Treatment Of Pancreatic Neuroendocrine Tumors Research Articles

Multicenter validation study of a treatment selection MAP for pancreatic neuroendocrine tumors.

Somatostatin analogs, molecular-targeted agents and cytotoxic anticancer agents are available as therapeutic agents for the systemic treatment of pancreatic neuroendocrine tumors, and we have developed a first-line treatment selection MAP to enable selection of the optimal treatment strategy for pancreatic neuroendocrine tumors. The purpose of this study was to validate the usefulness of the treatment selection MAP. Patients who had received systemic therapy for a pancreatic neuroendocrine tumor between January 2017 and December 2020 were compared according to whether they had been treated as recommended by the MAP (matched patients) or not (unmatched patients) to determine whether better outcomes were achieved by the matched patients. The primary endpoint was progression-free survival of the matched group and unmatched groups in the somatostatin analog, molecular-targeted agent and cytotoxic anticancer agents areas of the MAP. There were 41 (55%) MAP-matched patients in all areas among the 74 patients registered at seven hospitals. The MAP-matched rates were 100, 77 and 38% in the somatostatin analog area, molecular-targeted agent area and cytotoxic anticancer agents area, respectively. All of the unmatched patients had been selected for less intensive treatment. The median progression-free survival in the matched group and unmatched group in the molecular-targeted agent area of the MAP were 46.6 and 15.4months, respectively, and a multivariate analysis identified MAP-matched (hazard ratio 0.18 [95% confidence interval: 0.04-0.87], P=0.032) as the only significant independent favorable predictive factor. The usefulness of the MAP for treatment selection was validated in the molecular-targeted agent area of the MAP.

Endoscopic ultrasound-guided radiofrequency ablation of pancreatic tumors.

Surgery is a cornerstone in the management of pancreatic cancer and precancerous pancreatic lesions. However, many patients are not suitable candidates for surgery at the time of diagnosis for various reasons. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) appears to be a promising treatment option for patients who are ineligible for surgery for management of pancreatic adenocarcinoma (PDAC), and pancreatic neuroendocrine tumors (PNETs), and pancreatic cystic lesions (PCLs). EUS-RFA may serve as an adjunct to chemotherapy or palliative measures for inoperable cases of PDAC. Given its feasibility and efficacy, EUS-RFA has an evolving niche as a minimally invasive and potentially definitive treatment for PNETs and high-risk PCLs such as intraductal papillary mucinous neoplasms (IPMNs). EUS-RFA is a generally well tolerated procedure, with abdominal pain and acute pancreatitis being the most common adverse effects, though the risk can be mitigated through prophylactic measures. There is an increasing body of evidence to support the use of EUS-RFA in managing pancreatic lesions, either as definitive, adjunctive, or palliative treatment, depending on lesion type.

Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment of PNETs at an advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events that are involved in PNET development. Then, we discuss the epigenetic regulation of these signaling pathways in the context of both PNETs and commonly occurring-and therefore more extensively studied-malignancies. Finally, we will offer a perspective on the future research direction of the PNET epigenome and its potential applications in patient care.

When Should Lymphadenectomy Be Performed in Non-Metastatic Pancreatic Neuroendocrine Tumors? A Population-Based Analysis of the German Clinical Cancer Registry Group.

