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Simple Summary: Neuroendocrine neoplasms' (NENs) rarity and heterogeneity represent a clinical challenge. Somatostatin receptor (SST) positron emission tomography/computed tomography (PET/CT) availability and different reimbursement policies across countries account for its heterogenous employment on a single-case basis. The aim of this study was to prospectively collect data of the real-life use of and indications for [68Ga-DOTA0-1NaI3]octreotide ([68Ga]Ga-DOTANOC) PET/CT in a prospective 5-year electronic archive at a single center. Overall, more than 2000 scans were included. This systematic data collection in a high-volume diagnostic center represents a reliable cohort reflecting the trends of [68Ga]Ga-DOTANOC PET/CT use across different clinical indications and primary tumor sites. The recent introduction of novel treatments for advanced neuroendocrine tumors (NETs) and the well-established impact of clinical case discussion within dedicated multidisciplinary teams indicates the need to promote the centralization of rare diseases, such as NENs (neuroendocrine neoplasms). Data on the real-life use of and indications for [68Ga]Ga-DOTANOC PET/CT were collected from a prospective monocentric 5-year electronic archive including consecutive patients with confirmed and suspected NETs (September 2017 to May 2022). Overall, 2082 [68Ga]Ga-DOTANOC PET/CT scans (1685 confirmed NETs, 397 suspected NETs) were performed in 1537 patients. A high positivity rate was observed across different clinical settings (approximately 70%). Approximately 910/2082 scans were requested by the local oncology ward (851 confirmed NETs, 59 suspected NETs). The following observations were found: (i) the detection rate across all indications was 73.2% (higher for staging, peptide receptor radioligand therapy (PRRT) selection, and treatment response assessment); (ii) in suspected NETs, PET was more often positive when based on radiological findings. This systematic data collection in a high-volume diagnostic center represents a reliable cohort reflecting the global trends in the use of [68Ga]Ga-DOTANOC PET/CT for different clinical indications and primary tumor sites, but prompts the need for further multicenter data sharing in such a rare and slowly progressive disease setting. [ABSTRACT FROM AUTHOR]

Background and aim: Over the last few years, SARS-CoV-2 has been reported as a possible cause of acute pancreatitis (AP), but whether it is a relevant clinical–epidemiological entity is still a matter of debate. We aim to evaluate the epidemiological characteristics of AP during the first year of the COVID pandemic (2020) and compare them with the pre-COVID period (2008–2019) to identify any differences and clarify a potential causative role of SARS-CoV-2. Methods: We used a monocentric retrospective study of 132 AP patients during 2020 and 1987 AP patients during 2008–2019. Diagnosis and severity were classified according to the revised Atlanta criteria. Propensity score matching was performed according to clinical–epidemiological features, and outcome analysis was performed on two subgroups of 109 patients. Results: The total number of AP cases in 2020 is one of the lowest in the last 13 years (132 cases, median 161, IQR 146-183). No major epidemiological differences were noted. During 2020, we observed a significant modification of the distribution of etiologies (p < 0.001), mainly based on a decrease in biliary forms (59.6% vs. 43.2%) and an increase in alcoholic forms (6.9% vs. 12.9%). Idiopathic forms remain unchanged (20.5% vs. 21.9%). The proportion of AP of idiopathic etiology and SARS-CoV-2 infection was 0.008%. There were no differences in terms of severity distribution (p = 0.127), length of stay (p = 0.916), need for ICU (p = 0.139), or mortality (p = 0.462). Even among statistically matched groups, there were no differences between the length of stay (9 vs. 10 days, p = 0.890), need for ICU admission (1.8% vs. 3.7%, p = 0.683), or in-hospital mortality (0 vs. 1.8%, p = 0.342). Conclusions: The lower AP diagnoses indicate delayed and likely missed diagnoses, probably because of both hesitancy and organizational problems during the pandemic. The unchanged proportion of idiopathic forms supports the hypothesis that SARS-CoV-2 is not an AP trigger. [ABSTRACT FROM AUTHOR]

