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Simple Summary Pancreatic cancer and cholangiocarcinoma are aggressive diseases mostly diagnosed at an advanced and inoperable stage. This review presents the value of next-generation sequencing (NGS) when performed on small biopsies—including fine-needle aspiration/biopsy samples, brushings, pancreatic juice and bile, and also blood—in the field of pancreatobiliary neoplasia. NGS could guide physicians while evaluating pancreatic solid and cystic lesions or suspicious biliary strictures, performing surveillance in high-risk individuals, or monitoring the disease and assessing prognosis in already diagnosed cancer patients. Evidence suggests that NGS performed on small biopsies is a robust tool for the diagnosis and pre-operative risk stratification of pancreatic and biliary lesions, whereas it also carries significant prognostic and therapeutic value. However, effective standardization of the pre-analytical and analytical assay parameters used for each clinical scenario is needed to fully implement NGS into routine practice and provide more personalized management in patients with suspected or established pancreatobiliary neoplasia. Abstract Pancreatic cancer and cholangiocarcinoma are lethal diseases mainly diagnosed at an inoperable stage. As pancreatobiliary surgical specimens are often unavailable for further molecular testing, this review aimed to highlight the diagnostic, prognostic, and therapeutic impact of next-generation sequencing (NGS) performed on distinct small biopsies, including endoscopic ultrasound fine-needle aspirations and biopsies of pancreatic solid and cystic lesions, biliary duct brushings, and also “liquid biopsies” such as the pancreatic juice, bile, and blood. NGS could clarify indeterminate pancreatic lesions or biliary strictures, for instance by identifying TP53 or SMAD4 mutations indicating high-grade dysplasia or cancer. It could also stratify pancreatic cystic lesions, by distinguishing mucinous from non-mucinous cysts and identifying high-risk cysts that should be excised in surgically fit patients, whereas the combination of cytology, elevated cystic CEA levels and NGS could improve the overall diagnostic accuracy. When NGS is performed on the pancreatic juice, it could stratify high-risk patients under surveillance. On the plasma, it could dynamically monitor the disease course and response to therapy. Notably, the circulating tumor DNA (ctDNA) levels have been associated with staging, grading, and survival. Lastly, NGS has shown potential in identifying potentially actionable molecular alterations. In conclusion, NGS applied on small biopsies could carry significant diagnostic, prognostic, and therapeutic value.

Objective Fine needle aspiration (FNA) is a minimally invasive albeit highly effective modality used to detect solid and cystic pancreatic lesions. This manuscript aims to present our experience in diagnosing metastases to the pancreas and highlight the importance of immunocytochemistry in the diagnostic process. It also aims to provide a brief review of the literature on this topic. Methods We retrospectively searched our archives for cases of metastatic deposits to the pancreas diagnosed with FNA over a 5-year period. We also reviewed the literature for such cases. Results We describe seven cases from our archives that metastasised to the pancreas. Three of them (43%) represented metastatic renal cell carcinoma while the rest four comprised deposits from a lung adenocarcinoma, a colon adenocarcinoma, an adrenal leiomyosarcoma, and a small cell carcinoma of the urinary bladder, respectively. History of primary malignancy was available for all seven patients. All diagnoses were confirmed with the use of immunostains. In our literature review, similar to our case series, renal cell carcinoma was the most common metastasis to the pancreas managed with FNA (around one out of three patients; 35%). Of interest, our endoscopic ultrasound-FNA case of pancreatic metastasis from urinary bladder small cell carcinoma is the first reported. Conclusions As metastases to the pancreas are commonly accompanied by diverse prognostic signatures and management strategies compared to primary pancreatic malignancies, their accurate identification is imperative. Pancreatic FNA is a diagnostic modality that can confirm or exclude metastasis to the organ, especially when immunocytochemistry is applied.

Backgroung/Aim: Salivary gland malignancies are rare, with only a fraction due to metastases. We report a rare case of the Clear Cell Renal Cell Carcinoma (CCRCC), a subtype of the Renal Cell Carcinoma (RCC), metastasizing to the parotid gland more than five years following nephrectomy. Case report: A 75-year-old female presented with a unilateral left parotid mass that was growing over the period of 18 months. After clinical and laboratory examinations, the patient underwent left partial superficial parotidectomy with preservation of the facial nerve. The significance of the patient's history of the CCRCC was pivotal to the histopathological diagnosis of a metastatic CCRCC to the parotid. Conclusions: The unpredictable nature of the RCC results in the need for a long period of follow-up, as well as having a high degree of suspicion of metastasis in a patient presenting with a medical history of the RCC and a parotid mass.

An adrenal incidentaloma (AI) is an adrenal mass incidentally found via a radiological modality, independent of an endocrinological investigation. In this review, we aimed to investigate the possible reasons behind the increased frequency in AI detection, especially in ageing populations. The pathophysiological effects of insulin resistance (IR), hyperinsulinemia and various anabolic pathways are analyzed. In addition, we review data from studies indicating an increased incidence of adrenal adenomas and carcinomas in patients with type 2 diabetes mellitus (T2DM). The establishment of obesity as a global epidemic, with a higher prevalence in the female than in the male population, coincide with data regarding AIs and the conditions may share a pathophysiological basis. Furthermore, we discuss the bidirectional association of AIs with obesity, insulin resistance and T2DM, especially in patients with autonomous cortisol secretion. Lastly, as per the definition of an AI, we touch upon the evolution of radiological imaging as another possible cause of the rise in prevalence of AIs, especially concerning the greater use and precision of computed tomography (CT).

