Tumor Recurrence Research Articles

Rhabdomyosarcoma Presenting as an Infective Midline Nodule on the Chin in an Eight-year-old Child

Background and Aims: Rhabdomyosarcoma (RMS) is the most common subtype of soft tissue sarcoma (STS) in children. Early diagnosis is the most favourable prognostic factor and thus physicians need to include RMS in the differential diagnosis of more common diseases developing within the head and neck region. This report highlights the same while describing a case of an eight-year-old child who presented with a chin swelling which turned out to be an RMS. Methods: We present a rare case of an eight-year-old child with a midline painless mass. Results: This child had a transoral resection of the mass. He undertook further chemotherapy and was completely cured with no tumour recurrence. Conclusion: In a painless rapidly increasing mass in the head and neck area, despite rare, but RMS should be included as a differential diagnosis. This is important as early diagnosis and proper resection and treatment are paramount in the prognosis of the disease.

7065 Eradication Of Metastatic ER-Positive Breast, Ovarian, Endometrial And Lung Cancer In Mouse Xenografts And Patient Derived Organoids

Abstract Disclosure: D.J. Shapiro: None. D. Duraki: None. S. Ghosh: None. J. Zhu: None. C. Mao: None. J. Kim: None. M. Jabeen: None. M.W. Boudreau: None. M.P. Mulligan: None. R. Romero: None. Y. Han: None. J. Zhang: None. E.R. Nelson: None. O. Olopade: None. G. Chang: None. P.J. Hergenrother: Advisory Board Member; Self; Systems Oncology. We described the tumor protective estrogen-ER activated anticipatory Unfolded Protein Response (a-UPR) pathway. Here we report a previously undescribed multistep pathway by which very rapid estrogen-ER activation of the a-UPR authorizes and regulates subsequent transcription of the estrogen-ER transcriptome. We repurposed the tumor protective a-UPR through identification and optimization of the small molecule ErSO and its family of agents. ErSO acts non-competitively with estrogen to induce lethal hyperactivation of the a-UPR. In orthotopic mouse xenografts containing wild type or mutant ER, ErSO often induced complete regression without recurrence of large primary breast tumors and of most lung, bone and liver metastases, near complete regression of normally lethal brain metastases and complete destruction of patient derived organoids (PDOs) in Matrigel. Six research teams in four locations have confirmed the remarkable effectiveness of ErSO in ER-positive breast cancer. We next evaluated ErSO in diverse ER containing cancers in which estrogen is not the primary driver of proliferation. ErSO often induced complete regression in multiple orthotopic xenograft models of primary and metastatic ovarian cancer. Using fresh ovarian cancer organoids immediately after removal from patients by paracentesis, ErSO destroyed the organoids from some patients with advanced stage III and stage IV disease. ErSO was effective in a mouse xenograft model of endometrial cancer and, surprisingly, even in ERalpha positive lung cancer. Our ongoing studies demonstrate ErSO induces complete, or near complete regression, of primary and metastatic lung cancer in mice. Studies of ErSO’s mechanism of action using genome-wide CRISPR screens with positive selection, and other techniques, unveil a novel death pathway in which ErSO activation of the a-UPR triggers rapid calcium release into the cell body. The calcium opens the plasma membrane TRPM4 sodium channel, leading to an influx of extracellular sodium. This swells the cells, resulting in osmotic stress that sustains lethal a-UPR activation. A little-studied cytoskeleton regulator we identified, FGD3, plays a pivotal role in whether the cells rupture their membranes, inducing necrotic cell death. Notably, medium from diverse cancer cells killed by ErSO-induced necrosis robustly activates human macrophage and induces their migration - potentially facilitating immunotherapy. These studies describe a pathway from a multiprotein ER-SRC-PLC complex, through the a-UPR, to a novel cell swelling and necrosis pathway, that we are exploiting to target diverse, therapeutically challenging, ER-positive human cancers. Presentation: 6/2/2024

7962 Transformation of Poorly Differentiated Papillary Thyroid Carcinoma to Anaplastic Thyroid Carcinoma, an Atypical Course!

