Role of Nasal Nitric Oxide in Primary Ciliary Dyskinesia and Other Respiratory Conditions in Children.

Nitric oxide (NO) is produced within the airways and released with exhalation. Nasal NO (nNO) can be measured in a non-invasive way, with different devices and techniques according to the age and cooperation of the patients. Here, we conducted a narrative review of the literature to examine the relationship between nNO and some respiratory diseases with a particular focus on primary ciliary dyskinesia (PCD). A total of 115 papers were assessed, and 50 were eventually included in the review. nNO in PCD is low (below 77 nL/min), and its measurement has a clear diagnostic value when evaluated in a clinically suggestive phenotype. Many studies have evaluated the role of NO as a molecular mediator as well as the association between nNO values and genotype or ciliary function. As far as other respiratory diseases are concerned, nNO is low in chronic rhinosinusitis and cystic fibrosis, while increased values have been found in allergic rhinitis. Nonetheless, the role in the diagnosis and prognosis of these conditions has not been fully clarified.

Standardization of robotic right liver mobilization.

BACKGROUND: Since its introduction 2 decades ago, robotics has been increasingly used for resection of benign and malignant liver lesions. The robotic platform seems to preserve minimally invasive approach benefits, overcoming laparoscopy limitations. Robotic right liver mobilisation represents a key step for many robotic resections from non-anatomical resections of posterosuperior segments to right hepatectomy. METHODS: We present here a standardized technique of right hepatic lobe mobilisation including technical steps and videos. Robotic resection provide all benefits of minimally invasive approaches in terms of preserving abdominal wall, early alimentation, reduced respiratory stress, associated with more ergonomic conditions for surgeon. RESULTS: We present our standardized and feasible right liver lobe mobilisation needed for posterosuperior resections to the right hepatectomy. CONCLUSIONS: The standardisation of right liver lobe represented our aim to provide a safe and reproducible initial step for many procedures to reduce the conversion rate and to improve the learning curve in young surgeons.

Survival benefit of second line therapies for recurrent hepatocellular carcinoma: repeated hepatectomy, thermoablation and second-line transplant referral in a real life national scenario.

BACKGROUND: Despite second-line transplant(SLT) for recurrent hepatocellular carcinoma(rHCC) leads to the longest survival after recurrence(SAR), its real applicability has never been reported. The aim was to compare the SAR of SLT versus repeated hepatectomy and thermoablation(CUR group). METHODS: Patients were enrolled from the Italian register HE.RC.O.LE.S. between 2008 and 2021. Two groups were created: CUR versus SLT. A propensity score matching (PSM) was run to balance the groups. RESULTS: 743 patients were enrolled, CUR = 611 and SLT = 132. Median age at recurrence was 71(IQR 6575) years old and 60(IQR 53-64, p < 0.001) for CUR and SLT respectively. After PSM, median SAR for CUR was 43 months(95%CI = 37 - 93) and not reached for SLT(p < 0.001). SLT patients gained a survival benefit of 9.4 months if compared with CUR. MilanCriteria(MC)-In patients were 82.7% of the CUR group. SLT(HR 0.386, 95%CI = 0.23 - 0.63, p < 0.001) and the MELD score(HR 1.169, 95%CI = 1.07 - 1.27, p < 0.001) were the only predictors of mortality. In case of MC-Out, the only predictor of mortality was the number of nodules at recurrence(HR 1.45, 95%CI= 1.09 - 1.93, p = 0.011). CONCLUSION: It emerged an important transplant under referral in favour of repeated hepatectomy or thermoablation. In patients with MC-Out relapse, the benefit of SLT over CUR was not observed.

Robotic emergency liver resection of ruptured hepatocellular carcinoma.