Patient selection for lymphadenectomy remains a controversial aspect in the treatment of pancreatic neuroendocrine tumors (pNETs), given the growing importance of parenchyma-sparing resections and minimally invasive procedures. This population-based analysis was derived from the German Cancer Registry Group during the period from 2000 to 2021. Patients with upfront resected non-functional non-metastatic pNETs were included. Out of 5520 patients with pNET, 1006 patients met the inclusion criteria. Fifty-three percent of the patients were male. The median age was 64 ± 17 years. G1, G2, and G3 pNETs were found in 57%, 37%, and 7% of the patients, respectively. Lymph node metastasis (LNM) was present in 253 (24%) of all patients. LNM was an independent prognostic factor (HR 1.79, CI 95% 1.21-2.64, p = 0.001) for disease-free survival (DFS). The 3-, 5-, and 10-year disease-free survival in nodal negative tumors compared to nodal positive was 82% vs. 53%, 75% vs. 38%, and 48% vs. 16%. LNM was present in 5% of T1 tumors, 25% of T2 tumors, and 49% of T3-T4 tumors. In T1 tumors, G1 was the most predominant tumor grade (80%). However, in T2 tumors, G2 and G3 represented 44% and 5% of all tumors. LNM was associated with tumors located in the pancreatic head (p < 0.001), positive resection margin (p < 0.001), tumors larger than 2 cm (p < 0.001), and higher tumor grade (p < 0.001). The multivariable analysis showed that tumor size, tumor grade, and location were independent prognostic factors associated with LNM that could potentially be used to predict LNM preoperatively. LNM is an independent negative prognostic factor for DFS in pNETs. Due to the low incidence of LNM in T1 tumors (5%), parenchyma-sparing surgery seems oncologically adequate in small G1 pNETs, while regional lymphadenectomy should be recommended in T2 or G2/G3 pNETs.

Safety and efficacy of endoscopic ultrasound-guided radiofrequency ablation for pancreatic neuroendocrine neoplasms: Systematic review and meta-analysis.

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been constantly increasing, particularly in the treatment of pancreatic neuroendocrine neoplasms (pNENs). While emerging data in this field are accumulating, we aimed to assess the pooled efficacy and safety of EUS-RFA for pNENs. The PubMed/Medline, Embase, and Cochrane Library databases search was conducted to identify studies reporting EUS-RFA of pNENs with outcomes of interest (efficacy and safety). The primary outcome was radiological response. Efficacy was assessed by the pooled clinical response rate, whereas safety was assessed by the pooled adverse events (AEs) rate. Heterogeneity was assessed using I2. Pooled estimates and the 95% confidence interval (CI) were calculated using a random-effect model. Eleven studies involving 292 patients were included. The pooled technical success rate was 99.2% (95% CI 97.9-99.9%), with no heterogeneity. The pooled complete radiological response was 87.1% (95% CI 80.1-92.8%). The pooled partial response was 11.4% (95% CI 6.2-18.1%). The pooled clinical response rate for functional pNENs was 94.9% (95% CI 90.7-97.9%), with no heterogeneity. The pooled incidence of AEs was 20.0% (95% CI 14.0-26.7%); most AEs were mild to moderate in grade, while the pooled incidence of severe AEs was 0.9% (95% CI 0.2-2.3%). The most common AEs were transient mild abdominal pain in 19 patients (6.5%), and mild to moderate pancreatitis in 23 patients (7.9%). No cases of mortality were reported. Endoscopic ultrasound-guided radiofrequency ablation resulted on a feasible approach for pNENs treatment, with excellent technical success, high radiological and clinical response, and acceptable AE rate.

Chinese Medical Association consensus for standardized diagnosis and treatment of pancreatic neuroendocrine neoplasms.

Chinese Medical Association consensus for standardized diagnosis and treatment of pancreatic neuroendocrine neoplasms.

Controversies and prospects for surgical treatment of pancreatic neuroendocrine neoplasms with liver metastases

The incidence of pancreatic neuroendocrine neoplasm(pNEN) increased over the past two decades. Liver metastasis, the most common type of distal metastasis, is also one of the most important prognostic factors. Although several medical treatments, including biotherapy, chemotherapy, targeted therapy, peptide receptor radionuclide therapy and locoregional therapy, are available for pNEN with liver metastases, surgery is still the only possible treatment for cure. Currently, there are several controversies as regards surgical treatment for pNEN with liver metastases. These controversies include, but are not limited to, whether surgical resection is appropriate for pancreatic neuroendocrine tumor G3 with liver metastases, how to classify primary lesion and hepatic metastases comprehensively and accurately, what is the optimal surgical strategy for type Ⅱ liver metastases, who can benefit greatly from cytoreduction, and how to refine the Milan criteria for liver transplantation. This article aims to discuss those main controversies and provide prospects for future clinical trials.

An Overview of Pancreatic Neuroendocrine Tumors and an Update on Endoscopic Techniques for Their Management.

