Expression of coxsackie and adenovirurus receptor and its significance in human lung cancer

Abstract Objective  To study the relationship between the coxsackie and adenovirus receptor (CAR) and the development of human lung cancer. To optimize adenovirus vector-based gene therapy.

Leukemia following breast cancer: an international population-based study of 376,825 women

Abstract Purpose  To quantify long-term temporal trends in the excess absolute risk (EAR) of secondary leukemia among breast cancer (BC) survivors, using multivariate analyses to evaluate the effects of subtype, age at BC diagnosis, attained age, and calendar year.

Capecitabine and doxorubicin combination chemotherapy as salvage therapy in pretreated advanced gastric cancer

Abstract Purpose  The aim of this study was to evaluate the activity and the safety of a combination regimen of capecitabine and doxorubicin as salvage chemotherapy in advanced gastric cancer patients who had undergone one or two prior chemotherapy regimens.

Cost-Effectiveness of Letrozole in the Extended Adjuvant Treatment of Women with Early Breast Cancer

Abstract  Adjuvant tamoxifen therapy for 5 years reduces recurrence in hormone receptor positive, post-menopausal women with early breast cancer, but offers no advantage when prolonged to another 5 years, during which the risk of recurrence remains high. Treating patients, who remain disease-free after 5 years of tamoxifen, with letrozole significantly reduces recurrence, regardless of nodal status. This study evaluated the life-time cost-utility of extended adjuvant letrozole therapy in 62-year-old patients from a third-party payer perspective. A Markov model incorporated locoregional, contralateral, and metastatic recurrences. The comparator was placebo. Event rates were based on published trials. Utility values were taken from a clinical trial and published literature. Costs were obtained from published literature, provincial payment schedules, cancer agencies, and drug plans formularies. Resource use reflected Canadian treatment patterns. Robustness of the model was tested using deterministic and probabilistic sensitivity analyses. Extended adjuvant letrozole therapy of a cohort consisting of 50% node-negative and 50% node-positive patients prolonged their lives on average by 0.466 years or 0.267 quality-adjusted life years (QALYs) at an additional cost of Can$8,031 per patient, yielding an incremental cost-utility ratio (ICUR) of $34,058 per QALY. Letrozole was more cost-effective in node-positive than in node-negative patients (Can$26,553 vs Can$46,049 per QALY). Results were robust to variations in age, healthcare costs, and utilities. The degree of confidence that the cost per QALY would be below Can$50,000 reached 100% for node-positive and 77% for node-negative patients. Extended adjuvant letrozole is cost-effective in both node-negative and node-positive patients having ICURs below Can$50,000/QALY.

Topoisomerase I protein expression in primary colorectal cancer and recurrences after 5-FU-based adjuvant chemotherapy

Abstract Purpose  Our aim was to investigate whether chemotherapy with 5-FU induces an alteration in the levels of topoisomerase I (topo I) in colorectal neoplastic tissues

Pregnancy-related complications after vaginal radical trachelectomy for early-stage invasive uterine cervical cancer

Abstract Background  Pregnancy-related complications after vaginal radical trachelectomy (RT) for early-stage invasive uterine cervical cancer were studied in comparison with those occurring after laser conization. The strategy to reduce vaginal RT-related complications during pregnancy is also discussed.

Phase I and pharmacologic study of irinotecan and amrubicin in advanced non-small cell lung cancer

Abstract Purpose  We conducted a Phase I trial of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with amrubicin, a topoisomerase II inhibitor. The aim was to determine the maximum tolerated dose (MTD) of amrubicin combined with a fixed dose of CPT-11 as well as the dose-limiting toxicities (DLT) of this combination in patients with advanced non-small cell lung cancer.

Prognosis in epithelial ovarian cancer: Clinical analysis of 287 pelvic and para-aortic lymphadenectomy

Abstract Objective  To evaluate the relationship between the pelvic and para-aortic lymphadenectomy and the prognosis of epithelial ovarian cancer.

Intra-operative Sonography: A Valuable Aid During Breast-Conserving Surgery for Occult Breast Cancer

Abstract Background  Breast cancer is increasingly detected during an early non-palpable stage. Together with pre-operative marking of the mass, intra-operative imaging provides invaluable clues. This study was designed to evaluate the usefulness of intra-operative sonography in the hands of the surgeon.

Combination probe and dye-directed lymphatic mapping detects micrometastases in early colorectal cancer

Abstract  Nodal metastasis is the single most important prognostic factor in early colorectal cancer (CRC). Lymphatic mapping can identify sentinel nodes for focused histopathologic examination and thereby improve the nodal staging of CRC; however, the optimal technique for identifying sentinel nodes in CRC is unclear. We hypothesized that a combination of radiotracer and blue dye would more accurately identify tumor-positive sentinel nodes than blue dye alone. Lymphatic mapping was performed in 48 consecutive patients undergoing resection for CRC and in two original patients who underwent sentinel node mapping in 1996. Prior to resection, 1% vital blue dye and radiotracer were injected around the tumor in the subserosal layer. Nodes were designated as sentinel by blue coloration and/or radioactivity. Lymphatic mapping identified at least one sentinel node in 49 patients. Focused examination of multiple sentinel node sections by means of hematoxylin and eosin and immunohistochemical analysis showed that sentinel nodes accurately predicted the status of the nodal basin in 93.8% (46 of 49) of patients. Of the 19 patients with nodal metastases, 11 had macrometastases (>.2 mm), three had micrometastases (between 2 mm and 0.2 mm), and five had isolated tumor cells or clusters (<.2 mm) identified by immunohistochemical analysis only.Patients had significantly fewer blue/radioactive (“hot”) nodes than blue-only nodes (1.38 vs. 2.48 per patient; P = 0.0001). It is important to note that nodal metastases were more common in blue/ hot nodes than in blue-only nodes (27.3% [19 of 68] vs. 8.8% [11 of 124]; P = 0.005). Dual-agent lymphatic mapping more accurately identifies sentinel node metastases than blue dye alone. In addition, this technique allows a more focused histopathologic examination of these nodes, in conjunction with the revised American Joint Committee on Cancer guidelines, and thereby offers the potential for significant upstaging of CRC.

Primary systemic therapy does not eradicate disseminated tumor cells in breast cancer patients

Abstract Introduction  The presence of disseminated tumor cells in the bone marrow of breast cancer patients has proven to be an independent prognostic factor. The aim of this study was to investigate the status of tumor cell dissemination after primary systemic therapy in relation to therapy response.

