Neuroendocrine Tumor Metastases Research Articles

Risk factors for lymph node metastasis and indication of local resection in duodenal neuroendocrine tumors.

Background and AimThe risk factors for lymph node metastasis (LNM) of duodenal neuroendocrine tumors (DNETs) are not well identified, and a definitive standard of treatment for DNETs has not been established. In this study, we aimed to identify the risk factors for LNM and establish the indication of local resection for DNETs.MethodsWe retrospectively reviewed 55 patients with 60 non‐ampullary and nonfunctional DNETs. We evaluated the risk factors for LNM and compared the outcomes between endoscopic resection (ER) for DNETs <5 mm and laparoscopy and endoscopy cooperative surgery (LECS) for DNETs ≥5 mm.ResultsLNM was present in four (8.7%) patients. Univariate analysis revealed that tumor size ≥10 mm, positive lymphovascular invasion (LVI), and 0‐Is morphology were significantly associated with LNM (P = 0.008, P = 0.037, and P = 0.045, respectively). ER and LECS were performed for 18 and 11 DNETs, respectively. All lesions treated with ER or LECS were confined to the submucosal layer. The median tumor size was 3 mm in ER and 6 mm in LECS. Although there was no significant difference in the R0 (no residual tumor) resection rate, R0 resection was completely achieved in the LECS. No significant differences were observed in terms of complication rates. No recurrence was observed in any of the groups.ConclusionsTumor size ≥10 mm, positive LVI, and 0‐Is morphology were significant risk factors for LNM. We demonstrated that ER is feasible and could be safely applied for DNETs <5 mm, and LECS could be applied for DNETs 5–10 mm in size.

FAM83A promotes the progression and metastasis of human pancreatic neuroendocrine tumors by inducing the epithelial-mesenchymal transition via the PI3K/AKT and ERK pathways

Background: Family with sequence similarity 83, member A (FAM83A) has been reported to play an important role in cancer progression and metastasis. The purpose of this study was to clarify the role and mechanism of FAM83A in pancreatic neuroendocrine tumors (PanNETs). Methods: PanNET specimens and adjacent nontumor pancreatic tissues obtained from 68 patients who underwent curative surgery for PanNETs were assessed using immunochemical staining to identify FAM83A expression. The relationships between FAM83A expression, clinicopathological parameters and prognosis were statistically analyzed. PanNET cell lines were used to study the role of FAM83A in the progression and metastasis of PanNETs in vitro and in vivo. Results: FAM83A was overexpressed in PanNET specimens compared with adjacent nontumor tissues. Furthermore, FAM83A expression was closely associated with lymph node metastasis (P = 0.02), perineural invasion (P = 0.001), the WHO classification (P = 0.039), AJCC stage (P = 0.01) and shorter disease-free survival in patients with PanNETs (P &lt; 0.001). Enforced expression of FAM83A effectively promoted PanNET cell proliferation, migration, invasion and growth both in vitro and in vivo, whereas FAM83A inhibition exerted the opposite effects. Subsequent mechanistic investigations revealed that FAM83A promoted the progression and metastasis of PanNETs by inducing epithelial-mesenchymal transition (EMT) via the PI3K/AKT and ERK pathways. More importantly, specific inhibition of either the AKT or ERK pathways partially rescued the effect of FAM83A overexpression on promoting PanNET progression and metastasis. Conclusions: FAM83A plays an important role in the progression and metastasis of PanNET by inducing the EMT via the activation of the ERK and PI3K/AKT pathways and may serve as a valuable molecular target in PanNET treatment.

