Massive Weight Loss Decreases Corticosteroid-Binding Globulin Levels and Increases Free Cortisol in Healthy Obese Patients An adaptive phenomenon?

OBJECTIVE—Obesity, insulin resistance, and weight loss have been associated with changes in hypothalamic-pituitary-adrenal (HPA) axis. So far, no conclusive data relating to this association are available. In this study, we aim to investigate the effects of massive weight loss on cortisol suppressibility, cortisol-binding globulin (CBG), and free cortisol index (FCI) in formerly obese women. RESEARCH DESIGN AND METHODS—Ten glucose-normotolerant, fertile, obese women (BMI >40 kg/m2, aged 38.66 ± 13.35 years) were studied before and 2 years after biliopancreatic diversion (BPD) when stable weight was achieved and were compared with age-matched healthy volunteers. Cortisol suppression was evaluated by a 4-mg intravenous dexamethasone suppression test (DEX-ST). FCI was calculated as the cortisol-to-CBG ratio. Insulin sensitivity was measured by an euglycemic-hyperinsulinemic clamp, and insulin secretion was measured by a C-peptide deconvolution method. RESULTS—No difference was found in cortisol suppression after DEX-ST before or after weight loss. A decrease in ACTH was significantly greater in control subjects than in obese (P = 0.05) and postobese women (P ≤ 0.01) as was the decrease in dehydroepiandrosterone (P ≤ 0.05 and P ≤ 0.01, respectively). CBG decreased from 51.50 ± 12.76 to 34.33 ± 7.24 mg/l (P ≤ 0.01) following BPD. FCI increased from 11.15 ± 2.85 to 18.16 ± 6.82 (P ≤ 0.05). Insulin secretion decreased (52.04 ± 16.71 vs. 30.62 ± 16.32 nmol/m−2; P ≤ 0.05), and insulin sensitivity increased by 163% (P ≤ 0.0001). Serum CBG was related to BMI (r0 = 0.708; P = 0.0001), body weight (r0 = 0.643; P = 0.0001), body fat percent (r0 = 0.462; P = 0.001), C-reactive protein (r0 = 0.619; P = 0.004), and leptin (r0 = 0.579; P = 0.007) and negatively to M value (r0 = −0.603; P = 0.005). CONCLUSIONS—After massive weight loss in morbidly obese subjects, an increase of free cortisol was associated with a simultaneous decrease in CBG levels, which might be an adaptive phenomenon relating to environmental changes. This topic, not addressed before, adds new insight into the complex mechanisms linking HPA activity to obesity

Role of radiomics in predicting lymph node metastasis in gastric cancer: a systematic review

IntroductionGastric cancer (GC) is an aggressive and clinically heterogeneous tumor, and better risk stratification of lymph node metastasis (LNM) could lead to personalized treatments. The role of radiomics in the prediction of nodal involvement in GC has not yet been systematically assessed. This study aims to assess the role of radiomics in the prediction of LNM in GC.MethodsA PubMed/MEDLINE systematic review was conducted to assess the role of radiomics in LNM. The inclusion criteria were as follows: i. original articles, ii. articles on radiomics, and iii. articles on LNM prediction in GC. All articles were selected and analyzed by a multidisciplinary board of two radiation oncologists and one surgeon, under the supervision of one radiation oncologist, one surgeon, and one medical oncologist.ResultsA total of 171 studies were obtained using the search strategy mentioned on PubMed. After the complete selection process, a total of 20 papers were considered eligible for the analysis of the results. Radiomics methods were applied in GC to assess the LNM risk. The number of patients, imaging modalities, type of predictive models, number of radiomics features, TRIPOD classification, and performances of the models were reported.ConclusionsRadiomics seems to be a promising approach for evaluating the risk of LNM in GC. Further and larger studies are required to evaluate the clinical impact of the inclusion of radiomics in a comprehensive decision support system (DSS) for GC

The Role of Staging Laparoscopy for Gastric Cancer Patients: Current Evidence and Future Perspectives

A significant proportion of patients diagnosed with gastric cancer is discovered with peritoneal metastases at laparotomy. Despite the continuous improvement in the performance of radiological imaging, the preoperative recognition of such an advanced disease is still challenging during the diagnostic work-up, since the sensitivity of CT scans to peritoneal carcinomatosis is not always adequate. Staging laparoscopy offers the chance to significantly increase the rate of promptly diagnosed peritoneal metastases, thus reducing the number of unnecessary laparotomies and modifying the initial treatment strategy of gastric cancer. The aim of this review was to provide a comprehensive summary of the current literature regarding the role of staging laparoscopy in the management of gastric cancer. Indications, techniques, accuracy, advantages, and limitations of staging laparoscopy and peritoneal cytology were discussed. Furthermore, a focus on current evidence regarding the application of artificial intelligence and image-guided surgery in staging laparoscopy was included in order to provide a picture of the future perspectives of this technique and its integration with modern tools in the preoperative management of gastric cancer

Identification of spatially-resolved markers of malignant transformation in Intraductal Papillary Mucinous Neoplasms

The existing Intraductal Papillary Mucinous Neoplasm (IPMN) risk stratification relies on clinical and histological factors, resulting in inaccuracies and leading to suboptimal treatment. This is due to the lack of appropriate molecular markers that can guide patients toward the best therapeutic options. Here, we assess and confirm subtype-specific markers for IPMN across two independent cohorts of patients using two Spatial Transcriptomics (ST) technologies. Specifically, we identify HOXB3 and ZNF117 as markers for Low-Grade Dysplasia, SPDEF and gastric neck cell markers in borderline cases, and NKX6-2 and gastric isthmus cell markers in High-Grade-Dysplasia Gastric IPMN, highlighting the role of TNFα and MYC activation in IPMN progression and the role of NKX6-2 in the specific Gastric IPMN progression. In conclusion, our work provides a step forward in understanding the gene expression landscapes of IPMN and the critical transcriptional networks related to PDAC progression

Advancing Diabetes Research: a novel islet isolation method from living donors.

