Nonfunctioning Neuroendocrine Tumors Research Articles

The current status of somatostatin analogs in the treatment of neuroendocrine tumors and future perspectives.

Somatostatin analogs (SSAs) were developed as antisecretory agents to palliate hormonal symptoms in patients with functioning neuroendocrine tumors (NETs). Their antiproliferative activity has been established in the phase 3 PROMID and CLARINET trials. SSAs currently represent the standard first-line therapy for the majority of well-differentiated G1/G2 gastroenteropancreatic NETs as well as for pulmonary NETs. An update on the clinical applications of established SSAs for the treatment of NETs is provided. Perspectives on emerging nonpeptide SSAs such as paltusotine and innovative formulations of octreotide (CAM2029) are included. SSAs represent the cornerstone of treatment for both functioning and nonfunctioning NETs. While standard-dose SSAs have a defined place in the therapeutic algorithm of well-differentiated NETs, uncertainties remain on how to best integrate above-label doses of SSAs in the treatment sequence, particularly when tumor control is the goal. Octreotide and lanreotide appear to be clinically interchangeable, and no signs of superiority of one agent over the other has been observed so far. Whether SSAs may be exploited in the maintenance setting following more aggressive treatments, whether continuing SSAs beyond-progression after first-line therapy could be an effective treatment strategy, and whether new-generation SSAs such as pasireotide could overcome resistance to established SSAs are key areas of investigation.

7940 Insulinoma as a Rare Manifestation of MEN4

Abstract Disclosure: H. Han: None. J. Moalem: None. A.R. Shih: None. B.J. Gigliotti: None. Background/Objective: Multiple endocrine neoplasia 4 (MEN4) is a rare syndrome that is caused by germline mutations in CKDN1B. Its phenotypic expression is similar to multiple endocrine neoplasia 1 (MEN1). Manifestations include primary hyperparathyroidism (PHPT), pituitary adenomas, and pancreatic neuroendocrine tumors (NET). Prevalence of MEN4 is less than one per million. Case Report: A 55-year-old female with history of hypercalcemia presented with symptomatic hypoglycemia. She had a fasting plasma glucose of 41mg/dL, proinsulin of 84.3 pmol/L, insulin level of 24 uIU/mL, c-peptide of 5.2 ng/mL, and beta hydroxybutyrate level of 0.34 mmol/L, consistent with endogenous hyperinsulinism. She was incidentally noted to have PHPT. CT abdomen showed a 1.5 x 1.1 x 1.0 cm pancreatic lesion consistent with an insulinoma. Pathology from subsequent Whipple surgery showed that it was a well-differentiated neuroendocrine tumor with no metastasis. She became normoglycemic after surgery. Germline testing revealed a variant of unknown significance in CDKN1B (p.R93W). Discussion: Increasing evidence suggests that MEN4 exhibits subtle differences in penetrance and natural history compared to MEN1. A recent systemic review of MEN4 cases showed that most gastrointestinal NETs in MEN4 are non-functional NETs and gastrinomas; to date, no insulinomas have been reported. PHPT in MEN4 may exhibit a lower risk of recurrence after parathyroidectomy. This case highlights the importance of germline genetic testing when a patient presents with clinical manifestations of MEN1. Conclusion: This is the first reported case of insulinoma in MEN4. Presentation: 6/3/2024

The outcomes of robotic-assisted enucleation for tumors located in uncinate process of pancreas in 16 cases

