Intracranial seeding of pituitary neuroendocrine tumor: a case report.

Background: Pituitary neuroendocrine tumors (PitNETs) are predominantly benign, though a minority may exhibit invasive tendencies. A diagnosis of metastatic PitNETs, in the absence of malignant histology, hinges on the identification of craniospinal and/or systemic metastases. Only a minority of PitNETs exhibit intracranial seeding. Notably, craniotomy for PitNETs excision is a prominent catalyst for iatrogenic seeding. Case Description: This article presented a compelling case that 15 years following craniotomy for the resection of a somatotroph PitNET, a lesion emerged at the left frontal base within the ethmoid sinus. Subsequent post-operative pathology unveiled a mature plurihormonal pituitary specific transcription factor 1 (PIT-1)-lineage PitNET. Growth hormone (GH) levels decreased significantly from 22.8 ng/mL pre-operation to 2 ng/mL post-operative, and concurrently, prolactin (PRL) levels decreased from 26.7 ng/mL pre-operation to 4.5 ng/mL post-operation. Furthermore, in the follow-up examination conducted 5 months after the operation, both GH and PRL levels were found to be within the normal range for the patient. This robustly suggested that the initial surgical procedure played a key role in the development of the lesion. Conclusions: This underscores the paramount significance of strictly adhering to the non-tumor removal during craniotomy for PitNETs excision. Regardless of apparent complete resection on imaging, it remains imperative to conduct routine follow-up evaluations, encompassing both imaging studies and hormone level assessments.

Characteristics and risk differences of different tumor sizes on distant metastases of pancreatic neuroendocrine tumors: A retrospective study in the SEER database.

BACKGROUND: The rate of distant metastasis in patients with pancreatic neuroendocrine tumors (PNETs) is 20%-50% at the time of initial diagnosis. However, whether tumor size can predict distant metastasis for PNETs remains unknown up to date. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) population-based data to collect 6089 patients with PNETs from 2010 to 2019. The optimal cut-off point of tumor size to predict distant metastasis was calculated by Youden's index. Multivariate logistic regression analysis was used to figure out the association between tumor size and distant metastasis patterns. RESULTS: The most common metastatic site was liver (27.2%), followed by bone (3.0%), lung (2.3%) and brain (0.4%). Based on an optimal cut-off value of tumor size (25.5 mm) for predicting distant metastasis determined by Youden's index, patients were categorized into groups of tumor size < 25.5 mm and ≥ 25.5 mm. Multivariate logistic regression analyses showed that, compared with < 25.5 mm, tumor size ≥ 25.5 mm was an independent risk predictor of overall distant metastasis [odds ratio (OR) = 4.491, 95% confidence interval (CI): 3.724-5.416, P < 0.001] and liver metastasis (OR = 4.686, 95% CI: 3.886-5.651, P < 0.001). CONCLUSIONS: Tumor size ≥ 25.5 mm was significantly associated with more overall distant and liver metastases. Timely identification of distant metastasis for tumor size ≥ 25.5 mm may provide survival benefit for timely and precise treatment.

A Rare Presentation of Extrahepatic Biliary Neuroendocrine Tumor Diagnosed using 68Ga-DOTA-TOC Imaging, But Undetectable on 68Ga-FAPI Imaging.

Neuroendocrine tumors (NETs) are commonly seen in the small intestine and rarely found within the bile ducts. This low incidence is due to a smaller number of Kulchitsky cells in the extrahepatic biliary tree, which predisposes to the disease. The diagnosis of biliary tree carcinoid preoperatively is very rare, with most cases in the literature being incidentally diagnosed during surgery or being identified on the histopathology report postoperatively. Here, we present an interesting case of an extrahepatic biliary NET which was diagnosed preoperatively.

Treatment outcomes of endoscopic resection for nonampullary duodenal neuroendocrine tumors.

