Low expression of NQO1 predicts pathological complete response to neoadjuvant chemotherapy in breast cancer patients treated with TAC regimen.

The aim of this study was to evaluate preoperative tumour expression of NAD(P)H:quinone oxidoreductase 1 (NQO1) along with other biological markers as potential predictors of pathological complete response (pCR) to neoadjuvant docetaxel, doxorubicin, and cyclophosphamide-containing (TAC) chemotherapy in patients with primary breast cancer. Sixty-one patients who received neoadjuvant chemotherapy (NCT) with TAC regimen were enrolled in this prospective study. The pre- and post- NCT expression of oestrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 1 and 2 (EGFR and HER2), NQO1, Ki-67 proliferation index, multidrug resistance protein 1 (MDR1), p53 and BCL2 were evaluated by immunohistochemistry. The pCR was reached in 14 patients (23 % of the study group). Multivariate analysis demonstrated that patients with ER-, PR-, NQO1- negative, and Ki-67-positive tumours had a significantly higher chance to achieve pCR. Within the biological subtypes, the highest pCR rate (50 %) was seen in triple-negative (i.e. ER-, PR-, HER2-) tumours. Post-operative evaluation showed that in comparison to pre-operative tissue samples, NQO1 expression was significantly increased, while Ki-67 and HER2 decreased, in the residual tissue after NCT. In conclusion, the present data suggests that NQO1 expression may be a novel diagnostic biomarker for the prediction of positive response to NCT in patients with breast cancer.

[Appendiceal mucocele in differential diagnosis of tumors in pelvic region]. / Mukokéla apendixu v diferenciální diagnóze tumoru malé pánve.

OBJECTIVE: To report two cases of appendiceal mucocele in patients with suspected gynecological pathology. DESIGN: Case report. SETTING: Department of Obstetrics and Gynecology, Medical Faculty of Charles University and Faculty Hospital Hradec Králové. SUBJECT AND METHOD: We report two cases of appendiceal mucocele diagnosed and treated at our department. CONCLUSION: Appendiceal mucocele is a rare pathology, characterized by abnormal accumulation of mucous in appendix lumen. It is four times more common in females with a mean age of about 55 years. The pathogenesis could be neoplastic or non-neoplastic. Appendiceal mucocele with its anatomic location must be considered in terms of differential diagnosis of masses in pelvic region. Preoperative diagnosis is important, alerting the surgeon of an unintended rupture during surgery and avoiding the development of pseudomyxoma peritonei. US and CT were reported to be valuable.

Fulminant course of metastatic liposarcoma after delivery--case report.

Abdominal liposarcoma is a rare tumor of uncertain prognosis. Radical surgery is possible in about two-thirds of the patients, and the prognosis of patients with inoperable tumors is dismal. Only a few cases of liposarcoma complicating pregnancy have been documented. We report a case of a patient who was diagnosed with metastatic abdominal liposarcoma during the third trimester of the pregnancy. After induced vaginal delivery, palliative surgery was performed and one cycle of systemic combination chemotherapy was administered. Despite the multimodality treatment the patient died of progressive disease within one month after diagnosis. Autopsy revealed high-grade pleomorphic liposarcoma arising from the retroperitoneum with liver and lung metastases.

[Cooperation between a surgeon and an interventional radiologist in cases of internal bleeding]. / Spolupráce chirurga a intervencního radiologa pri vnitrních krváceních.

INTRODUCTION: Internal bleeding still remains a serious condition, which must be urgently diagnosed and treated. In the Faculty Hospital in Hradec Králové the diagnosis of the internal bleeding source and its consequent treatment is managed under cooperation between a surgeon and an interventional radiologist. A CASE-REVIEW: In the case-review section of this report, a total number of five patients with serious cases of internal bleeding, the source of which was diagnosed and treated under cooperation between the above mentioned specialists is presented. The patients concerned suffered from the following: a trauma to the liver parenchyma, posttraumatic arterioportal shunts, an intraheparic aneurysm, a relaps of the uterine carcinoma with hemorrhaging into the colon and the vagina, bleeding into retroperitoneum. In all the cases the lesion was successfully treated and the hemorrhage was managed. DISCUSSION: Exact location of the bleeding artery during an arteriogragraphic examination is a prerequisite of a successful treatment of the condition. Both, the absorbable materials which allow gradual recanalization of the embolized vessel, and the non-absorbable materials may be used to conduct embolization of the affected vessel. It is necessary to haemodynamically stabilize the patient prior to the procedure. CONCLUSION: In many cases, the cooperation between a surgeon and an interventional radiologist allows for the source of the internal bleeding to be located and managed. It is indicated in certain cases of benign and malignant disorders and in some cases of the parenchymatose organs trauma.

