Implantation Metastasis Research Articles

NCMP-04. IMPLANTATION METASTASIS FOLLOWING BIOPSY OF THALAMIC GERMINOMA – A CASE REPORT AND REVIEW OF LITERATURE

Abstract Germ cell tumors commonly develop in the pineal and suprasellar regions, with the most common germ cell tumor being germinomas. In this report, a 22-year-old male presented with progressive right-sided weakness and his imaging was consistent a thalamic high grade glioma. A stereotactic biopsy was performed, revealing a germinoma, but radiation therapy was not done and patient was lost to follow up. He was readmitted due to ulcerative tumor growth at the previous skin incision, and imaging revealed tumor progression with implantation metastasis along the tract of the previous biopsy. The scalp tumor was excised and histopathologic studies confirmed that it was proliferation of the previous germinoma. He was discharged well but was unfortunately unable to follow up at the clinic. Thalamic germinomas are difficult to diagnose and treat because of their rarity. Here we underscore the importance of careful patient selection, precise biopsy techniques, thorough postoperative management and close radiographic surveillance to minimize the risk of implantation metastasis and promptly treat it if it occurs.

Wound healing after surgical therapy for multiple myeloma: a case-control study.

The aim of this study was to observe the surgical wound healing process in patients with multiple myeloma who had undergone surgery. We collected clinical data on patients with multiple myeloma and observed wound healing following surgical therapy. Additionally, we compared the expression of angiogenesis markers in patients with and without multiple myeloma (undergoing surgical excision of other tumour tissues). In patients who had multiple myeloma bone disease, we examined several clinical features: haemoglobin levels; albumin levels; blood glucose levels; and surgery programme. We then compared expression levels of the angiogenesis markers CD31, CD34 and vascular endothelial growth factor (VEGF) in samples scraped from the skin margin of the surgical incision in 12 patients without multiple myeloma (control) and nine patients with multiple myeloma. All 61 patients with multiple myeloma observed showed no disunion, no delayed union and no infection in their wound healing. CD31 and VEGF expression was higher in the nine patients with multiple myeloma compared with the 12 control patients without. We observed no difference in CD34 expression between control and experimental groups. The results of this study suggest that patients with multiple myeloma who have undergone surgery recover well and produce higher quantities of new vessels compared with patients without multiple myeloma. This occurs through increased expression of CD31 and VEGF, angiogenic factors which promote wound healing. We did not observe higher expression of these factors contributing to increased incisional implantation metastasis.

Low Grade Extrauterine Endometrial Stromal Sarcoma Arising from Peritoneum Endometriosis: A Case Report and Literature Review

Introduction: Endometrial stromal sarcoma (ESS) is an uncommon condition that accounts for approximately 0.2% of all reproductive tract malignancies. Among the various subtypes of ESS, low-grade extrauterine endometrial stromal sarcoma (LG-EESS) is even rarer and has only been reported in a limited number of case studies. Case Presentation: We reported a case of LG-EESS in a 35-year-old woman with a five-year history of stage IV endometriosis. The patient presented with chronic abdominopelvic pain and dysmenorrhea. Transvaginal ultrasound showed bilateral tubo-ovarian complexes with multicystic structures, while MRI revealed solid lesions with T1 iso signal, T2 hypersignal, and diffusion restriction, indicating metastatic implantation extending to the peritoneum and subhepatic region. A core needle biopsy confirmed LG-EESS, and immunohistochemistry showed CD10 positivity, aiding in the diagnosis and distinguishing it from other tumors. Conclusions: Our case highlights the potential utility of preoperative diagnostic imaging, particularly MRI, in the evaluation of LG-EESS. Additionally, it emphasizes the importance of considering the possibility of extrauterine ESS, as this tumor exhibits histopathological features and clinical behavior similar to its uterine counterpart.

The probability of implantation metastasis after peripheral lung cancer biopsy.

At present, it is known that there is a possibility of pleural cavity and needle tract implantation metastasis after lung cancer puncture biopsy, but clinicians have not paid attention to this phenomenon, and the probability of occurrence is unknown. In this study, we aimed to study the probability of implantation metastasis after peripheral lung cancer biopsy. The intraoperative isolated completely collapsed fresh intact human lung lobes of 30 patients with peripheral lung cancer were taken, and the tumor body was punctured. The pleural pinholes and puncture needle tips were repeatedly rinsed with normal saline respectively. The flushing solution was prepared as inoculum, and then the inoculum was smeared for microscopic examination to find cancer cells. The inoculum was inoculated subcutaneously into nude mice, and then the probability of pleural cavity and needle tract implantation metastasis after lung biopsy was indirectly obtained by obtaining the nude mice tumorigenesis rate. The tumorigenesis rate of nude mice in the pleural pinholes group was 3.3%, and the tumorigenesis rate of nude mice in the puncture needle tip group was 3.3%. Patients with lung nodules suspected of being early stage cancer and who are fit for surgical resection may benefit from forgoing lung biopsies to avoid pleural cavity or needle tract seeding with tumor cells.