Abstract Disclosure: T. Altaweel: None. S. Makadsi: None. M. Hussein: None. J. Samantray: None. Introduction: Anaplastic thyroid cancers are undifferentiated, rare and aggressive. The transformation of papillary thyroid cancer to anaplastic thyroid cancer is documented in literature, however, rare. In this report, we present a case of Anaplastic thyroid carcinoma likely arising from a co-existing poorly differentiated Papillary carcinoma. Case Presentation: A 74-year-old male with past medical history of tobacco smoking who presented with the onset of voice hoarseness for 6 months. He has also noticed a left neck mass that is in the mid supraclavicular region. A Neck CT neck was performed at the time of presentation and was significant for a 4.6x3.4x5.9 cm left thyroid mass with displacement of the trachea. FNA biopsy showed papillary carcinoma with focal features of Tall Cell Variant. Poorly differentiated components with fragments of stroma and muscle were seen and suggested invasion. These findings raised the possibility of anaplastic thyroid carcinoma in the setting of papillary carcinoma and poorly differentiated carcinoma. BRAF V600E pathogenic variant mutation along with TERT mutation were found. Patient underwent direct laryngoscopy, bronchoscopy with biopsies, and tracheostomy with surgical pathology confirming papillary thyroid cancer with muscles invasion. Combination dabrafenib and trametinib were started. No surgical resection of thyroid tissue was planned. A follow up CT showed a significant decrease in the low-density soft tissue involving the medial thyroid gland bilaterally, consistent with interim positive response to therapy. Three months later, CT neck showed near complete resolution of low-density soft tissue involving the medial thyroid and parathyroid glands and subglottic trachea consistent with further interim positive response to therapy. Six months post initiation of therapy, CT Neck showed focal low density in the mid and inferior right thyroid gland which may represent residual and/or recurrent thyroid carcinoma. That density was further demonstrated on a repeat CT neck as a 1.8 cm hypodense nodule in the inferior right thyroid gland and concerning for recurrent thyroid tumor with possible infiltration of the trachea. Conclusion: ATC prognosis is affected by many factors such as metastasis, age, treatment strategies, socioeconomic status and the presence of BRAF V600E and TERT mutations. Diagnosis can be challenging. Our patient presented months after his symptoms started and this is an atypical course of Anaplastic Thyroid Carcinoma as it usually progresses aggressively and rapidly. Given the pathology reports and the more slow presentation of this patient’s carcinoma, it can be suggested that this is a case of papillary carcinoma with a later transformation to ATC. In these cases, surgical resection Presentation: 6/2/2024

6671 A Recurrent Mass After Thyroid Cancer Treatment

Abstract Disclosure: N. Sekhon: None. K.Z. Win: None. Background: Differentiated thyroid cancers have an excellent prognosis if completely resected and their recurrence rate varies depending on the nature and type of the thyroid tumor. We report a case of symptomatic recurrent mass 1.5 years after hemithyroidectomy for a small locally invasive follicular thyroid cancer. The recurrent mass mimicked malignancy on ultrasound but was pathologically determined to be a suture granuloma. Case: A 62-year-old male with history of follicular thyroid cancer s/p left thyroidectomy presented with a symptomatic neck mass, dysphagia, voice change, and worsening snoring. Thyroid tumor pathology was reported as follicular carcinoma pT1bpNX, 1.4 cm in size, clear margins, no vascular invasion with one focus of transcapsular invasion. He had normal surveillance investigations including thyroglobulin and thyroid ultrasound. He had a normal esophagogastroduodenoscopy which was performed for dysphagia and choking. The thyroid ultrasound showed an indeterminate solid heterogeneous and hypoechoic ovoid soft tissue node measuring 6 mm x 3 mm x 5 mm just right of midline and a 4 mm left neck hypoechoic nodule with no central fatty hilus located lateral to the jugular vein. The lymph node morphology was not typically benign and the patient underwent fine needle aspirate of the mass suggestive of a benign mass. This was followed by surgical removal of the mass and pathologic identification of a suture granuloma. There was resolution of dysphagia after removal of the mass. Discussion: Thyroid tumor recurrence rate is about 15% and is usually seen in aggressive forms or in incomplete resections due to the unrecognized extent of the tumor. Recurrences can be local, regional or distant. Suture granuloma is a rare complication after thyroidectomy and reflects an inflammatory response to retained foreign material. It develops slowly after the thyroidectomy and presents as a painless mass mimicking malignancy or lymph node metastasis. Other lesions that can mimic thyroid cancer on ultrasonography include chronic granulomatous lesions, traumatic neuroma and surgical clip. Conclusion: Our case highlights that suture granuloma should be considered in addition to malignant recurrence in cases of painless mass at the site of thyroidectomy.

