Characterization of Non-Food Foreign Bodies Aspirated by Children: A Systematic Review of the Literature.

BACKGROUND: Foreign Body Aspiration (FBA) represents a leading cause of death among unintentional injuries in children less than one year of age. This study reviewed case reports and case series reporting non-food FBA in children to characterize aspirated foreign bodies, describing the clinical presentations and the outcomes. METHODS: A systematic review was conducted according to the PRISMA checklist. Case reports and case series presenting non-food FBA in children (up to 18 years) were eligible to be included. Information regarding study characteristics, child demographics, foreign body characteristics, clinical presentation, and outcome were extracted. RESULTS: The review included 248 articles published between 1965 and 2023, corresponding to 294 cases. The male gender was the most prevalent (194 cases, 66%), and the median age was 3.5 years (Interquartile Range: 1-8 years). Button batteries were the objects most frequently reported (21 cases, 7.1%). Objects were located most often in the bronchus (102 cases, 35%). The most common symptom was cough (181 cases, 62%), followed by respiratory distress (160 cases, 54%) and wheezing/stridor (127 cases, 43%). CONCLUSIONS: The present systematic review may have relevant public health implications, since characterizing objects that cause foreign body injuries is essential to reduce the burden of this phenomenon.

Δ40p53 isoform up-regulates netrin-1/UNC5B expression and potentiates netrin-1 pro-oncogenic activity.

Netrin-1, a secreted protein recently characterized as a relevant cancer therapeutic target, is the antiapoptotic ligand of the dependence receptors deleted in colorectal carcinoma and members of the UNC5H family. Netrin-1 is overexpressed in several aggressive cancers where it promotes cancer progression by inhibiting cell death induced by its receptors. Interference of its binding to its receptors has been shown, through the development of a monoclonal neutralizing antinetrin-1 antibody (currently in phase II of clinical trial), to actively induce apoptosis and tumor growth inhibition. The transcription factor p53 was shown to positively regulate netrin-1 gene expression. We show here that netrin-1 could be a target gene of the N-terminal p53 isoform Δ40p53, independent of full-length p53 activity. Using stable cell lines, harboring wild-type or null-p53, in which Δ40p53 expression could be finely tuned, we prove that Δ40p53 binds to and activates the netrin-1 promoter. In addition, we show that forcing immortalized human skeletal myoblasts to produce the Δ40p53 isoform, instead of full-length p53, leads to the up-regulation of netrin-1 and its receptor UNC5B and promotes cell survival. Indeed, we demonstrate that netrin-1 interference, in the presence of Δ40p53, triggers apoptosis in cancer and primary cells, leading to tumor growth inhibition in preclinical in vivo models. Finally, we show a positive correlation between netrin-1 and Δ40p53 gene expression in human melanoma and colorectal cancer biopsies. Hence, we propose that inhibition of netrin-1 binding to its receptors should be a promising therapeutic strategy in human tumors expressing high levels of Δ40p53.

Safety and efficacy of a docetaxel-5FU-oxaliplatin regimen with or without trastuzumab in neoadjuvant treatment of localized gastric or gastroesophageal junction cancer: A retrospective study.

BACKGROUND: Triplet chemotherapy, with docetaxel-5FU-oxaliplatin FLOT regimen recently became the standard perioperative treatment for localized gastric cancer (GC). An adapted regimen called TeFOX was recently tested in metastatic setting and gave promising results. AIM: To determine safety and efficacy of TeFOX perioperative regimen. METHODS: This monocentric retrospective study aims to test efficacy and safety of the perioperative TeFOX regimen given alone or in combination with trastuzumab in patients with localized GC. TeFOX consist in docetaxel (50 mg/m²) with oxaliplatin 85 mg/m² and and leucovorin (400 mg/m2) 5 FU bolus (400 mg/m2) on day 1, followed by continuous infusion of 5FU for 46 h (2400 mg/m2) every 2 wk. RESULTS: Thirty-three consecutive patients were included in this retrospective study. Eighteen patients have a gastroesophageal junction cancer and 11 have a GC. Median follow-up of surviving patients was 32 mo. R0 resection was obtained in 30 (91) patients. Twelve patients (36) had a pathological complete response and 8 (24) patients a nearly complete pathological response. Median OS and PFS were not reached at data base lock. We have observed 6 metastatic relapses and 1 localized relapse. No relapse was observed in patients with pathological complete responses. The most common grade 3-4 adverse events were peripheral neuropathy (21) and asthenia (20). CONCLUSION: TeFOX regimen could be safely administrated in perioperative treatment of localized GC. TeFOX and the FLOT regimen have comparable efficacy and safety profiles.