Objective: To summarize the experience of robot-assisted enucleation of tumors located in uncinate process of pancreas. Methods: This is a retrospective case series study. The clinical data of patients with robot-assisted enucleation of tumors located in the uncinate process of pancreas at the Department of Gastroenterology and Pancreatic Surgery,Zhejiang Provincial People's Hospital from June 2019 to December 2023 were retrospectively analyzed. A total of 16 cases were enrolled,including 10 males and 6 females,with an age(M(IQR)) of 56(21)years (range: 28 to 77 years),and body mass index of 22.4(2.3)kg/m2 (range:19.8 to 25.6 kg/m2). Follow-up was asked every 6 to 12 months after the first 3-month postoperative follow-up through out-patient service or via telephone. Results: In total 16 cases,there were 11 cases with pancreatic enucleation,and 5 cases with resection of the uninate process. The operation time was 70(60) minutes (range: 40 to 165 minutes),and the blood loss was 30(13)ml (range: 10 to 80 ml). The rate of pancreatic fistula was 5/16. The length of stay was 8(6)days (range: 5 to 33 days). The pathological finding included non-functional neuroendocrine tumor(n=3),insulinoma(n=2),introductal papillary mucinous neoplasm (n=5),solid pseudopapillary neoplasm (n=2),mucinous cystadenoma (n=1),serous cystadenoma (n=2),pseudocyst (n=1). Follow-up as of March 12, 2024, the follow-up time was 16(12)months (range: 3 to 41 months). All patients had no new onset diabetes and no dyspepsia. Conclusion: Robot-assisted surgical system can be used for local resection of uncinate process tumors of pancreas,and the quality of life of patients can be improved.

EUS-Guided Radiofrequency Ablation Therapy for Pancreatic Neoplasia.

Radiofrequency ablation (RFA) under endoscopic ultrasound (EUS) guidance has been developed and utilized over the last decade to provide the loco-regional treatment of solid and cystic pancreatic neoplastic lesions. The advantage of this approach relies on the close proximity of the EUS transducer to the target pancreatic lesion, which, coupled with the development of specifically designed RFA ablation devices, has made the procedure minimally invasive, with a clear reduction in adverse events as compared to the high morbidity of the surgical approach. EUS-RFA has been applied so far to pancreatic functional and non-functional neuroendocrine neoplasms, pancreatic ductal adenocarcinoma or metastases to the pancreas, and pancreatic neoplastic cysts. Excluding neuroendocrine tumors, for other indications, most of these procedures have been performed in patients who refused surgery or were at high surgical risk. More studies evaluating EUS-RFA in selected patients, not at surgical risk, are gradually becoming available and will pave the road to extend the indications for this therapeutic approach, also in association with other oncological therapies. The present manuscript will critically review the available evidence in the field of the EUS-guided RFA of solid and cystic pancreatic neoplasms.

Large bilateral non-functional adrenal myelolipomas: A rare case report

Myelolipomas are rare, benign, and non-functional neuroendocrine tumors that are usually discovered incidentally. The widespread use of imaging modalities has increased the detection of incidental tumors over the last decades. Most myelolipomas are small, unilateral, and asymptomatic. Occasionally, tumors grow over time and become symptomatic due to the mass effect on adjacent structures. As a therapeutic approach, surgery is known as the standard treatment for symptomatic or large lesions. We report a patient presented with persisted abdominal pain which had been initiated two months ago. Ultrasonography examination showed large, bilateral, and well-defined hyperechoic lesions without calcification in both adrenal glands. Tumors were non-functional with hormone secretion-wise. After laparoscopic resection, on the macroscopic examination, two adrenal lesions with 60×50×40 mm and 35×30×10 mm size, respectively, were observed. The subsequent microscopic assessment also confirmed the diagnosis of bilateral adrenal myelolipomas.

Synchronous Solid Pseudopapillary Tumor and Nonfunctioning Neuroendocrine Tumor in the Pancreas

Solid pseudopapillary tumor (SPT) is known to be cured in more than 95% of patients after surgery. However, it is reported that 7% of this tumor can recur after resection, and continued surveillance is needed after surgery for SPT. In this case report, a pancreatic mass which had been detected during a routine health checkup was followed up and surgical resection (distal pancreatectomy) was performed due to an increase in size. Postoperative pathology revealed synchronous SPT and neuroendocrine tumor (NET). At twelve months after surgery, a recurrence of the mass in the head of the remnant pancreas was noted and further surgical resection (total pancreatectomy) was performed. Postoperative pathology confirmed the diagnosis of malignant SPT. To date, there are only a few reports of the synchronous SPT and NET, and there are no reports in Korea. Therefore, we report a case of the synchronous SPT and nonfunctional NET diagnosed after surgery.

