Outcomes of a 3-Year Prospective Surveillance in Individuals at High Risk of Pancreatic Cancer.

INTRODUCTION: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before. METHODS: HRI (subjects with a family history or mutation carriers with/without a family history were enrolled in 18 centers). They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195). RESULTS: During the study period (June 2015-September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/premalignancy-related events, and represented the study population. The median age was 51 (interquartile range 16) years. Familial PC cases accounted for 81.4% of HRI and individuals with pathogenic variant for 18.6%. Malignant (n = 8) and premalignant (1 PanIN3) lesions were found in 9 individuals. Five of these 8 cases occurred in pathogenic variant carriers, 4 in familial PC cases (2 tested negative at germline testing and 2 others were not tested). Three of the 8 PC were stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5%, and 3%, respectively. Median overall and disease-free survival of patients with resected PC were 18 and 12 months (95% CI not computable). Considering HRI who underwent baseline imaging, 6 pancreatic neuroendocrine neoplasms (1 resected) and 1 low-yield surgery (low-grade mixed-intraductal papillary mucinous neoplasm) were also reported. DISCUSSION: PC surveillance in a fully public health care system is feasible and safe, and leads to early PC or premalignant lesions diagnoses, mostly at baseline but also over time.

Antibiotic Strategies for Severe Community-Acquired Pneumonia.

Despite advancements in health systems and intensive care unit (ICU) care, along with the introduction of novel antibiotics and microbiologic techniques, mortality rates in severe community-acquired pneumonia (sCAP) patients have not shown significant improvement. Delayed admission to the ICU is a major risk factor for higher mortality. Apart from choosing the appropriate site of care, prompt and appropriate antibiotic therapy significantly affects the prognosis of sCAP. Treatment regimens involving ceftaroline or ceftobiprole are currently considered the best options for managing patients with sCAP. Additionally, several other molecules, such as delafloxacin, lefamulin, and omadacycline, hold promise as therapeutic strategies for sCAP. This review aims to provide a comprehensive summary of the key challenges in managing adults with severe CAP, focusing on essential aspects related to antibiotic treatment and investigating potential strategies to enhance clinical outcomes in sCAP patients.

Radiation Principles, Protection and Reporting for Interventional Pulmonology.

The use and availability of diverse advanced X-ray based imaging and guidance systems in the field of interventional pulmonology is rapidly growing. This popularity links inextricably to an increase in ionizing radiation use. Knowing ionizing radiation is hazardous, knowledge and competent use of X-ray imaging and guidance systems are important. The globally implemented As Low As Reasonably Achievable (ALARA) principle demands careful attention to minimizing radiation exposure while achieving the precise goals of the intervention and imaging therein. To allow careful and targeted weighing of risk against reward while using X-ray based equipment, proper background knowledge of physics as well as imaging system aspects are needed. This white paper summarizes the principles of ionizing radiation which are crucial to enhance awareness and interpretation of dosimetric quantities. Consecutively, a consensus on standards for reporting radiation exposure in interventional pulmonology procedures is indicated to facilitate comparisons between different systems, approaches and results. Last but not least, it provides a list of practical measures, considerations and tips to optimize procedural imaging as well as reduce radiation dose to patients and staff.

Antibiotic therapy for nonfermenting Gram-negative bacilli infections: future perspectives.

