Search

Background: The Italian National Institute of Health (Istituto Superiore di Sanità, ISS) considers health inequalities (HI) an important area of activity. As the scientific and technical body of the Ministry of Health and the National Health Service, ISS may play a key role to reduce HI. In order to enable ISS in addressing the new and crucial HI challenge, a Research Positioning Exercise was designed and implemented., Methods: The Exercise included: (i) workshop to strengthen the institutional interest in the field of HI; (ii) review and analysis of ISS publications (years 2000-2017) to identify HI research topics; (iii) survey among ISS researchers regarding main research challenges to address HI in the coming years; and (iv) analysis of input on research challenges from HI international experts., Results: The results of this Exercise suggest that the following points should be included in the future ISS agenda planning: (i) themes which ISS should continue working on (e.g. migrants/vulnerable groups); (ii) themes to be improved: (a) relationship between social determinants and mechanism of HI generation and (b) relationship between risk factors exposure and social determinants; and (iii) new themes to be addressed: (a) mechanisms underlying the resilience observed in Italy; (b) new socioeconomic indicators for HI monitoring; and (c) evidence-based policies aimed at reducing HI., Conclusion: Findings of this Exercise show that ISS researchers identified relevant areas, addressing inequalities in addressing the health. Because of ISS structural peculiarity that includes multidisciplinary expertise, the ISS could provide a significant contribution to HI research challenges and knowledge gaps., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Objectives: The risk factors for oesophageal achalasia, a precancerous condition that can lead to epidermoid carcinoma, are unknown. The aim of this study was to determine these factors., Methods: Beginning in 1973, patients presenting with achalasia from 1955 to 2016 periodically underwent clinical assessment, the barium swallow test (the oesophageal diameter and residual barium column were measured) and endoscopy according to a prospective protocol. We included patients with the minimum follow-up duration of 12 months., Results: Of 681 cases, 583 patients were considered. The median follow-up time was 147.13 months (interquartile range 70.42-257.82 months), and 17 epidermoid carcinomas and 1 carcinosarcoma were diagnosed. After excluding 4 achalasia patients admitted with a cancer diagnosis, the incidence rate of epidermoid carcinomas was 1.61/1000 persons-year, and the cumulative probability of developing cancer at 56.34 years of follow-up was 13%. Risk factors for cancer were a sigmoid oesophagus [risk ratio (RR) = 17.64, 95% confidence interval (CI) 4.13-75.43], duration of achalasia symptoms >280 months (RR = 19.62, 95% CI 4.59-83.80), duration of follow-up >353 months (RR = 5.96, 95% CI 2.50-14.18), oesophageal diameter at diagnosis >71 mm (RR = 21.07, 95% CI 9.29-47.82), residual barium column at diagnosis >23 cm (RR = 24.27, 95% CI 6.93-85.01) and residual barium column at the last follow-up >10 cm (RR = 8.15, 95% CI 2.40-27.62). Conversely, the risk of epidermoid carcinoma was lower when the residual barium swallow decreased by >57% (RR = 0.10, 95% CI 0.03-0.34)., Conclusions: Patients with achalasia carry a substantial risk of developing epidermoid carcinoma. Several factors, such as sigmoid achalasia and dysphagia lasting more than 23 years, are associated with an increased risk of cancer. An effective Heller myotomy may positively influence the carcinogenetic process., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: In Siewert type I/II oesophageal adenocarcinoma, the sensitivity and specificity of computed tomography (CT), positron emission tomography (PET)-CT and endoscopic ultrasound (EUS) for assessment of the N descriptor in defined groups of lymph nodes were investigated., Methods: CT, PET/CT, EUS images and the pathological data of 101 oesophageal adenocarcinomas submitted to primary resection were compared. The lymph nodes were identified as (a) right paratracheal/subcarinal/pulmonary ligament; (b) paraoesophageal; (c) paracardial; (d) left gastric artery, lesser curvature; (e) coeliac trunk, hepatic/splenic artery., Results: Of the 2451 lymph nodes identified, 273 (11.1%) were histologically positive. Overall sensitivity, specificity and negative and positive predictive value for detection of lymph nodes metastatic were respectively: CT sensitivity 39%, specificity 86%, negative 58% and positive 74% predictive value; PET/CT sensitivity 30%, specificity 