Background: The antiproliferative activity of a high dose of somatostatin analogs (HD-SSA) in treating gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) remains under debate. Methods: A systematic review and proportion meta-analysis were made. The primary endpoint was the efficacy measured as incidence density ratio (IDR) at one year. The secondary endpoints were the disease control rate (DCR) and severe adverse events (SAEs). The heterogeneity (I2), when high (>50%), was interpreted by performing a univariate metaregression analysis, analyzing as covariates: type and design of the study, location (Europe or USA), sample size, grading according to 2017 WHO, the metastatic disease rate, previous therapy including surgery, and quality of the study. Results: A total of 11 studies with 783 patients were included. The IDR was 62 new progressions of 100 patients treated with HD-SSA every one year. The heterogeneity was high. The study's year, type and design, primary tumor, grading, previous treatments, and quality of the studies did not influence the IDR. The IDR was significantly higher in USA centers and studies with more than 50 patients. The IDR was lower when a high rate of metastatic patients was present in the studies. The DCR was 45%. The heterogeneity was high. The DCR was lower in USA studies and in prospective trials. Conclusion: Given the limited efficacy of HD-SSA in preventing the disease progression in unresectable GEP-NENs after failure of standard dose SSA, the use of this therapeutic approach is advisable in selected cases when other antiproliferative treatments are not feasible. [ABSTRACT FROM AUTHOR]

Pancreatic surgery still remains burdened by high levels of morbidity and mortality with a relevant incidence of complications, even in high volume centers. This review highlights the interventional radiological management of complications after pancreatic surgery. The current literature regarding the percutaneous drainage of fluid collections due to pancreatic fistulas, percutaneous transhepatic biliary drainage due to biliary leaks and transcatheter embolization (or stent–graft) due to arterial bleeding is analyzed. Moreover, also, percutaneous intra-portal islet auto-transplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also examined. Moreover, a topic not usually treated in other similar reviewsas percutaneous intra-portal islet auto-transplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also one of our areas of focus. In islet auto-transplantation, the patient is simultaneously donor and recipient. Differently from islet allo-transplantation, it does not require immunosuppression, has no risk of rejection and is usually efficient with a small number of transplanted islets. [ABSTRACT FROM AUTHOR]

Simple Summary: The purpose of the present study is to describe the frequency of non-malignant [68Ga]Ga-DOTANOC uncinate process (UP) uptake and to evaluate its variations over time. Among the first 6 months of enrolment of a monocentric prospective observational electronic archive, analyses of a large number of PET/CT scans (n = 268) of NEN pts (n = 172) demonstrated that: UP uptake is a frequent finding (observed in almost half of the cases, slightly higher than previously reported), mostly presenting with a diffuse pattern and, interestingly, characterized by variations over time in almost one third of the cases. The consciousness of this diagnostic pitfall is of utmost importance for accurate [68Ga]Ga-DOTANOC PET/CT reporting, since the pancreas represents one of the most frequent sites of NEN. Purpose: [68Ga]Ga-DOTA-peptide uptake in the pancreatic head/uncinate process (UP) is a frequent PET/CT finding. Although mostly physiologic, it can represent a pitfall in PET/CT reading, especially when focal. An increased frequency of UP uptake has been reported in patients (pts) affected by diabetes mellitus (DM). The aim of the study is to describe the frequency of [68Ga]Ga-DOTANOC UP uptake to evaluate its variations over time and its possible correlation with DM. Methods: In September 2017, a monocentric prospective observational electronic archive was initiated at our center to collect clinical and imaging data of pts undergoing [68Ga]Ga-DOTANOC PET/CT. Among the pts enrolled in the first 6 months (Sept 2017 to Feb 2018), those presenting [68Ga]Ga-DOTANOC PET/CT uptake at UP level were included. Pts with UP lesions already documented on CT/MRI or those that underwent surgical excision of UP before PET/CT were excluded from the analysis. [68Ga]Ga-DOTANOC UP uptake was classified as diffuse or focal and compared with the pattern observed in previous PET/CT scans performed at our center. An increased frequency of UP uptake was also correlated with the presence of DM. Results: In the first 6 months, 253 pts were enrolled in the archive and 172 out of them were included in the analysis. UP increased uptake was frequently observed (77/172, 44.8%) and was mostly diffuse (62/77). In 75/172 pts (43.6%), previous [68Ga]Ga-DOTANOC PET/CT scans were available (overall 268 scans; number of previous PET per pt range: 1–20) and were retrospectively reviewed. Despite the fact that, in most pts, the uptake pattern was stable over time (54/75 pts, 72%), it changed in approximately one third of cases (21/75, 28%). Among DM pts (29/172), only 10/29 (34.4%) presented increased UP uptake. Conclusions: UP [68Ga]Ga-DOTANOC uptake is a frequent non-malignant finding (slightly higher than previously reported), mostly presenting with a diffuse pattern. However, contrary to previous reports, our data show that the pattern of uptake may vary over time in approximately one third of the cases and it is not more frequently observed in pts with DM. [ABSTRACT FROM AUTHOR]