The growing importance of advanced endoscopy in the diagnosis and treatment of pancreatic neuroendocrine neoplasms (PanNETs) necessitates a comprehensive understanding of various biochemical markers, genetic testing methods, radiological techniques, and treatment approaches that encompass multiple disciplines within and beyond gastrointestinal oncology. This review aims to highlight key aspects of these topics, with a specific focus on emerging EUS-guided procedures for the management of PanNETs.

Association of guideline adherence in diagnosis and treatment of pancreatic neuroendocrine tumors with survival.

e16241 Background: Clinical guidelines and their adherence are important instruments to ensure quality in diagnosis and treatment, especially when treating rare diseases like pancreatic neuroendocrine tumors (PanNET). However, data on guideline adherence and its impact on outcome in PanNET is limited. Methods: Cases of PanNET according to 2017 WHO definition at our university hospital between 2010 and 2019 were retrospectively identified. Adherence to ENETS guideline 2007/2012 and the German S2k guideline was evaluated among four categories (diagnostics: chromogranin A (CgA) testing, somatostatin receptor imaging, discussion in an interdisciplinary tumor board; pathology: reporting of grading, Ki67 and synaptophysin expression; surgical treatment; systemic treatment including aftercare). Guideline adherence within these categories was valued with one point per fulfilled criterion and a final score between 0-8 points was calculated. Data was analyzed using Student’s t-test, Chi-square test and Spearman’s correlation coefficient test. Results were considered significant at α = 0.05. Results: Overall, 115 patients (47% female) with a diagnosis of PanNET were identified. Mean age was 61 (±13.5) years. Mean overall survival (OS) was 45 months, mean recurrence free survival (RFS) was 47 months. During the study period 21 patients (18%) had died, 6 patients (5%) were lost-to-follow-up and 11 patients (10%) had a recurrent disease after initially curative resection. 24 patients (21%) presented with metastatic disease upon diagnosis. Guideline adherence concerning pathology reports (97%) as well as systemic (91%) and surgical treatment (75%) was high, while complete adherence in diagnostic modalities was low (5%). However, the latter was mainly driven by lack of CgA testing (31%), and somatostatin receptor imaging (11%) not being performed on initial diagnosis, but in most cases during follow-up. Subsequently, complete guideline adherence (8/8) across all categories was rare (3%). However, a higher overall score was associated with survival (p = 0.032, V = 0.321). Long term survivors had a higher mean overall adherence score (5.6 vs. 6.1; p = 0.05). In addition, the composite score of surgical and systemic therapy was significantly correlated with RFS (ρ = 0.254, p = 0.016). Conclusions: The quality in diagnosis and treatment of PanNET in our cohort was high. These are the first data to demonstrate a positive impact of guideline adherence on survival and RFS in PanNET.

Endoscopic Ultrasound-Guided Local Ablative Therapies for the Treatment of Pancreatic Neuroendocrine Tumors and Cystic Lesions: A Review of the Current Literature.

Since its emergence as a diagnostic modality in the 1980s, endoscopic ultrasound (EUS) has provided the clinician profound access to gastrointestinal organs to aid in the direct visualization, sampling, and subsequent identification of pancreatic pathology. In recent years, advancements in EUS as an interventional technique have promoted the use of local ablative therapies as a minimally invasive alternative to the surgical management of pancreatic neuroendocrine tumors (pNETs) and pancreatic cystic neoplasms (PCNs), especially for those deemed to be poor operative candidates. EUS-guided local therapies have demonstrated promising efficacy in addressing a spectrum of pancreatic neoplasms, while also balancing local adverse effects on healthy parenchyma. This article serves as a review of the current literature detailing the mechanisms, outcomes, complications, and limitations of EUS-guided local ablative therapies such as chemical ablation and radiofrequency ablation (RFA) for the treatment of pNETs and PCNs, as well as a discussion of future applications of EUS-guided techniques to address a broader scope of pancreatic pathology.

Sporadic pancreatic neuroendocrine neoplasms: A retrospective clinicopathological and outcome analysis from a Latvian study group.