Spontaneous bacterial peritonitis (SBP) is a common complication in patients with cirrhosis and has an incidence of up to 30% in hospitalized patients. Importantly, it may raise their mortality rate up to 30%. Hence, a delayed diagnosis is associated with poor prognosis. This systematic review aims to assess the diagnostic accuracy of ascitic fluid calprotectin for the early diagnosis of SBP in patients with ascites. This study was conducted in accordance with the PRISMA statement. A systematic literature search was conducted from inception to February 2020 in the following electronic bibliographic databases: MEDLINE, Scopus, The Cochrane Library and OpenGrey. Quality Assessment of Diagnostic Accuracy Studies tool was used to assess risk of bias. Ten studies were included in the qualitative and quantitative synthesis. Hierarchical summary receiver operating characteristic curves were plotted and the summary sensitivity of a positive ascitic fluid calprotectin assessment to detect SBP was 93% [95% confidence interval (CI) 90-95%] while the summary specificity was 89% (95% CI 80-95%), irrespectively of the method used. The positive likelihood ratio and negative likelihood ratio of the test were 8.7 (95% CI 4.4-17.1) and 0.08 (85% CI 0.06-0.12). All studies showed positive correlation between ascitic calprotectin and polymorphonuclear (PMN) leukocyte count. Ascitic calprotectin appears to be an excellent alternative to PMN leucocyte count of ≥250 cells/mm3 for the diagnosis of SBP with much faster time to diagnosis. Owing to its substantially high negative predictive value, the test can accurately exclude SBP avoiding unnecessary antibiotics in suspected patients.

The aim of this review is to explore and discuss disorders of glucose metabolism that can arise in individuals with adrenal gland disorders, as well as to enumerate the available therapeutic treatments for these while considering their benefits and drawbacks. Hyperfunctioning adrenal glands, as in hypercortisolism, hyperaldosteronism, and malignancy, or hypofunctioning of adrenal glands, as in adrenal insufficiency, can lead to carbohydrate metabolism dysregulation with subsequent glucometabolic repercussions, either hyperglycemia or hypoglycemia. Glycemic disorders further affect patients' quality of life and represent a therapeutic dilemma for physicians. Current management strategies for glycemic dysregulation in individuals with adrenal gland disorders are fighting the underlying causes, as well as utilizing antidiabetic therapies that aid in maintaining euglycemia. Further research focused on discovering drug preparations of greater accuracy and effectiveness tailored to patients with adrenal problems as well as studies investigating optimal lifestyle management models for these individuals will assist towards achieving optimal regulation of glucose metabolism.

Serous cystadenoma (SCA) is an uncommon benign pancreatic neoplasm that is most often managed conservatively with follow-up rather than surgical excision. Therefore, to avoid the serious complications of pancreatic surgery, SCA should be diagnosed accurately at the preoperative level. Preoperative SCA diagnosis requires a multimodal diagnostic approach that includes imaging, cystic fluid biochemical analysis and/or endoscopic ultrasound fine-needle aspiration (EUS-FNA). In this brief report, we describe six EUS-FNA cases from five patients that were reported as "benign, consistent with serous cystadenoma". Samples were hypocellular, composed of loose clusters and single cuboidal, bland-looking cells among epithelial sheets representing gastrointestinal contamination. Cell blocks were prepared and all six FNA cases revealed cuboidal cells with a positive α-inhibin immunophenotype, consistent with a diagnosis of SCA. As EUS-FNAs of SCA commonly result in non-diagnostic interpretations, cell block preparations with subsequent immunochemistry can increase their diagnostic accuracy and guide patient management.

The presence of malignant squamous cells in pancreatic cytopathology is a rare phenomenon that results either from a primary or a metastatic process. Pancreatic adenosquamous carcinoma (PASC) represents the most common variant of pancreatic ductal adenocarcinoma and is associated with a dismal prognosis. Within the period of 2013-2018, the archives of "Hygeia and Mitera Hospital" were searched for pancreatic cytopathology-related diagnoses that included the interpretation of "malignant squamous cells present." All fine needle aspirations (FNAs) of pancreatic lesions, including liver metastases in patients with known pancreatic primaries, were retrieved along with their relevant clinical information. Five pancreatic and two liver FNAs acquired from a total of six patients were reexamined. None of these patients had any documented history of primary squamous malignancy elsewhere. All pancreatic and one of the two liver FNAs showed malignant squamous cells, identified based on either morphology or immunochemistry. The other liver FNA represented a metastatic deposit which comprised of only a glandular component, whereas the associated pancreatic FNA exhibited both squamous and glandular counterparts. Most cases characteristically showed necrosis and keratinization. Of interest, two cases revealed the presence of tumor-associated giant cells. In conclusion, the presence of malignant squamous cells in pancreatic FNAs could mean the presence of PASC, especially when there is no documented history of a primary malignancy and a complete clinical and imaging workup has been performed. Immunochemistry on cell block material could help to confirm squamous differentiation in the absence of overt keratinization.