Tumor Type Research Articles

Impact of COVID-19 infection on genitourinary cancer management. SOGUG-COVID-19: A spanish, multicenter, observational study.

The COVID-19 pandemic is a great burden worldwide, but its impact on patients with genitourinary cancer (GUC) is poorly characterized. This study aimed to characterize the clinical features and evolution of GUC patients affected by COVID-19 in Spain. SOGUG-COVID-19 was an observational ambispective non-interventional study that recruited patients with SARS-CoV-2 infection who had been treated for GUC in 32 Spanish hospitals. Data were collected from patients' medical records in a short period of time, coinciding with the first waves of COVID-19, when the mortality was also higher in the general population. From November 2020 to April 2021, 408 patients were enrolled in the study. The median age was 70years, and 357 patients (87.5%) were male. Most frequent Cancer Origin was: prostate (40.7%), urothelial (31.4%) and kidney (22.1%). Most patients (71.3%) were diagnosed at the metastatic stage, and 33.3% had poorly differentiated histology. Anticancer treatment during the infection was reported in 58.3% of patients, and 21.3% had received immunotherapy prior to or concurrent with the infection. The most frequent COVID-19 symptoms were pyrexia (49.0%), cough (38.2%) and dyspnea (31.9%). Median age was higher for patients with pneumonia (p < 0.001), patchy infiltrates (p = 0.005), ICU admission (p < 0.001) and death (p < 0.001). Tumor stage was associated with complications (p = 0.006). The fatality rate was 19.9% and the 6-month COVID-19-specific survival rate was 79.7%. Patients with genitourinary cancers seem exceptionally vulnerable to COVID-19 regardless of tumor type or anticancer therapy. Age and tumor stage were the only identified risk factors for severe COVID-19.

Self-Reported Late Effects in Childhood Cancer Survivors in Kenya

Background: The number of children surviving cancer in low and middle-income countries is expected to grow in the coming years. Knowledge about late effects and follow-up preferences in Kenya is lacking.Objectives: This study assessed self-reported late effects in Kenyan childhood cancer survivors and explored their preferences for survivorship care.Methods: Childhood cancer survivors, having successfully completed treatment for at least one year, were interviewed using semi-structured questionnaires during clinic or home visits between 2021-2022. Medical records were reviewed for patient and treatment characteristics.Results: Twenty-six survivors of hematological malignancies (n=19, 73%), solid tumors (n=6, 23%), unknown tumor type (n=1, 4%), were interviewed. Most survivors (n=19, 73%) solely received chemotherapy and one survivor (4%) was irradiated. Median time since treatment completion was seven years. Fifteen survivors (58%) were previously lost to follow-up. Many survivors (n=19; 73%) self-reported late effects, predominantly pain and fatigue. Survivors (n=11, 42%) were limited in daily life activities: physical work (n=10, 38%), personal care (n=6, 23%), social activities (n=6, 23%). Eight survivors (31%) recalled being informed about late effects. Some survivors experienced a negative attitude toward cancer in regional hospitals. Follow-up duration was longer among informed patients (p=0.043). Survivors recommended education and survivor meetings and preferred their follow-up to be done at the referral center.Conclusions: Kenyan childhood cancer survivors self-report late effects, comparable in frequency, nature and severity to other survivors worldwide. Survivors and healthcare providers require education about the lifelong impact of childhood cancer and should have access to survivorship expertise to continue follow-up. Keywords: Pediatrics; survivorship; neoplasms; aftercare.