The mechanistic target of rapamycin (mTOR) is part of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AkT)/mTOR pathway and owes its name to the inhibitory effect of rapamycin. The mTOR has a central converging role for many cell functions, serving as a sensor for extracellular signals from energy status and nutrients availability, growth factors, oxygen and stress. Thus, it also modulates switch to anabolic processes (protein and lipid synthesis) and autophagy, in order to regulate cell growth and proliferation. Given its functions in the cell, its deregulation is implicated in many human diseases, including cancer. Its predominant role in tumorigenesis and progression of neuroendocrine tumors (NETs), in particular, has been demonstrated in preclinical studies and late clinical trials. mTOR inhibition by everolimus is an established therapeutic target in NETs, but there are no identified predictive or prognostic factors. This review is focused on the role of mTOR and everolimus in NETs, from preclinical studies to major clinical trials, and future perspectives involving mTOR in the treatment of NETs. [ABSTRACT FROM AUTHOR]

Advanced ductal pancreatic carcinoma (PC) remains a challenge for current surgical and medical approaches. It has recently been claimed that radiofrequency ablation (RFA) may be beneficial for patients with locally advanced or metastatic PC. Using the MEDLINE database, we found seven studies involving 106 patients in which PC was treated using RFA. The PC was mainly located in the pancreatic head (66.9%) with a median size of 4.6 cm. RFA was carried out in 85 patients (80.1%) with locally advanced PC and in 21 (19.9%) with metastatic disease. Palliative surgical procedures were carried out in 41.5% of the patients. The average temperature used was 90 °C (with a temperature range of 30-105 °C) and the ratio between the number of passes of the probe and the size of the tumor in centimeters was 0.5 (range of 0.36-1). The median postoperative morbidity and mortality were 28.3% and 7.5%, respectively; the median survival was 6.5 months (range of 1-33 months). In conclusion, RFA is a feasible technique: however, its safety and long-term results are disappointing; Thus, the RFA procedure should not be recommended in clinical practice for a PC patient. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin whose incidence is rising. Multimodal treatment is crucial in the non-metastatic, potentially curable setting. However, the optimal management of patients with non-metastatic MCC is still unclear. In addition, novel insights into tumor biology and newly developed treatments (e.g., immune checkpoint inhibitors) that dramatically improved outcomes in the advanced setting are being investigated in earlier stages with promising results. Nevertheless, the combination of new strategies with consolidated ones needs to be clarified. We reviewed available evidence supporting the current treatment recommendations of localized MCC with a focus on potentially ground-breaking future strategies. Advantages and disadvantages of the different treatment modalities, including surgery, radiotherapy, chemotherapy, and immunotherapy in the non-metastatic setting, are analyzed, as well as those of different treatment modalities (adjuvant as opposed to neoadjuvant). Lastly, we provide an outlook of remarkable ongoing studies and of promising agents and strategies in the treatment of patients with non-metastatic MCC. [ABSTRACT FROM AUTHOR]

