Current trends in the diagnosis of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a dreaded malignancy with a dismal 5-year survival rate despite maximal efforts on optimizing treatment strategies. Currently, early detection is considered to be the most effective way to improve survival as radical resection is the only potential cure. PDAC is often divided into four categories based on the extent of disease: resectable, borderline resectable, locally advanced, and metastatic. Unfortunately, the majority of patients are diagnosed with locally advanced or metastatic disease, which renders them ineligible for curative resection. This is mainly due to the lack of or vague symptoms while the disease is still localized, although appropriate utilization and prompt availability of adequate diagnostic tools is also critical given the aggressive nature of the disease. A cost-effective biomarker with high specificity and sensitivity allowing early detection of PDAC without the need for advanced or invasive methods is still not available. This leaves the diagnosis dependent on radiodiagnostic methods or endoscopic ultrasound. Here we summarize the latest epidemiological data, risk factors, clinical manifestation, and current diagnostic trends and implications of PDAC focusing on serum biomarkers and imaging modalities. Additionally, up-to-date management and therapeutic algorithms are outlined.

Current view of neoadjuvant chemotherapy in primarily resectable pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is now the 11th most common cancer and in 2018 there were 458,918 new cases worldwide. In the Czech Republic, a total of 2,173 patients were diagnosed in 2015, ranking the second in incidence worldwide. In contrast to other malignancies, recent research has not brought any major breakthrough in the treatment of PDAC and hence the prognosis remains very serious. Radical resection is the only curative approach, but after the initiation of the standard pathological evaluation of the resected tissue, according to the Leeds protocol, 80% of the resections are R1 (resections with microscopically positive margins). The results of studies in patients with borderline resectable or locally advanced PDAC prefer neoadjuvant chemotherapy or chemoradiotherapy. This approach leads to a higher number of radical R0 resections and better survival. For neoadjuvant treatment in patients with primarily resectable PDAC, most results come from retrospective analysis or phase II trials. However, recently, data from three randomized clinical trials with neoadjuvant therapy for resectable PDAC were presented. These results support the use of chemotherapy or chemoradiotherapy prior to surgery. In the trials published to date, there are differences in chemotherapeutic regimens, cytostatic doses, and the definition of resectability. Thus, up-front resection with adjuvant chemotherapy is still the standard of care and a well-designed randomized trial using neoadjuvant therapy is now necessary.

Is autoimmune pancreatitis a risk factor for pancreatic adenocarcinoma?

Immunoglobulin G4-related diseases (IgG4-RD) are a group of diseases characterized by high serum levels of immunoglobulin G4 (IgG4), increased lymphocyte and plasma cell with IgG4 positivity in the parenchyma of some organs, and storiform fibrosis. The most frequently affected organ is the pancreas. This is an autoimmune form of pancreatitis, which can be divided into two types: Type 1, which is significantly more common than Type 2, is high in IgG4 in the pancreatic parenchyma and shows a fundamental difference in the noted presence of extrapancreatic disorders. In general, chronic inflammation is a risk factor in the development of carcinomas. Chronic pancreatitis is an accepted risk factor for the development of pancreatic cancer. The question is whether this also applies to autoimmune pancreatitis (AIP), which has some mediators of inflammation in common with sporadic pancreatitis, and what role the presence of IgG4 plays. The vast majority of the work on this topic consists of case reports, yet, even based on our own experience, we would like to say that there is a relationship between the autoimmune form of pancreatitis and pancreatic cancer, which usually occurs in the first two years after diagnosis of AIP. Also significant is the fact that the group of people with AIP, who is a clinical manifestation of IgG4-RD, was found to have an even higher incidence of extrapancreatic cancer than in the pancreas itself. Differentiating AIP from pancreatic cancer can sometimes be problematic since these diseases can both present as focal pancreatic lesions. IgG4 has been considered useful for AIP diagnosis, however, IgG4 levels can be slightly elevated, as in the case with pancreatic adenocarcinoma. IgG4 levels of over twice the upper limit are rare among patients with pancreatic adenocarcinoma. However, cases of simultaneous presentation of pancreatic cancer and AIP have been documented and should not be neglected. AIP is a condition where regular followup is mandatory, including from the perspective of possible cancerogenesis.

Hereditary hemorrhagic telangiectasia (OslerWeberRendu syndrome) - Part II. Pharmacological therapy and international guidelines for the therapy 2020.

