen preservation was performed. Six months after surgery, the patient developed a left quadrant abdominal pain that worsened during exercise. There was no improvement of splenic venous flow and splenomegaly. LSPH remained with splenomegaly, which possibly triggered the patient’s abdominal pain. The patient underwent splenectomy 9 months after the tumor resection. After the splenectomy, the patient’s abdominal pain disappeared without any recurrence 8-year post-surgery.ConclusionsLSPH has not been a major focus in previous SPN pediatric patients, although most symptomatic LSPH patients required splenectomy. Careful post-operative observation for LSPH is important for pediatric SPN patients.