Trends in breast cancer treatment in Korea and impact of compliance with consensus recommendations on survival

Abstract  Although some studies suggest that conformity with consensus recommendations for breast cancer therapy is associated with increased survival, the data are not clear. We identified patients in four hospital-based breast cancer registries in Korea who had undergone primary curative surgery (stage 0–III) from 1993 through 2002 (n = 8,407). We collected demographic and clinical characteristics such as age, stage, treatment, and hormone receptor status. We gathered 1993–2004 mortality data by linkage to the National Statistical Office. During the follow-up period of 43,145 person–years (mean, 5.13 years), we identified 899 deceased cases. We used the standard Poisson regression model to estimate the hazard ratio (HR) for survival in relation to conformity with guidelines for chemo-, hormone, and locoregional therapy. Guideline compliance for systemic therapy increased from 24.0% in 1993 to 83.8% in 2002. Among mastectomy patients with <4 positive lymph nodes and tumors <5 cm, post-mastectomy radiotherapy was associated with poor survival (HR 2.07; 95% CI: 1.53–2.81). Tamoxifen use was associated with better survival among patients with hormone receptor-positive tumors (HR 0.57; 95% CI: 0.45–0.73) and with poorer survival among hormone receptor-negative patients who had affected nodes (HR 1.58; 95% CI: 1.01–2.44). Relative to conformity, non-conformity with both chemo- and hormone therapy guidelines was associated with a 76% higher risk of death. Compliance with consensus recommendations for chemo- and hormone therapy is significantly associated with better survival. Overuse of post-mastectomy radiotherapy and tamoxifen beyond the consensus recommendations may be harmful.

Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer

Abstract   Background: Brain metastases are frequently encountered in Her2 positive advanced breast cancer. It is still not clear, if trastuzumab treatment should be continued following their diagnosis. In this analysis we evaluated if trastuzumab was able to influence time to in-brain progression (TTP) and overall survival (OS). For this reason, we compared patients who continued on trastuzumab with a historical control group. Patients and Methods: Seventeen Her2 positive patients receiving whole brain radiotherapy for brain metastases and continuing on trastuzumab were identified. As historical control group, thirty-six patients treated before 2002 were identified from a breast cancer database. We performed a multivariate analysis (Cox regression) to explore which factors were potentially able to significantly influence TTP and OS. Results: Median TTP was 6 months, range 1–33+ months. Median OS was 7 months, range 1–38 months. Seventeen patients received trastuzumab after WBRT. Factors associated with prolonged TTP were KPS (p = 0.001), and intensified local treatment (p = 0.004). A trend towards longer TTP was observed in patients treated with trastuzumab (p = 0.068). OS was significantly influenced by KPS (p < 0.001), and continued antibody therapy (p = 0.001). Conclusion: Two parameters were significantly associated with prolonged OS: KPS and trastuzumab. While there was a trend towards prolonged TTP in patients with trastuzumab treatment after WBRT, this did not reach statistical significance. It appears therefore reasonable to suggest continuation of antibody therapy in patients with good performance status despite disease spreading to the brain. Concerning activity of trastuzumab in brain metastases themselves, no final conclusion is possible.

Long-term efficacy of preoperative radiotherapy for locally advanced low rectal cancer

Abstract Background and aims  The purpose of this study was to assess the long-term efficacy of preoperative radiotherapy for locally advanced low rectal cancer.

Surgical Site Infection Among Women Discharged with a Drain In Situ After Breast Cancer Surgery

Abstract Background  There are scarce data on the factors associated with surgical site infection (SSI) among women who are discharged with a drain in situ after breast cancer surgery. The aim of this study was to determine the incidence and the factors associated with SSI in a center where women are routinely discharged with a drain in place.

Immune response, depression and fatigue in relation to support intervention in mammary cancer patients

Abstract Goal of work  To study the effect of support intervention on immune function in breast cancer patients.

Activin A Causes Cancer Cell Aggressiveness in Esophageal Squamous Cell Carcinoma Cells

Abstract Background  Expression of activin A is associated with lymph node metastasis and clinical stage in esophageal cancer.

Variations in Surgical Treatment and Outcomes of Patients With Pancreatic Cancer: A Population-Based Study

Abstract Background  There is ongoing debate on how variations in surgical technique affect outcomes in pancreatic cancer. This population-based study examines current surgical practice and outcomes for cancer of the pancreatic head.

Evaluation of [18F]-choline PET/CT for staging and restaging of prostate cancer

Abstract Purpose  To evaluate the accuracy of [18F]-choline (FCH) positron emission tomography/computed tomography (PET/CT) for staging and restaging of prostate cancer.

Phase I and pharmacokinetic study of vatalanib plus capecitabine in patients with advanced cancer

Abstract  Angiogenesis inhibition is now a proven therapeutic strategy in treatment of several solid tumors. Vatalanib is a potent inhibitor of all known vascular endothelial growth factor receptor (VEGFR) tyrosine kinases. In view of the effectiveness of angiogenesis inhibitor therapy when combined with chemotherapy and the established role of capecitabine in treatment of colorectal and breast cancer, we undertook a phase I clinical trial of the combination of capecitabine and vatalanib with the goal of developing a combination oral regimen. The study objectives were to determine the maximally tolerated dose of vatalanib that could be safely administered daily with capecitabine given orally for 14 out of 21 days to patients with advanced cancer; to characterize the safety, tolerability, and pharmacokinetic profile of vatalanib given in combination with capecitabine; and to describe any pharmacokinetic interactions between the drugs. The study had an initial dose escalation phase followed by a dose expansion phase. During the dose escalation phase, cohorts of at least three patients each were treated with capecitabine and escalating doses of vatalanib until the maximally tolerated dose of vatalanib was determined. Vatalanib given continuously at a dose of 1,250 mg/day could be safely combined with capecitabine at a dose of 2,000 mg/m2/day given for 14 of 21 days. Dose-limiting toxicities of the combination included fatigue, hypertension, dizziness, and proteinuria. Vatalanib did not alter the pharmacokinetics of 5-FU, the active metabolite of capecitabine. Vatalanib and capecitabine can be safely combined without unexpected toxicities or significant pharmacokinetic interactions.

