Local control and short-term outcomes after video-assisted thoracoscopic surgery segmentectomy versus lobectomy for pT1c pN0 non-small-cell lung cancer.

OBJECTIVES: The aim of this study was to compare short-term outcomes and local control in pT1c pN0 non-small-cell lung cancer that were intentionally treated by video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy. METHODS: Multicentre retrospective study of consecutive patients undergoing VATS lobectomy (VL) or VATS segmentectomy (VS) for pT1c pN0 non-small-cell lung cancer from January 2014 to October 2021. Patients' characteristics, postoperative outcomes and survival were compared. RESULTS: In total, 162 patients underwent VL (n = 81) or VS (n = 81). Except for age [median (interquartile range) 68 (60-73) vs 71 (65-76) years; P = 0.034] and past medical history of cancer (32% vs 48%; P = 0.038), there was no difference between VL and VS in terms of demographics and comorbidities. Overall 30-day postoperative morbidity was similar in both groups (34% vs 30%; P = 0.5). The median time for chest tube removal [3 (1-5) vs 2 (1-3) days; P = 0.002] and median postoperative length of stay [6 (4-9) vs 5 (3-7) days; P = 0.039] were in favour of the VS group. Significantly larger tumour size (mean ± standard deviation 25.1 ± 3.1 vs 23.6 ± 3.1 mm; P = 0.001) and an increased number of lymph nodes removal [median (interquartile range) 14 (9-23) vs 10 (6-15); P < 0.001] were found in the VL group. During the follow-up [median (interquartile range) 31 (14-48) months], no statistical difference was found for local and distant recurrence in VL groups (12.3%) and VS group (6.1%) (P = 0.183). Overall survival (80% vs 80%) was comparable between both groups (P = 0.166). CONCLUSIONS: Despite a short follow-up, our preliminary data shows that local control is comparable for VL and VS.

Impact of Variations in the Nursing Care Supply-Demand Ratio on Postoperative Outcomes and Costs.

INTRODUCTION: Improving surgical outcomes is a priority during the last decades because of the rising economic health care burden. The adoption of enhanced recovery programs has been proven to be part of the solution. In this context, the impact of variations in the nursing care supply-demand ratio on postoperative complications and its economic consequences is still not well elucidated. Because patients require different amounts of care, the present study focused on the more accurate relationship between demand and supply of nursing care rather than the nurse-to-patient ratio. METHODS: Through a 3-year period, 838 patients undergoing elective and emergent colorectal and pancreatic surgery within the institutional enhanced recovery after surgery (ERAS) protocol were retrospectively investigated. Nursing demand and supply estimations were calculated using a validated program called the Projet de Recherche en Nursing (PRN), which assigns points to each patient according to the nursing care they need ( estimated PRN) and the actual care they received ( real PRN), respectively. The real/estimated PRN ratio was used to create 2 patient groups: one with a PRN ratio higher than the mean (PRN+) and a second with a PRN ratio below the mean (PRN-). These 2 groups were compared regarding their postoperative complication rates and cost-revenue characteristics. RESULTS: The mean PRN ratio was 0.81. A total of 710 patients (84.7%) had a PRN+ ratio, and 128 (15.3%) had a PRN- ratio. Multivariable analysis focusing on overall complications, severe complications, and prolonged length of stay revealed no significant impact of the PRN ratio for all outcomes ( P > 0.2). The group PRN- had a mean margin per patient of U.S. dollars 1426 (95% confidence interval, 3 to 2903) compared with a margin of U.S. dollars 676 (95% confidence interval, -2213 to 3550) in the PRN+ group ( P = 0.633). CONCLUSIONS: A PRN ratio of 0.8 may be sufficient for patients treated following enhanced recovery after surgery guidelines, pending the adoption of an accurate nursing planning system. This may contribute to better allocation of nursing resources and optimization of expenses on the long run.

Performance of prolonged air leak scoring systems in patients undergoing video-assisted thoracoscopic surgery segmentectomy.