8203 A Solitary Fibrous Tumor Mimicking a Non-functional Pituitary Macroadenoma

Abstract Disclosure: L. Bernacet Rivera: None. S. Omay: None. A. Huttner: None. S.E. Inzucchi: None. Background: A solitary fibrous tumor (SFT), also known as hemangiopericytoma (HPC), is a rare subset of soft tissue tumors of mesenchymal origin. This type of tumor tends to have aggressive behavior and a high risk of recurrence. Approximately less than 1% of central nervous system (CNS) tumors have been identified as part of this subtype. Case Presentation: A 73-year-old female with medical history of primary hypothyroidism, myelodysplastic syndrome (MDS), and IgM kappa MGUS initially presented to her primary care physician for evaluation of progressive visual loss over several weeks, accompanied by worsening headaches. Ophthalmologic exam revealed bitemporal hemianopsia which prompted urgent imaging. Pituitary MRI with IV contrast revealed a solid sellar mass with suprasellar extension measuring 1.8 x 1.3 x 1.9 cm. The lesion was noted to superiorly displace the optic chiasm as well as to cause mild impingement of the anterior cerebral arteries. Patient was urgently referred to neurosurgery and endocrinology for further evaluation. Initial neuroendocrine laboratory assessment, performed at 8 am, revealed a cortisol 16.5 ug/dL, free T4 1.2 ng/dL, TSH 0.77 mIU/L, prolactin 9.9 ng/mL, IGF-1 17 ng/mL, the latter value consistent with adult growth hormone deficiency. Her LH and FSH were 4.3 mIU/mL and 12.6 mIU/mL, respectively, lower than expected for a post-menopausal woman. She underwent a transnasal transsphenoidal resection of the sellar lesion. Surgery was difficult due to the fibrous nature of the tumor, for which complete resection was not achieved. Post-operative course was complicated by thrombocytopenia due to MDS. Hormonal workup following surgery was consistent with central adrenal insufficiency, hypogonadotropic hypogonadism, and central hypothyroidism. Pathology showed densely cellular spindle cell neoplasm with a collagenous background consistent with hemangiopericytoma. She underwent fractionated radiotherapy and tumor has since remained stable in size. Her visual symptoms resolved quickly following surgery. Discussion: SFT is an aggressive mesenchymal tumor which rarely appears in the sellar region. There are no identified brain MRI findings that would suggest the nature of this tumor. As a result, endocrinologists should be aware of this rare condition while evaluating pituitary neoplasms. Presentation: 6/3/2024

Surgical Management of Pediatric Patients with Intraocular Tumors

The incidence and prevalance of intraocular tumors in pediatric and adult populations are different. Moreover, the same type of tumor may show different clinicopathologic features in the pediatric group. Several types of treatment strategies have been described for benign and malign intraocular tumors: observation, cryotherapy, thermotherapy, laser photocoagulation, surgical excision, plaque brachytherapy, radiotherapy, chemotherapy, and enucleation. The purpose of treatment is to control tumor, preserve or prolonge patients life and to preserve eyeball and vision. Surgical excision or resection can be performed as a primary treatment or adjuvant or salvage procedure. Nowadays, surgical treatments like sclerouvectomy and/or vitrectomy is applied increasingly in pediatric population with intraocular tumor.

6793 The Potential Of Melatonin As A Treatment Option For Cushing’s Syndrome In Humans Based On Observations In Cushingoid Dogs

Abstract Disclosure: K. Fecteau: None. It is known that the secretion of cortisol and melatonin is circadian, with the former increasing during morning hours and the latter increasing during the dark hours of night. Studies investigating melatonin concentrations in patients with Cushing’s syndrome have reported differing results, with some having low melatonin concentrations, and others normal or high concentrations. Interestingly, adrenal glands have been shown to express melatonin receptors, and in vitro studies with human adrenal cells have shown a decrease in cortisol, as well as other adrenocortical steroids, when treated with melatonin. In human adrenal gland explants, melatonin reportedly inhibited ACTH stimulated circadian clock genes, as well as cortisol and progesterone production. Melatonin is often used as a first-line of treatment in dogs with atypical Cushing’s, where cortisol is normal, other adrenocortical steroids are elevated, and typical clinical signs of Cushing’s are present. Retrospective data collected in our diagnostic laboratory from dogs that had at least two submissions (before &amp; during treatment), showed 34 percent of dogs on melatonin improved clinically. Of the 34 percent, 26.4 percent experienced either similar or more aberrant steroid concentrations, and 7.6 percent experienced lower steroid concentrations. Approximately 40 percent of dogs had significantly lower androstenedione when retested on melatonin. In humans, Cushing’s disease is a rare cause of androgen excess, with one study reporting occurrence of less than 4 percent in women. Adrenocortical carcinoma is also rare, however, women with this type of tumor may exhibit clinical signs of androgen excess due to adrenal androgen hypersecretion, and up to 25 percent of women with clinical signs had normal testosterone and elevated androstenedione. Therefore, based on the effectiveness of melatonin on lowering androstenedione concentrations and improving clinical signs associated with increased androgens and glucocorticoids in dogs, it may be an inexpensive and conservative option, especially for patients presenting with clinical signs but diagnostic testing is either negative of equivocal for Cushing’s. Presentation: 6/2/2024

Population Pharmacokinetic Analysis of Tucatinib in Healthy Participants and Patients with Breast Cancer or Colorectal Cancer.