Combined Lanreotide Autogel and Temozolomide Treatment of Progressive Pancreatic and Intestinal Neuroendocrine Tumors: The Phase II SONNET Study.

In advanced neuroendocrine tumors (NET), antiproliferative treatment options beyond somatostatin analogs remain limited. Temozolomide (TMZ) has shown efficacy in NET alone or combined with other drugs. SONNET (NCT02231762) was an open, multicenter, prospective, phase II study to evaluate lanreotide autogel 120 mg (LAN) plus TMZ in patients with progressive advanced/metastatic grade 1/2 gastroenteropancreatic (GEP) NET or of unknown primary. Patients could be enrolled at first-line or higher therapy line. The primary endpoint was disease control rate ([DCR], rate of stable disease [SD], partial [PR], and complete response [CR]) at 6 months of LAN and TMZ. Patients with nonfunctioning (NF) NET without progression at 6 months were randomized to 6-month LAN maintenance or watch and wait, patients with functioning (F)-NET with clinical benefit (PR, SD) continued on LAN. Fifty-seven patients were recruited. The majority of patients received the study drug at second or higher treatment line and had an NET G2. DCR at 6 months LAN and TMZ was 73.5%. After 6 months of further LAN maintenance, 54.5% of patients with F-NET and 71.4% with NF-NET had SD or PR vs 41.7% with NF-NET on observation only. LAN and TMZ were effective in all subgroups analyzed. At 12 months of follow-up, median progression-free survival was 11.1 months. Median serum chromogranin A decreased except in NF-NET on observation. O6-methylguanine DNA methyltransferase promoter methylation appeared to better reflect TMZ response than loss of gene expression. During combination therapy, the most frequent treatment-emergent adverse events grade 3/4 reported were nausea (14%), thrombocytopenia (12.3%), and neutropenia (8.8%). Four deaths were reported resulting from severe adverse events not considered related to study medication. LAN plus TMZ is a treatment option for patients with progressive GEP-NET with more aggressive biological profile showing a manageable safety profile.

Predicting the survival probability of functional neuroendocrine tumors treated with peptide receptor radionuclide therapy: Serbian experience.

Peptide receptor radionuclide therapy (PRRT) is a treatment option for well-differentiated, somatostatin receptor positive, unresectable or/and metastatic neuroendocrine tumors (NETs). Although high disease control rates seen with PRRT a significant number NET patients have a short progression-free interval, and currently, there is a deficiency of effective biomarkers to pre-identify these patients. This study is aimed at determining the prognostic significance of biomarkers on survival of patients with NETs in initial PRRT treatment. We retrospectively analyzed 51 patients with NETs treated with PRRT at the Department for nuclear medicine, University Clinical Center Kragujevac, Serbia, with a five-year follow-up. Eligible patients with confirmed inoperable NETs, were retrospectively evaluated hematological, blood-based inflammatory markers, biochemical markers and clinical characteristics on disease progression. In accordance with the progression og the disease, the patients were divided into two groups: progression group (n=18) and a non-progression group (n=33). Clinical data were compared between the two groups. A total of 51 patients (Md=60, age 25-75 years) were treated with PRRT, of whom 29 (56.86%) demonstrated stable disease, 4 (7.84%) demonstrated a partial response, and 14 (27.46%) demonstrated progressive disease and death was recorded in 4 (7.84%) patients. The mean PFS was a 36.22 months (95% CI 30.14-42.29) and the mean OS was 44.68 months (95% CI 37.40-51.97). Univariate logistic regression analysis displayed that age (p<0.05), functional tumors (p<0.05), absolute neutrophil count (p<0.05), neutrophil-lymphocyte ratio-NLR (p<0.05), C-reactive protein-CRP (p<0.05), CRP/Albumin (p<0.05), alanine aminotransferase-ALT (p<0.05), were risk factors for disease progression. Multivariate logistic regression analysis exhibited that functional tumors (p<0.001), age (p<0.05), CRP (p<0.05), and ALT (p<0.05), were independent risk factors for the disease progression in patients with NETs. Tumor functionality was the most powerful prognostic factor. The median PFS (11.86 ± 1.41 vs. 43.38 ± 3.16 months; p=0.001) and OS (21.81 ± 2.70 vs 53.86 ± 3.70, p=0.001) were significantly shorter in patients with functional than non-functional NETs respectively. The study's results suggest that tumor functionality, and certain biomarkers may serve as prognostic survival indicators for patients with NETs undergoing PRRT. The findings can potentially help to identify patients who are at higher risk of disease progression and tailor treatment strategies accordingly.