Background: The incidence rate of duodenal neuroendocrine tumors has been increasing in recent years. Endoscopic resection [ER; endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD)] is recommended for nonampullary duodenal neuroendocrine tumors (NAD-NETs) ≤10 mm in diameter that are confined to the submucosal layer and without lymph node or distant metastasis. However, the efficacy and safety of and indications for EMR/ESD remain unclear. Methods: Between November 2011 and April 2021, 12 NAD-NETs in 12 patients who underwent either EMR or ESD were analyzed retrospectively. The rates of en bloc resection, complete resection, pathologic complete resection, margin involvement, lymphovascular invasion, perineural invasion, complications and prognosis were determined during follow-up (median observation period 53.0 months). Results: EMR was performed for two tumors, and ESD was performed for ten tumors. En bloc resection was performed for both tumors (100%) in the EMR group, and complete resection was achieved in one case (50%). Pathological complete resection was achieved in one case (50%), while in the ESD group, these three rates were 90% (9/10), 80% (8/10), and 80% (8/10), respectively. Intraoperative perforation occurred in one patient (10%) during ESD treatment, with no intraoperative or delayed bleeding in either group. Recurrence and distant metastasis were not observed during the mean follow-up period of 53.0 months (range, 18-131 months). Conclusions: For NAD-NETs that measure ≤10 mm in size, are confined to the submucosal layer and have neither suspicious lymph nodes nor distant metastasis, ER (EMR and ESD) may be a safe, effective, and feasible endoscopic technique for removing them.

Comparative analysis of international guidelines on the management of advanced non-functioning well-differentiated pancreatic neuroendocrine tumors.

This review presents a comprehensive comparative analysis of international guidelines for managing advanced, non-functioning, well-differentiated pancreatic neuroendocrine tumors (panNETs). PanNETs, which represent a significant proportion of pancreatic neuroendocrine neoplasms, exhibit diverse clinical behaviors and prognoses based on differentiation, grading, and other molecular markers. The varying therapeutic strategies proposed by different guidelines reflect their distinct emphases and regional considerations, such as the ESMO guideline's focus on advanced disease management and the ENETS guidance paper's multidisciplinary approach. This review examines the most recent guidelines from ESMO, NCCN, ASCO, ENETS, and NANETS, analyzing the recommendations for first-line therapies and subsequent treatment pathways in different clinical scenarios. Significant variations are observed in the recommendations, particularly concerning the choice and sequence of systemic therapies, the role of tumor grading and the Ki-67 index in therapeutic decisions, and the integration of regional regulatory and clinical practices. The analysis highlights the need for a tailored approach to managing advanced NF panNETs, advocating for flexibility in applying guidelines to account for individual patient circumstances and the evolving evidence base. This work underscores the complexities of managing this patient population and the critical role of a multidisciplinary team in optimizing treatment outcomes.

Super Mario sign at somatostatin receptor PET/CT.

68Ga-DOTA NOC PET-CT imaging has been shown to have high accuracy for the evaluation of neuroendocrine tumours. We present the case of a 59-year-old male with well differentiated gastric neuroendocrine tumour (grade II) treated with surgery. 68Ga-DOTA NOC PET/CT was performed to rule out metastasis. 68Ga-DOTA NOC showed physiological uptake in the bilateral adrenal and horseshoe kidney appearing as the famous character Super Mario. There is no evidence of any abnormal somatostatin avid lesion.

Management of Pancreatic Neuroendocrine Tumors (PNETs): Surgical strategies and controversies.

OBJECTIVE: Pancreatic neuroendocrine tumors (PNETs) are uncommon tumors which are increasing in incidence. The management of these tumors continues to evolve. This review examines the current role of surgery in the treatment of these tumors METHODS: Studies published over the past 10 years were identified using several databases including PubMed, MEDLINE, and Science Direct. Search terms included pancreatic neuroendocrine tumors, treatment, and surgery. Clinical practice guidelines and updates from several major groups were reviewed. RESULTS: Surgery continues to have a major role in the treatment of sporadic functional and Felibert non-functional PNETs. Pancreas-sparing approaches are increasingly accepted as alternatives to formal pancreatic resection in selected patients. Options such as watch and wait or endoscopic ablation may be reasonable alternatives to surgery for NF-PNETs < 2cm in size. Surgical decision-making in MEN-1 patients remains complex and in some situations such as gastrinoma quite controversial. The role of surgery has significantly diminished in patients with advanced disease due to the advent of more effective systemic and liver-directed therapies. However, the optimal treatments and sequencing in advanced disease remain poorly defined, and it has been suggested that surgery is underutilized in these patients. CONCLUSIONS: Surgery remains a major treatment modality for PNETs. Given the plethora of available treatments, ongoing controversies and the changing landscape, management has become increasingly complex. An experienced multidisciplinary team which includes surgery in essential to manage these patients.