Evaluation of selective defunctioning stoma after low anterior resection for rectal cancer

Abstract Background  Anastomotic leakage is a major concern after resection for low rectal cancer. Therefore, the use of a defunctioning stoma (DS) has been suggested, but limited data exist to clearly determine the necessity of a routine diversion. In our department, the indication of DS was evaluated subjectively by the operating surgeon. The aim of this study was to evaluate the selective use of fecal diversion.

Früherkennung und Prim?rpr?vention des Dickdarmkrebses

Zusammenfassung  Das kolorektale Karzinom (KRK) ist in der westlichen Welt und in Deutschland eine h?ufige Erkrankung mit hoher Sterblichkeit. Durch die Anwendung von Ma?nahmen der Prim?rpr?vention kann eine Inzidenzreduktion von ca. 50% erwartet werden. Prim?rpr?vention beim KRK ist nicht nur erwiesenerma?en effektiv, sondern auch ?konomisch sinnvoll. Diese Ma?nahmen sind zwar bekannt, werden jedoch nur von 20% der Bev?lkerung umgesetzt. Aus diesem Grund kommen heute den sekund?ren Pr?ventivma?nahmen in Form von Polypen- und Karzinomfrüherkennung eine umso gr??ere Bedeutung zu. Folgende zwei Screening-Optionen stehen in Deutschland optional zur Verfügung: Die Ileokoloskopie mit Vollendung des 55. Lebensjahres in 10-j?hrlichen Intervallen oder alternativ die Untersuchung auf okkultes Blut im Stuhl (FOBT) ab dem 50. Lebensjahr in j?hrlichem Intervall oder optional zur Koloskopie ab dem 56. Lebensjahr in zweij?hrigem Abstand. Aufgrund seiner Vorteile wird die prim?re Koloskopie inzwischen als Screening-Option der ersten Wahl in den Leitlinien empfohlen.

Percutaneous Hepatic Perfusion in Patients with Metastatic Liver Cancer: Anesthetic, Hemodynamic, and Metabolic Considerations

Abstract Background  Percutaneous hepatic perfusion (PHP), a regional cancer therapy, entails insertion of percutaneous catheters to isolate hepatic vasculature and enable simultaneous hepatic venous hemofiltration of high-dose chemotherapy. PHP has been shown to be safe and to benefit some patients with liver metastases.

Minimal clinical benefit of single agent Orathecin (Rubitecan) in heavily pretreated metastatic breast cancer

Abstract   Purpose: The purpose of this phase II study was to evaluate the efficacy and tolerability of Orathecin, an oral camptothecin analog that has exhibited antitumor activity in breast cancer patients during preclinical studies. Methods: Sixteen patients with metastatic breast cancer previously treated with anthracycline and taxane were utilized in the study. Orathecin was administered orally at 1.5 mg/m2 /day for the first five consecutive days of the cycle followed by 2 days of rest on a 7-day schedule. The end points of the study were efficacy and toxicity. Results: The median age of the patients was 51 years (range, 35–73). Eight patients (50%) had multiple disease sites, and nine patients (56%) received more than three chemotherapy regimens. All patients were evaluated for toxicity, three patients were removed from the study for toxicity or disease progression prior to 8 weeks and were thus not evaluated for efficacy. The median follow-up was 110 days (range, 15–554). There were no responses to treatment. Five of the 13 evaluable patients (38%) had stable disease, eight (61%) had progressive disease. Most adverse events were mild to moderate in intensity. The median time to progression (TTP) for evaluable patients was 109 days (range, 56–374 days) (lower 95% C.I., 57 days). The median survival time was 272 days (lower 95% C.I., 209 days). Conclusions: Orathecin at the dose and regimen used in this study resulted in no objective tumor responses for this heavily pretreated population. Accurate risk stratification strategies can improve patients‘ selection and contribute to determine the appropriate benefit of therapies in MBC.

Prognosis of Perihilar Cholangiocarcinoma: Hilar Bile Duct Cancer versus Intrahepatic Cholangiocarcinoma Involving the Hepatic Hilus

Abstract Background  Clinically hepatobiliary resection is indicated for both hilar bile duct cancer (BDC) and intrahepatic cholangiocarcinoma involving the hepatic hilus (CCC). The aim of this study was to compare the long-term outcome of BDC and CCC.

Tumor-associated carbonic anhydrases are linked to metastases in primary cervical cancer

Abstract   Purpose: Carbonic anhydrase IX (CA9) has emerged as an important surrogate marker for hypoxia in solid tumors. CA12 shares a role with CA9 in acidification of micromilieu but it is less strictly regulated by hypoxia than CA9. In this study, we investigated expression of CA9 and CA12 mRNA in primary cervical cancer. We also examined whether CA9 expression can be an indicator of reoxygenation of tumor by measuring its mRNA expression during fractionated radiotherapy. Methods: Tumor tissues were obtained from 59 patients with uterine cervical cancer who underwent radiotherapy, and a second biopsy was taken after patients had received either 10 or 20 Gy of radiation. The follow-up period ranged from 2.4 to 75 months (median=23 months). The ratio of CA9 and β-actin mRNA expression was determined both pre- and during radiation treatment by RT-PCR. Results: CA9 and CA12 mRNA expression was detected in 62.7 and 88.1% of tumors (i.e. patients), respectively, and co-expression was observed in 61% of patients. Multivariate analysis revealed that CA9 expression was the most significant factor associated with metastasis-free survival (P=0.008, hazard ratio 34.8), whereas CA12 mRNA expression was linked to a lower risk of metastasis (P=0.007, hazard ratio of 0.07). Tumor CA9 expression was not altered following either 10 or 20 Gy of radiotherapy. Conclusion: The strong correlation between CA9 expression and metastasis suggests that CA9 expression might be an important indicator for identifying patients who require more aggressive systemic therapy.

Effects of the mTOR inhibitor sirolimus in patients with hepatocellular and cholangiocellular cancer

Abstract Background  Hepatocellular cancer (HCC), as well as cholangiocellular cancer (CCC), has an extremely poor prognosis due to the extent of tumor at diagnosis and the underlying liver disease. Sirolimus is used in the transplantation setting as an immunosuppressive agent, but it also possesses antiproliferative and antiangiogenic properties. The objective of the study was to evaluate the effect of sirolimus on HCC and CCC.

Treatment-induced menstrual changes in very young (<35?years old) breast cancer patients

Summary Purpose  To evaluate the treatment-induced menstrual changes in very young (< 35 years old) breast cancer patients.