Tucatinib is a highly selective, oral, reversible, human epidermal growth factor receptor 2 (HER2)-specific tyrosine kinase inhibitor. Tucatinib is approved at a 300-mg twice-daily dose in adults in combination with trastuzumab and capecitabine for advanced HER2-postitive (HER2+) unresectable or metastatic breast cancer and in combination with trastuzumab for RAS wild-type HER2+ unresectable or metastatic colorectal cancer. This study sought to characterize the pharmacokinetics (PK) and assess sources of PK variability of tucatinib in healthy volunteers and in patients with HER2+ metastatic breast or colorectal cancers. A population pharmacokinetic model was developed based on data from four healthy participant studies and three studies in patients with either HER2+ metastatic breast cancer or metastatic colorectal cancer using a nonlinear mixed-effects modeling approach. Clinically relevant covariates were evaluated to assess their impact on exposure, and overall model performance was evaluated by prediction-corrected visual predictive checks. A two-compartment pharmacokinetic model with linear elimination and first-order absorption preceded by a lag time adequately described tucatinib pharmacokinetic profiles in 151 healthy participants and 132 patients. Tumor type was identified as a significant covariate affecting tucatinib bioavailability and clearance, resulting in a 1.2-fold and 2.1-fold increase in tucatinib steady-state exposure (area under the concentration-time curve) in HER2+ metastatic colorectal cancer and HER2+ metastatic breast cancer, respectively, compared with healthy participants. No other covariates, including mild renal or hepatic impairment, had an impact on tucatinib pharmacokinetics. The impact of statistically significant covariates identified was not considered clinically meaningful. No tucatinib dose adjustments are required based on the covariates tested in the final population pharmacokinetic model. NCT03723395, NCT03914755, NCT03826602, NCT03043313, NCT01983501, NCT02025192.

7446 Primary Adrenal Mature Teratoma Initially Diagnosed As An Adrenal Myelolipoma

Abstract Disclosure: A. White-Cotsmire: None. B. Kodali: None. A.M. Avram: None. S.S. Shah: None. Background: Teratomas are a type of germ cell tumor containing different types of tissue (e.g., hair, teeth, bone adipose, muscle). Most teratomas are benign (i.e., mature), but they may also be malignant (i.e., immature). Both immature and mature teratomas contain derivatives of ectoderm, endoderm, and mesoderm; however, immature teratomas are differentiated by the presence of embryonic, usually neuroectodermal, tissue. Mature teratomas have the potential for malignant transformation (1–2% of cases), usually squamous cell carcinoma within the teratoma. Extra-gonadal teratomas are rare (only 1–5%); reported locations include sacrococcygeal, head and neck, retroperitoneum, mediastinum, brain and spine, liver, and rarely adrenal glands. (1) Only 18 cases of adult primary adrenal teratomas have been reported since 1952. (2)Clinical Case: A 48-year-old woman with 4 days of worsening abdominal pain underwent CT imaging, which demonstrated a 6cm complex left adrenal mass containing peripheral and scattered internal-coarse calcifications with internal soft tissue and fat components, suggestive of adrenal myelolipoma with probable sequela of previous hemorrhage. Subsequent endocrine follow-up ruled out a cortisol secreting tumor with a negative dexamethasone suppression test and pheochromocytoma with normal serum free metanephrines and normetanephrines. Dedicated adrenal protocol CT scan further characterized the mass as a mature adrenal teratoma containing a rudimentary mandible and two teeth within the soft tissue associated with internal microscopic fat. The left renal vein was anteriorly displaced by this left adrenal mass and severely narrowed by the large adrenal mass, with development of left retroperitoneal collateral venous drainage from the left kidney into the lumbar venous system. The patient opted for conservative management with active clinical surveillance. Conclusion: This is a rare case of adrenal mature teratoma in an adult, originally diagnosed as an adrenal myelolipoma. This case highlights the use of more dedicated adrenal imaging for the characterization of adrenal tumors and the broad differential of benign non-functional adrenal tumors, including myelolipomas, lipomas, angiomyolipomas, and nonfunctional adenomas. However, a definitive diagnosis can only be confirmed by surgical removal of the tumor, usually through a laparoscopic approach, with histopathologic evaluation.