8322 Mast Cells: a New Player in Gonadotroph Tumors

Abstract Disclosure: M. Ilie: None. M. Lepetit: None. M. Chanal: None. A. Vasiljevic: None. E. Jouanneau: None. O. Gandrillon: None. F. Picard: None. G. Raverot: None. P. Bertolino: None. Context: While gonadotroph tumors lack both prognostic markers and medical treatment options, the tumor microenvironment (TME) stands as a promising therapeutic and prognostic tool. Aim: Identify new TME players in gonadotroph tumors, gain insight into the mechanisms of tumorigenesis driven by these TME cells, and identify new TME-related prognostic markers and therapeutic targets. Methods: Data analysis of single-cell transcriptomics of 6 gonadotroph tumors and spatial transcriptomics of 3 gonadotroph tumors. Immunohistological validation on a cohort of 50 gonadotroph tumors, including 10 paired recurrent tumors. Results: 24,471 sequenced cells from the 6 tumors were analyzed. As expected, we found all previously TME-reported cell types (including stromal, endothelial, monocytes/macrophages, stem, and T cells) and identified mast cells as a new population in gonadotroph tumors. Tryptase immunostaining and whole slides analysis confirmed the presence of mast cells in all 50 gonadotroph tumors (range 0.01-4.33%). Ligand-receptor networks analysis, done with CellPhoneDB, identified bilateral crosstalk between mast cells and endothelial cells. VEGFA was the top ranked secreted ligand signaling from mast cells towards endothelial cells, suggesting a proangiogenic role for mast cells. Consistent with this hypothesis, the percentage of mast cells was very strongly correlated with the percentage of endothelial cells in the 6 tumors (Spearman’s rho=0.94, p=0.01). Spatial transcriptomics analysis showed that mast cells and endothelial cells were frequently colocalized, which was confirmed by double tryptase/CD34 immunofluorescence. We further found mast cells to express more VEGFA than TNF in the 6 sequenced tumors, which is suggestive of a pro-tumorigenic role. Using a clinical cohort, we confirmed the association of mast cells with a bad prognosis, as tumors progressing/relapsing more rapidly after surgery had more mast cells (p=0.002). In addition, more mast cells were present in the recurrent compared to the initial tumor for a same patient (p=0.007). Finally, bioinformatic analysis using Nichenet pinpointed KITLG (acting via KIT) to be one of the probable drivers of VEGFA expression in mast cells. Interestingly, KITLG-KIT was also the top ranked interaction between endothelial and mast cells. Conclusion: We identified and validated the presence of mast cells in gonadotroph tumors. The phenotype of mast cells was indicative of a bad prognosis, which was confirmed in a clinical cohort of 40 patients. Moreover, bilateral crosstalk between mast cells and endothelial cells was indicative of a mutual potentiation, suggesting that KIT and VEGFA targeting might be beneficial for the treatment of gonadotroph tumors. Presentation: 6/1/2024

Sex differences in the molecular profile of adult diffuse glioma are shaped by IDH status and tumor microenvironment.

Sex differences in adult diffuse glioma (ADG) are well-established clinically, yet the underlying molecular mechanisms remain inadequately understood. Here, we aim to reveal molecular features and cellular compositions unique to each sex in ADG to comprehend the role of sex in disease etiology. We quantified sex differences in transcriptome of ADG using multiple independent glioma patient datasets. Next, we delved into the single-cell landscape to examine sex differences in gene expression and cellular composition. To explore how sex influences disease progression, we analyzed paired samples from primary and recurrent ADG cases, aiming to identify sex-specific differences in molecular and cellular features. Our analysis revealed that mutations in isocitrate dehydrogenase (IDH) genes and the tumor microenvironment emerged as primary influencers of sex-differential molecular enrichments. In IDHwt tumors, genes in neuronal signaling pathway are found to be enriched in male tumors, while genes in hypoxia and inflammatory response pathways are enriched in female tumors. This pattern was reversed in IDHmut gliomas. We hypothesized that these distinctions could be attributed to heterogeneous cellular composition between sexes. Using single-cell data, we observed distinctive patterns of sex differences in cell states, cell composition and cell-cell interaction in IDHwt and IDHmut tumors separately. Further, by comparing molecular changes in paired primary and recurrent ADG samples, we identified sex-specific differences in molecular characteristics and cellular compositions of recurrent tumors. Our results provide a comprehensive multi-level characterization of sex differences in ADG, such findings provide novel insights into glioma disease progression in each sex.