[A contribution to contemporary absolute and relative contraindications for breast conserving surgeries (BCS) in early carcinoma of the breast in the first or second stage]. / K soucasným absolutním a relativním kontraindikacím prs setrících výkonu (BCS) u casného karcinomu prsu 1. a 2. stadia.

Absolute and relative contraindications for BCS (Breast Conserving Surgery) are stated according to the EUSOMA (European Society of Mastology). Statement includes the risk factors for local recidive, and unfavourable progress of the illness itself. Stress is put on the health treatment fallowing BCS.

[Secondary malignant tumors of the mammary gland]. / Sekundární maligní nádory prsní zlázy.

The authors present three case-reviews of rare metastatic affections of the female mammary gland by the following disorders--a malignant lymphoma, a Grawitz carcinoma of the kidney and by a malignant melanoma. Histological examinations of the tumors and restrospective examinations of the respective patients anamneses resulted in the primary focus determination in two cases.

[A contemporary approach to ductal and lobular carcinoma of the mammary gland in situ]. / Soucasný prístup k duktálnímu a lobulárnímu karcinomu mlécné zlázy in situ.

The statement discusses epidemiology data about DCIS and LCIS, their classification evaluates predictive prognosis factors. Surgical methods are stated, as well as the following health treatment. We present the basic oncology reguirement for the surgical treatment at DCIS, meaning "tumor free margins". DCIS is clinically more serious and significant than LCIS.

[Mesenchymal extraperitoneal tumors in the elderly]. / Mezenchymální extraperitoneální nádory u senioru.

Incidence rates of solid tumors increase with age in our population. Epithelial tumors are the most frequent tumors of the old age. On the contrary, extraperitoneal mesenchymal tumors are rare. Surgical treatment remains the most important and the most effective therapeutic modality to manage solid tumors. The risk level of the surgical treatment in the elderly is influenced by many factors, which may often be substancially reduced. Therefore, the elderly should not be excluded from curative surgical procedures on their calendary age basis.

[Intraoperative enteroscopy--personal experience from 1995 to 2002]. / Intraoperacní enteroskopie--vlastní zkusenosti z období 1995-2002.

Authors present their experience with the intraoperative enteroscopy method--an invasive technique of small bowel examination. It is performed under narcosis at an operating theatre (i.e. in co-operation with surgeon and anaesthesiologist). The endoscopy-performing physician becomes one of the members of the operating team. The advantage of the method is the possibility to examine of the whole small intestine and to solve immediately the pathological findings by endoscopic or surgical intervention. The examination is invasive and the correct indication is mandatory. Authors report their results of 18 intraoperative panendoscopies of small intestine.

Initial study of using a laminar fluid diffusion interface for sample preparation in high-performance liquid chromatography.

This report describes a new microfluidic device called the H Filter for sample preparation prior to HPLC. The H Filters make possible a diffusional transfer of an analyte from a sample stream into a stream of a "receiver" fluid. Existing mathematical models can be used for optimizing experimental conditions. The authors have selected the extraction of the antibiotic cephradine from blood to demonstrate the utility of the new device. The extracts of blood samples spiked with cephradine levels between 0.2 and 100 microg/ml were analyzed using a C8 reversed-phase column and UV detection at 260 nm. The HPLC results were in good agreement with theory. The recovery of 32.2+/-2.8% was uniform over the entire range of cephradine concentrations. The new method completely avoids the use of centrifuges, that is otherwise typical for most current methodologies for the preparation of blood samples prior to HPLC analysis.

Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.

Proteome study of colorectal carcinogenesis.

