Possible Approach to Esophageal Lung with Long Tracheobronchial Gap

Esophageal lung is a rare bronchopulmonary foregut malformation characterized by an anomalous origin of one of the main bronchi which arises from the esophagus. Less than 30 cases are reported in the literature. Therefore, there are no standardized guidelines for the treatment of this condition. We report a case of right esophageal lung diagnosed in a neonate. The patient was treated with thoracoscopic closure of the ectopic main bronchus in the neonatal period, followed by delayed pneumonectomy at 5 months of age. No prosthetic substitute was implanted in the ipsilateral hemithorax after pneumonectomy. The patient is now 4 years old and doing well, postpneumonectomy syndrome was never observed. Our strategy and the possible alternatives are discussed here

Respiratory morbidity in children with repaired congenital esophageal atresia with or without tracheoesophageal fistula

Congenital esophageal atresia with or without tracheoesophageal fistula (CEA \ub1 TEF) is a relatively common malformation that occurs in 1 of 2500-4500 live births. Despite the refinement of surgical techniques, a considerable proportion of children experience short- and long-term respiratory complications, which can significantly affect their health through adulthood. This review focuses on the underlying mechanisms and clinical presentation of respiratory morbidity in children with repaired CEA \ub1 TEF. The reasons for the short-term pulmonary impairments are multifactorial and related to the surgical complications, such as anastomotic leaks, stenosis, and recurrence of fistula. Long-term respiratory morbidity is grouped into four categories according to the body section or function mainly involved: upper respiratory tract, lower respiratory tract, gastrointestinal tract, and aspiration and dysphagia. The reasons for the persistence of respiratory morbidity to adulthood are not univocal. The malformation itself, the acquired damage after the surgical repair, various co-morbidities, and the recurrence of lower respiratory tract infections at an early age can contribute to pulmonary impairment. Nevertheless, other conditions, including smoking habits and, in particular, atopy can play a role in the recurrence of infections. In conclusion, our manuscript shows that most children born with CEA \ub1 TEF survive into adulthood, but many comorbidities, mainly esophageal and respiratory issues, may persist. The pulmonary impairment involves many underlying mechanisms, which begin in the first years of life. Therefore, early detection and management of pulmonary morbidity may be important to prevent impairment in pulmonary function and serious long-term complications. To obtain a successful outcome, it is fundamental to ensure a standardized follow-up that must continue until adulthood

Safety and preliminary activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody gatipotuzumab with the anti-EGFR tomuzotuximab in patients with refractory solid tumors

Colorectal cancer; Lung cancer; Monoclonal antibodyCáncer colorrectal; Cáncer de pulmón; Anticuerpo monoclonalCàncer colorectal; Càncer de pulmó; Anticòs monoclonalBackground The phase I GATTO study (NCT03360734) explored the feasibility, tolerability and preliminary activity of combining gatipotuzumab, a novel humanized monoclonal antibody binding to the tumor-associated epitope of mucin 1 (TA-MUC1) and an anti-epidermal growth factor receptor (anti-EGFR) antibody in refractory solid tumors. Patients and methods Initially the study enrolled primary phase (PP) patients with EGFR-positive metastatic solid tumors, for whom no standard treatment was available. Patients received gatipotuzumab administered at 1400 mg every 2 weeks, 6 weeks after the start of the glyco-optimized anti-EGFR antibody tomuzotuximab at 1200 mg every 2 weeks. As this regimen was proven safe, enrollment continued in an expansion phase (EP) of patients with refractory metastatic colorectal cancer, non-small-cell lung cancer, head and neck cancer and breast cancer. Tomuzotuximab and gatipotuzumab were given at the same doses and gatipotuzumab treatment started 1 week after the first dose of the anti-EGFR antibody. Additionally, investigators could use a commercial anti-EGFR antibody in place of tomuzotuximab. Results A total of 52 patients were enrolled, 20 in the PP and 32 in the EP. The combined treatment was well tolerated and no dose-limiting toxicity was observed in the whole study, nor related serious adverse event or death. Preliminary activity of the combination was observed, with one and four RECIST partial responses in the PP and EP, all in colorectal cancer patients. The trial was accompanied by a comprehensive translational research program for identification of biomarkers, including soluble TA-MUC1 (sTA-MUC1) in serum. In the EP, patients with baseline sTA-MUC1 levels above the median appeared to have improved progression-free survival and overall survival. Conclusions Combination of a TA-MUC1-targeting antibody and an EGFR-targeting antibody is safe and feasible. Interesting antitumor activity was observed in heavily pretreated patients. Future studies should test this combination together with chemotherapy and explore the potential of sTA-MUC1 as a companion biomarker for further development of the combination.This work was supported by Glycotope GmbH (no grant number)