Facilitated transport membranes obtained by coupling polyvinylamine with highly charged carboxymethylated nanocellulose fibers were studied considering both water sorption and gas permeation experiments. In particular, the effect of the L-arginine as a mobile carrier was investigated to understand possible improvements in CO2 transport across the membranes. The results show that L-arginine addition decreases the water uptake of the membrane, due to the lower polyvinylamine content, but was able to improve the CO2 transport. Tests carried on at 35 °C and high relative humidity indeed showed an increase of both CO2 permeability and selectivity with respect to nitrogen and methane. In particular, the CO2 permeability increased from 160 to about 340 Barrer when arginine loading was increased from 0 to 45 wt%. In the same conditions, selectivity with respect to nitrogen was more than doubled, increasing from 20 to 45. Minor improvements were instead obtained with respect to methane; CO2/CH4 selectivity, indeed, even in presence of the mobile carrier, was limited to about 20. [ABSTRACT FROM AUTHOR]

Predicting grade 1 (G1) and 2 (G2) primary pancreatic neuroendocrine tumour (panNET) is crucial to foresee panNET clinical behaviour. Fifty-one patients with G1-G2 primary panNET demonstrated by pre-surgical [68Ga]Ga-DOTANOC PET/CT and diagnostic conventional imaging were grouped according to the tumour grade assessment method: histology on the whole excised primary lesion (HS) or biopsy (BS). First-order and second-order radiomic features (RFs) were computed from SUV maps for the whole tumour volume on HS. The RFs showing the lowest p-values and the highest area under the curve (AUC) were selected. Three radiomic models were assessed: A (trained on HS, validated on BS), B (trained on BS, validated on HS), and C (using the cross-validation on the whole dataset). The second-order normalized homogeneity and entropy was the most effective RFs couple predicting G2 and G1. The best performance was achieved by model A (test AUC = 0.90, sensitivity = 0.88, specificity = 0.89), followed by model C (median test AUC = 0.87, sensitivity = 0.83, specificity = 0.82). Model B performed worse. Using HS to train a radiomic model leads to the best prediction, although a "hybrid" (HS+BS) population performs better than biopsy-only. The non-invasive prediction of panNET grading may be especially useful in lesions not amenable to biopsy while [68Ga]Ga-DOTANOC heterogeneity might recommend FDG PET/CT. [ABSTRACT FROM AUTHOR]

Simple Summary: The most effective and safest approach for the treatment of advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP–NENs) remains unknown. A systematic review was done to clarify this point. A network meta-analysis was used to overcome the multiarm problem. Our study confirmed that somatostatin analogs (SSAs) alone remain the best choice for well-differentiated GEP–NENs. 177Lu-Dotatate plus SSA is a valid alternative for midgut NENs since it has been shown to be slightly more efficacious but yielding a higher risk for toxicity than SSAs. Several new therapies have been approved to treat advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP–NENs) in the last twenty years. In this systematic review and meta-analysis, we searched MEDLINE, ISI Web of Science, and Scopus phase III randomized controlled trials (RCTs) comparing two or more therapies for unresectable GEP–NENs. Network metanalysis was used to overcome the multiarm problem. For each arm, we described the surface under the cumulative ranking (SUCRA) curves. The primary endpoints were progression-free survival and grade 3–4 of toxicity. We included nine studies involving a total of 2362 patients and 5 intervention arms: SSA alone, two IFN-α plus SSA, two Everolimus alone, one Everolimus plus SSA, one Sunitinib alone, one 177Lu-Dotatate plus SSA, and one Bevacizumab plus SSA. 177Lu-Dotatate plus SSA had the highest probability (99.6%) of being associated with the longest PFS. This approach was followed by Sunitinib use (64.5%), IFN-α plus SSA one (53.0%), SSA alone (46.6%), Bevacizumab plus SSA one (45.0%), and Everolimus ± SSA one (33.6%). The placebo administration had the lowest probability of being associated with the longest PFS (7.6%). Placebo or Bevacizumab use had the highest probability of being the safest (73.7% and 76.7%), followed by SSA alone (65.0%), IFN-α plus SSA (52.4%), 177Lu-Dotatate plus SSA (49.4%), and Sunitinib alone (28.8%). The Everolimus-based approach had the lowest probability of being the safest (3.9%). The best approaches were SSA alone or combined with 177Lu-Dotatate. [ABSTRACT FROM AUTHOR]