Evaluation of 68Ga-FAPI PET/CT and 18F-FDG PET/CT for the diagnosis of recurrent colorectal cancers

ObjectiveThe present study aimed to compare the diagnostic value of gallium-68-labeled fibroblast activation protein inhibitor positron emission tomography/computed tomography (68Ga-FAPI PET/CT) and fluorine-18-labeled fluorodeoxyglucose PET/CT (18F-FDG PET/CT) for detecting recurrent colorectal cancers (CRCs). Materials and MethodsFifty-six patients (age: 18–80 years, 31 men and 25 women) with suspected recurrent CRC were enrolled and underwent 18F-FDG PET/CT and 68Ga-FAPI PET/CT sequentially within 1 week. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were estimated and compared between the two modalities by using Student’s t-test. The Wilcoxon signed-rank test was used to compare peritoneal carcinoma index (PCI) scores between the two imaging modalities. Results68Ga-FAPI PET/CT showed higher sensitivity for detecting recurrence (93 % vs. 79 %); lymph node metastasis (89 % vs. 78 %), particularly peritoneal lymph node metastasis (92 % vs. 63 %); and metastatic implantation on the intestinal wall (100 % vs. 25 %) compared to 18F-FDG PET/CT. However, 68Ga-FAPI PET/CT showed lower sensitivity for detecting bone metastasis (67 % vs. 100 %). The mean SUVmax values of peritoneal metastases and metastatic implantation on the intestinal wall were 4.28 ± 2.70 and 7.58 ± 1.66 for 18F-FDG PET/CT and 5.66 ± 1.97 and 6.70 ± 0.25 for 68Ga-FAPI PET/CT, respectively. Furthermore, 68Ga-FAPI PET/CT showed significantly higher TBR for peritoneal metastatic lesions (4.22 ± 1.47 vs. 1.41 ± 0.89, p < 0.0001) and metastatic implantation on the intestinal wall (5.63 ± 1.24 vs. 2.20 ± 0.5, p = 0.02) compared to 18F-FDG PET/CT. For the same patient, 68Ga-FAPI PET/CT yielded a more accurate PCI score and a greater area under the curve value for the receiver operating characteristic curve (p < 0.01) than 18F-FDG PET/CT. Conclusion68Ga-FAPI PET/CT was superior to 18F-FDG PET/CT for detecting recurrence and peritoneal metastases. Hence, we propose the combination of these two modalities for better clinical diagnosis and management of patients with CRC.

Esophageal Implantation Metastasis of Gastric Cancer During Specimen Retrieval After Endoscopic Submucosal Dissection.

Esophageal Implantation Metastasis of Gastric Cancer During Specimen Retrieval After Endoscopic Submucosal Dissection.

Tumor recurrence and survival prognosis in patients with advanced gastric cancer after radical resection with radiotherapy and chemotherapy.

