The iGreenGO Study: The Clinical Role of Indocyanine Green Imaging Fluorescence in Modifying the Surgeon's Conduct During the Surgical Treatment of Advanced Gastric Cancer-Study Protocol for an International Multicenter Prospective Study.

Background: The near-infrared/indocyanine green imaging fluorescence (NIR/ICG) technology is showing promising results in several fields of surgical oncology. The clinical value of NIR/ICG technology in the surgical treatment of advanced gastric cancer (AGC) is not clearly established. Methods: This is the protocol of the "iGreenGO" (indocyanine Green Gastric Observation) Study, a national prospective multicenter study. Western patients who undergo curative-intent gastrectomy with D2 lymphadenectomy for AGC constitute the study cohort. All the patients undergo preoperative upper gastrointestinal endoscopy for submucosal peritumoral ICG injection at the most 20 h before surgery. Intraoperative endoscopic injection before starting surgical dissection is also allowed. The primary endpoint is the "change in the surgical conduct" (CSC), i.e., the need to perform further dissection after intraoperative NIR/ICG technology activation at the end of D2 lymphadenectomy. Secondary endpoints include the pattern of abdominal fluorescence distribution according to tumor and patient characteristics, the preoperative clinical variables potentially associated with CSC, and the incidence of stage migration due to NIR/ICG application. Discussion: The iGreenGO Study is the first study to investigate the clinical role of NIR/ICG technology for the surgical treatment of AGC in a large cohort of Western patients. Results from the present study can further clarify the role of NIR/ICG technology in surgical lymphadenectomy for AGC.

Global distribution of prophylactic total gastrectomy in E-cadherin (CDH1) mutations.

Individuals with germline E-cadherin (CDH1) mutations are at high risk of developing diffuse gastric cancer (GC) and prophylactic total gastrectomy (PTG) represents the only life-saving treatment. We reviewed all PTGs reported in literature associated with CDH1 germline mutations. A total of 224 PTGs were reported. The majority were described in the United States of America (50%), the Netherlands (17.8%), and Canada (12.5%). GC was identified in 85.4% of cases after PTG, with a high rate of "no cancer" at histopathology identified in the United States of America (19.6%). Considering the mutation type, a total of 61 different germline mutations was reported, primarily non-missense versus missense alterations (86.9% v 13.1%). Twenty-one PTGs were performed in individuals with no family history of GC, and tumor was detected in 33.3% of investigated cases; regarding individuals with a family history of GC, tumor was identified in 85% of cases. PTG remains the best treatment for individuals harboring germline CDH1 mutations and fulfilling specific clinical criteria; in other CDH1-associated conditions, PTG should be suggested, but not strongly recommended. Additional studies are required to assess the cancer risk in those conditions.

COVID-19 outbreak and acute cholecystitis in a Hub Hospital in Milan: wider indications for percutaneous cholecystostomy.

BACKGROUND: COVID-19 pandemic has impacted the Italian National Health Care system at many different levels, causing a complete reorganization of surgical wards. In this context, our study retrospectively analysed the management strategy for patients with acute cholecystitis. METHODS: We analysed all patients admitted to our Emergency Department for acute cholecystitis between February and April 2020 and we graded each case according to 2018 Tokyo Guidelines. All patients were tested for positivity to SARS-CoV-2 and received an initial conservative treatment. We focused on patients submitted to cholecystostomy during the acute phase of pandemic and their subsequent disease evolution. RESULTS: Thirty-seven patients were admitted for acute cholecystitis (13 grade I, 16 grade II, 8 grade III). According to Tokyo Guidelines (2018), patients were successfully treated with antibiotic only, bedside percutaneous transhepatic gallbladder drainage (PC) and laparoscopic cholecystectomy (LC) in 29.7%, 21.6% and 48.7% of cases respectively. Therapeutic strategy of three out of 8 cases, otherwise fit for surgery, submitted to bedside percutaneous transhepatic gallbladder drainage (37.5%), were directly modified by COVID-19 pandemic: one due to the SARS-CoV-2 positivity, while two others due to unavailability of operating room and intensive care unit for post-operative monitoring respectively. Overall success rate of percutaneous cholecystostomy was of 87.5%. The mean post-procedural hospitalization length was 9 days, and no related adverse events were observed apart from transient parietal bleeding, conservatively treated. Once discharged, two patients required readmission because of acute biliary symptoms. Median time of drainage removal was 43 days and only 50% patients thereafter underwent cholecystectomy. CONCLUSIONS: Percutaneous cholecystostomy has shown to be an effective and safe treatment thus acquiring an increased relevance in the first phase of the pandemic. Nowadays, considering we are forced to live with the SARS-CoV-2 virus, PC should be considered as a virtuous, alternative tool for potentially all COVID-19 positive patients and selectively for negative cases unresponsive to conservative therapy and unfit for surgery.