Results of video-assisted thoracoscopic surgery for esophageal cancer during the induction period

Abstract Objective  The attainment of proficiency in thoracoscopic radical esophagectomy for thoracic esophageal cancer requires much experience. We aimed to master this procedure safely with our regular surgical team members under the direction of an experienced surgeon. We evaluated the efficacy of instruction during the induction period and the significance of our results.

High-Resolution Anoscopy in the Diagnosis of Anal Cancer Precursor Lesions in Renal Graft Recipients

Abstract Background  Renal graft recipients are one of the population groups known to be at high risk of developing anal cancer. This study investigated the presence of subclinical anal squamous intraepithelial lesions and the diagnostic ability of high-resolution anoscopy in detecting these lesions in renal graft recipients followed-up in Manaus.

Detection of circulating tumor cells in patients with pancreatic cancer: a preliminary result

Abstract Background/Purpose  It has been reported that circulating tumor cells (CTCs) can be used to predict survival in metastatic breast cancer. In this preliminary study, we examined the level of CTCs in pancreatic cancer (PC) patients to elucidate whether we could predict survival in PC.

Endoskopische Resektion und minimal-invasive Verfahren beim Magenkarzinom

Zusammenfassung  Die endoskopische Therapie des Magenfrühkarzinoms ist in der westlichen Welt noch nicht vollst?ndig etabliert. Neuerdings ist die Entdeckung früher Tumorstadien und die Option der kurativen operativen Therapie, ggf. auch durch endoskopische Operation, das Ziel diagnostischer endoskopischer Ma?nahmen. Die endoskopische Resektion des mukosalen Magenfrühkarzinoms (EMR) ist in Japan inzwischen die Behandlungsmethode der Wahl. Mittlerweile gibt es erfolgreiche Standardtechniken der endoskopischen Resektion. Eine mit modifizierten Nadelmessern durchgeführte direkte „Dissektion“ der Submukosa wurde als endoskopische Submukosadissektion (ESD) klassifiziert. Eine internationale Studiengruppe unter Deutscher Leitung untersuchte die Durchführbarkeit der ESD. Die Ergebnisse zeigen, dass Diagnose und Therapie des Magenfrühkarzinoms au?erhalb von Japan zwar m?glich sind, aber offensichtlich mit deutlich differenten Ergebnissen. Vor einer breiten Anwendung der EMR oder der ESD beim Magenfrühkarzinom durch in Diagnostik und Therapie von gastrointestinalen Neoplasien unerfahrene Institutionen und au?erhalb von prospektiven Studien ist daher abzuraten. Minimal-invasive chirurgische Therapieverfahren und lokale Exzisionstechniken sind individuell zu diskutieren.

A multicenter randomized phase II trail of Oxaliplatin in the patients with colorectal cancer

Abstract Objective  To evaluate the efficacy and safety of Oxaliplatin in the patients with colorectal cancer.

Lower Use of Hospice by Cancer Patients who Live in Minority Versus White Areas

Background  Although hospice care can alleviate suffering at the end of life for patients with cancer, it remains underutilized, particularly by African Americans and Hispanics.

Software-based Fusion of PET and CT Images for Suspected Recurrent Lung Cancer

Abstract Purpose  The purpose of this study was to compare the diagnostic performance of the manual fusion of positron emission tomography (PET) and computed tomography (CT) images with that of CT alone and that of side-by-side PET and CT (PET/CT) in patients with suspected recurrent lung cancer.

Intraoperative Frozen Section Analysis of Sentinel Lymph Node in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Abstract Background  Recently, many studies have demonstrated the feasibility and accuracy of sentinel lymph node (SLN) biopsy for patients treated with neoadjuvant chemotherapy (NAC). However, no studies have been conducted to evaluate the accuracy of frozen section (FS) analysis of SLN in NAC-treated patients. The aim was to evaluate the accuracy of intraoperative FS analysis of SLNs in breast cancer patients treated with NAC in comparison with that in those not treated.

The Neuregulin Family of Genes and their Multiple Splice Variants in Breast Cancer

Abstract  The neuregulin family consists of four genes, NRG1–4 which can each encode products containing a domain related to the epidermal growth factor family of ligands. Each gene is subject to complex control of transcription and to splicing of their mRNA product to give many variant proteins. These do not contain secretory sequences but some, through their transmembrane sequence, are routed via the Golgi where they are glycosylated, to the cell surface. Here they may be released by regulated proteolysis to act as soluble proteins which can interact and activate members of the EGF receptor family of receptor tyrosine kinases. Other splice variants do not encode transmembrane sequences and these are found either in the cytoplasm or, if they encode a nuclear localisation sequence, in distinct compartments in the nucleoplasm. It has been shown that the variants containing a full EGF domain can act as receptor agonists but the function of the cytoplasmic and nuclear products is unknown as yet. All four neuregulin genes are expressed and play an important role in mammary gland development. They are also expressed at elevated levels in some cases of ductal carcinoma in situ of the breast and breast cancer. They seem to be active in this setting and their presence may affect the efficacy of treatment with endocrine agents or with signal transduction inhibitors directed at the EGF receptor family members. Much remains to be learned however of their normal function and their influence on breast cancer development, progression and response to therapy.

The effect of anti-VEGF therapy on immature myeloid cell and dendritic cells in cancer patients

Abstract  Impairment of dendritic cells (DC), the most effective activators of anticancer immune responses, is one mechanism for defective antitumor immunity, but the causes of DC impairment are incompletely understood. We evaluated the association of impaired DC differentiation with angiogenesis-associated molecules D-dimer, vascular endothelial growth factor (VEGF), urokinase plasminogen activator (uPA), and plasminogen activator inhibitor (PAI-1) in peripheral blood from 41 patients with lung, breast, and colorectal carcinoma. Subsequently, we studied the effect of administration of the anti-VEGF antibody (bevacizumab) on DC maturation and function in vivo. Compared with healthy volunteers, cancer patients had a bias toward the immunoregulatory DC2, had deficits in DC maturation after overnight in vitro culture, and had a significant increase in immature myeloid cell progenitors of DC (0.50 ± 0.31% vs. 0.32 ± 0.16% of peripheral blood mononuclear cells, respectively, P = 0.011). A positive correlation was found between the percentage of DC2 and PAI-1 (R = 0.50) and between immature myeloid cells and VEGF (R = 0.52). Bevacizumab administration to cancer patients was associated with a decrease in the accumulation of immature progenitor cells (0.39 ± 0.30% vs. 0.27 ± 0.24%, P = 0.012) and induced a modest increase in the DC population in peripheral blood (0.47 ± 0.23% vs. 0.53 ± 0.30%). Moreover, anti-VEGF antibody treatment enhanced allo-stimulatory capacity of DC and T cell proliferation against recall antigens. These data suggest that DC differentiation is negatively associated with VEGF levels and may be one explanation for impaired anticancer immunity, especially in patients with advanced malignancies.