Intravenous thrombolysis in the emergency department for the treatment of acute ischaemic stroke

BACKGROUND AND AIMS: Thrombolytic therapy with intravenous recombinant tissue plasminogen activator (rt-PA) improves outcome in patients with ischaemic stroke treated within 3 h of symptom onset, but its extended implementation is limited. A pilot study was designed to verify whether evaluation of patients with acute ischaemic stroke and their treatment with intravenous rt-PA in the emergency department (ED), followed by transportation to a semi-intensive stroke care unit, offers a safe and effective organisational solution to provide intravenous thrombolysis to acute stroke patients when a stroke unit (SU) is not available. METHODS: After checking for inclusion and exclusion criteria, ED doctors contacted the stroke team with a single page, located family members and urgently obtained computed tomography scan and laboratory tests. A stroke team investigator clinically assessed the patient, obtained written informed consent and supervised intravenous rt-PA in the ED. After treatment, the patient was transferred to the SU for rehabilitation and treatment of complications, under supervision of the same stroke team investigator. RESULTS: 52 patients were treated with intravenous rt-PA within 3 h of symptom onset. 20 patients (38%) improved neurologically after 24 h, the number increased to 30 (58%) after one week. At 3 months 22 patients had a favourable outcome (43%). The 3-month mortality rate was 12%. Symptomatic cerebral haemorrhage was observed in two patients (4%). CONCLUSIONS: Intravenous rt-PA administration in the ED is an effective organisational solution for acute ischaemic stroke when an SU is not established

Labeling male anorectal malformations: objective evaluation of radiologic imaging before surgery

PurposeProne cross-table lateral x-ray (CTLxR) and colostogram aid surgical planning for anorectal malformations (ARMs) without perineal fistulas. We suggest objective imaging tools to classify ARMs.MethodsThree observers prospectively evaluated CTLxR and colostograms of male ARM patients (2012–2022) without perineal fistulas. The level of the rectal pouch was estimated with pubococcygeal (PC) and ischiatic (I) lines. On CTLxR, we described the “pigeon sign”, defined as the rectal pouch ending with a beak-like image, suspicious for a rectourinary fistula. ARM was defined as rectobulbar when the rectal pouch was below the I line, rectoprostatic when between PC and I lines, and rectovesical when above the PC line. Concordance was assessed with Fleiss' kappa. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the “pigeon sign” were calculated.ResultsThirteen patients were included in this study. The interobserver agreement on CTLxR was 69.2% (k = 0.54) on pouch ending, 84.6% (k = 0.69) on the “pigeon sign”, and 76.9% (k = 0.69) on diagnosis; concordance between observers and intraoperative diagnosis was 66.6% (k = 0.56). The “pigeon sign” had 75% sensitivity, 100% specificity, 100% PPV, and 50% NPV. The interobserver agreement on colostograms was 84.6% (k = 0.77) on pouch ending and 89.7% (k = 0.86) on diagnosis; concordance between observers and intraoperative diagnosis was 92.3% (k = 0.90).ConclusionPC and I lines and the “pigeon sign” are useful tools in examining CTLxR and colostograms. Adequate CTLxR interpretation may modify surgical strategy

A maChine and deep Learning Approach to predict pulmoNary hyperteNsIon in newbornS with congenital diaphragmatic Hernia (CLANNISH): Protocol for a retrospective study

Introduction Outcome predictions of patients with congenital diaphragmatic hernia (CDH) still have some limitations in the prenatal estimate of postnatal pulmonary hypertension (PH). We propose applying Machine Learning (ML), and Deep Learning (DL) approaches to fetuses and newborns with CDH to develop forecasting models in prenatal epoch, based on the integrated analysis of clinical data, to provide neonatal PH as the first outcome and, possibly: Favorable response to fetal endoscopic tracheal occlusion (FETO), need for Extracorporeal Membrane Oxygenation (ECMO), survival to ECMO, and death. Moreover, we plan to produce a (semi)automatic fetus lung segmentation system in Magnetic Resonance Imaging (MRI), which will be useful during project implementation but will also be an important tool itself to standardize lung volume measures for CDH fetuses. Methods and analytics Patients with isolated CDH from singleton pregnancies will be enrolled, whose prenatal checks were performed at the Fetal Surgery Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milan, Italy) from the 30th week of gestation. A retrospective data collection of clinical and radiological variables from newborns' and mothers' clinical records will be performed for eligible patients born between 01/01/2012 and 31/12/2020. The native sequences from fetal magnetic resonance imaging (MRI) will be collected. Data from different sources will be integrated and analyzed using ML and DL, and forecasting algorithms will be developed for each outcome. Methods of data augmentation and dimensionality reduction (feature selection and extraction) will be employed to increase sample size and avoid overfitting. A software system for automatic fetal lung volume segmentation in MRI based on the DL 3D U-NET approach will also be developed. Ethics and dissemination This retrospective study received approval from the local ethics committee (Milan Area 2, Italy). The development of predictive models in CDH outcomes will provide a key contribution in disease prediction, early targeted interventions, and personalized management, with an overall improvement in care quality, resource allocation, healthcare, and family savings. Our findings will be validated in a future prospective multicenter cohort study

