Non-bacterial thrombotic endocarditis in pancreatic cancer and other high-risk malignancies: the case for prophylactic treatment

ABSTRACT Non-bacterial thrombotic endocarditis (NBTE) typically affects patients with underlying adenocarcinoma, often of pancreatic origin. If untreated, it can lead to serious morbidity and mortality, including recurrent ischaemic stroke. NBTE is frequently missed or confused with infective endocarditis, leading to inappropriate management. We present the case of a 54-year-old male with newly diagnosed pancreatic malignancy (CA19–9 >120 000) who suffered recurrent deep-vein-thromboses and multiple ischaemic strokes despite full anticoagulation therapy. Transoesophageal echocardiography was correctly performed, but only after a second stroke was NBTE considered. We recommend early clinical suspicion and investigation for NBTE in patients with known or suspected malignancy presenting with neurological symptoms consistent with stroke. Initial calculations indicate this could also be cost-effective. Further, the patient’s significantly elevated tumour-markers and NBTE-severity raise the possibility of a link; if further research established a reliable relationship, routine surveillance of high-risk malignancies could identify patients who might benefit from earlier echocardiography and anticoagulation management.

Carcinoma of Tail of Pancreas: A Case Report

Background: A typical manifestation of pancreatic tail cancer is large intestinal obstruction with perforation. Clinically the cancer of pancreas is usually complicated to diagnose. Most cancer patients are not having symptoms throughout during the initial stages of the cancer, which often leads to a delay in diagnosis. Treatment choices include surgery, chemotherapy, and palliative care. It is more common in African-Americans, slightly more common in men. Case Presentation: A female patient of 40 years from Wardha was admitted to Female surgery Ward, Unit-3, AVBRH on 18th December with a chief complaint of pain in epigastric region since 2weeks. Patient was apparently all right 2 months back then she was complaining of pain in the epigastric region which was insidious in onset, gradually progressive in nature, burning type of pain with radiating to left upper back. No history of fever, nausea vomiting, clay-coloured stools. After that patient was undergone on routine investigation in that total WBC count was increased i.e., 13000/cu mm and haemoglobin level were decreased i.e., 9.7gm%, liver biopsy revealed that metastasis of Adenocarcinoma probably of pancreatic origin, Computed tomography and ultrasound and it revealed that heterogenous iso-echoic mass in the tail of pancreas based on investigation she was diagnosed as a case of Carcinoma tail of pancreas and she was undergone on treatment of antibiotic before chemotherapy .after that chemotherapy treatment was done for management of pain. Conclusion: Pancreatic adenocarcinoma presents differently from large intestinal cancer and should be explored in the differential diagnosis of large intestinal obstruction.

Pancreatic Origin Hepatoid Adenocarcinoma with Liver Metastasis

Hepatoid Adenocarcinoma (HAC) is a rare form of aggressive extrahepatic neoplasm with similar morphologic features to Hepatocellular Carcinoma (HCC). HAC with pancreatic origin is rare and the exact incidence is unknown. Given shared morphological and Immunohistochemical (IHC) characteristics, it may be difficult to distinguish metastatic HAC with liver involvement from primary HCC. We present a rare case of ductal type pancreatic hepatoid adenocarcinoma involving the pancreatic head, ampulla of Vater, and liver, and illustrate strategies for diagnosis and treatment. A 65-year-old woman presented with epigastric pain, vomiting, melena, and weight loss. There was direct hyperbilirubinemia with elevated hepatic markers. Imaging displayed a pancreatic head mass with moderate biliary obstruction and a hepatic lobe lesion. Fine needle biopsy of the liver mass initially was consistent with HCC, and biopsies of the pancreatic mass and ampulla walls showed pancreatic adenocarcinoma. Due to the unusual finding of co-existing HCC and pancreatic adenocarcinoma, the hepatic mass biopsy was sent for external evaluation, which revealed poorly differentiated adenocarcinoma, consistent with HAC of pancreatic origin. The tumor was positive for mucicarmine stain, HepPar1, CEA, and CK7. It was negative for MOC-31, Arginase, ALBISH, MGB, ER, TTF-1, GCDFP15, CK-20 and CDX2, thus confirming HAC. The patient was referred to outpatient chemotherapy with gemcitabine and paclitaxel however demonstrated progression and expired following recurrent bilateral pulmonary emboli. HAC may present with non-specific symptoms, is highly aggressive, and may be difficult to distinguish from primary HCC from histopathologic characteristics alone. Accurate diagnosis requires clinicohistopathologic and IHC analysis.