Maximum tumor diameter is not an independent prognostic factor in high-risk localized prostate cancer

Abstract Objectives  Previous studies suggest that maximum tumor diameter (MTD) is a predictor of recurrence in prostate cancer (PC). This study investigates the prognostic value of MTD for biochemical recurrence (BCR) in patients with PC, after radical prostatectomy (RP), with emphasis on high-risk localized prostate cancer.

The Diasporin Pathway: a tumor progression-related transcriptional network that predicts breast cancer survival

Abstract  Microarray expression signature analyses have suggested that extracellular matrix (ECM) gene dysregulation is predictive of metastasis in both mouse mammary tumorigenesis and human breast cancer. We have previously demonstrated that such ECM dysregulation is influenced by hereditary germline-encoded variation. To identify novel metastasis efficiency modifiers, we performed expression QTL (eQTL) mapping in recombinant inbred mice by characterizing genetic loci modulating metastasis-predictive ECM gene expression. Three reproducible eQTLs were observed on chromosomes 7, 17 and 18. Candidate genes were identified by correlation analyses and known associations with metastasis. Seven candidates were identified (Ndn, Pi16, Luc7l, Rrp1b, Brd4, Centd3 and Csf1r). Stable transfection of the highly metastatic Mvt-1 mouse mammary tumor cell line with expression vectors encoding each candidate modulated metastasis-predictive ECM gene expression. Implantation of these cells into mice demonstrated that candidate gene ectopic expression impacts tumor progression. Gene expression analyses facilitated the construction of a transcriptional network that we have termed the ‘Diasporin Pathway’. This pathway contains the seven candidates, as well as metastasis-predictive ECM genes and metastasis suppressors. Brd4 and Rrp1b appear to form a central node within this network, which likely is a consequence of their physical interaction with the metastasis efficiency modifier Sipa1. Furthermore, we demonstrate that the microarray gene expression signatures induced by activation of ECM eQTL genes in the Mvt-1 cell line can be used to accurately predict survival in a human breast cancer cohort. These data imply that the Diasporin Pathway may be an important nexus in tumor progression in both mice and humans.

COUP-TFI modulates estrogen signaling and influences proliferation, survival and migration of breast cancer cells

Abstract  We previously showed that COUP-TFI interacts with the Estrogen Receptor alpha (ERα) to recruit Extracellular signal Regulated Kinases (ERKs) in an Estradiol (E2)-independent manner, resulting in an enhancement of ERα transcriptional activity. However, the involvement of COUP-TFI in physiologically relevant functions of ERα, such as the mitogenic activity that E2 has on breast cancer cells, remains poorly understood. Here, we first showed that the amounts of COUP-TFI protein are higher in dedifferentiated mammary cell lines (MDA-MB-231) and tumor breast cells as compared to the differentiated MCF-7 cell line and normal breast cells. To evaluate the functional relevance of the COUP-TFI/ERα interplay in mammary cells, we generated MCF-7 cells that stably over-express COUP-TFI. We found that the over-expression of COUP-TFI enhances motility and invasiveness of MCF-7 cells. COUP-TFI also promotes the proliferation of MCF-7 cells through ERα-dependent mechanisms that target cell cycle progression and cell survival. To further investigate the mechanisms underlying these effects of COUP-TFI, we evaluated the expression of known E2-target genes in breast cancer, and found that COUP-TFI differentially regulated genes involved in cell proliferation, apoptosis, and migration/invasion. Notably, Cathepsin D (CTSD) transcript and protein levels were significantly higher in presence and absence of E2 in MCF-7 over-expressing COUP-TFI. Chromatin Immunoprecipitation assays showed that ERα, phospho-RNA Polymerase II, as well as p68 RNA Helicase, a phospho-Serine 118 dependent co-activator of ERα, were preferentially recruited onto the CTSD gene proximal promoter in COUP-TFI over-expressing cells. These results suggest that COUP-TFI selectively regulates the expression of endogenous E2-target genes and consequently modifies ERα positive mammary cells response to E2.

The potential of 211Astatine for NIS-mediated radionuclide therapy in prostate cancer

Abstract Purpose  We reported recently the induction of selective iodide uptake in prostate cancer cells (LNCaP) by prostate-specific antigen (PSA) promoter-directed sodium iodide symporter (NIS) expression that allowed a significant therapeutic effect of 131I. In the current study, we studied the potential of the high-energy alpha-emitter 211At, also transported by NIS, as an alternative radionuclide after NIS gene transfer in tumors with limited therapeutic efficacy of 131I due to rapid iodide efflux.

HPV status and regional metastasis in the prognosis of oral and oropharyngeal cancer

Abstract  Prognostic factors are important for treatment decisions as they help adapt the therapy on a case-to-case basis. Nodal status, number of positive nodes, and presence of extracapsular spread are considered to be the important prognostic factors in head and neck cancer. Some studies suggest that human papillomavirus (HPV) status also influences the outcome of the treatment. This influence can be explained by the variation in tendency to develop regional metastases and by variation in the type of neck node involvement. The study objectives were to compare patients with HPV positive and HPV-negative tumors for survival and prevalence and type of regional metastasis, to identify prognostic factors and to test whether HPV presence is an independent factor of survival. The study included 81 patients treated by surgery including neck dissection for oral or oropharyngeal squamous cell cancer. A computerized medical report was completed for each patient. Analysis of the tumor specimen for the HPV DNA presence was done on paraffin-fixed tissue. HPV DNA detection and typing were performed by PCR with GP5 + /GP6 + BIO primers and reverse line blot hybridization. Overall, 64% (52/81) of tumors were HPV positive with 80% in the tonsillar site. HPV-positive patients had significantly better both overall (73 vs. 35%) (P = 0.0112) and disease-specific (79 vs. 45%) (P = 0.0015) survival rates than HPV-negative patients. No significant differences were found in the pN classification, in the number of positive nodes and the presence of extracapsular spread in the involved nodes between HPV positive and HPV-negative tumors. Multivariate analysis showed that significant prognostic factors of survival were the presence of HPV in the tumor, extracapsular spread and tumor size. HPV was the most significant prognostic factor in the studied group of patients with oropharyngeal tumors (HR = 0.27, 95%CI 0.12–0.61) and possibly should be considered in treatment decisions.