DAXX is associated with early recurrence of pancreatic neuroendocrine tumors after R0 resection

IntroductionATRX, DAXX, MEN1, and PTEN mutations are proposed drivers of pancreatic neuroendocrine tumor tumorigenesis and independent prognostic factors for metastasis and mortality. However, their implications after R0 resection remain debated. Thus, we sought to identify genomic signatures of pancreatic neuroendocrine tumor disease-specific mortality and recurrence after surgery for curative intent. MethodsPancreatic neuroendocrine tumor patients who underwent whole exome sequencing with available survival data were identified using cBioPortal. Clinicopathologic variables, genomics, and outcomes were analyzed. ResultsSeventy patients who underwent R0 resection were identified. Forty-five of 70 patients were disease free at last follow-up, whereas 25 of 70 patients had disease-specific mortality or recurrent disease and therefore were categorized as part of the recurrent cohort. There were no significant differences in age (P = .245), sex (P = .201), or median follow-up (38.9 vs 33.7 months, P = .122) between groups. Clinicopathologically, the recurrent cohort had significantly greater tumor size (median 5.0 cm vs 3.2 cm, P = .012) and were more likely to have vascular invasion (88% vs 40%, P = .000), positive lymph nodes (68.0% vs 35.6%, P = .013), and metastatic disease (44% vs 4.4%, P < .000). For both cohorts, most tumors were well or moderately differentiated. Tumor mutation burden was greater in the recurrent cohort (median 0.77 vs 0.43 mutations/Mb, P = .004). DAXX mutations were more frequent in the recurrent cohort (36% vs 11%, P = .026) and in those with vascular invasion (51% vs 92%, P = .010). ConclusionOur analysis demonstrated the prognostic significance of DAXX mutations after curative-intent surgery. Future studies investigating DAXX mutations as a biomarker for aggressive features to guide treatment are warranted.

Mitotic spindle positioning protein serves as prognostic biomarker in patients with colorectal cancer

Background Colorectal cancer (CRC) ranks among the most aggressive types of cancer globally. Currently, clinical tumor prognostic biomarkers still lack accuracy. Mitotic spindle positioning (MISP) protein connects microtubules to the actin cytoskeleton and adhesive plaques, playing a critical role in spindle positioning, orientation, and the process of cell division. MISP can regulate the malignant biological functions of pancreatic cancer and intrahepatic cholangiocarcinoma and it acts as biomarker for prognosis, but its role in CRC remains unclear. Methods This study has collected 37 CRC tissue samples and 37 corresponding adjacent nontumor tissue samples, and 57 additional CRC tissues samples. Clinical data were obtained from the patients with CRC. MISP mRNA and protein expression levels were analyzed in normal control and CRC tissues using the GEPIA and Human Protein Atlas website. MISP protein levels in the collected tissues were analyzed using immunohistochemistry. Results MISP mRNA and protein expression levels were significantly increased in CRC tissues compared to adjacent nontumor tissues. Higher MISP protein levels were associated with distant metastasis, recurrence, and lower survival rates. Kaplan–Meier analysis showed that high expression levels of MISP protein were associated with recurrence and death in CRC patients. In addition, a high expression level of MISP protein, lymph node metastasis, and distance metastasis were risk factors for recurrence and a poor prognosis in patients with CRC. Conclusion Elevated MISP protein correlated with tumor metastasis, recurrence, and lower survival rates in patients with CRC, and thus, MISP has the potential to become a prognostic marker for CRC.

Sebaceous Adenoma in a Geriatric Poodle Dog: A Case Report

A 14-year-old black male Poodle was brought to the Animal Teaching Hospital, Udayana University by its owner with clinical signs of frequent licking of its left front paw. Upon examination, red bumps were observed on the left front leg, accompanied by small, round black spots scattered on the dorsal side of the body. Additionally, black nodules were present on the lower eyelids and hind limbs. Surgical intervention was undertaken to excise the tumor mass, with the animal under anesthesia induced by ketamine at 5 mg/kg BW intravenously. The reddish nodule was excised by performing an elliptical incision at the base of tumor. Postoperatively, the animal received an antibacterial injection comprising ceftriaxone and tazobactam at 25 mg/kg BW intramuscularly and antiseptic wound dressing for supportive care. Microscopic examination revealed neoplastic cells arranged into lobules of varying sizes and shapes within the tumor mass. These lobules consisted of differentiated sebocytes and basaloid cells. At the periphery of the neoplastic lobules, the basaloid cells displayed several layers and exhibited invasion with moderate anisocytosis. The mitotic index was no more than ten cells in one field of view. Based on these histopathological features, the tumor was confirmed to be a sebaceous adenoma. After a 10-month follow-up period, there were no signs of tumor recurrence observed.