BACKGROUND: The spontaneous rupture of hepatocellular carcinoma (HCC) is a rare complication. The management of this complication needs a stepwise, multidisciplinary approach which considers first of all clinical conditions of the patient and also the possibility of the best curative treatment. METHODS: We report our experience of an emergency robotic liver resection for a ruptured HCC in an elderly patient. Minimally invasive liver resection is currently recognised as a safe and feasible approach to the treatment of HCC in elderly patients. RESULTS: Our patient presented haemodynamic stability, which allows us to perform a robotic resection of segment 3. To our knowledge, this is the first report of the application of a robotic platform in an emergency setting for liver resection. CONCLUSIONS: Rupture of HCC is an uncommon complication, burdened by a high rate of mortality. Its management still remains controversial. Treatment should be individualised taking into consideration the clinical status of the patient, tumour features and possibility of centre therapeutic strategy.

Hepatocellular Carcinoma with Bile Duct Tumor Thrombus: A Case Report and Literature Review of 890 Patients Affected by Uncommon Primary Liver Tumor Presentation.

Bile duct tumor thrombus (BDTT) is an uncommon finding in hepatocellular carcinoma (HCC), potentially mimicking cholangiocarcinoma (CCA). Recent studies have suggested that HCC with BDTT could represent a prognostic factor. We report the case of a 47-year-old male patient admitted to the University Hospital of Bari with abdominal pain. Blood tests revealed the presence of an untreated hepatitis B virus infection (HBV), with normal liver function and without jaundice. Abdominal ultrasonography revealed a cirrhotic liver with a segmental dilatation of the third bile duct segment, confirmed by a CT scan and liver MRI, which also identified a heterologous mass. No other focal hepatic lesions were identified. A percutaneous ultrasound-guided needle biopsy was then performed, detecting a moderately differentiated HCC. Finally, the patient underwent a third hepatic segmentectomy, and the histopathological analysis confirmed the endobiliary localization of HCC. Subsequently, the patient experienced a nodular recurrence in the fourth hepatic segment, which was treated with ultrasound-guided percutaneous radiofrequency ablation (RFA). This case shows that HCC with BDTT can mimic different types of tumors. It also indicates the value of an early multidisciplinary patient assessment to obtain an accurate diagnosis of HCC with BDTT, which may have prognostic value that has not been recognized until now.

The Effect of a Liver Transplant Program on the Outcomes of Resectable Hepatocellular Carcinoma: A Nationwide Multicenter Analysis.

OBJECTIVE: To evaluate the effect of a liver transplantation (LT) program on the outcomes of resectable hepatocellular carcinoma (HCC). BACKGROUND: Surgical treatment of HCC includes both hepatic resection (HR) and LT. However, the presence of cirrhosis and the possibility of recurrence make the management of this disease complex and probably different according to the presence of a LT program. METHODS: Patients undergoing HR for HCC between January 2005 and December 2019 were identified from a national database of HCC. The main study outcomes were major surgical complications according to the Comprehensive Complication Index, posthepatectomy liver failure (PHLF), 90-day mortality, overall survival, and disease-free survival. Secondary outcomes were salvage liver transplantation (SLT) and postrecurrence survival. RESULTS: A total of 3202 patients were included from 25 hospitals over the study period. Three of 25 (12%) had an LT program. The presence of an LT program within a center was associated with a reduced probability of PHLF (odds ratio=0.38) but not with overall survival and disease-free survival. There was an increased probability of SLT when HR was performed in a transplant hospital (odds ratio=12.05). Among transplant-eligible patients, those who underwent LT had a significantly longer postrecurrence survival. CONCLUSIONS: This study showed that the presence of a LT program was associated with decreased PHLF rates and an increased probability to receive SLT in case of recurrence.

Awake robotic liver surgery: A case report.

