The Esophageal Adenocarcinoma Epidemic Has Reached Hungary: A Multicenter, Cross-Sectional Study.

BACKGROUND: The epidemiology of esophageal cancer has changed dramatically over the past 4 decades in many Western populations. We aimed to understand the Hungarian epidemiologic trends of esophageal squamous cell cancer (SCC) and adenocarcinoma (AC). METHODS: We performed a cross-sectional study using data from esophageal cancer patients diagnosed between 1992 and 2018 at eight tertiary referral centers in four major cities of Hungary. We retrospectively identified cases in the electronic databases of each center and collected data on gender, age at diagnosis, year of diagnosis, specialty of the origin center, histological type, and localization of the tumor. Patients were grouped based on the two main histological types: AC or SCC. For statistical analysis, we used linear regression models, chi-square tests, and independent sample t tests. RESULTS: We extracted data on 3,283 patients with esophageal cancer. Of these, 2,632 were diagnosed with either of the two main histological types; 737 had AC and 1,895 SCC. There was no significant difference in the gender ratio of the patients between AC and SCC (80.1 vs 81.8% males, respectively; p = 0.261). The relative incidence of AC increased over the years (p < 0.001, b = 1.19 CI: 0.84-1.54). AC patients were older at diagnosis than SCC patients (64.37 ± 11.59 vs 60.30 ± 10.07 years, p < 0.001). The age of patients at the diagnosis of primary esophageal cancer increased over time (p < 0.001, R = 0.119). CONCLUSIONS: The rapid increase in the relative incidence of AC and simultaneous decrease of the relative incidence of SCC suggest that this well-established Western phenomenon is also present in Hungary.

[Predictive markers of immunotherapy of colorectal cancer]. / A kolorektális karcinómák immunterápiára való alkalmasságának patológiai vizsgálata.

Colorectal carcinomas are heterogeneous in their morphologic, immunologic and molecular aspects. The smooth and sharply demarcated medullary carcinomas present with an expansive border and high tumor stroma ratio. The high load of cancer neoantigens as a consequence of microsatellite instability results in numerous reactive regional lymph nodes. In contrast, the low grade, MSS type carcinomas are spiculated, desmoplastic and hard, frequently with smaller and sometimes also desmoplastic lymph node metastases. This macroscopic and histological heterogeneity is mirrored on the immunohistochemical and molecular level and is decisive from prognostic and predictive point of view. As immunotherapy opened a new front in the therapy of colorectal cancer, the pathology report has to quantify and qualify the characteristics of the tumor microenvironment, the peritumoral and intratumoral lymphoid infiltration and tumor stroma ratio in order to improve patient selection.

[A diagnostic challenge: paraduodenal pancreatitis. Two case reports]. / Egy diagnosztikus kihívás: paraduodenalis pancreatitis. Két eset bemutatása.

The paraduodenal, or groove pancreatitis is a lesser-known type of chronic pancreatitis, often mimicking malignancy, hence resulting in serious differential diagnostic challenges. Herein we report two cases of this entity. Both required analysis of the surgical specimen in order to ensure the diagnosis due to inadequate preoperative histological sampling and a vague clinical presentation. In the first case, strong suspicion of malignancy following imaging, while in the second, severe gastric outlet stenosis indicated the resection. In our report, we give a clinicopathological summary from the literature of this entity, including its epidemiology, clinical presentation and applicable diagnostic methods as well as macroscopic and microscopic pathomorphology. The pathogenesis of this disease is complex. Beside the role of alcohol, anatomic variations of the pancreatic ductal system, pancreatic islets in duodenal wall resulting from incomplete involution of dorsal pancreas, or Brunner gland hyperplasia (often observed as part of the lesion) can all play a role in the disturbance of pancreatic fluid discharge in the minor papilla area, eventually leading to this specific localised inflammation. In addition, recent investigations revealed a susceptible role of genetic polymorphism in the persistent inflammatory disorders of the pancreas. Besides summarizing the differential diagnostic aspects, we also discuss therapeutic possibilities, underlining the conservative methods, which can be used with good efficacy after a successful identification of this entity. Orv Hetil. 2019; 160(22): 873-879.

Characteristics of advanced- and non advanced sporadic polypoid colorectal adenomas: correlation to KRAS mutations.

