White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma

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Muscle and adipose tissue morphology, insulin sensitivity and beta-cell function in diabetic and nondiabetic obese patients: effects of bariatric surgery

Obesity is characterized by insulin-resistance (IR), enhanced lipolysis, and ectopic, inflamed fat. We related the histology of subcutaneous (SAT), visceral fat (VAT), and skeletal muscle to the metabolic abnormalities, and tested their mutual changes after bariatric surgery in type 2 diabetic (T2D) and weight-matched non-diabetic (ND) patients. We measured IR (insulin clamp), lipolysis ((2)H5-glycerol infusion), ß-cell glucose-sensitivity (ß-GS, mathematical modeling), and VAT, SAT, and rectus abdominis histology (light and electron microscopy). Presurgery, SAT and VAT showed signs of fibrosis/necrosis, small mitochondria, free interstitial lipids, thickened capillary basement membrane. Compared to ND, T2D had impaired ß-GS, intracapillary neutrophils and higher intramyocellular fat, adipocyte area in VAT, crown-like structures (CLS) in VAT and SAT with rare structures (cyst-like) ~10-fold larger than CLS. Fat expansion was associated with enhanced lipolysis and IR. VAT histology and intramyocellular fat were related to impaired ß-GS. Postsurgery, IR and lipolysis improved in all, ß-GS improved in T2D. Muscle fat infiltration was reduced, adipocytes were smaller and richer in mitochondria, and CLS density in SAT was reduced. In conclusion, IR improves proportionally to weight loss but remains subnormal, whilst SAT and muscle changes disappear. In T2D postsurgery, some VAT pathology persists and beta-cell dysfunction improves but is not normalized

WAT to BAT transdifferentiation of omental fat in adult humans affected by pheochromocytomas

In small mammals and to some extent also in humans, White Adipose Tissue (WAT) and Brown Adipose Tissue (BAT) are contained together in discrete locations at subcutaneous or visceral level forming a multi-depots organ [1]. We have recently described paucilocular cells immunoreactive for uncoupling protein 1 (UCP1-ir) as morphological marker of WAT-BAT transformation in the adipose organ of cold-exposed mice (hyper-adrenergic stimulation) [2]. In this study, we examined biopsies of omental WAT depot, in 20 controls and in 12 patients affected by pheochromocytomas used as model of adrenergic stimulation in humans. Histological examination was performed by light microscopy, immunohistochemistry and Electron Microscopy. qPCR was carried out to asses relative expression of “brown” genes. Control tissues were all formed by unilocular UCP1-negative adipocytes. Half of the omental fat samples from pheochromocytomas showed UCP1-ir multilocular cells forming BAT-islands among WAT. Several UCP1-ir paucilocular cells were also detected. Higher density of TH-ir fibres and capillaries were found in the transformed tissues. Ultrastructural examination, highlighted poorly differentiated cells in pericapillary position with features similar to those identified in supraclavicular human BAT [3]. In light of the protective role exerted by BAT against the development of obesity and other metabolic diseases, WAT to BAT plasticity could be an important target for the development of therapeutic strategies in the treatment of obesity and type II diabetes in humans

Emergency surgery for splenic flexure cancer: results of the SFC Study Group database

Background: The effectiveness of surgical treatment for splenic flexure carcinomas (SFCs) in emergency settings remains unexplored. This study aims to compare the perioperative and long-term outcomes of different alternatives for emergency SFC resection. Method: This multicenter retrospective study was based on the SFC Study Group database. For the present analysis, SFC patients were selected if they had received emergency surgical resection with curative intent between 2000 and 2018. Extended right colectomy (ERC), left colectomy (LC), and segmental left colectomy (SLC) were evaluated and compared. Results: The study sample was composed of 90 SFC patients who underwent emergency ERC (n = 55, 61.1%), LC (n = 18, 20%), or SLC (n = 17, 18.9%). Bowel obstruction was the most frequent indication for surgery (n = 75, 83.3%), and an open approach was chosen in 81.1% of the patients. A higher incidence of postoperative complications was observed in the ERC group (70.9%) than in the LC (44.4%) and SLC groups (47.1%), with a significant procedure-related difference for severe postoperative complications (Dindo-Clavien ≥ III; adjusted odds ratio for ERC vs. LC:7.23; 95% CI 1.51-34.66; p = 0.013). Anastomotic leakage occurred in 8 (11.2%) patients, with no differences between the groups (p = 0.902). R0 resection was achieved in 98.9% of the procedures, and ≥ 12 lymph nodes were retrieved in 92.2% of patients. Overall and disease-free survival rates at 5 years were similar between the groups and were significantly associated with stage pT4 and the presence of synchronous metastases. Conclusion: In the emergency setting, ERC and open surgery are the most frequently performed procedures. ERC is associated with increased odds of severe postoperative complications when compared to more conservative SFC resections. Nonetheless, all the alternatives seem to provide similar pathologic and long-term outcomes, supporting the oncological safety of more conservative resections for emergency SFCs

