Short- and Long-Term Advantages of Laparoscopic Gastrectomy for Elderly Patients with Locally Advanced Cancer.

Minimally invasive surgery has provided several clinical advantages in locally advanced gastric cancer (LAGC) care, although a consensus on its application criteria remains unclear. Surgery remains a careful choice in elderly patients, who frequently present with frailty, comorbidities, and other disabling diseases. This study aims to assess the possible advantages of laparoscopic gastric resections in elderly patients presenting with LAGC. This retrospective study analyzed a single-center series of elderly patients (≥75 years) undergoing curative resections for LAGC between 2015 and 2020. A comparative analysis of open versus laparoscopic approaches was conducted, focusing on postoperative complications, length of hospital stay (LOS), and long-term survival. A total of 62 patients underwent gastrectomy through an open or a laparoscopic approach (31 pts each). The study population did not show statistically significant differences in demographics, operative risk, and neoadjuvant chemotherapy. The laparoscopic group reported significantly minimized overall complications (45.2 vs. 71%, p = 0.039) and pulmonary complications (0 vs. 9.7%, p = 0.038) as well as a shorter LOS (8 vs. 12 days, p = 0.007). Lymph node harvest was equal between the groups, although long-term overall survival presented significantly better after laparoscopic gastrectomy (p = 0.048), without a relevant difference in terms of disease-free and disease-specific survivals. Laparoscopic gastrectomy proves effective in elderly LAGC patients, offering substantial short- and long-term postoperative benefits.

Implementing protocol-based relaparoscopy for severe complications in laparoscopic colorectal surgery.

BACKGROUND: Although laparoscopy has demonstrated growing applications for either primary colorectal resections or reoperations, no standardized criteria for implementing laparoscopy in revisional surgery have been reported. This study analyzes a single-center series of major complications after laparoscopic colorectal surgery, undergoing laparoscopic (LR), or open reoperations in compliance with a hemodynamics-based institutional management. METHODS: This study retrospectively analyzes a series of consecutive patients who primarily underwent either laparoscopic left colectomy or low anterior resection in a tertiary referral center between 2016 and 2021. Major complications requiring reoperation (MCR) were managed through an interdisciplinary protocol and submitted to reoperation according to patient hemodynamics and intra-abdominal contamination. A cohort analysis primarily assessed treatment failure rates (i.e., 90-day mortality and need for further surgery), while postoperative morbidity was secondarily examined. RESULTS: Out of 1137 laparoscopic colorectal resections, 497 patients met eligibility criteria, while 45 (9.1%) developed MCRs were managed according to the standardized interdisciplinary protocol. Revisional surgery was performed through either LR (66.7%) or (33.3%). Treatment failure was 13.3% overall, including additional surgery (11.1%) and 90-day mortality (6.6%) after reoperation. In both overall and anastomotic leak-specific MCRs, relaparoscopy resulted in minimized length of hospital stay, postoperative morbidity, and intensity of care. CONCLUSIONS: Relaparoscopy for MCR preserves clinical benefits related to minimally invasive colorectal surgery. Further studies should investigate applicative determinants and impediments related to the center volume.

[Management of patent foramen ovale in non-cardiac surgery]. / Gestione della pervietà del forame ovale nella chirurgia non cardiaca.

Patent foramen ovale (PFO) is a remnant of normal fetal anatomy which may persist into adulthood, mostly asymptomatic. In some adults, PFO may result in a potential for shunting venous thromboembolism to the arterial circulation; less frequently it can cause interatrial, right-to-left shunting of deoxygenated blood. The pathogenesis of several medical conditions is related to the presence of PFO. Some randomized clinical trials have shown evidence of benefit for device closure as compared with medical therapy in patients with cryptogenic stroke. The literature reported several cases of carbon dioxide embolism during general laparoscopic surgery and sometimes stroke after laparoscopic or neurosurgery but there are neither prospective studies addressing these issues, nor randomized clinical trials assessing the effectiveness of pharmacotherapy or interventional procedures at decreasing risk. The European position paper suggests routine monitoring in non-cardiac surgery of patients with a PFO and no actual indications for closure. This article aims to further stratify the risk of periprocedural stroke and paradoxical embolism in this category of patients.

Methylene Blue Reduces Mortality in Critically Ill and Perioperative Patients: A Meta-Analysis of Randomized Trials.