Development of cancer is a complex process involving multiple changes in gene expression. To unravel these alterations, a proteome approach aimed at the identification of qualitative and quantitative changes in protein composition, including their post-translational modifications, attracts great attention. Our study was focused on the identification of proteins whose amount is altered in the course of malignant transformation of colon mucosa. Proteins extracted from tissue specimens or cell lysates were separated by two-dimensional gel electrophoresis (2-DE). Comparative analyses of 2-DE protein patterns were done using computerized image analysis. Selected proteins exhibiting statistically significant abundance alterations comparing healthy and diseased tissues were identified by mass spectrometry. Globally, we have found 57 proteins that exhibited either a significant decrease or increase in amount in pathological tissues, and 18 of these were annotated by mass spectrometry. The alterations in the expression of nine proteins were common for both precancerous and neoplastic tissues suggesting their role in colon tumorigenesis. The epithelial origin of all identified spots was checked in two cell lines Caco-2 and DLD-1 originating from well-differentiated and poorly differentiated colon carcinoma, respectively.

Simultaneous analysis of homocysteine and methionine in plasma.

The new isocratic cation exchange method separates up to eight different amino thiols. The separated sample components are detected electrochemically using a gold electrode and the integrated pulsed amperometry. The eluent composition is, for example, 0.15 M sodium perchlorate, 0.02 M perchloric acid and 5% acetonitrile. The report describes the optimization of chromatographic parameters such as column diameter and eluent composition. Quantitative performance is discussed for eight different amino thiols using standards. Also presented is a long term quantitative study for homocysteine and methionine in plasma samples. The preparation of plasma samples is simpler than with the previously reported version of the method. Only a reduction step is required, and neither column switching nor derivatization are necessary.

Simplified in-line sample preparation for amino acid analysis in carbohydrate containing samples.

This report describes a new, automated chromatographic procedure eliminating carbohydrates from amino acid samples prior to their analysis by anion-exchange chromatography and integrated amperometric detection. In the first step, a sample is brought onto a short cation-exchange column (trap column) in hydrogen form. Carbohydrates are passing through this column, while only amino acids are retained. Subsequently, the cation-exchange column, holding the amino acid fraction, is switched in-line with the gradient pump and separator column. The mobile phase used at the beginning of the separation (NaOH; pH 12.7) transfers amino acids from the trap column onto the anion-exchange column and the amino acid separation is completed without any interference by carbohydrates. All common amino acids are recovered following the carbohydrate removal step. The average value of their recovery is 88.1%. The calibration plots were tested between 12.5 and 500 pmol (amounts injected). The mean value of correlation coefficients of calibration plots was calculated as 0.99. The mean value of relative standard deviations from five replicates was 3.9%. The usefulness of the method is illustrated with two chromatograms of a carrot juice sample obtained before and after the in-line removal of carbohydrates.

Pegylated liposomal doxorubicin in combination with hyperthermia for treatment of skin metastases of breast carcinoma: a case report.

BACKGROUND: Incorporation of doxorubicin hydrochloride into pegylated liposomes (PLD) may decrease chemotherapy side effects and increase the activity. Hyperthermia could further potentiate its effectiveness. CASE REPORT: A patient with skin metastases of breast carcinoma was treated with intravenous infusion of PLD (Caelyx) in combination with ultrasound hyperthermia. Each cycle consisted of infusion of 40 mg PLD absolute dose, followed by 2 fractions of hyperthermia 41-43 degrees C for 45 min 1 and 48 h after infusion. A complete remission was observed after the combination treatment with no significant toxicity. CONCLUSION: Present observations suggest that the combination of PLD with hyperthermia of skin metastases of breast carcinoma may be an active and well tolerated treatment.

The peripheral blood leukocyte phenotype in patients with breast cancer: effect of doxorubicin/paclitaxel combination chemotherapy.

Presence of functional immune system is critical for any attempt aimed at improving survival of breast cancer patients by strategies based on immune system manipulation. We evaluated by flow cytometry the phenotype of peripheral blood leukocyte of 43 breast cancer patients. In 11 patients, the phenotype was evaluated before and during the chemotherapy by combination of doxorubicin and paclitaxel (AT). Compared with controls breast cancer patients had significantly higher relative and absolute numbers of CD3 HLA-DR+, CD3+CD69+ and CD14+CD16+, and significantly lower percentages of CD3 and CD8+CD28+ cells. After one cycle of AT, the absolute numbers of CD3 , CD3+CD4+, CD3+CD8+ and CD8+CD28+ cells increased significantly. Present data show a presence of T-cell activation in breast cancer patients. Administration of AT may lead to an increase in functional T-cells in peripheral blood, indicating a potential for combining chemotherapy with immunotherapy in the treatment of breast cancer patients.