Advanced gastric cancer is a common malignancy that is often diagnosed at an advanced stage and is still at risk of recurrence after radical surgical treatment. Chemoradiotherapy, as one of the important treatment methods for gastric cancer, is of great significance for improving the survival rate of patients. However, the tumor recurrence and survival prognosis of gastric cancer patients after radiotherapy and chemotherapy are still uncertain. To analyze the tumor recurrence after radical radiotherapy and chemotherapy for advanced gastric cancer and provide more in-depth guidance for clinicians. A retrospective analysis was performed on 171 patients with gastric cancer who received postoperative adjuvant radiotherapy and chemotherapy in our hospital from 2021 to 2023. The Kaplan-Meier method was used to calculate the recurrence rate and survival rate; the log-rank method was used to analyze the single-factor prognosis; and the Cox model was used to analyze the prognosis associated with multiple factors. The median follow-up time of the whole group was 63 months, and the follow-up rate was 93.6%. Stage II and III patients accounted for 31.0% and 66.7%, respectively. The incidences of Grade 3 and above acute gastrointestinal reactions and hematological adverse reactions were 8.8% and 9.9%, respectively. A total of 166 patients completed the entire chemoradiotherapy regimen, during which no adverse reaction-related deaths occurred. In terms of the recurrence pattern, 17 patients had local recurrence, 29 patients had distant metastasis, and 12 patients had peritoneal implantation metastasis. The 1-year, 3-year, and 5-year overall survival (OS) rates were 83.7%, 66.3%, and 60.0%, respectively. The 1-year, 3-year, and 5-year disease-free survival rates were 75.5%, 62.7%, and 56.5%, respectively. Multivariate analysis revealed that T stage, peripheral nerve invasion, and the lymph node metastasis rate (LNR) were independent prognostic factors for OS. Postoperative intensity-modulated radiotherapy combined with chemotherapy for gastric cancer treatment is well tolerated and has acceptable adverse effects, which is beneficial for local tumor control and can improve the long-term survival of patients. The LNR was an independent prognostic factor for OS. For patients with a high risk of local recurrence, postoperative adjuvant chemoradiation should be considered.

Lapatinib antitumor effect is associated with PI3K and MAPK pathway: An analysis in human and canine prostate cancer cells.

The aberrant activation of HER2 has a pivotal role in bone metastasis implantation and progression in several tumor types, including prostate cancer (PC). Trastuzumab and other anti-HER2 therapies, such as lapatinib, have been used in human breast cancer HER2 positive. Although HER2 overexpression has been reported in PC, anti-HER2 therapy response has revealed conflicting results. We investigated the potential of lapatinib in inhibiting cell migration and inducing apoptosis in two human (LNCaP and PC3) and two canine PC cell lines (PC1 and PC2). Cell migration and apoptosis were evaluated by Annexin V/PI analysis after lapatinib treatment. The transcriptome analysis of all cell lines before and after treatment with lapatinib was also performed. We found increased apoptosis and migration inhibition in LNCaP cells (androgen-sensitive cell line), while PC1, PC2, and PC3 cells showed no alterations after the treatment. The transcriptome analysis of LNCaP and PC3 cell lines showed 158 dysregulated transcripts in common, while PC1 and PC2 cell lines presented 82. At the doses of lapatinib used, we observed transcriptional modifications in all cell lines. PI3K/AKT/mTOR pathway were enriched in human PC cells, while canine PC cells showed enrichment of tyrosine kinase antitumor response and HER2-related pathways. In canine PC cells, the apoptosis failed after lapatinib treatment, possibly due to the downregulation of MAPK genes. Prostate cancer cells insensitive to androgens may be resistant to lapatinib through PI3K gene dysregulation. The association of lapatinib with PI3K inhibitors may provide a more effective antitumor response and clinical benefits to PC patients.

Abstract 6902: Development of a stable luciferase expressing PDX-derived cell line for translational in vitro and in vivo testing

Abstract Despite much effort invested in developing novel cancer therapies, more than 90% of clinical studies fail due to toxicity or lack of efficacy in patients. This can mainly be ascribed to lack of relevant and translational preclinical models. A common model used in preclinical studies is the xenograft model using immortalized cancer cells. Cell line-based models are cost efficient and can be genetically manipulated but are often criticized for lacking translational value. A murine model with higher clinical relevance is the patient derived xenografts (PDX) model established by implanting patients’ tumor tissue onto immunodeficient mice. Knowledge of patient therapy response, mutational status and tumor heterogeneity makes it a relevant model. However, PDX models are costly, not applicable for in vitro assays or subjective to genetic manipulation. To more closely mimic in vivo tumors we have established a PDX-derived cell line (PDXc) and characterized it extensively in a head-to-head comparison to the parental PDX model. Cells were isolated from a subcutaneous (SC) glioblastoma (GBM) PDX tumor (ST146), processed into single cells and cultivated in vitro. Once the PDXc were stable over several passages the cells were re-implanted into mice. Tumor take and growth rate were evaluated against the parental PDX model and common characteristics of the model such as EFGR and Vimentin expression were determined by IHC. We furthermore generated a stable Luciferase expressing PDXc using 3rd generation lentiviral particles and implanted the cells in an intracranial (IC) model of GBM. Tumor growth was evaluated using bioluminescence imaging (BLI) and MRI. Upon multiple passages and freeze cycles the cell line (ST146c) exhibited a stable in vitro doubling time (2.6 ± 0.2 days) with a morphology like other GBM cell lines with formation of neurospheres. STR analysis confirmed a genetic identical profile to ST146. ST146c implanted into mice had similar tumor take and growth rates to the parental PDX when injected IC (&amp;gt;90%, Td=3 d) and SC (&amp;gt;75%, Td=6 d). We also showed that ST146c had more homogeneous tumor growth. Ex vivo analysis showed similar expressions of EGFR (-), Vimentin (+++) and Ki67 (++) between the models. The BLI signal obtained from luciferase expressing ST146c implanted orthotopically was correlated to tumor volume obtained by MRI. We developed a PDX cell line that preserved critical in vitro and in vivo characteristics of the PDX model such as doubling time, tumor take rate and marker expression making it feasible to use the PDXc model in future preclinical studies. This will allow in vitro screens with patient derived tumor cells. Furthermore, the expression of luciferase in the PDXc enables intracranial and metastatic implantation with tumor monitoring using BLI. This platform consisting of in vitro and in vivo PDX models could be used as a predictive translational platform for testing new cancer therapies. Citation Format: Sigrid Cold, Rikke N. Bøge, Emma Papin, Ida T. Michler, Lotte K. Kristensen, Trine B. Engel, Andreas Kjaer, Carsten H. Nielsen, Sebastian Gnosa. Development of a stable luciferase expressing PDX-derived cell line for translational in vitro and in vivo testing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6902.