7120 Pituitary Prolactinoma Transforming To Invasive Aggressive Adenoma After 10 Years of Acting As Benign Adenoma

Abstract Disclosure: S.N. Polis: None. S. Nakhle: None. N.J. Vernetti: None. Prolactinomas are the most common type of secretory pituitary tumors. Symptoms occur due to hyperprolactinemia and compressive symptoms with larger tumors. The majority of the prolactinomas are benign adenomas, with up to 30-40% of them being invasive. Malignant prolactinomas are rare, counting only 0.2% of pituitary tumors with an average latency period of 4.7 years. We present a 70-year-old woman who was found to have asymptomatic mild hyperprolactinemia in 2009 with pituitary MRI that showed a 3 mm left pituitary adenoma. Treatment with cabergoline started three years later due to an increase in prolactin above 300 ng/ml. Annual pituitary MRI showed a stable mass. After four years of treatment, pituitary MRI showed an increase in pituitary adenoma size to 8 mm and prolactin level remained elevated above 300 ng/ml. The patient complained of facial and acral numbness and emotional outbursts, so cabergoline was changed to bromocriptine. A few months later, a decision was made to stop treatment as she was asymptomatic and prolactin levels remained stable with a stable adenoma on imaging. 18 months later, prolactin increased to 544 ng/ml and pituitary MRI showed an increase adenoma size to 14mm, contacting the chiasm, and cabergoline was restarted. The prolactin levels continued to climb after 5 months of treatment despite titrating the dose to 1 mg daily. The patient started to develop vision impairment and visual field testing confirmed a new central vision defect. The patient was eventually referred to neurosurgery and went for transsphenoidal surgery. Prolactin level dropped to 50 ng/ml post operatively. The pathology report showed Ki 67 10-20%. Cabergoline was restarted and the patient was enrolled in a clinical trial for temozolomide for 18 months. During that time, prolactin levels remained stable so treatment was discontinued. A year later, cabergoline was restarted as prolactin levels increased to 219 ng/ml and pituitary MRI showed an 8 mm sellar mass with optic chiasm compression. For the next year, multiple medical treatments including high dose cabergoline (1 mg daily) and temozolomide were attempted, which were intolerable due to side effects. Prolactin continued to climb (&amp;gt; 1700 ng/ml). Four years later, the patient went for a second transsphenoidal surgery. Surgical pathology revealed Ki67 20%. Prolactin levels dropped to 242 ng/ml, but a month later, went up again to over 600 ng/ml. Cabergoline was restarted with a plan for an open craniotomy and radiotherapy. Conclusion: We present this interesting case of pituitary prolactinoma that behaved as benign adenoma for over 10 years prior to invasion and showing aggressive behavior requiring multiple surgeries. This unusual presentation is worrisome for malignancy and prompting consideration for closer and longer follow up for prolactinomas, especially the ones resistant to medical treatment. Presentation: 6/2/2024

5118 When Thyroid Gland Is Not Made Of Thyroid Cells

Abstract Disclosure: A. Bulut: None. L. Ma: None. J.P. Noordzij: None. S.Y. Lee: None. Introduction: Neurofibroma is a type of peripheral nerve tumor that can arise sporadically or be a part of neurofibromatosis type 1 (NF1), a rare genetic disorder. Neurofibromas within the thyroid gland are extremely rare. Here, we present the fifth reported case of primary neurofibroma of thyroid gland. Case: A 60-year-old woman with history of systemic lupus erythematosus and hypertension presented with enlargement of left thyroid gland. She was diagnosed with Graves’ disease 40 years ago, which was treated with right thyroid lobectomy one year after the initial diagnosis. Five years after the surgery, she had recurrence of her symptoms and received radioactive iodine ablation with subsequent hypothyroidism. On presentation to endocrine clinic, she had thyroid ultrasound (US), which showed surgically absent right thyroid lobe and enlarged heterogenous left thyroid lobe measuring 5.1 cm x 3.8 cm x 3.9 cm with scant blood flow without discrete nodules. In interim, patient developed dysphagia and globus sensation. Repeat thyroid US showed enlargement of left lobe to 5.6 cm x 3.7 cm x 4.7 cm. Patient underwent completion thyroidectomy. Surgical pathology showed neurofibroma (S-100+, CD34+ and MSA-) without any thyroid parenchyma. Whole-body scan revealed no other evidence of tumors. Patient was referred for genetic analysis. Discussion: Neurofibromas are benign peripheral nerve system tumors primarily consist of Schwann cells along with other components of perineurium. They can occur as a sporadic lesion which accounts for 90% of solitary neurofibroma cases or be a part of NF1 on rare occasions. NF1 is an autosomal dominant genetic disorder due to germline mutation in NF1 gene located on chromosome 17q11.2, whose manifestations include café-au-lait macules, Lisch nodules, skeletal abnormalities, neurological deficits, and other benign and malignant tumors. Neurofibromas are the hallmarks of NF1. There are only few cases in the literature reported neurofibromas adjacent to or originating from thyroid gland. To the best of our knowledge, there have been only four other cases reporting primary neurofibroma of thyroid gland, one of which developed from thyroid capsule. Our patient most likely has primary neurofibroma of thyroid gland given the lack of syndromic features, however, genetic testing is needed in order to rule out NF1. In conclusion, clinicians should consider neurofibroma in their differential in cases of enlarging thyroid gland or nodules, especially in the presence of other clinical features. Presentation: 6/1/2024