BACKGROUND: In recent years, minimally invasive liver resection has become a standard of care for liver tumors. Considering the need to treat increasingly fragile patients, general anesthesia is sometimes avoided due to respiratory complications. Therefore, surgical treatment with curative intent is abandoned in favor of a less invasive and less radical approach. Epidural anesthesia has been shown to reduce respiratory complications, especially in elderly patients with pre-existing lung disease. CASE SUMMARY: A 77-year-old man with hepatitis-C-virus-related chronic liver disease underwent robotic liver resection for hepatocellular carcinoma. The patient was suffering from hypertension, diabetes and chronic obstructive pulmonary disease. The National Surgical Quality Improvement Program score for developing pneumonia was 9.2%. We planned a combined spinal-epidural anesthesia with conscious sedation to avoid general anesthesia. No modification of the standard surgical technique was necessary. Hemodynamics were stable and bleeding was minimal. The postoperative course was uneventful. CONCLUSION: Robotic surgery in locoregional anesthesia with conscious sedation could be considered a safe and suitable approach in specialized centers and in selected patients.

Spending Time with Mothers as a Resource for Children with Chronic Diseases: A Comparison of Asthma, Type 1 Diabetes, and Cancer during COVID-19 Pandemic.

Due to the COVID-19 pandemic, many families had to manage new difficulties, especially those of chronically ill children. More and more research has focused on the negative effects of the pandemic on psychological wellbeing, while less is known about the resources. The present study aimed to explore the role of time spent with mothers in chronically ill children's populations during the COVID-19 pandemic. Moreover, it explored the differences in mothers' and children's psychosocial functioning in three clinical populations. Four groups were recruited and compared: 7-15 year old children with asthma (45), type 1 diabetes (52), and cancer (33), as well as their healthy counterparts (41), and their respective mothers. They were administered standardized questionnaires and ad hoc surveys assessing psychological wellbeing and worries. Children of the four groups scored significantly differently with respect to the concerns for contagion, internalizing symptoms, and prosocial behaviors; mothers had worries about the consequences of their children's contagion related to the chronic illness, as well as time with the child. The multiple linear regression model showed an association of being affected by cancer, suffering from type 1 diabetes, and spending less time with the child with an increase in children's internalizing problems. Time with mothers seemed to be a resource for psychological wellbeing during the pandemic. Clinical implications are discussed.

Percutaneous insertion of a novel dedicated metal stent to treat malignant hilar biliary obstruction.

BACKGROUND: Percutaneous bilateral biliary stenting is an established method for the management of unresectable malignant hilar biliary obstruction. AIM: To evaluate the efficacy and safety of a novel uncovered biliary stent, specifically designed for hilar reconstruction. METHODS: This, single-center, retrospective study included 18 patients (mean age 71 ± 11 years; 61.1% male) undergoing percutaneous transhepatic Moving cell stent (MCS) placement for hilar reconstruction using the stent-in-stent technique for malignant biliary strictures, between November 2020 and July 2021. The Patients were diagnosed with cholangiocarcinoma (12/18; 66.6%), gallbladder cancer (5/18; 27.7%), and colorectal liver metastasis (1/18; 5.5%). Primary endpoints were technical (appropriate stent placement) and clinical (relief from jaundice) success. Secondary endpoints included stent patency, overall survival, complication rates and stent-related complications. RESULTS: The technical and clinical success rates were 100% (18/18 cases). According to Kaplan-Meier analysis, the estimated overall patient survival was 80.5% and 60.4% at 6 and 12 mo respectively, while stent patency was 90.9% and 68.2% at 6 mo and 12 mo respectively. The mean stent patency was 172.53 ± 56.20 d and median stent patency was 165 d (range 83-315). Laboratory tests for cholestasis significantly improved after procedure: mean total bilirubin decreased from 15.2 ± 6.0 mg/dL to 1.3 ± 0.4 mg/dL (P < 0.001); mean γGT decreased from 1389 ± 832 U/L to 114.6 ± 53.5 U/L (P < 0.001). One periprocedural complication was reported. Stent-related complications were observed in 5 patients (27.7%), including 1 occlusion (5.5%) and 1 stent migration (5.5 %). CONCLUSION: Percutaneous hilar bifurcation biliary stenting with the MCS resulted in excellent clinical and technical success rates, with acceptable complication rates. Further studies are needed to confirm these initial positive results.

Impact of COVID-19 in Children with Chronic Lung Diseases.

