Leaderless, mutualistic, and organic agricultural co-production as a socially-ecologically sustainable rural-urban practice. A local Italian experience, an international perspective to rethink the territory and the city

In an expanding world demanding more and more resources and causing interconnected crisis, the systemic nature of tragic social and ecological incidents is not (yet) widely acknowledged. The social and ecological limits of the current industry-based economic paradigm let us forerun the onset of possible emergencies to be possibly tackled through preventive design and positive transformation, where the rethinking of the territory, the city, and their supporting environments is necessarily involved. In this perspective, nurturing initiatives to ensure distributed food provision seems a good start in such a transformation, at least as a socio-economic sustainability tool and as a satisfier of basic human needs. We present an example of communal self-management for organic agricultural production, inspired to the model of Community-Supported Agriculture (CSA). This project was started in the urban sprawl of massively industrialised North-Eastern Italy by committed individuals and grassroot groups, already active in discourses on ecological sustainability, social equity, social and solidarity economy, transition and post-growth. From individual-to-collective self-determination and bottom-up initiative potentials through food plans and other tools to be participatorily defined with all the actors of a given area, a CSA can represent the trigger of a virtuous paradigmatic shift in more or less institutional policies for the maintenance, regeneration, and strengthening of territory and urban environments

Study Protocol of the ESAP Study: Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodenectomy for Ampullary Neoplasm—A Pancreas2000/EPC Study

Background: Lesions of the Ampulla of Vater are a rare condition and represent <10% of peri-ampullary neoplasms. Nevertheless, ampullary adenomas have the potential for malignant transformation to ampullary carcinomas by an adenoma-to-carcinoma sequence. Thus, adequate patient selection and complete resection (R0) of non-invasive ampullary lesions either by endoscopic papillectomy (EP), surgical ampullectomy (SA), or pancreaticoduodenectomy (PD) is essential. Although PD was traditionally performed, recent studies reported considerable efficacy and fewer complications following EP and SA. Since consistent comparative data are lacking, the Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodectomy (ESAP) study will provide evidence for a therapeutic standard and post procedure morbidity in ampullary lesions. Methods: International multicenter retrospective study. Adult patients (>18 years of age) who underwent SA or PD for ampullary neoplasm between 2004 and 2018 or EP between 2007 and 2018 will be evaluated. Main inclusion criteria are ampullary lesions strictly located to the ampulla. This includes adenoma, adenocarcinoma (T1 and T2), neuroendocrine tumors, gastrointestinal stroma tumors and other rare conditions. Exclusion criteria are peri-ampullary lesions, e.g., from the duodenal wall or the head of the pancreas, and interventions for tumor stages higher than T2. The main objective of this study is to analyze rates of complete resection (R0), recurrence and necessity for complementary interventions following EP, SA, and PD. Treatment-quality for each procedure will be defined by morbidity, mortality and complication rates and will be compared between EP, SA, and PD. Secondary objectives include outcome for patients with incomplete resection or initially understated tumors, lesions of the minor papilla, hereditary syndromes, neuroendocrine tumors, mesenchymal lesions, and other rare conditions. Additionally, we will analyze therapy by argon plasma coagulation and radiofrequency ablation. Furthermore, outcome in curative and palliative interventions can be distinguished. Conclusion: The ESAP study will provide evidence for therapeutic algorithms and data for the implementation of guidelines in the treatment of different types of ampullary tumors, including recurrent, or incomplete resected lesions

Systematic Review with Meta-Analysis: Endoscopic and Surgical Resection for Ampullary Lesions

Ampullary lesions (ALs) can be treated by endoscopic (EA) or surgical ampullectomy (SA) or pancreaticoduodenectomy (PD). However, EA carries significant risk of incomplete resection while surgical interventions can lead to substantial morbidity. We performed a systematic review and meta-analysis for R0, adverse-events (AEs) and recurrence between EA, SA and PD. Electronic databases were searched from 1990 to 2018. Outcomes were calculated as pooled means using fixed and random-effects models and the Freeman-Tukey-Double-Arcsine-Proportion-model. We identified 59 independent studies. The pooled R0 rate was 76.6% (71.8–81.4%, I2 = 91.38%) for EA, 96.4% (93.6–99.2%, I2 = 37.8%) for SA and 98.9% (98.0–99.7%, I2 = 0%) for PD. AEs were 24.7% (19.8–29.6%, I2 = 86.4%), 28.3% (19.0–37.7%, I2 = 76.8%) and 44.7% (37.9–51.4%, I2 = 0%), respectively. Recurrences were registered in 13.0% (10.2–15.6%, I2 = 91.3%), 9.4% (4.8–14%, I2 = 57.3%) and 14.2% (9.5–18.9%, I2 = 0%). Differences between proportions were significant in R0 for EA compared to SA (p = 0.007) and PD (p = 0.022). AEs were statistically different only between EA and PD (p = 0.049) and recurrence showed no significance for EA/SA or EA/PD. Our data indicate an increased rate of complete resection in surgical interventions accompanied with a higher risk of complications. However, studies showed various sources of bias, limited quality of data and a significant heterogeneity, particularly in EA studies

Vertebral carcinomatosis eleven years after advanced gastric cancer resection: A case report.

