Coexistence of mature cystic teratoma and adenocarcinoma in situ within atypical proliferative mucinous tumour of ovary--a case report of 35-year-old woman.

Combined ovarian tumors are found in common pathologic practice due to amazing potential of ovarian tissue to copy almost every tissue of human body and imitate many neoplasms of various other organs in a very flexible way. A multicystic tumor is presented in this case report of 35-year-old woman. It consisted of a cyst with sebum and hair and cavities with papillomatous projections and mucus. The ovarian tumor was diagnosed a mature cystic teratoma presenting mainly as dermoid cyst and mucinous adenocarcinoma in situ, arising within atypical proliferative mucinous tumor. This report demonstrates how histoformative properties are reflected in ovarian tumorigenesis. Such a stunning histoformativity makes ovaries the possible site of primary origin for malignant tumors that mimic extra ovarian differentiation. In the authors' point of view, the diagnosis of primary ovarian mucinous tumor within cystic teratoma is firm, whenever simultaneous extraovarian involvement by mucinous neoplasm is excluded.

Acardius acephalus fetus--report of distinctive anatomical anomalies with regards to pathophysiology of TRAP sequence.

Acardiac fetuses are consequences of twin reversed arterial perfusion (TRAP). Here the authors present a case of 40-year-old gravida IX who gave birth to a healthy, 2,900 g female child by a cesarean section. Additionally amorphic 1,020 g maldeveloped fetus was removed. There was a diamnion monochorionic type of twin placenta with incorrect single umbilical arteries (SUA) both in umbilical cord of healthy fetus and in atrophic second umbilical cord. A malformed fetus developed a rather well formed lower leg with four digital foot and oval shape amorphous body mass with omphalocele and eventration of the intestines. X-ray picture showed well visible metatarsal and femur bone and anatomically undefined bones cluster in the central part. A cavity of fetal body contained intestines--the only one well-formed organ, nests of heterotopic pilosebaceous residues, remnants of adrenal glands, well-formed ganglia, and nests of neural tissue covered by neuroepithelium.

Anterior pedicle screw fixation for multilevel cervical corpectomy and spinal fusion.

BACKGROUND: Prevention of graft dislodgement in multilevel cervical corpectomy and fusion has been an unresolved problem. Anterior plate fixation has a significant failure rate. External support with a halo-vest is uncomfortable for patients. In the present study, we report a new surgical technique of anterior pedicle screw (APS) fixation for multilevel cervical corpectomy and spinal fusion, and describe the safety and utility of the system. METHOD: After cervical corpectomy, the pedicles on the right side were visualised under oblique fluoroscopy. Guide wires were inserted into the pedicles from the inner wall of the excavated vertebral body until they were hidden in the pedicles. After a fibula autograft was placed, the graft was penetrated in the reverse direction by the guide wires. After drilling and tapping, cannulated screws were inserted into the pedicles through the grafted fibula along the guide wires. FINDINGS: In 9 patients with cervical myelopathy, the surgery was accomplished with a fibula autograft using APS fixation. A total of 22 APSs were inserted, and 21 screws were placed precisely in the pedicles. There were no neurovascular complications. Patients were allowed to ambulate without a halo-vest on the second day after the surgery. Post-operatively, no dislodgement of the grated fibula occurred, and all patients improved neurologically. CONCLUSIONS: The insertion of APSs is feasible and safe. APS fixation enables us to obtain rigid fixation anteriorly, and we propose that APS fixation is an attractive option for multilevel cervical corpectomy and fusion.

The Bak protein expression in germinal centers of hypertrophied adenoids in children.