Abstract 3077: Integrin expression during ovarian cancer progression

Abstract During peritoneal dissemination, ovarian cancer cells exfoliate from the primary tumor and aggregate in the peritoneal fluid. This elicits survival signals via changes in mitochondrial morphology and function. As spheroids adhere to secondary sites, mitochondrial function is restored in the form of recovery of mitochondrial morphology, increased mitochondrial membrane potential, glucose uptake and increased proliferation. These findings suggested a mitochondrial phenotypic switch from mitophagy in spheroids to upregulation of mitobiogenesis upon spheroids adhesion to secondary sites. Hence, our objective was to identify critical receptors that facilitate the adhesion of spheroids to secondary sites, focusing on integrins that facilitate cell-extracellular matrix (ECM) attachment and activate downstream signaling cascades. To investigate changes in integrin expression, we mimicked three major stages of ovarian cancer progression by developing adherent stage, spheroid stage and adherent spheroid stage using our mouse ovarian surface epithelial (MOSE) cell lines representing benign (MOSE-E) stage as well as slow-developing (MOSE-L) and fast-developing disease (MOSE-LTICv) in biologically relevant conditions. Using RT qPCR and Western blotting, we determined gene and protein expression levels of integrins and adhesion related genes. Confocal microscopy was used to determine protein localization during ovarian cancer progression. RT qPCR result indicated differential up-regulated expression of integrins in both spheroid and adherent spheroid stage, suggesting the role of different integrins during the stages of ovarian cancer progression. Specifically, we observed a decrease (integrin ɑ5, ɑ6) or increase (ɑ2𝛃;1) of integrins after aggregation and an upregulation of 𝛃;1, α2, αV, α3, α5 and immunomodulatory integrins such as αE and αM in adherent spheroids, indicating their role in mediating specific steps during progression of ovarian cancer from tumorigenesis to metastatic implantation. We also observed increased expression levels of extracellular matrix proteins and their modulators, and cell-to-cell adhesion genes during ovarian cancer progression that was more pronounced in the MOSE-LTICv cells which suggests their association with an aggressive cancer phenotype. Overall, this project will aid in the identification of adhesion targets to develop new anti-metastatic treatments that will reduce mortality in women with ovarian cancer. Citation Format: Nazia Bano, Eva M. Schmelz. Integrin expression during ovarian cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3077.

Liver transplantation for unresectable Klatskin tumor: first long-term outcomes – a single center experience