5118 When Thyroid Gland is Not Made of Thyroid Cells

Abstract Disclosure: A. Bulut: None. L. Ma: None. J.P. Noordzij: None. S.Y. Lee: None. Introduction: Neurofibroma is a type of peripheral nerve tumor that can arise sporadically or be a part of neurofibromatosis type 1 (NF1), a rare genetic disorder. Neurofibromas within the thyroid gland are extremely rare. Here, we present the fifth reported case of primary neurofibroma of thyroid gland. Case: A 60-year-old woman with history of systemic lupus erythematosus and hypertension presented with enlargement of left thyroid gland. She was diagnosed with Graves’ disease 40 years ago, which was treated with right thyroid lobectomy one year after the initial diagnosis. Five years after the surgery, she had recurrence of her symptoms and received radioactive iodine ablation with subsequent hypothyroidism. On presentation to endocrine clinic, she had thyroid ultrasound (US), which showed surgically absent right thyroid lobe and enlarged heterogenous left thyroid lobe measuring 5.1 cm x 3.8 cm x 3.9 cm with scant blood flow without discrete nodules. In interim, patient developed dysphagia and globus sensation. Repeat thyroid US showed enlargement of left lobe to 5.6 cm x 3.7 cm x 4.7 cm. Patient underwent completion thyroidectomy. Surgical pathology showed neurofibroma (S-100+, CD34+ and MSA-) without any thyroid parenchyma. Whole-body scan revealed no other evidence of tumors. Patient was referred for genetic analysis. Discussion: Neurofibromas are benign peripheral nerve system tumors primarily consist of Schwann cells along with other components of perineurium. They can occur as a sporadic lesion which accounts for 90% of solitary neurofibroma cases or be a part of NF1 on rare occasions. NF1 is an autosomal dominant genetic disorder due to germline mutation in NF1 gene located on chromosome 17q11.2, whose manifestations include café-au-lait macules, Lisch nodules, skeletal abnormalities, neurological deficits, and other benign and malignant tumors. Neurofibromas are the hallmarks of NF1. There are only few cases in the literature reported neurofibromas adjacent to or originating from thyroid gland. To the best of our knowledge, there have been only four other cases reporting primary neurofibroma of thyroid gland, one of which developed from thyroid capsule. Our patient most likely has primary neurofibroma of thyroid gland given the lack of syndromic features, however, genetic testing is needed in order to rule out NF1. In conclusion, clinicians should consider neurofibroma in their differential in cases of enlarging thyroid gland or nodules, especially in the presence of other clinical features. Presentation: 6/1/2024

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.