BACKGROUND: since December 2019, the world has become victim of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The aim of our narrative review is to analyze the impact of COVID-19 in children suffering from chronic lung disease (CLD). METHODS: we searched the MEDLINE/Pubmed database using the terms "SARS-CoV-2" or "COVID-19" or "Coronavirus Diseases 2019"; AND "chronic lung diseases" or "chronic respiratory diseases" or "asthma" or "cystic fibrosis" or "primary ciliary dyskinesia" or "bronchopulmonary dysplasia"; and limiting the search to the age range 0-18 years. RESULTS AND CONCLUSIONS: although COVID-19 rarely presents with a severe course in children, CLD may represent a risk factor; especially when already severe or poorly controlled before SARS-CoV-2 infection. On the other hand, typical features of children with CLD (e.g., the accurate adoption of prevention measures, and, in asthmatic patients, the regular use of inhaled corticosteroids and T2 inflammation) might have a role in preventing SARS-CoV-2 infection. Moreover, from a psychological standpoint, the restrictions associated with the pandemic had a profound impact on children and adolescents with CLD.

Impact of preoperative chemoradiation with higher dose intensity modulated radiotherapy on pathological complete response for locally advanced rectal cancer: a systematic review.

INTRODUCTION: Neoadjuvant chemoradiation (CRT) followed by total mesorectal excision is the current standard-of-care for locally advanced UICC II-III stage rectal cancer (LARC). A pathological complete response (pCR) correlates with survival. Improvements of pCR, including dose escalation, should be explored. The aim of this explorative analysis is to assess the impact on pCR of intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB). AREAS COVERED: A literature search via PICO (Population, Intervention, Comparison, Outcome) in MEDLINE/PubMed and EMBASE and a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Metanalysis) methodology were performed. Studies that reported pCR rate in patients with LARC in clinical stage T2N+M0 or cT3/4 N0/+M0 treated with preoperative CRT with SIB-IMRT/VMAT (Volumetric Modulated Arc Therapy) were included. Sixty-two studies were identified, but only eight clinical trials with a total of 311 patients were included . Median follow-up was 16-61 months. pCR reached the value of 38%. Good survival outcomes were observed with a mild toxicity profile. EXPERT OPINION: Radiotherapy dose intensification in LARC showed a slight increase of pCR compared to historical studies. Prospective evaluations are necessary to define which patients would benefit most.

Benchmarking postoperative outcomes after open liver surgery for cirrhotic patients with hepatocellular carcinoma in a national cohort.

BACKGROUND: Benchmark analysis for open liver surgery for cirrhotic patients with hepatocellular carcinoma (HCC) is still undefined. METHODS: Patients were identified from the Italian national registry HE.RC.O.LE.S. The Achievable Benchmark of Care (ABC) method was employed to identify the benchmarks. The outcomes assessed were the rate of complications, major comorbidities, post-operative ascites (POA), post-hepatectomy liver failure (PHLF), 90-day mortality. Benchmarking was stratified for surgical complexity (CP1, CP2 and CP3). RESULTS: A total of 978 of 2698 patients fulfilled the inclusion criteria. 431 (44.1%) patients were treated with CP1 procedures, 239 (24.4%) with CP2 and 308 (31.5%) with CP3 procedures. Patients submitted to CP1 had a worse underlying liver function, while the tumor burden was more severe in CP3 cases. The ABC for complications (13.1%, 19.2% and 28.1% for CP1, CP2 and CP3 respectively), major complications (7.6%, 11.1%, 12.5%) and 90-day mortality (0%, 3.3%, 3.6%) increased with the surgical difficulty, but not POA (4.4%, 3.3% and 2.6% respectively) and PHLF (0% for all groups). CONCLUSION: We propose benchmarks for open liver resections in HCC cirrhotic patients, stratified for surgical complexity. The difference between the benchmark values and the results obtained during everyday practice reflects the room for potential growth, with the aim to encourage constant improvement among liver surgeons.

The largest western experience on salvage hepatectomy for recurrent hepatocellular carcinoma: propensity score-matched analysis on behalf of He.RC.O.Le.Study Group.