The malignant potential of colorectal adenomas highly correlates with their pathological characteristics, such as size, histology and grade of dysplasia. Currently, based on these parameters, adenomas are characterized as "non-advanced or advanced" and patient surveillance is adjusted accordingly. The aim of this study was to investigate the correlation between the KRAS mutations and characteristics of non-advanced and advanced colorectal adenomas for predicting the risk of increased malignant potential of adenomas that may influence the decision to offer follow-up endoscopic surveillance. We used a mutagenic polymerase chain reaction - restriction fragment length polymorphism method to determine KRAS mutations in 164 colorectal sporadic polypoid adenomas (51 non-advanced-, 113 advanced adenomas) and in 40 early colorectal carcinomas. The method of mutation detection was validated according to recommendation for KRAS mutation testing in colorectal carcinoma of the European Quality Assurance Program. The limit of detection of the assay was 3 % mutated DNA with a good reproducibility. Evaluation of pathological characteristics was performed according to European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis. The morphological parameters of the adenoma such as size, histology, grade of dysplasia are highly correlated with one another: an increasing adenoma size raised the proportion of villous histology and degree of dysplasia (all p < 0.0001). KRAS mutations were detected in 31 % of the non-advanced adenomas, in 57.5 % of the advanced adenomas and in 62.5 % of the early carcinomas. Most mutations occurred at codon 12 rather than at codon 13 (72 %, 82 %, 76 % versus 22 %, 17 %, 24 %, respectively). There was no significant difference in association of KRAS mutation with age, gender, location among non-advanced-, and advanced adenomas and early carcinomas. KRAS mutation was found more often in tubulovillous and villous adenomas, whereas wild-type KRAS was observed more frequently in tubular adenomas (P < 0.0001) and there was an increased prevalence of KRAS mutations in larger adenomas (P < 0.0001). In this study KRAS mutation occurred with the same frequency in adenomas with low-grade (48 %) and high-grade (50 %) dysplasia. KRAS mutation is very strongly associated with a villous architecture and through villous component expansion, KRAS mutations may increase risk of tumor progression in sporadic colorectal polypoid adenomas.

[Massive fundic gland polyposis caused by chronic proton pump inhibitor therapy]. / Tartós protonpumpagátló kezelés hatására kialakuló masszív fundusmirigy-polyposis.

We report two cases of a massive fundic gland polyposis associated with protracted proton pump inhibitor (PPI) therapy. Both patients were females aged 51. On repeated endoscopy, the number of fundic gland polyps was increasing steeply, and they resulted in a passage disorder. In the first case, the enormous number of polyps made endoscopic removal impossible, so the patient was treated by total gastrectomy. Although our case is the second one reported in the world, we would like to draw the attention to this rare complication of long lasting PPI therapy.

Angiomatoid fibrous histiocytoma: pleomorphic variant associated with multiplication of EWSR1-CREB1 fusion gene.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor which exceptionally occurs in visceral organs or bones. Histologically this is a bland, monomorphic tumor and only occasionally shows pleomorphism. Vast majority of the soft tissue cases share the same translocation and the resulting EWSR1-CREB1 gene fusion as background pathogenetic alteration. Here we report a 10-year-old boy with subcutaneous tumor of the right shoulder. Histological, immunohistochemical and FISH analyses of the case revealed pleomorphic phenotype, characteristic immunophenotype and multiplication of the EWSR1-CREB1 fusion gene in the nuclei of the tumor cells. The possible explanation of the fusion gene multiplication, its relation to the morphology and the clinical outcome are discussed in the context of the published literature.

[The significance of elastic staining in detecting vascular invasion in colorectal carcinoma]. / Az elasztikus rostfestés jelentôôsége a colorectalis carcinomák vascularis invázióinak kimutatása szempontjából.

Venous invasion (VI) is one of the most important prognostic factors in colorectal carcinomas (CRC). The interobserver variation of this feature varies between 10% and 89.5%, mainly due to the specimen processing and staining. VI was assessed using haematoxylin and eosin (H+E) alone in 611 cases and with elastic stain (orcein-haematoxylin) in 243 CRCs. The stage, the pattern of invasion and the presence of intramural and extramural VI were determined. VI was identified in 27.45% of the H+E stained sections and in 67.1% using elastic stain counterstained with haematoxylin. The incidence of VI proved stage dependent as it has been noted in 13% of Dukes A, 36% of Dukes B, 80% of Dukes C and in 83% of CRCs with distant metastasis. The pattern of invasion is strongly connected to the VI, accordingly, VI could be identified in 82% of CRCs with invasive and only in 44% with expansive margin. The use of elastic stain did not help in differentiation of extramural tumour deposits due to the damage of elastic membranes in the vascular walls and the presence of elastic fibres in the lymph node capsule. As a conclusion, the routine use of elastic stains in our practice doubled the identification of VI. The frequency of VI depends on the stage and pattern of invasion in CRCs. As it is more likely to occur in the advanced CRCs, the use of elastic stain is even more suggested in Dukes B carcinomas with invasive margin.

