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.

Differential expression of the Ca2+ binding S100A6 protein in normal, preneoplastic and neoplastic colon mucosa.

The expression of calcium-binding protein S100A6 was investigated in normal colon tissue, in colon adenomas and in colorectal carcinomas. Using an immunoblotting approach we detected four S100A6 variants with Mwt of 10 kDa and pI of 5.05 (isoform I), 5.15 (isoform II), 5.23 (isoform III) and 5.32 (isoform IV) that were differentially expressed in the analysed samples. The quantitative examination of S100A6 variant expression in 25 pairs of colorectal carcinoma and matched control mucosa proved a statistically significant increased abundance of S100A6 isoforms I (P = 0.004) and III (P = 0.025) in malignant tissue, and conversely, an increased level of S100A6 isoform IV in healthy tissue (P = 0.022). The expression of isoforms I and III and the loss of isoform IV were also observed in colon cancer cell lines. In addition, the immunohistochemical study of 16 primary colorectal carcinomas revealed both in the non-paired Student t-test and in the Mann Whitney test the statistically significant accumulation of S100A6 protein (P < 0.001) in the invasive margin of the tumour. The immunohistochemical analysis of S100A6 protein in polyps differing in clinical severity gave a strong staining that was maximal in dysplastic lesions. Thus, our results indicate a possible, statistically significant correlation (non-paired Student t-test P = 0.036) between S100A6 expression and colon carcinoma progression.

Overexpression of calcium-binding protein calgranulin B in colonic mucosal diseases.

Subtractive two-dimensional gel electrophoresis (2-DE) has been used for the study of the protein patterns of the normal colonic mucosa and the specimens collected from patients diagnosed for inflammatory bowel disease (IBD), colonic polyps and colorectal cancer. We found a 13 kDa protein that was detected in five of seven adenomas and in 13 of 15 colorectal carcinomas while it was absent or only slightly expressed in normal colonic mucosa. Furthermore, this protein occurred in all specimens collected from patients suffering from IBD and its quantity reflected the increased severity of inflammation. The combination of microsequencing and mass spectrometry led to the identification of the 13 kDa spot as calgranulin B. Our results indicate that the production of calgranulin B is unregulated in inflammatory, preneoplastic and neoplastic lesions of colonic mucosa.

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.

The association between specific nutritional antioxidants and manifestation of colorectal cancer.

Determination of specific antioxidants for examination of oxidative balance and immune responses may be of value in the early diagnosis of colorectal cancer. In the present report, we investigated urinary excretion of zinc, copper, and neopterin and serum levels of vitamins A, C, and E in 30 patients (age = 64 +/- 12 y) with colorectal cancer at the time of diagnosis and in 30 control subjects (age = 61 +/- 11 y) with benign disorders not associated with a systemic inflammatory response. Urinary excretion of zinc, copper, and neopterin was significantly elevated, and serum concentration of vitamin A was decreased in patients with colorectal cancer; these changes are characteristics of systemic immune activation. These phenomena may be of use for the detection of tumor progression and immune response to neoplasm.

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.

Mitogen-induced lymphocyte proliferation and systemic immune activation in cancer patients.

AIMS AND BACKGROUND: Proliferative response of lymphocytes to mitogens is known to be decreased in cancer patients. Depressed proliferation of lymphocytes in other disorders has been linked to systemic inflammatory response. METHODS: Lymphocyte proliferation in response to phytohemagglutinin (PHA) and concanavalin A, as well as urinary neopterin, plasma interferon-gamma and interleukin-4, were investigated in 41 patients with solid tumors. RESULTS: The proliferative response to PHA was significantly depressed in cancer patients at most of the concentrations examined. Urinary neopterin and plasma interferon-gamma were significantly elevated in cancer patients, whereas interleukin-4 was undetectable in all the subjects. A negative correlation was observed between urine neopterin and lymphocyte proliferative response to mitogens. CONCLUSIONS: Lymphocyte proliferative response to PHA is significantly diminished in cancer patients, and this depression appears to be partly linked to systemic inflammatory response. Plasma interferon-gamma was significantly increased in cancer patients, whereas interleukin-4 was undetectable.

[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.

[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.

[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.

[Aberrant mammae, personal experience]. / Mamma aberrata, nase zkusenosti.

The authors present information of a group of 63 patients (60 women and 3 men) treated in 1976-1998 where supernumerous aberrant or accessory mammary gland tissue was found. The diagnosis in the majority of the patients was based on histological examination. The tissue of an aberrant mammary gland is subject to the same physiological influences as the mamma proper and can be affected by the same pathological processes--benign and malignant. This is the reason why the authors recommend early extirpation.

[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.

[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.

[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.

[Activation of the immune system in colorectal carcinoma and its assessment]. / Aktivace imunitního systému u kolorektálního karcinomu a moznost jeho stanovení.

The immune system of the patients with colorectal cancer is activated. Urinary neopterin is an index of this systemic immune activation, reflecting the circulating activity of interferon-gamma. We have measured urinary neopterin excretion in 34 patients with colorectal cancer. This excretion was significantly higher in our patients compared to reference group (325 +/- 267 vs 169 +/- 62 mumol/mol creatinine, neopterin concentrations were considerably higher in Dukes' stage D disease compared with Dukes' stage B and C disease/561 +/- 372 vs 188 +/- 47 and 250 +/- 142 mu/mol creatinine. Increased neopterin detected the presence of metastatic disease with 90% sensitivity and 87.5% specificity. Authors conclude that urinary neopterin measurement may be useful in the staging of colorectal cancer.