Hereditary hemorrhagic telangiectasia also known as Osler-Weber-Rendu syndrome, is an disorder that causes abnormal blood vessel formation with bleeding. Inhibition of angiogenesis amelioretes bleeding complication. Anti-angiogenic agents such as bevacizumab, aflibercept, thalidomid, lenadomid and other new anti-angiogenic thyrosinkinase inhibitors, as well as sirolimus and takrolimus have emerged as a promising systemic or local therapy in reducing bleeding complications but are not curative. Other pharmacological agents include iron supplementation, antifibrinolytics and hormonal treatment. This review concentrates on new anti-agioproliferative drugs with effect in HHT- discusses the new biology of HHT, management issues that face the practising hematologist, and considerations of future directions in HHT treatment.

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) Part I. Pathophysiology, clinical symptoms and recommend screening for vascular malformations.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant disorder that causes abnormal blood vessel formation. Patients with HHT may have telangiectasias and later may develop arteriovenous malformations in various organs. Pacients suffer from many complications caused by the malformations and therefore by patients with HHT must by performed screening of this arteriovenous malformations. Optimal treatment of this malformations is best delivered throught a multidisciplinary approach. Farmacological treatment is described in next paper.

Small bowel adenocarcinoma diagnosed by video capsule endoscopy in a patient with celiac disease: a case report and review of literature.

Celiac disease is an immune mediated entheropathy triggered by gluten in genetically predisposed individuals. Patients with celiac disease are at a higher risk of gastrointestinal malignancies. Diagnosis at an advance stage is one of the factors of an unfavorable prognosis of these complications. Our patient is a woman who was diagnosed with celiac disease at 53 years of age. After two years on a gluten-free diet she developed sideropenic anemia. No source of bleeding was found on the esophagogastroduodenoscopy or colonoscopy. Video capsule endoscopy revealed exulcerated bleeding stenosis in the jejunum, in front of which the capsule lodged. There were no signs of infiltration on simultaneous CT enterography. The patient was operated on and the infiltration of the jejunum was resected. The specimen was evaluated by a histopathologist as a moderately differentiated adenocarcinoma. Due to the risk factors, the patient received adjuvant chemotherapy. The knowledge of the malignant complications of celiac disease, their risk factors and the possibilities of modern enteroscopic methods could help in the early diagnosis and improvement of the prognosis of these diseases. Due to a lack of data and an absence of guidelines, treatment of a small bowel adenocarcinoma is based on an expert agreement and guidelines for colon cancer. Surgical treatment is the only potentially curative option. For stage II with risk factors and stage III adjuvant chemotherapy should be considered.

Multiple neuroendocrine tumor of the small bowel: a case report and a review of literature.

Primary malignant tumors of small bowel constitute only about 1-2% of all gastrointestinal neoplasms. Although neuroendocrine tumors (NETs) are relatively rare, they still represent the second most common malignancy of the small bowel (after adenocarcinoma). Clinical manifestations include abdominal pain, bowel obstruction, diarrhea, weight loss and bleeding. The differential diagnosis of obscure gastrointestinal bleeding can sometimes be challenging for endoscopy as well as for radiology methods. We present the case of an 80-year-old man suffering from severe hypochromic anemia. Routine endoscopic methods did not show any appropriate pathology. Finally, a single ulcerative infiltration of the ileum was diagnosed by capsule endoscopy (CE). CT enterography did not reveal any other lesions. In accordance with a positive chromogranin A, endoscopic and radiologic methods, a suspicion of NET was expressed. During the surgery, 7 lesions were found and a resection of 120 cm of ileum was performed. The histology confirmed a diagnosis of NET grade 1, with a total number of 15 NET lesions in the specimen. The following octreotide scan did not show any residual infiltration. We present a patient with 15 NET lesions in the ileum diagnosed by CE and successfully cured by surgical resection of the ileum. Key words: capsule endoscopy - carcinoid syndrome - gastrointestinal carcinoids - neuroendocrine tumor - obscure gastrointestinal bleeding - small bowel - surgery.

Surgical Treatment of Ampullary Adenocarcinoma - Single Center Experience and a Review of Literature.

