Surgical Resection Of Tumor Research Articles

Effect of vestibular loss on head-on-trunk stability in individuals with vestibular schwannoma

The vestibulo-collic reflex generates neck motor commands to produce head-on-trunk movements that are essential for stabilizing the head relative to space. Here we examined the effects of vestibular loss on head-on-trunk kinematics during voluntary behavior. Head and trunk movements were measured in individuals with vestibular schwannoma before and then 6 weeks after unilateral vestibular deafferentation via surgical resection of the tumor. Movements were recorded in 6 dimensions (i.e., 3 axes of rotation and 3 axes of translation) using small light-weight inertial measurement units while participants performed balance and gait tasks. Kinematic measures differed between individuals with vestibular schwannoma (at both time points) and healthy controls for the more challenging exercises, namely those performed in tandem position or on an unstable surface without visual input. Quantitative assessment of the vestibulo-ocular reflex (VOR) revealed a reduction in VOR gain for individuals with vestibular schwannoma compared to control subjects, that was further reduced following surgery. These findings indicated that the impairment caused by either the tumor or subsequent surgical tumor resection altered head-on-trunk kinematics in a manner that is not normalized by central compensation. In contrast, we further found that head-on-trunk kinematics in individuals with vestibular schwannoma were actually comparable before and after surgery. Thus, taken together, our results indicate that vestibular loss impacts head-on-trunk kinematics during voluntary balance and gait behaviors, and suggest that the neural mechanisms mediating adaptation alter the motion strategies even before surgery in a manner that may be maladaptive for long-term compensation.

Resection of the Primary Tumor and Survival in Patients with Single-Site Synchronous Oligometastatic Non-Small Cell Lung Cancer: Propensity-Matched Analysis of the National Cancer Database.

Local therapy for the primary tumor is postulated to remove resistant cancer cells as well as immunosuppressive cells from the tumor microenvironment, potentially improving response to systemic therapy (ST). We sought to determine whether resection of the primary tumor was associated with overall survival (OS) in a multicentric cohort of patients with single-site synchronous oligometastatic non-small cell lung cancer. Using the National Cancer Database (2018 to 2020), we evaluated patients with clinical stage IVA disease who received ST and stratified the cohort based on receipt of surgery for the primary tumor (S). We used multivariable and propensity score-matched analysis to study factors associated with S (logistic regression) and OS (Cox regression and Kaplan-Meier), respectively. Among 12,215 patients identified, 2.9% (N = 349) underwent S and 97.1% (N = 11,886) ST (chemotherapy or immunotherapy) without surgery. Patients who underwent S were younger, more often White, had higher income levels, were more likely to have private insurance, and were more often treated at an academic facility. Among those who received S, 22.9% (N = 80) also underwent resection of the distant metastatic site. On multivariable analysis, metastasis to bone, N+ disease, and higher T-stages were independently associated with less S. On Cox regression, S and resection of the metastatic site were associated with improved survival (hazard ratio 0.67, 95% CI 0.56 to 0.80 and hazard ratio 0.80, 95% CI 0.72 to 0.88, respectively). After propensity matching, OS was improved in patients undergoing S (median 36.8 vs 20.8 months, log-rank p < 0.001). Advances in ST for non-small cell lung cancer may change the paradigm of eligibility for surgery. This study demonstrates that surgical resection of the primary tumor is associated with improved OS in selected patients with single-site oligometastatic disease.

Magnetocaloric‐Responsive Hydrogel Nanoarchitectonics for Pyroptosis‐Relay‐Immunotherapy to Suppress Post‐Operation Tumor Recurrence and Metastasis

AbstractAlthough a widely used option in contemporary anticancer treatment, surgery still causes serious issues, including post‐operation recurrence and the development of metastases. Immunotherapy, often following surgical resection of a tumor, has demonstrated benefits in improving the therapeutical outcomes of surgery. However, antigen generation and presentation play an essential role in reversing limited T‐cell responses or immunological resistance. Thus, a gelatin‐tannic acid gel (GelTA) crosslinked bimetallic (Zn0.35Fe0.65) magnetocaloric‐responsive hydrogels (GelTAMNPs) are developed to mediate pyroptosis‐relay‐immunotherapy for suppressing post‐operation tumor recurrence and metastasis. After surgical resection of tumor, GelTAMNPs generate hyperthermia inducible by alternating magnetic field and release ions (Fe3+, Fe2+, and Zn2+), reinforcing pyroptosis. Subsequently, the cell contents and cytokines released due to pyroptosis act as a “relay baton” passed from the tumor to the lymph nodes, leading to an enhanced systemic immune response. Combined with the PD‐1 immune checkpoint blockade, the recurrence and metastasis are significantly suppressed. An in vivo preclinical study on B16F10 tumor‐bearing mice demonstrates a long‐lasting immunological activation due to post‐surgical administration of GelTAMNPs. Altogether, the presented hydrogel exhibits a potential high magnetic sensitive pyroptosis‐relay‐immunotherapeutic platform for postoperative adjuvant treatment.