Vasodilatory hypotension is common in critically ill and perioperative patients, and is associated with adverse outcomes. As a nitric oxide production inhibitor, methylene blue (MB) exerts its vasoconstrictor property and is an adjuvant for catecholamine-refractory vasodilatory shock. However, the effects of MB on clinically relevant outcomes remain unclear. Therefore, the authors performed a meta-analysis of randomized trials on MB in critically ill and perioperative patients. The authors searched through databases for randomized trials on MB in critically ill and perioperative patients, which yielded 11 studies consisting of 556 patients. The primary outcome was mortality at the longest follow-up. Secondary outcomes included hemodynamic parameters and organ dysfunction (PROSPERO: CRD42023409243). Nine out of the 11 included randomized trials reported mortality, which was significantly lower in the MB group (risk ratio, 0.60 [95% CI 0.43-0.84] p = 0.003), with findings confirmed in septic shock and cardiac surgery subgroups. The authors found reduced lengths of stay in the intensive care unit (mean difference [MD], -0.9 days [95% CI -1.06 to -0.77] p < 0.001) and in the hospital (MD, -2.2 days [95% CI, -2.68 to -1.70] p < 0.001) in the MB group. MB was associated with increased mean arterial pressure (MD, 8.4 mmHg [95% CI 5.01-11.75] p < 0.001) and systemic vascular resistance (MD, 94.5 dyn/s/cm5 [95% CI 17.73-171.15] p = 0.02), with no difference in cardiac output (standardized MD, 0.16 [95% CI, -0.25 to 0.57] p = 0.45). This meta-analysis showed that MB reverses vasodilation in critically ill and perioperative patients and might improve survival. Further adequately powered randomized trials are needed to confirm these findings.

Positive single-center randomized trials and subsequent multicenter randomized trials in critically ill patients: a systematic review.

BACKGROUND: It is unclear how often survival benefits observed in single-center randomized controlled trials (sRCTs) involving critically ill patients are confirmed by subsequent multicenter randomized controlled trials (mRCTs). We aimed to perform a systemic literature review of sRCTs with a statistically significant mortality reduction and to evaluate whether subsequent mRCTs confirmed such reduction. METHODS: We searched PubMed for sRCTs published in the New England Journal of Medicine, JAMA, or Lancet, from inception until December 31, 2016. We selected studies reporting a statistically significant mortality decrease using any intervention (drug, technique, or strategy) in adult critically ill patients. We then searched for subsequent mRCTs addressing the same research question tested by the sRCT. We compared the concordance of results between sRCTs and mRCTs when any mRCT was available. We registered this systematic review in the PROSPERO International Prospective Register of Systematic Reviews (CRD42023455362). RESULTS: We identified 19 sRCTs reporting a significant mortality reduction in adult critically ill patients. For 16 sRCTs, we identified at least one subsequent mRCT (24 trials in total), while the interventions from three sRCTs have not yet been addressed in a subsequent mRCT. Only one out of 16 sRCTs (6%) was followed by a mRCT replicating a significant mortality reduction; 14 (88%) were followed by mRCTs with no mortality difference. The positive finding of one sRCT (6%) on intensive glycemic control was contradicted by a subsequent mRCT showing a significant mortality increase. Of the 14 sRCTs referenced at least once in international guidelines, six (43%) have since been either removed or suggested against in the most recent versions of relevant guidelines. CONCLUSION: Mortality reduction shown by sRCTs is typically not replicated by mRCTs. The findings of sRCTs should be considered hypothesis-generating and should not contribute to guidelines.

Intraoperative hypotension and postoperative outcomes: a meta-analysis of randomised trials.