The aim of this study was to evaluate pro-apoptotic Bak expression in the germinal centers of adenoid in children on the assumption of the potential usefulness of Bak as adenoid function marker. The study involved 95 children undergoing adenoidectomy; divided into three age groups: aged up to 5 years (25 children), 5-10 years (54 children) and over 10 years (16 children). The analyzed material was adenoids removed on the ground of hypertrophy. Immunohistochemical analyses were carried out using goat polyclonal Bak antibodies (DAKO) directed against human Bak protein. The presence of Bak positive lymphocytes within germinal centers and Bak immunostaining were scored. The immunohistochemical staining showed the Bak positive lymphocytes mainly within the germinal centers of the lymphoid follicles. The Bak reactivity was also present in hyperplastic lymphoid tissue within the subepithelial B lymphocytes. We have not found statistically significant correlation between Bak expression and clinical status and change in Bak expression level according to age. The apoptotic presence within the germinal centers are the manifestation of which is Bak expression and its lack in the mantle zone, what we confirmed in our former study by describing Bcl-2 expression, seems to be a proper B cells maturation marker within lymphoid follicles. Our finding shows that these processes are not influenced by age and supports our thesis that adenoid involution is rather the effect of changes in the number of lymphoid follicles that changes in them.

Men who were thin during early adulthood exhibited greater weight gain-associated visceral fat accumulation in a study of middle-aged Japanese men.

OBJECTIVE: This study aimed to assess the relationship between weight gain from early adulthood and visceral fat accumulation. METHODS: The participants were 549 men aged 42 to 64 years who were randomly selected from the local resident registry for the National Institute for Longevity Sciences' neighbourhood. They were asked to recall their weight at 18 years of age, and then, post-18 weight-change values were calculated for each participant (their current weight minus their weight at 18). The participants were divided according to their median body mass index (BMI) at 18 years of age (initial BMI) (<20.14 and ≥20.14 kg m-2). Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured on computed tomography scans. RESULTS: The participants with initial BMI of <20.14 kg m-2 exhibited greater post-18 weight changes than those with initial BMI of ≥20.14 kg m-2. The participants' post-18 weight-change values were negatively correlated with their initial BMI and positively correlated with both VFA and SFA. The slope of the regression line for the relationship between post-18 weight change and VFA was steeper in the participants with initial BMI of <20.14 kg m-2 (ß = 4.36) than in those with initial BMI of ≥20.14 kg m-2 (ß = 3.23). CONCLUSIONS: Visceral fat accumulation is affected not only by an individual's post-18 weight gain but also by their initial BMI. Men who were thin in early adulthood experienced greater weight gain-associated VFA increases, but the same was not true for SFA.

Serum erythropoietin and angiogenetic factors in human colorectal cancer.

AIMS AND BACKGROUND: Erythropoietin, VEGF, VE-cadherin are involved in angiogenesis. Besides that erythropoietin stimulates erythropoiesis and increases haemoglobin and hematocrit levels as well. Moreover, erythropoietin could directly stimulate colorectal cancer cell growth due to the presence of both erythropoietin receptor and erythropoietin production in malignant cells of this neoplasm. Therefore we aimed at measurement and comparison of serum erythropoietin with VEGF, VE-cadherin levels, blood haemoglobin and hematocrit in colorectal cancer patients of different clinicopathological profiles. METHODS: We applied ELISA kits to evaluate preoperative serum levels of endogenous erythropoietin, VEGF and VE-cadherin in samples from 92 colorectal cancer patients and control group of 16 healthy volunteers. RESULTS: Endogenous erythropoietin was significantly elevated in preoperative sera in colorectal cancer patients (p = 0.013) compared with healthy volunteers, however, erythropoietin levels were not significantly higher with the advancement of colorectal cancer. There were significantly higher levels of erythropoietin in the group of anaemic men in comparison to men with normal haemoglobin levels (p < 0.0001). VEGF and VE-cadherin did not correlate with erythropoietin. Erythropoietin levels negatively correlated with haemoglobin and hematocrit levels in all cancer patients; particularly in node positive cancers (N+), moderately differentiated tumours (G2) and deeply invading neoplasms (pT3+pT4). CONCLUSIONS: Erythropoietin levels increase in colorectal cancer but circulating erythropoietin does not associate with progression of the disease. Thus, the use of recombinant erythropoietin seems to be safe. Our results suggest that negative feedback regulation persists between haemoglobin and erythropoietin in colorectal cancer. Production of erythropoietin remains therefore anaemia-associated, hypoxia-dependent and doesn't seem to be autonomic despite abundant expression of erythropoietin by colorectal cancers.