Disparities in Survival and NCCN Guideline-Concordant Care in Patients With Extremity Soft Tissue Sarcoma.

Based on the NCCN Guidelines for Soft Tissue Sarcoma (STS), treatment of extremity STS (ESTS) includes radiation therapy (RT) and surgical resection for tumors that are high-grade and >5 cm. ​​The aim of this study was to describe the association between neighborhood socioeconomic status (nSES), concordance with NCCN Guidelines recommendations, and outcomes in patients with ESTS. Patients with ESTS diagnosed from 2006 through 2018 were identified in SEER registries. The analytic cohort was restricted to patients with high-grade tumors >5 cm without nodal or distant metastases who received limb-sparing surgery. Patient demographics and tumor characteristics associated with receipt of RT were analyzed using adjusted regression analyses. Kaplan-Meier curves and adjusted accelerated failure time models were used to examine disparities in cancer-specific survival. Of 2,249 patients, 29.0% (n=648) received neoadjuvant RT, 49.7% (n=1,111) received adjuvant or intraoperative RT, and 21.3% (n=476) did not receive RT. In adjusted analyses, lower nSES was associated with lower likelihood of receiving RT (odds ratio, 0.70 [95% CI, 0.57-0.87]; P<.001). Low nSES was associated with worse cancer-specific survival (hazard ratio, 1.19 [95% CI, 1.01-1.40]; P=.04). Race and ethnicity were not significant predictors of receipt of RT or cancer-specific survival in the fully adjusted models. Patients from lower nSES areas were less likely to receive NCCN Guideline-recommended RT for their ESTS and had worse cancer-specific survival. Efforts to better define and resolve disparities in the treatment and survival of patients with ESTS are warranted.

Spontaneous delayed CSF rhinorrhea associated with encephalocele following surgical resection of a giant frontoparietal meningioma, an extremely rare entity and overlook of English literature

Introduction and importance: Spontaneous cerebrospinal fluid (CSF) rhinorrhea without a history of head trauma is rare. The authors describe a scarce case of spontaneous, nontraumatic, delayed CSF rhinorrhea due to ethmoidal encephalocele associated with frontoparietal giant meningioma. Case presentation: A 49-year-old male complained of a slowly growing skull mass lasting 10 years since a blunt head trauma and progressive hemiparesis 3 months ago and was referred to our center. There was a heterogeneous extra-axial mass (77×77×70 mm) with calcified components at his right frontal lobe, demonstrating notable adjacent parenchymal edema and a midline shift to the left. There was a sizeable extra-axial mass (113×95×80 mm) in his right front-temporoparietal lobe associated with adjacent invasion to calvarium leading to the lytic and sclerotic appearance of the calvarial bone showing intense heterogeneous contrast enhancement and an adjacent enhancing dural tail. A considerable mass effect on the adjacent frontotemporal cortex is evident, with mild parenchymal edema leading to a notable midline shift to the left, right uncal herniation, and left ventriculomegaly. On postoperation day 5, the patient developed a recurrent CSF leak exacerbated by hydrocephalus. He was rescheduled to undergo endoscopic endonasal surgery and dural repair on postoperative day 7. The postoperative course was uneventful. Clinical discussion: Frontoparietal lobe encephaloceles represent the least common cause of spontaneous CSF rhinorrhea. Early diagnosis and surgical management remain crucial to minimize the subsequent complications. Conclusion: The ventricular anatomy and CSF fluid dynamics alteration following tumor surgical resection seem to contribute to an environment by which a herniated ethmoidal encephalocele developed a delayed nontraumatic CSF leak.

An Observational Comparative Study to Evaluate the Use of Image-Guided Surgery in the Management and Outcome of Supratentorial Intracranial Space-Occupying Lesions.