INTRODUCTION: Intraoperative hypotension is associated with adverse postoperative outcomes; however these findings are supported only by observational studies. The aim of this meta-analysis of randomised trials was to compare the postoperative effects permissive management with targeted management of intraoperative blood pressure. METHODS: We searched PubMed, Cochrane, and Embase up to June 2023 for studies comparing permissive (mean arterial pressure ≤60 mm Hg) with targeted (mean arterial pressure >60 mm Hg) intraoperative blood pressure management. Primary outcome was all-cause mortality at the longest follow-up available. Secondary outcomes were atrial fibrillation, myocardial infarction, acute kidney injury, delirium, stroke, number of patients requiring transfusion, time on mechanical ventilation, and length of hospital stay. RESULTS: We included 10 randomised trials including a total of 9359 patients. Mortality was similar between permissive and targeted blood pressure management groups (89/4644 [1.9%] vs 99/4643 [2.1%], odds ratio 0.88, 95% confidence interval [CI], 0.65-1.18, P=0.38, I2=0% with nine studies included). Atrial fibrillation (102/3896 [2.6%] vs 130/3887 [3.3%] odds ratio 0.71, 95% CI 0.53-0.96, P=0.03, I2=0%), and length of hospital stay (mean difference -0.20 days, 95% CI -0.26 to -0.13, P<0.001, I2=0%) were reduced in the permissive management group. No significant differences were found in subgroup analysis for cardiac and noncardiac surgery. CONCLUSION: Pooled randomised evidence shows that a target intraoperative mean arterial pressure ≤60 mm Hg is not associated with increased mortality; nevertheless it is surprisingly associated with a reduced rate of atrial fibrillation and of length of hospital stay. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023393725.

Etomidate as an induction agent for endotracheal intubation in critically ill patients: A meta-analysis of randomized trials.

PURPOSE: We performed a meta-analysis of randomized controlled trials to evaluate if etomidate impacted mortality in critically ill adults when compared with other induction agents. MATERIALS AND METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials which compared etomidate with any other induction agent in critically ill adult patients undergoing endotracheal intubation. The primary outcome was mortality at the main timepoint defined by the study. We conducted a fixed-effects meta-analysis for the risk ratio. Using that risk ratio and 95% confidence interval, we then estimated the probability of any harm (RR > 1) and the number needed to harm ≤100 (RR ≥ 1.05). RESULTS: We included 11 randomized trials comprising 2704 patients. We found that etomidate increased mortality (319/1359 [23%] vs. 267/1345 [20%]; risk ratio (RR) = 1.16; 95% confidence interval (CI), 1.01-1.33; P = 0.03; I2 = 0%; number needed to harm = 31). The probabilities of any increase and a 1% increase (NNH ≤100) in mortality were 98.1% and 92.1%, respectively. CONCLUSIONS: This meta-analysis found a high probability that etomidate increases mortality when used as an induction agent in critically ill patients with a number needed to harm of 31.

Propofol and survival: an updated meta-analysis of randomized clinical trials.

BACKGROUND: Propofol is one of the most widely used hypnotic agents in the world. Nonetheless, propofol might have detrimental effects on clinically relevant outcomes, possibly due to inhibition of other interventions' organ protective properties. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate if propofol reduced survival compared to any other hypnotic agent in any clinical setting. METHODS: We searched eligible studies in PubMed, Google Scholar, and the Cochrane Register of Clinical Trials. The following inclusion criteria were used: random treatment allocation and comparison between propofol and any comparator in any clinical setting. The primary outcome was mortality at the longest follow-up available. We conducted a fixed-effects meta-analysis for the risk ratio (RR). Using this RR and 95% confidence interval, we estimated the probability of any harm (RR > 1) through Bayesian statistics. We registered this systematic review and meta-analysis in PROSPERO International Prospective Register of Systematic Reviews (CRD42022323143). RESULTS: We identified 252 randomized trials comprising 30,757 patients. Mortality was higher in the propofol group than in the comparator group (760/14,754 [5.2%] vs. 682/16,003 [4.3%]; RR = 1.10; 95% confidence interval, 1.01-1.20; p = 0.03; I2 = 0%; number needed to harm = 235), corresponding to a 98.4% probability of any increase in mortality. A statistically significant mortality increase in the propofol group was confirmed in subgroups of cardiac surgery, adult patients, volatile agent as comparator, large studies, and studies with low mortality in the comparator arm. CONCLUSIONS: Propofol may reduce survival in perioperative and critically ill patients. This needs careful assessment of the risk versus benefit of propofol compared to other agents while planning for large, pragmatic multicentric randomized controlled trials to provide a definitive answer.

Heart Rate Variability in Subjects with Severe Allergic Background Undergoing COVID-19 Vaccination.

Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination is the world's most important strategy for stopping the pandemic. Vaccination challenges the body's immune response and can be complicated by hypersensitivity reactions. The autonomic nervous system can modulate the inflammatory immune response, therefore constituting a potential marker to characterize individuals at high risk of hypersensitivity reactions. Autonomic nervous system functionality was assessed through measurement of the heart rate variability (HRV) in subjects with a history of severe allergic reactions and 12 control subjects. HRV parameters included the mean electrocardiograph RR interval and the standard deviation of all normal R-R intervals (SDNN). All measurements were performed immediately before the anti-SARS-CoV-2 vaccination. The median RR variability was lower in the study than in the control group: 687 ms (645-759) vs. 821 ms (759-902); p = 0.02. The SDNN was lower in the study group than in the control group: 32 ms (23-36) vs. 50 ms (43-55); p < 0.01. No correlation was found between age and the SDNN. Autonomic nervous system activity is unbalanced in people with a severe allergy background.

Development of a predictive model for unplanned intensive care unit admission after pancreatic resection within an enhanced recovery pathway.

BACKGROUND: It is unclear whether routine postoperative admission to the intensive care unit (ICU) can improve outcomes for patients undergoing elective pancreatic surgery. Aim of the study was to determine preoperative and intraoperative predictors of unplanned ICU access in patients undergoing pancreatectomy treated within an established enhanced recovery pathway (ERP) and compare outcomes between direct and late ICU admission. METHODS: A retrospective observational study was conducted on adult patients who underwent pancreatic resection (2015-2019) within an ERP. Patients with preoperatively planned ICU admission were excluded from the study. Multiple multivariate logistic regression models were constructed to verify the association of preoperative and intraoperative variables with study outcomes. RESULTS: The study included 1486 consecutive patients (cancer diagnosis 60%, pancreaticoduodenectomy 60%; laparoscopic approach 20%; vascular resection 9%). Sixty-six (4.4%) patients had an unplanned ICU admission. Direct admission occurred in 22 (33%) patients and late ICU admission in 44 (67%) patients. Mortality was significantly lower in direct admission group (n = 3, 14%) compared to late admission (n = 25, 57%; p > 0.001). A comprehensive model including preoperative and intraoperative variables identified ASA score ≥ 3 (OR 5.59, p value < 0.001), history of hypertension (OR 2.29, p = 0.029), chronic obstructive pulmonary disease (OR 3.05, p = 0.026), proximal pancreatic resection (OR 2.79, p value 0.046), multivisceral resection (OR 8.86, p value < 0.001), high intraoperative blood loss (OR 1.01 per ml, p < 0.001), and increased serum lactate at the end of surgery (OR 1.25, p = 0.017) as independent factors associated with ICU admission. Area under the ROC curve was 0.891. CONCLUSION: Patient comorbidities, surgical complexity, and lactic acidosis at the end of surgery were associated with unplanned postoperative ICU admission. Late ICU admission had very high mortality rates compared to direct admission. Our findings suggest that patients with a combination of preoperative and intraoperative risk factors could benefit from upfront postoperative ICU admission to potentially improve postoperative outcomes.

The impact of preoperative anemia on pancreatic resection outcomes.

BACKGROUND: Preoperative anemia is a risk factor for blood transfusions and delayed postoperative recovery, but few data are available for pancreatic surgery. Aim of the study was to analyze the impact of preoperative anemia on outcomes after pancreatic resection. METHODS: Retrospective review of 1107 patients resected at San Raffaele Hospital (2015-2018). Preoperative anemia was defined as hemoglobin lower than 130 g/L for men and 120 g/L for women. Primary outcome was 90-day comprehensive complication index (CCI). Analysis was stratified according to type of surgery; proximal resections (pancreaticoduodenectomy and total pancreatectomy) versus distal pancreatectomy. RESULTS: In 776 proximal resection patients, preoperative anemia was associated with increased CCI (24 ± 25 vs. 19 ± 23, p = 0.018) and perioperative allogenic blood transfusions (n = 124, 46% vs. n = 129, 26%; p < 0.001). Multivariate analysis showed that anemia was associated with a 7% (95%CI 0.02-0.57 p = 0.047) increase in CCI, and was an independent factor associated with perioperative blood transfusion (OR 2.762, 95%CI 1.72-4.49, p < 0.001). In 331 distal pancreatectomies, anemia was not associated to increased morbidity but only to an increased risk of perioperative blood transfusion. CONCLUSION: Preoperative anemia is an independent risk factor for increased complication severity and blood transfusion in patients undergoing major pancreatic resection.

Continuous positive airway pressure and pronation outside the Intensive Care Unit in COVID-19 acute respiratory distress syndrome.