Although pancreatic neuroendocrine neoplasms (PNEN) are rare, there has been a constant increase in incidence. Furthermore, PNEN present unique clinical behaviors and long-term survival can be expected even in the presence of metastases as compared with ductal adenocarcinoma of the pancreas. Determining the best therapeutic approach and proper timing of therapy requires knowledge of reliable prognostic factors. Therefore, the aim of this study was to explore clinicopathological features, treatment, and survival outcomes of patients with PNEN based on Latvian gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) registry data. Patients with confirmed PNEN at Riga East Clinical University Hospital and Pauls Stradins Clinical University Hospital, between 2008 and 2020, were retrospectively analyzed. Data were collected and included in EUROCRINE, an open-label international endocrine surgical registry. In total, 105 patients were included. The median age at diagnosis was 64 years (IQR 53.0-70.0) for males and 61 years (IQR 52.5-69.0) for females. In 77.1% of patients, tumors were hormonally nonfunctional. Among those with functioning PNEN, 10.5% of patients presented with hypoglycemia and were diagnosed with insulinoma, 6.7% of patients presented with symptoms related to carcinoid syndrome; 30.5% of patients showed distant metastases at the time of diagnosis, and surgery was performed in 67.6% of patients. Notably, for five patients with nonfunctional PNEN <2 cm, a "watch and wait" approach was used; none of the patients developed metastatic disease. The median length of hospital stay was 8 days (IQR 5-13). Major postoperative complications were found in 7.0% of patients, and reoperation was conducted for 4.2% of patients, due to postpancreatectomy bleeding (2/71) and abdominal collection (1/71). The median follow-up period was 34 months (IQR 15.0-68.8). The OS at the last follow-up was 75.2% (79/105). The observed 1-, 5- and 10-year survival rates were 87.0, 71.2 and 58.0, respectively. Seven of the surgically treated patients had tumor recurrence. The median time of recurrence was 39 months (IQR 19.0-95.0). A univariable Cox proportional hazard analysis provided evidence that a nonfunctional tumor, a larger tumor size, the presence of distant metastases, a higher tumor grade, and the tumor stage were strong, negative predictors of OS. Our study represents the general trends of clinicopathological features and treatment of PNEN in Latvia. For PNEN patients, tumor functionality, size, distant metastases, grade, and stage may be useful to predict OS and must be confirmed in further studies. Furthermore, a "surveillance" strategy might be safe for selected patients with small asymptomatic PNEN.

Endoscopic Ultrasound-guided Radiofrequency Ablation Versus Surgical Resection for Treatment of Pancreatic Insulinoma

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is emerging as a safe and effective treatment for pancreatic neuroendocrine tumors. We aimed to compare EUS-RFA and surgical resection for the treatment of pancreatic insulinoma (PI). Patients with sporadic PI who underwent EUS-RFA at 23 centers or surgical resection at 8 high-volume pancreatic surgery institutions between 2014 and 2022 were retrospectively identified and outcomes compared using a propensity-matching analysis. Primary outcome was safety. Secondary outcomes were clinical efficacy, hospital stay, and recurrence rate after EUS-RFA. Using propensity score matching, 89 patients were allocated in each group (1:1), and were evenly distributed in terms of age, sex, Charlson comorbidity index, American Society of Anesthesiologists score, body mass index, distance between lesion and main pancreatic duct, lesion site, size, and grade. Adverse event (AE) rate was 18.0% and 61.8% after EUS-RFA and surgery, respectively (P < .001). No severe AEs were observed in the EUS-RFA group compared with 15.7% after surgery (P< .0001). Clinical efficacy was 100% after surgery and 95.5% after EUS-RFA (P= .160). However, the mean duration of follow-up time was shorter in the EUS-RFA group (median, 23 months; interquartile range, 14-31 months vs 37 months; interquartile range, 17.5-67 months in the surgical group; P < .0001). Hospital stay was significantly longer in the surgical group (11.1 ± 9.7 vs 3.0 ± 2.5 days in the EUS-RFA group; P < .0001). Fifteen lesions (16.9%) recurred after EUS-RFA and underwent a successful repeat EUS-RFA (11 patients) or surgical resection (4 patients). EUS-RFA is safer than surgery and highly effective for the treatment of PI. If confirmed in a randomized study, EUS-RFA treatment can become first-line therapy for sporadic PI.