Intraarterial chemotherapy of malignant melanoma metastatic to the liver.

BACKGROUND/AIMS: The prognosis of malignant melanoma metastatic to the liver is poor. The aim of the present report was to analyze retrospectively the effectiveness of regional chemotherapy and biologic therapy in patients with hepatic metastases of malignant melanoma. METHODOLOGY: Seven patients with hepatic metastases of malignant melanoma were treated by intraarterial administration of the combination of cisplatin, vinblastine and dacarbazine, or melphalan, with or without interleukin-2, interferon-alpha and interferon-gamma. RESULTS: The median survival of 4 patients with metastatic involvement initially limited to the liver is 19+ months in contrast to a median survival of 5 months in patients with concurrent extrahepatic disease. Intraarterial administration of cytokines led to an initial decrease in circulating lymphocyte numbers, with subsequent return to pretreatment levels, and to an increase in urinary neopterin, a marker of immune activation. CONCLUSIONS: Regional intraarterial administration of chemotherapy with or without cytokines may be effective for controlling hepatic metastases of malignant melanoma in patients with disease limited to the liver, but little benefit is evident in patients who present with concurrent extrahepatic disease.

Regional administration of irinotecan in combination with 5-fluorouracil and leucovorin in patients with colorectal cancer liver metastases--a pilot experience.

BACKGROUND/AIMS: Regional chemotherapy represents an effective approach for the control of isolated liver metastases of colorectal cancer. Fluoropyrimidines have been the basis of systemic and regional chemotherapy of this disease for several decades, but recent studies have demonstrated that the addition of irinotecan (CPT-11) ameliorates the results of systemic treatment. METHODOLOGY: Fifteen patients with isolated liver metastases of colorectal carcinoma were treated with regional administration of CPT-11 in combination with 5-fluorouracil/folinic acid (5-FU/FA). CPT-11 (100-200 mg, mean: 93 +/- 25, range: 51-125 mg/m2) was administered weekly in combination with 5-FU (1000-2000 mg, 857 +/- 182, range: 538-1301 mg/m2) and FA (100-350 mg). Peripheral blood leukocyte phenotype was examined during the treatment in selected patients. RESULTS: One patient achieved complete response, 4 patients had partial response, 7 patients had stable disease, 1 patient progressed and 2 patients were not evaluable. The response rate was 38% in evaluable patients, and a more than 50% decrease in serum carcinoembryonic antigen levels was observed in 12 out of 14 patients. The treatment was generally well tolerated. All patients, except one, are currently alive at mean follow-up of 11 +/- 6 (median: 10, range: 5-24) months. The therapy is still being continued in 8 patients. CONCLUSIONS: Weekly CPT-11/5-FU/FA is highly effective in the treatment of patients with metastatic colorectal cancer limited to the liver, even after failure of previous 5-FU/FA. The present regimen should be tested as a first line treatment in phase III trial.

New technique for increasing retention of arginine on an anion-exchange column.

A method is described for enhancing retention of arginine on a pellicular anion-exchange column. Arginine exhibits adjustable increases of retention time that are dependent on the acidity of standard or sample matrix. This effect is based on interactions of the protonated form of arginine with the residual cation-exchange groups on the core beads of pellicular particles. The relative magnitude of retention time shift of arginine is evaluated for identical concentrations of hydrochloric, sulfuric, and perchloric acids. Although the direct addition of acid is very effective in influencing the retention of arginine, it affects peak shapes and retention of other peaks in the chromatographic separation. The new technique-acid coinjection-achieves a similar retention enhancement for arginine with only a minimal effect on the rest of the separation. Detection limits, reproducibility results, and calibration data are presented for the chromatography of amino acids with acid coinjection. Improved resolution of arginine is demonstrated with chromatograms of soybean hydrolysate and cell culture samples.