Alternative Lengthening of Telomeres (ALT) in Pancreatic Neuroendocrine Tumors: Ready for Prime-Time in Clinical Practice?

Purpose of Review Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by some types of malignancies, including pancreatic neuroendocrine tumors, to overcome the issue of telomere shortening, thus supporting tumor growth and cell proliferation. This review is focused on the most important achievements and opportunities deriving from ALT assessment in PanNET onco-pathology, highlighting the most promising fields in which such biomarker could be implemented in clinical practice. Recent Findings In pancreatic neuroendocrine tumors (PanNET), ALT is strongly correlated with the mutational status of two chromatin remodeling genes, DAXX and ATRX. Recent advances in tumor biology permitted to uncover important roles of ALT in the landscape of PanNET, potentially relevant for introducing this biomarker into clinical practice. Indeed, ALT emerged as a reliable indicator of worse prognosis for PanNET, helping in clinical stratification and identification of “high-risk” patients. Furthermore, it is a very specific marker supporting the pancreatic origin of neuroendocrine neoplasms and can be used for improving the diagnostic workflow of patients presenting with neuroendocrine metastasis from unknown primary. The activation of this process can be determined by specific FISH analysis. Summary ALT should be introduced in clinical practice for identifying “high-risk” PanNET patients and improving their clinical management, and as a marker of pancreatic origin among neuroendocrine tumors.

Investigation of Nano-Bio Interactions within a Pancreatic Tumor Microenvironment for the Advancement of Nanomedicine in Cancer Treatment

Pancreatic cancer is one of the deadliest types of cancer, with a five-year survival rate of only 10%. Nanotechnology offers a novel perspective to treat such deadly cancers through their incorporation into radiotherapy and chemotherapy. However, the interaction of nanoparticles (NPs) with cancer cells and with other major cell types within the pancreatic tumor microenvironment (TME) is yet to be understood. Therefore, our goal is to shed light on the dynamics of NPs within a TME of pancreatic origin. In addition to cancer cells, normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) were examined in this study due to their important yet opposite roles of suppressing tumor growth and promoting tumor growth, respectively. Gold nanoparticles were used as the model NP system due to their biocompatibility and physical and chemical proprieties, and their dynamics were studied both quantitatively and qualitatively in vitro and in vivo. The in vitro studies revealed that both cancer cells and CAFs take up 50% more NPs compared to NFs. Most importantly, they all managed to retain 70–80% of NPs over a 24-h time period. Uptake and retention of NPs within an in vivo environment was also consistent with in vitro results. This study shows the paradigm-changing potential of NPs to combat the disease.

Targeted Cancer Therapy: What’s New in the Field of Neuroendocrine Neoplasms?