Surgery for pancreatic neuroendocrine tumors during the COVID-19 pandemic: a retrospective cohort from a high-volume center.

During the COVID-19 pandemic, pancreatic surgery for pancreatic neuroendocrine tumors (PNETs) with surgical indications was postponed or canceled. Patients with PNET patients who underwent pancreatic surgery during the COVID-19 restriction period (3 years) were compared with a similar cohort of patients who underwent surgery in the previous 3 years. Data on patients' characteristics, waiting time, and surgical and pathology outcomes were evaluated. During the study period, 370 patients received surgery for PNETs, 205 (55%) during the first period, and 165 (45%) during the pandemic. A lengthening of the waiting list (182 [IQR 100-357] vs. 60 [40-88] days, p < 0.001) and increased use of anti-tumor medical treatments (any therapy, peptide receptor radionuclide therapy, and somatostatin analogs; all p < 0.001) was found. During the pandemic, surgery occurred after a median of 381 days [IQR 200-610] from diagnosis (vs. 103 [IQR 52-192] of the pre-COVID-19 period, p < 0.001). No statistically significant differences in tumor size and grading distribution were found between the two periods (both p > 0.05), yet only a modest increase of the median Ki67 values in cases operated during the pandemic (4% vs. 3%, p = 0.03). Lastly, these latter patients experienced less major postoperative complications (13% vs. 24%, p = 0.007). During COVID-19, the surgical waiting list of PNET patients was drastically extended, and bridge therapies were preferred. This did not result in more advanced cases at final pathology. PRRT and SSA are valid alternative therapies for PNETs when surgery is not feasible.

Progastrin-Releasing Peptide As a Diagnostic Biomarker of Pulmonary and Non-Pulmonary Neuroendocrine Neoplasms.

BACKGROUND: Progastrin-releasing peptide (ProGRP) is the precursor of the gastrin-releasing peptide, a neuropeptide secreted by cells of neural and endocrine origin. Recently, ProGRP has emerged as a circulating biomarker for small cell lung cancer (SCLC), a subtype of aggressive and poorly differentiated neuroendocrine neoplasm (NEN). Given the ability of the neuroendocrine SCLC cells to secrete this peptide, we performed an in-depth narrative review aimed at collecting, summarizing, and critically analyzing the available literature about the possible value of ProGRP as a biomarker for pulmonary NENs other than SCLC, and for NENs of non-pulmonary origin. METHODS: We conducted an extensive search on international databases (PubMed, Web of Science, and Scopus). RESULTS: We selected 21 pertinent published articles (12 original studies and 9 case reports). Overall, the original studies included 1,711 patients, and the case reports described the clinical course of 10 patients. CONCLUSION: The data analyzed suggest a potential role for ProGRP as a diagnostic biomarker for typical and atypical lung carcinoids, pulmonary large cell neuroendocrine carcinoma, medullary thyroid carcinoma, non-pulmonary neuroendocrine carcinomas, prostate cancer with neuroendocrine differentiation, and the pancreatobiliary neuroendocrine carcinoma. Despite these promising results, additional studies are needed, to clarify the role of ProGRP as the diagnostic biomarker for specific NENs.

Ectopic Cushing's Syndrome in Pediatric Age.

