SIMEU position paper on non-invasive respiratory support in COVID-19 pneumonia.

The rapid worldwide spread of the Coronavirus disease (COVID-19) crisis has put health systems under pressure to a level never experienced before, putting intensive care units in a position to fail to meet an exponentially growing demand. The main clinical feature of the disease is a progressive arterial hypoxemia which rapidly leads to ARDS which makes the use of intensive care and mechanical ventilation almost inevitable. The difficulty of health systems to guarantee a corresponding supply of resources in intensive care, together with the uncertain results reported in the literature with respect to patients who undergo early conventional ventilation, make the search for alternative methods of oxygenation and ventilation and potentially preventive of the need for tracheal intubation, such as non-invasive respiratory support techniques particularly valuable. In this context, the Emergency Department, located between the area outside the hospital and hospital ward and ICU, assumes the role of a crucial junction, due to the possibility of applying these techniques at a sufficiently early stage and being able to rapidly evaluate their effectiveness. This position paper describes the indications for the use of non-invasive respiratory support techniques in respiratory failure secondary to COVID-19-related pneumonia, formulated by the Non-invasive Ventilation Faculty of the Italian Society of Emergency Medicine (SIMEU) on the base of what is available in the literature and on the authors' direct experience. Rationale, literature, tips & tricks, resources, risks and expected results, and patient interaction will be discussed for each one of the escalating non-invasive respiratory techniques: standard oxygen, HFNCO, CPAP, NIPPV, and awake self-repositioning. The final chapter describes our suggested approach to the failing patient.

Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment modality for patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs). The aim of this study was to determine the time to progression of patients treated with PRRT and to identify the prognostic factors related to treatment response. METHODS: Patients with sporadic GEP NETs prospectively treated with PRRT were retrospectively analysed. The primary end point was progression-free survival (PFS). RESULTS: A total of 69 patients (37 men and 32 women; 45 with pancreatic and 24 with gastrointestinal lesion; 22 NET G1 and 41 NET G2) were treated with (90)Y or (177)Lu. The objective response rate was 27.5% (partial response, PR), while 50.7% had stable disease and 23.2% had progressive disease. Significant differences in PFS were observed in relationship to the stage of the disease (44 months for stage III, 23 months for stage IV), the evidence of a PR 6 months after the end of the PRRT (39 months in patients with a PR, 22 months in patients without a PR) and previous transarterial chemoembolization (TACE, yes 13 months vs no 31 months). Stage IV, NET G2 and previous TACE were found to be significant factors for tumour progression at multivariate analysis. CONCLUSION: Low tumour burden and a low proliferation index represent independent prognostic factors for long PFS, while previous chemoembolization techniques represent independent prognostic factors for early tumour progression and shorter PFS. Our data suggest that chemoembolization techniques to reduce the hepatic tumour burden should be avoided.

Risk factors for disease progression in advanced jejunoileal neuroendocrine tumors.

BACKGROUND: Knowledge of clinical course in advanced jejunoileal neuroendocrine tumors (NETs) is poor. AIM: To investigate progression-free survival (PFS), overall survival (OS), and possible predictors for disease progression (DP) in advanced jejunoileal NETs. PATIENTS AND METHODS: We carried out a multicenter, retrospective analysis of incoming patients with sporadic advanced jejunoileal NETs. PFS and OS were assessed by Kaplan-Meier analysis. Risk factors for progression were analyzed by the Cox proportional hazards method. RESULTS: Of the 114 patients enrolled, 46.5% had functioning tumors, 93.9% had stage IV disease, and 57.3 and 42.7% were G1 and G2 tumors, respectively. During a median follow-up of 48 months (interquartile range 29-84 months), DP occurred in 61.4% of patients, after 19 months (interquartile range 10-41 months) from diagnosis. Median PFS was 36 months. The 2-year and 5-year PFS were 59 and 33%, respectively, while 5-year OS was 77.5%. Ki67 was the sole strong independent risk factor for unfavorable outcome according to multivariate analysis, being significantly associated with both PFS and OS. CONCLUSIONS: DP occurred in the majority of patients with advanced jejunoileal NETs, with median PFS being 36 months. Ki67 was a significant predictor of DP and should be considered in determining appropriate treatments and planning follow-up for these patients.

Pancreatic endocrine tumors less than 4 cm in diameter: resect or enucleate? a single-center experience.