Tumor microenvironment-activated polypeptide nanoparticles for oncolytic immunotherapy

Cationic oncolytic polypeptides have gained increasing attention owing to their ability to directly lyse cancer cells and activate potent antitumor immunity. However, the low tumor cell selectivity and inherent toxicity induced by positive charges of oncolytic polypeptides hinder their systemic application. Herein, a tumor microenvironment-responsive nanoparticle (DNP) is developed by the self-assembly of a cationic oncolytic polypeptide (PLP) with a pH-sensitive anionic polypeptide via electrostatic interactions. After the formation of DNP, the positive charges of PLP are shielded. DNPs can keep stable in physiological conditions (pH 7.4) but respond to acidic tumor microenvironment (pH 6.8) to release oncolytic PLP. As a result, DNPs evoke potent immunogenic cell death by disrupting cell membranes, damaging mitochondria and increasing intracellular levels of reactive oxygen species. In vivo results indicate that DNPs significantly improve the biocompatibility of PLP, and inhibit tumor growth, recurrence and metastasis by direct oncolysis and activation of antitumor immune responses. In summary, these results indicate that pH-sensitive DNPs represent a prospective strategy to improve the tumor selectivity and biosafety of cationic polymers for oncolytic immunotherapy.

ZFHX2-AS1 interacts with DKC1 to regulate ARHGAP5 pseudouridylation and suppress ovarian cancer progression

Ovarian cancer (OCa) remains a highly lethal disease, largely due to late-stage diagnosis and limited treatment options for recurrent metastatic tumors. Long non-coding RNAs (lncRNAs) have been recognized as key regulators of cancer hallmarks, yet their specific roles in driving OCa progression are not fully understood. In this study, we employed an integrated approach combining clinical correlation, functional assays, and mechanistic investigations to reveal that lncRNA ZFHX2-AS1 is significantly downregulated in OCa tissues and cells, with its reduced expression associated with poor clinical outcomes. Using in vitro and in vivo models, we demonstrated that overexpression of ZFHX2-AS1 suppresses OCa cell proliferation, migration and invasion, whereas ZFHX2-AS1 knockdown enhances these malignant phenotypes. Mechanistically, we defined that ZFHX2-AS1 interacts with and attenuates the enzymatic activity of the pseudouridine synthase DKC1, thereby reducing pseudouridylation and stabilizing the oncogenic ARHGAP5 mRNA. Re-expression of ARHGAP5 could partially reverse the tumor-suppressive effects of ZFHX2-AS1. Further, we found that ARHGAP5 promotes epithelial-mesenchymal transition (EMT) by regulating Rho GTPases activities, and that ZFHX2-AS1 inhibits EMT in OCa by downregulating ARHGAP5 expression and suppressing the Rho GTPase signaling pathway. Taken together, our findings identify ZFHX2-AS1 as a potent tumor suppressor in OCa, acting through the modulation of DKC1-mediated pseudouridylation of ARHGAP5 and the inhibition of the Rho GTPase pathway, thus offering a potential therapeutic target for combating OCa progression.

Pediatric Metastatic Extracranial High-Grade Glioma: A Case Report and Literature Review

Abstract We report a case of a 10-year-old male with a right frontal diffuse pediatric-type high-grade glioma (HGG), H3-wildtype (WT) and IDH-WT, diagnosed at the age of 9 years, who underwent gross total resection, 60 Gy focal proton radiation in 30 fractions to the resection cavity with concurrent temozolomide followed by maintenance chemotherapy with temozolomide and lomustine. One month after completion of maintenance chemotherapy, he developed subcutaneous swelling in the right temporal region and was treated with antibiotics for presumed lymphadenitis. Two months later, he developed a recurrent painless right parietal soft tissue mass that failed to respond to antibiotic therapy. This prompted evaluation by MRI which revealed new enhancing masses in the cerebellum and extracranial soft tissue mass in right temporal region. He underwent gross total resection of both masses. Pathologic analysis confirmed both masses as recurrent HGG. Molecular markers, however, differed between the two sites of recurrence. He proceeded to complete hypofractionated proton therapy to sites of recurrence. Three months later he was found to have tumor dissemination into the spine and brain for which he received proton therapy to the whole spine and brain. Due to the presence of CDK4 amplification at diagnosis and at both sites of tumor recurrence, he then received palliative treatment with the CDK4/6 inhibitor, abemaciclib, for the final five months of his life. Since extracranial HGG is a rare presentation, with few cases reported in the pediatric population, we report this case and review previously published literature.