Tumor-to-tumor metastasis: an extremely rare combination with renal cell carcinoma as the donor and a pancreatic neuroendocrine tumor as the recipient

BackgroundTumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize hematogenously into another tumor. Herein, we report an extremely rare case of a renal cell carcinoma metastasis into a pancreatic neuroendocrine tumor exhibiting a tumor-to-tumor metastasis. Ours is the third reported case worldwide.Case presentationThe patient, a 72-year-old male, was referred to our hospital for further examination and treatment due to high levels of prostate-specific antigen. A left renal tumor and pancreatic head tumor were revealed incidentally on screening computed tomography. There were suspected to be a renal cell carcinoma and primary pancreatic neuroendocrine tumor or pancreatic metastasis from the renal cell carcinoma according to preoperative examination. The left nephrectomy and subtotal stomach-preserving pancreaticoduodenectomy were performed because of the pancreatic tumor indicated for operation in either case of diagnosis. Postoperative pathological examination showed a diagnosis of clear cell renal cell carcinoma for the left renal tumor. The pancreatic tumor was diagnosed with clear cell renal cell carcinoma metastasis into the pancreatic neuroendocrine tumor, that is to say tumor-to-tumor metastasis.ConclusionIn some cases, conservative approach is selected for pancreatic neuroendocrine tumor patients who meet some requirements. However, if such patients exhibit tumor-to-tumor metastasis which combines with renal cell carcinoma and pancreatic neuroendocrine tumor as this case, conservative approach leads to progression of renal cell carcinoma. Therefore, conceiving the possibility of tumor-to-tumor metastasis, it is necessary to carefully choose a treatment plan for pancreatic neuroendocrine tumor patients associated with renal cell carcinoma, not easily choosing conservative approach.

Study Protocol for a Trial: A Single-Arm, Open-Labeled Study Evaluating Transcatheter Arterial Embolization Plus Everolimus Combination Therapy for Patients With Liver Metastasis of Gastroenteropancreatic Neuroendocrine Tumors.

The number of patients with non-functional neuroendocrine tumors (NETs) has increased recently, and the rate of liver metastasis of NETs is about 20% in patients at the first diagnosis. Transcatheter arterial embolization (TAE) and everolimus are therapies with reported efficacy, but few reports have described their combined treatment. We therefore aim to evaluate the efficacy and safety of combination therapy with everolimus and TAE in patients with liver metastasis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in a prospective study. We design a single-arm, open-label, prospective study to evaluate the efficacy and safety of combination therapy with everolimus and TAE in patients with liver metastases of GEP-NETs. The study started in June 2021 at Okayama University Hospital and is expected to enroll 18 patients over a 2-year period. This study is a prospective study investigating a new treatment method for a rare disease called GEP-NETs. We may obtain useful information that contributes to the treatment guidelines in this study. However, NET is a rare disease, and although the number of cases is statistically established, it may not be possible to accurately assess causality.TRIAL REGISTRATION NUMBER: jRCT1061210015.

Advances in basic and translational research in neuroendocrine neoplasms

With the development of diagnostic techniques and the improvement of people's living standards, the detection rate of neuroendocrine tumor has been increasing and people are paying more and more attention to it. With multiple treatment modalities, the clinical research progress of neuroendocrine tumor is remarkable. However, due to the tumor heterogeneity, metastasis and recurrence of neuroendocrine tumor remains a difficult problem for clinicians. The efficacy of neuroendocrine tumor still needs to be improved. Therefore, the biological behavior of neuroendocrine tumor needs to be further studied. In recent years, with the development of molecular biology, the basic and transformation research of neuroendocrine tumor has made some progress. In this paper, we focus on the hot topics of neuroendocrine tumor, such as multiomics (copy number variation, genomics, transcriptomics), tumor microenvironment (immune microenvironment, tumor microvasculature, tumor-associated fibroblasts, etc.), preclinical research model construction (cell lines, organoids, patient derived xenograft models, genetically engineered mice), etc. Specifically, the related clinical transformation significance will be elaborated.

Risk Factors for Lymph Node Metastasis and Oncologic Outcomes in Small Rectal Neuroendocrine Tumors with Lymphovascular Invasion