PURPOSE OF REVIEW: Serious infections caused by nonfermenting Gram-negative bacteria (NF-GNB) pose a significant challenge for clinicians due to the limited treatment options available, which are frequently associated with issues of toxicity and unfavourable pharmacokinetic profiles. The aim of this review is to provide a brief overview of the existing data concerning the ongoing development of antiinfective agents targeting NF-GNB. RECENT FINDINGS: Several agents exhibiting efficacy against NF-GNB are under clinical investigation. Durlobactam-sulbactam and cefepime-taniborbactam emerge as promising therapeutic avenues against carbapenem-resistant Acinetobacter baumanii . Cefepime-zidebactam may serve as a suitable treatment option for urinary tract infections caused by a wide range of NF-GNB. Cefepime-enmetazobactam demonstrates potent in vitro activity against various NF-GNB strains; however, its role as an anti- Pseudomonal agent is inadequately substantiated by available data. Xeruborbactam is a wide ß-lactamase inhibitor that can be associated with a range of agents, enhancing in-vitro activity of these against many NF-GNB, including those resistant to newer, broader spectrum options. Lastly, murepavadin appears to be a potential pathogen-specific solution for severe Pseudomonas infections; however, additional investigation is necessary to establish the safety profile of this compound. SUMMARY: Each of the novel molecules reviewed possesses an interesting range of in-vitro activity against NF-GNB. In addition, some of them have already been proved effective in vivo, underscoring their potential as future treatment options.

Proposed quality indicators and recommended standard reporting items in performance of EBUS bronchoscopy: An official World Association for Bronchology and Interventional Pulmonology Expert Panel consensus statement.

BACKGROUND: Since their introduction, both linear and radial endobronchial ultrasound (EBUS) have become an integral component of the practice of Pulmonology and Thoracic Oncology. The quality of health care can be measured by comparing the performance of an individual or a health service with an ideal threshold or benchmark. The taskforce sought to evaluate quality indicators in EBUS bronchoscopy based on clinical relevance/importance and on the basis that observed significant variation in outcomes indicates potential for improvement in health care outcomes. METHODS: A comprehensive literature review informed the composition of a comprehensive list of candidate quality indicators in EBUS. A multiple-round modified Delphi consensus process was subsequently performed with the aim of reaching consensus over a final list of quality indicators and performance targets for these indicators. Standard reporting items were developed, with a strong preference for items where evidence demonstrates a relationship with quality indicator outcomes. RESULTS: Twelve quality Indicators are proposed, with performance targets supported by evidence from the literature. Standardized reporting items for both radial and linear EBUS are recommended, with evidence supporting their utility in assessing procedural outcomes presented. CONCLUSION: This statement is intended to provide a framework for individual proceduralists to assess the quality of EBUS they provide their patients through the identification of clinically relevant, feasible quality measures. Emphasis is placed on outcome measures, with a preference for consistent terminology to allow communication and benchmarking between centres.

Repeated endoscopic ultrasound-guided fine-needle biopsy of solid pancreatic lesions after previous nondiagnostic or inconclusive sampling.

OBJECTIVES: Repeated endoscopic ultrasound (EUS)-guided tissue acquisition represents the standard practice for solid pancreatic lesions after previous nondiagnostic or inconclusive results. Since data are lacking, we aimed to evaluate the diagnostic performance of repeated EUS fine-needle biopsy (rEUS-FNB) in this setting. The primary outcome was diagnostic accuracy; sample adequacy, sensitivity, specificity, and safety were secondary outcomes. METHODS: Consecutive patients undergoing rEUS-FNB for solid pancreatic lesions at 23 Italian centers from 2019 to 2021 were retrieved. Pathology on the surgical specimen, malignant histology together with ≥6-month follow-up, and benign pathology together with ≥12-month follow-up were adopted as gold standards. RESULTS: Among 462 patients, 56.5% were male, with a median age of 68 (59-75) years, malignancy prevalence 77.0%. Tumor size was 26 (20-35) mm. Second-generation FNB needles were used in 89.6% cases. Diagnostic accuracy, sensitivity, and specificity of rEUS-FNB were 89.2%, 91.4%, and 81.7%, respectively (19 false-negative and 12 false-positive results). On multivariate analysis, rEUS-FNB performed at high-volume centers (odds ratio [OR] 2.12; 95% confidence interval [CI] 1.10-3.17; P = 0.03) and tumor size (OR 1.03; 95% CI 1.00-1.06; P = 0.05) were independently related to diagnostic accuracy. Sample adequacy was 94.2%. Use of second-generation FNB needles (OR 5.42; 95% CI 2.30-12.77; P < 0.001) and tumor size >23 mm (OR 3.04; 95% CI 1.31-7.06; P = 0.009) were independently related to sample adequacy. CONCLUSION: Repeated EUS-FNB allowed optimal diagnostic performance after nondiagnostic or inconclusive results. Patients' referral to high-volume centers improved diagnostic accuracy. The use of second-generation FNB needles significantly improved sample adequacy over standard EUS-FNB needles.