B-355 Assessment of Calcitonin Cutoff Values for Post-Thyroidectomy Surveillance in Patients with Medullary Thyroid Carcinoma: Findings from a Single-Center Investigation

Abstract Background Patients with sporadic or hereditary Medullary Thyroid Carcinoma (MTC) often undergo total thyroidectomy and lymph node dissection, with postoperative surveillance relying on serum calcitonin levels and ultrasound examinations. According to American Thyroid Association (ATA) guidelines, detectable levels of serum calcitonin and Carcinoembryonic Antigen (CEA) post-thyroidectomy suggest potential disease persistence or recurrence, necessitating frequent monitoring for early detection. This study sought to reassess the role of postoperative calcitonin levels in identifying possible tumor recurrence. Methods A retrospective analysis was conducted using Siemens Atellica to test calcitonin levels in 562 samples collected between 09/27/2022 and 08/11/2023, at least 3 months post-total thyroidectomy. Imaging studies performed within 6 months of the calcitonin assessment were also reviewed. Sample pools with calcitonin concentrations near 3.00 and 5.00 pg/mL were utilized to determine the limit of quantification (LoQ). CEA results were included for comparison. Additionally, 16 serum samples were analyzed using the Roche Cobas system at a reference laboratory. Results Precision analysis around 3.00 and 5.00 pg/mL revealed coefficients of variation (CVs) of 16.49% and 8.87%, respectively. Comparison of calcitonin levels between Siemens Atellica and Roche Cobas systems demonstrated consistent levels &amp;lt; 5.00 pg/mL in 15 out of 16 samples, indicating alignment and reliability between the platforms. A calcitonin cutoff of 1.89 pg/mL yielded 43% sensitivity and 67% specificity, while a cutoff of 5.00 pg/mL resulted in 0% sensitivity and 100% specificity. Conclusions Our findings suggest that a 5 pg/mL calcitonin cutoff on the Siemens Atellica platform may be suitable for identifying tumor persistence or recurrence in post-thyroidectomy patients within our institution. However, individual laboratories should establish their LoQ criteria when interpreting calcitonin levels for postoperative monitoring of tumor recurrence.

PDOC-08 THE CLINICAL CHARACTERISTICS OF CHILDREN WITH CRANIOPHARYNGIOMA AND THEIR MANAGEMENT IN UGANDA: A RETROSPECTIVE REVIEW

Abstract BACKGROUND Craniopharyngiomas are benign brain tumors that mostly arise in the sellar/suprasellar region. Histologically though benign, these tumors can locally infiltrate with involvement of surrounding structures. They have a 5-year survival rate of above 80% in High Income Countries (HIC). Craniopharyngioma management includes surgery, radiotherapy and intracystic treatments, which requires a multi-disciplinary team. The morbidity associated with treatment must be weighed against tumor recurrence and quality of life after treatment. Endocrine deficiencies, especially growth hormone deficiency and visual deficits are common presenting features. OBJECTIVE To describe the clinical characteristics and management of children with craniopharyngioma managed at Mulago National Referral Hospital from March 2019 to December 2023. METHODOLOGY: A retrospective descriptive study was conducted among patients&amp;lt; 18 years of age, admitted to the Mulago National Referral Hospital (MNRH) from March 2019 to December 2023 with a radiological diagnosis of a craniopharyngioma. RESULTS A total of 151 children with a diagnosis of a brain tumor during this period were identified and of these 40 (26%) were diagnosed with craniopharyngioma. The median age was 8.4 years and 22 (55%) were males. Only 2 children had maximal safe resection (sub-total resection), one of whom later received adjuvant external beam radiotherapy. Thirty-eight patients had insertion of Ommaya reservoirs as their tumors were predominantly cystic. Two patients received intracystic bleomycin and 11 received radical external beam radiotherapy. Twenty-seven patients had no additional therapy after Ommaya reservoir placement. Fifteen (39%) of the patients had endocrine deficits with hypothyroidism, hypocortisolism and growth hormone deficiency being the most common. The median follow-up time was 1.45 years. The overall survival was 67.5%, 95%CI (42.5-83.5). CONCLUSION Management of patients with craniopharyngioma in Uganda is mostly conservative with the aim of intervention to preserve quality of life. Limited access to radiation therapy contributed to the poorer survival compared to HIC.

