Kristóf Dede

Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis

Adherent and tight junction molecules have been described to contribute to carcinogenesis and tumor progression. Additionally, the group of claudin-low tumors have recently been identified as a molecular subgroup of breast carcinoma. In our study, we examined the expression pattern of claudins, beta-catenin and E-cadherin in invasive ductal (IDCs) and lobular (ILCs) carcinomas and their corresponding lymph node metastases (LNMs). Tissue microarrays of 97 breast samples (60 invasive ductal carcinomas, 37 invasive lobular carcinomas) and their corresponding LNMs have been analyzed immunohistochemically for claudin-1, -2, -3, -4, -5, -7, beta-catenin and E-cadherin expression. The stained slides were digitalized with a slide scanner and the reactions were evaluated semiquantitatively. When compared to LNMs, in the IDC group beta-catenin and claudin-2, -3, -4 and -7 protein expression showed different pattern while claudin-1, -2, -3, -4 and -7 were differently expressed in the ILC group. Lymph node metastases developed a notable increase of claudin-5 expression in both groups. Decrease or loss of claudin-1 and expression of claudin-4 in lymph node metastases correlated with reduced disease-free survival in our patients. According to our observations, the expression of epithelial junctional molecules, especially claudins, is different in primary breast carcinomas compared to their lymph node metastases as demonstrated by immunohistochemistry. Loss of claudin junctional molecules might contribute to tumor progression, and certain claudin expression pattern might be of prognostic relevance.

Decreased expression of histamine H1 and H4 receptors suggests disturbance of local regulation in human colorectal tumours by histamine

Production of histamine in colon tumours has been described earlier. Histamine-mediated signals have been shown to be implicated in tumour growth, and the effects of histamine are largely determined locally by the histamine receptor expression pattern. We analysed histamine receptor expression in human colorectal cancer, adenoma and normal mucosa by quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunostaining. Real-time RT-PCR results revealed significantly decreased (p<0.001) H1R and H4R mRNA levels in tumours compared to normal colonic mucosa, without any significant change in H2R mRNA expression. H3R was absent in most samples; it was detected at low levels in 7.9% of the cases. Protein analysis showed a similar decrease in histamine receptor expression in carcinoma and adenoma compared to normal mucosa controls. Based on these results, we performed further Western blot analysis on Dukes-classified and -selected tumour samples. We found significantly decreased H4R levels in neoplastic samples compared to normal colonic tissue, but there was no significant correlation between histamine receptor expression profile and the Dukes stage of tumours. Immunohistochemical staining revealed expression patterns of H1R, H2R and H4R similar to those suggested by the mRNA and Western blot results. In the present study, we demonstrate that H1R, H2R and H4R are expressed in colon carcinoma and the adjacent normal mucosa. The results suggest a dramatic alteration in the distribution of histamine receptors in colon cancer. These findings raise the perspective of targeted pharmacological studies with selective histamine receptor antagonists or agonists in the therapy of colorectal tumours.

Inflammation of ectopic pancreatic tissue in a Meckel's diverticulum causing acute abdominal symptoms: a case report and review of the literature.

An unusual case of acute abdomen was caused by the inflammation of ectopic pancreatic tissue in a Meckel’s diverticulum. A 49-year-old man presented with acute abdominal pain, and the clinical diagnosis of acute appendicitis was established. During laparotomy, a normal appendix of unusual localization near the gallbladder and a Meckel’s diverticulum with an inflamed tip were found. Histological examination showed acute inflammation of heterotopic pancreatic tissue along with normal ectopic gastric and duodenal mucosa within the wall of the diverticulum. Fat necrosis was also ascertained. The authors believe that this is the first report of acute inflammation of ectopic pancreatic tissue and the presence of normal ectopic gastric and duodenal tissue in the same Meckel’s diverticulum.

Decreased functional activity of multidrug resistance protein in primary colorectal cancer

BackgroundThe ATP-Binding Cassette (ABC)-transporter MultiDrug Resistance Protein 1 (MDR1) and Multidrug Resistance Related Protein 1 (MRP1) are expressed on the surface of enterocytes, which has led to the belief that these high capacity transporters are responsible for modulating chemosensitvity of colorectal cancer. Several immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) studies have provided controversial results in regards to the expression levels of these two ABC-transporters in colorectal cancer. Our study was designed to determine the yet uninvestigated functional activity of MDR1 and MRP1 transporters in normal human enterocytes compared to colorectal cancer cells from surgical biopsies.Methods100 colorectal cancer and 28 adjacent healthy mucosa samples were obtained by intraoperative surgical sampling. Activity of MDR1 and MRP1 of viable epithelial and cancer cells were determined separately with the modified calcein-assay for multidrug resistance activity and sufficient data of 73 cancer and 11 healthy mucosa was analyzed statistically.ResultsSignificantly decreased mean MDR1 activity was found in primary colorectal cancer samples compared to normal mucosa, while mean MRP1 activity showed no significant change. Functional activity was not affected by gender, age, stage or grade and localization of the tumor.ConclusionWe found lower MDR activity in cancer cells versus adjacent, apparently, healthy control tissue, thus, contrary to general belief, MDR activity seems not to play a major role in primary drug resistance, but might rather explain preferential/selective activity of Irinotecan and/or Oxaliplatin. Still, this picture might be more complex since chemotherapy by itself might alter MDR activity, and furthermore, today limited data is available about MDR activity of cancer stem cells in colorectal cancers.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1675739129145824