Staphylococcus aureus colonization and risk of surgical site infection in children undergoing clean elective surgery: A cohort study

Staphylococcus aureus persistently colonizes the skin and nasopharynx of approximately 20% to 30% of individuals, with the highest rates in younger children. To avoid clinical problems for carriers and the spread of S aureus to other hospitalized patients, screening and decolonization of carriers undergoing surgery has been recommended. However, the best approach to patients undergoing clean surgery is not precisely defined. To evaluate whether children carrying S aureus admitted to the hospital for clean elective surgery have an increased risk of postoperative surgical infections, 393 infants and children (77.1% males; mean age\u200a\ub1\u200astandard deviation, 7.6\u200a\ub1\u200a4.5 years) who were scheduled for clean elective surgery procedures were evaluated for S aureus carriage on the day of intervention and 5 days after it. Both anterior nares and pharyngeal swabs were collected. S aureus was identified using the RIDAGENE methicillin-resistant S aureus (MRSA) system (R-Biopharm AG, Darmstadt, Germany), according to the manufacturer's instructions. At admission, 138 (35.1%) children screened positive for S aureus. MRSA was identified in 40 (29.0% of S aureus positive subjects) cases. The carriage rates of S aureus and MRSA varied considerably with age, and in children <2 years old the rate was significantly lower than in any other age group (P\u200a<\u200a.05). Surgical site infection was demonstrated in 4 out of 109 (3.7%) children who were initially colonized by S aureus and in 5 out of 201 (2.5%) children with a negative screening, without any statistically significant difference between groups (P\u200a=\u200a.72). None of these children had MRSA. These results seem to suggest that children undergoing clean elective surgery do not need to be screened for S aureus colonization because, although positive, they have no increased risk of surgical site infection. Following this statement, preoperative procedures should be simplified with relevant advantages from a clinical, social, and economic point of view

Guideline Application in Real world: multi-Institutional Based survey of Adjuvant and first-Line pancreatic Ductal adenocarcinoma treatment in Italy. Primary analysis of the GARIBALDI survey

Background: Information about the adherence to scientific societies guidelines in the ‘real-world’ therapeutic management of oncological patients are lacking. This multicenter, prospective survey was aimed to improve the knowledge relative to 2017-2018 recommendations of the Italian Association of Medical Oncology (AIOM). Patients and methods: Treatment-naive adult patients with pancreatic adenocarcinoma were enrolled. Group A received adjuvant therapy, group B received primary chemotherapy, and group C had metastatic disease. The results on patients accrued until 31 October 2019 with a mature follow-up were presented. Results: Since July 2017, 833 eligible patients of 923 (90%) were enrolled in 44 Italian centers. The median age was 69 years (range 36-89 years; 24% &gt;75 years); 48% were female; 93% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; group A: 16%, group B: 30%; group C: 54%; 72% Nord, 13% Center, 15% South. In group A, guidelines adherence was 68% [95% confidence interval (CI) 59% to 76%]; 53% of patients received gemcitabine and 15% gemcitabine þ capecitabine; median CA19.9 was 29 (range 0-7300; not reported 15%); median survival was 36.4 months (95% CI 27.5-47.3 months). In group B, guidelines adherence was 96% (95% CI 92% to 98%); 55% of patients received nab-paclitaxel þ gemcitabine, 27% FOLFIRINOX, 12% gemcitabine, and 3% clinical trial; median CA19.9 was 337 (range 0-20220; not reported 9%); median survival was 18.1 months (95% CI 15.6-19.9 months). In group C, guidelines adherence was 96% (95% CI 94% to 98%); 71% of patients received nabpaclitaxel þ gemcitabine, 16% gemcitabine, 8% FOLFIRINOX, and 4% clinical trial; liver and lung metastases were reported in 76% and 23% of patients, respectively; median CA19.9 value was 760 (range 0-1374500; not reported 9%); median survival was 10.0 months (95% CI 9.1-11.1 months). Conclusions: The GARIBALDI survey shows a very high rate of adherence to guidelines and survival outcome in line with the literature. CA19.9 testing should be enhanced; nutritional and psychological counseling represent an unmet need. Enrollment to assess adherence to updated AIOM guidelines is ongoing