BACKGROUND: Adenocarcinomas of ampulla of the Vater are relatively uncommon tumors of the gastrointestinal tract. In premalignant lesions endoscopic treatment predominate. According to some authors even early adenocarcinomas (limited to mucosa) can be solved endoscopically. In malignant lesions affecting deeper layers (including submucosa) surgical therapy is the most important. The article summarises the current view for a surgical treatment of ampullary adenocarcinomas and presents results concerning our group of patients. MATERIALS AND METHODS: In 2012-2016 a total number of 17 patients underwent resection for a tumor of ampulla of the Vater. Patients underwent standard staging, were presented before a multidisciplinary committee and referred to a surgical treatment. The main measured parameters were the type of surgical procedure, 30-day morbidity and mortality, histopathologic result and subsequent oncologic treatment. The Leeds Pathology Protocol was used to evaluate the specimens after pancreaticoduodenectomy (PD). RESULTS: PD (n = 9) was a more often performed procedure than the transduodenal surgical ampullectomy (TSA) (n = 8). TSA predominated in polymorbid patients. Histological results (n = 17) established adenoma with high-grade dysplasia in 4 patients, the diagnosis of adenocarcinoma was set in 13 patients. Eight patients underwent adjuvant oncologic therapy (2 had adjuvant chemotherapy, 6 had combination of chemoradiotherapy). CONCLUSION: Premalignant neoplasias of ampulla of the Vater can be mostly solved by endoscopy. If endoscopic resection is not possible surgical therapy is indicated. PD is preferred procedure in the diagnosis of adenocarcinoma. In high-risk and polymorbid patients, with no suspicion for a metastatic lymph nodes, TSA can be considered. Endoscopic ultrasonography is the imaging modality of choice for local staging of ampulla of the Vater and has important role in deciding between endoscopic, local surgical excision (TSA) or radical resection (PD). Our results confirmed rightfulness to perform TSA especially in elderly or polymorbid patients, where in histopathologic specimens evaluation in TSA procedures early T stage and more favorable grading predominated.Key words: adenocarcinoma of the ampulla of Vater - duodenum - endoscopic resection - ampullectomy - pancreaticoduodenectomy - surgery.

[PET-CT documented remission of multicentric Castleman disease after treatment with rituximab: case report and review]. / PET-CT dokumentovaná remise multicentrické formy Castlemanovy choroby po lécbe rituximabem Popis prípadu a prehled literatury.

We describe a case of multicentric Castleman disease with generalized lymphadenopathy and splenomegaly, accompanied by typical B symptoms - loss of 15 kg, fever of non-infectious origin, night sweats, symptoms of anemia. Histological examination of the nodes with the highest accumulation of fluorodeoxyglucose, taken from mediastinum by thoracoscopy, revealed plasmocellular type of Castleman disease. Tests for HIV and human herpesvirus 8 (HHV-8) were negative. Three recurrences of herpes zoster indicating an alteration of immunity preceded the dia-gnosis of disease. Treatment was initiated with combination of thalidomide, dexamethasone, and cyclophosphamide. The response after 2 months therapy was not clear and patient doesn't tolerated the therapy well. Therefore, this treatment was terminated and R-CHOP (Mabthera - rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone) was selected as a second-line therapy. Lymphadenopathy and splenomegaly were reduced during the 2 cycles of treatment, however, serious infectious complications accompanied the therapy. Therefore, only use of Mabthera monotherapy 375 mg /m2 was administered in 28-day intervals. This treatment has shown efficacy and tolerability. PET-CT scan has demonstrated disappearance of lymphadenopathy and splenomegaly, in addition, normalized accumulation of fluorodeoxyglucose. Monotherapy with Mabthera has proved to be effective and well tolerated drug in this case. Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab). In the case of ineffectiveness of one treatment option must be tested other alternative. In this case the therapy based on thalidomide wasn't successful, whereas the treatment with Mabthera has achieved disappearance of disease symptoms.

Management of pheochromocytomas and paragangliomas: Review of current diagnosis and treatment options.

Pheochromocytomas (PCCs) are rare neuroendocrine tumors derived from the chromaffin cells of the adrenal medulla. When these tumors have an extra-adrenal location, they are called paragangliomas (PGLs) and arise from sympathetic and parasympathetic ganglia, particularly of the para-aortic location. Up to 25% of PCCs/PGLs are associated with inherited genetic disorders. The majority of PCCs/PGLs exhibit indolent behavior. However, according to their affiliation to molecular clusters based on underlying genetic aberrations, their tumorigenesis, location, clinical symptomatology, and potential to metastasize are heterogenous. Thus, PCCs/PGLs are often associated with diagnostic difficulties. In recent years, extensive research revealed a broad genetic background and multiple signaling pathways leading to tumor development. Along with this, the diagnostic and therapeutic options were also expanded. In this review, we focus on the current knowledge and recent advancements in the diagnosis and treatment of PCCs/PGLs with respect to the underlying gene alterations while also discussing future perspectives in this field.