HEPATOFLUO: A prospective monocentric study assessing the benefits of indocyanine green (ICG) fluorescence for hepatic surgery.

BACKGROUND AND OBJECTIVES: Fluorescence imaging using indocyanine green (ICG) is undergoing extensive development. This study aimed to assess the merits of ICG in regard to hepatic surgery. METHODS: Patients with liver lesions that required a resection were eligible. They received an injection of ICG the day before the surgery. Step 1 allowed assessment of use of the medical device under surgical conditions. Steps 2 and 3 assessed the capacity of the MD to detect known tumorous lesions and to spot a predefined area of the liver following injection of ICG into the portal vein (ICGp). RESULTS: The 1st step allowed for validation of the MD use with three patients. Between 04-2013 and 04-2015, 45 pts were included (40 eligible) in steps 2 and 3. All of the tumorous lesions (95/119) exhibited fluorescence. Four new metastasis were detected in 3 pts, and two missing metastases in 1 pt. False positive were 22%. The maximal depth for detection by fluorescence was 13 mm. Injection of ICGp allowed the corresponding anatomical area to be identified in 16/20 patients. CONCLUSION: This study confirmed that intraoperative fluorescence is a helpful and relevant tool for the liver surgeon (NCT 01738217).

Comparable long-term oncologic outcomes of laparoscopic versus open pancreaticoduodenectomy for adenocarcinoma: a propensity score weighting analysis.

BACKGROUND: To date, no study has reported long-term oncologic outcome for patients undergoing laparoscopic pancreaticoduodenectomy (LPD) compared to open surgery (OPD). The aim of this study is assess long-term oncologic outcomes for patients with adenocarcinoma undergoing LPD versus OPD using propensity score weighting modeling to minimize selection bias. PATIENTS AND METHODS: All patients undergoing PD at Institut Mutualiste Montsouris between January 2000 and April 2010 were included. Propensity scores were calculated using multivariate logistic regression, relating preoperative covariates to surgical approach. Logistic regression was performed, and Cox proportional hazards models for postoperative outcomes were constructed, with and without adjustment for propensity scores weights. RESULTS: Among 87 patients who underwent PD, 40 underwent LPD and 25 OPD for confirmed adenocarcinoma. Preoperative covariates across both groups were comparable. The median follow-up time was 34.5 months. During follow-up, metastasis was identified in 16 (40%) LPD and 7 (28%) OPD patients. After propensity score adjustment, the median overall survival (OS) was 35.5 versus 29.6 months, respectively. The 1-, 3-, and 5-year OS rates were 80.5, 49.2, 39.7% and 77.8, 46.4, 30% in the LP and OPD groups (P = 0.41, 0.42, 0.25), respectively. The median recurrence-free survival (RFS) was 21.5 versus 13.7 months (LPD vs. OPD), and the 1-, 3-, and 5-year RFS rates were 70.9, 33.3, 21.9% and 62.3, 37.9, 25.7% in the LP and OPD groups (P = 0.27, 0.37, 0.39), respectively. CONCLUSIONS: Due to the early adoption of LPD, this study is the first to report on long-term oncologic safety of LPD: LPD is non-inferior to OPD with respect to long-term outcomes for patients with adenocarcinoma.

Efficacy of high-intensity focused ultrasound-assisted hepatic resection (HIFU-AR) on blood loss reduction in patients with liver metastases requiring hepatectomy: study protocol for a randomized controlled trial.