Elevated sortilin expression discriminates functional from non-functional neuroendocrine tumors and enables therapeutic targeting.

A subset of neuroendocrine tumors (NETs) can cause an excessive secretion of hormones, neuropeptides, and biogenic amines into the bloodstream. These so-called functional NETs evoke a hormone-related disease and lead to several different syndromes, depending on the factors released. One of the most common functional syndromes, carcinoid syndrome, is characterized mainly by over-secretion of serotonin. However, what distinguishes functional from non-functional tumors on a molecular level remains unknown. Here, we demonstrate that the expression of sortilin, a widely expressed transmembrane receptor involved in intracellular protein sorting, is significantly increased in functional compared to non-functional NETs and thus can be used as a biomarker for functional NETs. Furthermore, using a cell line model of functional NETs, as well as organoids, we demonstrate that inhibition of sortilin reduces cellular serotonin concentrations and may therefore serve as a novel therapeutic target to treat patients with carcinoid syndrome.

Efficacy and tolerability of somatostatin analogues according to gender in patients with neuroendocrine tumors.

As the incidence of neuroendocrine tumors has been rising, gender differences in epidemiology and clinical behavior have emerged, and interest into a gender-driven management of these tumors has grown with the aim to improve survival and quality of life of these patients. Somatostatin Analogues represent the first line of systemic treatment of both functional and non-functional neuroendocrine tumors, through the expression of somatostatin receptors (SSTRs) in the tumor cells, and proved effective in controlling hormonal hypersecretion and inhibiting tumor growth, improving progression-free survival and overall survival of these patients. Aim of the present review is to investigate any differences by gender in efficacy and safety of SSTS-targeted therapies, that represent the mainstay treatment of neuroendocrine tumors, as they emerge from studies of varying design and intent. Although preclinical studies have provided evidence in favor of differences by gender in tumor expression of SSTR, as well as of the role of sex hormones and related receptors in modulating SSTRs expression and function, the clinical studies conducted so far have not shown substantial differences between males and females in either efficacy or toxicity of SSTR-targeted therapies, even if with sometimes inconsistent results. Moreover, in most studies gender was not a predictor of response to treatment. Studies specifically designed to address this issue are needed to develop gender-specific therapeutic algorithms, improving patients' prognosis and quality of life.

Clinical presentation and recurrence of pituitary neuroendocrine tumors: results from a single referral center in Colombia.

Pituitary neuroendocrine tumors (PitNETs) represent 15-18.2% of all intracranial tumors. Their clinical presentation can range from chronic headache, visual defects, hypopituitarism to hormone excess syndromes. PitNETS are commonly classified as functioning neuroendocrine tumors (F-PitNETs) and non-functioning neuroendocrine tumors (NF-PitNETs). At the moment, new classification has emerged based on cell lineages. Almost 50% of all patients with PitNETs require surgical intervention, and about 25% of these have residual and persistent disease that may require additional management. A retrospective cohort of medical records of patients with PitNETs, aiming to describe the incidence of recurrence of patients who received surgical treatment over a 12month follow up period at San Jose Hospital (SJH) in Bogotá, Colombia, over an observation period of 10years. Furthermore, clinical presentation, biochemical characteristics and immunohistochemistry, postoperative complications are detailed. Eight hundred and eighty-seven patients with pituitary tumors were included in the cohort; 83% (737/887) had a diagnosis of PitNET. Of these, 18.9% (140) received surgical management. The majority 58% (98/140) had nonfunctional-PitNETs (NF-PitNETs), followed by growth-hormone-secreting pituitary adenoma (22.1%; 33/140), adrenocorticotropic- hormone-secreting pituitary adenoma (9.3%; 13/140), and prolactinomas (9.3%; 13/140). A recurrence was found in 45.71% (64/140), subclassified as biochemical in 15.71% (22/140), controlled with medications in 20% (28/140), and remission occurred in 18.57% (26/140). Clinical presentation and incidence of recurrence in patients with PitNETs in a referral center in Colombia are similar to other surgical cohorts with low cure rates and high recurrence.