Sex Drives Functional Changes in the Progression and Regression of Liver Fibrosis.

Liver fibrosis is a common and reversible feature of liver damage associated with many chronic liver diseases, and its onset is influenced by sex. In this study, we investigated the mechanisms of liver fibrosis and regeneration, focusing on understanding the mechanistic gaps between females and males. We injected increasing doses of carbon tetrachloride into female and male mice and maintained them for a washout period of eight weeks to allow for liver regeneration. We found that male mice were more prone to developing severe liver fibrosis as a consequence of early chronic liver damage, supported by the recruitment of a large number of Ly6Chigh MoMφs and neutrophils. Although prolonged liver damage exacerbated the fibrosis in mice of both sexes, activated HSCs and Ly6Chigh MoMφs were more numerous and active in the livers of female mice than those of male mice. After eight weeks of washout, only fibrotic females reported no activated HSCs, and a phenotype switching of Ly6Chigh MoMφs to anti-fibrogenic Ly6Clow MoMφs. The early stages of liver fibrosis mostly affected males rather than females, while long-term chronic liver damage was not influenced by sex, at least for liver fibrosis. Liver repair and regeneration were more efficient in females than in males.

Reliability of grading preoperative pancreatic neuroendocrine tumors on EUS specimens: a systematic review with meta-analysis of aggregate and individual data.

BACKGROUND AND AIMS: Therapy and prognosis of pancreatic neuroendocrine tumors (PanNETs) are strictly related to the Ki-67 index, which defines tumor grading. The criterion standard for the assessment of grading of PanNETs is EUS-guided FNA (EUS-FBAFNA) or EUS-guided fine-needle biopsy sampling (EUS-FNB). Because data on diagnostic accuracy of EUS-FNA and EUS-FNB are heterogeneous, we aimed to analyze the variability in concordance between EUS grading and surgical grading. METHODS: The MEDLINE, SCOPUS, and EMBASE databases were searched until November 2021 to identify studies reporting the concordance rate between EUS grading and surgical grading. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled events were calculated using a random-effects model and expressed in terms of pooled prevalence rates. A multivariate meta-regression was performed to find possible sources of heterogeneity. Where available, individual data were analyzed. RESULTS: Twenty-six studies with 864 patients undergone EUS-FNA or EUS-FNB and surgical resection for PanNETs were included. The pooled estimate rate for the overall concordance of EUS grading and surgical grading was 80.3% (95% confidence interval, 75.6-85.1). Undergrading (EUS grading < surgical grading) was significantly more frequent with respect to overgrading (14.7% vs 3.5%, P < .001). Individual data analysis showed that among nonconcordant patients, the median Ki-67 difference was 3% (interquartile range, 2-6.15). The type of World Health Organization classification adopted and the median lesion diameter were significantly associated with heterogeneity at meta-regression. CONCLUSIONS: EUS is an accurate technique in defining grading in patients with PanNETs, but a margin of error still exists, which should be the focus of future studies to minimize the risk of over- and/or undertreatment.

Migration rate using fully covered metal stent in anastomotic strictures after liver transplantation: Results from the BASALT study group.