Sleep disturbances: one of the culprits of obesity-related cardiovascular risk?

Growing evidence suggested that Sleep Disorders (SD) could increase the risk of developing obesity and could contribute to worsen obesity-related cardiovascular risk. Further, obesity per se has been reported to blunt sleep homeostasis. This happens through several mechanisms. First of all, the excessive adipose tissue at neck and chest levels could represent a mechanical obstacle to breathe. Moreover, the visceral adipose tissue is known to release cytokines contributing to low-grade chronic inflammation that could impair the circadian rhythm. Also, nutrition plays an important role in sleep homeostasis. High fat and/or high carbohydrate diets are known to have a negative impact on both sleep quality and duration. In addition, obesity predisposes to a condition called "obstructive sleep apnea" that has a detrimental effect on sleep. SD could increase the risk and/or could contribute to worsen cardiovascular risk usually associated with obesity. The chronic low grade inflammation associated with obesity has been reported to increase the risk of developing hypertension, type 2 diabetes and dyslipidemia. In turn, improving quality of sleep has been reported to improve the management of these cardiovascular risk factors. Thus, the aim of this manuscript is to provide evidence on the association of obesity and SD and on how they could contribute to the risk of developing cardiovascular risk factors such as hypertension, dyslipidemia and type 2 diabetes in obesity.

Surgical Strategy During the COVID-19 Pandemic in a University Metropolitan Hospital in Milan, Italy.

The COVID-19 pandemic has spread rapidly, forcing some drastic changes not only in our daily lives, but also in our clinical and surgical activities. Given our extensive Italian experience, we hereby describe how our surgical unit activity has changed and how, in some cases, it was necessary to modify surgical strategies. We hope our experience can be shared with our global colleagues who are suffering under similar condition.

Parathyroid carcinoma.

Parathyroid carcinoma (PC) is a rare disease with an indolent behavior due to the low malignant potential. The etiology is unknown. Somatic mutations of CDC73 gene, the same gene involved in the hyperparathyroidism-jaw tumor syndrome, can be identified in up to 70% of patients with PC and in one-third of cases the mutations are germline. Therefore, in patients who carry germline CDC73 gene mutations, its finding permits to identify the carriers among relatives and sometimes to early detect a parathyroid lesion in such subjects. The diagnosis of PC is commonly made after surgery, however there are some clinical/biochemical features that should raise the suspicion of PC, namely markedly elevated serum calcium and PTH levels, a large parathyroid lesion with suspected ultrasonographic features of malignancy, the damages of kidney and bones. The best chance of cure is the complete surgical resection with the en-bloc excision at the first operation, however several recurrences are often observed during the follow-up. Since PC is an indolent tumor with long-lasting survival and the death is due to complications of untreatable hypercalcemia, multiple surgical interventions with debulking of tumoral tissues along with medical treatment for reducing hypercalcemia are often needed. Patients with PC should be followed up along their lifetime.

Efficacy and Safety of Everolimus in Extrapancreatic Neuroendocrine Tumor: A Comprehensive Review of Literature.