In this work, the behavior of new GO-based mixed matrix membranes was tested in view of their use as CO2-selective membrane in post combustion carbon capture applications. In particular, the new materials were obtained by mixing of Pebax® 2533 copolymer with different types of graphene oxide (GO). Pebax® 2533 has indeed lower selectivity, but higher permeability than Pebax® 1657, which is more commonly used for membranes, and it could therefore benefit from the addition of GO, which is endowed with very high selectivity of CO2 with respect to nitrogen. The mixed matrix membranes were obtained by adding different amounts of GO, from 0.02 to 1% by weight, to the commercial block copolymers. Porous graphene oxide (PGO) and GO functionalized with polyetheramine (PEAGO) were also considered in composites produced with similar procedure, with a loading of 0.02%wt. The obtained films were then characterized by using SEM, DSC, XPS analysis and permeability experiments. In particular, permeation tests with pure CO2 and N2 at 35°C and 1 bar of upstream pressure were conducted for the different materials to evaluate their separation performance. It has been discovered that adding these GO-based nanofillers to Pebax® 2533 matrix does not improve the ideal selectivity of the material, but it allows to increase CO2 permeability when a low filler content, not higher than 0.02 wt%, is considered. Among the different types of GO, then, porous GO seems the most promising as it shows CO2 permeability in the order of 400 barrer (with an increase of about 10% with respect to the unloaded block copolymer), obtained without reducing the CO2/N2 selectivity of the materials, which remained in the order of 25. [ABSTRACT FROM AUTHOR]

In the present study, the separation performance of new self-standing polyvinylamine (PVAm) membranes loaded with few-layer graphene (G) and graphene oxide (GO) was evaluated, in view of their use in carbon capture applications. PVAm, provided by BASF as commercial product named LupaminTM, was purified obtaining PVAm films with two degrees of purification: Low Grade (PVAm-LG) and High Grade (PVAm-HG). These two-grade purified PVAm were loaded with 3 wt% of graphene and graphene oxide to improve mechanical stability: indeed, pristine tested materials proved to be brittle when dry, while highly susceptible to swelling in humid conditions. Purification performances were assessed through FTIR-ATR spectroscopy, DSC and TGA analysis, which were carried out to characterize the pristine polymer and its nanocomposites. In addition, the membranes′ fracture surfaces were observed through SEM analysis to evaluate the degree of dispersion. Water sorption and gas permeation tests were performed at 35 °C at different relative humidity (RH), ranging from 50% to 95%. Overall, composite membranes showed improved mechanical stability at high humidity, and higher glass transition temperature (Tg) with respect to neat PVAm. Ideal CO2/N2 selectivity up to 80 was measured, paired with a CO2 permeability of 70 Barrer. The membranes' increased mechanical stability against swelling, even at high RH, without the need of any crosslinking, represents an interesting result in view of possible further development of new types of facilitated transport composite membranes. [ABSTRACT FROM AUTHOR]

The mechanistic target of rapamycin (mTOR) is part of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AkT)/mTOR pathway and owes its name to the inhibitory effect of rapamycin. The mTOR has a central converging role for many cell functions, serving as a sensor for extracellular signals from energy status and nutrients availability, growth factors, oxygen and stress. Thus, it also modulates switch to anabolic processes (protein and lipid synthesis) and autophagy, in order to regulate cell growth and proliferation. Given its functions in the cell, its deregulation is implicated in many human diseases, including cancer. Its predominant role in tumorigenesis and progression of neuroendocrine tumors (NETs), in particular, has been demonstrated in preclinical studies and late clinical trials. mTOR inhibition by everolimus is an established therapeutic target in NETs, but there are no identified predictive or prognostic factors. This review is focused on the role of mTOR and everolimus in NETs, from preclinical studies to major clinical trials, and future perspectives involving mTOR in the treatment of NETs., Competing Interests: The authors declare no conflict of interest.