BACKGROUND AND STUDY AIM: The traditional endoscopic therapy of anastomotic strictures (AS) after orthotopic liver transplantation (OLT) is multiple ERCPs with the insertion of an increasing number of plastic stents side-by-side. Fully covered self-expanding metal stents (cSEMS) could be a valuable option to decrease the number of procedures needed or non-responders to plastic stents. This study aims to retrospectively analyse the results of AS endoscopic treatment by cSEMS and to identify any factors associated with its success. PATIENTS AND METHODS: Ninety-one patients (mean age 55.9 ± 7.6 SD; 73 males) from nine Italian transplantation centres, had a cSEMS positioned for post-OLT-AS between 2007 and 2017. Forty-nine (54%) patients were treated with cSEMS as a second-line treatment. RESULTS: All the procedures were successfully performed without immediate complications. After ERCP, adverse events occurred in 11% of cases (2 moderate pancreatitis and 8 cholangitis). In 49 patients (54%), cSEMSs migrated. After cSEMS removal, 46 patients (51%) needed further endoscopic (45 patients) or radiological (1 patient) treatments to solve the AS. Lastly, seven patients underwent surgery. Multivariable stepwise logistic regression showed that cSEMS migration was the only factor associated with further treatments (OR 2.6, 95% CI 1.0-6.6; p value 0.03); cSEMS implantation before 12 months from OLT was associated with stent migration (OR 5.2, 95% CI 1.7-16.0; p value 0.004). CONCLUSIONS: cSEMS appears to be a safe tool to treat AS. cSEMS migration is the main limitation to its routinary implantation and needs to be prevented, probably with the use of new generation anti-migration stents.

Colonoscopy-related adverse events and mortality in an Italian organized colorectal cancer screening program.

BACKGROUND: Post-colonoscopy adverse events are a key quality indicator in population-based colorectal cancer screening programs, and affect safety and costs. This study aimed to assess colonoscopy-related adverse events and mortality in a screening setting. METHODS: We retrieved data from patients undergoing colonoscopy within a screening program (fecal immunochemical test every 2 years, 50-69-year-olds, or post-polypectomy surveillance) in Italy between 2002 and 2014, to assess the rate of post-colonoscopy adverse events and mortality. Any admission within 30 days of screening colonoscopy was reviewed to capture possible events. Mortality registries were also matched with endoscopy databases to investigate 30-day post-colonoscopy mortality. Association of each outcome with patient-/procedure-related variables was assessed using multivariable analysis. RESULTS: Overall, 117 881 screening colonoscopies (66 584, 56.5 %, with polypectomy) were included. Overall, 497 (0.42 %) post-colonoscopy adverse events occurred: 281 (0.24 %) bleedings (3.69‰/0.68‰, operative/diagnostic procedures) and 65 (0.06 %) perforations (0.75‰/0.29‰, respectively). At multivariable analysis, bleeding was associated with polyp size (≥ 20 mm: odds ratio [OR] 16.29, 95 % confidence interval [CI] 9.38-28.29), proximal location (OR 1.46, 95 %CI 1.14-1.87), and histology severity (high risk adenoma: OR 5.6, 95 %CI 2.43-12.91), while perforation was associated with endoscopic resection (OR 2.91, 95 %CI 1.62-5.22), polyp size (OR 4.34, 95 %CI 1.46-12.92), and proximal location (OR 1.94, 95 %CI 1.12-3.37). Post-colonoscopy mortality occurred in 15 /117 881 cases (1.27/10 000 colonoscopies). CONCLUSIONS: In an organized screening program, post-colonoscopy adverse events were rare but not negligible. The most frequent event was post-polypectomy bleeding, especially after resection of large (≥ 20 mm) and proximal lesions.

Full medical treatment of COVID-19 associated large pneumothorax - A case report.

A 52-year-old man was re-admitted two weeks after recovering from severe COVD-19 following a 3-days history of cough and worsening shortness of breath. The chest radiograph showed a large right-sided pneumothorax. The first attempt at drainage, performed through a large bored tube, failed. Due to the large dimension of the pneumothorax, and the lung condition (extensive consolidation and diffuse bullous dystrophies), the only thoracic surgical approach prospected was a pneumonectomy. Willing to preserve the lung, the pulmonology team attempted a multi-phase medical-oriented strategy based on medical thoracoscopy. Therefore, the patient underwent 5 chest tube insertions, 2 talc pleurodesis, and an intrapleural blood patch. Air leakage resolution was progressively achieved, and the patient became asymptomatic.