Dynamic Changes in Lipid Droplet-Associated Proteins in the "Browning" of White Adipose Tissues

The morphological and functional differences between lipid droplets (LDs) in brown (BAT) and white (WAT) adipose tissues will largely be determined by their associated proteins. Analysing mRNA expression in mice fat depots we have found that most LD protein genes are expressed at higher levels in BAT, with the greatest differences observed for Cidea and Plin5. Prolonged cold exposure, which induces the appearance of brown-like adipocytes in mice WAT depots, was accompanied with the potentiation of the lipolytic machinery, with changes in ATGL, CGI-58 and G0S2 gene expression. However the major change detected in WAT was the enhancement of Cidea mRNA. Together with the increase in Cidec, it indicates that LD enlargement through LD-LD transference of fat is an important process during WAT browning. To study the dynamics of this phenotypic change, we have applied 4D confocal microscopy in differentiated 3T3-L1 cells under sustained β-adrenergic stimulation. Under these conditions the cells experienced a LD remodelling cycle, with progressive reduction on the LD size by lipolysis, followed by the formation of new LDs, which were subjected to an enlargement process, likely to be CIDE-triggered, until the cell returned to the basal state. This transformation would be triggered by the activation of a thermogenic futile cycle of lipolysis/lipogenesis and could facilitate the molecular mechanism for the unilocular to multilocular transformation during WAT browning. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease

Emergency surgery for splenic flexure cancer: results of the SFC Study Group database.

BACKGROUND: The effectiveness of surgical treatment for splenic flexure carcinomas (SFCs) in emergency settings remains unexplored. This study aims to compare the perioperative and long-term outcomes of different alternatives for emergency SFC resection. METHOD: This multicenter retrospective study was based on the SFC Study Group database. For the present analysis, SFC patients were selected if they had received emergency surgical resection with curative intent between 2000 and 2018. Extended right colectomy (ERC), left colectomy (LC), and segmental left colectomy (SLC) were evaluated and compared. RESULTS: The study sample was composed of 90 SFC patients who underwent emergency ERC (n = 55, 61.1%), LC (n = 18, 20%), or SLC (n = 17, 18.9%). Bowel obstruction was the most frequent indication for surgery (n = 75, 83.3%), and an open approach was chosen in 81.1% of the patients. A higher incidence of postoperative complications was observed in the ERC group (70.9%) than in the LC (44.4%) and SLC groups (47.1%), with a significant procedure-related difference for severe postoperative complications (Dindo-Clavien ≥ III; adjusted odds ratio for ERC vs. LC:7.23; 95% CI 1.51-34.66; p = 0.013). Anastomotic leakage occurred in 8 (11.2%) patients, with no differences between the groups (p = 0.902). R0 resection was achieved in 98.9% of the procedures, and ≥ 12 lymph nodes were retrieved in 92.2% of patients. Overall and disease-free survival rates at 5 years were similar between the groups and were significantly associated with stage pT4 and the presence of synchronous metastases. CONCLUSION: In the emergency setting, ERC and open surgery are the most frequently performed procedures. ERC is associated with increased odds of severe postoperative complications when compared to more conservative SFC resections. Nonetheless, all the alternatives seem to provide similar pathologic and long-term outcomes, supporting the oncological safety of more conservative resections for emergency SFCs

