Pancreatic neuroendocrine neoplasms (pNENs) are relatively rare. Hypoxia and lipid metabolism-related gene acetyl-CoA synthetase 2 (ACSS2) is involved in tumor progression, but its role in pNENs is not revealed. This study showed that hypoxia can upregulate ACSS2, which plays an important role in the occurrence and development of pNENs through lipid metabolism reprogramming. However, the precise role and mechanisms of ACSS2 in pNENs remain unknown.

mRNA and protein levels of ACSS2 and 3-hydroxy-3-methylglutaryl-CoA synthase1 (HMGCS1) were detected using quantitative real-time PCR (qRT-PCR) and Western blotting (WB). The effects of ACSS2 and HMGCS1 on cell proliferation were examined using CCK-8, colony formation assay and EdU assay, and their effects on cell migration and invasion were examined using transwell assay. The interaction between ACSS2 and HMGCS1 was verified by Co-immunoprecipitation (Co-IP) experiments, and the functions of ACSS2 and HMGCS1 in vivo were determined by nude mouse xenografts.

We demonstrated that hypoxia can upregulate ACSS2 while hypoxia also promoted the progression of pNENs. ACSS2 was significantly upregulated in pNENs, and overexpression of ACSS2 promoted the progression of pNENs and knockdown of ACSS2 and ACSS2 inhibitor (ACSS2i) treatment inhibited the progression of pNENs. ACSS2 regulated lipid reprogramming and the PI3K/AKT/mTOR pathway in pNENs, and ACSS2 regulated lipid metabolism reprogramming through the PI3K/AKT/mTOR pathway. Co-IP experiments indicated that HMGCS1 interacted with ACSS2 in pNENs. Overexpression of HMGCS1 can reverse the enhanced lipid metabolism reprogramming and tumor-promoting effects of knockdown of ACSS2. Moreover, overexpression of HMGCS1 reversed the inhibitory effect of knockdown of ACSS2 on the PI3K/AKT/mTOR pathway.

Our study revealed that hypoxia can upregulate the lipid metabolism-related gene ACSS2, which plays a tumorigenic effect by regulating lipid metabolism through activating the PI3K/AKT/mTOR pathway. In addition, HMGCS1 can reverse the oncogenic effects of ACSS2, providing a new option for therapeutic strategy.

Pancreatic neuroendocrine tumors are rare neoplasms for which few predictive and/or prognostic biomarkers have been validated. Our previous work suggested the potential of the combined expression of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) as prognostic factors for relapse and survival.

In this new multicenter study we evaluated immunohistochemistry expression in 76 patients with advanced PanNET who were treated with capecitabine-temozolomide or everolimus. Based on the immunohistochemistry panel, an immunohistochemistry prognostic score (IPS) was developed.

In patients treated with capecitabine and temozolomide, low IPS was an independent prognostic factor for progression-free-survival and overall-survival. Similar findings were observed with highest IPS for overall-survival in patients treated with everolimus.

From our knowledge, it is the first time that a simple IPS could be useful to predict outcome for patients with metastatic pancreatic neuroendocrine tumors treated with everolimus or capecitabine and temozolomide.

Neuroendocrine neoplasms of the pancreas (pNEN) have an increasing incidence and prevalence. Thus, this entity is of increasing clinical significance. Patients with pNEN become clinically apparent due to different and unspecific symptoms. Some tumours secrete hormones and peptides and become clinically symptomatic. In general, these tumours can metastasise early and even small tumours lead to distant metastases. Nonetheless, primary tumour size and grading are important prognostic factors. On the basis of a systematic literature research and the formulation of key issues according to the PICO system, therapeutic concepts were established. These concepts were evaluated with a Delphi process among the members of the pancreas research group and the indications for surgery group of the German Society of General and Visceral Surgery. Thus this article gives an overview of the surgical treatment modalities and indications for the treatment of pNEN. Surgery is still the gold standard in treatment and the only potential chance of cure. Surgery is indicated for sporadic as well as hereditary pNEN > 2 cm independent of the functional activity. A so called "wait and see" strategy might be indicated in smaller pNEN; however, there is little evidence for this approach. In this respect, pNEN of 1 - 2 cm represent a surgical indication. The treatment of hereditary pNEN is challenging and should be interdisciplinary. Even in the case of distant metastases, a curative approach might be feasible and multimodal treatment is indicated.

The incidental detection of benign to low-grade malignant small pancreatic neoplasms increased in the last decades. The surgical management of these patients is still under debate. The aim of this paper is to evaluate the safety and feasibility of robotic enucleations and to compare the outcomes with non-parenchymal sparing robotic resections.

The study included a total of 25 patients. Nine of them underwent a robotic enucleation (EN Group) and 16 patients received a robotic demolitive resection (DR Group). Perioperative and medium-term outcomes were compared between the two groups.

Patients' baseline characteristics were similar in the two groups except for presence of symptoms and tumor size, due to the inclusion criteria. Operative time was significantly shorter and postoperative results were better for EN group, including a significant shorter hospitalization (5 vs. 8 days, p = 0.027), reduced pancreatic leaks (22% vs. 50%, p = 0.287) and a better preservation of glandular function (100% vs. 62.5%, p = 0.066). Mortality rate was zero in both groups, with all patients free from disease at a median follow-up of 18 months.

The risks of under/overtreatment remain still unavoidable for benign to low-grade malignant small pancreatic neoplasms. Simple enucleation should be performed whenever oncological appropriate, to achieve the best postoperative outcomes. The adoption of robotic technique might widen the indications for parenchymal sparing, minimally invasive surgery.

Incidental diagnosis of pancreatic neuroendocrine tumors (PanNETs) greatly increased in the last years. In particular, more frequent diagnosis of small PanNETs leads to many challenging clinical decisions. These tumors are mostly indolent, although a percentage (up to 39%) may reveal an aggressive behaviour despite the small size. Therefore, there is still no unanimity about the best management of tumor smaller than 2 cm. The risks of under/overtreatment should be carefully evaluated with the patient and balanced with the potential morbidities related to surgery. The importance of the Ki-67 index as a prognostic factor is still debated as well. Whenever technically feasible, parenchyma-sparing surgeries lead to the best chance of organ preservation. Lymphadenectomy seems to be another important prognostic issue and, according to recent findings, should be performed in noninsulinoma patients. In the case of enucleation of the lesion, a lymph nodal sampling should always be considered. The relatively recent introduction of minimally invasive techniques (robotic) is a valuable option to deal with these tumors. The current management of PanNETs is analysed throughout the many available published guidelines and evidences with the aim of helping clinicians in the difficult decision-making process.

Pancreatic neuroendocrine neoplasms (PNENs) are rare, accounting for less than 5% of all pancreatic tumors. High-grade pancreatic neuroendocrine carcinomas (hgPNECs) represent about 5% of all PNENs. They show highly aggressive behavior with dismal prognosis. Throughout the last two decades, there has been a notable progress in basic and clinical research of PNENs and a therapeutic trend towards both more aggressive and minimally invasive surgery. Despite these advances, hgPNECs as a distinct clinical entity remains largely unexplored among surgeons. This review of current development in pathology reporting and surgical treatment of hgPNECs aims at increasing the awareness of an evolving field in pancreatic surgery.