Emerging human alveolar echinococcosis in Hungary (2003-2018): a retrospective case series analysis from a multi-centre study.

BACKGROUND: Human alveolar echinococcosis (AE) caused by Echinococcus multilocularis is an underreported, often misdiagnosed and mistreated parasitic disease mainly due to its low incidence. The aim of this study was to describe the epidemiological and clinical characteristics of human AE patients in Hungary for the first time. METHOD: Between 2003 and 2018, epidemiological and clinical data of suspected AE patients were collected retrospectively from health database management systems. RESULTS: This case series included a total of 16 AE patients. The mean age of patients was 53 years (range: 24-78 years). The sex ratio was 1:1. Four patients (25%) revealed no recurrence after radical surgery and adjuvant albendazole (ABZ) therapy. For five patients (31.3%) with unresectable lesions, a stabilization of lesions with ABZ treatment was achieved. In seven patients (43.8%), progression of AE was documented. The mean diagnostic delay was 33 months (range: 1-122 months). Three AE related deaths (fatality rate 18.8%) were recorded. CONCLUSIONS: AE is an emerging infectious disease in Hungary with a high fatality rate since based on our results, almost every fifth AE patient died in the study period. Differential diagnosis and appropriate surgical and medical therapy for AE is an urging challenge for clinicians in Hungary, as well as in some other European countries where E. multilocularis is prevalent.

Autochthonous human alveolar echinococcosis in a Hungarian patient.

BACKGROUND: Alveolar echinococcosis is a zoonotic parasitic disease causing a severe clinical condition and is known as the most deadly of all helminth infections. Moreover, this disease is also an increasing concern in Northern and Eastern Europe due to its spread in the wildlife animal host. CASE PRESENTATION: An asymptomatic 70-year-old woman from south-western Hungary was diagnosed with multiple liver lesions. Imaging techniques (ultrasound, computed tomography and magnetic resonance imaging), serology (ELISA, indirect hemagglutination and Western blot), and conventional staining methods (hematoxylin-eosin and periodic acid-Schiff) were used for the detection of the disease. A histopathological re-evaluation of formalin-fixed paraffin block by immunohistochemical staining with the monoclonal antibody Em2G11 definitively confirmed the diagnosis of alveolar echinococcosis. CONCLUSIONS: To our knowledge, this is the first confirmed autochthonous case of human alveolar echinococcosis in Hungary. To what extent diagnostic difficulties may contribute to underestimate this zoonosis in Eastern Europe is unknown. Differential diagnosis with alveolar echinococcosis should be considered for patients with multiple, tumor-like cystic lesions of the liver, in countries where this parasite is emerging.

Cystathionine ß-synthase overexpression drives metastatic dissemination in pancreatic ductal adenocarcinoma via inducing epithelial-to-mesenchymal transformation of cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest of all cancer types with a constant rise in global incidence. Therefore, better understanding of PDAC biology, in order to design more efficient diagnostic and treatment modalities, is a priority. Here we found that the expression levels of cystathionine ß-synthase (CBS), a transsulfuration enzyme, is markedly elevated in metastatic PDAC cells compared to cell lines isolated from non-metastatic primary tumors. On human immunohistochemical samples from PDAC patients we also found higher CBS staining in cancerous ductal cells compared to in non-tumor tissue, which was further elevated in the lymph node metastasis of the same patients. In mice, orthotopically injected CBS-silenced T3M4 cells induced fewer liver metastases compared to control cells indicating important roles for CBS in PDAC cancer cell invasion and malignant transformation. Wound healing and colony formation assays in cell culture confirmed that CBS-deficient metastatic T3M4 and non-metastatic BxPC3 primary tumor cells migrate slower and have impaired anchorage-independent growth capacities compared to control T3M4 cells. CBS silencing in T3M4 cells lowered WNT5a and SNAI1 gene expression down to levels that were observed in BxPC3 cells as well as resulted in an increase in E-cadherin and a decrease in Vimentin signals in mouse tumors when injected orthotopically. These observations suggested a primary role for the epithelial to mesenchymal transformation of cancer cells in CBS-mediated tumor aggressiveness. Under normal conditions, STAT3, an upstream regulator of Wnt signaling pathways, was less phosphorylated and more oxidized in shCBS T3M4 and BxPC3 compared to control T3M4 cells, which is consistent with decreased transcriptional activity at lower CBS levels due to less protection against oxidation. Sulfur metabolome analyses suggested that this CBS-mediated protection against oxidative modifications is likely to be related to persulfide/sulfide producing activities of the enzyme rather than its canonical function to produce cystathionine for cysteine synthesis. Taken together, CBS overexpression through regulation of the EMT plays a significant role in PDAC cancer cell invasion and metastasis.

[Pathology of pancreatic ductal adenocarcinoma]. / A hasnyálmirigy duktális adenokarcinómájának patológiája.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. At the time of diagnosis, the cancer is usually at an advanced stage and only a minority of the cases are eligible for surgical resection. To improve prognosis, it is crucial to diagnose and treat the disease at an early stage. This article reviews the cytopathology and histopathology of PDAC and its precursors. The three main aspects of PDAC pathology are the primary confirmation of cancer, the macroscopic and microscopic evaluation of pancreatic resection specimens and molecular testing. It is beneficial to run the diagnostics and to treat the patients at specialized pancreatic cancer centers, where every member of the team is confronted with many cases.

[Comparison of open and laparoscopic minor liver resections for malignant tumours - based on the experience of the first 50 cases]. / Malignus májdaganatok miatt végzett laparoszkópos minor reszekciók eredményei az elso 50 eset kapcsán.

INTRODUCTION: Laparoscopic resection of liver malignancies is gaining acceptance. Besides the advantages of minimally-invasive techniques, publications so far show no oncologic compromise of laparoscopy. AIM: Our aim was to compare the results of our first fifty laparoscopic minor liver resections with traditional open procedures. METHOD: We investigated laparoscopic and open minor liver resections performed in our institute between 01. 01. 2013 and 31. 03. 2017. Data were analysed retrospectively. Resection of maximum two segments was considered a minor resection. We compared the number of resected segments, intraoperative blood loss, operative time, 30 day morbidity and mortality, hospital stay, R1 resection ratio and resection margin width. RESULTS: During the given period, 123 open and 55 laparoscopic minor liver resections of malignant liver tumours were performed. Open and laparoscopic groups were similar considering age, sex and health status. The ratio of bi-segmentectomies was significantly higher in the open group (p<0.001). Operation time (p = 0.91) and peri-operative transfusion ratio did not differ in the two groups (p = 0.102). 30 day morbidity and mortality were consistent (p = 0.50; p = 0.34), but patients in the laparoscopic group spent shorter time in hospital (p = 0.0001). The average width of resection margins and the ratio of R1 resections showed no difference between open and laparoscopic groups (p = 0.447; p = 0.263). CONCLUSION: Our investigation indicates that in malignant liver tumours, laparoscopic resection significantly shortens hospital stay without oncologic compromise, even though 30 day morbidity and mortality does not show difference. We conclude that laparoscopic minor resection of malignant liver tumours is safe and feasible. Orv Hetil. 2019; 160(3): 104-111.