2020 WSES guidelines for the detection and management of bile duct injury during cholecystectomy.

Bile duct injury (BDI) is a dangerous complication of cholecystectomy, with significant postoperative sequelae for the patient in terms of morbidity, mortality, and long-term quality of life. BDIs have an estimated incidence of 0.4-1.5%, but considering the number of cholecystectomies performed worldwide, mostly by laparoscopy, surgeons must be prepared to manage this surgical challenge. Most BDIs are recognized either during the procedure or in the immediate postoperative period. However, some BDIs may be discovered later during the postoperative period, and this may translate to delayed or inappropriate treatments. Providing a specific diagnosis and a precise description of the BDI will expedite the decision-making process and increase the chance of treatment success. Subsequently, the choice and timing of the appropriate reconstructive strategy have a critical role in long-term prognosis. Currently, a wide spectrum of multidisciplinary interventions with different degrees of invasiveness is indicated for BDI management. These World Society of Emergency Surgery (WSES) guidelines have been produced following an exhaustive review of the current literature and an international expert panel discussion with the aim of providing evidence-based recommendations to facilitate and standardize the detection and management of BDIs during cholecystectomy. In particular, the 2020 WSES guidelines cover the following key aspects: (1) strategies to minimize the risk of BDI during cholecystectomy; (2) BDI rates in general surgery units and review of surgical practice; (3) how to classify, stage, and report BDI once detected; (4) how to manage an intraoperatively detected BDI; (5) indications for antibiotic treatment; (6) indications for clinical, biochemical, and imaging investigations for suspected BDI; and (7) how to manage a postoperatively detected BDI

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Vascular applications of Very-High Frequencies Ultrasonography

The aim of this thesis is to evaluate vascular applications of very high frequencies ultrasound (VHFUS) through the analysis of preliminary results obtained from two different scientific studies. VHFUS allows visualization of the vessel wall ultrastructure of several arterial districts with a correlation between the different ultrasound interfaces and the layers that histologically compose the vessel wall. Compared to what previously seen with conventional ultrasound, arterial wall showed an additional echogenic interface, possibly corresponding to the external elastic lamina (media-adventitia interface), allowing the measure of many wall parameters: most important being intima-media thickness (IMT), adventitia thickness (AT) and global thickness (IMAT). These new diagnostic possibilities have been applied in two different clinical scenarios, analyzing the preliminary results of two different scientific studies: • The first work evaluates patency, caliber and ultrastructure of the vessel wall of the interdigital arteries of hands in patients with secondary Raynaud's phenomenon, comparing the results with those obtained in healthy subjects population. Preliminary data shows significant differences in intimal thickness and "Media to lumen ratio" between the two study groups. Furthermore, considering only the cryoglobulinemic patients compared to the control group, significant differences were identified for the above-mentioned parameters as well as for the intima-media thickness and lumen diameter. • The second work shows preliminary results obtained from the FUCHSIA study (Very high-Frequency Ultrasonography for arterial phenotyping in patients with Cervico-Cerebral Artery Dissection (CCeAD), Hypertension, Spontaneous Coronary Artery Dissection (SCAD) and FibroMuscular DysplasIA (FMD). This study is based on the identification of radial vascular wall abnormalities by very high frequency ultrasound in patients with fibromuscular dysplasia. This case-control study aim is to indentify radial vascular wall abnormalities analyzing this disease with VHFUS and automated image analysis. Furthermore, the disarray level of the vessels echogenic interfaces was assessed calculating the root mean square error (RMSE) between 20 profiles crossing the two interfaces and the profile obtained averaging them. For each echogenic interface, the RMSE was normalized for the maximum value of the corresponding mean profile (RMSE/mean). Results show a similar radial internal diameter in the two group, the maximum values of the mean profiles corresponding to the two interfaces tended to be lower in FMD patients. RMSE/mean was significantly higher in FMD than in C both for 1st and 2nd echogenic interface. IMT, AT and IMAT were significantly higher in FMD: the difference in IMT and IMAT remained significant even when considering age and mean BP as covariates. Wall/lumen ratio was similar and wall cross sectional area (WCSA) increased in FMD, calculated with either IMT or IMAT. In conclusion wall ultrastructure of radial arteries of hypertensive FMD patients was extensively altered: a peculiar “blurred” pattern, characterized of loss of echogenicity and inhomogeneity of the two echogenic layers, independent of age and mean BP. Increased wall thickness and WCSA were also found, indicating a eutrophic remodeling