Increased expression of connexins 26 and 43 in lymph node metastases of breast cancer.

BACKGROUND: Gap junctions are intercellular channels composed of connexins, which mediate the direct passage of small molecules between neighbouring cells. They are involved in regulation of cell cycle, cell signalling, and differentiation, and probably invasion and metastasis. The role of connexins in the metastatic process is controversial, because some studies indicate that connexin expression is inversely correlated with metastatic capacity. In contrast, others demonstrate that connexins may be involved in metastasis. In addition, connexin status in breast cancer metastasis has not been widely studied. METHODS: We evaluated by immunohistochemistry the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in primary breast tumours (PTs) and matched paired metastases to lymph nodes (MLNs). RESULTS: In PTs, we observed predominantly cytoplasmic localisation of evaluated connexins, indicating alterations in connexin expression in breast cancer cells. We demonstrated that expression of Cx26 and Cx43 was increased in MLNs compared with PTs (p<0.00001 and p<0.001, for CX26 and Cx43, respectively). In addition, Cx26 and Cx43 negative PTs developed Cx26 and Cx43 positive MLNs. Furthermore, besides increased cytoplasmic staining, enhanced membranous localisation of Cx43, typical of normal cells, was found in MLNs. Additionally, membranous Cx26 expression appeared only in metastatic breast cancer cells. CONCLUSIONS: These findings suggest that connexins may contribute to the efficient metastasising of breast cancer to the lymph nodes.

P53 correlates positively with VEGF in preoperative sera of colorectal cancer patients.

Diversity of P53 impact on tumor angiogenesis is due to the fact that wild-type P53 decreases expression of vascular endothelial growth factor (VEGF), but mutant P53 upregulates it. Therefore, we aimed at uncovering relations between preoperative serum levels of VEGF and P53 in colorectal cancer (CRC) patients. Preoperative blood samples of 125 CRC patients and 16 control healthy volunteers were examined with an ELISA-kit for serum P53 levels and VEGF. P53 did not correlate with VEGF in the whole group of CRC patients. However, P53 associated with VEGF in case of colorectal cancer patients, whose serum values of VEGF were higher than in controls (VEGF{H} >5.9333 pg/ml) (r=0.274, p<0.009). We revealed a positive correlation between P53 and VEGF{H} in subsets of poorly differentiated (G3) cancers (p<0.02), lymph node positive (p<0.007), pT3 or pT4 patients (p<0.004) without analogous relation in moderately differentiated (G2) tumors, node negative patients or pT1 or pT2 patients. P53 and IGF-I negatively correlated in all CRC patients (p<0.04) and VEGF{H} individuals of pT3 or pT4 (p<0.05) without any significant linkage in tumors of pT1 or pT2. The positive correlation between serum P53 and VEGF points at mutation of P53 and is a highly probable sign of poor prognosis in colorectal cancer. For now it can not be excluded that the binary analysis of serum P53 and VEGF could help select CRC patients endangered by rapid growth and lymph node metastases.

To give or not to give recombinant EPO to anemia endangered cancer patients.

EPO is known as an inducer of maturation and proliferation of erythrocytes. Moreover, it favours angiogenesis. In several studies it was encountered that EPO is a trophic agent that mediates survival and inhibits apoptosis of hypoxia affected cells, particularly those which build masses of irregularly vascularized cancers. The main task concerning EPO for oncologists is the choice to give or not to give recombinant EPO to anemia endangered cancer patients. EPO can do the quality of life better and cause recovery from anemia post chemotherapy and radiation of cancer patients. Nevertheless, EPO therapy shortens survival of patients in some cancers, in which antiapoptotic effect of EPO predominates directly in malignant cells. Thus, separately in every type of cancer, therapeutic use of recombinant EPO calls for prior investigations, if EPO signaling causes proliferation of cancer cells by direct stimulation of EPOR positive malignant cells. Unless the proliferative effect of EPO on cancer cells is excluded, its use in the therapy of anemia in cancer patients is not quite safe.