8234 Composite Pheochromocytoma-Ganglioneuroma: Two Clinical Cases Presenting To St. Elizabeth’s Medical Center

Abstract Disclosure: M. El Najjar: None. E. Naous: None. C. Blake: None. A.T. Sweeney: None. Introduction: Pheochromocytomas (PCCS) are rare catecholamine producing tumors that originate from the chromaffin cells of the adrenal medulla. In 3-9% of cases, they may be accompanied by other tumors. Ganglioneuromas are the most encountered tumor type that occur with PCC and are termed composite PCC-GN. The entity is very rare with &amp;lt; 35 cases reported. Herein, we present 2 cases of composite PCC-GN. Case Presentation: Patient 1 (Pt1) &amp; Patient 2 (Pt2): were 35- &amp; 54-year-old obese females. Pt1 had controlled hypertension and symptoms of anxiety along with palpitations, diaphoresis and flushing. Pt2 had type 2 diabetes and complained of abdominal pain. Metabolic studies showed elevated total plasma fractionated metanephrines(MNs). MNs in Pt1 and Pt2 were: 76 and 61pg/ml respectively (normal &amp;lt;57 pg/ml) and normetaneprines levels were 161 and 116pg/ml respectively (normal &amp;lt;148 pg/ml). Abdominal computed tomography (CT) scans demonstrated right adrenal masses in both cases with Pt1 having a 2.3 x 2.3 x 2.6 cm mass (Figure1) with smooth margins measuring 36 Hounsfield units (HU) on non-contrast(NC) CT imaging with 0% washout on delayed imaging after IV contrast. Pt2 on NCCT had a 4.5 x 3.5 cm right adrenal mass measuring 73 HU and a subsequent abdominal MRI(Figure2) demonstrated the mass to have heterogenous signal intensity. Both patients were prepared with pre-operative a and b blockade and underwent laparoscopic robotic adrenalectomies without complications. Pathological analyses in both cases revealed composite PCC-GN. Pt2 underwent genetic testing which did not reveal any known mutations. Surveillance in both patients demonstrated no recurrence. Clinical lesson: The clinical presentation of PCC-GNs is indistinguishable from isolated PCCs. The definitive diagnosis is through histopathological analysis. Histologically the composite tumor is composed of two distinct patterns with PCC showing angular cells with granular, basophilic cytoplasm, arranged in nests, while GNs show ganglion cells in fibrous stroma. Immunohistochemistry show the PCCs staining for chromogranin A and synaptophysin while GNs stain for S-100 protein and neurofilament antibody. Most cases occur in patients between 40 - 60 years old. Most PCC-GNs are functional, with increased MNs. PCC-GN composite tumors may occur sporadically but have also been described as part of syndromes such as MEN2A and NF1. The definitive treatment for PCC-GN is complete surgical excision which is associated with an excellent prognosis. The probability of recurrence is low though distant metastases have rarely been reported. Therefore, lifetime surveillance is critical. Presentation: 6/3/2024

The application of the combination between artificial intelligence and endoscopy in gastrointestinal tumors

AbstractGastrointestinal (GI) tumors have always been a major type of malignant tumor and a leading cause of tumor‐related deaths worldwide. The main principles of modern medicine for GI tumors are early prevention, early diagnosis, and early treatment, with early diagnosis being the most effective measure. Endoscopy, due to its ability to visualize lesions, has been one of the primary modalities for screening, diagnosing, and treating GI tumors. However, a qualified endoscopist often requires long training and extensive experience, which to some extent limits the wider use of endoscopy. With advances in data science, artificial intelligence (AI) has brought a new development direction for the endoscopy of GI tumors. AI can quickly process large quantities of data and images and improve diagnostic accuracy with some training, greatly reducing the workload of endoscopists and assisting them in early diagnosis. Therefore, this review focuses on the combined application of endoscopy and AI in GI tumors in recent years, describing the latest research progress on the main types of tumors and their performance in clinical trials, the application of multimodal AI in endoscopy, the development of endoscopy, and the potential applications of AI within it, with the aim of providing a reference for subsequent research.

An Exogenous Ketone Ester Slows Tumor Progression in Murine Breast and Renal Cancer Models.

Ketone esters (KEs) exhibit promise as anti-cancer agents but their impact on spontaneous metastases remains poorly understood. Although consumption of a ketogenic diet (KD) that is low in carbohydrates and high in fats can lead to KE production in vivo, the restrictive composition of KDs may diminish adherence in cancer patients. We investigated the effects of an exogenous ketone ester-supplemented (eKET), carbohydrate-replete diet on tumor growth, metastasis, and underlying mechanisms in orthotopic models of metastatic breast (4T1-Luc) and renal (Renca-Luc) carcinomas. Mice were randomized to diet after tumor challenge. Administration of KEs did not alter tumor cell growth in vitro. However, in mice, our eKET diet increased circulating β-hydroxybutyrate and inhibited primary tumor growth and lung metastasis in both models. Body composition analysis illustrated the overall safety of eKET diet use, although it was associated with a loss of fat mass in mice with renal tumors. Immunogenetic profiling revealed divergent intratumoral eKET-related changes by tumor type. In mammary tumors, Wnt and TGFβ pathways were downregulated, whereas in renal tumors, genes related to hypoxia and DNA damage repair were downregulated. Thus, our eKET diet exerts potent antitumor and antimetastatic effects in both breast and renal cancer models, albeit with different modes of action and physiologic effects. Its potential as an adjuvant dietary approach for patients with diverse cancer types should be explored further.

Real-world pan-tumor comprehensive genomic profiling sample adequacy and success rates in tissue and liquid specimens.

Real-world success rate of liquid and tissue-based comprehensive genomic profiling (CGP) is unknown. We analyzed real-world pan-tumor cohorts that underwent CGP during clinical care via FoundationOne CDx (F1CDx) and FoundationOne Liquid CDx (F1LCDx) to determine tissue and liquid sample adequacy based on tumor type. Pan-tumor presequencing adequacy was high (>90%) by both tissue-based F1CDx (median: 92.3%; range: 88.2%-96.9%) and liquid-based F1LCDx (median: 94.8%; range: 86.6%-96.7%). Similarly, postsequencing analysis revealed that most tissue and liquid samples yielded successful sequencing results with a median sequencing success rate of 97.9% and 98.1% for F1CDx and F1LCDx, respectively. One exception is central nervous system (CNS) tumors, for which F1CDx had dramatically higher sample sufficiency (96.9%) and postsequencing success rate (97.0%) compared with F1LCDx (86.6% and 92.9%, respectively). The pan-tumor median sample-to-success rate was 90.4% (range: 84.8%-94.4%) for F1CDx. The equivalent rate for F1LCDx was slightly higher at 93.2% (range: 80.4%-95.7%). Conversely, when examining the prevalence of F1LCDx results with high tumor fraction (TF≥1%), the sample-to-high TF results rate was dramatically lower (median: 37.7%, range: 2.1% [CNS tumors]-46.0%). In conclusion, except in CNS tumors or when accounting for liquid TF, success rates of F1CDx and F1LCDx are equivalently high. These results may guide informed decision on when to pursue tissue vs liquid testing of patients with cancer.

Tumor necrosis factor superfamily signaling: life and death in cancer.

Immune checkpoint inhibitors have shaped the landscape of cancer treatment. However, many patients either do not respond or suffer from later progression. Numerous proteins can control immune system activity, including multiple tumor necrosis factor (TNF) superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) members; these proteins play a complex role in regulating cell survival and death, cellular differentiation, and immune system activity. Notably, TNFSF/TNFRSF molecules may display either pro-tumoral or anti-tumoral activity, or even both, depending on tumor type. Therefore, TNF is a prototype of an enigmatic two-faced mediator in oncogenesis. To date, multiple anti-TNF agents have been approved and/or included in guidelines for treating autoimmune disorders and immune-related toxicities after immune checkpoint blockade for cancer. A confirmed role for the TNFSF/TNFRSF members in treating cancer has proven more elusive. In this review, we highlight the cancer-relevant TNFSF/TNFRSF family members, focusing on the death domain-containing and co-stimulation members and their signaling pathways, as well as their complicated role in the life and death of cancer cells.

Ascites production and prognosis after ventriculoperitoneal shunt for diffuse midline gliomas in children: A case series.

DMG is a highly invasive and lethal type of brain tumor. As these tumors progress, they often compromise the CSF circulation, leading to hydrocephalus. Ventriculoperitoneal shunt (VPS) is commonly employed to manage hydrocephalus; however, the complication of VPS-induced ascites, particularly in the presence of tumor cells, is a significant concern that merits attention. This case series details 3 pediatric patients diagnosed with brainstem DMG harboring the H3 K27M mutation. Each developed hydrocephalus underwent VPS insertion. Post-operatively, all patients developed carcinomatous ascites with tumor cells detected within the ascitic fluid. All 3 patients were diagnosed with intra-abdominal metastasis of DMG H3K27M mutant cancer cells, each presenting with distinct complications. Initially, the patients' primary head tumors responded to treatment, and their hydrocephalus resolved. However, some time after discharge, each patient developed malignant ascites and received palliative chemotherapy to control symptoms and improve quality of life. Despite the interventions, all 3 patients died within 1 month of developing malignant ascites, with central respiratory failure being the direct cause of death. These cases underscore the importance of continuous monitoring of both the CSF and ascitic fluid in patients with gliomas. Regular assessments of biochemical composition, cytology, and other diagnostic tests are crucial for early detection of disease progression. This proactive approach facilitates timely clinical judgment and intervention, potentially improving patient outcomes.