Background/AimsSmall rectal neuroendocrine tumors (NETs) are often managed with local resection (endoscopic or transanal excision) owing to their low risk of metastasis and recurrence. However, the clinical significance of lymphovascular invasion in resected specimens remains controversial. In this study, we aimed to analyze the frequency of and risk factors for lymph node metastasis proven by histopathologic examination after radical resection.MethodsWe retrospectively reviewed the records of 750 patients diagnosed with a rectal NET at four academic medical centers in South Korea between 2001 and 2019. The frequency of histopathologically proven lymph node metastasis and the associated risk factors were analyzed for small tumors (≤1.5 cm) with lymphovascular invasion.ResultsAmong 750 patients, 75 had a small tumor (≤1.5 cm) with lymphovascular invasion, of whom 31 patients underwent endoscopic resection only and 44 patients underwent additional radical surgery. Among the 41 patients who underwent surgery and had available data, the rate of regional lymph node metastasis was 48.8% (20/41). In multivariate analysis, the Ki-67 index (odds ratio, 6.279; 95% confidence interval, 1.212 to 32.528; p=0.029) was an independent risk factor for lymph node metastasis. During the mean follow-up period of 37.7 months, only one case of recurrence was detected in the surgery group. The overall survival was not significantly different between radical resection and local resection (p=0.332).ConclusionsRectal NETs with lymphovascular invasion showed a significantly high rate of regional lymph node metastasis despite their small size (≤1.5 cm).

Management and Survival Analysis of Gastrointestinal Neuroendocrine Tumors by Different Tumor Characteristics: Tertiary Center Experience.

Gastrointestinal neuroendocrine tumor (GI-NET) is a group of neoplasia consisting of amine and acid producing cells with different hormonal profiles. Although the entire GIS accounts for about 2% of tumors, recent research reveals that the incidence rate has increased. Given the increasing incidence in GI-NETs, more and more extensive research is needed on this subject. In this regard, the demographic and clinicopathological features of the patients diagnosed with GI-NET and their relationship with survival were investigated in the present study. Thirty-four patients diagnosed with GI-NETs between January 2009 and December 2019 at the Department of Gastroenterology, Inonu University Faculty of Medicine were analyzed retrospectively. Gender, age, tumor localization, metastasis status, tumor number, tumor diameter, tumor grade, Ki-67 index, and the relationships of these factors with overall survival were examined. Of the patients, 61.8% included in the study were male and 38.2% were female. The average age of the patients was 60.74 years. The most common tumor location was in the stomach (26.5%) and liver (26.5%). Apart from this, 17.6% of NETs were seen in the pancreas, 11.8% in the colon, 8.8% in the rectum, 5.9% in the small intestine, and 2.9% in the appendix. No significant relationship was observed between tumor location and gender (p = .326) and age (p = .641). The tumor diameter ranged from 0.2 cm to 13.91 cm, but the average tumor diameter was 3.84 cm. Solitary tumor was found in 51.5% of cases and multiple tumors in 48.5% of cases. The most common grade was Grade 1 with 41.2% of occurrence. The average of Ki-67 index was 18.36%. There was metastasis in 52.9% of cases. The rate of medical treatment was 48.5%. The median overall survival time of the patients was 23.1 months. In addition, 1-year overall survival was 74.9%, 2-year overall survival was 44.6%, and 5-year overall survival was 35.7%. A statistically significant difference was found between tumor grade and the presence of metastasis, and the overall survival (p = .003 and p = .005). The tumor grade and the presence of metastasis in gastrointestinal neuroendocrine tumors were found to be the most important prognostic factors affecting overall survival.

Metastatic Carcinoid Tumor to the Heart, A Dreadful Complication of Neuroendocrine Tumors Yet Under Estimated: About an Observation

Cardiac metastases are uncommon in neuroendocrine tumors (NET). Features of patients with metastatic carcinoid tumor involving the heart have not been well described. Although carcinoid tumors have been described in almost every organ, few reported cases of confirmed cardiac involvement. The overall incidence of myocardial carcinoid metastases among patients with metastatic carcinoid disease is about 4%. There is limited knowledge on the prevalence, clinical presentation, and management of heart metastasis. The availability and increasing use of modern imaging techniques leads to more frequent discovery of rare metastatic sites. Our aim is to further clarify the clinical manifestations of heart metastasis, to increase the knowledge of rare localizations of NET metastasis and insist on the systematic screening of metastatic carcinoid heart disease as an integral part of the echocardiographic evaluation in patients with carcinoid syndrome. We report the case of a 67-year-old male with history of a low differentiated neuroendocrine tumor, presenting with palpitations and dyspnea and which investigations have led to diagnose myocardial metastasis signing the progression of the NETs.