BACKGROUND: We aimed to evaluate, in a large Western cohort, perioperative and long-term oncological outcomes of salvage hepatectomy (SH) for recurrent hepatocellular carcinoma (rHCC) after primary hepatectomy (PH) or locoregional treatments. METHODS: Data were collected from the Hepatocarcinoma Recurrence on the Liver Study Group (He.RC.O.Le.S.) Italian Registry. After 1:1 propensity score-matched analysis (PSM), two groups were compared: the PH group (patients submitted to resection for a first HCC) and the SH group (patients resected for intrahepatic rHCC after previous HCC-related treatments). RESULTS: 2689 patients were enrolled. PH included 2339 patients, SH 350. After PSM, 263 patients were selected in each group with major resected nodule median size, intraoperative blood loss and minimally invasive approach significantly lower in the SH group. Long-term outcomes were compared, with no difference in OS and DFS. Univariate and multivariate analyses revealed only microvascular invasion as an independent prognostic factor for OS. CONCLUSION: SH proved to be equivalent to PH in terms of safety, feasibility and long-term outcomes, consistent with data gathered from East Asia. In the awaiting of reliable treatment-allocating algorithms for rHCC, SH appears to be a suitable alternative in patients fit for surgery, regardless of the previous therapeutic modality implemented.

Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: a propensity score matching analysis.

BACKGROUND: Surgical resection is a first-line curative option for hepatocellular carcinoma, but its role is still unclear in elderly patients. The aim of our study was to compare short- and long-term outcomes of laparoscopic and open liver resection in elderly patients with hepatocellular carcinoma. METHODS: The study included 665 consecutive hepatocellular carcinoma liver resection cases in patients with ≥70 years of age treated in eight European hospital centres. Patients were divided into laparoscopic and open liver resection groups. Perioperative and long-term outcomes were compared between these groups. RESULTS: After a 1:1 propensity score matching, 219 patients were included in each group. Clavien-Dindo grades III/IV (6 vs. 20%, p = 0.04) were lower in the laparoscopic than in the open matched group. Hospital stay was shorter in the laparoscopic than in the open matched group (5 vs. 7 days, p < 0.001). There were no significant differences between laparoscopic and open groups regarding overall survival and disease-free survival at 1-, 3- and 5- year periods. CONCLUSION: Laparoscopic liver resection for hepatocellular carcinoma is associated with good short-term outcomes in patients with ≥70 years of age compared to open liver resection. Laparoscopic liver resection is safe and feasible in elderly patients with hepatocellular carcinoma.

Non-surgical treatment of hilar cholangiocarcinoma.

Cancer of the biliary confluence also known as hilar cholangiocarcinoma (HC) or Klatskin tumor, is a rare type of neoplastic disease constituting approximately 40%-60% of intrahepatic malignancies, and 2% of all cancers. The prognosis is extremely poor and the majority of Klatskin tumors are deemed unresectable upon diagnosis. Most patients with unresectable bile duct cancer die within the first year after diagnosis, due to hepatic failure, and/or infectious complications secondary to biliary obstruction. Curative treatments include surgical resection and liver transplantation in highly selected patients. Nevertheless, very few patients are eligible for surgery or transplant at the time of diagnosis. For patients with unresectable HC, radiotherapy, chemotherapy, photodynamic therapy, and liver-directed minimally invasive procedures such as percutaneous image-guided ablation and intra-arterial chemoembolization are recommended treatment options. This review focuses on currently available treatment options for unresectable HC and discusses future perspectives that could optimize outcomes.

Totally laparoscopic right hemicolectomy with up-down approach. A single institution experience.

