Ferenc Salamon

The comparison of thrombocytosis and platelet-lymphocyte ratio as potential prognostic markers in colorectal cancer

The aim of the present study was to analyse the preoperative platelet count and the platelet-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC) of different stages and with hepatic metastasis of CRC (mCRC) and to compare these factors as potential prognostic markers. Clinicopathological data of 10 years were collected retrospectively from 336 patients with CRC and 118 patients with mCRC. Both in the CRC and the mCRC group overall survival (OS) was significantly worse in patients who had elevated platelet count (hazard ratio [HR] = 2.2, p < 0.001 and HR = 2.9, p = 0.018, respectively). Multivariate analysis indicated that elevated platelet count was an independent prognostic factor of CRC (HR = 1.7, p = 0.035) and mCRC (HR = 3.1, p = 0.017). Disease-free survival (DFS) was significantly worse in patients with elevated platelet count in the CRC group (HR = 2.0, p = 0.011). In the multivariate analysis the PLR was not a prognostic factor in either of the two cohorts (HR = 0.92, p < 0.001 and HR = 0.89, p = 0.789, respectively). The platelet count is a valuable prognostic marker for the survival in patients both with CRC and mCRC while the PLR is not prognostic in either group.

Expression of Tight Junction Molecules in Breast Carcinomas Analysed by Array PCR and Immunohistochemistry

In the past few decades an enormous amount of data became known to clarify the molecular composition and architecture of tight junctions (TJs). Despite the efforts, the expression and function of several TJ genes and proteins in breast carcinoma are still not known and some of the data are contradictory. The expression of forty-four TJ associated genes was examined at mRNA level in eighteen invasive ductal breast carcinoma samples and corresponding normal breast tissues by using low density array PCR. Expressions of claudins (CLDNs) 5, 10, 16, 17, and 18, and ZO-1, ZO-2 were evaluated by immunohistochemistry as well. Using immunohistochemical phenotype as a surrogate for the genetic subtype, 11 luminal A, 3 luminal B, 3 triple negative and one HER2+ cases were included. Ten genes were significantly downregulated in tumors compared with normal breast tissues (CLDNs 5, 10, 16, 18, 19, CTNNAL1, JAM-B, ZO-1, ZO-2 and PARD3), whereas one gene (CLDN17) was significantly up-regulated in tumors when compared with normal breast. At protein level CLDNs 5, 10, 16, 18, ZO-1 and ZO-2 were downregulated in tumors as compared with normal breast tissue. CLDN17 showed variable expression in tumor tissues in comparison to normal breast. In the single HER2+ tumor when compared with the other subtypes CLDNs 5, 16, 17, 18, CTNNAL1, JAM-B, ZO-1, ZO-2 and PARD3 genes were found to be upregulated. We found altered TJ genes and proteins whose expression has not yet been associated with breast carcinoma. Our findings show a tendency of TJ genes and proteins to be downregulated in breast cancer. Further studies are necessary to examine whether the downregulation of the above mentioned TJ associated genes and proteins may contribute to the malignant progression of invasive ductal breast carcinomas.

Relationship of postoperative thrombocytosis and survival of patients with colorectal cancer