The role of quantitative tumor burden based on [68Ga]Ga-DOTA-NOC PET/CT in well-differentiated neuroendocrine tumors: beyond prognosis.

We aimed to elucidate the role of quantitative tumor burden based on PET/CT of somatostatin receptors in well-differentiated neuroendocrine tumors (NETs). This study enrolled patients with [68Ga]Ga-DOTA-NOC PET/CT-positive advanced NETs who did not receive medical treatment prior to PET/CT. Tumor burden was calculated using methods based on the background threshold and relative fixed threshold values (30%, 40%, and 50%). The prognostic value of the measured tumor burden in reference to overall survival (OS) and progression-free survival (PFS) on treatment with octreotide long-acting repeatable (LAR) was assessed using Cox regression analysis, Harrell's C-index, and survival analysis. A classification and regression tree (CART) was used to determine the optimal threshold for tumor burden. A total of 204 patients were included. Somatostatin receptor-expressing tumor volume (SRETV) and liver SRETV derived from a relative fixed threshold of 30% (SRETV30 and liver SRETV30) were statistically significantly associated with OS (C-index: 0.802 [95% confidence interval (CI), 0.658-0.946] and 0.806 [95% CI, 0.664-0.948], respectively). Extrahepatic tumor burden was not correlated with OS (hazard ratio: 0.617, 95% CI: 0.241-1.574, P = 0.312). Among 155 patients with non-functional NETs with a ki-67 index of ≤ 10%, those with a high SRETV30 (P = 0.016) or high liver SRETV30 (P = 0.014) showed statistically significantly worse PFS on treatment with octreotide LAR. Patients receiving a higher dose of octreotide LAR normalized by SRETV30 or liver SRETV30 (a normalized dose or a liver normalized dose) showed prolonged PFS on treatment with octreotide LAR and a prolonged OS. Quantitative tumor burden based on [68Ga]Ga-DOTA-NOC PET/CT was correlated with OS and PFS in patients with non-functional NETs with a ki-67 index of ≤ 10% who received octreotide LAR. Calculating normalized and liver normalized doses may help in selecting the starting dose of octreotide LAR.

EUS-guided radiofrequency ablation of pancreatic/peripancreatic tumors and oligometastatic disease: an observational prospective multicenter study.

Background and study aims Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is an emerging and minimally invasive technique that seems promising for treatment of focal pancreatic and peripancreatic lesions. Our aim was to prospectively evaluate the feasibility, safety, and technical and clinical success of pancreatic and extra-pancreatic EUS-RFA. Patients and methods We prospectively collected clinical and technical data for all patients who underwent EUS-RFA at two Belgian academic centers from June 2018 to February 2022. Feasibility, adverse events (AEs), and follow-up were also assessed. Results Twenty-nine patients were included, accounting for 35 lesions: 10 non-functioning neuroendocrine tumors (29 %), 13 pancreatic insulinomas (37 %), one adenocarcinoma (3 %), and 11 intra-pancreatic and extra-pancreatic metastatic lesions (31 %). Technical success was achieved in 100 % of cases, with a median of three power applications per lesion (interquartile range 2). The majority of patients (59 %) presented no collateral effects, three (10.3 %) developed non-severe acute pancreatitis, and four (14 %) had mild abdominal pain. At 6 months follow-up (n = 25), 36 % of patients showed radiological complete response, 16 % presented a significant partial response and 48 % showed < 50 % decrease in diameter. At 12 months (n = 20), 30 % showed complete necrosis and 15 % > 50 % decrease in diameter. Hypoglycemia related to insulinoma was immediately corrected in all 13 cases, with no recurrence during follow-up. Conclusions EUS-RFA is feasible, safe, and effective for treatment of pancreatic and peripancreatic tumors. Larger and longer multicenter prospective studies are warranted to establish its role in management of focal pancreatic lesions and oligometastatic disease. Symptomatic insulinoma currently represent the best indication.