OBJECTIVES: We assessed the accuracy of 3 validated lobectomy scoring systems to predict prolonged air leak (PAL) in patients undergoing video-assisted thoracoscopic surgery (VATS) segmentectomy. METHODS: We reviewed all consecutive patients who had a VATS segmentectomy between January 2016 and October 2020. We determined PALs on postoperative day 5. These findings were correlated with the calculated Brunelli (gender, age, body mass index [BMI], forced expiratory volume in 1 s < 80 and pleural adhesion), Epithor (gender, location, dyspnoea score, BMI, type of resection and pleural adhesion) and European Society of Thoracic Surgeons (ESTS) (gender, BMI and forced expiratory volume in 1 s) scores of each patient. RESULTS: A total of 453 patients (mean age: 66.5 years, female/male sex ratio: 226/227) underwent a VATS segmentectomy for malignant (n = 400) and non-malignant (n = 53) disease. Postoperative cardiopulmonary complications and in-hospital mortality rates were 19.6% and 0.4%, respectively. Median chest tube drainage duration and hospital stay were 2 (interquartile range: 1-4) and 4 (interquartile range: 3-7) days, respectively. On day 5, the prevalence of PAL was 14.1%. The ESTS, Brunelli and Epithor scores for the treated population were, respectively, class A (6.8%), class B (3.2%), class C (10.8%) and class D (28.2%); very low and low (0%), moderate (5%), high (6.3%) and very high (21%); and class A (7%), class B (13.2%), class C (24%) and class D (27.8%). All scores correlated with PAL (p ≤ 0.001). The areas under the receiver operating characteristic (ROC) curve were 0.686, 0.680 and 0.644, respectively. CONCLUSIONS: All 3 scoring systems were correlated with PAL > 5 days following the VATS segmentectomies. ESTS scores seem easier to introduce in clinical practice, but validation by a multicentre cohort is mandatory.

An aberrant right hepatic artery arising from the gastroduodenal artery: a pitfall encountered during pancreaticoduodenectomy.

PURPOSE: Among the variations of the right hepatic artery (RHA), the identification of an aberrant RHA arising from the gastroduodenal artery (GDA) is vital for avoiding damage to the RHA during surgery, since ligation of the GDA is necessary during pancreaticoduodenectomy (PD). However, this variation is not frequently reported. The purpose of this study was to focus on an aberrant RHA arising from the GDA, which was not noted in the classifications reported by Michels and Hiatt. METHODS: A total of 574 patients undergoing a PD between Jan 2001 and Dec 2015 at a tertiary care hospital in Switzerland (n = 366) and between Jan 2009 and May 2015 at a hospital in Japan (n = 208) were included in the analysis. Of these, preoperative CT angiography or/and MRI angiography findings were available for 532 patients. We retrospectively analyzed the hepatic artery variations, patient demographics, and surgical outcomes. RESULTS: Among the 532 patients who received a PD, an RHA originating from the GDA was observed in 19 cases (3.5%). Eleven patients (2.1%) had both an aberrant RHA and an aberrant left hepatic artery (LHA) (Hiatt Type 4). Six patients (1.2%) had a replaced CHA arising from the SMA (Hiatt Type 5). We could, therefore, correctly identify the aberration in all cases. CONCLUSIONS: We observed rarely reported but important aberrant RHA variations arising from the GDA. To prevent injury during PD in patients with this type of aberrant RHA, intensive preparations using CT and/or MRI imaging before surgery and intraoperative liver Doppler ultrasonography are considered to be essential.

Fluorescence-based bowel anastomosis perfusion evaluation: results from the IHU-IRCAD-EAES EURO-FIGS registry.

BACKGROUND: Anastomotic leakage (AL) is one of the dreaded complications following surgery in the digestive tract. Near-infrared fluorescence (NIRF) imaging is a means to intraoperatively visualize anastomotic perfusion, facilitating fluorescence image-guided surgery (FIGS) with the purpose to reduce the incidence of AL. The aim of this study was to analyze the current practices and results of NIRF imaging of the anastomosis in digestive tract surgery through the EURO-FIGS registry. METHODS: Analysis of data prospectively collected by the registry members provided patient and procedural data along with the ICG dose, timing, and consequences of NIRF imaging. Among the included upper-GI, colorectal, and bariatric surgeries, subgroup analysis was performed to identify risk factors associated with complications. RESULTS: A total of 1240 patients were included in the study. The included patients, 74.8% of whom were operated on for cancer, originated from 8 European countries and 30 hospitals. A total of 54 surgeons performed the procedures. In 83.8% of cases, a pre-anastomotic ICG dose was administered, and in 60.1% of cases, a post-anastomotic ICG dose was administered. A significant difference (p < 0.001) was found in the ICG dose given in the four pathology groups registered (range: 0.013-0.89 mg/kg) and a significant (p < 0.001) negative correlation was found between the ICG dose and BMI. In 27.3% of the procedures, the choice of the anastomotic level was guided by means of NIRF imaging which means that in these cases NIRF imaging changed the level of anastomosis which was first decided based on visual findings in conventional white light imaging. In 98.7% of the procedures, the use of ICG partly or strongly provided a sense of confidence about the anastomosis. A total of 133 complications occurred, without any statistical significance in the incidence of complications in the anastomoses, whether they were ICG-guided or not. CONCLUSION: The EURO-FIGS registry provides an insight into the current clinical practice across Europe with respect to NIRF imaging of anastomotic perfusion during digestive tract surgery.

Uniportal ligamentum-based approach to posterolateral segments 9 and 10.