Objective: to demonstrate the first long-term outcomes of treatment of unresectable hilar cholangiocarcinoma (HCCA) after combined neoadjuvant therapy followed by liver transplantation (LT). Materials and methods. From 2017 to 2023, at the Russian Research Center of Radiology and Surgical Technologies, 10 patients were included in the treatment protocol for unresectable HCCA. Combined neoadjuvant therapy included endobiliary photodynamic therapy (EPDT), regional chemotherapy (RCT) and systemic polychemotherapy (SPCT). Each modality was applied at least three times over a period of four to six months. Patients were placed on the LT waitlist when tumor marker CA19-9 reduced, there was no radiological evidence of disease progression, and there was no evidence of acute cholangitis. Before LT, the recipients underwent diagnostic laparoscopy to exclude carcinomatosis and also evaluation of regional lymph nodes with urgent morphologic examination. In the absence of extrahepatic tumor spread, LT from a deceased donor was performed according to the classical technique with paracaval and hepatoduodenal lymph node dissection, biliodigestive anastomosis using the Roux-en-Y procedure. The operation was performed in six patients. Patient age ranged from 40 to 55 years (mean, 46.3). The mean time from start of treatment to LT was 9.1 months (range 6 to 14). The mean CA19-9 level at the time of LT was 66.5 IU/mL (8 to 212). Results. After combined neoadjuvant treatment, the CA19-9 marker normalized in four patients and there was a 3–4-fold decrease in two patients. Radiological evaluation indicated stable disease in five patients, and a partial response in one. Disease progression was noted in four out of 10 patients. Currently, one of the 6 patients is alive with a follow-up of 34 months. Median (Me) overall survival is 28 months; Me overall survival after LT is 22.2 months; Me survival before progression is 27 months. During long-term follow-up of patients after LT, three patients out of six had disease progression: implantation metastasis (n = 2) at 25 and 27 months follow-up (metastasectomy was performed), carcinomatosis (n = 1) at 20 months follow-up. Conclusion. LT for unresectable Klatskin tumor is effective when combined neoadjuvant treatment is used and there is no acute cholangitis. However, the use of endobiliary manipulations (drainage change, EPDT) are risk factors for the development of implantation metastasis.

Percutaneous Needle Guided Localization of Asynchronous Metastatic Implants: A Novel Approach to Successful Surgical Metastectomy

Percutaneous Needle Guided Localization of Asynchronous Metastatic Implants: A Novel Approach to Successful Surgical Metastectomy

The place of multiple primary cancers in urologic oncology

Background. In Russia, statistical record of multiple primary cancers has been implemented only recently, and there are few scientific publications. Multiple primary malignant neoplasms of the urologic locations are described even less in literature. The problem of multiple tumors becomes more pressing with each passing year.Aim. To perform retrospective study of statistical data on urologic multiple primary cancer from one department.Materials and methods. An analysis of retrospective data from medical histories of patients who received treatment between 1997 and 2020 in urologic oncology departments where the authors worked: Omsk Regional Oncological Dispensary (1997–2005), Moscow Oncology Clinical Hospital No. 1 (2003–2005), Moscow City Oncology Hospital No. 62 was performed.Results. During the analyzed period, 23,299 hospitalizations including repeated were registered for 19,040 patients. Year-by-year data analysis showed 1,817 patients with multiple tumors, among them 1,508 patients with multiple primary malignant tumors, one and/or more of which were urologic pathology. The most common diseases were bladder cancer (n = 631), renal cancer (n = 618), prostate cancer (n = 614). A significant number of patients (n = 125; 8.29 %) had multiple tumors in 3 or more urologic locations. Tumors of the upper urinary tract were observed in 78 patients, testicle – in 36, penis – in 22, adrenal gland – in 10, urethra – in 4. Women comprised 28.05 % (n = 423) of the patients, men – almost 72 % (n = 1,085). This patient distribution by sex reflects the fact that urologic oncology includes both tumors of the urinary tract and male sex organs.Conclusion. Currently, the questions of terminology of multiple primary tumors remain open: multiple primary, multilocular, bilateral tumors, and mixed tumors. There is a lack of understanding in definition of the border between implantation metastases and multiple primary tumors in upper tract urothelial carcinoma and bladder cancer, between metastatic or bilateral tumors in bilateral renal cell carcinoma of the same morphology, etc.

Fruquintinib plus oxaliplatin combined with S-1 (SOX) as neoadjuvant therapy for locally advanced gastric adenocarcinoma (FRUTINEOGA): A multicenter, phase II study.