BACKGROUND: Liver resection is the only potentially curative treatment for colorectal liver metastases (LM). It is considered a safe procedure, but is often associated with blood loss during liver transection. Blood transfusions are frequently needed, but they are associated with increased morbidity and risk of recurrence. Many surgical devices have been developed to decrease blood loss. However, none of them has proven superior to the standard crushing technique. We developed a new, powerful intra-operative high-intensity focused ultrasound (HIFU) transducer which destroys tissue by coagulative necrosis. We aim to evaluate whether HIFU-assisted liver resection (HIFU-AR) results in reduced blood loss. METHODS: This is a prospective, single-centre, randomized (1:1 ratio), comparative, open-label phase II study. Patients with LM requiring a hepatectomy for ≥ 2 segments will be included. Patients with cirrhosis or sinusoidal obstruction syndrome with portal hypertension will be excluded. The primary endpoint is normalized blood loss in millilitres per square centimetre of liver section plane. Secondary endpoints are: total blood loss, transection time, transection time per square centimetre of liver area, haemostasis time, clip density on the liver section area, rate and duration of the Pringle manœuvre, rate of patients needing a blood transfusion, length of hospital stay, morbidity, patients with positive resection margin, and local recurrence. Assuming a blood loss of 7.6 ± 3.7 mL/cm2 among controls, the study will have 85% power to detect a twofold decrease of blood loss in the experimental arm, using a Wilcoxon (Mann-Whitney) rank-sum test with a 0.05 two-sided significance level. Twenty-one randomized patients per arm are required. Considering the risk of contraindications at surgery, up to eight patients may be enrolled in addition to the 42 planned, with an enrolment period of 24 months. Randomization will be stratified by surgeon. DISCUSSION: We previously demonstrated the safety and efficacy of intra-operative HIFU in patients operated on for LM. We also demonstrated the efficacy of HIFU-AR in a preclinical study. Participants in the HIFU-AR group of this randomized trial can expect to benefit from reduced blood loss and decreased ischemia of liver parenchyma. TRIAL REGISTRATION: Clinicaltrial.gov, NCT02728167 . Registered on 22 March 2016.

Identification of intra-hepatic communicating veins through the arch sign on CT-scan.

PURPOSE: Knowledge of vascular outflow is essential in liver surgery. Communicating veins between the right hepatic vein (RHV) and the middle hepatic vein (MHV) have been described and allowed us to perform new surgical procedures. The aim of this study was to predict the existence of intra-hepatic venous anastomosis by identifying communicating veins on 2D CT-scan imaging. METHODS: We retrospectively analysed data from 32 patients operated on for liver tumours between 2004 and 2013 who underwent a bisegmentectomy VI-VII enlarged to the RHV and/or a bisegmentectomy VII-VIII and/or a left hepatectomy enlarged to the MHV and who had pre and post-operative CT-scans. Patients with cirrhosis were excluded. We first analysed post-operative images and, in patients with a proven collateral vein, looked for evidence of this on pre-operative imaging. We then validated this pre-operative sign against post-operative imaging. RESULTS: Collaterals from both the RHV and the MHV formed an arch visible on pre-operative imaging which predicted the development of intrahepatic venous anastomosis in 20 patients. In 14 patients, a perfect match between the arch sign and development of collaterals was observed (n = 28). Sensitivity, specificity, negative and positive predictive values were 87, 80, 80, and 87%, respectively. Positive and negative likelihood ratio tests were 4.3 and 0.16, respectively. CONCLUSION: Communicating veins between the RHV and the MHV are frequent and can be predicted by the arch sign on 2D CT-scan. Hence the arch sign can be very useful when planning liver surgery.

Portal supply of segment IV of the liver based on CT-scan.

BACKGROUND: The portal vascularization of segment IV (S4) of the liver has not been well described. Knowledge of the portal supply to S4 is of great interest for liver surgery and for interventional radiological procedures. This study aimed to analyse the distribution of portal vein branches supplying S4. METHODS: We retrospectively analysed data from patients operated on for liver tumours between 2007 and 2016. Patients with involvement of S4 branches or the left portal vein, previous liver surgery or poor quality imaging were excluded. Branches originating from the right portal vein and/or from the transverse part of the left portal vein (TPLPV) and/or from the umbilical part of the portal vein (UPLPV) were identified. RESULTS: In 102 patients who underwent a right hepatectomy, S4 was vascularized by 2-8 branches of the left portal vein, with 84.3 % of patients having 3-6 branches. Only eleven patients (10.8 %) had portal branches originating from the TPLPV, with no impact on the number of branches coming from the UPLPV. Three patients (2.9 %) had one branch from the right portal vein. In patients with only two or three branches supplying S4, the branches had a larger diameter and typically arose from a short common trunk which divided further within its first centimetres. CONCLUSIONS: Portal vascularization of S4 varies widely (2-8 branches) between patients and originates predominantly from the junction between the left portal vein and the round ligament. There is no anatomical rationale to divide S4 into S4a and S4b.