BACKGROUND: The efficacy and safety of continuous positive airway pressure and respiratory physiotherapy outside the Intensive Care Unit during a pandemic. METHODS: In this cohort study performed in February-May 2020 in a large teaching hospital in Milan, COVID-19 patients with adult respiratory distress syndrome receiving continuous positive airway pressure (positive end-expiratory pressure =10 cm H2O, FiO2=0.6, daily treatment duration: 4×3h-cycles) and respiratory physiotherapy including pronation outside the Intensive Care Unit were followed-up. RESULTS: Of 90 acute respiratory distress syndrome (ARDS) patients treated with continuous positive airway pressure (45/90, 50% pronated at least once) outside the Intensive Care Unit and with a median (interquartile) follow-up of 37 (11-46) days, 45 (50%) were discharged at home, 28 (31%) were still hospitalized, and 17 (19%) died. Continuous positive airway pressure failure was recorded for 35 (39%) patients. Patient mobilization was associated with reduced failure rates (P=0.033). No safety issues were observed. CONCLUSIONS: Continuous positive airway pressure with patient mobilization (including pronation) was effective and safe in patients with ARDS due to COVID-19 managed outside the Intensive Care Unit setting during the pandemic.

Impact of care pathway adherence on recovery following distal pancreatectomy within an enhanced recovery program.

BACKGROUND: In bowel surgery, adherence to enhanced recovery program (ERP) has been associated with improved recovery. The objective of this study was to evaluate the impact of adherence to ERP elements on outcomes, and identify factors associated with successful recovery following distal pancreatectomy (DP). METHODS: Data for 376 patients who underwent DP managed within an ERP including 16 perioperative elements were reviewed. Primary endpoint was successful recovery, a composite outcome defined as length of hospital stay≤7 days, no severe complications nor readmissions. RESULTS: Patients had a mean (SD) overall adherence of 76 (14)%. Overall, 166 (44%) patients had a successful recovery. There was a positive association between overall adherence and successful recovery (OR 1.19, 95%CI 1.08-1.31 for every additional element, p = 0.001), while an inverse relationship was found with comprehensive complication index (8% reduction, 95%CI -15 to -2%, p = 0.011). Adherence to postoperative phase interventions had the greatest impact on recovery (OR 1.29, 95%CI 1.13-1.47 for every additional postoperative element; p < 0.001). At multivariable regression, early termination of IV fluids was the only ERP element associated with successful recovery (OR 2.80, 95%CI 1.73-4.54; p < 0.001). CONCLUSION: Increased adherence to ERP elements was associated with successful early recovery and reduction of postoperative complication severity.

Application of ERAS protocol in esophagectomy: a national survey among Italian centers performing esophageal surgery.

The application of enhanced recovery after surgery guidelines for esophageal surgery in different units remains unclear. This survey intended to investigate how such protocol is applied among Italian esophageal surgery units. A survey with 40 questions was mailed to Italian centers that performed at least 10 esophagectomies per year. It included questions about the type of hospital and unit and pre-, intra- and post-operative items. Difficulties encountered were investigated. Thirteen (65%) centers answered the survey, and all met the minimal safety requirements, e.g., the presence of intensive care units and 24-h on-call operative endoscopy and radiology facilities. Fifty percent of esophagectomies with a minimally invasive approach were performed in 84.6% of the centers. Regarding pre-operative items, the highest scores were for the application of nutritional support, dysphagia palliation and presence of a multidisciplinary tumor board, whereas the lowest score was for the use of immunonutrition. Regarding intra-operative items, hypothermia prevention and the use of goal-directed fluid therapy and volatile anesthesia were diffusely adopted, whereas the rate of using abdominal drains was high. Regarding post-operative items, nausea prevention, multimodal analgesia and early mobilization were applied frequently, whereas the use of nasogastric tubes and regular transfer to intensive care units was diffused. The primary barriers in enhanced recovery after surgery protocol application were resistance and a lack of paramedic personnel. This survey's results highlight the efforts undertaken by several centers to apply enhanced recovery after surgery philosophy and in this regard, demonstrate a good standing in Italy.

Prevalence, Characteristics, Risk Factors, and Outcomes of Invasively Ventilated COVID-19 Patients with Acute Kidney Injury and Renal Replacement Therapy.

BACKGROUND: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems. OBJECTIVE: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients. METHODS: Observational study in a tertiary care hospital in Milan, Italy. RESULTS: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients. CONCLUSIONS: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality.