Transport of Protein Disulfide Isomerase from the Endoplasmic Reticulum to the Extracellular Space without Passage through the Golgi Complex.

Protein disulfide isomerase-A1 (PDIA1) is a master regulator of oxidative protein folding and proteostasis in the endoplasmic reticulum (ER). However, PDIA1 can reach the extracellular space, impacting thrombosis and other pathophysiological phenomena. Whether PDIA1 is externalized via passive release or active secretion is not known. To investigate how PDIA1 negotiates its export, we generated a tagged variant that undergoes N-glycosylation in the ER (Glyco-PDIA1). Addition of N- glycans does not alter its enzymatic functions. Upon either deletion of its KDEL ER-localization motif or silencing of KDEL receptors, Glyco-PDIA1 acquires complex glycans in the Golgi and is secreted. In control cells, however, Glyco-PDIA1 is released with endoglycosidase-H sensitive glycans, implying that it does not follow the classical ER-Golgi route, nor does it encounter glycanases in the cytosol. Extracellular Glyco-PDIA1 is more abundant than actin, lactate dehydrogenase or other proteins released by damaged or dead cells, suggesting active transport through a Golgi-independent route. The strategy we describe herein can be extended to dissect how select ER-residents reach the extracellular space.

Profound architectural and functional readjustments of the secretory pathway in decidualization of endometrial stromal cells.

Certain cell types must expand their exocytic pathway to guarantee efficiency and fidelity of protein secretion. A spectacular case is offered by decidualizing human endometrial stromal cells (EnSCs). In the midluteal phase of the menstrual cycle, progesterone stimulation induces proliferating EnSCs to differentiate into professional secretors releasing proteins essential for efficient blastocyst implantation. Here, we describe the architectural rearrangements of the secretory pathway of a human EnSC line (TERT-immortalized human endometrial stromal cells (T-HESC)). As in primary cells, decidualization entails proliferation arrest and the coordinated expansion of the entire secretory pathway without detectable activation of unfolded protein response (UPR) pathways. Decidualization proceeds also in the absence of ascorbic acid, an essential cofactor for collagen biogenesis, despite also the secretion of some proteins whose folding does not depend on vitamin C is impaired. However, even in these conditions, no overt UPR induction can be detected. Morphometric analyses reveal that the exocytic pathway does not increase relatively to the volume of the cell. Thus, differently from other cell types, abundant production is guaranteed by a coordinated increase of the cell size following arrest of proliferation.

Water Dimer under Electric Fields: An Ab Initio Investigation up to Quantum Accuracy.

It is well-established that strong electric fields (EFs) can align water dipoles, partially order the H-bond network of liquid water, and induce water splitting and proton transfers. To illuminate the fundamental behavior of water under external EFs, we present the first benchmark, to the best of our knowledge, of DFT calculations of the water dimer exposed to intense EFs against coupled cluster calculations. The analyses of the vibrational Stark effect and electron density provide a consistent picture of the intermolecular charge transfer effects driven along the H-bond by the increasing applied field at all theory levels. However, our findings prove that at extreme field regimes (∼1-2 V/Å) DFT calculations significantly exaggerate by ∼10-30% the field-induced strengthening of the H-bond, both within the GGA, hybrid GGA, and hybrid meta-GGA approximations. Notably, a linear correlation emerges between the vibrational Stark effect on OH stretching and H-bond strengthening: a 1 kcal mol-1 increase corresponds to an 80 cm-1 red-shift in OH stretching frequency.

Endoscopic sinusectomy: 'a rose by any other name'. A systematic review of different endoscopic procedures to treat pilonidal disease.

AIM: Pilonidal sinus or Pilonidal Disease (PD) is a relatively common, benign but challenging condition. Although commonly encountered in practice, its ideal treatment is controversial. One of the most validated treatments is video-assisted surgery. In this context, very similar endoscopic techniques have been published under different names. The aim of this systematic review is to assess the differences among these proposed techniques and their outcomes. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed during all stages of this systematic review. A systematic search of the English literature was performed on multiple databases from 1 January 2014 to 3 April 2022. The primary outcome measure was the IDEAL framework stage of innovation. The key secondary outcome measures were the adherence to the IDEAL reporting guidelines, the Blencowe framework and the core outcome set (COS) for studies evaluating the introduction and evaluation of novel surgical techniques, the qualitative assessment using appropriate tools, the procedural variations and outcomes of each technique. RESULTS: A total of 38 articles were included reporting a very similar technique under eight different acronyms. The number of patients varied from 9 to 250. Mean follow-up ranged from 1 to 60 months. There was only one published study of IDEAL 3. The majority (58%) were IDEAL 2a studies. Reporting of domains in the IDEAL reporting guidelines and Blencowe framework was poor, with most studies not reporting the component steps of procedures or efforts to standardize them. Half of COS domains were markedly underreported. The quality of the evidence was categorized as having a risk of bias from moderate to critical level in all nine comparative non-randomized series. Postoperative complications occurred in 0%-6% of cases, including surgical site infection, poor or failed wound healing bleeding, granuloma, haematoma, and pain requiring intervention. The recurrence rate varied from 0% to 22%. CONCLUSION: The study demonstrates that reporting on technical aspects of interventions for PD is poor, thus warranting a better-quality control of surgical techniques. It is advisable to group all endoscopic procedures under the umbrella term of 'endoscopic sinusectomy', thus embracing the two main principles of this technique, that is, video assistance and PD ablation.

Long term results of video-assisted anal fistula treatment for complex anal fistula: another shattered dream?

AIM: Complex anal fistula represents a burden for patients, and its management is a challenge for surgeons. Video-assisted anal fistula treatment (VAAFT) is one sphincter-sparing technique. However, data on its long-term effectiveness are scant. We aimed to explore the outcomes of VAAFT in a retrospective cohort of patients referred to a tertiary centre. METHOD: Consecutive adult patients with a minimum of 2 years' follow-up after VAAFT were reviewed. Patients were followed up to 5 years postoperatively. Failure was defined as incomplete healing of the external orifice(s) during the first 6 months. Recurrence was defined as new radiologically and/or clinically confirmed onset of the fistula after primary healing. A generalized linear model was fitted to evaluate the association between failure and sociodemographic characteristics. Predictors of recurrence were determined in a subgroup analysis of patients found to be free from disease at 6 months postoperatively. RESULTS: Overall, 106 patients (70% male; mean age 41 years) were reviewed. Of these 86% had a previous seton placement. Fistulas were either high trans-sphincteric (74%), suprasphincteric (12%) or extrasphincteric (13%). Eight (7%) patients experienced postoperative complications, none of which required reintervention. Mean follow-up was 53 ± 13.2 months. VAAFT failed in 14 (13%) patients. The overall recurrence rate ranged from 29% at 1 year to 63% at 5 years. Multiple external orifices, suprasphincteric fistula, younger age, previous surgery and higher complexity of the fistulous tract were independent risk factors for recurrence. CONCLUSION: VAAFT is a safe sphincter-sparing technique. The initially high success rate decreases over time and relates to a higher degree of complexity.

Efficacy and safety of Propionibacterium extract gel versus glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized controlled trial.

AIM: Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF. METHOD: Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis. RESULTS: A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between-treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow-up visit. There were no other significant differences between the two groups for any of the other outcomes. CONCLUSION: While there was no difference in healing rates between the two treatments, PeG was more cost-effective and associated with fewer adverse events.

Alternative detection of SARS-CoV-2 RNA by a new assay based on mass spectrometry.

OBJECTIVES: Accurate detection of SARS-CoV-2 RNA is essential to stopping the spread of SARS-CoV-2. The aim of this study was to evaluate the performance of the recently introduced MassARRAY® SARS-CoV-2 Panel and to compare it to the cobas® SARS-CoV-2 Test. METHODS: The MassARRAY® SARS-CoV-2 Panel consists of five assays targeting different sequences of the SARS-CoV-2 genome. Accuracy was determined using national and international proficiency panels including 27 samples. For clinical evaluation, 101 residual clinical samples were analyzed and results compared. Samples had been tested for SARS-CoV-2 RNA with the cobas® SARS-CoV-2 Test. RESULTS: When accuracy was tested with the MassARRAY® SARS-CoV-2 Panel, 25 of 27 (92.6%) samples revealed correct results. When clinical samples were analyzed with the MassARRAY® SARS-CoV-2 Panel and compared to the cobas® SARS-CoV-2 Test, 100 samples showed concordant results. One sample was found to be inconclusive with the MassARRAY® SARS-CoV-2 Panel. When time-to-results were compared, the new assay showed longer total and hands-on times. CONCLUSIONS: The MassARRAY® SARS-CoV-2 Panel showed a good performance and proved to be suitable for use in the routine diagnostic laboratory. Especially during phases of shortage of reagents and/or disposables, the new test system appears as beneficial alternative to standard assays used for detection of SARS-CoV-2 RNA.

Effects of deployment of electric vehicles on air quality in the urban area of Turin (Italy).

This study aims to evaluate and quantify the environmental, health, and economic benefits due to the penetration of electric vehicles in the fleet composition by replacing conventional vehicles in an urban area. This study has been performed for the city of Turin, where road transport represents one of the main primary emission sources. Air pollution data were evaluated by ADMS-Roads, the flow traffic data used for simulation come from a real-time monitoring. Instead, statistics on mortality and hospitalizations due to cardiovascular and respiratory diseases were collected from the regional health information system and the National Health Institute and implemented in the BenMap software to evaluate the health and economic impacts. In both cases, two scenarios to evaluate the annual benefits of reducing PM10, PM2.5 and NO2 were used: reduction to the levels gained by the assumptions of 2025 and 2030 Scenario and the PM10, PM2.5 and NO2 concentrations were considered for evaluating short-term and long-term effects. The analysis performed doesn't include background pollution levels, i.e. the concentrations percentage reductions are only related to the local contribution, therefore derived from the contribution only of traffic source. The results show that fleet electrification has a potential benefit for concentrations reduction in comparison to the base Scenario, especially related to NO2, less for PM10 and PM2.5. Regarding 2025 Scenario (4 % (passenger car) and 5 % (light-duty vehicles) electric vehicles), reductions of 52 % of NO2, 35 % of PM10 and 49 % of PM2.5 are observed. Meanwhile, as regards 2030 Scenario reductions of 87 % of NO2, 36 % of PM10 and 50 % of PM2.5 are reached. Also, in terms of social costs a decrease of 47 % for the 2025 Scenario and 66 % for the 2030 Scenario in comparison to the base Scenario is arise.

Synthesis of Fe2SiO4-Fe7Co3 Nanocomposite Dispersed in the Mesoporous SBA-15: Application as Magnetically Separable Adsorbent.

The mixture containing alloy and oxide with iron-based phases has shown interesting properties compared to the isolated species and the synergy between the phases has shown positive effect on dye adsorption. This paper describes the synthesis of Fe2SiO4-Fe7Co3-based nanocomposite dispersed in Santa Barbara Amorphous (SBA)-15 and its application in dye adsorption followed by magnetic separation. Thus, it was studied the variation of reduction temperature and amount of hydrogen used in synthesis and the effect of these parameters on the physicochemical properties of the iron and cobalt based oxide/alloy mixture, as well as the methylene blue adsorption capacity. The XRD and Mössbauer results, along with the temperature-programmed reduction (TPR) profiles, confirmed the formation of Fe2SiO4-Fe7Co3-based nanocomposites. Low-angle XRD, N2 isotherms, and TEM images show the formation of the SBA-15 based mesoporous support with a high surface area (640 m2/g). Adsorption tests confirmed that the material reduced at 700 °C using 2% of H2 presented the highest adsorption capacity (49 mg/g). The nanocomposites can be easily separated from the dispersion by applying an external magnetic field. The interaction between the dye and the nanocomposite occurs mainly by π-π interactions and the mixture of the Fe2SiO4 and Fe7Co3 leads to a synergistic effect, which favor the adsorption.

Evaluation of air quality and mobility policies in 14 large Italian cities from 2006 to 2016.

Despite a connection between road traffic and air pollution has been clearly identified, few integrated analyses on air quality and mobility policies are currently available worldwide. Aim of this work is to build a framework for the evaluation of the impact of mobility policies on air quality in 14 major Italian cities, on a long-time scale (2006-2016). Air quality data was collected from all PM10, PM2.5, and NO2 monitoring stations, installed in compliance with the European directive 2008/50/EC. A large dataset was collected, including public transport, environmental, and fuel categorization of the private vehicular fleet, low emissions zones and modal split. In the analyzed time period, both public transportation use and private motorization decreased. Considering the environmental classification standards of vehicles, Northern cities are more readily switching to newer and less polluting cars (e.g. Euro 5 and Euro 6). There has been a general reduction in PM and NO2 concentration. Nevertheless, exceedances are still above the targeted limit value, mainly in some Northern cities who made major investments in sustainable and shared mobility: this highlights a strong influence of climatic conditions and other sources. Dramatic variations in the CO/NO ratio were observed in Turin, while smaller changes are observed in Milan, Rome and Palermo.

Endoscopic pilonidal sinus treatment (EPSiT) in recurrent pilonidal disease: a prospective international multicenter study.

BACKGROUND: Pilonidal disease (PD) is a common disease of the natal cleft, which can lead to complications including infection and abscess formation. Various operative management options are available, but the ideal technique is still debatable. Recurrent PD after surgical treatment is frequent event for the 25-30% of cases. The present study evaluated endoscopic pilonidal sinus treatment (EPSiT) in recurrent and multi-recurrent PD. METHODS: Of the consecutive prospective patients with recurrent PD, 122 were enrolled in a prospective international multicenter study conducted at a secondary and tertiary colorectal surgery centers. Primary endpoint was to evaluate short- and long-term outcomes: healing rate/time, morbidity rate, re-recurrence rate, and patient's quality of life (QoL). RESULTS: Complete wound healing rate was occurred in 95% of the patient, with a mean complete wound healing time of 29 ± 12 days. The incomplete healing rate (5%) was significantly related to the number of external openings (p = 0.008), and recurrence was reported in six cases (5.1%). Normal daily activity was established on the first postoperative day, and the mean duration before patients returned to work was 3 days. QoL significantly increased between the preoperative stage and 30 days after the EPSiT procedure (45.3 vs. 7.9; p < 0.0001). CONCLUSIONS: The EPSiT procedure seems to be a safe and effective technique in treating even complex recurrent PD. It enables excellent short- and long-term outcomes than various other techniques that are more invasive.

5-Fluorouracil degradation rate could predict toxicity in stages II-III colorectal cancer patients undergoing adjuvant FOLFOX.

5-Fluorouracil is commonly used for gastrointestinal cancer treatment in an adjuvant setting; however, the toxicity can lead to a reduction, delay, or discontinuation of treatment. We retrospectively investigated the association between the 5-fluorouracil degradation rate (5-FUDR) and genetic polymorphisms of TSER, DPYD, and MHTFR with toxicity in colorectal cancer patients treated with adjuvant FOLFOX. Pretreatment 5-FUDR and MTHFR A1298T or C677T, TSER, and DPYD gene polymorphisms were characterized in stages II-III colorectal cancer patients. Patients were classified into three metabolic classes according to the 5-FUDR value. Association with toxicities was evaluated retrospectively using logistic regression analysis. Overall, 126 patients were selected (35 women, 91 men). Seven patients were poor metabolizers, 116 patients were normal metabolizers and three patients were ultra-rapid metabolizers. The median 5-FUDR was 1.53 ng/ml/10 cells/min (range: 0.42-2.57 ng/ml/10 cells/min). Severe, rate-limiting toxicities (grades 3-4) were encountered in 22.2% of patients. No associations between MTHFR or TSER polymorphisms and toxicity were detected, whereas 5-FUDR showed a statistically significant association with toxicity (P=0.0047). The DPYD heterozygous mutation was detected in only one patient, who showed grade 4 hematological toxicity and a lower 5-FUDR value. The 5-FUDR value seems not to be affected by MTHFR and TSER polymorphisms. Compared with the available pharmacogenomics tests, the pretreatment evaluation of 5-FUDR increases the proportion of identified colorectal patients at high risk for severe toxicity. Thus, it appears to be a suitable pretreatment toxicity biomarker in a subgroup of patients in whom dose-intensity maintenance is the key factor.

Early onset pancreatic cancer: risk factors, presentation and outcome.

BACKGROUND: About 10% of pancreatic cancer patients are aged ≤50 at diagnosis and defined as Early Onset Pancreatic Cancer (EOPC). There is limited information regarding risk factors for EOPC occurrence and their outcome. AIM: To investigate risk factors, presentation features and outcome of EOPC patients. METHODS: Consecutive, histologically confirmed, pancreatic cancer patients enrolled. Data regarding environmental and genetic risk factors, clinical and pathological information, treatment and survival were recorded. EOPC patients (aged ≤50 at diagnosis) were compared to older subjects. RESULTS: Twenty-five of 293 patients (8.5%) had EOPC. There was no difference regarding sex distribution, medical conditions and alcohol intake between EOPC and older subjects. EOPC patients were more frequently current smokers (56% vs 28% p = 0.001) and started smoking at a significantly lower mean age (19.8 years, 95%CI 16.7-22.9) as compared to older patients (26.1, 95%CI 24.2-28) (p = 0.001). Current smoking (OR 7.5; 95%CI 1.8-30; p = 0.004) and age at smoking initiation (OR 0.8 for every increasing year; 95%CI 0.7-0.9; p = 0.01) were significant and independent risk factors for diagnosis of EOPC. There were no differences regarding genetic syndromes and pancreatic cancer family history. EOCP presented less frequently with jaundice (16% vs 44%, p = 0.006) and had a higher rate of unresectable disease, albeit not significantly (84% vs 68%, p = 0.1). EOPC patients were more frequently fit for surgery or chemotherapy than their counterpart, resulting in similar stage-specific survival probability. CONCLUSION: EOPC seems related to active and early smoking but not to familial syndromes. Young patients display aggressive disease but not worse outcome.

Neoadjuvant chemotherapy for resectable colorectal liver metastases: what is the evidence? Results of a systematic review of comparative studies.

BACKGROUND: The role of preoperative chemotherapy for resectable colorectal liver metastases is still highly controversial. The purpose of this systematic review is to summarize the current evidence on this topic. METHODS: A systematic literature search was performed to identify all studies published from January 2003 up to and including January 2014 regarding patients with initially resectable colorectal liver metastases. Data were examined for information about indications, operation, neoadjuvant and adjuvant therapies, perioperative results, and survival. RESULTS: Fourteen retrospective studies published between 2003 and 2014 satisfied the inclusion criteria, including 1607 patients who underwent pre-operative chemotherapy and liver resection (NEO-CHT group), and 1785 patients submitted to hepatectomy with or without post-operative chemotherapy (SURG group). Postoperative mortality rates ranged from 0 to 5% in the NEO-CHT group and from 0 to 4% in SURG group. Complications ranged from 7 to 63% in both groups. Adopted pre-operative chemotherapy protocols were highly heterogeneous. The 5-year overall survival rates ranged from 38.9 to 74% in the NEO-CHT group and from 20.7 to 56% in the SURG group, with no significant difference in seven of eight studies. DISCUSSION: This review shows that there is a lack of clear evidence on the role of neoadjuvant chemotherapy in the treatment of resectable colorectal metastases in the literature. The majority of studies were retrospective and there was high heterogeneity among them in the treatment protocols. The EORTC 40983 trial and the majority of retrospective studies did not find any overall survival advantage in patients treated with neoadjuvant therapy. Additional high-quality studies (randomized) are needed to shed light on this topic.

Robotic right colectomy: A worthwhile procedure? Results of a meta-analysis of trials comparing robotic versus laparoscopic right colectomy.

BACKGROUND: Robotic right colectomy (RRC) is a complex procedure, offered to selected patients at institutions highly experienced with the procedure. It is still not clear if this approach is worthwhile in enhancing patient recovery and reducing post-operative complications, compared with laparoscopic right colectomy (LRC). Literature is still fragmented and no meta-analyses have been conducted to compare the two procedures. This work aims at reducing this gap in literature, in order to draw some preliminary conclusions on the differences and similarities between RRC and LRC, focusing on short-term outcomes. MATERIALS AND METHODS: A systematic literature review was conducted to identify studies comparing RRC and LRC, and meta-analysis was performed using a random-effects model. Peri-operative outcomes (e.g., morbidity, mortality, anastomotic leakage rates, blood loss, operative time) constituted the study end points. RESULTS: Six studies, including 168 patients undergoing RRC and 348 patients undergoing LRC were considered as suitable. The patients in the two groups were similar with respect to sex, body mass index, presence of malignant disease, previous abdominal surgery, and different with respect to age and American Society of Anesthesiologists score. There were no statistically significant differences between RRC and LRC regarding estimated blood loss, rate of conversion to open surgery, number of retrieved lymph nodes, development of anastomotic leakage and other complications, overall morbidity, rates of reoperation, overall mortality, hospital stays. RRC resulted in significantly longer operative time. CONCLUSIONS: The RRC procedure is feasible, safe, and effective in selected patients. However, operative times are longer comparing to LRC and no advantages in peri-operative and post-operative outcomes are demonstrated with the use of the robotic surgical system.

Prognostic assessment of different lymph node staging methods for pancreatic cancer with R0 resection: pN staging, lymph node ratio, log odds of positive lymph nodes.

BACKGROUND AND AIMS: Survival after surgical resection of pancreatic adenocarcinoma is poor. Several prognostic factors such as the status of the resection margin, lymph node status, or tumour grading have been identified. The aims of the present study were to evaluate and compare the prognostic assessment of different lymph nodes staging methods: standard lymph node (pN) staging, metastatic lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in pancreatic cancer after pancreatic resection. MATERIALS AND METHODS: Data were retrospectively collected from 143 patients who had undergone R0 pancreatic resection for pancreatic ductal adenocarcinoma. Survival curves (Kaplan-Meier and Cox proportional hazard models), accuracy, and homogeneity of the 3 methods (LNR, LODDS, and pN) were compared to evaluate the prognostic effects. RESULTS: Multivariate analysis demonstrated that LODDS and LNR were an independent prognostic factors, but not pN classification. The scatter plots of the relationship between LODDS and the LNR suggested that the LODDS stage had power to divide patients with the same ratio of node metastasis into different groups. For patients in each of the pN or LNR classifications, significant differences in survival could be observed among patients in different LODDS stages. CONCLUSION: LODDS and LNR are more powerful predictors of survival than the lymph node status in patients undergoing pancreatic resection for ductal adenocarcinoma. LODDS allows better prognostic stratification comparing LNR in node negative patients.

Changes in the surgical approach to colonic emergencies during a 15-year period.

PURPOSE: The present study aims to determine the morbidity and mortality of emergency colonic surgery and the factors associated with adverse outcome, and to evaluate any change in incidence of the different types of pathological conditions and in the surgical approach over the last 15 years. MATERIALS AND METHODS: A total of 319 patients who underwent emergency colonic surgery between January 1997 and December 2011 were retrospectively analyzed. Patients were divided into two groups according to the date of surgery, namely group 1, between 1997 and 2006, and group 2, between 2006 and 2011. The differences in terms of postoperative outcomes between the groups were analyzed. RESULTS: Overall postoperative morbidity and mortality rates were 25.3 and 17.2%, respectively; no differences were found between the groups. Group 2 showed a significantly increased rate of primary resection and anastomosis (p < 0.001), as well as an increase in laparoscopic approach compared with group 1 (p < 0.001). CONCLUSIONS: Emergency colon surgery is today primarily performed for benign diseases, of these the most common is diverticular disease followed by ischemic colitis. Age, comorbidities, and ischemic colon disease are predictors of adverse outcomes, while the surgical procedure per se is not.

Lymph-node ratio classification strongly correlates with cancer survivals of patients who underwent r0 resection for gastric cancer with more than 15 nodes harvested.

BACKGROUND: During the last few years, the gastric cancer nodal staging has been extensively revised. Lately, a new system emerged in this field with the purpose of implementing the prognostic stratification: the lymph-node ratio (LNR). The aim of this study was to investigate the prognostic value of the LNR in relation to cancer survivors undergoing resection for gastric adenocarcinoma. METHODS: Off 227 patients undergoing surgical resection for gastric cancer at our Department, 129 curative gastric resections with more than 15 nodes harvested were selected. The LNR was calculated and patients were stratified into 6 subgroups based on the ratio values. The subgroups were compared for data analysis. Survivals were calculated by the Kaplan-Meier method, and the mean follow-up period was 40 months. ROC curves were calculated in order to analyze the performance of the LNR system. RESULTS: LNR stratification correlated with the stage of the disease, with the rate of patients undergoing chemotherapy and patients presenting with a relapse of disease at follow-up. Moreover, an increased ratio correlated with a worse overall, a disease-free and a disease-specific survival of the patients. The ROC curves documented a significant performance of the stratification system with the endpoints of disease-free and disease-specific survivals. CONCLUSION: LNR stratification correlated with cancer-related survivals in our case series. It is a reliable system that might improve current nodal staging and thereby the identification of patients with a higher risk of recurrence or cancer-related mortality.

Duodenopancreatectomy: open or minimally invasive approach?

BACKGROUND: Minimally invasive pancreaticoduodenectomy (MIPD) is a complex procedure, offered to selected patients at institutions highly experienced with the procedure. It is still not clear if this approach may enhance patient recovery and reduce postoperative complications comparing to open pancreaticoduodenectomy (OPD), as demonstrated for other abdominal procedures. METHODS: A systematic literature review was conducted to identify studies comparing MIPD and OPD. Perioperative outcomes (e.g., morbidity and mortality, pancreatic fistula rates, blood loss) constituted the study end points. Metaanalyses were performed using a random-effects model. RESULTS: For the metaanalysis, 8 studies including 204 patients undergoing MIPD and 419 patients undergoing OPD were considered suitable. The patients in the two groups were similar with respect to age, sex and histological diagnosis, and different with respect to tumor size, rate of pylorus preservation, and type of pancreatic anastomosis. There were no statistically significant differences between MIPD and OPD regarding development of delayed gastric emptying (DGE), pancreatic fistula, wound infection, or rates of reoperation and overall mortality. MIDP resulted in lower post-operative complication rates, less intra-operative blood loss, shorter hospital stays, lower blood transfusion rates, higher numbers of harvested lymph nodes, and improved negative margin status rates. However, MIPD was associated with longer operating times when compared to OPD. CONCLUSIONS: The MIPD procedure is feasible, safe, and effective in selected patients. MIPD may have some potential advantages over OPD, and should be performed and further developed by use in selected patients at highly experienced medical centers.

Feasibility of carbon dioxide insufflation and impact on epicardial approach utilization for ventricular tachycardia ablation in a midvolume referral center.

BACKGROUND: Epicardial access is often crucial for successful ventricular tachycardia (VT) ablation, but it is often burdened by significant procedural risk. Intentional coronary vein exit and intrapericardial CO2 insufflation (EpiCO2) can facilitate subxiphoid pericardial access. OBJECTIVE: This prospective study aimed to assess procedural feasibility, safety, and impact of the introduction of intrapericardial CO2 insufflation for epicardial access in a referral center for VT ablation. METHODS: All consecutive patients treated with epicardial VT ablation between November 2022 and January 2024 with the EpiCO2 technique at Pisa University Hospital were prospectively enrolled and compared in terms of feasibility, efficiency, and safety with a local retrospective cohort of patients treated with subxiphoid dry puncture between July 2018 and October 2022. RESULTS: Twenty-two consecutive patients (90.9% male; mean age, 54.3 years) underwent VT ablation with EpiCO2 during the study period. Epicardial access was achieved in all patients; median time from coronary sinus (CS) cannulation to epicardial access was 33 minutes. Intentional vein exit was successful in all cases, whereas CO2 insufflation was not feasible in 1 patient. There were no major complications and no significant bleeding. Since EpiCO2 introduction, epicardial approach utilization increased from 17.8% to 40% of all VT procedures. Comparison with 20 standard dry approach epicardial ablations showed no significant differences in terms of total procedural duration (322.5 [interquartile range, 296.75-363.75] minutes vs 359 [interquartile range, 323-409] minutes; P = .08). CONCLUSION: In our single-center experience, EpiCO2 was feasible and safe and led to significant increase in procedural volume without affecting total procedural time compared with standard dry puncture.