BACKGROUND: Cushing's syndrome due to ectopic ACTH secretion is a rare clinical condition resulting from a dysregulated ACTH secretion by neuroendocrine tumors, which can have various localizations and different histological differentiations. The overall incidence of endogenous Cushing's syndrome is 0.7-2.4 per million people per year. Children account for just 10% of all new cases that are reported each year. CASE REPORT: When the patient first presented clinically, she was a 17-year-old girl who displayed symptoms of schizophrenia (delirium, psychotic episodes, and hallucinations). Blood tests showed diabetes mellitus and hypokalemia. She was also affected by high blood pressure and osteoporosis complicated by D9-D10 and L1-L5 vertebral collapses. For these reasons, she was treated with aripiprazole, insulin glargine, potassium chloride, spironolactone, enalapril, and calcium carbonate. After two months of treatment, she was referred to the pediatrician endocrinologist, who diagnosed hypercortisolism after prescribing hormone tests (Table 1). After receiving her diagnosis, she began taking 1000 mg of metyrapone and had a whole-body CT scan, which revealed bilateral adrenal hyperplasia. The results of the 68Ga-PET/DOTATOC and 18FDG-PET scans were negative. The clinical course was intermittent in the months that followed, with hypercortisolism and eucortisolism alternating. After one year of treatment, a 68Ga-PET/DOTATOC showed a nodule in the thymic lodge (Fig. 1). The patient underwent a thymectomy. Unfortunately, after surgery, she continued to have high levels of cortisol, for which she continued metyrapone 750 mg/die. 68Ga-PET/DOTATOC repeated three months after surgery showed again an uptake corresponding to the thymic lodge (Fig. 2). In order to remove the neuroendocrine lesion, she had a new surgery, which resulting a finally resolutive. ACTH levels were monitored before, during, and post-surgery (Table 2). The laboratory provided the ACTH results very quickly and thoracic surgeons waited for hormonal results before concluding the procedure. The adopted strategy permitted us to monitor the outcome of the surgery. CONCLUSION: The heterogeneity of ectopic Cushing's syndrome makes diagnosis difficult. Treatment of ectopic Cushing's syndrome requires close clinical, biochemical, and instrumental observation. Metyrapone is a drug able to control hypercortisolism in a lasting way with a good level of safety. 68Ga-PET/DOTATOC proves to be a tracer with good sensitivity and specificity for the identification of ACTH-secreting neuroendocrine lesions. The short half-life of ACTH is found to be a strategy to monitor the complete surgical resection of the neuroendocrine lesion. A multidisciplinary approach improves therapeutic success and reduces the risk of recurrence.

MEN1 Deficiency-Driven Activation of the ß-Catenin-MGMT Axis Promotes Pancreatic Neuroendocrine Tumor Growth and Confers Temozolomide Resistance.

O6-methylguanine DNA methyltransferase (MGMT) removes alkyl adducts from the guanine O6 position (O6-MG) and repairs DNA damage. High MGMT expression results in poor response to temozolomide (TMZ). However, the biological importance of MGMT and the mechanism underlying its high expression in pancreatic neuroendocrine tumors (PanNETs) remain elusive. Here, it is found that MGMT expression is highly elevated in PanNET tissues compared with paired normal tissues and negatively associated with progression-free survival (PFS) time in patients with PanNETs. Knocking out MGMT inhibits cancer cell growth in vitro and in vivo. Ectopic MEN1 expression suppresses MGMT transcription in a manner that depends on ß-Catenin nuclear export and degradation. The Leucine 267 residue of MEN1 is crucial for regulating ß-Catenin-MGMT axis activation and chemosensitivity to TMZ. Interference with ß-Catenin re-sensitizes tumor cells to TMZ and significantly reduces the cytotoxic effects of high-dose TMZ treatment, and MGMT overexpression counteracts the effects of ß-Catenin deficiency. This study reveals the biological importance of MGMT and a new mechanism by which MEN1 deficiency regulates its expression, thus providing a potential combinational strategy for treating patients with TMZ-resistant PanNETs.

Small-Cell Neuroendocrine Cervical Carcinoma Mimicking a Polyp in a 20-Year-Old Patient With a Five-Year Follow-Up: A Case Report.

Small-cell neuroendocrine cervical carcinoma (NECC) is a rare histology, and diagnosis and treatment of this condition are challenging because of its rarity, non-specific abdominopelvic symptoms, and less favorable prognosis compared to other cervical cancers. Here, we present a case of a 20-year-old patient diagnosed with small-cell NECC, defined within a cervical polyp, initially mimicking a benign lesion. Because of the difficulty in diagnosis, the patient underwent thorough diagnostics and interventions, including imaging, histopathology, and immunohistochemistry. Initially, the patient underwent a distinctive treatment plan encompassing four cycles of cisplatin and etoposide chemotherapy with minimal side effects. Subsequently, she received comprehensive surgical interventions, including hysterectomy, lymphadenectomy, and bilateral salpingectomy. Ovarian preservation, justified by the patient's youth and small cervical lesions (<4 cm) without parametrial disease or metastatic signs, was pursued. For long-term outcomes, the patient demonstrated no metastasis or recurrence during a five-year follow-up. This case emphasizes the requirement for strengthened awareness of neuroendocrine tumors in cervical masses, particularly in young patients, and the importance of individualized treatment approaches for optimal clinical outcomes. Continued documentation of such cases increases our understanding of managing infrequent cervical malignancies.