BRONCHOPULMONARY CARCINOID AND TYPE 1 MULTIPLE ENDOCRINE NEOPLASIA (MEN)

BRONCHOPULMONARY CARCINOID AND TYPE 1 MULTIPLE ENDOCRINE NEOPLASIA (MEN)

Diagnosis and management of small bowel neuroendocrine tumors: A state-of-the-art.

This review provides an update on the epidemiology, pathophysiology, symptoms, diagnosis and treatment of neuroendocrine neoplasms (NENs) of the small bowel (SB). These NENs are defined as a group of neoplasms deriving from neuroendocrine cells. NENs are currently the most common primary tumors of the SB, mainly involving the ileum, making the SB the most frequently affected part of the gastrointestinal tract. SB NENs by definition are located between the ligament of Treitz and the ileocecal valve. They are characterized by small size and induce an extensive fibrotic reaction in the small intestine including the mesentery, resulting in narrowing or twisting of the intestine. Clinical manifestations of bowel functionality are related to the precise location of the primary tumor. The majority of them are non-functional NENs and generally asymptomatic; in an advanced stage, NENs present symptoms of mass effect by non-specific abdominal pain or carcinoid syndrome which appears in patients with liver metastasis (around 10%). The main manifestations of the carcinoid syndrome are facial flushing (94%), diarrhea (78%), abdominal cramps (50%), heart valve disease (50%), telangiectasia (25%), wheezing (15%) and edema (19%). Diagnosis is made by imaging or biochemical tests, and the order of request will depend on the initial diagnostic hypothesis, while confirmation will always be histological. All patients with a localized SB NEN with or without near metastasis in the mesentery are recommended for curative resection. Locoregional and distant spread may be susceptible to several therapeutic strategies, such as chemotherapy, somatostatin analogs and palliative resection.

EUS-guided intra-tumoral therapies

EUS-guided treatments for focal tumor lesions has been developed since 20 years using at onset of the technique mainly local and guided alcohol injection [1-4]. Pancreatic tumors are the most assessed targeted lesions for EUS treatment because of their accessibility and because EUS management could be a safe alternative to surgery. More and more pancreatic tumors are discovered mainly fortuitously due to the advances in conventional imaging (abdominal ultrasound, CT, MRI) resulting in the question of surgical management of an asymptomatic pancreatic lesion ("incidentaloma”) [5–8]. The lesions detected include mostly pancreatic cystic neoplasms (PCN) and neuroendocrine tumors (NET) mainly well differentiated. Clinically, NET are mostly non-functional and do not induce secretory disorders [5–8]. Once their nature is yielded by diagnostic tests like EUS-FNA, incidental nonfunctional NET currently lead to difficult management when their largest diameter is less than 2 cm [2,4,9,10]. EUS-guided treatment for pancreatic adenocarcinoma have also been developed with recent prospective observational study and randomized control study [11,12]. Thus, therapeutic surgical choices could be challenged by EUS- guided treatment [2,4,9].

Comparison of two chromogranin A assays and investigation of nonlinear specimens

BackgroundAs a marker for functional and non-functional neuroendocrine tumors, serum chromogranin A (CgA) concentrations have shown value for detecting and monitoring disease. Here we describe a comparison between an established micro-titer plate assay (Cisbio CgA ELISA) and an analyzer-based assay (B·R·A·H·M·S CgA II KRYPTOR). Reference limits were established along with a performance evaluation of the KRYPTOR assay. Nonlinearity observed in approximately 0.03% of patients was also investigated. MethodsSamples were tested according to kit manufacturer's protocols. Reference limits were established for both assays testing the same cohort of healthy volunteers. Potential causes of nonlinearity investigated were HAMA, macromolecule effects and elevated serum creatinine. ResultsKRYPTOR vs. Cisbio: slope=0.692, y-intercept=−40.0 (r2=0.967, n=186). Upper reference limits were 160 and 103 ng/mL for the Cisbio and KRYPTOR assays, respectively. Linearity: slope=1.012 (r2=0.998) with 95.0–105.5% recoveries. Precision: repeatability ≤2.4%, within-laboratory ≤3.1% (79 and 738 ng/mL). Limit of detection: 8 ng/mL. Strong nonlinear specimens (n=6) retested for HAMA interference generated differences (block-no block) ranging −3.2–4.2%. Polyethylene glycol precipitation recoveries ranged from 157 to >5714% for affected specimens versus 71–79% for normal specimens. Eight of 14 nonlinear specimens (57%) had elevated serum creatinine results (>1.20 mg/dL). ConclusionsThe CgA II KRYPTOR assay performs acceptably for quantifying CgA in human serum. While adequate correlation is observed against the Cisbio ELISA, there is significant disagreement overall. Efforts to identify a cause of the nonlinearity observed in a small percentage of patients were inconclusive, but neither HAMA interference, macromolecule effects nor renal failure appear as major factors.

Prognostic Factors of Small Non-Functional Pancreatic Neuroendocrine Tumors and the Risk of Lymph Node Metastasis: A Population-Level Study.

BackgroundSmall non-functional neuroendocrine tumors (NF-PNETs) are a heterogeneous subset of tumors with controversy regarding their optimal management. We aimed to analyze the prognostic factors of patients with small NF-PNETs and create a risk score for lymph node metastasis (LNM).MethodsData of 751 patients with NF-PNETs ≤ 2 cm were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate survival analysis was performed to analyze the prognostic factors. Logistic regression was used to identify risk factors for LNM.ResultsOf the 751 patients, 99 (13.2%) were confirmed to have LNM. In multivariate survival analysis, LNM (hazard ratio [HR], 2.12; 95% CI, 1.04–4.32, p = 0.040) was independently associated with disease-specific survival. Logistic regression identified that tumor location in the head of the pancreas (odds ratio [OR], 4.33; 95% CI, 2.75–6.81; p < 0.001), size ≥ 1.5–2 cm (OR, 1.84; 95% CI, 1.17–2.87; p = 0.009), and grade III–IV (OR, 7.90; 95% CI, 1.79–34.90; p = 0.006) were independent risk factors of LNM. According to the OR value, the risk of LNM was scored as follows: a score of 1 for tumors located in the body/tail of the pancreas and 4 for those located in the head; a score of 1 for tumors <1 cm and 2 for those ≥1.5–2 cm; and a score of 1 for tumors with grade I–II and 8 for those with grade III–IV. Finally, the median score for this cohort was 4, with an interquartile range of 3–6. Therefore, patients were classified as three groups based on the risk score system: a total score of 1–3 for low risk, 4–6 for intermediate risk (OR, 2.98; 95% CI, 1.59–5.60; p = 0.001), and 7–14 for high risk (OR, 8.94; 95% CI, 4.50–17.7; p < 0.001), with an incidence of LNM 5.0%, 13.5%, and 31.8%, respectively (p < 0.001).ConclusionSurgical resection with regional lymphadenectomy is recommended for small NF-PNETs with malignant potential of LNM. A risk score for LNM based on tumor grade, location, and size may preoperatively predict LNM of small NF-PNETs and guide clinical practice.

Efficacy and safety of endoscopic ultrasound-guided radiofrequency ablation for management of pancreatic lesions: a systematic review and meta-analysis.