Single-stage surgical correction of anorectal malformation associated with rectourinary fistula in male neonates

INTRODUCTION: The treatment of children affected by anorectal malformations (ARM) is characterized by some unsolved problems. The three-stage surgical correction has been known to be most effective in preventing complications, but recently new approaches have been proposed. We describe our experience with the newer approaches. METHODS: Twenty three male newborns, affected by ARM and recto-urinary fistula, were treated in 2 different centers in 8 years. Nineteen neonates (birth weight 2.4 - 3.5 kg) received a primary posterior sagittal anorectoplasty (PSARP) at the Department of Pediatric Surgery of the Chittagong Medical College Hospital (group 1). Four term neonates (birth weight 2.9 - 3.4 kg) received a primary pull-through with combined abdomino-perineal approach at the Pediatric Surgery Department of Fondazione C\ue0 Granda of Milan (group 2). RESULTS: Among patients of Group 1, 11 patients had a recto-bulbar fistula and 8 a recto-prostatic fistula. Among the Group 2, 2 had a recto-bulbar fistula and 2 a recto-prostatic fistula. The site of fistula was decided at the time of surgery. In Group 1, 5 post-surgical complications were recorded (26%); 1 child died of sepsis, 3 had dehiscence and 1 stenosis, which resolved with dilatation. In Group 2, the only post-operative complication of small rectal prolapse resolved spontaneously after a few months on follow-up. Group 2 patients were followed-up in a dedicated multidisciplinary colorectal center. CONCLUSIONS: Primary repair of ARMs with recto-urinary fistula is a feasible, safe and effective technique in the neonatal period. A combined abdominal and perineal approach seems to guarantee better results. A dedicated team is mandatory, both for the surgical correction and for a long-term follow-up

Germinal BRCA1-2 pathogenic variants (gBRCA1-2pv) and pancreatic cancer: epidemiology of an Italian patient cohort

Objective: Germline BRCA1-2 pathogenic variants (gBRCApv) increase the risk of pancreatic cancer and predict for response to platinating agents and poly(ADP-ribose) polymerase inhibitors. Data on worldwide gBRCApv incidence among pancreatic ductal adenocarcinoma (PDAC) patients are sparse and describe a remarkable geographic heterogeneity. The aim of this study is to analyze the epidemiology of gBRCApv in Italian patients. Materials and methods: Patients of any age with pancreatic adenocarcinoma, screened within 3 months from diagnosis for gBRCApv in Italian oncologic centers systematically performing tests without any selection. For the purposes of our analysis, breast, ovarian, pancreas, and prostate cancer in a patient’s family history was considered as potentially BRCAassociated. Patients or disease characteristics were examined using the c2 test or Fisher’s exact test for qualitative variables and the Student's t-test or ManneWhitney test for continuous variables, as appropriate. Results: Between June 2015 and May 2020, 939 patients were tested by 14 Italian centers; 492 (52%) males, median age 62 years (range 28-87), 569 (61%) metastatic, 273 (29%) with a family history of potentially BRCA-associated cancers. gBRCA1-2pv were found in 76 patients (8.1%; 9.1% in metastatic; 6.4% in non-metastatic). The gBRCA2/ gBRCA1 ratio was 5.4 : 1. Patients with gBRCApv were younger compared with wild-type (59 versus 62 years, P ¼ 0.01). The gBRCApv rate was 17.1% among patients &lt;40 years old, 10.4% among patients 41-50 years old, 9.2% among patients 51-60 years old, 6.7% among patients aged 61-70 years, and 6.2% among patients &gt;70 years old (none out of 94 patients &gt;73 years old). gBRCApv frequency in 845 patients &lt;74 years old was 9%. Patients with/without a family history of potentially BRCA-associated tumors had 14%/6% mutations. Conclusion: Based on our findings of a gBRCApv incidence higher than expected in a real-life series of Italian patients with incident PDAC, we recommend screening all PDAC patients &lt;74 years old, regardless of family history and stage, due to the therapeutic implications and cancer risk prevention in patients' relatives. Key words: germline BRCA, epidemiology, pancreatic cancer genetics, familial cance