Spleen-Preserving Retrograde Distal Pancreatectomy for Malignant Insulinoma

Introduction: Distal pancreatectomy is performed primarily for malignant and premalignant diseases of the pancreas. Neuroendocrine tumors within the body and tail of the pancreas can be resected or enucleated depending upon the size and relationship of the tumor with the pancreatic duct.1,2 This video presents the technical details of a spleen-preserving laparoscopic distal pancreatectomy using a retrograde dissection (Kimura technique) for malignant pancreatic neuroendocrine tumor treatment. Operative Technique: A 47-year-old woman with medical history of hypertension and hypothyroidism comes to endocrinology presenting 3 months history of lumbar pain and 6 months history of neuroglycopenic symptoms. The work-up demonstrated hyperinsulinemic hypoglycemia produced by a 2.7 cm insulin-producing tumor of the body of the pancreas. A 1 cm cyst of the tail of the pancreas, a 5 mm sellar mass, and an adenoma of one parathyroid gland with elevated parathyroid hormone and calcium are seen as well, indicatory of a multiple endocrine neoplasia type 1.3–5 A five-trocar laparoscopic distal pancreatectomy was performed with one surgeon between the legs and two more surgeons on each side of the patient. The liver was retracted for better visibility and started with the section of splenocolic ligament to release the splenic angle of the colon and move it to the midline. Short gastric vessels of the gastrosplenic ligament are sectioned to address the posterior face of the stomach, through the lesser sac. The stomach was retracted cephalad, allowing for a better exposure of the pancreas. The insulinoma became visible on the anteroinferior margin and was well delimited with intraoperative manipulation. Pancreas is accessed through the retroperitoneum. Splenic vessels are dissected. The splenic artery and vein are identified and referred to be able to dissect along the upper edge of the pancreas, in a retrograde approach to preserve vascular structures. Ligaclips are placed on the branches of the splenic vessels. Transection is performed at the level of the junction of the head and neck of the pancreas, leaving enough space between the mass using a linear stapler capable of 60 mm long cuts and with 3.5 mm open staple height. The integrity of the piece is verified and is extracted with a laparoscopic specimen retrieval bag. In the case of this patient with previous surgery, an existing Pfannenstiel-type scar is used to avoid extension of the laparoscopic scars. Blake-type drain is placed in situ. Results: The postoperative course was uneventful. No postoperative diabetes was observed and no treatment for hypoglycemia was necessary. Early oral feeding postoperatively was well tolerated. The patient was discharged home 3 days after surgery with a placed drain. Histology analysis confirmed the full resection of the intrapancreatic neuroendocrine tumor. No competing financial interests exist. Runtime of video: 9 mins 24 secs

Survival benefit of pancreatic enzyme replacement therapy in patients undergoing treatment of pancreatic neuroendocrine tumours

Treatment with somatostatin analogues (SSAs) or pancreaticoduodenectomy frequently causes malnutrition-inducing pancreatic exocrine insufficiency. This single-centre retrospective cohort study aimed to establish whether pancreatic enzyme replacement therapy (PERT) improves survival or nutritional status in SSA or pancreaticoduodenectomy-treated patients with pancreatic neuroendocrine tumours (pNETs). SSA and/or pancreaticoduodenectomy-treated patients with pNETs, diagnosed between 2009 and 2019, (n=77) were retrospectively identified from departmental databases. Data was sourced from clinical records. Overall survival and percentage monthly weight changes were compared between PERT-treated (n=45) and non-PERT-treated (n=32) patients. PERT-treated patients experienced significantly greater median monthly weight gain (+0.01% vs-0.10%, p=0.038) and 5-year survival (81% vs 51%, p=0.007). PERT was not, however, independently associated with survival (Hazard ratio 0.47, 95% CI 0.14-1.62, p=0.232). Considering SSA-treated patients (n=50) only, PERT-treated patients (n=24) showed numerically but non-significantly improved monthly weight gain (+0.04% vs-0.18%, p=0.139) and median survival (55.5, 95% CI 10.2-100.7 vs 42.4, 95% CI 11.7-73.2 months, p=0.082). PERT may improve survival and nutrition in SSA and pancreaticoduodenectomy-treated patients with pNETs, however, low patient numbers precluded the reliable mitigation of confounding in this study. A further multi-centre study is required to define the benefits of PERT in this population.