Previous Laparotomy is Not a Contraindication to Laparoscopy-assisted Gastrectomy for Early Gastric Cancer

Abstract Background  Laparoscopic procedures have generally been considered to be contraindicated in patients with a history of laparotomy because of a high risk of enteric injury during the procedure. Laparoscopy-assisted gastrectomy (LAG) has been used increasingly in the treatment of early gastric cancer, but its indication for patients with a history of laparotomy remains unclear. The aim of the present study was to estimate whether LAG is contraindicated for the patient with a history of laparotomy (PSURG).

Phase I trial of pemetrexed plus oxaliplatin administered every other week in patients with metastatic cancer

Summary   Purpose: To identify the maximum tolerated dose (MTD) and describe dose-limiting toxicities (DLT) of pemetrexed and oxaliplatin given on a once-every-2-week schedule in patients with metastatic cancer. Patients and methods: Twenty-five patients were enrolled. Due to toxicities observed at the first dose level in unselected patients, a second MTD was determined in patients who had received zero to two prior chemotherapy regimens. Results: DLT was observed at dose level 1—pemetrexed 400 mg/m2 and oxaliplatin 85 mg/m2—in the form of grade 3 fatigue in two of six patients. Enrollment was then limited to lightly pretreated patients and DLT was observed at dose level 2—pemetrexed 500 mg/m2 and oxaliplatin 85 mg/m2—in the form of neutropenic fever in one of five patients. Complete response was confirmed in one patient (squamous cell carcinoma of the head and neck) and partial response was confirmed in three patients. Conclusions: The combination of pemetrexed and oxaliplatin can be safely administered at doses of 400 to 500 mg/m2 of pemetrexed and 85 mg/m2 in patients without extensive prior therapy and 300 and 85 mg/m2, respectively, every 2 weeks in patients with more extensive prior therapy. Based on promising results observed in this study, a phase II trial in patients with recurrent head and neck cancer has been initiated.

Gefitinib (Iressa, ZD1839) inhibits SN38-triggered EGF signals and IL-8 production in gastric cancer cells

Abstract  Epidermal growth factor receptor (EGFR) and its ligands are involved in tumor growth, metastasis, angiogenesis, and resistance to chemotherapy. In the experiments described here using AGS gastric cancer cells, SN38 (the active metabolite of CPT-11) induced tyrosine phosphorylation of EGFR within 5 min, and this was followed by the induction of transcripts and/or proteins of heparin-binding EGF-like growth factor, amphiregulin, transforming growth factor-, and interlukin-8 (IL-8). SN38 also activates nuclear factor-B and activator protein-1, both of which are critical for the transcription of the IL-8 gene. However, the blocking of EGFR activation by gefitinib (Iressa, ZD1839), an EGFR-TKI (tyrosine kinase inhibitor), abrogates all the above reactions. The SN38-triggered mechanisms include the generation of reactive oxygen species (ROS) and the activation of protein kinase C (PKC), followed by metalloproteinase activation and the sequential ectodomain shedding of EGFR ligands. These findings suggest that EGF signaling is enhanced by CPT-11 and point to the potential benefit of the use of a combination of CPT-11 with gefitinib in the treatment of certain gastric cancers.

Role of insulin-like growth factor binding proteins (IGFBPs) in breast cancer proliferation and metastasis

Abstract  Cancers of the breast, prostate, and lung commonly metastasize to the bone resulting in osteolysis, pathologic fracture, pain and significant clinical morbidity. To date, the reason for such selectivity in the site of metastasis remains largely unknown. The bone is a rich source of many chemokines and growth factors, including: insulin-like growth factor (IGF) I and II, transforming growth factor-β (TGF-β), interleukins, and tumour necrosis factor-α (TNF-α) [1]. We propose that exposure of breast cancer cells to the bone microenvironment results in alterations in gene expression that favour the growth and proliferation of tumour cells in the bone. To investigate this hypothesis, MDA-MB-231 breast carcinoma cells were exposed to bone-derived conditioned media (BDCM) generated by culturing fetal rat calvaria for 24 h under serum free conditions. Using cDNA microarray technology, we have identified the insulin-like growth factor family of binding proteins (IGFBPs) as genes whose expression profiles are consistently and significantly altered with exposure to this simulated bone environment in vitro, when compared to untreated controls. Our data suggests that the upregulation of IGFBP-3 seen with exposure to the bone microenvironment is directly linked to an increase in TGF-β mediated cell proliferation. Furthermore, this process appears to be functioning through an IGF-independent mechanism.

Elevated transcript level of hyaluronan synthase1 gene correlates with poor prognosis of human colon cancer

Abstract  Hyaluronan plays important roles in the complex processes of tumor invasion and metastasis. It is now known that three hyaluronan synthase (HAS) isoforms catalyze hyaluronan synthesis, which raises the question of how they are involved in malignant tumor progression. In this study, we examined the correlation between tumor progression and transcriptional levels of three HAS isoforms in specimens of human colon cancers. Tumor tissues from 31 patients with different diagnostic grades were assessed to determine the level of each HAS isoform by real time RT-PCR. The mean expression coefficients for HAS1, HAS2 and HAS3 in the cancerous parts were 0.82-, 0.91- and 1.22-fold, respectively; of those in the noncancerous parts at Dukes' stage A; 1.00-, 0.95- and 1.06-fold, respectively, at stage B; and 1.95-, 1.16- and 1.19-fold, respectively, at stage C. In survival analysis, a significant correlation was observed between poor survival and the HAS1 transcript level. When the ratio of tumor to normal tissue in the HAS1 level was compared with that of the HA receptor transcript level, there was a positive correlation with that of the CD44 variant 6 level at Dukes' stage C. Our current results therefore suggest that HAS1 plays a role in the malignant progression of human colon cancer cells.