Expression of insulin receptor substrate 1 in primary breast cancer and lymph node metastases.

BACKGROUND: Insulin receptor substrate 1 (IRS-1) transmits signals from the insulin-like growth factor I receptor (IGF-IR) and insulin receptor (IR) and has been associated with the pathogenesis of cancer. IRS-1 downregulation has been suggested to play a role in breast cancer progression, but no simultaneous assessments of IRS-1 expression in primary breast cancer and metastases have been performed. AIMS: To assess IRS-1 expression in primary and metastatic breast cancer. METHODS: IRS-1 expression was analysed by means of immunohistochemistry in 109 samples of primary breast cancer and in 42 matched primary and metastatic tumours. In addition, IRS-1 expression was correlated with selected clinicopathological features, including oestrogen receptor alpha (ERalpha) and proliferation marker Ki-67 status. RESULTS: Positive cytoplasmic IRS-1 immunostaining was found in 69.7% (76 of 109) and 76.2% (32 of 42) of the primary and metastatic tumours, respectively. Both IRS-1 positive and IRS-1 negative primary tumours produced IRS-1 positive and IRS-1 negative metastases. IRS-1 expression in primary tumours correlated with poorly differentiated (G3) breast cancer (p < 0.005) and with lymph node involvement (p <0.05). In the subgroup of ERalpha positive primary tumours, IRS-1 expression positively correlated with Ki-67 (p < 0.02, r = 0.351), but in the subgroup of ERalpha negative primary tumours there was a negative correlation (p < 0.03, r = -0.509). IRS-1 expression in lymph node metastases correlated with neither ERalpha nor Ki-67. CONCLUSIONS: IRS-1 might be involved in breast cancer progression. Knowledge about differences between primary and metastatic tumours might help to understand mechanisms of breast cancer progression and lead to the development of more effective anticancer drugs.

Expression of the Insulin Receptor Substrate 1 in primary tumors and lymph node metastases in breast cancer: correlations with Bcl-xL and Bax proteins.

In our previous investigation Insulin Receptor Substrate 1 (IRS-1) correlated with proliferation marker Ki-67 in human breast cancer. The aim of the present study was to assess relationships between IRS-1 expression and anti-apoptotic Bcl-xL as well as proapoptotic Bax proteins, assessed by immunohistochemistry, in primary tumors and lymph node metastases of breast cancer. IRS-1 is positively associated with both Bcl-xL and Bax in primary and metastatic tumors. Thus, our results could suggest that IRS-1 might affect turnover of cancer cells and breast cancer progression through activation of mitogenesis and participation in the regulation of the balance between anti- and proapoptotic pathways.

Aggressive, solid variant of alveolar rhabdomyosarcoma with cutaneous involvement in a juvenile labrador retriever.

An 8.5-month-old male Labrador retriever presented with a cutaneous mass in the right maxillofacial region and swelling of the gingiva. The dog received antibiotic and anti-inflammatory treatment. After 3 weeks the dog returned, presenting with disseminated cutaneous tumours on the neck, trunk and groin. One of the nodules was resected and a cutaneous round cell tumour was diagnosed on microscopical examination. The dog was humanely destroyed. Necropsy examination revealed disseminated tumours in the skin, internal organs and skeletal muscles. Microscopically, all of the tumours were composed of small round cells, arranged in nests. Immunohistochemically, the neoplastic cells expressed vimentin, desmin, MyoD1, myogenin and smooth muscle actin, but were negative for CD3, CD18, CD79αcy, cytokeratin AE1/AE3, chromogranin A, class II molecules of the major histocompatibility complex, neuron-specific enolase and S100. The average Ki67 index was 89.5%. The final diagnosis was a solid variant of alveolar rhabdomyosarcoma (ARMS). This is the first report of the cutaneous multifocal form of ARMS in veterinary oncology.

Proton magnetic resonance spectroscopy for assessment of human body composition.