98%, negative 58% and positive 93% predictive value; EUS sensitivity 50%, specificity 81%, negative 72% and positive 62% predictive value. The sensitivity of CT, PET/CT and EUS in the thoracic nodal groups (a) and (b) was, respectively, 58.3%, 7.1% and 87.5% and 33.3%, 20% and 80%. Sensitivity was below 47% for all tests in the abdominal nodal groups. In contrast, specificity (88.6-100%) was super imposable in all nodal groups. The strength of agreement among the 3 imaging techniques was poor (kappa < 0.30) for the thoracic anatomical groups of interest: (a) lower paratracheal/subcarinal/pulmonary ligament and (b) paraoesophageal; it was moderate/good (kappa >0.30) for the abdominal N groups of interest: c, d and e., Conclusions: The diagnostic performance of CT, PET and EUS for assessing the N descriptor in the paracardial and abdominal stations close to the primary tumour is not satisfactory. EUS can efficiently assess the presence/absence of nodal metastases in the thoracic stations., Clinical Trial Registration: ClinicalTrials.gov number: NCT03529968., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Pharyngo-oesophageal perforation is a rare, life-threatening complication of anterior cervical discectomy and fusion surgery; its management remains poorly defined. We reviewed our experience to understand the treatment of this dreadful complication., Methods: Data regarding the demographics, clinical course, diagnosis, management and outcomes of 15 cases of pharyngo-oesophageal perforations in 14 patients were collected during the period from 2003 to 2016., Results: Pharyngo-oesophageal perforation occurred at a median of 32 days (range 1 day-102 months) after anterior cervical discectomy and fusion surgery. Clinical manifestations included neck abscesses and cutaneous fistulas (10 cases), cervical swelling (two cases), salivary leakage from cervicotomy (two cases), dysphagia, halitosis and regurgitation (one case). In all cases, conservative management was utilized. Two patients affected by minor external fistulas were successfully managed conservatively. In 13 cases, the following surgery was performed: (i) radical bone debridement, total or partial removal of spine fixation devices, autologous bone graft insertion or plate/cage replacement in one case each; (ii) anatomical suture of the fistula; or (iii) suture line reinforcement with myoplasty (in 11/13 cases). Perforation recurred in three cases. One patient underwent reoperation. The other two patients were treated conservatively At a median follow-up of 82 months (range 1-157 months), all patients exhibited permanent resolution of the perforation., Conclusions: Patients with minimal leaks in the absence of systemic infection can be managed conservatively. For cases of large fistulas with systemic infection, we recommend partial or total removal of the fixation devices, direct suture of the oesophageal defect and coverage with tissue flaps., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Type III-IV hiatal hernia (HH) is associated with a true short oesophagus in more than 50% of cases; dedicated treatment of this condition might be appropriate to reduce the recurrence rate after surgery. A case series of patients receiving surgery for Type III-IV hernia was examined for short oesophagus, and the results were analysed., Methods: From 1980 to 1994, 60 patients underwent an open surgical approach, and the position of the oesophago-gastric junction was visually localized; from 1995 to 2013, 48 patients underwent a minimally invasive approach, and the oesophago-gastric junction was objectively localized using a laparoscopic-endoscopic method. The patients underwent a timed clinical-instrumental follow-up that included symptoms assessment, barium swallow and endoscopy. The results were considered to be excellent in the absence of symptoms and oesophagitis; good, if symptoms occurred two to four times a month in the absence of oesophagitis; fair, if symptoms occurred two to four times a week in the presence of hyperaemia, oedema and/or microscopic oesophagitis; and poor, if symptoms occurred on a daily basis in the presence of any grade of endoscopic oesophagitis, HH of any size or type, or the need for antireflux medical therapy. The follow-up time was calculated from the time of surgery to the last complete follow-up., Results: Among the open surgery patients, 78% underwent abdominal fundoplication, 10% the Belsey Mark IV procedure, 8% laparotomic Collis-Nissen fundoplication and 3% the Pearson operation. Among the minimally invasive surgery patients, 44% underwent a laparoscopic floppy Nissen procedure and 56% a left thoracoscopic Collis-laparoscopic Nissen procedure. The