Endo-therapies for biliary duct-to-duct anastomotic stricture after liver transplantation: Outcomes of a nationwide survey.

BACKGROUND: The most appropriate endo-therapeutic approach to biliary anastomotic strictures is yet to be defined. AIM: To retrospectively report on the endo-therapy of duct-to-duct anastomotic strictures during 2013 in Italy. METHODS: Data were collected from 16 Endoscopy Units at the Italian Liver Transplantation Centers (BASALT study group). RESULTS: Complete endo-therapy and follow-up data are available for 181 patients: 101 treated with plastic multistenting, 26 with fully covered self-expandable metal stenting and 54 with single stenting. Radiological success was achieved for 145 patients (80%), that is, 88% of plastic multistenting, 88% of self-expandable metal stenting and 61% of single stenting (P < 0.001 vs plastic multistenting; P < 0.05 vs self-expandable metal stenting). After first-line endo-therapy failure, the patients underwent a second-line endo-therapy with plastic multistenting for 25%, fully covered self-expandable metal stenting for 53% and single stenting for 22% of cases, and radiological success was achieved for 84%, that is, 100%, 85% and 63% with plastic multistenting, self-expandable metal stenting and single stenting (P < 0.05 vs plastic multistenting or self-expandable metal stenting) respectively. Procedure-related complications occurred in 7.8% of endoscopic retrograde cholangiopancreatographies. Overall, clinical success was achieved in 87% of patients after a median follow-up of 25 months. CONCLUSION: Plastic multistenting is confirmed as the preferred first-line treatment, while fully covered self-expandable metal stenting as rescue option for biliary anastomotic strictures. Single stenting has sub-optimal results and should be abandoned.

PET/CT incidental detection of second tumor in patients investigated for pancreatic neoplasms.

BACKGROUND: Positron Emission Tomography/computed tomography (PET/CT) is an imaging technique which has a role in the detection and staging malignancies (both in first diagnosis and follow-up). The finding of an unexpected region of FDG (Fluorodeoxyglucose) uptake can occur when performing whole-body FDG-PET, raising the possibility of a second primary tumor. The aim of this study was to evaluate our experience of second primary cancer incidentally discovered during PET/CT examination performed for pancreatic diseases, during the initial work-up or follow-up after surgical resection. METHODS: In this study, a retrospective evaluation of a prospectively collected data base was performed. Three hundred ninety- nine patients with pancreatic pathology were evaluated by whole body PET/CT imaging from January 2004 to December 2014. Among them, 348 patients were scanned before surgical resection and 51 during the course of their follow-up (pancreatic cancer). Median follow-up time was 29 months (range 14-124). RESULTS: Fifty-six patients (14%) had incidental uptake of FDG in their organs: 31 patients had focal uptake and 25 showed diffuse with or without focal uptake. All patients with focal uptake were investigated, and invasive malignancy was diagnosed in 22 patients: 14 colon, 4 lung, 1 larynx, 1 urothelial, 1 breast cancer, and 1 colon metastasis from pancreatic cancer. Twenty patients underwent resection, and 6 endoscopic removal of colonic polyps. Three patients were not operated for advanced disease, and two patients did not show any pathology (PET/CT false positive). Of the 10 patients investigated for diffuse uptake, no malignancy was found; none of these patients developed a second cancer during the follow-up. CONCLUSIONS: As in other malignancies, unexpected FDG uptake can occur in patients having PET/CT investigation for pancreatic diseases. Focal uptake is likely to be a malignancy and deserves further investigations, although the stage and the poor prognosis of primary pancreatic cancer should be kept in mind. Some selected patients may benefit from the aggressive treatment of incidental lesions and show survival benefit.

Invitation strategies for colorectal cancer screening programmes: The impact of an advance notification letter.