Radiofrequency ablation (RFA) has been used to treat various abdominal tumors including pancreatic tumors. Multiple approaches such as laparoscopic, open, and percutaneous have been used for pancreatic tissue ablation. More recently, endoscopic ultrasound (EUS)-guided RFA has emerged as a new technique for pancreatic tissue ablation. The role of EUS-RFA in management of pancreatic lesions is still not well-established. In this study, our aim is to assess efficacy and safety of EUS-RFA for management of pancreatic lesions. MEDLINE, Scopus, and Cochrane Library databases were searched to identify studies reporting EUS-RFA of pancreatic lesions with outcomes of interest. Studies with <5 patients were excluded. Clinical success was defined as symptom resolution, decrease in tumor size, and/or evidence of necrosis on radiologic imaging. Efficacy was assessed by the pooled clinical response rate whereas safety was assessed by the pooled adverse events rate. Heterogeneity was assessed using I2. Pooled estimates and the 95% CI were calculated using random-effect model. Ten studies (5 retrospective and 5 prospective) involving 115 patients with 125 pancreatic lesions were included. 152 EUS-RFA procedures were performed. The lesions comprised of 37.6% non-functional neuroendocrine tumors (NFNETs), 15.4% were insulinomas, 26.5% were pancreatic cystic neoplasms (PCNs), and 19.7% were pancreatic adenocarcinomas. The majority were present in the pancreatic head (40.2%), 38.3% in the body, 11.2% in the tail, and 10.3% in the uncinate process. Pooled overall clinical response rate was 88.9% (95% CI: 82.4-93.7, I2=38.1%). Pooled overall adverse events rate was 6.7% (95% CI: 3.4-11.7, I2=34.0%). The most common complication was acute pancreatitis (3.3%) followed by pancreatic duct stenosis, peripancreatic fluid collection, and ascites (2.8%) each. Only one case of perforation was reported with pooled rate of (2.1%). This study demonstrates that EUS-RFA is an effective treatment modality for pancreatic lesions, especially functional neuroendocrine tumors such as insulinomas.

Efficacy and the safety of endoscopic ultrasound guided radiofrequency ablation of pancreatic cancer: A systematic review and meta-analysis.

e16276 Background: Endoscopic ultrasound-guided RFA (EUS-RFA) is a minimally invasive emerging modality that may be an alternative to surgical resection for the management of unresectable pancreatic cancer (UPC). In this review, we highlighted the efficacy, clinical and technical success of the EUS-RFA for UPC. Methods: Studies were selected with a comprehensive search strategy for EUS-RFA and pancreatic cancer on PubMed, Google Scholar, and Embase databases as of October 2021. The primary outcomes were the technical (TS) and clinical success rate (CS) of the EUS-RFA procedure, while the secondary outcome was the adverse events (AEs) rate. Results: Twelve studies including 114 patients with 50% (57) females were included. Common pancreatic tumors were locally advanced pancreatic ductal adenocarcinoma (LAPDAC) 38.3% (49), followed by nonfunctional neuroendocrine tumor (NNET) 32% (41), pancreatic cystic neoplastic lesions 14.8% (19), insulinoma 12.5% (16) and others 2.3% (3). The most common site of the tumor was pancreatic head 45.7% (59) followed by body, neck, and tail 47.6% (61). The average number of ablation sessions per patient was 1.4 based on the total of 115 EUS-RFA sessions performed in 84 neoplastic lesions. The pooled TS rate of EUS-RFA calculated from the total number of procedures was 99.2% [95% CI = 0.90-0.98, I2 = 0%]. The pooled CS rate calculated from the total number of pancreatic lesions was 91.9% [95% CI = 0.77-0.92, I2 = 0%]. Clinical improvement in symptoms was reported in five studies whereas complete resolution or decrease in tumor size was reported in all studies. The pooled AEs rate was 24.6% [95% CI = 0.17-0.39, I2 = 30%]. Common AEs were abdominal pain 10.5% (12), and pancreatitis 3.5% (4). Conclusions: EUS-RFA is a promising and safe modality that can be used for the management of UPC in selected patients with a high TS (99.2%) and CS rates (91.9%). Large clinical trials are needed to identify safety, clinical outcomes, and overall survival benefits of EUS-RFA.[Table: see text]