Endoscopic ultrasonography-based intratumoral and peritumoral machine learning radiomics analyses for distinguishing insulinomas from non-functional pancreatic neuroendocrine tumors.

Objectives: To develop and validate radiomics models utilizing endoscopic ultrasonography (EUS) images to distinguish insulinomas from non-functional pancreatic neuroendocrine tumors (NF-PNETs). Methods: A total of 106 patients, comprising 61 with insulinomas and 45 with NF-PNETs, were included in this study. The patients were randomly assigned to either the training or test cohort. Radiomics features were extracted from both the intratumoral and peritumoral regions, respectively. Six machine learning algorithms were utilized to train intratumoral prediction models, using only the nonzero coefficient features. The researchers identified the most effective intratumoral radiomics model and subsequently employed it to develop peritumoral and combined radiomics models. Finally, a predictive nomogram for insulinomas was constructed and assessed. Results: A total of 107 radiomics features were extracted based on EUS, and only features with nonzero coefficients were retained. Among the six intratumoral radiomics models, the light gradient boosting machine (LightGBM) model demonstrated superior performance. Furthermore, a peritumoral radiomics model was established and evaluated. The combined model, integrating both the intratumoral and peritumoral radiomics features, exhibited a comparable performance in the training cohort (AUC=0.876) and achieved the highest accuracy in predicting outcomes in the test cohorts (AUC=0.835). The Delong test, calibration curves, and decision curve analysis (DCA) were employed to validate these findings. Insulinomas exhibited a significantly smaller diameter compared to NF-PNETs. Finally, the nomogram, incorporating diameter and radiomics signature, was constructed and assessed, which owned superior performance in both the training (AUC=0.929) and test (AUC=0.913) cohorts. Conclusion: A novel and impactful radiomics model and nomogram were developed and validated for the accurate differentiation of NF-PNETs and insulinomas utilizing EUS images.

Evaluation of a blood miRNA/mRNA signature to follow-up Lu-PRRT therapy for G1/G2 intestinal neuroendocrine tumors.

Background: 177Lu-oxodotreotide peptide receptor therapy (LuPRRT) is an efficient treatment for midgut neuroendocrine tumors (NETs) of variable radiological response. Several clinical, biological, and imaging parameters may be used to establish a relative disease prognosis but none is able to predict early efficacy or toxicities. We investigated expression levels for mRNA and miRNA involved in radiosensitivity and tumor progression searching for correlations related to patient outcome during LuPRRT therapy. Methods: Thirty-five patients received LuPRRT for G1/G2 midgut NETs between May 2019 and September 2021. Peripheral blood samples were collected prior to irradiation, before and 48 h after the second and the fourth LuPRRT, and at 6-month follow-up. Multiple regression analyses and Pearson correlations were performed to identify the miRNA/mRNA signature that will best predict response to LuPRRT. Results: Focusing on four mRNAs and three miRNAs, we identified a miRNA/mRNA signature enabling the early identification of responders to LuPRRT with significant reduced miRNA/mRNA expression after the first LuPRRT administration for patients with progressive disease at 1 year (p < 0.001). The relevance of this signature was reinforced by studying its evolution up to 6 months post-LuPRRT. Moreover, nadir absolute lymphocyte count within the first 2 months after the first LuPRRT administration was significantly related to low miRNA/mRNA expression level (p < 0.05) for patients with progressive disease. Conclusion: We present a pilot study exploring a miRNA/mRNA signature that correlates with early hematologic toxicity and therapeutic response 12 months following LuPRRT. This signature will be tested prospectively in a larger series of patients.

Autoimmune Gastritis and Hypochlorhydria: Known Concepts from a New Perspective.