Neuroendocrine tumors (NETs) are a heterogeneous family of neoplasms of increasing incidence and high prevalence due to their relatively indolent nature. Their wide anatomic distribution and their characteristic ability to secrete hormonally active substances pose unique challenges for clinical management. They are also characterized by the common expression of somatostatin receptors, a target that has been extremely useful for diagnosis and treatment (i.e., somatostatin analogues (SSAs) and peptide-receptor radionuclide therapy (PRRT)). Chemotherapy is of limited use for NETs of non-pancreatic origin, and the only approved targeted agents for advanced progressive NETs are sunitinib for those of pancreatic origin, and everolimus for lung, gastrointestinal and pancreatic primaries. Despite recent therapeutic achievements, thus, systemic treatment options remain limited. In this review we will discuss the state-of-the-art targeted therapies in the field of NETs, and also future perspectives of novel therapeutic drugs or strategies in clinical development, including recently presented results from randomized trials of yet unapproved antiangiogenic agents (i.e., pazopanib, surufatinib and axitinib), PRRT including both approved radiopharmaceuticals (177Lu-Oxodotreotide) and others in development (177Lu-Edotreotide, 177Lu-Satoreotide Tetraxetan), immunotherapy and other innovative targeted strategies (antibody-drug conjugates, bites,…) that shall soon improve the landscape of personalized treatment options in NET patients.

An Unexpected Case Report of Adrenal Lymphangioma: Mimicking Metastatic Tumor on Imaging in a Patient With Pancreatic Cancer

Adrenal lymphangioma is a very rare benign lesion worldwide and remains challenging for early diagnosis, especially when the patient has some complicated clinical disease. This is an unusual case of a 68-year-old man who was admitted to our hospital with a history of pancreatic tumor. Computed tomography (CT) images and subsequent magnetic resonance imaging (MRI) revealed a mass located in the left adrenal gland, presenting a similar enhancement pattern of the pancreatic tumor, and according to the imaging features, the patient was suspected to have an adrenal metastatic tumor originating from the pancreatic tumor. The patient underwent a surgical resection of the pancreatic tumor and the left adrenal gland. The pathologic diagnosis proved to be lymphangioma deriving from the left adrenal gland. This is the first report presenting an atypical adrenal lymphangioma mimicking a metastatic tumor of pancreatic origin, which might be suggestive in the diagnosis of adrenal lesions and the subsequent clinical treatment, especially when patient has a particular medical history. As we know, imaging examination is helpful for accurate preoperative diagnosis; however, the diagnosis of malignant tumor solely based on imaging procedures should be made cautiously by radiologists.

Ovarian metastases of pancreatic adenocarcinoma: clinical presentation, role of surgery, and potential value of the mutational profile for the differential diagnosis with primary mucinous ovarian carcinoma

Background: Ovarian metastases (OM) of pancreatic adenocarcinoma (PA) (OM-PA) can mimic primary ovarian mucinous carcinoma (POMC) on imaging and histology. These metastases are often symptomatic and not highly chemosensitive, so that oophorectomy may be considered. Aims: The aims of this study were to compare the characteristics of OM-PA and POMC, and discuss the role of surgery. Patients and Methods: Clinical, imaging, and histological data of patients with OM-PA and POMC (2000–2017) in three tertiary centers were reviewed. Twenty-six genes were analyzed by next generation sequencing (NGS) on both primary PA and OM-PA. Results: Twenty-two women with OM-PA ( n = 13, 11 with surgical resection) or POMC ( n = 9) were selected. OM-PA were smaller than POMC ( p = 0.02); imaging, histological, and immunohistochemistry data did not clearly differentiate OM-PA from POMC in 12 of 22 cases (54%). Seven PA/OM-PA pairs were analyzed, and a concordant KRAS mutation was identified in all cases. In four OM-PA, concordant mutations were also found in TP53 ( n = 3), SMAD4 ( n = 1), MET ( n = 1), and PDGFRA ( n = 1) genes. The aim of oophorectomy in 11 OM-PA was for antalgic ( n = 6) or curative ( n = 5) intent. Pain improved in 4/6 of the former patients, but 2/6 had significant morbidity, and 2/6 died of rapid tumor progression. After oophorectomy, median progression-free and overall survivals were 6 (0–11) and 8 months (1–131), respectively. Conclusion: Analysis of mutation profiles in both primary PA and ovarian tumors, especially KRAS, can help to determine the pancreatic origin of OM-PA. Surgical resection of OM-AP in highly selected patients may improve pelvic symptoms but may also cause significant morbidity. The benefit to survival requires further studies.