Addressing the Role of Angiogenesis in Patients with Advanced Pancreatic Neuroendocrine Tumors Treated with Everolimus: A Biological Prospective Analysis of Soluble Biomarkers and Clinical Outcomes.

Simple SummaryDespite the approval of new targeted therapies for pancreatic neuroendocrine tumors (PanNETs) over the past decades, the early identification of resistant tumors remains the major challenge, mainly because clear signs of tumor shrinkage are rarely achieved by imaging assessment. Starting from the hypothesis that angiogenesis can be implicated in the resistance to mTOR inhibitors, we evaluated a specific angiogenesis panel (through the measurement of soluble biomarkers for angiogenesis turnover, circulating endothelial cells, and circulating progenitors) as possible predictors of resistance to everolimus or everolimus efficacy in PanNETs. Our study showed that none of the investigated categories of biomarkers had a predictive value for everolimus resistance or efficacy. However, we suggest that circulating endothelial progenitors might be surrogate biomarkers for angiogenesis activity in PanNETs during everolimus treatment, and their baseline levels might correlate with survival outcomes. These data have never been reported before for NETs.Background: The success of targeted therapies in the treatment of pancreatic neuroendocrine tumors has emphasized the strategy of targeting angiogenesis and the PI3K/AKT/mTOR pathway. However, the major challenge in the targeted era remains the early identification of resistant tumors especially when the efficacy is rarely associated to a clear tumor shrinkage at by imaging assessment. Methods: In this prospective study (NCT02305810) we investigated the predictive and prognostic role of soluble biomarkers of angiogenesis turnover (VEGF, bFGF, VEGFR2, TSP-1) circulating endothelial cells and progenitors, in 43 patients with metastatic panNET receiving everolimus. Results: Among all tested biomarkers, we found a specific subpopulation of circulating cells, CD31+CD140b-, with a significantly increased tumor progression hazard for values less or equal to the first quartile. Conclusion: Our study suggested the evidence that circulating cells might be surrogate biomarkers of angiogenesis activity in patients treated with everolimus and their baseline levels can be correlated with survival. However, further studies are now needed to validate the role of these cells as surrogate markers for the selection of patients to be candidates for antiangiogenic treatments.

11-Year Single Center Experience in The Surgical Treatment of Pancreatic Neuroendocrine Tumors

Giriş: Pankreatik nöroendokrin tümörler (pNET) nadir görülen hastalıklardır ve cerrahi ön planlı tedavi yüz güldürücüdür. Bu çalışmada hastanemizde son 11 yılda pankreatik nöroendokrin tümör nedeniyle cerrahi tedavi uygulanmış hastaları geriye dönük inceleyerek; bulgularımızı literatüre sunmayı amaçladık. Materyal Metod: Ocak 2011 ile Mart 2022 tarihleri arasında pNET nedeniyle başvuran hastaların dosyaları geriye dönük incelendi. Çoklu veri eksiği olan, operasyon yapılmamış ve 18 yaşından küçük olan hastalar çalışma dışı bırakıldı. Hastalar yaş, cinsiyet, operasyon türü, tümör boyutu, tipi ve histolojik özellikleri, hastanede kalış, nüks hastalık ve sağ kalım açısından değerlendirildi. Bulgular: Çalışmaya alınan 33 hastanın 13’ü kadın 20’si erkektı ve yaş ortanca değeri 56 (18-86) idi. Fonksiyonel tümörü olan 8 hasta vardı ve biri somatostatinoma olup diğerleri insülinomaydı. Hastaların 7’sine enükleasyon; 26’sına pankreatektomi yapıldı. Ana lezyonu adenokanser ve seröz kistadenom olup rezeksiyon uygulanan ve spesmen patolojisinde insidental pNET saptanan üç hasta vardı. Tümörü grade 1, 2 ve 3 olan sırasıyla 23, 7 ve 3 hastamız vardı. Tümör çapı ortanca değeri 24 (3-80) mm idi. Hastanede yatış süresi ortanca değeri 7 (2-50) gündü. Takip süresi ortanca değeri 24 (1-71) ay; hastalıksız sağ kalım 14 (1-71) aydı. Tartışma ve Sonuç: pNET’ler nadir görülen ve insidental olarak da saptanabilen, titizlikle yönetilmesi gereken hastalıklardır. pNET’in cerrahi ve konservatif tedavisinde fikir birliği sağlanabilmesi için daha geniş serileri içeren çalışmalar yapılması gerekmektedir.