The objective of this article is to study the effect of neuronavigation on the outcome of surgery for supratentorial tumors, such as the extent of resection, size of craniotomy, and overall morbidity and mortality by comparing with conventional excision. A total of 50 patients undergoing intracranial surgery for supratentorial space-occupying lesions from 2020 to 2022 were included in the study. One intervention group consisted of patients undergoing surgical resection of supratentorial tumors utilizing image guidance versus the control group, which consisted of patients undergoing surgical excision of supratentorial tumor excision without image guidance. Parameters used to compare the outcome were the extent of resection of the lesions, craniotomy size, and overall morbidity and mortality. There was no significant reduction in craniotomy size or prolongation of operative duration with the use of neuronavigation. There was no significant difference in postoperative hospital stay between the two groups. Neuronavigation-assisted cases did not show any significant reduction in the occurrence of postoperative neurological deficits or any reduction of overall morbidity and mortality.

Association between personality types and low anterior resection syndrome in rectal cancer patients following surgery.

Low anterior resection syndrome (LARS) has had many impacts on the lives of patients and substantial differences in emotional and social functions. The aim of this study was to investigate the correlation analysis of different personality traits in rectal cancer patients with LARS after undergoing curative surgery. This study was designed as a prospective cohort study. The inclusion criteria included (1) participants diagnosed with rectal cancer who underwent surgical resection of malignant tumors and (2) ECOG 0-1. The primary outcome was the correlation between different personality traits and low anterior resection syndrome in rectal cancer patients after radical surgery. Low anterior resection syndrome incidence rates were estimated by questionnaires and personality groups by the Type A and Type D Scale-14 Personality Inventory. For all 161 participants in this study, the presence of a tumor at the lower anal verge and the receipt of neoadjuvant CCRT had a statistically significant positive correlation with the LARS score at 1 month, 6 months, and 1 year (Pearson correlation coefficient = -0.283, -0.374, and - 0.205, respectively), with a p value of less than 0.05. Personalities with Type A, Type D, and Type D-SI scores had a statistically significant positive correlation with LARS score at 1 month (Pearson correlation coefficient = 0.172, 0.162, and 0,164, p value = 0.03, 0.04, and 0.04). Type A and Type D personalities are highly linked to LARS. Personalized support approaches can ultimately assist rectal cancer patients in overcoming difficulties after surgery and recovery and enhance their functional outcomes.

Intraoperative Neurophysiologic Monitoring and Mapping During Surgery on Intramedullary Spinal Cord Tumors in Children and Adolescents.

Surgical resection of intramedullary spinal cord tumors carries significant risks of neurologic deficits, especially in cases of infiltrative tumors. In pediatric patients, this type of surgery may be associated with a high risk of poor neurologic outcome. Intraoperative neurophysiologic monitoring has been adopted as part of the clinical routine by many centers as a useful adjunct for intraoperative assessment of neurologic integrity. To what extent intraoperative neurophysiologic mapping strategies may further support intraoperative decision-making is still a matter of debate. Here, we report on a small cohort of five pediatric patients in whom mapping with the double-train paradigm was used to identify the dorsal column and corticospinal tract and to guide the surgical resection. We also discuss the possible benefits and challenges regarding the available literature.

Intratumor injected gold molecular clusters for NIR-II imaging and cancer therapy

Surgical resections of solid tumors guided by visual inspection of tumor margins have been performed for over a century to treat cancer. Near-infrared (NIR) fluorescence labeling/imaging of tumor in the NIR-I (800 to 900 nm) range with systemically administrated fluorophore/tumor-targeting antibody conjugates have been introduced to improve tumor margin delineation, tumor removal accuracy, and patient survival. Here, we show Au25 molecular clusters functionalized with phosphorylcholine ligands (AuPC, ~2 nm in size) as a preclinical intratumorally injectable agent for NIR-II/SWIR (1,000 to 3,000 nm) fluorescence imaging-guided tumor resection. The AuPC clusters were found to be uniformly distributed in the 4T1 murine breast cancer tumor upon intratumor (i.t.) injection. The phosphocholine coating afforded highly stealth clusters, allowing a high percentage of AuPC to fill the tumor interstitial fluid space homogeneously. Intra-operative surgical navigation guided by imaging of the NIR-II fluorescence of AuPC allowed for complete and non-excessive tumor resection. The AuPC in tumors were also employed as a photothermal therapy (PTT) agent to uniformly heat up and eradicate tumors. Further, we performed in vivo NIR-IIb (1,500 to 1,700 nm) molecular imaging of the treated tumor using a quantum dot-Annexin V (QD-P3-Anx V) conjugate, revealing cancer cell apoptosis following PTT. The therapeutic functionalities of AuPC clusters combined with rapid renal excretion, high biocompatibility, and safety make them promising for clinical translation.