Clinical Effects of Laparoscopic Surgery in Radical Surgery for Colorectal Cancer

Objective: To investigate the clinical application effect of laparoscopic surgery in radical surgery for colorectal cancer. Methods: 78 patients who were treated with radical surgery for colorectal cancer in a tertiary hospital during the period from January 2021 to December 2023 were selected as the study subjects in this study. According to the different surgical methods, the patients were divided into the laparoscopic surgery group (40 cases in the experimental group) and the traditional open surgery group (38 cases in the control group). The operation time, intraoperative bleeding, postoperative recovery (including postoperative anal exhaustion time, time to get out of bed, and hospitalization time), complication rate, and therapeutic effect were observed in the two groups. Results: Patients in the experimental group were better than the control group in terms of intraoperative blood loss, operation time, postoperative anal exhaust time, time to get out of bed, and postoperative hospitalization time (P &lt; 0.05). Patients in the experimental group had significantly better treatment effects and complication rates than those in the control group (P &lt; 0.05). Conclusion: Compared with the open group, the overall prognosis of laparoscopic colorectal cancer patients is better, and laparoscopy has a protective effect on tumor recurrence or metastasis after radical surgery for colorectal cancer, and it can reduce the incidence of postoperative abdominal infection.

PAD4 Inhibitor-Loaded Layered Double Hydroxide Nanosheets as a Multifunctional Nanoplatform for Photodynamic Therapy-Mediated Tumor Metastasis Treatment.

Photodynamic therapy (PDT) is demonstrated to be effective in inducing antitumor immune responses for tumor metastasis treatment. However, tumor hypoxia, inferior tissue penetration of light, and low singlet oxygen (1O2) quantum yield significantly hamper the efficacy of PDT, thus weakening its immune function. Moreover, PDT-mediated neutrophil extracellular traps (NETs) formation can further reduce the therapeutic effectiveness. Herein, the use of defect-rich CoMo-layered double hydroxide (DR-CoMo-LDH) nanosheets as a carrier to load a typical peptidyl arginine deiminase 4 inhibitor, i.e., YW4-03, to construct a multifunctional nanoagent (403@DR-LDH) for PDT/immunotherapy, is reported. Specifically, 403@DR-LDH inherits excellent 1O2 generation activity under 1550nm laser irradiation and improves the half-life of YW4-03. Meanwhile, 403@DR-LDH plus 1550nm laser irradiation can stimulate immunogenic cell death to promote the maturation of dendric cells and activation/infiltration of T cells and significantly downregulate H3cit protein expression to inhibit NETs formation, synergistically promoting the antitumor metastasis effect. Taken together, 403@DR-LDH can kill cancer cells and inhibit tumor growth/metastasis under 1550nm laser irradiation. Single-cell analysis indicates that 403@DR-LDH can regulate the ratio of immune cells and immune-related proteins to improve the tumor immune microenvironment, showing strong efficacy to inhibit the tumor growth, metastasis, and recurrence.

Lysosome Targeted Nanoparticle Aggregation Reverses Immunosuppressive Tumor Microenvironment for Cancer Immunotherapy.

Nanotechnology has proven its enormous application value in clinical practice. However, current research on nanomedicines mainly focuses on developing nanoparticles as delivery carriers to maximize the bioavailability of therapeutic agents, with little attention on exploring their potential to directly regulate physiological processes. In this study, inspired by the lysosomal swelling caused by excessive accumulation of undegraded substances, this work presents a lysosomal-targeting aggregated nanoparticle (LTANP) for cancer treatment. By rationally engineering surface composition, properties, and interparticle interactions, LTANP achieves efficient tumor accumulation and selective targeted aggregation in lysosomes of cancer cells, leading to unrelievable lysosomal swelling, and ultimately inducing lysosomal membrane permeabilization (LMP) of cancer cells. Further analysis shows that nanoparticle aggregation-mediated LMP can effectively trigger immunogenic cell death (ICD) by impairing autophagy-lysosome pathway, evoking robust antitumor immune responses and reversing tumor immunogenicity from "cold" to "hot" in a melanoma model. Additionally, LTANP can combine with clinically approved programmed death ligand-1 (PD-L1) antibodies to further unleash T cell-mediated antitumor immunity, significantly enhancing antitumor performance, inhibiting tumor recurrence and metastasis. This work demonstrates the potential of rationally engineered nanostructures in directly combating cancer and provides novel insights for the development of advanced nanoparticle-based cancer treatment.

Current approaches to facial nerve schwannoma surgery.