Incidence of ovarian metastasis in neuroendocrine tumors of the cervix

<h3>Objectives:</h3> To report on the incidence of ovarian metastasis in patients with high grade neuroendocrine tumors of the cervix (NEC) who underwent surgical resection. <h3>Methods:</h3> This was a single institution retrospective chart review. The electronic medical record was searched for all patients with a diagnosis of NEC at The Ohio State University from January 2010 to March 2020. Patients without complete pathologic records were excluded. <h3>Results:</h3> From January 2010 to March 2020, 43 patients were identified with NEC. Of those patients, 16 had undergone surgical resection including hysterectomy, bilateral salpingectomy and oophorectomy, and lymph node dissection. Of the 16 patients, zero had evidence of metastatic disease to their ovaries. The median age of patients in our cohort was 35.5 years with a mean age of 40.5 (28-70y). 13 of the 16 patients were considered pre-menopausal at the time of their surgery (defined as age 50 or younger). Of the 16 patients who underwent surgical management, 2 had adjuvant chemotherapy alone, 7 had adjuvant chemotherapy with adjuvant radiotherapy, 2 had adjuvant chemoradiotherapy, and 3 had adjuvant radiation therapy. Of the 16 patients in the study, 13 received neoadjuvant chemotherapy as part of their treatment. For those who had chemotherapy as part of their treatment plan, the most commonly used regimen was cisplatin with etoposide with a median of 3 cycles neoadjuvant and 3 cycles in the adjuvant setting. Based on the FIGO 2018 staging classifications, 6 patients had stage I disease (1 1A2, 2 IB1, 1 IB2, 2 IB3). 10 of the 16 patients had advanced stage disease defined as IIB through IVB (2 IIB, 1 IIIB, 3 IIIC1, 2 IIIC2, 2 IVB). <h3>Conclusions:</h3> The incidence of ovarian metastasis in patients with NEC has not been reported in the literature. Here we demonstrate in our limited series that ovarian metastasis in NEC of the cervix is rare. Current practice of ovarian retention in NEC is based on expert opinion and is not standard of care across the field of gynecologic oncology. Our data support that ovarian retention in NEC is safe. Previously published data from our institution demonstrate that 82% of patients with stage I disease had no evidence of disease at time of their last follow up with the use of a multimodality treatment approach (McCann 2013). In our cohort, radiation therapy is often employed in the treatment of NEC. Ovarian retention with transposition out of the radiated field may be a reasonable option for women who would benefit from preservation of ovarian function. Commonly used chemotherapeutic agents were cisplatin with etoposide, both with limited gonadotoxicity. Given the low incidence of ovarian metastasis in NEC, ovarian cryopreservation or oocyte harvesting is a reasonable option for patients who desire the ability to have offspring with the assistance of a surrogate in the future. Further studies with a multi-institutional collaboration to better define the incidence of NEC metastasis to the ovary is necessary.

Thoracic Splenosis Mimicking Metastatic Neuroendocrine Tumor (NET)

A 64-year-old man presented with abdominal pain. CT scan showed a 5mm left ureter stone, mesenteric root mass as well as a left lung pleuralbased lesion. Metastatic Neuroendocrine Tumor (NET) was suspected, hence a Gallium-68 Dotatate PET was performed. It showed intense uptake in the mesenteric mass, as well as in the pleural nodule, and no intense uptake in the liver. The liver is the most common site for small bowel NET metastasis. It is unusual to have pleural metastasis without liver metastasis. A review of this patient’s past medical history revealed a motor vehicle accident 20 years ago which required an exploratory laparotomy and splenectomy. Gallium 68 Dotatate PET scan can detect splenosis because it has somatostatin receptors. In patients with an existing neoplasm, metastases should be ruled out before confirming the diagnosis of splenosis. CT-guided biopsy of pleura nodule was performed, which confirmed the diagnosis of splenosis.

Risk factors for lymph node metastasis in rectal neuroendocrine tumors: A recursive partitioning analysis based on multicenter data.