A blinded study using laser induced endogenous fluorescence spectroscopy to differentiate ex vivo spine tumor, healthy muscle, and healthy bone

Ten patients undergoing surgical resection for spinal tumors were selected. Samples of tumor, muscle, and bone were resected, de-identified by the treating surgeon, and then scanned with the TumorID technology ex vivo. This study investigates whether TumorID technology is able to differentiate three different human clinical fresh tissue specimens: spine tumor, normal muscle, and normal bone. The TumorID technology utilizes a 405 nm excitation laser to target endogenous fluorophores, thereby allowing for the detection of tissue based on emission spectra. Metabolic profiles of tumor and healthy tissue vary, namely NADH (bound and free emission peak, respectively: 487 nm, 501 nm) and FAD (emission peak: 544) are endogenous fluorophores with distinct concentrations in tumor and healthy tissue. Emission spectra analyzed consisted of 74 scans of spine tumor, 150 scans of healthy normal bone, and 111 scans of healthy normal muscle. An excitation wavelength of 405 nm was used to obtain emission spectra from tissue as previously described. Emission spectra consisted of approximately 1400 wavelength intensity pairs between 450 and 750 nm. Kruskal–Wallis tests were conducted comparing AUC distributions for each treatment group, α = 0.05. Spectral signatures varied amongst the three different tissue types. All pairwise comparisons among tissues for Free NADH were statistically significant (Tumor vs. Muscle: p = 0.0006, Tumor vs. Bone: p < 0.0001, Bone vs. Muscle: p = 0.0357). The overall comparison of tissues for FAD (506.5–581.5 nm) was also statistically significant (p < 0.0001), with two pairwise comparisons being statistically significant (Tumor vs. Muscle: p < 0.0001, Tumor vs. Bone: p = 0.0045, Bone vs. Muscle: p = 0.249). These statistically significant differences were maintained when stratifying tumor into metastatic carcinoma (N = 57) and meningioma (N = 17). TumorID differentiates tumor tissue from normal bone and normal muscle providing further clinical evidence of its efficacy as a tissue identification tool. Future studies should evaluate TumorID’s ability to serve as an adjunctive tool for intraoperative assessment of surgical margins and surgical decision-making.

Epidemiology, characteristics, and prognostic factors of lymphoplasmacyte-rich meningioma: a systematic literature review

BackgroundsLymphoplasmacyte-rich meningioma(LPM) is a rare subtype of meningioma with a low degree of malignancy and an overall preferable prognosis. The purpose of this article is to increase the understanding of the disease, reduce misdiagnosis, and improve prognosis.MethodsA search was conducted in the PubMed database for English articles published from 1993 to 2023. The keywords were "lymphoplasmacyte-rich (all fields) and meningioma (all fields) and English (lang)" and "lymphoplasmacyte-rich meningioma (title/abstract) and English (lang)".We further analyzed the clinical manifestations, imaging manifestations, pathological features, treatment strategies, and prognosis of LPM.The possible prognostic indicators were analyzed by the log-rank test and Pearson’s chi-squared test.ResultsFourteen reports with 95 LPM patients were included in this report, including 47 males and 48 females who were diagnosed between the ages of 9 and 79, with an average age of 45 years. The most common clinical manifestations are headache and limb movement disorders. In most cases, the tumor occurred on the convex portion of the brain. All tumors showed significant enhancement, with homogeneous enhancement being more common, and most patients showed peritumoral edema. Postoperative pathological EMA, LCA, and vimentin positivity were helpful for the final diagnosis of the patient. Log-rank tests showed a correlation between complete resection and better prognosis and recurrence.ConclusionThere is a lack of significant differences in the clinical symptoms and imaging manifestations of LPM compared to other diseases that need to be differentiated, and a clear diagnosis requires pathological examination. After standardized surgical treatment, the recurrence rate and mortality rate of LPM are both low. Complete surgical resection of tumors is associated with a better prognosis and lower recurrence rate.