BACKGROUND: The usefulness of magnetic resonance spectroscopy (MRS)-based techniques for assessment of human body composition has not been established. OBJECTIVE: We compared a proton MRS-based technique with the total body water (TBW) method to determine the usefulness of the former technique for assessment of human body composition. DESIGN: Proton magnetic resonance spectra of the chest to abdomen, abdomen to pelvis, and pelvis to thigh regions were obtained from 16 volunteers by using single, free induction decay measurement with a clinical magnetic resonance system operating at 1.5 T. The MRS-derived metabolite ratio was determined as the ratio of fat methyl and methylene proton resonance to water proton resonance. The peak areas for the chest to abdomen and the pelvis to thigh regions were normalized to an external reference (approximately 2200 g benzene) and a weighted average of the MRS-derived metabolite ratios for the 2 positions was calculated. TBW for each subject was determined by the deuterium oxide dilution technique. RESULTS: The MRS-derived metabolite ratios were significantly correlated with the ratio of body fat to lean body mass estimated by TBW. The MRS-derived metabolite ratio for the abdomen to pelvis region correlated best with the ratio of body fat to lean body mass on simple regression analyses (r = 0.918). The MRS-derived metabolite ratio for the abdomen to pelvis region and that for the pelvis to thigh region were selected for a multivariate regression model (R = 0.947, adjusted R(2) = 0.881). CONCLUSION: This MRS-based technique is sufficiently accurate for assessment of human body composition.

Free and small peptide-bound [14C]hydroxyproline synthesis in vitro in ethanol-induced hepatic injury in the rat liver.

To clarify the significance of free and small peptide-bound hydroxyproline synthesis in ethanol-induced liver injury, we measured the in vitro synthesis of [14C]hydroxyproline in the 67% ethanol-soluble fraction in rat liver slices, together with hepatic protein-bound [14C]hydroxyproline synthesis. The synthesis of free and small peptide-bound [14C]hydroxyproline was 11.1 +/- 2.0 dpm x 10(-4)/g liver/3 hr and the synthesis of protein-bound [14C]hydroxyproline was 10.1 +/- 3.3 dpm x 10(-4)/g liver/3 hr in control rat liver. In the ethanol-fed rat liver, the synthesis of free and small peptide-bound [14C]hydroxyproline significantly increased 1.5-fold and the synthesis of protein-bound [14C]hydroxyproline significantly increased 1.6-fold, while the hepatic collagen content did not change. There was a significant correlation between free and small peptide-bound [14C]hydroxyproline synthesis and protein-bound [14C]hydroxyproline synthesis. These results suggest that free and small peptide-bound hydroxyproline synthesis plays an important role in regulating the content of hepatic collagens.

Collagenase and collagenolytic cathepsin in normal and fibrotic rat liver.

Collagenase and collagenolytic cathepsin activities in normal and carbon tetrachloride-induced fibrotic livers of rats were simultaneously determined at 35 and 25 degrees C for 18 h, using the same 14C-labeled neutral soluble collagen as a substrate. Collagenolytic cathepsin had higher activity under the assay conditions at both 35 and 25 degrees C than collagenase in normal and fibrotic livers. On sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis, the collagen was visibly degraded by collagenolytic cathepsin, but not by collagenase. These results indicate that, unlike collagenase, collagenolytic cathepsins exist as active forms in the rat liver, and can participate in the degradation of collagens, especially of soluble collagens including procollagens.

Diagnostic value of serum markers of connective tissue turnover for predicting histological staging and grading in patients with chronic hepatitis C.