Pancreatic islet isolation is critical for type 2 diabetes research. Although -omics approaches have shed light on islet molecular profiles, inconsistencies persist; on the other side, functional studies are essential, but they require reliable and standardized isolation methods. Here, we propose a simplified protocol applied to very small-sized samples collected from partially pancreatecto-mized living donors. Islet isolation was performed digesting tissue specimens collected during surgery within a collagenase P solution, followed by a Lympholyte density gradient separation; finally, functional assays and a staining with dithizone were carried out. Isolated pancreatic islets exhibited functional responses to glucose and arginine stimulation mirroring donors' metabolic profiles, with insulin secretion significantly decreasing in diabetic islets compared to non-diabetic islets; conversely, proinsulin secretion showed an increasing trend from non-diabetic to diabetic islets. This novel islet isolation method from living patients undergoing partial pancreatectomy offers a valuable opportunity for targeted study of islet physiology, with the primary advantage of being time-effective and successfully preserving islet viability and functionality. It enables the generation of islet preparations closely reflecting donors’ clinical profiles, simplifying the isola-tion process and eliminating the need for a Ricordi chamber. Thus, this method holds promises for advancing our understanding of diabetes and for new personalized pharmacological approaches

The Clinical Frailty Scale (CFS) as an Independent Prognostic Factor for Patients ≥80 Years with Small Bowel Obstruction (SBO)

Background: SBO is a potentially life-threatening condition that often affects older patients. Frailty, more than age, is expected to play a crucial role in predicting SBO prognosis in this population. This study aims to define the influence of Clinical Frailty Scale (CFS) on mortality and major complications in patients ≥80 years with diagnosis of SBO at the emergency department (ED). Methods: All patients aged ≥80 years admitted to our ED for SBO from January 2015 to September 2020 were enrolled. Frailty was assessed through the CFS, and then analyzed both as a continuous and a dichotomous variable. The endpoints were in-hospital mortality and major complications. Results: A total of 424 patients were enrolled. Higher mortality (20.8% vs 8.6%, p<0.001), longer hospital stay (9 [range 5-14] days vs 7 [range 4-12] days, p=0.014), and higher rate of major complications (29.9% vs 17.9%, p=0.004) were associated with CFS ≥7. CFS score and bloodstream infection were the only independent prognostic factors for mortality (OR 1.72 [CI: 1.29-2.29], p<0.001; OR 4.69 [CI: 1.74-12.6], p=0.002, respectively). Furthermore, CFS score, male sex and surgery were predictive factors for major complications (OR 1.41 [CI: 1.13-1.75], p=0.002; OR 1.67 [CI: 1.03-2.71], p=0.038); OR 1.91 [CI: 1.17-3.12], p=0.01; respectively). At multivariate analysis, for every 1-point increase in CFS score, the odds of mortality and the odds of major complications increased 1.72-fold and 1.41-fold, respectively. Conclusion: The increase in CFS is directly associated with an increased risk of mortality and major complications. The presence of severe frailty could effectively predict an increased risk of in-hospital death regardless of the treatment administered. The employment of CFS in elderly patients could help the identification of the need for closer monitoring and proper goals of care

Prolonged pre-firing pancreatic compression with linear staplers in distal pancreatectomy: a valuable technique for post-operative pancreatic fistula prevention

Purpose: Post-operative pancreatic fistula (POPF) remains the main complication after distal pancreatectomy (DP). The aim of this study is to evaluate the potential benefit of different durations of progressive stapler closure on POPF rate and severity after DP. Methods: Patients who underwent DP between 2016 and 2023 were retrospectively enrolled and divided into two groups according to the duration of the stapler closure: those who underwent a progressive compression for < 10 min and those for ≥ 10 min. Results: Among 155 DPs, 83 (53.5%) patients underwent pre-firing compression for < 10 min and 72 (46.5%) for ≥ 10 min. As a whole, 101 (65.1%) developed POPF. A lower incidence rate was found in case of ≥ 10 min compression (34-47.2%) compared to < 10 min compression (67- 80.7%) (p = 0.001). When only clinically relevant (CR) POPFs were considered, a prolonged pre-firing compression led to a lower rate (15-20.8%) than the < 10 min cohort (32-38.6%; p = 0.02). At the multivariate analysis, a compression time of at least 10 min was confirmed as a protective factor for both POPF (OR: 5.47, 95% CI: 2.16-13.87; p = 0.04) and CR-POPF (OR: 2.5, 95% CI: 1.19-5.45; p = 0.04) development. In case of a thick pancreatic gland, a prolonged pancreatic compression for at least 10 min was significantly associated to a lower rate of CR-POPF compared to < 10 min (p = 0.04). Conclusion: A prolonged pre-firing pancreatic compression for at least 10 min seems to significantly reduce the risk of CR-POPF development. Moreover, significant advantages are documented in case of a thick pancreatic gland