Long-term results of interstitial brachytherapy (LDR-Brachytherapy) in the treatment of patients with prostate cancer

Abstract  Permanent interstitial brachytherapy represents the most conformal form of radiation therapy of the prostate and the number of patients with prostate cancers treated with permanent radioactive implants is increasing world wide. In the meanwhile long-term data on tumor control and treatment morbidity become available. Biochemical and clinical tumor control appears to be as effective as after radical prostatectomy or external beam radiation therapy in early prostate cancer. The risk of postreatment urinary incontinence and bowel dysfunction is low and erectile function can be preserved in the majority of patients. However, prostate brachytherapy requires a careful selection of patients as pretreatment factors predict for long-term outcome. The need for combined modality approaches in intermediate and high-risk patients remains controversely discussed. The continous refinement of intraoperative planning techniques and the elucidation of the etiology of urinary, sexual, and bowel dysfunction should result in further improvements in biochemical outcomes and decreased morbidity. Improved and standardized postimplantation evaluation will make outcome data more reliable and comparable.

Role of human papillomavirus in penile cancer, penile intraepithelial squamous cell neoplasias and in genital warts

Abstract  Using PCR, the overall prevalence of human papillomavirus (HPV) DNA in penile carcinoma is about 40–45%, which is similar to the detection rate of HPV-DNA in vulvar carcinoma (50%). In analogy to vulvar cancer two different pathways of penile carcinogenesis seem to exist. In contrast to basaloid and warty penile cancers which are regularly HPV-associated (about 80–100%), only a part of keratinizing and verrucous penile carcinomas appear to be related with HPV (33–35%). Penile intraepithelial neoplasias comprising Bowen's disease, erythroplasia of Queyrat and bowenoid papulosis are precursor lesions of basaloid and warty carcinomas of the penis.Precursors of keratinizing carcinomas and verrucous carcinomas are not established. Whether lichen sclerosus and squamous-cell hyperplasia precede penile keratinizing carcinoma is a matter of discussion. Giant condylomata acuminata may precede the development of verrucous carcinomas in some cases. Since high risk HPVs are more frequently found in verrucous carcinomas than in giant condylomas, HPV typing may be a helpful diagnostic step to differentiate giant condyloma from verrucous carcinoma.

Paraneoplastic neurological syndrome: patient with anti-Yo antibody and breast cancer: a case report

Abstract.   Presented here is the case of a paraneoplastic cerebral degeneration (PCD) in a female patient with breast cancer and the indication of anti-Yo antibodies in the cerebrospina fluid (CSF) and serum. The patient's primary indications were dizziness and a severe gait ataxia. The indication of anti-Yo antibodies led to the conclusion of the existence of a paraneoplastic cerebral degeneration. The antibodies in question are anti-Purkinje-cell autoantibodies acting against the antigens common to tumor and Purkinje cells which occur in association with a certain percentage of breast or ovarian cancers. The diagnosis of the primary tumor, that is clinically undetectable with conventional imaging processes, is performed with the aid of positron emission tomography (PET) to detect the presence of axillary lymph node metastases. The micro-invasive mammary carcinoma was able to be localized with the aid of MR mammography and, after MR mammography marking, was removed. The patient subsequently received adjuvant treatment with epirubicine and cyclophosphamide. This treatment failed to influence the paraneoplastic neurological symptoms.

Rationale for Fixed Dosing of Pertuzumab in Cancer Patients Based on Population Pharmacokinetic Analysis

Objective  Our objectives were to develop the population pharmacokinetic (PK) for pertuzumab and examine the variability of steady-state trough serum concentrations (CSS,trough) and exposure after fixed, body-weight-based, or body-surface area (BSA)-based dosing methods in cancer patients.

Geographical Variation in Surveillance Strategies After Curative-Intent Surgery for Upper Aerodigestive Tract Cancer

Abstract Background  Analysis of geographical variation in utilization of medical resources is often used to identify regions of overutilization or underutilization.

Utility of computed tomographic colonography in surveillance for hereditary nonpolyposis colorectal cancer syndrome

Abstract  Computed tomographic colonography (CTC) is suggested to be an alternative to colonoscopy as a surveillance tool in subjects with a high risk for colorectal cancer (CRC). To evaluate the utility of CTC we successively examined 78 subjects, all with a DNA mismatch repair gene mutation, by CTC and colonoscopy. We detected altogether 37 polyps or tumors in 28 subjects (prevalence 35.9%), adenomas in 13 subjects (16.7%), CRC in two (2.6%), and hyperplastic polyps in 13 (16.7%). A great majority of the polyps were diminutive. The per-patient sensitivity for detecting all lesions with CTC was 0.25 and 0.29 by two radiologists and the specificities 0.82 and 0.76. For lesions of 10 mm or larger the sensitivities were 0.6 and 1.0 and the specificities 0.96 by each examiner. Each diagnosed the two cancers correctly. We concluded that CTC has an acceptable accuracy for large lesions in the colon but the detection rate for small polyps is not comparable to that in colonoscopy. Therefore CTC remains a second choice in surveillance for use when colonoscopy for some reason is incomplete or unsuitable.

Medication use during pregnancy and the risk of childhood cancer in the offspring

Abstract  The young age at onset of many cancers in childhood has led to investigations on maternal exposures during pregnancy. Data from a population-based case-control study in Germany (1992–1997) that included 1,867 cases and 2,057 controls was used to investigate this question. Maternal use of vitamin, folate or iron supplementation was associated with a reduced risk of non-Hodgkin lymphoma and tumors and, less clearly, with leukemia, but not with CNS tumors. An increased risk of neuroblastoma was associated most markedly with diuretics and other antihypertensives, but also with vitamin, folate or iron supplementation. No associations were seen with pain relievers, antinauseants or cold medications, nor with delivery by Caesarian section. The strengths of this study are its population base, the large number of cases and the inclusion of different case groups to identify disease specificity of associations. The limitation of this study is an exposure assessment relying on maternal self-reports. In conclusion, these data indicate a potential influence of some maternal medication during pregnancy on the risk of childhood cancer in the offspring; however, no clear picture is seen.

Expression of Elk-1 in non-small cell lung cancer detected by western blot and tissue microarray

Abstract Objective  The aim of this study was to investigate the Elk-1 (Ets like transcription factor-1) expression in non-small cell lung cancer (NSCLC) and normal lung tissues and the relationship between its expression and clinicopathological characters.

Local Involvement of the Urinary Bladder in Primary Colorectal Cancer: Outcome with En Bloc Resection

Abstract Background  Colorectal cancers that adhere to the urinary bladder require en bloc partial or total cystectomy to achieve negative tumor margins.

Local Involvement of the Urinary Bladder in Primary Colorectal Cancer: Outcome with En-Bloc Resection

Abstract Background  Colorectal cancers that adhere to the urinary bladder require en-bloc partial or total cystectomy to achieve negative tumor margins.