Association between allelic polymorphisms of metabolizing enzymes (CYP 1A1, CYP 1A2, CYP 2E1, mEH) and occurrence of colorectal cancer in Hungary.

BACKGROUND: Genetic polymorphisms of metabolizing enzymes may affect the risk of cancer formation in humans. Since the diet can contain polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HAs), the relationship between polymorphisms of enzymes involved in PAH and HA metabolism and the occurrence of sporadic colorectal cancer was studied. PATIENTS AND METHODS: Five hundred colorectal cancer patients and 500 controls were genotyped for cytochrome P450 enzymes (CYP) 1A1 Ile/Val, CYP 1A2*1F, CYP 2E1 c1/c2, microsomal epoxy hydrolase (mEH) exon 3 Tyr113His and exon 4 His139Arg polymorphisms by allele-specific polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism (RFLP). RESULTS: The presence of CYP 1A1 Val, CYP 2E1 c2 and mEH exon 3 His alleles was statistically significantly associated with the occurrence of colorectal cancer (OR: 1.44 95% CI: 1.04-2.00; OR: 1.74 95% CI: 1.15-2.65; OR: 1.79 95% CI: 1.10-2.92, respectively). CONCLUSION: These findings suggest that allelic polymorphism of metabolizing enzymes play an important role in human colorectal carcinogenesis by affecting the metabolism of dietary carcinogens.

[Gastric micropneumatosis: a rare endoscopic entity]. / A gyomor micropneumatosisa: egy ritka endoszkópos kórkép.

The rarely described gastric micropneumatosis is caused by accumulating air in the mucus membrane. It may associate mainly with Helicobacter pylori positive atrophic gastritis or with pneumatosis due to gas producing bacteria or non-infectious causes. In our case the disorder was diagnosed in a 69 years old patient, taking clopidogrel, living in a nursing home, with history of hypertension, general arteriosclerosis, cerebral infarction, who was admitted to our department because of melaena and hematemesis. Upper endoscopy revealed a map-like, slightly raised, palm-sized area with yellowish spots on the posterior wall of the markedly inflamed stomach at the level of fundus - corpus border. Based on histology findings, that showed empty spaces among corpus glands, 10-20 microm in diameter, with no epithelial lining, the diagnosis was gastric micropneumatosis. The impaired mucosal integrity caused by mesenteric ischaemia and repeated vomiting were supposed as possible etiological factors, because 72 hours after the patient had stopped vomiting, control endoscopy showed regression, and the empty spaces were no more detectable in the histology samples. By this case report the authors would like to draw attention to a seldom diagnosed gastric injury, and discuss the factors that may predispose the development of gastric micropneumatosis.

[Inflammatory fibroid polyp of the ileum causing intestinal invagination]. / Invaginatiót okozó lobos fibroid polyp az ileumban.

Inflammatory fibroid polyps are rare benign tumor-like lesions of the gastrointestinal tract. Most frequently they are localized in the gastric antrum but can develop anywhere in the GI tract. In the small intestine the ileum is the most common site, where these polyps can cause invagination and intussusception. This happened to the patient we describe here. The latest immunohistochemical, ultrastructural and molecular genetic studies are suggestive of dendritic cell origin of inflammatory fibroid polyps, with myofibroblastic differentiation in some cases.

[Pneumatosis cystoides intestinalis, as a rare complications of coeliac disease]. / Pneumatosis cystoides intestinalis, mint a coeliakia egy lehetséges ritka szövodménye.

Intestinal pneumatosis cystoides is rarely diagnosed clinical entity characterized by multiple gas containing cysts inside the wall of the gastrointestinal tract. Primary (15%) and secondary (85%) forms are known. In the more frequent secondary forms small intestine and the right side of the colon are mainly affected, and the underlying pathology can be gastrointestinal, pulmonary or immunological. The 64 year old male patient reported by the authors showed clinical signs of severe malabsorption (his body weight: 47,5 kg, height: 178 cm, BMI: 15). The intestinal pneumatosis was diagnosed by exploration performed because of suspected perforation (pneumoperitoneum). Due to severe malabsorption the patient was admitted to Gastroenterological Department. Duodenoscopy and small bowel biopsy was performed. Small intestinal histology and presence of anti-gliadin and anti-endomysium antibody confirmed the suspected diagnosis of coeliakia. Parenteral nutrition, special gliadin free diet, hyperbaric oxygen inhalation, steroid, and metronidazole treatment resulted in a gradual improvement in the nutritional and general condition of the patient. After one year the patient is without complaints, he gained 24,5 kg body weight BMI: 22,5). The author's case points to a rare serious complication of non-treated coeliakia. Recognition of intestinal pneumatosis in time could have prevented surgical intervention in the high risk patient.