BACKGROUND: Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs. PATIENTS AND METHODS: A systematic review of the published data was performed concerning the use of everolimus in extrapancreatic NET, with the aim of summarizing the current knowledge on its efficacy and tolerability. Moreover, the usefulness of everolimus was evaluated according to the different sites of the primary. RESULTS: The present study included 22 different publications, including 874 patients and 456 extrapancreatic NETs treated with everolimus. Nine different primary sites of extrapancreatic NETs were found. The median progression-free survival ranged from 12.0 to 29.9 months. The median time to progression was not reached in a phase II prospective study, and the interval to progression ranged from 12 to 36 months in 5 clinical cases. Objective responses were observed in 7 prospective studies, 2 retrospective studies, and 2 case reports. Stabilization of the disease was obtained in a high rate of patients, ranging from 67.4% to 100%. The toxicity of everolimus in extrapancreatic NETs is consistent with the known safety profile of the drug. Most adverse events were either grade 1 or 2 and easy manageable with a dose reduction or temporary interruption and only rarely requiring discontinuation. CONCLUSION: Treatment with everolimus in patients with extrapancreatic NETs appears to be a promising strategy that is safe and well tolerated. The use of this emerging opportunity needs to be validated with clinical trials specifically designed on this topic. IMPLICATIONS FOR PRACTICE: The present study reviewed all the available published data concerning the use of everolimus in 456 extrapancreatic neuroendocrine tumors (NETs) and summarized the current knowledge on the efficacy and safety of this drug, not yet approved except for pancreatic NETs. The progression-free survival rates and some objective responses seem promising and support the extension of the use of this drug. The site-by-site analysis seems to suggest that some subtypes of NETs, such as colorectal, could be more sensitive to everolimus than other primary NETs. No severe adverse events were usually reported and discontinuation was rarely required; thus, everolimus should be considered a valid therapeutic option for extrapancreatic NETs.

Para- and perirenal fat thickness is an independent predictor of chronic kidney disease, increased renal resistance index and hyperuricaemia in type-2 diabetic patients.

BACKGROUND: Many interfering factors may reduce the reliability of waist circumference (WC) measurement in estimating the risk for chronic kidney disease (CKD) associated with obesity. Therefore, we determined the independent associations of para- and perirenal ultrasonographic fat thickness with the main markers of kidney function. METHODS: A cross-sectional study was performed in 151 type-2 diabetic subjects. Para- and perirenal fat thickness was measured from the inner side of the abdominal musculature to the surface of the kidneys. CKD was defined as eGFR < 60 mL min(-1)1.73 m(-2). RESULTS: Using both univariate and multivariate regression analyses, eGFR, renal resistance index and uricaemia were best predicted by para- and perirenal fat thickness even when BMI and waist circumference were further added in the statistical model (r(2): 0.366, P = 0.001; r(2): 0.529, P = 0.005; r(2): 0.310, P = 0.026, respectively), whereas waist circumference and BMI did not contribute independently of para- and perirenal fat thickness. Albuminuria was predicted by waist circumference but not by para- and perirenal fat thickness. In subjects with waist circumference above the diagnostic values of metabolic syndrome (48M/59F), eGFR significantly and progressively declined across tertiles of para- and perirenal fat thickness (87.0 ± 27.9 vs 83.5 ± 26.0 vs 62.3 ± 30.6 mL min(-1) 1.73 m(-2), adjusted P < 0.0001) despite comparable waist circumference, and an increasing frequency of CKD was observed across tertiles of subjects with waist circumference both below and above the metabolic syndrome diagnostic values (P < 0.05). CONCLUSIONS: Para- and perirenal fat thickness is an independent predictor of kidney dysfunction in type-2 diabetes explaining an important proportion of the variance of eGFR, renal resistance index and uricaemia.

Waist circumference is strongly associated with renal resistive index in normoalbuminuric patients with type 2 diabetes.

OBJECTIVE: Anthropometric parameters may play a role in modulating the risk of kidney dysfunction. The aim of this study was to evaluate whether anthropometric indices and the metabolic syndrome are associated with alterations of the renal resistive index (RI) in normoalbuminuric type 2 diabetic (T2DM) patients. METHODS: A sample of 99 consecutively recruited patients with T2DM (76 male and 23 female) was examined. The RI was assessed by duplex Doppler sonography. RESULTS: In univariate analysis, a significant association between the RI values and age (r = 0.507, p < 0.0001), gender (being higher in women, p = 0.002), systolic blood pressure (r = 0.285, p = 0.011), smoking habit (being lower in current smokers, p = 0.047), estimated glomerular filtration rate (r = -0.435, p < 0.0001), and intima-media thickness of the carotid arteries (r = 0.271, p = 0.020) was observed. As far as anthropometric parameters are concerned, a strong correlation between waist circumference (WC; r = 0.401, p < 0.0001), BMI (r = 0.337, p = 0.003) and RI values was found but only WC maintained a significant correlation after adjusting for several confounders (p = 0.001). CONCLUSIONS: In normoalbuminuric T2DM patients, the intrarenal hemodynamic abnormalities seem primarily associated with WC.