AIM: To estimate the impact of an advance notification letter on participation in sigmoidoscopy (FS) and fecal immunochemical test (FIT) screening. METHODS: Eligible subjects, invited in 3 Italian population based programmes using FS and in 5 using FIT, were randomised (1:1:1), within GP, to: A) standard invitation letter; B) advance notification followed after 1month by the standard invitation; and C) B+indication to contact the general practitioner (GP) to get advice about the decision to be screened. We calculated the 9-month attendance and the incremental cost of each strategy. We conducted a phone survey to assess GP's utilization and predictors of participation. RESULTS: The advance notification was associated with a 20% increase in the attendance among 15,655 people invited for FS (B vs A - RR: 1.17, 95% CI: 1.10-1.25; C vs A - RR: 1.19, 95% CI: 1.12-1.27); the incremental cost ranged between 10 and 9 Euros. Participation in FIT screening (N=23,543) was increased only with simple pre-notification (B vs A - RR: 1.06, 95% CI: 1.02-1.10); the incremental cost was 22.5 Euros. GP consultation rate was not increased in group C. CONCLUSIONS: An advance notification represents a cost-effective strategy to increase participation in FS screening; its impact on the response to FIT screening was limited.

Offering people a choice for colorectal cancer screening.

OBJECTIVES: To assess the population coverage and diagnostic yield of offering an immunochemical faecal occult blood test (FIT) to non-responders to a flexible sigmoidoscopy (FS) invitation. DESIGN: A cohort study conducted in a population-based colorectal cancer (CRC) screening programme. In this programme, eligible men and women aged 58 (Turin; 43,748 subjects) or 60 (Verona; 19,970 subjects) are invited, with a personal letter signed by their general practitioner, to undergo an FS. Bowel preparation is limited to a single enema self-administered at home. Subjects in whom one distal polyp >5 mm (≥ 10 mm in Turin) or at least one adenoma (one advanced adenoma or more than two adenomas in Turin) is detected at FS are referred for colonoscopy. People who do not respond to the invitation to undergo an FS are invited to have an FIT (OC-Sensor; Eiken, Tokyo, Japan; single sample, cut-off 100 ng/ml). Attendance rate and neoplasia yield were analysed in four consecutive birth cohorts. RESULTS: Overall participation rate for the FS invitation was 39.3% in Verona and 29.9% in Turin. Of the eligible non-responders to the FS invitation, 19.3% (95% CI 18.9% to 19.7%) underwent an FIT. As a result, the proportion of people undergoing screening by FS or FIT was 55.2% in Verona and 39.3% in Turin, with no gender differences in either centre. FIT detected 8.3% of all advanced adenomas and 20.4% of all CRCs diagnosed at screening. CONCLUSIONS: A strategy involving the sequential offer of FS and FIT is a feasible and efficient approach. FIT in people not attending for FS increases screening uptake and detection of advanced adenomas and CRCs.

Factors associated with risk of death in hospitalized patients for exacerbation of chronic obstructive pulmonary disease: an updated scoping review.

INTRODUCTION: The Exacerbation of Chronic Obstructive Pulmonary Disease (ECOPD), especially if leading to hospitalization, increases the risk of death. Our scoping review aims to identify updated mortality risk factors for both short- and long-term periods. AREAS COVERED: A comprehensive search, covering the period from January 2013 to February 2024, was performed to identify eligible studies that consider factors associated with death in hospitalized ECOPD. We considered short-term mortality, up to one year (including in-hospital mortality, IHM) and long-term mortality over one year, without time limits. We excluded studies concerning the intensive care area. EXPERT OPINION: We considered 38 studies, 32 and 8 reporting data about short- and long-term mortality, respectively. Two studies consider both periods. Several factors, some already known, others newly identified, have been evaluated and discussed. Some of these were related to the characteristics and severity of COPD (age, body mass index, lung impairment), and some considered the response to ECOPD. In this last context, we focused on the increasing role of biomarkers in predicting the mortality of patients, particularly IHM. Our factors associated with a worse prognosis may be helpful in clinical practice to identify patients at risk and, subsequently, determine a personalized approach.