Facial nerve schwannomas (FNSs) are exceedingly rare benign tumors. This study aims to report on a series of excised FNSs, providing clinical information and details on their surgical management, including novel approaches. We retrospectively reviewed patients who underwent surgical excision of FNSs in a private otology clinic and public tertiary referral center. The main outcome measures were facial nerve function, complete tumor removal, postoperative complications, tumor recurrence, and hearing. Seventeen patients (10 men and 7 women) with a mean age of 44.23 years (SD, 12.21) underwent surgery during the study period. The most common symptom was facial nerve dysfunction (58.8%). Facial and otoneurologic symptoms (hearing loss, tinnitus, and vertigo) were observed in 88.8% and 77.7% of patients, respectively. The middle cranial fossa (MCF) was the most common approach (six patients, 35.2%), followed by translabyrinthine (TL), transmastoid (TM), and combined TM-MCF (three patients, 17.6% each). Exclusive endoscopic transcanal suprageniculate (ETS) and mastoid combined with cervical approaches were applied once in two patients, 5.8% each. Total tumor removal was achieved in all cases. No significant postoperative complications were observed. The mean follow-up period was 193.2 months (SD, 119.5) and no tumor recurrence was observed. This study provides further evidence for the safety and efficacy of various surgical approaches for FNS, and incorporates the endoscopic transcanal approach. 4.

Effect of pituitary stalk preservation during craniopharyngioma removal on pituitary function, extent of resection, and recurrence: systematic review and meta-analysis.

Optimal management of the pituitary stalk during craniopharyngioma resection remains a controversial subject. This meta-analysis aimed to evaluate the effect of pituitary stalk preservation on postoperative diabetes insipidus (DI), anterior pituitary function (PF), extent of resection, and recurrence. Medline was searched via Ovid for relevant articles from inception to September 2, 2022. Studies reporting the rates of DI or anterior PF postoperatively or at last follow-up, extent of resection, or tumor recurrence at last follow-up were eligible for inclusion. The risk ratio (RR) for each outcome was calculated. Random-effects meta-analyses were performed with additional stratification by age. To assess for risk of bias across studies, funnel plots and the Egger's test were utilized. In total, 3488 abstracts and 150 full-text articles were reviewed, resulting in 33 studies with a total of 2366 patients for inclusion. In the comparative meta-analysis, pituitary stalk preservation significantly decreased the risk of DI postoperatively (17 studies, RR 0.67, 95% CI 0.55-0.81, I2 = 75%), DI at last follow-up (6 studies, RR 0.54, 95% CI 0.41-0.72, I2 = 20%), and abnormal anterior PF postoperatively (15 studies, RR 0.78, 95% CI 0.69-0.89, I2 = 49%) but not abnormal anterior PF at last follow-up (4 studies, RR 0.38, 95% CI 0.09-1.63, I2 = 64%). There were no significant differences in the rates of incomplete resection (12 studies, RR 1.59, 95% CI 0.77-3.28, I2 = 68%) or tumor recurrence (9 studies, RR 1.18, 95% CI 0.92-1.51, I2 = 0%) between the preservation and sacrifice groups. However, subgroup analysis of pediatric patients revealed a higher risk of incomplete resection (RR 3.29, 95% CI 1.17-9.26, I2 = 70%) in the stalk preservation group. Pituitary stalk preservation was demonstrated to confer protective benefit on PF, although the benefit persisted on long-term follow-up for posterior PF only. Stalk preservation in pediatric patients should be given careful consideration, as it is associated with higher rates of incomplete resection. These results should be interpreted with caution due to inclusion of small studies and inadequate reporting of outcomes in the literature.

Implantable Microneedle-Mediated Eradication of Postoperative Tumor Foci Mitigates Glioblastoma Relapse.

Glioblastoma multiforme (GBM) remains incurable despite multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin (2-3cm) of the initial resected lesion due to the unreachable residual cancerous cells. Here, a completely biodegradable microneedle for surgical cavity delivery glioblastoma-associated macrophages (GAMs)-activating immune nano-stimulator that mitigates glioblastoma relapse is reported. The residual tumor lesion-directed biocompatible microneedle releases the nano-stimulator and toll-like receptor 9 agonist in a controlled manner until the microneedles completely degrade over 1 week, efferently induce in situ phonotypic shifting of GAMs from anti- to pro-inflammatory and the tumor recurrence is obviously inhibited. The implantable microneedles offer a significant improvement over conventional transdermal ones, as they are 100% degradable, ensuring safe application within surgical cavities. It is also revealed that the T cells are recruited to the tumor niche as the GAMs initiate anti-tumor response and eradicate residual GBM cells. Taken together, this work provides a potential strategy for immunomodulating the postoperative tumor niche to mitigate tumor relapse in GBM patients, which may have broad applications in other malignancies with surgical intervention.