Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

<p>Abstract</p> <p>Background</p> <p>Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma.</p> <p>Methods</p> <p>Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m²daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival.</p> <p>Results</p> <p>Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable.</p> <p>Conclusion</p> <p>Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future.</p> <p>Trial registration</p> <p>NCT00953394</p

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

EFFETTI DELL’ATTIVITA’ FISICA SULLA FUNZIONE ENDOTELIALE IN ATLETI VETERANI

L’invecchiamento è caratterizzato da modificazioni strutturali e funzionali della parete arteriosa.Tali modificazioni includono un aumento dello spessore medio-intimale ed una ridotta compliance dei vasi di grosso calibro. Lo scopo del nostro studio è quello di valutare, in un gruppo di atleti veterani, gli effetti dell’attività fisica di endurance sulle modificazioni della funzione endoteliale indotti dall’invecchiamento, confrontandola con un gruppo di anziani sani sedentari. La funzione endoteliale è stata valutata mediante la flow-mediated-dailation (FMD) a livello dell’arteria omerale, prima e dopo un follow-up di dieci anni. I risultati dello studio hanno dimostrato una marcata riduzione della vasodilatazione, endotelio-mediata, nei soggetti sedentari rispetto agli atleti veterani, nei quali l’esercizio fisico regolare sembra prevenire la disfunzione endoteliale indotta dall’invecchiamento

A multicentre observational study evaluating the effectiveness of a phlebotomy check-list in reducing preanalytical errors

Several preanalytical errors are attributable to inappropriate or poorly standardized activities during the venous blood collection. We designed a multicenter observational study to establish whether the implementation of a phlebotomy check-list in 7 phlebotomy centers and 4 emergency departments is effective in reducing the rate of preanalytical errors related to the blood drawing. The investigation was divided in two 3-month periods during which 5 common preanalytical errors were systematically recorded. After the introduction of the phlebotomy check-list, the rate of preanalytical errors was significantly decreased in phlebotomy centers (0.04% vs. 0.05%, P=0.001), but remained unchanged in emergency departments (0.83% vs. 0.82%, P=0.84). A significant decrease was achieved for sample identification errors and clotted specimens in phlebotomy centers and emergency departments, whereas a significant reduction in hemolysis was noticed only in phlebotomy centers. The rate of inappropriate filling and wrong containers remained unchanged. The results obtained in this study show that the introduction of a phlebotomy check-list may help in reducing preanalytical errors related to misidentification and undue clotting

Blood collection systems in clinical laboratories: local adaptation of the EFLM guidelines

The importance of the process of purchasing or changing blood collection devices is often overlooked. This is likely attributable to many factors such as the limited knowledge that policymakers, healthcare administrators and also laboratory managers have on the significance of preanalytical quality, but also to the lack of validated criteria for analyzing the quality of blood collection devices. Since a gap remains to be filled between companies\u2019 and laboratory\u2019s validation, the EFLM Working Group on Preanalytical Phase (WG-PRE) has published a comprehensive document, which contains essential prerequisites and technical issues (e.g., physical imperfections, defects of functioning, safety deficiencies) to support local clinical laboratories for the development of tenders for blood tubes and for the validation of new materials ahead of local routine use. This consensus document is a national adaptation of these guidelines

Phenotype microarray analysis may unravel genetic determinants of the stress response by Rhodococcus aetherivorans BCP1 and Rhodococcus opacus R7

In the present study, the response of Rhodococcus aetherivorans BCP1 and Rhodococcus opacus R7 to various stress conditions and several antimicrobials was examined by PM in relation with genetic determinants, as revealed by annotation analysis of the two genomes. Comparison between metabolic activities and genetic features of BCP1 and R7 provided new insight into the environmental persistence of these two members of the genus Rhodococcus

Effect of physical activity on heart rate variability and carotid intima-media thickness in older people

We investigated the effect of physical activity on heart rate variability (HRV) and carotid intima-media thickness (IMT) in elderly subjects and the relationship between HRV and IMT. Thirty-two elderly sedentary subjects and 32 age-matched endurance athletes underwent ultrasonography of the carotid wall for measuring IMT, and 24-h ECG monitoring for measuring HRV. Elderly athletes had evidence of increased vagal activity in the time (SDANN, rMSSD, and pNN50; p < 0. 01) and frequency domain (HF and LF/HF ratio, p < 0. 01) with respect to sedentary subjects. Moreover, athletes showed lower IMT than control subjects (p < 0. 01). In the whole population SDNN was inversely related to IMT, respectively (r = -0. 60 and r = -0. 58, p < 0. 0001), while LF/HF ratio related positively to IMT. In conclusion, this study demonstrated that in aging HRV is negatively associated with IMT, a putative index of atherosclerosis, confirming cardiac autonomic neuropathy as part of the pathophysiological pathway for atherosclerosis. It confirms that the regular physical activity represents a valuable strategy to counter age-related impairments of cardiac autonomic activity and artery structural changes. © 2013 SIMI

Awake Major Abdominal Surgeries in the COVID-19 Era

Background. During the outbreak of coronavirus disease 2019 (COVID-19), allocating intensive care beds to patients needing acute care surgery became a very difficult task. Moreover, since general anesthesia is an aerosol-generating procedure, its use became controversial. This strongly restricted therapeutic strategies. Here, we report a series of undeferrable surgical cases treated with awake surgery under neuraxial anesthesia. Contextual benefits of this approach are deepened. Methods. During the first pandemic surge, thirteen patients (5 men and 8 women) with a mean age of 80 years, needing undelayable surgery due to abdominal emergencies, underwent awake open surgery at our Hospital. Prior to surgery, all patients underwent nasopharyngeal swab tests for COVID-19 diagnosis. In all cases, regional anesthesia (spinal, epidural, or combined spinal-epidural anesthesia) was performed. Intraoperative and postoperative pain intensities have been monitored and regularly assessed. A distinct pathway has been set up to keep patients of uncertain COVID-19 diagnosis separated from all other patients. Postoperative course has been examined. Results. The mean operative time was 87 minutes (minimum 60 minutes; maximum 165 minutes). In one case, conversion to general anesthesia was necessary. Postoperative pain was always well controlled. None of them required postoperative intensive care support. No perioperative major complications (Clavien–Dindo ≥3) occurred. Early readmission after surgery never occurred. All nasopharyngeal swabs resulted negative. Conclusions. In our experience, awake laparotomy under regional anesthesia resulted feasible, safe, painless, and, in specific cases, was the only viable option. This approach allowed prevention of the need of postoperative intensive monitoring during the COVID-19 era. In such a peculiar time, we believe it could become part of an ICU-preserving strategy and could limit viral transmission inside theatres