Pathology of pancreatic ductal adenocarcinoma: Facts,challenges and future developments

Despite major improvements concerning its diagnosis and treatment, pancreatic ductal adenocarcinoma (PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology, as interface discipline between basic and clinical medicine, has substantially contributed to the recent developments and has laid the basis for further progress. The definition and classification of precursor lesions of PDAC and their molecular characterization is a fundamental step for the potential identification of biomarkers and the development of imaging methods for early detection. In addition, by integrating findings in humans with the knowledge acquired through the investigation of transgenic mouse models for PDAC, a new model for pancreatic carcinogenesis has been proposed and partially validated in individuals with genetic predisposition for PDAC. The introduction and validation of a standardized system for pathology reporting based on the axial slicing technique has shown that most pancreatic cancer resections are R1 resections and that this is due to inherent anatomical and biological properties of PDAC. This standardized assessment of prognostic relevant parameters represents the basis for the successful conduction of multicentric studies and for the interpretation of their results. Finally, recent studies have shown that distinct molecular subtypes of PDAC exist and are associated with different prognosis and therapy response. The prospective validation of these results and the integration of molecular analyses in a comprehensive pathology report in the context of individualised cancer therapy represent a major challenge for the future.     

The diagnostic and prognostic role of liquid-based cytology: are we ready to monitor therapy and resistance?

Here, we evaluate the diagnostic and prognostic role of liquid-based cytology (LBC) in different body lesions, including thyroid, lung, effusions and malignant breast lesions. LBC has gained consensus after being applied to both non-gynecologic and fine-needle aspiration cytology. Although some remain sceptical regarding the diagnostic efficacy of LBC, mainly when used alone, in recent years, good results have been obtained as long as it showed a high diagnostic accuracy. Here, we discuss the additional possibility of storing material for the application of ancillary techniques (immunocytochemistry–molecular analysis) with several diagnostic and prognostic advantages, which may pave the way for the challenging evaluation of both monitoring responses to treatment and resistance to targeted therapies in thyroid, lung, breast carcinoma or malignant effusions. Furthermore, it provides the use of several molecular spots as specific targets for personalized therapy.     

Susceptibility of CTLA-4 −1661A/G polymorphism towards severity of rheumatic heart disease

AimGenetic contribution in acute rheumatic fever (ARF)/rheumatic heart disease (RHD) has been suggested but not according to severity of the valve involvement. This study attempts to identify the relevance of CTLA-4 polymorphism with severity of the disease.MethodsIn a case-control design, 291 healthy controls and 83 patients were genotyped for association between RHD and single-nucleotide polymorphisms −1661A/G of CTLA-4.ResultsSegregation of patients on the basis of severity i.e., MVL (Mitral Valve Lesion) and CVL (Combined Valve Lesion) revealed that the frequency of CTLA-4 −1661G allele depleted as the disease progressed to CVL (p < 0.05). Patients in the age group of 31–45 years were significantly more susceptible (p < 0.046). Whereas, female patients were more susceptible than the male patients.ConclusionOur study suggests the risk associated with decreased frequency of CTLA-4 −1661G allele in the CVL group and in females.     

Safety of Transesophageal Echocardiography to Guide Structural Cardiac Interventions

BackgroundDespite the widespread use of transesophageal echocardiography (TEE) to guide structural cardiac interventions, studies evaluating safety in this context are lacking.ObjectivesThis study sought to determine the incidence, types of complications, and factors associated with esophageal or gastric lesions following TEE manipulation during structural cardiac interventions.MethodsThis was a prospective study including 50 patients undergoing structural cardiac interventions in which TEE played a central role in guiding the procedure (mitral and tricuspid valve repair, left atrial appendage closure, and paravalvular leak closure). An esophagogastroduodenoscopy (EGD) was performed before and immediately after the procedure to look for new injuries that might have arisen during the course of the intervention. Patients were divided in 2 cohorts according to the type of injury: complex lesions (intramural hematoma, mucosal laceration) and minor lesions (petechiae, ecchymosis). The factors associated with an increased risk of complications were assessed.ResultsPost-procedural EGD showed a new injury in 86% (n = 43 of 50) of patients, with complex lesions accounting for 40% (n = 20 of 50) of cases. Patients with complex lesions presented more frequently with an abnormal baseline EGD (70% vs. 37%; p = 0.04) and had a higher incidence of post-procedural dysphagia or odynophagia (40% vs. 10%; p = 0.02). Independent factors associated with an increased risk of complex lesions were a longer procedural time under TEE manipulation (for each 10-min increment in imaging time, odds ratio: 1.27; 95% confidence interval: 1.01 to 1.59) and poor or suboptimal image quality (odds ratio: 4.93; 95% confidence interval: 1.10 to 22.02).ConclusionsMost patients undergoing structural cardiac interventions showed some form of injury associated with TEE, with longer procedural time and poor or suboptimal image quality determining an increased risk. Imaging experts performing this technique should be aware of the nature of potential complications, to take the necessary precautions to prevent their occurrence and facilitate early diagnosis and treatment.     

Granulomatous/sarcoid-like reactions in the setting of programmed cell death-1 inhibition: a potential mimic of disease recurrence

Nivolumab and pembrolizumab are humanized IgG4 monoclonal antibodies against programmed cell death 1 (PD-1). Although these agents are effective in treating advanced melanoma, non-small-cell lung carcinoma, and other types of cancers, various adverse events have been reported. Cutaneous adverse events are particularly prevalent and, while granulomatous/sarcoid-like reactions are uncommon, they are increasingly recognized as immune-related adverse events associated with immune checkpoint inhibitors. Herein, we report two cases of granulomatous/sarcoid-like reaction with foreign material, mimicking metastatic malignancy after PD-1 inhibitor treatment. Clinicians should be aware of the existence of cutaneous lesions and perform biopsy if needed to prevent misdiagnosis and unnecessary adjustments to immunotherapy.