e16063 Background: Neoadjuvant chemotherapy (NCT) has become the standard treatment for patients (pts) with locally advanced GC, and SOX is the most common neoadjuvant regimen in China. Fruquintinib is a VEGFR inhibitor that blocks new blood vessel growth associated with tumor proliferation. It is a potent, highly selective small-molecule inhibitor of VEGFR-1,-2, and -3. The generally good tolerability in pts and fruquintinib’s low potential for drug-drug interaction suggest that it may be highly suitable for combinations with other antineoplastic therapies. We aimed to investigate the efficacy and toxicity of fruquintinib plus SOX as neoadjuvant treatment for locally advanced GC. Methods: It was a prospective, multicenter, phase II study in pts with stage III (cT3/4aN+M0) GC. Pts received 2 to 4 cycles of fruquintinib (5mg qd D1-14, Q3W) plus SOX (oxaliplatin 130mg/m2 D1, S-1 40-60mg bid D1-14 depending on body surface area (BSA), Q3W). Pts underwent D2 gastrectomy after neoadjuvant treatment. The primary endpoint was pathological response rate (pRR), and the secondary endpoints were disease-free survival (DFS), overall survival (OS), objective response rate (ORR), major pathological response rate (MPR), and R0 resection rate. Results: Up to February 3, 2023, 19 pts were eligible for the study. Median age was 62 years (29-73), 68.4% were male, and 21.1% were ECOG 1. Seven pts dropped out of clinical trial for AEs (2 pts), violation of treatment protocol (1 pt), staging error (2 pts), and refusal of surgery (2 pts). Twelve pts underwent surgery, 1 patient was found with peritoneal implantation, 11 patients underwent gastrectomy. Among the 11 pts, 9 pts achieved pRR (81.8%) and 3 pts achieved MPR (27.3%). The pathologic CR rate was 27.3% (3 of 11 pts). Moreover, 11 pts had curative intended operations and R0 resection rate was 90.9%. Among all the 19 pts, 16 pts received at least one dose of the combination treatment. A total of 2 pts had target lesions, 1 patient had complete response and 1 had partial response. Among the other 14 pts without target lesions, 1 (7.1%) had progressive disease with peritoneal implantation metastasis, and none had complete response. Furthermore, the most common TEAEs of grade ≥ 3 occurred in 19 pts were decreased appetite (21.1%), hypertension (21.1%), nausea (15.8%), vomiting (10.5%), oral mucositis (10.5%), fatigue (5.3%), diarrhea (5.3%) and respiratory infections (5.3%). There were neither new safety signals nor AEs inducing treatment deaths. Conclusions: The combination of fruquintinib and SOX as neoadjuvant treatment in patients with locally advanced GC is safe. The combination demonstrates promising evidence of anti-tumor efficacy in terms of pathological response. Clinical trial information: NCT05122091 .

Abstract #1406407: A Rare Case of Pituitary Metastasis from Esophageal Adenocarcinoma

Metastases to the pituitary gland are uncommon. Metastatic lesions represent < 1 % of sellar masses (1). Breast and lungs are the most common primary tumors associated with pituitary metastasis, representing nearly 60% of cases (1). Esophageal adenocarcinoma is a very rare cause of pituitary metastasis and only a few cases have been reported. We present a very rare case of a patient with pituitary metastasis from esophageal adenocarcinoma. 49-year-old male presented with a 2-month history of progressive fatigue, chills, lightheadedness, poor appetite, headaches, and decreased peripheral vision. One month before admission he was diagnosed with an invasive moderately differentiated esophageal adenocarcinoma. Head CT showed a heterogeneous hyperdense pituitary mass. Pituitary MRI confirmed a 2.13 x 0.9 cm heterogeneously enhancing, lobulated sellar mass with suprasellar extension and at least 2 sub-centimeters areas of enhancement within the right frontal lobe. CT chest, abdomen, and pelvis with splenomegaly, multiple lesions in the lungs, liver, and bilateral adrenal glands, concerning for metastases. Laboratories showed a cortisol level of 1.2 mcg/dL, TSH 1.074 (0.46-4.7 uIU/mL), free T4 < 0.42 (0.7-1.30 ng/dL). Prolactin 3.9 (2.5-17.0 ng/mL)), LH < 0.1 (0.8-7.6 mIU/mL), FSH 0.9 (0.7-11.1 mIU/mL), total testosterone < 4.33 (240-871 ng/dL), and IGF-1 76 (53.3-215 ng/mL). No evidence of diabetes insipidus. The patient was started on levothyroxine 150 mcg daily and hydrocortisone 15 mg in the morning and 5 mg in the afternoon. Ophthalmologic evaluation showed multiple elevated retinal lesions in both eyes, concerning for metastatic implants. No acute intervention per neurosurgery. After discharge, an adrenal biopsy confirmed metastatic esophageal adenocarcinoma. The patient underwent whole brain radiotherapy (WBRT) and was started on FOLFOX, trastuzumab, pembrolizumab, and zometa. MRI 3 months later showed decrease in size of enhancing lesion most suspicious for metastasis within the right frontal lobe and sella turcica. Pituitary metastases are usually diagnosed in the 6th and 7th decade of life with widespread metastatic disease. Esophageal adenocarcinoma is a rare cause of pituitary metastasis with few cases reported. Patients may be asymptomatic, but others may present with diabetes insipidus, visual disturbances, headaches, and panhypopituitarism (2). Our patient presented at a younger age with symptoms indicative of pituitary failure. Although these may be nonspecific, it is important to maintain awareness of them so that testing and treatment can be performed in a timely fashion.