Modern molecular and imaging diagnostics in pancreatic neuroendocrine neoplasms

New molecular diagnostic and radiologic imaging techniques can be used to assess the extent, risk of recurrence, prognosis and response to treatment of pancreatic neuroendocrine neoplasms (pNENs). They therefore represent a decisive help in setting the indications for surgical treatment, especially in advanced stages. This article presents a narrative assessment of the options and evidence for modern molecular and radiologic imaging diagnostics of pNENs based on the current literature. While circulating DNA, circulating tumor cells and microRNAs have not yet become established in everyday clinical practice, the current literature suggests apromising role for the so-called NETest. Recent studies demonstrated its possible importance for the surgical management of pNENs. Besides [68Ga]Ga-DOTA-SSA-PET and [18]FDG-PET, which remain the gold standards for imaging NENs, radiomics represent an exciting alternative to biopsies and will possibly play an increasingly important role in the future. There are new promising alternatives to chromograninA, which has been clinically widespread since the 1970s despite several drawbacks, to map the extent, risk of recurrence, prognosis and response to treatment of pancreatic pNENs. In terms of personalized medicine, modern molecular and radiological diagnostics should play an increasing role for indicating and planning surgical treatment and for follow-up in the future.

Enucleation Is a Feasible Procedure for Well-Differentiated pNEN-A Matched Pair Analysis.

Simple SummaryNeuroendocrine neoplasms of the pancreas (pNEN) are rare malignancies with an increasing incidence rate. Optimal treatment strategies for non-functional and well-differentiated tumors in particular are still controversially discussed. Enucleation and formal oncological resection of pNEN are well-established operative treatment strategies. However, the risk of metastases requiring radical formal resection has to be weighed against the risk of overtreatment and potentially higher postoperative complication rates, especially in cases of well-differentiated pNEN, which carry a lower risk for the development of metastases in the future. Thus, this study compared enucleation and formal resection for well-differentiated non-functional pNEN. Postoperative complication rates and overall as well as disease-free survival were similar in the cohorts studied. Postoperative diabetes was developed significantly less often after enucleation. Thus, enucleation is a safe surgical procedure with good long-term outcomes for a selected group of patients.The extent of surgical resection in the treatment of pancreatic neuroendocrine neoplasms (pNEN) is still controversial. This study aimed to evaluate the outcomes of enucleation for well-differentiated non-functional (nf) pNEN. Patients undergoing enucleation (2001–2020) were analyzed. Clinicopathological parameters, perioperative outcomes and survival were assessed. The analysis was performed as a nested case-control study and matched-pair analysis with formal resection. Sixty-one patients undergoing enucleation were identified. Compared to patients undergoing formal resection, enucleation was associated with a significantly shorter median length of operative time (128 (IQR 95–170) versus 263 (172–337) minutes, p < 0.0001) and a significantly lower rate of postoperative diabetes (2% versus 21%, p = 0.0020). There was no significant difference in postoperative pancreatic fistula rate (18% versus 16% type B/C, p = 1.0), Clavien−Dindo ≥ III complications (20% versus 26%, p = 0.5189), readmission rate (12% versus 15%, p = 0.6022) or length of hospital stay (8 (7–11) versus 10 (8–17) days, p = 0.0652). There was no 30-day mortality after enucleation compared to 1.6% (n = 1) after formal resection. 10-year overall survival (OS) and disease-free survival (DFS) was similar between the two groups (OS: 89% versus 77%, p = 0.2756; DFS: 98% versus 91%, p = 0.0873). Enucleation presents a safe surgical approach for well-differentiated nf-pNEN with good long-term outcomes for selected patients.