Stereotactic Body Radiotherapy (SBRT) of Pancreatic Cancer-A Critical Review and Practical Consideration.

Pancreatic cancer is the third leading cause of cancer death in the developed world and is predicted to become the second by 2030. A cure may be achieved only with surgical resection of an early diagnosed disease. Surgery for more advanced disease is challenging and can be contraindicated for many reasons. Neoadjuvant therapy may improve the probability of achieving R0 resection. It consists of systemic treatment followed by radiation therapy applied concurrently or sequentially with cytostatics. A novel approach to irradiation, stereotactic body radiotherapy (SBRT), has the potential to improve treatment results. SBRT can deliver higher doses of radiation to the tumor in only a few treatment fractions. It has attracted significant interest for pancreatic cancer patients, as it is completed quickly, requires less time away from full-dose chemotherapy, and is well-tolerated than conventional radiotherapy. In this review, we aim to provide the reader with a basic overview of current evidence for SBRT indications in the treatment of pancreatic tumors. In the second part of the review, we focus on practical information with respect to SBRT treatment plan preparation the performance of such therapy. Finally, we discuss future directions related to the use of magnetic resonance linear accelerators.

The Role of Circulating MicroRNAs in Patients with Early-Stage Pancreatic Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is increasing in incidence and is still associated with a high rate of mortality. Only a minority of patients are diagnosed in the early stage. Radical surgery is the only potential curative procedure. However, radicality is reached in 20% of patients operated on. Despite the multidisciplinary approach in resectable tumors, early tumor recurrences are common. Options on how to select optimal candidates for resection remain limited. Nevertheless, accumulating evidence shows an important role of circulating non-coding plasma and serum microRNAs (miRNAs), which physiologically regulate the function of a target protein. miRNAs also play a crucial role in carcinogenesis. In PDAC patients, the expression levels of certain miRNAs vary and may modulate the function of oncogenes or tumor suppressor genes. As they can be detected in a patient's blood, they have the potential to become promising non-invasive diagnostic and prognostic biomarkers. Moreover, they may also serve as markers of chemoresistance. Thus, miRNAs could be useful for early and accurate diagnosis, prognostic stratification, and individual treatment planning. In this review, we summarize the latest findings on miRNAs in PDAC patients, focusing on their potential use in the early stage of the disease.

Causes of Exocrine Pancreatic Insufficiency Other Than Chronic Pancreatitis.

Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malnutrition, results from primary pancreatic disease or is secondary to impaired exocrine pancreatic function. Although chronic pancreatitis is the most common cause of EPI, several additional causes exist. These include pancreatic tumors, pancreatic resection procedures, and cystic fibrosis. Other diseases and conditions, such as diabetes mellitus, celiac disease, inflammatory bowel disease, and advanced patient age, have also been shown to be associated with EPI, but the exact etiology of EPI has not been clearly elucidated in these cases. The causes of EPI can be divided into loss of pancreatic parenchyma, inhibition or inactivation of pancreatic secretion, and postcibal pancreatic asynchrony. Pancreatic enzyme replacement therapy (PERT) is indicated for the conditions described above presenting with clinically clear steatorrhea, weight loss, or symptoms related to maldigestion and malabsorption. This review summarizes the current literature concerning those etiologies of EPI less common than chronic pancreatitis, the pathophysiology of the mechanisms of EPI associated with each diagnosis, and treatment recommendations.

Triple malignancy (NET, GIST and pheochromocytoma) as a first manifestation of neurofibromatosis type-1 in an adult patient.

BACKGROUND: Neurofibromatosis type-1 (NF1), also called von Recklinghausen disease, is a rare genetic disease which can lead to the development of benign or even malignant tumors. NF1 is mostly diagnosed in children or early adolescents who present with clinical symptoms. A curative therapy is still missing and the management of NF1 is based on careful surveillance. Concerning tumors which affect the gastrointestinal tract in patients with NF1, the most common is a gastrointestinal stromal tumor (GIST). CASE PRESENTATION: We present a case of a 58-year-old adult patient with dyspeptic symptoms who was incidentally diagnosed with triple malignancy (pheochromocytoma, multiple GISTs of small intestine and an ampullary NET) as a first manifestation of NF1. The patient underwent surgical treatment (adrenalectomy and pancreaticoduodenectomy) with no complications and after 2 years remains in oncological remission. CONCLUSION: NF1 is a rare genetic disease which can cause various benign or malignant tumors. The coincidence of GIST and NET is almost pathognomonic for NF1 and should raise a suspicion of this rare disorder in clinical practice.