Autoimmune atrophic gastritis is an immune-mediated disease resulting in autoimmune destruction of the specialized acid-producing gastric parietal cells. As a consequence, in autoimmune atrophic gastritis, gastric acid secretion is irreversibly impaired, and the resulting hypochlorhydria leads to the main clinical manifestations and is linked, directly or indirectly, to the long-term neoplastic complications of this disease. In the last few years, autoimmune atrophic gastritis has gained growing interest leading to the acquisition of new knowledge on different aspects of this disorder. Although reliable serological biomarkers are available and gastrointestinal endoscopy techniques have substantially evolved, the diagnosis of autoimmune atrophic gastritis is still affected by a considerable delay and relies on histopathological assessment of gastric biopsies. One of the reasons for the diagnostic delay is that the clinical presentations of autoimmune atrophic gastritis giving rise to clinical suspicion are very different, ranging from hematological to neurological-psychiatric up to gastrointestinal and less commonly to gynecological-obstetric symptoms or signs. Therefore, patients with autoimmune atrophic gastritis often seek advice from physicians of other medical specialties than gastroenterologists, thus underlining the need for increased awareness of this disease in a broad medical and scientific community.

Correlation between Neurotransmitters (Dopamine, Epinephrine, Norepinephrine, Serotonin), Prognostic Nutritional Index, Glasgow Prognostic Score, Systemic Inflammatory Response Markers, and TNM Staging in a Cohort of Colorectal Neuroendocrine Tumor Patients.

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body's epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor-node-metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson's correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation's findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.

Update in the management of gastroenteropancreatic neuroendocrine tumors.

Neuroendocrine neoplasms are a diverse group of neoplasms that can occur in various areas throughout the body. Well-differentiated neuroendocrine tumors (NETs) most often arise in the gastrointestinal tract, termed gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Although GEP-NETs are still uncommon, their incidence and prevalence have been steadily increasing over the past decades. The primary treatment for GEP-NETs is surgery, which offers the best chance for a cure. However, because GEP-NETs are often slow-growing and do not cause symptoms until they have spread widely, curative surgery is not always an option. Significant advances have been made in systemic and locoregional treatment options in recent years, including peptide-receptor radionuclide therapy with α and ß emitters, somatostatin analogs, chemotherapy, and targeted molecular therapies.

Predictors of Outcomes in Gastric Neuroendocrine Tumors: A Retrospective Cohort.

Introduction/Aim: Gastric neuroendocrine tumors (GNETs) frequently have an indolent clinical course, despite their metastatic potential. The aim of the study was to identify prognostic factors associated with overall survival and risk of metastases and to evaluate the impact of serial measurements of chromogranin A (CgA). Methods: The authors performed a retrospective cohort study including consecutive patients with GNET diagnosed between 2010 and 2019, with a minimum follow-up of 1 year. Univariate and multivariate analyses were performed. Results: We included 132 patients with GNET (type I, 113 patients; type II, 1 patient; type III, 14 patients; type IV, 2 patients; not classifiable, 2 patients), with 61% being female and a mean age at diagnosis of 66 years. During the follow-up period (median 66 months), 3 (2.3%) patients died due to metastatic disease (1 patient with type III and 2 patients with type IV). Male gender (p = 0.030), type III/IV (p < 0.001), Ki-67 index >20% (p < 0.001), grade 2/3 (p < 0.001), invasion beyond the submucosa (p < 0.001), and presence of metastases (p < 0.001) were identified as risk factors for mortality in the univariate analysis. Metastasis developed in 7 patients (5.3%). Multivariable analysis revealed that Ki-67 >20% (p = 0.016) was an independent risk factor for metastasis. Overall, CgA showed a sensitivity of 20% for detection of recurrence and a specificity of 79% (sensitivity of 8% and specificity of 71% in type I GNETs). Conclusion: Identification of risk factors for the presence of metastases and for mortality in these groups of patients can help in individualizing the therapeutic strategy. CgA seems to be a weak marker for monitoring patients with GNET.