The well-differentiated rectal neuroendocrine tumors (RNETs) can also have lymph node metastasis (LNM). Large multicenter data were reviewed to explore the risk factors for LNM in RNETs. Further, we developed a model to predict the risk of LNM in RNETs. In total, 223 patients with RNETs from the Fujian Medical University Union Hospital, the First Affiliated Hospital of Fujian Medical University, and the First Affiliated Hospital of Xiamen University were retrospectively enrolled. Logistic regression analysis was performed to study the factors affecting LNM, and recursive partitioning analysis (RPA) was performed to stratify the risk of LNM. Among the 223 patients diagnosed with RNETs, the incidence of LNM was 10.8%. Univariate and multivariate regression analyses revealed that tumor size, World Health Organization (WHO) grade, and depth of tumor invasion were independent risk factors for LNM (p < 0.05). The area under the curve was 0.948 (95% confidence interval: 0.890-1.000). Furthermore, the incidence of LNM in patients divided into low- and high-risk groups according to RPA was 1.1% and 56.4%, respectively. Compared with tumor size, the depth of tumor invasion and WHO grade are more important factors in predicting LNM. Then, we developed a model based on RPA to predict the risk of LNM in RNETs and identify patients who are suitable for local resection.

Alternative Lengthening of Telomeres Phenotype Predicts Progression Risk in Noninsulinomas in a Chinese Cohort

Introduction: Recent studies have suggested that alternative lengthening of telomeres (ALT) is associated with metastasis and poor survival in pancreatic neuroendocrine tumors (PanNETs). This study evaluated whether this association is applicable to Chinese patients as well as the potential somatic mutations associated with ALT. Methods: We assessed the prevalence of ALT by performing telomere-specific fluorescence in situ hybridization and analyzed DAXX/ATRX expression using immunohistochemistry in 112 Chinese patients with PanNETs to evaluate the association between ALT and clinical outcomes. A subset of the noninsulinoma samples (28/60) was subjected to Sanger sequencing and targeted sequencing. Results: The ALT-positive phenotype was identified in 23.2% (26/112) of the samples. The clinicopathologic factors significantly associated with progression in the noninsulinoma (n = 60) cohort were the female sex (p = 0.006), Ki-67 index (p < 0.001), World Health Organization grade (p = 0.031), and ALT positivity (p = 0.013). Patients with ALT-positive PanNETs had significantly shorter progression-free survival than those with ALT-negative PanNETs in the entire cohort (p < 0.001), noninsulinoma subgroup (p = 0.01), and G2 subgroup (p = 0.001). ALT-positive samples frequently harbored somatic mutations in DAXX, ATRX, MEN1, SETBP1, PRKDC, and GNAS. Conclusions: We confirmed that ALT positivity is an effective risk predictor, especially in the noninsulinoma and G2 subgroups. ALT is also related to somatic mutations in MEN1, SETBP1, PRKDC, and GNAS, in addition to DAXX and ATRX.

Diagnostic and prognostic impact of cytokeratin 19 expression analysis in human tumors: a tissue microarray study of 13,172 tumors

To evaluate cytokeratin 19 (CK19) expression in normal and cancerous tissues, 15,977 samples from 122 tumor types and 608 samples of 76 normal tissue types were analyzed by immunohistochemistry (IHC). In normal tissues, CK19 expression occurred in epithelial cells of most glandular organs but was strictly limited to the basal cell layer of nonkeratinizing squamous epithelium and absent in the skin. CK19 expression in ≥90% of cases was seen in 34% of the tumor entities including the adenocarcinomas of the pancreas (99.4%), colorectum (99.8%), esophagus (98.7%), and stomach (97.7%), as well as breast cancer (90.0%-100%), high-grade serous (99.1%) or endometrioid (97.8%) ovarian cancer, and urothelial carcinoma (92.6%-100%). A low CK19 positivity rate (0.1-10%) was seen in 5 of 122 tumor entities including hepatocellular carcinoma and seminoma. A comparison of tumor versus normal tissue findings demonstrated that upregulation and downregulation of CK19 can occur in cancer and that both alterations can be linked to unfavorable phenotypes. CK19 downregulation was linked to high grade (p=0.0017) and loss of estrogen receptor- and progesterone receptor-expression (p<0.0001 each) in invasive breast carcinoma of no special type. CK19 upregulation was linked to nodal metastases in neuroendocrine tumors and papillary thyroid carcinomas (p<0.05 each) and to poor grade in clear cell renal cell carcinoma (p<0.05). CK19 upregulation was particularly common in squamous cell carcinomas. We concluded that CK19 IHC might separate primary liver cell carcinoma from liver metastases, seminoma from other testicular tumors, and helps in the detection of early neoplastic transformation in squamous epithelium.