Uniportal VATS posterolateral segmentectomy (S9 and S10) can be an option for treatment of early-stage lung cancer or in cases of central metastases.  Lower lobe segmentectomy is challenging because the pyramidal shape of the basilar segments makes the identification of the intersegmental plane difficult, and the segmental arterial and venous supply is highly variable. Although identifying the segmental arterial branches is easier with a fissure-based technique, the ligamentum-based approach has emerged as a valid and safe alternative in cases of fused fissure.  This video tutorial illustrates the technical aspects of the uniportal VATS ligamentum-based S9+10 segmentectomy of the right lower lobe.

Neutrophils suppress tumor-infiltrating T cells in colon cancer via matrix metalloproteinase-mediated activation of TGFß.

High T-cell infiltration in colorectal cancer (CRC) correlates with a favorable disease outcome and immunotherapy response. This, however, is only observed in a small subset of CRC patients. A better understanding of the factors influencing tumor T-cell responses in CRC could inspire novel therapeutic approaches to achieve broader immunotherapy responsiveness. Here, we investigated T cell-suppressive properties of different myeloid cell types in an inducible colon tumor mouse model. The most potent inhibitors of T-cell activity were tumor-infiltrating neutrophils. Gene expression analysis and combined in vitro and in vivo tests indicated that T-cell suppression is mediated by neutrophil-secreted metalloproteinase activation of latent TGFß. CRC patient neutrophils similarly suppressed T cells via TGFß in vitro, and public gene expression datasets suggested that T-cell activity is lowest in CRCs with combined neutrophil infiltration and TGFß activation. Thus, the interaction of neutrophils with a TGFß-rich tumor microenvironment may represent a conserved immunosuppressive mechanism in CRC.

Surgical site infections after pancreatic surgery in the era of enhanced recovery protocols.

Few data exist on risk factors (RF) for surgical site infections (SSI) among patients treated in an enhanced recovery after surgery (ERAS) pathway. This study aimed to assess RF for SSI after pancreas surgery in a non-ERAS group and an ERAS cohort.An exploratory retrospective analysis of all pancreas surgeries prospectively collected (01/2000-12/2015) was performed. RF for SSI were calculated using uni- and multivariable binary logistic regressions in non-ERAS and ERAS patients.Pancreas surgery was performed in 549 patients. Among them, 144 presented a SSI (26%). In the non-ERAS group (n = 377), SSI incidence was 27% (99/377), and RF for SSI were male gender and preoperative biliary stenting. Since 2012, 172 consecutive patients were managed within an ERAS pathway. Forty-five patients (26%) had SSI. On multivariable analysis no RF for SSI in the ERAS cohort was found. In the ERAS group, patients with a pathway compliance ≤70% had higher occurrence of SSI (30/45 = 67% vs. 7/127 = 6%, p < 0.001) and patients with and without SSI had similar median overall compliances (77%, IQR 71-80 vs. 80%, IQR 73-83, p = 0.097).In the non-ERAS cohort, male gender and preoperative biliary stenting were RF for SSI, whereas in the ERAS group no RF for SSI was found. In an ERAS pathway, having an overall compliance >70% might diminish the SSI rate.

Acute appendicitis in overweight patients: the role of preoperative imaging.

BACKGROUND: The diagnosis of acute appendicitis in overweight patients is challenging due to the limited value of the clinical examination. The benefits of ultrasonography and abdominal CT have been studied in the general population, but there is limited data regarding their use in overweight and obese patients with suspected appendicitis. This study analyzes the role of preoperative radiological modalities in overweight patients with suspected appendicitis. METHODS: Retrospective analysis of a prospectively acquired database including 705 patients operated for suspected acute appendicitis. Patients were divided into two groups according to their BMI (BMI ≥25 kg/m(2) (n = 242) and BMI <25 kg/m(2) (n = 463)). The use of preoperative radiological modalities, laboratory findings and outcome parameters were analyzed. RESULTS: Ultrasonography was the preferred radiological assessment in our cohort (68 % in BMI <25 kg/m and 52.4 % in BMI ≥25 kg/m(2)). However, it was non-conclusive in 42 % of overweight as compared to 6 % in patients with a BMI < 25 (p < 0.0001). This difference was particularly obvious between female patients (8 % of non-conclusive US for BMI <25 kg/m(2) vs 52 % for BMI ≥25 kg/m(2), p < 0.0001). Significantly more CT scans were performed in overweight patients (37 % vs. 20 %; p <0.0001). The accuracy of CT did not differ according to BMI (85 % vs. 88 %; p = 0.76). Preoperative radiological imaging did not significantly delay surgery. Laparoscopy was the preferred approach for both groups (98.2 % vs 98.7 %, P = 0.86) with an overall conversion rate of 4 %. The overall rate of negative appendectomy was 10 %. CONCLUSIONS: The role of ultrasonography in patients with BMI ≥25 kg/m(2) with suspected acute appendicitis is questionable due to its high rate of non-conclusive findings. Therefore, abdominal CT scans should be preferred to investigate suspected appendicitis in overweight patient if clinical findings are not conclusive.

Genotypic features of lentivirus transgenic mice.

Lentivector-mediated transgenesis is increasingly used, whether for basic studies as an alternative to pronuclear injection of naked DNA or to test candidate gene therapy vectors. In an effort to characterize the genetic features of this approach, we first measured the frequency of germ line transmission of individual proviruses established by infection of fertilized mouse oocytes. Seventy integrants from 11 founder (G0) mice were passed to 111 first generation (G1) pups, for a total of 255 events corresponding to an average rate of transmission of 44%. This implies that integration had most often occurred at the one- or two-cell stage and that the degree of genotypic mosaicism in G0 mice obtained through this approach is generally minimal. Transmission analysis of eight individual proviruses in 13 G2 mice obtained by a G0-G1 cross revealed only 8% of proviral homozygosity, significantly below the 25% expected from purely Mendelian transmission, suggesting counter-selection due to interference with the functions of targeted loci. Mapping of 239 proviral integration sites in 49 founder animals revealed that about 60% resided within annotated genes, with a marked tendency for clustering in the middle of the transcribed region, and that integration was not influenced by the transcriptional orientation. Transcript levels of a set of arbitrarily chosen target genes were significantly higher in two-cell embryos than in embryonic stem cells or adult somatic cells, suggesting that, as previously noted in other settings, lentiviral vectors integrate preferentially into regions of the genome that are transcriptionally active or poised for activation.

Expression of FGF-2 in neural progenitor cells enhances their potential for cellular brain repair in the rodent cortex.

Strategies to enhance the capacity of grafted stem/progenitors cells to generate multipotential, proliferative and migrating pools of cells in the postnatal brain could be crucial for structural repair after brain damage. We investigated whether the over-expression of basic fibroblast growth factor 2 (FGF-2) in neural progenitor cells (NPCs) could provide a robust source of migrating NPCs for tissue repair in the rat cerebral cortex. Using live imaging we provide direct evidence that FGF-2 over-expression significantly enhances the migratory capacity of grafted NPCs in complex 3D structures, such as cortical slices. Furthermore, we show that the migratory as well as proliferative properties of FGF-2 over-expressing NPCs are maintained after in vivo transplantation. Importantly, after transplantation into a neonatal ischaemic cortex, FGF-2 over-expressing NPCs efficiently invade the injured cortex and generate an increased pool of immature neurons available for brain repair. Differentiation of progenitor cells into immature neurons was correlated with a gradual down-regulation of the FGF-2 transgene. These results reveal an important role for FGF-2 in regulating NPCs functions when interacting with the host tissue and offer a potential strategy to generate a robust source of migrating and immature progenitors for repairing a neonatal ischaemic cortex.

GABA regulates dendritic growth by stabilizing lamellipodia in newly generated interneurons of the olfactory bulb.

The initial formation and growth of dendrites is a critical step leading to the integration of newly generated neurons into postnatal functional networks. However, the cellular mechanisms and extracellular signals regulating this process remain mostly unknown. By directly observing newborn neurons derived from the subventricular zone in culture as well as in olfactory bulb slices, we show that ambient GABA acting through GABA(A) receptors is essential for the temporal stability of lamellipodial protrusions in dendritic growth cones but did not interfere with filopodia dynamics. Furthermore, we provide direct evidence that ambient GABA is required for the proper initiation and elongation of dendrites by promoting the rapid stabilization of new dendritic segments after their extension. The effects of GABA on the initial formation of dendrites depend on depolarization and Ca2+ influx and are associated with a higher stability of microtubules. Together, our results indicate that ambient GABA is a key regulator of dendritic initiation in postnatally generated olfactory interneurons and offer a mechanism by which this neurotransmitter drives early dendritic growth.

A versatile tool for conditional gene expression and knockdown.

Drug-inducible systems allowing the control of gene expression in mammalian cells are invaluable tools for genetic research, and could also fulfill essential roles in gene- and cell-based therapy. Currently available systems, however, often have limited in vivo functionality because of leakiness, insufficient levels of induction, lack of tissue specificity or prohibitively complicated designs. Here we describe a lentiviral vector-based, conditional gene expression system for drug-controllable expression of polymerase (Pol) II promoter-driven transgenes or Pol III promoter-controlled sequences encoding small inhibitory hairpin RNAs (shRNAs). This system has great robustness and versatility, governing tightly controlled gene expression in cell lines, in embryonic or hematopoietic stem cells, in human tumors xenotransplanted into nude mice, in the brain of rats injected intraparenchymally with the vector, and in transgenic mice generated by infection of fertilized oocytes. These results open up promising perspectives for basic or translational research and for the development of gene-based therapeutics.