Bone metastasis is an uncommon event in advanced gastric cancer patients and bone metastases are rarely detected as isolated lesions. However, eleven years after treatment for locally advanced gastric cancer, including total gastrectomy followed by adjuvant chemotherapy, a 49-year-old female was admitted to the IX Division of General Surgery of the Second University of Naples (Naples, Italy) exhibiting severe progressive neurological symptoms. Magnetic resonance imaging indicated vertebral abnormalities, with evidence of marrow infiltration in several vertebral bodies; however, a contrast-enhanced computed tomography scan did not detect disease progression to other sites. Biopsy of the soft tissue at the level of the second lumbar vertebra (L2) revealed a metastatic lesion derived from gastric mucinous adenocarcinoma. The patient was initially treated with radiotherapy directed to the L2-L4 vertebral bodies to control the pain. Subsequently, systemic chemotherapy according to a FOLFOX-4 (leucovorin, fluorouracil and oxaliplatin) regimen commenced. However, after eight cycles, pulmonary progression of the disease occurred. Thus, palliative care was administered and the patient succumbed one month later. The late relapse of gastric cancer in the current patient may be associated with the theory of tumour dormancy

Lumen-apposing metal stent through the meshes of duodenal metal stents for palliation of malignant jaundice

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard procedure for malignant jaundice palliation; however, it can be challenging when a duodenal self-expandable metal stent (SEMS) is already in place. Patients and methods The primary aim of our study was to evaluate the technical feasibility of the placement of a lumen apposing metal stent (LAMS) through the mesh (TTM) of duodenal stents. The secondary aims were to evaluate clinical outcomes and adverse events (AEs) related to the procedures. Results Data from 23 patients (11 F and 12 M; mean age: 69.5 ± 11 years old) were collected. In 17 patients (73.9 %) TTM LAMS placement was performed as first intention, while in six patients (26.1 %) it was performed after a failed ERCP. Thirteen patients (56.5 %) underwent the procedure due to advanced pancreatic head neoplasia. One technical failure was experienced (4.3 %). The TTM LAMS placement led to a significant decrease in the serum levels of bilirubin, ALP, GGT, WBC and CRP. No cases of duodenal SEMS occlusion occurred and no other AEs were observed during the follow-up. Conclusions Concomitant malignant duodenal and biliary obstruction is a challenging condition. Palliation of jaundice using TTM LAMS in patients already treated with duodenal stent is associated to promising technical and clinical outcomes

the novel role of epigenetics in primary prevention of cardiovascular diseases

A great deal of evidences indicate that impaired fetal growth and in utero exposure to risk factors, especially maternal hypercholesterolemia, may be relevant for human pathophysiological signs of atherosclerosis and subsequent development of cardiovascular disease (CVD) during different life stages. Despite the underlying mechanisms of fetal programming are still unknown, epigenetics has been suggested as one of the possible explanations for the associations between intrauterine risk factors and CVD development. Indeed, a lot of translational studies support the hypothesis that epigenetic changes are related to increased CVD risk although it is still not possible to establish a direct causality in humans. Notably, epigenetic modifications can be reversible through therapeutic approaches employing histone deacetylase inhibitors, histone acetyltransferase inhibitors and commonly used drugs like statins. Thus, the whole comprehension of these mechanisms will provide in the next future the rationale for the development of novel tools to be used in the primary prevention and therapy of CVD

The dual targeting of insulin and insulin-like growth factor 1 receptor enhances the mTOR inhibitor-mediated antitumor efficacy in hepatocellular carcinoma

Deregulation of mTOR and IGF pathways is frequent in hepatocellular carcinoma (HCC), thus mTOR and IGF1R represent suitable therapeutic targets in HCC. The aim of this study was to evaluate the effects of mTOR inhibitors (mTORi) and OSI-906, blocker of IGF1R/IR, on HCC cell proliferation, viability, migration and invasion, and alpha-fetoprotein (α-FP) secretion. In HepG2 and HuH-7 we evaluated, the expression of mTOR and IGF pathway components; the effects of Sirolimus, Everolimus, Temsirolimus and OSI-906 on cell proliferation; the effects of Sirolimus, OSI-906, and their combination, on cell secretion, proliferation, viability, cell cycle, apoptosis, invasion and migration. Moreover, intracellular mechanisms underlying these cell functions were evaluated in both cell lines. Our results show that HepG2 and HuH-7 present with the same mRNA expression profile with high levels of IGF2. OSI-906 inhibited cell proliferation at high concentration, while mTORi suppressed cell proliferation in a dose-time dependent manner in both cell lines. The co-treatment showed an additive inhibitory effect on cell proliferation and viability. This effect was not related to induction of apoptosis, but to G0/G1 phase block. Moreover, the co-treatment prevented the Sirolimus-induced AKT activation as escape mechanism. Both agents demonstrated to be differently effective in inhibiting α-FP secretion. Sirolimus, OSI-906, and their combination, blocked cell migration and invasion in HuH-7. These findings indicate that, co-targeting of IGF1R/IR and mTOR pathways could be a novel therapeutic approach in the management of HCC, in order to maximize antitumoral effect and to prevent the early development of resistance mechanisms

A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma. Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies. Methods: The researchers conducted a systematic literature review for each research question on scientific data- bases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost. Results: The average cost of the first year of treatment was euro2,558.91 and euro3,287.40 for subjects with micro- prolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after ini- tial treatment were euro798.13 and euro1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of euro3,201.15 compared to bromocriptine, based on a willingness-to-pay of euro40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic sur- gery was more cost-effective than cabergoline, with an ICER of euro44,846.64. Considering a willingness-to-pay of euro40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that. Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources

“New records of rare species in the Mediterranean Sea” (October 2021)

“New records of rare species in the Mediterranean Sea” (October 2021