Abstract 2499: Complement activation at the interface between cancer cells and adipocytes

Abstract Introduction: Ovarian cancer (OC) preferred site of metastasis is the fat-rich omentum. The interaction between cancer cells and adipocytes induces genotypical and phenotypical changes favoring increased invasiveness and metastatic potential of OC cells. In this study we stablish a novel in-vitro direct co-culture model by using immortalized human visceral pre-adipocytes and OC cells to understand the genotypical and phenotypical changes that adipocytes coculture generates over OC cells. Materials and Methods: OVCAR5 or OVCAR8 OC cells expressing either GFP or RFP were co-cultured with matured primary immortalized human visceral pre-adipocyte (VNPAD). The cells were seeded together in direct monolayer co-culture. After co-culture, OC cells were sorted by FACS and used to evaluate cell proliferation, resistance to cisplatin and transcriptomic changes. Results: Direct co-culture (3 days) of adipocytes and OC cells increased proliferation (p &amp;lt; 0.001), invasiveness (p &amp;lt; 0.005), and induced epithelial to mesenchymal transition (EMT) of OC cells relative to cells cultured alone. Co-culture with adipocytes also increased resistance to platinum (cisplatin IC50 from 3.90 µM to 7.07 µM for OVCAR5, and from 7.54 µM to 9.35 µM for OVCAR8 cells). RNAseq of co-cultured OVCAR5 cells detected 7783 differentially expressed genes (FDR&amp;lt;0.05, fold change &amp;gt;2). The most affected pathways included the PI3K/AKT pathway, inflammatory response, complement activation, and lipid localization. Activation of the complement (C) system in cells co-cultured with adipocytes was associated with upregulation of both C3 and C5 which was confirmed by quantitative RT-PCR, western blot and ELISA. Treatment of primary OC cells with media conditioned by adipocytes increased the expression of C3 and C5 (P&amp;lt;0.05). Similarly, treatment of OVCAR5 cells with a lipid mixture increased expression of C3 and C5 (mRNA and protein). The co-culture of OC cells with adipocytes and the treatment with lipids activated the PI3K pathway and the integrated stress response (ISR) pathway mediated by ATF4. shRNA knockdown of C3 and a chemical inhibitor for the C3 and C5 receptor (sb290157) reverted the increased proliferative phenotype and activation of PI3K in cocultured OC cells. Stable knockdown of C3 with shRNA in OVCAR5 cells reduced tumor volume and tumor weight in an intraperitoneal OC xenograft model (p&amp;lt;0.05). IHC of paired primary tumors and metastatic implants in the omentum showed increased C3 expression adjacent to fat (p&amp;lt;0.05). Conclusion: Co-culture of adipocytes and cancer cells drives changes in proliferation and cisplatin responsiveness in OC cells. These changes are induced by transfer of lipids from adipocytes to cancer cells and subsequent activation of the complement proteins C3 and C5 through the ISR pathway and ATF4. Citation Format: Andres Felipe Valdivia, Hao Huang, Horacio Cardenas, Aloysius Klingelhutz, Daniela Matei. Complement activation at the interface between cancer cells and adipocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2499.

An unusal presentation of mature ovarian teratoma in a young girl: A rare case report

Introduction: Solid teratomas are relatively more common in infants and children (accounting for 15% of ovarian tumor). Though the peak age incidence is at second decade [1]. Metastatic implantation of glial tissue on surfaces of visceral or parietal peritoneum is called as Gliomatosis peritonei (GP) and its occurrence is very rare.Case Report: A 10 year old girl presented with the complaints of vague abdominal pain and discomfort for two months. Ultrasonography of the abdomen showed a heterogenous solid cystic tumor of 12 X 15 x 10 cm noted in left side of the ovary adherent to the fallopian tube. Left salpingoopherectomy was done and histopathology show features of mature solid ovarian teratoma with Gliomatosis peritonei.Conclusion: Gliomatosis peritonei is implantation of mature glial tissue on surfaces of peritoneum. It is often associated with ovarian teratoma of any grade. This is always present with massive peritoneal implantation, optimal resection is difficult. Although residual peritoneal disease can be totally quiescent over a long period, long-term follow-up is needed for patients with residual disease. A more conservative surgical approach may be carried out in patients with massive peritoneal spread.