Laparoscopic or open appendectomy

UNLABELLED Despite the fact that laparoscopic appendectomy was one of the first performed minimally invasive surgical procedures, the benefits and indications of its use are still controversial. METHODS Data of patients with the diagnosis of appendicitis operated either with laparoscopic (LA) or open (OA) appendectomy were collected and analyzed. PATIENTS This study involved 273 consecutive patients who had undergone appendectomy with the diagnosis of acute appendicitis at the Uzsoki Teaching Hospital, Department of Surgery between January 2005 and December 2007. 185 patients (68%) operated with the laparoscopic, 88 (32%) with the open technique, in the third year 89% of the cases underwent laparoscopic appendectomy. RESULTS The conversion rate was 27%, the reason of the conversion was the progression of the disease in 35 patients (70%) and technical in 15 cases (30%). The wound infection rate was 8% in the LA and 18% in the OA group ( p = 0.022). No significant difference was found in the reoperation rate and in the hospital readmission rate between the two groups. There was one insufficiency which was treated with conservative therapy. The hospital stay was significantly lower in the laparoscopic group ( p = 0.031). CONCLUSIONS This study demonstrated that laparoscopic appendectomy has significant advantages over open appendectomy. In our practice, laparoscopic appendectomy is the first choice of procedure in acute appendicitis.

Mikroszatellita-instabilitás előfordulása, intratumoralis heterogenitása, prognosztikus és prediktív potenciálja primer colorectalis carcinomák és párosított májáttéteik sebészi kezelését követően

Absztrakt Bevezetes: A vastagbeldaganatokra jellemző genetikai instabilitas megnyilvanulhat tobb uton: kromoszomalis instabilitas, mikroszatellita-instabilitas, illetve „CpG-island methylator phenotype”. Ezek pontosabb karakterizalasaval a rendelkezesre allo kezelesek elviekben optimalizalhatok lehetnek. Celkitűzes: A szerzők a mikroszatellita-instabilitas előfordulasat, heterogenitasat, prognosztikus es prediktiv potencialjat vizsgaltak 122 primer colontumor szisztematikusan szelektalt regioiban es 69 parositott majmetasztazisban. Modszer: Szoveti multiblokkok kialakitasa utan az MLH1, MSH2, MSH6 es PMS2 kifejeződeset vizsgaltak immunhisztokemiai modszerrel. Eredmenyek: A betegek 11,5%-a (14/122) rendelkezett mikroszatellita-instabil fenotipusu daganattal. A kulonboző tumorregiok feherjekifejeződeseben nem volt jelentős kulonbseg. A primer tumor–majmetasztazis parok eseteben 20,2%-ban a kettő mas mismatch repair statusba volt sorolhato. A relapsusmentes es teljes tulelest tekintve a mismatch repair statu...

Autoimmune pancreatitis mimicking pancreatic tumor

Autoimmune pancreatitis (AIP) is a rare disease of unknown pathomechanism. It belongs to the IgG4-related disease family and responds well to steroids, although the relapse rate can reach up to 20–30%. Differentiating AIP from the more common pancreatic cancer can be very challenging. About 20% of AIP is diagnosed postoperatively during final histological examination. Each of the investigative tools can add something to the definitive diagnosis; the question remains whether it is possible to prevent an unnecessary resection. Through our case we would like to demonstrate the differential diagnostic opportunities and present the literary background of this issue. In conclusion, we can state that whenever a focal pancreatic lesion is encountered AIP should always be considered.

From project based sample collection to a biobank

The research group takes samples for molecular genetical examinations from tumors removed during operations within ischemic time interval. Samples are stored in liquid nitrogen. Clinical data of these patients are recorded in an informatics system developed by the group. Patients are followed in an out-patient clinic set up for this purpose not financed by the National Health Insurance Fund. Tissue samples and follow up data are used to cooperate with molecular genetical laboratories.

Reszekábilis colorectalis eredetű májáttét esetén javasolt-e a preoperatív szisztémás kezelés? Onkosebészeti nézőpont

Surgical resection is still the only curative treatment for colorectal liver metastases, but this is one part of a complex therapy. Nowadays a patient with colorectal liver metastasis is not treated only by a surgeon or by an oncologist or even only by an invasive radiologist. Collective decisions, complement treatments give the only chance to treat these patients for longer time. Patients with colorectal liver metastases could be regarded as patients with chronic disease. Specially interesting are the various treatment options of resectable colorectal liver metastases. The efficiency and necessity of preoperative chemotherapy are still a hot spot in the treatment of resectable liver metastases. In this study, we try to summarize the international and local experiences and the current evidence of the use of preoperative chemotherapy in the treatment of colorectal liver metastases. Orv Hetil. 2018; 159(21): 823-830.

Laparoscopic resection of a liver metastasis from segment VII. Case report

The technique and clinical results of liver surgery are constantly evolving in recent years, and this development felt most intensely in the field of laparoscopic liver surgery. Based on the results of comparative studies reported to date, laparoscopic surgery is not inferior to open surgery. Although a very small percentage of liver resections are performed with laparoscopic technique, clearly it has a role in oncological surgery. The minor, major, anatomical, or even multi-stage liver resections can be performed with laparoscopy. The previously general recommendation, that lesions in the front segments of the liver are recommended for the minimally invasive technique is currently outdated. The authors present the history of a 70-year-old female, who underwent complex oncosurgical treatment of a locally advanced rectum carcinoma and a pure laparoscopic resection of a solitary hepatic metastasis of segment VII. With this case report the authors want to underline that malignant lesions in the posterior segments of the liver can be removed safely with laparoscopy.