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.

The study was carried out to assess the possible involvement of excess AVP and free water retention in the development of late hyponatremia by comparing the postnatal course of plasma AVP and urinary excretion of AVP and sodium as well as creatinine, osmolar and free water clearances in premature infants with (group S) and without (group NS) NaCl supplementation. Plasma total protein and albumin concentrations were also determined. Group NS consisted of 8 infants with a birth weight of 1,150–1,730 g (mean: 1,440 g) and gestational age of 28–32 weeks (mean: 30.4 weeks). Group S included 8 infants with a mean birth weight of 1,390 g (range: 980–1,700 g) and a mean gestational age of 30.1 weeks (range: 27–32 weeks). Measurements were made on the 7th day and weekly thereafter until the 5th week of life. NaCl supplementation was given in a dose of 3–5 and 1.5–2.5 mmol/kg/day for 8–21 and 22–35 days, respectively. Infants receiving sodium supplements had significantly greater urinary sodium excretion (p < 0.01), retained more sodium (p < 0.01), maintained plasma sodium at normal levels and gained weight at slightly higher rates when compared with those on low sodium. Plasma AVP tended to be higher in group S but did not differ significantly from that in NS group. Urinary AVP excretion, however, either expressed in ng/day or ng/l00 ml GFR, was significantly higher in group S, although the age-related increase could not be seen when correction was made for GFR. The respective values of AVP excretion in weeks 1,2-3 and 4-5 were 1.02 ± 0.17,3.19 ± 0.47 and 2.44 ± 0.22 ng/day in group S and 0.60 ± 0.12, 0.96 ± 0.12 (p < 0.001) and 1.61 ± 0.26 ng/day (p < 0.01) in group NS. NaCl supplementation and the increased AVP excretion was associated with significant decreases in GFR (p < 0.05), free water excretion (p < 0.01), plasma total protein (p < 0.01) and plasma albumin (p < 0.01) concentrations. These data suggest that NaCl supplementation prevents late hyponatremia at the expense of AVP-mediated water retention and subsequent volume expansion.

Patients with metastatic colorectal cancer receive chemotherapy prior liver resection more and more frequently. This preoperative treatment has many effects which have to be analysed, like the safety of liver resection, toxicity, tissue regeneration, radiological and pathological response and survival data. The aim of the study was to evaluate the safety of bevacizumab containing preoperative chemotherapy and functional recovery of the liver after resection for colorectal liver metastases (CLM) and to analyse radiological and pathological data. Data of three groups of 120 consecutive patients-(1) CTX + BV: cytotoxic chemotherapy + bevacizumab, (2) CTX: cytotoxic chemotherapy, (3) NC: no treatment before liver resection-were analysed. Postoperative liver function and complications were compared, clinical, radiological and pathological data were evaluated. Between 01.12.2006 and 31.12.2010 41 resections was performed after chemotherapy + bevacizumab (CTX + BV) and 27 resections was performed after preoperative chemotherapy without bevacizumab (CTX). There were 60 hepatic resections in this period without neoadjuvant treatment (NC). 8 patients had repeated resections. The postoperative complication rate was 40 % but there was no statistical difference between the groups (P = 0.72). Only the type of resection was associated with a significantly higher complication rate (p = 0.03). The subgroup of patients, who received irinotecan had a higher complication rate in the CTX group than in the BV + CTX group (55 % vs 41 %). Preoperative administration of bevacizumab was associated with higher peak postoperative AST, ALT levels but did not affect functional recovery of the liver. The RECIST system was not able to predict the outcome after chemotherapy in every patient and in many cases this system overestimated the effect of chemotherapy. On histopathological examination the presence of necrosis was not associated with chemotherapy or pathological response. Use of chemotherapy before hepatic resection of CLM was not associated with a significant increase in complication rates. The functional recovery of the liver was not affected by the preoperative administration of chemotherapy. The use of combined neoadjuvant chemotherapy is safe before hepatic resection.

Ouabain or an isomer has been identified as endogenous ouabain-like substance (EOLS). The role of EOLS in the adaptation of premature infants to alterations of sodium balance was investigated by measuring urinary ouabain excretion serially in 9 low birth weight premature infants with (group S, mean birth weight 1,578 g, mean gestational age 30.4 weeks) and without (group NS, mean birth weight 1,537 g, mean gestational age 30.8 weeks) NaCl supplementation. The study was performed on the 7th day and weekly thereafter until the 5th week of life. NaCl supplementation was given in a dose of 3–5 and 1.5–2.5 mmol/kg/day at the postnatal ages of 8–21 and 22–35 days, respectively. Prior to NaCl supplementation, urinary ouabain excretion was similar in the two groups (146.2 ± 16.8 pg/kg/h in group S versus 180.0 ± 9.6 pg/kg/h in group NS) and remained at about the same level throughout the study when supplemental NaCl was provided. In infants of group NS, urinary ouabain excretion increased significantly by the 3rd week (p < 0.01) and no consistent change occurred later on. As a result, the differences in urinary ouabain excretion between the two groups proved to be significant during weeks 2–5 (p < 0.001). Essentially the same pattern of ouabain excretion was seen when it was expressed in terms of pg/mg creatinine. In infants receiving high sodium diet there was a significant positive correlation between urinary sodium and ouabain excretion. It is concluded that premature infants receiving low sodium intake have elevated EOLS excretion by the 3rd week of life. Although the relationship between ouabain and sodium excretion in supplemented premature infants suggests some physiological significance for sodium excretion, ouabain does not appear to be regulated by extracellular volume.

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