Risk factors for complications after surgery for pancreatic neuroendocrine tumors

BackgroundSurgical resection is the only potentially curative treatment for pancreatic neuroendocrine tumors. The choice for the type of procedure is influenced by the expected oncological benefit and the anticipated risk of procedure-specific complications. Few studies have focused on complications in these patients. This cohort study aimed to assess complications and risk factors after resections of pancreatic neuroendocrine tumors. MethodsPatients undergoing resection of a pancreatic neuroendocrine tumor were identified within 2 centers of excellence. Complications were assessed according to the Clavien-Dindo classification and the comprehensive complication index. Logistic regression was performed to compare surgical procedures with adjustment for potential confounders (Clavien-Dindo ≥3). ResultsThe cohort comprised 123 patients, including 12 enucleations, 50 distal pancreatectomies, 51 pancreatoduodenectomies, and 10 total/combined pancreatectomies. Mortality was 0.8%, a severe complication occurred in 41.5%, and the failure-to-rescue rate was 2.0%. The median comprehensive complication index was 22.6 (0–100); the comprehensive complication index increased after more extensive resections. After adjustment, a pancreatoduodenectomy, as compared to a distal pancreatectomy, increased the risk for a severe complication (odds ratio 3.13 [95% confidence interval 1.32–7.41]). Of the patients with multiple endocrine neoplasia type 1 or von Hippel-Lindau, 51.9% developed a severe complication vs 38.5% with sporadic disease. After major resections, morbidity was significantly higher in patients with multiple endocrine neoplasia type 1/von Hippel-Lindau (comprehensive complication index 45.1 vs 28.9, P = .029). ConclusionSurgery for pancreatic neuroendocrine tumors is associated with a high rate of complications but low failure-to-rescue in centers of excellence. Complications are procedure-specific. Major resections in patients with multiple endocrine neoplasia type 1/von Hippel-Lindau appear to increase the risk of complications.

The Role of Stereotactic-Body-Radiation-Therapy in Neuroendocrine Pancreatic Tumors

Introduction: Surgery is standard treatment for pancreatic-neuroendocrine-tumors (TNP) although it is occasionally associated with high-rates of morbid-mortality. Radiotherapy can be an effective alternative in selected patients. Our objective is to evaluate the efficacy of SBRT (Stereotactic-body-radiation-therapy) as a radical treatment for TNP. Materials and Methods: Between December 2017 and November 2020, we prospectively analyzed 13 patients with pathological diagnosis of TNP of <2cm treated with SBRT as a part of an IRB-approved study. The endpoints of the study are local-control, tolerance, progression-free-survival and overall-survival. Before SBRT, two internal fiducial markers were placed into the tumor by endoscopic ultrasound puncture and a simulation-CT was obtained. Clinical-target-volume (CTV) included pancreatic tumor. Planning-target-volume (PTV) was CTV with 5mm expansion. Patients received 40Gy in 5 fractions on every other day. Results: Patients’ characteristics: 6 female (46%) and 7 males (54%) with a mean age of 55.6 years-old. Tumor location: head 3p (23%), neck 3p (23%), body 6p (46%) and tail of pancreas 1p (8%). Octreoscan prior to radiotherapy was positive in 8p (61.5%). FDG-PET was negative for all but one patient (SUV <4). With a median follow-up of 13.6 months (range 1.8- 34.4), all patients are without evidence of relapse. Acute tolerance was excellent. Only 3p (23%) showed asthenia. One p developed peptic ulcer on follow-up. Conclusions: SBRT is feasible and well tolerated and could be an alternative in selected patients with diagnoses of TNP, although further studies are necessary.