Impact of instrumentation material on local recurrence: a case-matched series using carbon fiber-PEEK vs. titanium.

Spine metastases are a major burden of oncologic care, contributing to substantial morbidity. A well-established treatment paradigm for patients with metastatic epidural spinal cord compression includes separation surgery followed by stereotactic body radiotherapy (SBRT). Innovations in implant technology have brought about the incorporation of Carbon fiber-reinforced polyetheretherketone (CFR-PEEK) instrumentation for spinal fixation. We present our experience of CFR-PEEK instrumentation, comparing outcomes and complication profiles with a matched cohort of titanium instrumented cases for spine metastatic disease. Oncology patients who underwent spinal fusion for metastatic spine disease from 2012 to 2023 were retrospectively reviewed. Ninety-nine cases with CFR-PEEK fusions were case-control matched with 50 titanium controls (2:1 ratio) based upon primary tumor type and spinal instability neoplastic score (SINS) location. Demographic, clinical, radiographic and progression free survival (PFS) were analyzed. In the study years, 263 patients underwent spinal decompression and fusion, for which 148 patients met predetermined inclusion criteria. Of these, 49 had titanium instrumentation, and 99 had CFR-PEEK. Complication profiles, including hardware failure and infection were similar between the groups. There was no significant difference in PFS between all CFR-PEEK and titanium patients (143 days versus 214 days; p = 0.41). When comparing patients in which recurrence was noted, CFR-PEEK patients had recurrence detected two times earlier than titanium patients (94 days versus 189 days; p = 0.013). In this case matched cohort, CFR-PEEK demonstrated decreased overall PFS suggestive of earlier local recurrence identification. Long-term studies are warranted for better evaluation of the impact on survival and systemic disease progression.

The Immune Modulation HLA-G*01:01:01 Full Allele Is Associated with Gastric Adenocarcinoma Development.

The Human Leukocyte Antigen (HLA) system contains a set of genes involved at many levels in the innate and adaptive immune response. Among the non-classical HLA class I genes, HLA-G stands out for the numerous studies about its pivotal role in regulating/modulating immune responses. Also, its involvement in extravillous cytotrophoblast function, viral infections, autoimmunity, and cancer has been extensively documented. The present study explores for the first time the relationship between natural alleles of HLA-G, rather than STSs, SNPs, or partial gene polymorphisms, and the development of gastric adenocarcinoma, by analyzing the genetic profile of a cohort of 40 Spanish patients with this type of tumor using DNA extracted from paired biopsies of tumoral and adjacent non-tumoral gastric tissue. Our results reveal a significant statistical relationship between the presence of the HLA-G*01:01:01 allele and the development of gastric cancer, while other common alleles such as -G*01:04 or -G*01:05N did not demonstrate a significant correlation. Studying the involvement of HLA genes in the development of many diseases is relevant to understanding their pathophysiology. However, the absence of specific mechanisms underlying these associations suggests that investigating complete HLA natural alleles' extended haplotypes or complotypes may offer a more precise and valuable approach to elucidating the association of HLA with the pathogenesis of disease.

The three YTHDF paralogs and VIRMA are strong cross-histotype tumor driver candidates among m6A core genes.

N6-Methyladenosine (m6A) is the most abundant internal modification in mRNAs. Despite accumulating evidence for the profound impact of m6A on cancer biology, there are conflicting reports that alterations in genes encoding the m6A machinery proteins can either promote or suppress cancer, even in the same tumor type. Using data from The Cancer Genome Atlas, we performed a pan-cancer investigation of 15 m6A core factors in nearly 10000 samples from 31 tumor types to reveal underlying cross-tumor patterns. Altered expression, largely driven by copy number variations at the chromosome arm level, results in the most common mode of dysregulation of these factors. YTHDF1, YTHDF2, YTHDF3and VIRMA are the most frequently altered factors and the only ones to be uniquely altered when tumors are grouped according to the expression pattern of the m6A factors. These genes are also the only ones with coherent, pan-cancer predictive power for progression-free survival. On the contrary, METTL3, the most intensively studied m6A factor as a cancer target, shows much lower levels of alteration and no predictive power for patient survival. Therefore, we propose the non-enzymatic YTHDF and VIRMA genes as preferred subjects to dissect the role of m6A in cancer and as priority cancer targets.