OBJECTIVE: Pancreatic endocrine tumors (PETs) are usually small, benign or low-grade malignant, and surgery should preserve the pancreatic parenchyma as much as possible. The aim of the study was to evaluate the postoperative and long-term survival of patients undergoing enucleation in small PETs. METHODS: Of 82 patients having PETs, 46 with tumor less than 4 cm in diameter, without distant metastases and with R0 resection by final pathologic examination, were included in this study. Enucleation was performed when the tumor did not involve the main pancreatic duct and in the absence of peripancreatic lymphadenopathy (group A); a typical resection was carried out in all other cases (group B). The 2 groups were compared regarding postoperative mortality and morbidity, pancreatic fistula, postoperative hospital stay, reoperation, World Health Organization classification, TNM stage, recurrence, and long-term survival. RESULTS: There were 15 patients (32.6%) in group A and 31 (67.4%) in group B. Postoperative and long-term results were similar in the 2 groups, whereas World Health Organization classification was significantly different; enucleation was performed more frequently than typical R0 resection in benign tumors (P = 0.009). CONCLUSIONS: Enucleation should be reserved for patients having benign PETs less than 4 cm in diameter and far from the main pancreatic duct.

Standardized uptake values of (68)Ga-DOTANOC PET: a promising prognostic tool in neuroendocrine tumors.

UNLABELLED: Despite the fact that several studies have been published regarding the prognostic factors of neuroendocrine tumors (NETs), there are some cases in which available data are not sufficient to predict disease progression and to define a correct therapeutic approach. To our knowledge, the role of maximum standardized uptake value (SUVmax) as a prognostic factor has never been studied in NET patients. Therefore, we prospectively investigated whether (68)Ga-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-octreotide ((68)Ga-DOTANOC) PET SUVmax could be used as an accurate noninvasive marker for disease prognosis. METHODS: Forty-seven patients with NETs were studied with (68)Ga-DOTANOC PET. All patients underwent a baseline visit and laboratory and radiologic examinations. Follow-up was performed in all cases. RESULTS: SUVmax was significantly higher in patients with pancreatic NET and in those with well-differentiated NETs. Moreover, SUVmax was significantly higher in patients with an elevated expression of 2A-somatostatin receptor. During the follow-up, the disease was stable or presented a partial response in 25 patients, and in 19 cases the disease progressed. The patients with stable disease or a partial response had an SUVmax significantly higher than did those in the progressive disease group, with the best cutoff ranging from 17.9 to 19.3. At univariate and multivariate analysis, the significant positive prognostic factors were well-differentiated NET, an SUVmax of 19.3 or more, and a combined treatment with long-acting somatostatin analogs and radiolabeled somatostatin analogs. CONCLUSION: We demonstrated, for the first time to our knowledge, that (68)Ga-DOTANOC PET SUVmax correlates with the clinical and pathologic features of NETs and is also an accurate prognostic index.

Patient-reported outcomes in patients with endocrine tumors of the ileum.

BACKGROUND: Patients with ileal endocrine tumors have a good survival rate. AIM: To assess the quality of life of patients with endocrine tumors of the ileum. PATIENTS: Forty-four consecutive patients (30 males, 14 females, mean age 61.1 years, range 26-79) with proven endocrine tumor of the ileum were studied. METHODS: Italian version of the SF-12 Health Survey (SF-12) questionnaire able to explore the physical and mental aspects of daily life were used. Forty-four sex-matched and age-matched Italian normative participants were also considered for SF-12 evaluation. RESULTS: The overall analysis of the SF-12 questionnaire in the 44 patients showed values of physical component summary (PCS) and mental component summary (MCS) scores representative of a relatively good quality of life and not significantly different from those of the normative population (PCS: 46.5+/-10.3 vs. 47.0+/-4.7, P = 0.792; MCS: 45.9+/-10.8 vs. 49.1+/-2.0, P = 0.057). PCS was significantly impaired in nonsmokers (P = 0.028), in those who underwent less invasive surgery (P = 0.007), in those who had pain at onset of the disease (P = 0.002), and in those who received multimodality treatment (P = 0.013). To evaluate the factors independently related to PCS, a multivariate analysis was performed and we found that specific surgery (P = 0.046) and presence of pain at onset of the disease (P = 0.001) were the only two factors that showed an independent relationship with PCS. CONCLUSION: The patients with endocrine tumor of the ileum seem to perceive their quality of life as relatively good.

Plasma acylated ghrelin levels are higher in patients with chronic atrophic gastritis.