Wnt/β-catenin-C-kit axis may play a role in adenoid cystic carcinoma prognostication

Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. ACC is composed of myoepithelial and epithelial neoplastic cells which grow slowly and have a tendency for neural invasion. The long term prognosis is still relatively poor. Although several gene abnormalities, such as fusions involving MYB or MYBL1 oncogenes and the transcription factor gene NFIB, and overexpression of KIT have been reported in ACC, their precise functions in the pathogenesis of ACC remain unclear. We recently demonstrated that the elevated expression of Semaphorin 3A (SEMA3A), specifically expressed in myoepithelial neoplastic cells, might function as a novel oncogene-related molecule to enhance cell proliferation through activated AKT signaling in 9/10 (90%) ACC cases. In the current study, the patient with ACC whose tumor was negative for SEMA3A in the previous study, revisited our hospital with late metastasis of ACC to the cervical lymph node eight years after surgical resection of the primary tumor. We characterized this recurrent ACC, and compared it with the primary ACC using immunohistochemical methods. In the recurrent ACC, the duct lining epithelial cells, not myoepithelial neoplastic cells, showed an elevated Ki-67 index and increased cell membrane expression of C-kit, along with the expression of phosphorylated ERK. Late metastasis ACC specimens were not positive for β-catenin and lymphocyte enhancer binding factor 1 (LEF1), which were detected in the nuclei of perineural infiltrating cells in primary ACC cells. In addition, experiments with the GSK-3 inhibitor revealed that β-catenin pathway suppressed not only KIT expression but also proliferation of ACC cells. Moreover, stem cell factor (SCF; also known as KIT ligand, KITL) induced ERK activation in ACC cells. These results suggest that inactivation of Wnt/β-catenin signaling may promote C-kit-ERK signaling and cell proliferation of in metastatic ACC.

Oncogenic aberrations in primary gastric cancer tumors to predict metachronous peritoneal metastasis.

392 Background: Peritoneal metastases (PM) in gastric cancer (GC) portend a poor prognosis. Yet, there are a paucity of data on underlying genomic alterations predictive of GCPM. Methods: Two-hundred and nine patients who underwent primary tumor (PT) surgical resection were included in the prospective cohort. Whole exome sequencing (WES) of these resected PT GC specimens (average coverage 129X for tumor samples, 70X coverage for matched normal/blood controls) were undertaken. Participants were followed-up longitudinally for peritoneal metastases. Results: Fifty-one (51/209, 24.4%) patients developed PM after a median follow-up duration of 87.0 months and had poorer survival outcomes compared to patients without metastasis (log-rank, p&lt;0.001). Patients with bulkier and more advanced tumors were at increased hazard of PM (T-stage and N-stage stratified analysis, log-rank, p&lt;0.0001). Consistent with known clinical outcomes, The Cancer Genome Atlas (TCGA) genomically stable (GS) subtype (log-rank, p=0.0059) and mesenchymal subtype GC were associated with a higher proclivity for peritoneal organotropism (log-rank, p=0.020). Among patients who developed PM, TP53 was the most commonly altered driver mutation (25/51, 49.0%), followed by ARID1A (9/51, 17.6%), CDH1 (8/51, 15.7%), PIK3CA (6/51, 11.8%). Comparing the PTs of patients with PM against those PTs without PM, ELF3, CDH1 and PIGR were significantly associated with PM (all adjusted p&lt;0.05). Amongst TCGA GS tumors, ARID1A mutations (p=0.018) were significantly associated with PM compared to patients with GS tumors with no metastasis. CDH1 mutations were found to significantly co-occur with PIGR and RHOA mutations and was mutually exclusive to TP53. ARID1A mutations were also found to significantly co-occur with multiple other mutations such as PTEN, PIK3CA, ERBB2, and KRAS. Conclusions: CDH1, PIGR, ELF3 mutations in primary GC tumors were found to be significantly associated with metachronous PM.

Clinical characteristics of intradermal nevus in the external auditory canal.