Polymorphisms of glutathione-S-transferase and arylamine N-acetyltransferase enzymes and susceptibility to colorectal cancer.

BACKGROUND: Glutathione-S-transferases (GSTs) and N-acetyltransferases (NATs) are involved in the metabolism of a wide range of carcinogenic chemicals. Allelic polymorphism of these enzymes is associated with variations in enzyme activity, hence it may affect the concentration of activated carcinogenic chemicals in the body. Previous studies suggest a possible cancer risk-modifying effect of these allelic polymorphisms, but the results are still controversial. We evaluated the effect of GSTM1, GSTT1, GSTP1, NAT1 and NAT2 enzymes on individual susceptibility to colorectal cancer, with particular attention to possible interactions between the studied genotypes. MATERIALS AND METHODS: Five hundred colorectal cancer patients and 500 matched cancer-free controls were included in the study. The allelic polymorphisms of GSTM1, GSTT1 and GSTP1, NAT1 and NAT2 enzymes were determined by PCR-based methods, from peripheral blood leukocytes, and allelic distributions were compared between colorectal cancer patients and controls. RESULTS: The GSTM1 0 allele (OR: 1.48, 95% CI: 1.15-1.92) and rapid acetylator genotypes of NAT2 (OR: 1.52, 95% CI: 1.17-1.98) were associated with an elevated risk No statistically significant correlation between NAT1, GSTT1, GSTP1 genotypes and colorectal cancer was found. Remarkably increased risk was associated with the GSTM1 0 allele--NAT2 rapid acetylator genotype combination (OR: 2.39, 95% CI: 1.75-3.26) and with the GSTM1 0 allele--NAT2 and NAT1 rapid acetylator triple combination (OR: 3.28, 95% CI: 2.06-5.23). Carrying 4 or 5 putative "high-risk" alleles substantially increased the risk of colorectal cancer (OR: 3.69, 95% CI: 2.33-5.86). CONCLUSION: The genotype of certain metabolizing enzymes affects the risk for colorectal cancer. This effect is particularly important when certain allelic combinations are studied. In the near future, individual level risk assessment may be reached by further increasing the number of studied polymorphisms, combining them with traditional epidemiological risk factors.

[Dual tumours in the GI tract: synchronous and metachronous stromal (GIST) and epithelial/neuroendocrine neoplasms]. / Kettôs tumorok a gasztrointesztinális traktusban: szinkron és metakron stromális (GIST) és epiteliális/neuroendokrin daganatok.

Gastrointestinal stromal tumours (GIST) constitute the most frequent group of mesenchymal tumours in the gastrointestinal tract (GI). During the last several decades major advances have been taken in the diagnostics, treatment, and understanding of its pathogenesis. However, much less is known about the either metachronous or synchronous concurrence of GIST and other tumours of different histogenesis. In the present study clinicopathological data of 43 patients with histologically proved gastrointestinal stromal tumour were studied mainly in regard of the occurrence of a secondary neoplasm. Among the 43, 7 cases were found with secondary tumour mainly of epithelial origin. In three cases (cases 3, 5, and 7) GIST concurred with colorectal adenocarcinoma, in one case (case 1) GIST occurred in a patient with a 3-years-history of chronic lymphocytic leukaemia (CLL), in other two (cases 2 and 4) the stromal tumour was combined with in situ adenocarcinoma of the stomach and carcinoid of the pancreas, respectively. In case 6, GIST concurred with a duodenal Brunner gland adenoma. In five cases the stromal tumour and the other neoplasm occurred synchronously, and in four of them, being the stromal tumour clinically silent, GISTs were intraoperative findings. This confirms the importance of surgical intraabdominal control before closure. In one hand the repeated concurrence of GIST and colorectal adenocarcinoma in our series, and on the other hand, that of GIST and adenocarcinoma of the stomach in the literature, may indicate an at least partly common factor, which may be involved in the pathogenesis of these neoplasms.

Ciliated hepatic foregut cyst.

Ciliated hepatic foregut cyst is a rare, benign, most often solitary and unilocular, rarely multilocular cyst made up of a ciliated pseudostratified columnar epithelium, a subepitheial connective tissue layer, a smooth muscle layer and an outer fibrous capsule. The lesion is usually found incidentally by ultrasonography, during surgical exploration or autopsy. Recent publications characterizes of its fine needle aspiration biopsy features. The lesion is mostly asymptomatic, however one case caused portal vein compression and another which showed malignant trasformation through squamous metaplasia which warns to examine these lesions cautiously. As the lesion is extremely rare it is difficult to estimate its prevalence and its nature, so every single case presentation could be important.