Large-cell neuroendocrine tumor of the prostate: a\xa0case report and review of the literature

BackgroundPrimitive neuroendocrine prostate neoplasms are rarely reported. This entity comprises carcinoïd tumors and poorly differentiated neuroendocrine tumors, mainly those of the small-cell type. Large-cell-type primitive tumors are exceptional, and only nine cases are reported in the literature. Similar to neuroendocrine tumors of the prostate, large-cell-type primitive tumors may be observed in the context of conventional adenocarcinoma during androgen deprivation therapy or as prostatic metastasis of a distant neuroendocrine tumor, mainly pulmonary neoplasms.Case presentationWe report a Caucasian case of a mixed prostatic carcinoma, with the largest component being the large-cell neuroendocine carcinoma, in a patient who underwent a total prostatectomy for a localized cancer. Diagnostic, histological, therapeutic and evolutive aspects are reported and discussed.ConclusionsLarge-cell primitive prostate neuroendocrine carcinoma is a rare but aggressive histological entity, which can be associated or not with an adenocarcinomatous component. Mixed forms have a better outcome, mainly when diagnosed at an early stage.

Feasibility and Early Clinical Experience of Online Adaptive MR-Guided Radiotherapy of Liver Tumors.

Simple SummaryStereotactic body radiotherapy is used in the treatment of liver tumors. However, adjacent organs at risk (OAR) frequently limit the applicable dose to the target volume. The introduction of hybrid magnetic resonance imaging (MRI)-guided radiotherapy systems may allow dose escalation strategies with better OAR sparing due to improved soft tissue visualization, adaptive treatment planning and real-time motion management. Here we report the feasibility and early results of online adaptive MR-guided radiotherapy of primary and secondary liver tumors in eleven patients. The treatment was feasible and successfully completed in all patients. After a median follow-up of five months, no local failure occurred and no ≥ grade 2 toxicity was observed. The technique should be compared to conventional SBRT in further studies to assess the advantages of the technique.Purpose: To assess the feasibility and early results of online adaptive MR-guided radiotherapy (oMRgRT) of liver tumors. Methods: We retrospectively examined consecutive patients with primary or secondary liver lesions treated at our institution using a 0.35T hybrid MR-Linac (Viewray Inc., Mountain View, CA, USA). Online-adaptive treatment planning was used to account for interfractional anatomical changes, and real-time intrafractional motion management using online 2D cine MRI was performed using a respiratory gating approach. Treatment response and toxicity were assessed during follow-up. Results: Eleven patients and a total of 15 lesions were evaluated. Histologies included cholangiocarcinomas and metastases of neuroendocrine tumors, colorectal carcinomas, sarcomas and a gastrointestinal stroma tumor. The median BED10 of the PTV prescription doses was 84.4 Gy (range 59.5–112.5 Gy) applied in 3–5 fractions and the mean GTV BED10 was in median 147.9 Gy (range 71.7–200.5 Gy). Online plan adaptation was performed in 98% of fractions. The median overall treatment duration was 53 min. The treatment was feasible and successfully completed in all patients. After a median follow-up of five months, no local failure occurred and no ≥ grade two toxicity was observed. OMRgRT resulted in better PTV coverage and fewer OAR constraint violations. Conclusion: Early results of MR-linac based oMRgRT for the primary and secondary liver tumors are promising. The treatment was feasible in all cases and well tolerated with minimal toxicity. The technique should be compared to conventional SBRT in further studies to assess the advantages of the technique.

Application of molecular probes in nuclear imaging of neuroendocrine tumors.