Melanocytic nevus occurring in the external auditory canal (EAC) is uncommon. Therefore, in the absence of sufficient clinical experience, this disease may be challenging to be suspected even with a physical examination. Herein, clinical and demographic features of intradermal nevus in the EAC were investigated. Patients with an intradermal nevus on histopathological examination (n = 15; 2 men and 13 women; P = .005) were included from a pool of patients who underwent surgical resection for EAC tumors between November 2011 and March 2022. Data were retrospectively collected on their sex, appearance of the lesions, surgical method, and outcomes. Nine patients had a dome shape and 6 patients had a papillomatous shape. Ten patients had dark colors and 5 patients had pale colors. All pale colors appeared only in the dome-shaped nevus, and only dark colored papillomatous nevi were observed. A significant difference was noted in terms of the frequency of occurrence by colors (dark or pale) according to shape (dome or papillomatous) (P = .044). No patient showed recurrence or EAC stenosis after circumferential excision. In women, a dome-shaped or papillomatous mass with dark color in the EAC may likely be predicted as the nevus. However, it can also occur in men, and even if it is a pale color, in the case of a dome shape, taking the nevus into account is important. Moreover, successful treatment outcomes were achieved through circumferential excision.

Abstract A021: Adjuvant iC9.B7-H3 CAR T cell-based immunotherapy effectively eradicates local and distant metastases in pancreatic ductal adenocarcinoma

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Despite negative margin resections of the cancer and systemic therapy, PDAC often recurs. Pancreatic cancer-associated fibroblasts (CAFs) contribute to a highly desmoplastic tumor microenvironment (TME), preventing T cell infiltration. Moreover, CAF-secreted factors suppress the anti-tumor activity of T cells and shift tumor cells toward invasive proliferative and mesenchymal phenotypes. Therefore, targeting CAFs can enhance T-cell infiltration and improve treatment outcomes. In this study, we investigate using Chimeric Antigen Receptor (CAR) T cells targeting B7-H3 to eliminate PDAC metastatic disease in a preclinical mouse model. B7-H3, an immune checkpoint molecule, is highly expressed on PDAC cells and CAFs. Our CART-B7-H3 construct includes an inducible caspase 9 (iC9) suicide gene, which allows for the controlled elimination of the CAR T cells in the event of overwhelming cytokine release syndrome. Methods: The efficacy of iC9.B7-H3 CAR T cells was tested in vitro against human PDAC and fibroblast cell lines at various ratios. The antitumor activity of iC9.B7-H3 CAR T cells was assessed in PDAC cells after exposure to CAF-conditioned media, simulating TME with immunosuppressive cytokines. To validate the therapeutic potential of iC9.B7-H3 CAR T cells in vivo, NSG mice were orthotopically engrafted with patient-derived PDAC6 cells and hCAF1 cells at a ratio of 1:9, reflecting a clinically relevant model. After three weeks, the mice underwent surgical resection of the primary tumor (distal pancreatectomy and splenectomy) and were subsequently treated systemically with iC9.B7-H3 CAR T cells. Results: In vitro, at a high effector-to-target (E:T) ratio, iC9.B7-H3 CAR T cells effectively eliminated PDAC cells and CAFs. However, their anti-tumor activity was diminished when the E:T ratio was lowered (PDAC6 tumor cell killing (TCK): 92±5% at 1:1, hCAF1 TCK: 81.67±5% at 1:1, compared to PDAC6 TCK: 26±5% at 1:10, hCAF1 TCK: 0% at 1:10, P&amp;lt;0.0001). PDAC cells co-cultured with CAF cells demonstrated reduced susceptibility to elimination by iC9.B7-H3 CAR T cells compared to PDAC cells alone (PDAC3 TCK: 92±5% at 1:1, PDAC3+hCAF1 (1:9 ratio) TCK: 81±5% at 1:1, P=0.002). However, incubation with CAF-conditioned media did not significantly affect the elimination of PDAC cells by iC9.B7-H3 CAR T cells, which may suggest that CAFs may require direct cell-cell contact to exert their effects. In vivo, iC9.B7-H3 CAR T cells effectively eradicated both local and distant PDAC metastases for the length of the experiment (160 days), indicating long-term efficacy in the treatment of PDAC metastases with no adverse side effects. Conclusion: These data suggest that iC9.B7-H3 CAR T cells may be an effective adjuvant treatment for the eradication of micro-metastases and the prevention of disease recurrence in PDAC patients. Citation Format: Shahrzad Arya, Seyed Amir Sanatkar, Cristina Martin, Marco Ventin, Jingyu Jia, Giulia Cattaneo, Gabriella Lionetto, David T. Ting, Xinhui Wang, Sandra Ryeom, Cristina R. Ferrone, Soldano Ferrone. Adjuvant iC9.B7-H3 CAR T cell-based immunotherapy effectively eradicates local and distant metastases in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A021.