PURPOSE: Chronic hepatitis C is an insidiously progressive disease, in which repeated assessment of liver histology is required. Various serum fibrotic markers have now been introduced. Our present aim was to assess, by receiver operating characteristic analysis, the usefulness of serum fibrotic markers for diagnosing fibrotic staging and necroinflammatory grading in chronic hepatitis C. METHODS: Serum levels of procollagen type III N-terminal peptide (PIIINP), 7S fragment of type IV collagen (PIVNP), hyaluronan (HA), matrix metalloproteinase (MMP)-1, MMP-2, and tissue inhibitor of metalloproteinases (TIMP)-1 were measured in 169 patients with chronic hepatitis C. RESULTS: The accuracy of these tests for discriminating stages greater than F2 from stages less than F1 was superior to that for discriminating stage F3 from stages less than F2. The most useful test for predicting stages greater than F2 was the serum HA test (cutoff value, 50 ng/ml; sensitivity, 75%; specificity, 80%), and the next-most useful was the serum MMP-2 test (cutoff value, 550 ng/ml; sensitivity, 75%; specificity, 70%). The usefulness of these tests for discriminating moderate grade from grades less than mild was superior to that for discriminating grades more than mild from minimal grade. The most useful test for predicting moderate grade was the serum HA test (cutoff value, 60 ng/ml; sensitivity, 77%; specificity, 74%), and the second-most useful was the serum PIVNP test (cutoff value, 6.5 ng/ml: sensitivity, 74%; specificity, 75%). The combination of the most useful and next-most useful test results increased the accuracy of the diagnosis of staging and grading. CONCLUSIONS: These serum fibrotic markers, especially the serum HA test, would be clinically useful for assessing staging and grading in patients with chronic hepatitis C.

Comparison of clinical laboratory liver tests between asymptomatic HBV and HCV carriers with persistently normal aminotransferase serum levels.

We examined the clinicopathological state in asymptomatic hepatitis C virus (HCV) carriers with persistently normal aminotransferase serum levels in comparison with asymptomatic hepatitis B virus (HBV) carriers. The findings showed that the thymol turbidity test (TTT) values and zinc sulfate turbidity test (ZTT) values were significantly higher in asymptomatic HCV carriers than in asymptomatic HBV carriers, whose values were within the normal limits. Multivariate analysis showed that the independent predictor of serum TTT and ZTT levels was the HCV infection. In clinical state, simple and cheap tests such as TTT and ZTT are useful for mass screening to detect HCV carriers in medical check-ups of healthy workers.

Interferon alpha inhibits intrahepatic recurrence in hepatocellular carcinoma with chronic hepatitis C: a pilot study.

The aim of the present study is to evaluate whether interferon alpha (IFNalpha) therapy can inhibit intrahepatic recurrence after the curative treatment of small HCC with underlying chronic hepatitis C. Forty patients were enrolled in this study. They had solitary, small HCC

Antiplatelet action of losartan involves TXA2 receptor antagonism but not TXA2 synthase inhibition.

Various AT1 receptor antagonists including losartan are known to inhibit human platelet activation by antagonising TXA2/PGH2 receptors (TP receptors). Presently, we check a hypothesis that losartan, an imidazole derivative in contrast with valsartan, a non-imidazole compound, may inhibit human platelet activation also through inhibition of TXA2 synthesis. Inhibitory action of losartan (2-n butyl-4-chloro-5-hydroxymethyl-1-beta(2'-(1H-tetrazol-5yl)biphenyl-4-yl)methyl] imidazole), its active metabolite EXP 3174 (2-n-butyl-4-chloro-1-beta (2-(1H-tetrazol-5-yl) biphenyl-4-yl) methyl]imidazole-5-carboxylic acid) and valsartan ((S)-N-valeryl-N-(beta2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]valine), on collagen-induced platelet aggregation and TXA2 generation was compared to effects achieved by each compound on U46619-induced aggregation in aspirinized platelets. Losartan and aspirin inhibited collagen-induced platelet aggregation with approximately the same potency, whereas EXP 3174 and valsartan showed much weaker antiplatelet effects. Interestingly, losartan, EXP 3174 and valsartan displayed similar potencies as inhibitors of U46619-induced aggregation in asprinized platelets as in collagen-induced aggregation in non-aspirinized platelets. None of the above three AT1 antagonists, up to a concentration of 300 microM, did influence collagen-induced TXA2 synthesis in human platelets. In conclusion, antiplatelet effects of AT1 antagonists, irrespective of the presence or absence of non-condensed imidazole in their chemical structure, involve antagonism of TP receptors but not inhibition of TXA2 synthesis in platelets.