postoperative mortality and complication rates were 1.6% (1/60) and 15% for open surgery and 4.1% (2/48) and 12.5% for minimally invasive surgery. A total of 105 patients were followed up for a median period of 96 months. Five relapses occurred after open surgery (5/59, 8%) and two after minimally invasive surgery (2/46, 4%). Among the 105 patients, excellent, good, fair and poor outcomes were observed in 38%, 44%, 9% and 9%, respectively., Conclusions: These data suggested that the selective treatment of short oesophagus in association with a Type III-IV hernia reduced the anatomical recurrence rate and achieved satisfactory outcomes., Clinicaltrialsgov Id: NCT01606449., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Controversy exists regarding surgery for true short oesophagus (TSOE). We compared the results of thoracoscopic Collis gastroplasty-laparoscopic Nissen procedure for the treatment of TSOE with the results of standard laparoscopic Nissen fundoplication., Methods: Between 1995 and 2013, the Collis-Nissen procedure was performed in 65 patients who underwent minimally invasive surgery when the length of the abdominal oesophagus, measured intraoperatively after maximal oesophageal mediastinal mobilization, was ≤1.5 cm. The results of the Collis-Nissen procedure were frequency-matched according to age, sex and period of surgical treatment with those of 65 standard Nissen fundoplication procedures in patients with a length of the abdominal oesophagus >1.5 cm. Postoperative mortality and morbidity were evaluated according to the Accordion classification. The patients underwent a timed clinical-instrumental follow-up that included symptoms assessment, barium swallow and endoscopy. Symptoms, oesophagitis and global results were graded according to semi-quantitative scales. The results were considered to be excellent in the absence of symptoms and oesophagitis, good if symptoms occurred two to four times a month in the absence of oesophagitis, fair if symptoms occurred two to four times a week in the presence of hyperaemia, oedema and/or microscopic oesophagitis and poor if symptoms occurred on a daily basis in the presence of any grade of endoscopic oesophagitis, hiatal hernia of any size or type, or the need for antireflux medical therapy. The follow-up time was calculated from the time of surgery to the last complete follow-up., Results: The postoperative mortality rate was 1.5% for the Collis-Nissen and 0 for the Nissen procedure. The postoperative complication rate was 24% for the Collis-Nissen and 7% for Nissen (P = 0.001) procedure. The complication rate for the Collis-Nissen procedure was 43% in the first 32 cases and 6% in the last 33 cases (P < 0.0001). The median follow-up period was 96 months. The results were: excellent in 27% of Collis-Nissen and 29% of Nissen; good in 64% of Collis-Nissen and 55% of Nissen; fair in 3% of Collis-Nissen and 11% of Nissen and poor in 6% of Collis-Nissen and 5% of Nissen (P = 0.87)., Conclusions: In patients affected by a TSOE, the Collis-Nissen procedure may achieve equally satisfactory results as the standard Nissen procedure in uncomplicated patients., Clinical Registration Number: NCT02288988., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

TLRs are a family of molecules that function as sensors for the detection of pathogens. TLR-9, expressed on B cells and pDCs, recognizes CpG motifs of unmethylated bacterial DNA and plays a role in the development of autoimmunity. The present study was designed to investigate the effects of IFN-alpha in combination with CpG ODN on the activation of CD27(-) naïve B cells and on Ig production. We provide evidence that CpG ODN not only induces a total and T-dependent, specific IgM response by naïve B cells but also their phenotypic differentiation in plasma cells, as demonstrated by the up-regulation of CD38 expression. We found that TLR-9 stimulation with CpG ODN induces IL-1beta, TNF-alpha, IL-10, and IL-6 production. Interestingly, we also found that CpG ODN induces naïve B cell maturation into memory cells, as demonstrated by the induction of CD27, AID mRNA expression, and IgG production. More importantly, our results demonstrate that IFN-alpha amplifies the inductive effect of CpG ODN on naïve B activation and on Ig production through a mechanism involving TLR-9/MyD88-dependent signaling. Moreover, we found that IFN-alpha enhances the frequency of CpG ODN-induced memory B cells. Our results may contribute to clarify the events promoting IFN-alpha-induced amplification of naïve B cell activation via TLR-9 for a better understanding of the pathogenesis of autoimmune disorders and may guide treatments targeting this pathway within B cells.