Neuroendocrine tumors are a type of heterogeneous tumors originating from neuroendocrine cells derived from the neural crest，which can secrete a variety of amines and peptide hormones.Based on different molecular biomarkers，histologic types and differentiation degrees，individualized nuclear imaging can provide information for the early diagnosis，clinical staging，treatment guidance，and detection of the recurrence and metastasis of neuroendocrine tumor. In this paper，we review the development and application of nuclear medicine molecular imaging probes such as glucose analogs，somatostatin analogues，amine precursors，hormone analogs and enzyme inhibitors in the diagnosis and treatment of neuroendocrine tumors.

C-Myc promotes lymphatic metastasis of pancreatic neuroendocrine tumor through VEGFC upregulation.

Pancreatic neuroendocrine tumor (pNET) is a pancreatic neoplasm with neuroendocrine differentiation. pNET in early stage can be treated with surgical resection with long‐term survival, whereas the prognosis of pNET with locoregional or distant metastasis is relatively poor. Lymphangiogenesis is essential for tumor metastasis via the lymphatic system and may overhead distant metastasis. c‐Myc overexpression is involved in tumorigenesis. The role of c‐Myc in lymphangiogenesis is unclear. In this study, we evaluated the mechanism and effect of c‐Myc on lymphangiogenesis of pNET via interaction of lymphatic endothelial cells (LECs) and pNET cells. Lymph node metastasis was evaluated in pNET xenograft mice. Potential target agents to inhibit lymph node metastasis were evaluated in an animal model. We found that vascular endothelial growth factor C (VEGFC) expression and secretion was increased in pNET cell lines with c‐Myc overexpression. c‐Myc transcriptionally upregulates VEGFC expression and the secretion of pNET cells by directly binding to the E‐box of the VEGFC promoter and enhances VEGF receptor 3 phosphorylation and the tube formation of LECs. c‐Myc overexpression is associated with lymph node metastasis in pNET xenograft mice. Combinational treatment with an mTOR inhibitor and c‐Myc inhibitor or VEGFC‐neutralizing chimera protein reduced lymph node metastasis in the mice with c‐Myc overexpression. The mTOR inhibitor acts on lymphangiogenesis by reducing VEGFC expression in pNET cells and inhibiting the tube formation of LECs. In conclusion, mTOR and c‐Myc are important for lymphangiogenesis of pNET and are potential therapeutic targets for prevention and treatment of lymph node metastasis in pNET.

Liver Transplantation for Neuroendocrine Metastases

Neuroendocrine tumor (NET) metastasis localized to the liver is an accepted indication for liver transplantation as such tumors have a low biological aggressiveness in terms of malignancy and are slow growing. Moreover, the long-term results are comparable with and in some cases even better than those of transplantations performed for primary liver cancer. However, compared with nonmalignant conditions, neuroendocrine liver metastasis (NELM) may result in an inferior outcome of transplantation. In the face of the scarcity of donated organs and recent improved results of non-surgical treatment for NELM, controversy over patient selection and timing for liver transplantation continues. In this review, we provide an overview of the diagnostic workup and selection criteria of patients with NELM being considered for liver transplantation. Thereafter, we provide a critical analysis of the reported outcomes of orthotopic liver transplantation.

Safety of ultrasound-guided distal radial artery access for abdominopelvic transarterial interventions: a prospective study

We aimed to evaluate ultrasound-guided distal radial artery (DRA) access to perform abdominopelvic endovascular procedures. A prospective, observational study was carried out in a single center between December 2017 and February 2019. Forty-two abdominopelvic endovascular procedures were performed by the same operator in 37 patients with DRA access using a 5 F sheath. Most patients were male (67.6%) with a mean age of 62.0±11.4 years (age range, 27.6-82.8 years). Patient characteristics, including Barbeau's test classification, radial and ulnar sizes and technical success, were evaluated. Patients with a DRA smaller than 1.7 mm could not be safely punctured and were not included. Procedures included chemoembolization of hepatocellular carcinoma in 35 cases (83.3%), embolization of hepatic metastasis in neuroendocrine tumors in 4 cases (9.5%) and other embolization procedures in 3 cases (7.1%). The mean diameters of the DRA, proximal radial artery and proximal ulnar artery were 2.31, 2.63, and 2.09 mm, respectively. Out of 42 DRA puncture attempts, 97.6% (41/42) were successfully performed. There were no postoperative complications related to the access site, such as pain, palsy, paresthesia, occlusion, finger ischemia, bleeding, hematoma, and pseudoaneurysm. Transient forearm discomfort was reported in 7.1% of patients (3/42); one occurrence was associated with kinking rectification, and two occurrences were attributed to small arteries and/or vasospasm. Ultrasound-guided DRA access seems to be feasible and safe to perform in abdominopelvic endovascular procedures in patients with a DRA considered amenable to be safely punctured, with high technical success rates.