OBJECTIVES: Ghrelin is mainly produced by the endocrine cells of the gastric oxyntic mucosa. For this reason we decided to investigate the modification of the circulating levels not only of total but also of acylated ghrelin in a series of patients with chronic atrophic gastritis. DESIGN: Twenty-five patients with chronic atrophic gastritis and 25 healthy subjects were studied. In all 50 subjects gastrin and total and acylated ghrelin levels were evaluated. All patients underwent endoscopy with multiple biopsies, and the possibility of Helicobacter pylori infection was investigated. RESULTS: Significantly higher acylated ghrelin levels (82.8 +/- 61.3 vs. 35.1 +/- 17.1 pmol/l), acylated/total ghrelin ratio (0.422 +/- 0.202 vs. 0.152 +/- 0.085) and gastrin levels (1071 +/- 816 vs. 66 +/- 22 ng/l) were observed in the 25 patients with chronic atrophy than in the healthy subjects. Otherwise, no significant relationships were found when total ghrelin was correlated with the presence of atrophy, or with gastrin levels. In the healthy subjects, but not in the patients, acylated and total ghrelin levels were significantly higher in female than in male patients. CONCLUSIONS: The increase in acylated ghrelin levels and in the acylated/total ghrelin ratio in patients with atrophy of the body and fundus can be explained by hypothesizing an increase in the acylating process in the presence of gastric atrophy. It suggests that there may be a compensatory increase in plasma active ghrelin concentration in response to gastric atrophy, a condition which causes a loss of ghrelin-producing cells and an increase in gastric pH.

Chromogranin A: is it a useful marker of neuroendocrine tumors?

PURPOSE: We evaluated the pattern of chromogranin A (CgA) plasma levels in a large number of patients with neuroendocrine tumors (NETs), in a series of patients with chronic atrophic gastritis (CAG) with and without enterochromaffin-like (ECL) cell hyperplasia, and in healthy participants (HPs). PATIENTS AND METHODS: Two hundred thirty-eight patients with NETs, 42 patients with CAG with or without ECL cell hyperplasia, and 48 HPs were studied. All patients underwent a baseline visit, biochemical routine check-up, imaging techniques, endoscopy, and histologic determination. RESULTS: CgA plasma levels were higher in patients with NETs compared with CAG patients or HPs (P < .001). In the NET group, we observed higher CgA levels in patients with diffuse disease compared with patients with local or hepatic disease (P < .001). CgA plasma levels were significantly higher in patients with Zollinger-Ellison syndrome compared with other types of endocrine tumors (P < .001). We found the best cutoff range between HPs and NET patients to be 18 to 19 U/L (sensitivity, 85.3%; specificity, 95.8%). Comparing all participants without neoplasia (HPs, CAG patients, and disease-free patients) and patients with endocrine tumors, the best cutoff range was 31 to 32 U/L (sensitivity, 75.3%; specificity, 84.2%). Setting the specificity at 95%, the cutoff range was 84 to 87 U/L (sensitivity, 55%). CONCLUSION: Our study confirms the high specificity and sensitivity of CgA in diagnosing an endocrine tumor. It is necessary to use a cutoff range of 84 to 87 U/L to obtain a high specificity in diagnosing NETs, with the aim of excluding patients in whom the CgA was elevated as a result of other non-neoplastic diseases.

Endocrine tumors of the ileum: factors correlated with survival.

AIM: To evaluate the most important factors correlated with survival in patients with endocrine tumors of the ileum, both at the time of diagnosis and during the follow-up period. METHODS: Fifty-nine patients with ileal endocrine tumors diagnosed in our institution between 1990 and 2004 were studied. RESULTS: The study included 36 men (61%) and 23 women (39%). The median age of the patients at the time of diagnosis was 61.4 (range 18-83) years. The median follow-up period was 71.9 (range 5-287) months. Forty patients (67.8%) were still alive at the end of the study; the median survival time was 172 months, and the 5-year survival rate was 78.9%. By univariate analysis, the survival rate was significantly related to female sex (p = 0.024) and flushing alone (p = 0.028) and associated with diarrhea at diagnosis (p = 0.015), weight loss at diagnosis (p = 0.038), Ki-67 level (p = 0.025), stage of disease at diagnosis (p = 0.012), presence of liver metastases at follow-up (p = 0.005), presence of diffuse metastases at diagnosis (p = 0.005) and at follow-up (p = 0.007), and type of surgical approach (overall: p = 0.018; not operated vs. radical surgery: p = 0.008; not operated vs. palliative surgery: p = 0.045). Using multivariate analysis, only female gender (p = 0.012) and the presence of liver metastases at follow-up (p = 0.004) were significantly related to survival. CONCLUSION: In the present study, female gender and the appearance of liver metastases at follow-up seem to be the main conditions which determine the poor prognosis of patients with ileal endocrine tumors.