Introdução/Objetivo: Os tumores neuroendócrinos gástricos (TNEs-G) têm frequentemente um curso indolente, apesar do seu potencial metastático. O objetivo deste trabalho foi identificar fatores de prognóstico associados à sobrevida global e à metastização nos doentes com TNEs-G e avaliar o impacto da análise seriada de cromogranina A (CgA). Methods: Estudo retrospectivo incluindo doentes consecutivos admitidos por TNE-G entre 2010 e 2019, com um follow-up mínimo de 1 ano. Foi realizada análise univariada e multivariada. Results: Foram incluídos 132 doentes com TNE-G (Tipo I, 113 doentes; Tipo II, 1 doente; Tipo III, 14 doentes; Tipo IV, 2 doentes; Não classificável, 2 doentes), sendo 61% mulheres, com idade média de 66 anos. Durante o periodo de follow-up (mediana 66 meses), 3 (2.3%) doentes faleceram por doença metastática (1 doente com Tipo III e 2 com Tipo IV). O sexo masculino (p = 0,030), tipo III/IV (p < 0,001), Ki-67 index >20% (p < 0,001), Grau 2/3 (p < 0,001), invasão além da submucosa (p < 0,001) e presença de metástases (p < 0,001) foram identificados como fatores de risco para mortalidade na análise univariada. Sete doentes desenvolveram metástases (5,3%). A análise multivariáda revelou que o Ki-67 >20% (p = 0,016) era um factor de risco independente para metastização.Globalmente, a CgA mostrou uma sensibilidade de detecção de recorrência de 20% e uma especificidade de 79% (sensibilidade de 8% e especificidade de 71% em em TNEs-G do Tipo I). Conclusão: A identificação dos fatores de risco para a presença de metástases e para a mortalidade neste grupo de pacientes pode ajudar a individualizar a estratégia terapêutica. A CgA parece ser um marcador fraco para a monitorização de doentes com TNEs-G.

Portuguese Pancreatic Club Perspectives on Endoscopic Ultrasound-Guided and Surgical Treatment of Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine tumors (panNETs) are a group of neoplasms with heterogenous biological and clinical phenotypes. Although historically regarded as rare, the incidence of these tumors has been increasing, mostly owing to improvements in the detection of small, asymptomatic tumors with imaging. The heterogeneity of these lesions creates significant challenges regarding diagnosis, staging, and treatment. Endoscopic ultrasound (EUS) has improved the characterization of pancreatic lesions. Furthermore, EUS nowadays has evolved from a purely diagnostic modality to allow the performance of minimally invasive locoregional therapy for pancreatic focal lesions. The choice of treatment as well as the treatment goals depend on several factors, including tumor secretory status, grading, staging, and patient performance status. Surgery has been the mainstay for the management of these patients, particularly for localized, low-grade, large panNETs >2 cm. Over the last decade, a significant body of evidence has been accumulated evaluating the role of EUS for the ablative therapy of panNETs, namely by the use of chemoablative agents and radiofrequency. Although endoscopic techniques are not routinely recommended by international guidelines, they may be considered for the treatment of smaller lesions in patients who are unwilling or unfit for pancreatic surgery. In this review, we summarize the existing evidence on the interventional techniques for the treatment of patients with panNETs, focusing on the EUS-guided and surgical approaches.

Os tumores neuroendócrinos do pâncreas (panNETs) são um grupo de neoplasias com comportamento biológico e clínico heterogéneo. Embora historicamente considerados raros, a incidência desses tumores tem aumentado, algo que se atribui principalmente à melhoria na deteção de pequenos tumores assintomáticos em exames de imagem. A heterogeneidade destas lesões cria desafios significativos no que respeita ao seu diagnóstico, estadiamento e tratamento. A ultrassonografia endoscópica melhorou a caracterização das lesões pancreáticas. Concomitantemente, a ultrassonografia endoscópica, para além da vertente diagnóstica, evoluiu no sentido do desenvolvimento de capacidades terapêuticas, permitindo a realização de terapêutica locorregional de lesões pancreáticas focais de forma minimamente invasiva.A seleção do tratamento, bem como a definição dos seus objetivos, depende de diversos fatores, incluindo a atividade secretora da neoplasia, a sua atividade mitótica, o estadiamento e o status funcional do doente. A cirurgia é considerada a pedra basilar do tratamento destes doentes, particularmente para panNETs localizados, de baixo grau, com >2 cm. Ao longo da última década foi gerado um conjunto significativo de evidência relativamente ao papel da ultrassonografia endoscópica na terapêutica ablativa dos panNETs, nomeadamente através da utilização de agentes quimioablativos e de radiofrequência. Embora as recomendações internacionais não recomendem a utilização rotineira destas técnicas para o tratamento dos panNETs, as mesmas podem ser consideradas no tratamento de lesões de menores dimensões em doentes que não desejem ou que sejam considerados inaptos para cirurgia pancreática. Esta revisão visa resumir a evidência existente relativa às técnicas de intervenção para o tratamento de pacientes com panNETs, com foco nas abordagens cirúrgica e guiada por ultrassonografia endoscópica.