METASTATIC OVARIAN NEUROENDOCRINE TUMOR IN THE HEART FIRST PRESENTING ON EKG

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Neuroendocrine tumors (NETs) of the gynecological tract are rare, they are most commonly seen in the lungs and gastrointestinal (GI) tracts. Cardiac metastasis in ovarian NETs is uncommon with only 7 such cases previously reported. We present a case of a right ventricular (RV) neuroendocrine cardiac tumor, initially noted due to EKG abnormalities, initiating from the right ovary. CASE PRESENTATION: A 70-year-old female with a history of uterine fibroids was evaluated preoperatively for an elective hysterectomy. Her EKG showed inferior and anteroseptal T wave changes. Cardiology then preformed an echocardiogram (TTE) showing a RV thrombus. Patient was admitted to the hospital where a repeated TTE demonstrated a 4x7cm mass arising from the RV apex with obstruction of the RV outflow tract. Cardiac MRI then demonstrated a right ventricular mass measuring 4.7x6.2cm extending from the apex to the base at the level of the outflow tract. The mass was invading the RV free wall and apical septum. Patient was then transferred to an outside hospital for cardiac biopsy, where pathology demonstrated a poorly differentiated carcinoma with neuroendocrine differentiation. A PET scan then demonstrated a hypermetabolic 7cm right ventricular mass, and a bulky uterus with a 6.6cm mass in the posterior aspect of the uterus arising form the right ovary. Repeat MRI showed an unchanged 7.1 cm mass in the cul-de-sac likely reflecting neoplastic involvement of the right ovary. She was initiated on chemotherapy with carboplatin and etoposide. Follow up TTE has shown a decrease in the size of the mass to 4.2x2.7cm. DISCUSSION: Secondary cardiac tumors are found in up to 8% of patients who died of metastatic cancer. Mesothelioma is the most common to metastasize to the heart with others being melanoma, lung, breast, renal, esophageal, and ovarian cancers. One study of 106 patients with primary ovarian tumors found that 10.3% had metastasis to the heart. The cause of such high levels of metastasis to the heart is likely the anatomy of the ovarian venous, which drain directly into the inferior venacava. Treatment options, depend on the stage of disease, including surgical removal of the ovarian tumor which is the mainstay of management, chemotherapy is typically reserved for advanced stage or recurrent disease. In the case above with a secondary cardiac metastatic lesion surgical resection was considered, but felt not to be a surgical candidate due to the extent of myocardial infiltration. CONCLUSIONS: Primary ovarian NETs are rare and metastasis to the heart is ever rarer. When discovered, it is important to ensure there is no GI metastatic primary tumor as this guides further treatment. An echocardiogram should be performed in all women with ovarian NETs as they can frequently metastasize to the heart. Finally the mainstay of treatment is surgical removal in isolated lesions and chemotherapy in more advanced disease. Reference #1: Damen N. Ovarian carcinoid presenting with right heart failure. BMJ Case Rep. 2014; bcr2014204518 Reference #2: Silvestri F, Bussani R, Pavletic N, Mannone T. Metastases of the heart and pericardium. G Ital Cardiol 1997; 27:1252. Reference #3: Bussani R, De-Giorgio F, Abbate A, Silvestri F. Cardiac metastases.J Clin Pathol. 2007; 60:27–34. DISCLOSURES: No relevant relationships by Chad Conner, source=Web Response No relevant relationships by Nikola Perosevic, source=Web Response No relevant relationships by Bryan Stringer, source=Web Response