INTRODUCTION Thrombocytosis accompanying solid tumors and predicting the prognosis of malignant tumors has been the subject of intensive research lately. Reports so far have evaluated the role of preoperative platelet count. In our present study we looked at the effect of tumor removal on platelet count and the predictive power of postoperative thrombocytosis on the survival of patients with colorectal cancer (CRC). METHODS We retrospectively evaluated the clinical and histopathological data of 336 patients operated due to CRC between 2001 and 2011. Thrombocytosis was defined as a platelet count exceeding 400 × 10(3)/μL. Preoperative platelet count was compared with the value measured 1 month postoperatively. RESULTS The platelet count significantly decreased after the removal of the primary tumor (paired Wilcoxon test p < 0.001). In univariate analysis preoperative thrombocytosis was a significant marker of overall survival (OS) with HR 2.2, p < 0.001 while the postoperative thrombocytosis was nearly significant with HR = 1.59, p = 0.087. In multivariate setting, when corrected for location, stage, tumor size and controlling for gender and age (> 65 years vs. ≤ 65 years), both pre- and postoperative thrombocytosis were significant independent prognostic markers with HR 1.80, p = 0.20 and HR = 1.98, p = 0.018, respectively. DISCUSSION AND CONCLUSION Although the pathomechanism of thrombocytosis related to solid tumors is not known the decrease of platelet count after the removal of the primary tumor raises the possibility that the tumor may play an active role in the development of thrombocytosis. Furthermore, the observation of postoperative thrombocytosis with significant worse outcome underlines the predictive power of elevated platelet count.

Binding of Trastuzumab to ErbB2 Is Inhibited by a High Pericellular Density of Hyaluronan

Although trastuzumab is an efficient drug, primary and acquired resistance is a challenging problem. The authors have previously shown in mouse xenograft experiments that masking ErbB2 by hyaluronan leads to diminished binding of the antibody and consequent resistance. In the current work, they correlated trastuzumab binding with the pericellular density of hyaluronan in ErbB2-overexpressing human breast cancer samples. A method for quantifying the relative binding of trastuzumab was developed involving constant and low-frequency background subtraction, segmenting the image to membrane and background pixels followed by evaluation of trastuzumab fluorescence, normalized with the expression level of ErbB2, only in the membrane. The normalized binding of trastuzumab showed a negative correlation with the pericellular density of hyaluronan (r = −0.52) with the effect being the most pronounced in the extreme cases (i.e., low and high hyaluronan densities predicted strong and weak binding of trastuzumab, respectively). Removal of hyaluronan by hyaluronidase digestion unmasked the trastuzumab binding epitope of ErbB2 demonstrated by a significantly increased normalized binding of the antibody. The results show that the accumulation of pericellular hyaluronan plays a crucial role in masking ErbB2.

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.

Laparoscopic resection of a mesenteric cyst

Mesenteric cysts are rare intraabdominal tumors, which cause plain symptoms. Despite the modern imaging techniques, the correct preoperative diagnosis is difficult. The optimal treatment is surgical excision of the cysts with open surgery, laparoscopy, or even retroperitoneoscopy. Surgical excision needs to be considered in case of complaints, growing cyst, or suspicion of malignancy. Indications for urgent surgery treatment are: bleeding, volvulus, torquation or ileus. Most frequently, mesenterial cysts are diagnosed during the operation of an unknown palpable abdominal cystic resistance. We present a case of a 32-year-old female patient with a jejunal mesenteric cyst, treated by laparoscopic resection. Postoperative period was uneventful, and after an early discharge the patients recovery was free of symptoms. Histopathological examination revealed a benign cyst. We conclude that laparoscopic resection of abdominal cysts with unknown origin is a safe operation and can be recommended.

Changing Pattern of Bladder Cancer Cytology. (Haynal Imre University Experience).

Urinary cytology reports of 151 patients with histologically verified tumors from the periods 1981– 1985 and 1991–1995 were analyzed. No significant change in the overall sensitivity of tumor detection (76% and 76.8%, respectively) was found. In the group of well-differentiated (G0–G1) tumors, however, 60% of the more recent cases were cytologically positive or suspicious, 23% more than ten years ago. A decrease in the detection rate of G2 tumors in the last period (72% versus 89%) was probably caused by false negative reports due to frequent inflammatory changes in the specimens. Poorly differentiated (G3–G4) transitional cell tumors resulted in a high rate of positive cytological diagnoses (93% in both periods). In cases with negative cytology at clinical suspicion of tumor, repeated sampling increased the detection rate of G0–G1 lesions from 53% up to 60%. Optimal sampling and preparation technique, cytopathologists training and improved follow-up of patients are preconditions of sensitive and specific urinary cytology.