Abstract A024: B cells facilitate lymph node colonization in pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC) has a low survival rate. Several factors contribute to its dismal prognosis, including resistance to available therapies and high invasiveness. Lymph nodes act as an early systemic source of circulating malignant cells in PDAC, allowing their dissemination to other organs early in disease progression. Lymphatic colonization is linked to worse prognosis. Therefore, a better understanding of mechanisms regulating lymph node metastasis is clinically needed. To study each step in the metastatic cascade to the lymph nodes, we have developed a mouse co-clinical model of resectable pancreatic cancer. This model consists of subcutaneous injection of highly metastatic pancreatic cancer cells, followed by surgical resection of the primary tumor. Following resection, mice spontaneously develop lymph nodes metastasis at a comparable frequency to human PDAC post-surgical recurrence, on a similar time scale relative to the lifespans of mice and humans. Expression of nuclear tdTomato allows detection of single cancer cells seeding the draining lymph nodes early in disease progression, even before metastases are histological detectable. Using this model, we are gaining insights into the first steps of metastatic seeding of lymph nodes, and have identified a pro-metastatic role for B cells. These findings will enhance our understanding of lymphatic colonization in PDAC and potentially inform immunotherapeutic interventions to disrupt the metastatic cascade. Citation Format: Alice Bertocchi, Megan T. Hoffman, Li Qiang, Lauren Hsu, Michael Dougan, Judith Agudo, Stephanie K. Dougan. B cells facilitate lymph node colonization in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A024.

Abstract C102: Investigating rapid metastatic recurrence of pancreatic cancer after resection in a novel, immune-competent, Myc-dependent murine model

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a median survival time of 10-12 months and an overall 5-year survival rate of 12%. Current treatment includes chemotherapy and surgery; however, only 20% of patients are eligible for resection due to the majority presenting with locally advanced or metastatic disease. Alarmingly, 20-30% of patients who undergo resection of their primary tumor experience rapid liver metastasis within 6 months of surgery. This “rapid recurrence” (rrPDAc) is devastating and poorly understood, contributing to the nihilism surrounding pancreatic cancer. Whether rapid metastases seed before surgery, or surgery results in seeding is unknown. We hypothesize both cases would be affected by systemic and microenvironmental changes that occur due to surgical intervention. In RNA-seq of human rrPDAc primary tumors, we identified increased expression of MYC-targets when compared to those who recurred 18 months or later after surgery (LTR). Cyclic immunofluorescence of primary tumors revealed increased pS62-Myc, replication stress, and DNA damage repair in rrPDAC compared to LTR primary tumors. Furthermore, we identified differences in the tumor immune microenvironments between rrPDAC and LTR, in the absence of substantial clinical differences. To study this phenomenon, we developed an immune competent mouse model of surgically resected human PDAC that models rapid recurrence compared to control mice. Our lab has developed an inducible, p48-Cre-recombinase driven LSL-KrasG12D/+ LSL-ROSA-MYC+/+ mouse model that reproducibly develops ADM to PanIN to PDAC lesions that highly recapitulate human disease progression and are liver metastatic. Considering the role MYC plays in regulation of the immune microenvironment, we hypothesized cell lines derived from this model would perform well in a model of rapid recurrence. We derived several cell lines from these tumors and implanted them orthotopically in syngeneic mice, monitoring tumor development over fourteen days with ultrasound. Mice are then randomized into anesthesia only control, sham operation, and tumor resection groups and tracked via twice-weekly trans-abdominal ultrasound. Mice that undergo surgical tumor resection develop liver metastases 11 days earlier than anesthesia only controls (p &amp;lt;0.0001) and sham mice developed liver metastases 10 days earlier than controls (p=0.02, suggesting that surgical intervention perturbs the development of metastatic lesions. This model will allow for investigation into rrPDAc and the role surgery may play in exacerbation of metastasis. Citation Format: Jackie L. Phipps, Isabel English, Jennifer Chu, Gustavo Salgado Garza, Jason Link, Ellen Langer, Motoyuki Tsuda, Kevin MacPherson, Carl Pelz, Jonathan Brody, Brett Sheppard, Rosalie Sears, Patrick Worth. Investigating rapid metastatic recurrence of pancreatic cancer after resection in a novel, immune-competent, Myc-dependent murine model [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C102.