AIM: Many laparoscopic techniques have been described for the treatment of right colon cancer. The purpose of this study is to communicate our experience in the totally laparoscopic treatment of right colon cancer and to report our short-term results in order to confirm the feasibility and safeness of this demanding procedure. MATERIAL OF STUDY: From November 2017 to April 2020, we performed 384 surgical operations for colorectal cancers, of these 81 have involved tumors of the right colon in urgent and elective conditions. Right hemicolectomies with a totally laparoscopic approach were performed, by the same surgical team, in 55 patients in elective surgery. RESULTS: During the study period we evaluated intra and postoperative complications in terms of: demographic data and preoperative clinical characteristics, intraoperative and postoperative outcomes (operative time, blood loss, conversion rate, surgical complications, hospitalization, readmission, and mortality), pathological outcomes. DISCUSSION: Our experience confirms that totally laparoscopic approach, with up to down dissection, for the treatment of right colon cancer, performed by expert surgeons is a safe and feasible technique. CONCLUSION: This procedure allows the mesocolon excision with outstanding number of harvested lymph nodes ensuring low complications and better oncological cleaning. KEY WORDS: Central Vascular Ligation, Colorectal Cancer, Fluorescence GLaparoscopy, Right Hemicolectomy, Complete Mesocolic Excision, Surgery.

Pediatric flexible bronchoscopy: A single-center report.

INTRODUCTION: Pediatric flexible laryngotracheal bronchoscopy (FB) is an integral part of diagnostics and treatment at tertiary pediatric respiratory centers. AIM: FBs performed between 2013 and 2018 at our Pediatric Allergy and Respiratory Medicine Unit of the Department of Women's and Children's Health at Padua University were examined in terms of the indications, findings, and adverse events. MATERIALS AND METHODS: The electronic medical records of pediatric patients who underwent FB at least once between 1 January 2013 and 31 December 2018 were considered. Patients' clinical data, indications for FB, anatomical findings, information derived from bronchoalveolar lavage (BAL) and bronchial brushing, and possible adverse events were analyzed. RESULTS: There were 447 pediatric FBs performed in 428 patients (aged from 1 month to 18 years) for diagnostic purposes (92.4%), to clear secretions (3.6%), or to monitor a known condition (4.0%). The main indications were recurrent lower respiratory tract infections (LRTI, 32.2%) and chronic wet cough (9.4%). Lower airway malacia was the most common abnormal finding in these two groups (36.1% and 28.6%, respectively). BAL bacterial culture was positive in 55 children (39.6%) with recurrent LRTI and in 25 (59.5%) with chronic wet cough, being Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis the microorganisms most commonly isolated. FB proved a safe procedure and was well tolerated. CONCLUSIONS: Pediatric FB is an essential tool at our tertiary pediatric respiratory center. It helps establish the anatomical conditions underlying several chronic respiratory conditions and any correlated microbiological findings, with a significant impact on further patient management.

Inter-society consensus for the use of inhaled corticosteroids in infants, children and adolescents with airway diseases.

BACKGROUND: In 2019, a multidisciplinary panel of experts from eight Italian scientific paediatric societies developed a consensus document for the use of inhaled corticosteroids in the management and prevention of the most common paediatric airways disorders. The aim is to provide healthcare providers with a multidisciplinary document including indications useful in the clinical practice. The consensus document was intended to be addressed to paediatricians who work in the Paediatric Divisions, the Primary Care Services and the Emergency Departments, as well as to Residents or PhD students, paediatric nurses and specialists or consultants in paediatric pulmonology, allergy, infectious diseases, and ear, nose, and throat medicine. METHODS: Clinical questions identifying Population, Intervention(s), Comparison and Outcome(s) were addressed by methodologists and a general agreement on the topics and the strength of the recommendations (according to the GRADE system) was obtained following the Delphi method. The literature selection included secondary sources such as evidence-based guidelines and systematic reviews and was integrated with primary studies subsequently published. RESULTS: The expert panel provided a number of recommendations on the use of inhaled corticosteroids in preschool wheezing, bronchial asthma, allergic and non-allergic rhinitis, acute and chronic rhinosinusitis, adenoid hypertrophy, laryngitis and laryngospasm. CONCLUSIONS: We provided a multidisciplinary update on the current recommendations for the management and prevention of the most common paediatric airways disorders requiring inhaled corticosteroids, in order to share useful indications, identify gaps in knowledge and drive future research.