Cutaneous metastasis from primary gastric cancer: a case report and review of the literature.

Cutaneous metastases of internal neoplasms are uncommon. They can be metachronous or synchronous to the primary tumor and typically appear late in the course of advanced malignant disease. Gastric cancer rarely is reported as a cause of cutaneous metastasis; the most common metastatic sites are the liver, peritoneal cavity, and lymph nodes. We report a case of cutaneous metastasis from a primary gastric tumor that had been treated 6 years prior. There was no visceral invasion. The patient was treated successfully via a relaparotomy to exclude any macroscopic abdominal recurrence and complete excision of the lesion with a plastic flap to compensate for the tissue lost in the resection. Treatment plans vary depending on the diameter and number of lesions, the presence of visceral metastases, and the physical status of the patient. Therapy generally includes local excision, irradiation, or chemotherapy.

Posterior approach for laparoscopic pancreaticoduodenectomy to prevent replaced hepatic artery injury.

BACKGROUND: Laparoscopic pancreaticoduodenectomy (PD) has become more popular despite its complexity and tendency for higher morbidity.1 Replaced right hepatic artery (RRHA) and replaced common hepatic artery (RCHA), both originating from the superior mesenteric artery (SMA), are the most significant and relatively common vascular anomalies in patients undergoing PD, occurring in 8.6-21 and 0.4-4.5% of cases, respectively.2,3 An inadvertent injury to theses arteries may result in an intra- or postoperative bleeding, hepatic or bile duct ischemia, and consequent leakage or delayed stricture in the bilioenteric anastomosis.2-4 Therefore, preservation of these aberrant hepatic arteries is essential unless their resection is oncologically indicated.2 We describe a posterior approach that can be advantageous in laparoscopic PD for patients with a RRHA or RCHA. METHODS: The posterior approach was used in 81 laparoscopic PDs at the Institute Mutualiste Montsouris between 1994 and 2012.5 In brief, retropancreatic dissection is performed to complete kocherization and expose the posterolateral aspect of the SMA. The origin of the RRHA or RCHA can then be identified and dissected. After division of the pancreatic neck, the portal vein and RRHA or RCHA are separated off the pancreatic neck. In case of the RCHA, the gastroduodenal artery originating from the RCHA is divided during this dissection. RESULTS: The video shows a secure procedure to preserve a RCHA in laparoscopic PD by early identification and dissection of the aberrant artery via the posterior approach. CONCLUSIONS: The posterior approach can help to prevent inadvertent RRHA or RCHA injury in laparoscopic PD.

Isolated limb perfusion with the tumor-targeting human monoclonal antibody-cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma.

BACKGROUND: L19-TNF is a tumor-targeting immunocytokine composed of the human L19 antibody binding to extra domain B (ED-B) of fibronectin of newly formed blood vessels, and of human TNF. This exploratory trial evaluates safety and clinical activity of L19-TNF plus melphalan-containing isolated limb perfusion (ILP) in extremity melanoma patients. METHODS: Seven and 10 patients received 325 µg and 650 µg of L19-TNF, respectively, during the ILP. Patients were studied for safety, tolerability, and clinical activity of this experimental L19-TNF ILP procedure. RESULTS: Non-hematologic toxicity of L19-TNF ILP was very low, but severe myelosuppression was seen in four patients. Although L19-TNF was administered at a TNF-equivalent dose of only 3.13 and 6.25% of the approved TNF (Beromun®) dose of 4 mg, L19-TNF ILP induced objective responses in 86 and 89% of patients, respectively, including a complete response (CR) in 5/10 patients treated with L19-TNF ILP at 650 µg that was durable at 12 months in four patients. No CR was seen at 325 µg of L19-TNF. CONCLUSIONS: ILP with L19-TNF had a favorable safety and a promising activity profile at a dose of 650 µg of L19-TNF, supporting the exploration of higher L19-TNF doses and a Phase II trial comparing L19-TNF ILP with standard melphalan-containing ILP.