Trap-Door Thoracotomy and Clamshell Thoracotomy as Surgical Approaches for Neuroblastoma and Other Thoracic Tumors in Children.

Solid tumors of the cervicothoracic junction, the posterior mediastinum, or bilateral dorsal thoracic tumors represent a challenge in pediatric surgical oncology. The aim of this study was to evaluate trap-door thoracotomy and clamshell thoracotomy as surgical approaches. A single-center retrospective study of children with solid tumors in these specific localizations was performed. From 2015 to 2023, 26 children (17 girls; 9 boys) were treated at a median age of 54 months (range 8-229). Tumor resection was performed for neuroblastoma (n = 11); metastatic disease (n = 7); malignant rhabdoid tumor (n = 4); Ewing sarcoma (n = 1); inflammatory myofibroblastic tumor (n = 1); rhabdomyosarcoma (n = 1); and neurofibroma (n = 1). The surgical goal of macroscopic complete excision was achieved in all of the 14 children who underwent trap-door thoracotomy and in 11 of the 12 children who underwent clamshell thoracotomy. There were no major complications. At a median follow-up of 8 months (range 0-60), the disease was under local control or in complete remission in 66.7% of the children. In conclusion, surgical resection of solid tumors of the cervicothoracic junction in children can be performed safely and successfully with trap-door thoracotomy and with clamshell thoracotomy for posterior mediastinal or bilateral dorsal thoracic tumors.

Familial multiple endocrine neoplasia type 1 with intrathoracic low-grade fibromyxoid sarcoma

BackgroundMultiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by endocrine tumors with mainly a parathyroid, pancreatic, or anterior pituitary origin. Low-grade fibromyxoid sarcoma (LGFMS) is a rare low-grade soft tissue tumor. There is one known report of a patient with MEN1 complicated by LGFMS, which is very rare. Our report represents the second documented case, providing valuable insights.Case presentationA 31-year-old man with the chief complaint of a cough underwent chest contrast-enhanced computed tomography, which revealed a giant hypoabsorptive tumor with a maximum diameter of 23 cm in the left thoracic cavity. The patient was diagnosed with MEN1, as he also possessed a pancreatic neuroendocrine tumor and parathyroid tumor, and because his father had been found to have MEN1. To control hypercalcemia, surgery for the parathyroid tumor was initially performed, followed by surgical resection of the giant thoracic tumor for diagnosis and treatment. Histopathological examination findings of the tumor resulted in a diagnosis of LGFMS.ConclusionWe experienced a very rare MEN1 with LGFMS. Although endocrine tumors generally occur more frequently in MEN1, non-endocrine tumors such as the present case should also be noted, reinforcing the importance of systemic imaging scrutiny in addition to early diagnosis and long-term follow-up of MEN1 patients.

Red blood cell transfusion in patients undergoing elective primary glioblastoma resection.

Red blood cell (RBC) transfusion in patients undergoing major elective cranial surgery is associated with increased postoperative morbidity and mortality. This study aims to identify the clinical outcome of transfused glioblastoma patients undergoing primary surgical tumor resection and identify risk factors for RBC transfusion. Between 2009 and 2019, 406 patients underwent elective primary glioblastoma resection. For multivariate analysis to assess risk factors for RBC transfusion, logistic regression was conducted. The impact of RBC transfusion on overall survival was assessed using Kaplan-Meier analysis. In total, 36 (8.9%) patients received RBC transfusion. Preoperative anemia rate was significantly higher in transfused patients compared to patients without RBC transfusion (33.3 vs 6.5%; p<0.0001). Postoperative complications as well as hospital length of stay (LOS) (p<0.0001) were significantly increased in transfused patients compared to non-transfused patients. After multivariate analysis, risk factors for RBC transfusion were preoperative anemia (p<0.0001), intraoperative blood loss (p<0.0001), female gender (p=0.0056) and radiation (p=0.0064). Kaplan-Meier curves revealed that RBC transfusion and being elderly (age ≥75 years) were relevant for overall survival. RBC transfusion is associated with increased postoperative morbidity and mortality in patients undergoing elective primary glioblastoma resection. Preoperative anemia and intraoperative blood loss are major risk factors for RBC transfusion. Preoperative anemia management and blood conservation strategies are crucial in patients undergoing elective primary glioblastoma resection.