A NOTCH1 Mutation Found in a Newly Established Ovarian Cancer Cell Line (FDOVL) Promotes Lymph Node Metastasis in Ovarian Cancer

Peritoneal implantation and lymph node metastasis have different driving mechanisms in ovarian cancer. Elucidating the underlying mechanism of lymph node metastasis is important for treatment outcomes. A new cell line, FDOVL, was established from a metastatic lymph node of a patient with primary platinum-resistant ovarian cancer and was then characterized. The effect of NOTCH1-p.C702fs mutation and NOTCH1 inhibitor on migration was evaluated in vitro and in vivo. Ten paired primary sites and metastatic lymph nodes were analyzed by RNA sequencing. The FDOVL cell line with serious karyotype abnormalities could be stably passaged and could be used to generated xenografts. NOTCH1-p.C702fs mutation was found exclusively in the FDOVL cell line and the metastatic lymph node. The mutation promoted migration and invasion in cell and animal models, and these effects were markedly repressed by the NOTCH inhibitor LY3039478. RNA sequencing confirmed CSF3 as the downstream effector of NOTCH1 mutation. Furthermore, the mutation was significantly more common in metastatic lymph nodes than in other peritoneal metastases in 10 paired samples (60% vs. 20%). The study revealed that NOTCH1 mutation is probably a driver of lymph node metastasis in ovarian cancer, which offers new ideas for the treatment of ovarian cancer lymph node metastasis with NOTCH inhibitors.

Implantation metastasis of colorectal cancer following percutaneous biliary drainage

Introduction. Malignant biliary obstruction represents a poor prognostic sign of metastatic colorectal carcinoma. Percutaneous transhepatic biliary drainage (PTBD) is the procedure of choice for palliative biliary decompression, and this method has both diagnostic and therapeutic values. One of the wellknown complications following this procedure is the development of catheter tract metastases that occur in 0.6?6% of cases post-PTBD. In this case report, we present a patient with implantation metastases of colorectal cancer following PTBD. Case report. In the last six years, 89 patients underwent PTBD procedure at the Oncology Institute of Vojvodina. Among these patients, catheter tract implantation metastasis developed in one patient (1.1%). In this report, we present a patient who underwent right hemicolectomy in January 2015 at the Oncology Institute due to colon cancer located in the transverse colon. In January of 2018, a computed tomography scan of the abdomen showed metastatic disease and chemotherapy was initiated. However, 29 months following the start of chemotherapy, the patient developed jaundice, and as a result, PTBD procedure was performed. A control computed tomography scan of the abdomen in March of 2021 showed a de novo subcutaneous nodule 20 mm in diameter located at the level of ninth right rib. The nodule had been considered a part of the scar that formed at a place of catheter entry, and was still present eight months after PTBD procedure. Biopsy of the subcutaneous mass and pathohistological analysis confirmed well differentiated colon adenocarcinoma. Conclusion. Catheter tract implantation metastasis is not a rare complication following PTBD for malignant biliary obstruction. It generally has a poor prognosis. Nevertheless, literature review shows that radical surgical excision of the catheter tract tissue with hepatectomy can prolong survival in select group of patients.

Metástase de condrossarcoma simulando tumor primário de estômago: relato de caso

Gastric tumors are an important cause of cancer deaths. The main type is the primary gastric adenocarcinoma, and rarely secondary metastatic implants can be present. A 79-years-old woman sought medical attention due to a complaint of epigastralgia, unintentional weight loss, two cases of melena in the past two months, and a prior history of a chondrosarcoma of the thigh treated 13 years before. A neoplastic lesion was detected at the stomach during evaluation, and a gastrectomy was opted as a treatment. The immunohistochemical evaluation was compatible with a chondrosarcoma metastatic implant on the stomach. The patient obtained a survival superior to 5 years after surgery. Only one case of gastric metastasis from chondrosarcoma was described in the literature. We observed a great benefit in the use of surgical resection of the gastric lesion, showing that surgery may be considered in selected individuals with chondrosarcoma metastasis.