Genetic variation in the major mitotic checkpoint genes does not affect familial breast cancer risk

Abstract  Aneuploidy, an aberrant number of chromosomes, is a very common characteristic of many types of cancers, including tumors of the breast. There is increasing evidence that defects in the spindle assembly checkpoint, which controls correct chromosome segregation between two daughter cells, might contribute to tumorigenesis. In the present study we examined the effect of promoter and coding single nucleotide polymorphisms (SNPs) in six major spindle checkpoint genes (BUB1B, BUB3, CENPE, MAD2L1, MAD2L2, TTK) on familial breast cancer (BC) risk. A case–control study was carried out with a total of nine SNPs using 441 German, familial BC cases and 552 controls matched by age, ethnicity and geographical region. Neither the individual SNPs in the studied genes nor the haplotypes in the BUB1B, CENPE and TTK genes caused any significant effect on the risk of BC. We used the multifactor-dimensionality reduction method in order to identify gene-gene interactions among the six mitotic checkpoint genes, but no association was detected. Therefore, our results indicate that the investigated SNPs in the mitotic checkpoint genes do not affect the risk of familial BC.

The role of the hypoxia-inducible BH3-only proteins BNIP3 and BNIP3L in cancer

Abstract  In this review, we summarize current knowledge of the biological functions of the atypical BH3-only proteins BNIP3 and BNIP3L, focusing on the role of these proteins in cancer. Hypoxia increases the expression of BNIP3 through the transcription factor HIF-1, but despite a considerable number of investigations, it has proven difficult to establish a clear role for BNIP3 in the cellular hypoxic response. BNIP3 can induce a form of cell death that shows features of both necrosis and apoptosis, but unusually for a BH3-only protein, death occurs independently of the BH3 domain and is critically dependent on a C-terminal transmembrane domain, which also localizes the protein to the mitochondria. BNIP3 expression does not always result in cell death, suggesting that additional factors may suppress BNIP3 or cooperate with it to induce death. BNIP3 is highly expressed in some tumors, including those of the breast, lung and cervix. However, in colorectal and pancreatic cancers BNIP3 is frequently epigenetically silenced, possibly reflecting different functions for BNIP3 in different tissues. Recent reports have shown that BNIP3 can induce autophagy and there is some evidence to suggest this may represent an emerging role for BH3-only proteins in general. However, the mechanism through which BNIP3 induces autophagy and the cellular consequences of this are yet to be established.

De l’intérêt de la collaboration entre généticiens et psycho-oncologues pour mieux appréhender la démarche en oncogénétique

Résumé:  Cet article présente l’organisation de la consultation pluridisciplinaire d’oncogénétique de l’Institut Curie, ses intervenants, son déroulement temporel et les enjeux de chaque étape. Un cas clinique permet d’illustrer les enjeux personnels et familiaux qui doivent être explorés lors de la mise en œuvre de cette démarche et lors de l’accompagnement et du suivi de la consultante ainsi que le subtilmélange entre les aspects objectifs de compréhension et de rétention d’une information complexe et ceux—plus subjectifs—des représentations et des intuitions de la personne qui consulte. Il souligne l’importance d’une collaboration renforcée entre les équipes de génétique et de psycho-oncologie.

A Phase II Prospective Multi-institutional Trial of Adjuvant Active Specific Immunotherapy Following Curative Resection of Colorectal Cancer Hepatic Metastases: Cancer and Leukemia Group B Study 89903

Abstract Background  Patients with curatively resected colorectal cancer hepatic metastases often harbor occult metastatic disease and are at high risk of experiencing recurrence. This patient cohort is ideally suited to test novel therapies such as immunotherapy. We treated patients—post-hepatic resection—with anti-idiotype monoclonal antibody vaccines to the tumor-associated antigens carcinoembryonic antigen (CeaVac) and human milk fat globule (TriAb), both of which are co-expressed in more than 90% of colorectal cancer patients.

Smoking-gene Interaction and Disease Development: Relevance to Pancreatic Cancer and Atherosclerosis

Abstract  There is little doubt that cigarette smoking remains a major environmental health risk that humans are facing in the twenty-first century. Cigarette smokers are more likely to develop many forms of diseases than nonsmokers, including cancers and vascular diseases. With the availability of the human genome sequence, we become more aware of the genetic contributions to these common diseases, especially the interactive relations between environmental factors (e.g., smoking) and genes on disease susceptibility, development, and prognosis. Although smoking is responsible for up to 30% of pancreatic cancers and about 10% of cases are ascribed to genetic reasons, some genetic variants do not predispose carriers to disease development unless they are exposed to a specific adverse environment such as smoking. This smoke-gene interaction could potentially be responsible for most of the cases. Certain polymorphisms in genes such as CYP1A1 have been shown particularly sensitive to smoking-induced pathogenesis, including pancreatic cancer and atherosclerosis. We found that individuals with CYP1A1 CC genotype had a more than three fold increase in risk for severe coronary atherosclerosis when they smoked. Patients with endothelial nitric oxide synthase (eNOS) intron 4 27 repeat homozygotes were more likely to develop severe coronary stenosis when they smoked. On the other hand, DNA variants at the eNOS gene also dictate how smoking affects the expression of eNOS. We showed that GSTM1 deficiency was not involved in smoking-induced vascular diseases, but p53 polymorphisms tended to modify the disease severity in smokers. We are still at an early stage of defining the pairs and mechanisms of smoke-gene interaction, and this etiologic mechanism may hold great potential for risk assessment, treatment strategy, and prognostic predictions.

BRCA1, BRCA2, TP53, and CDKN2A germline mutations in patients with breast cancer and cutaneous melanoma

Abstract Purpose  From epidemiological studies it appears that breast cancer (BC) and cutaneous melanoma (CMM) in the same individual occur at a higher frequency than expected by chance. Genetic factors common to both cancers can be suspected. Our goal was to estimate the involvement of “high risk” genes in patients presenting these two neoplasia, selected irrespectively from family history and age at diagnosis.

Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer

Abstract Background   TOP2A gene encodes topoisomerase II alpha, the direct molecular target of anthracyclines. This gene is frequently coamplified with HER2. The aims of this study were to analyse the pattern of TOP2A amplification and protein expression in relation to the molecular subgroups of breast cancers; and to define the impact of TOP2A amplification on the outcome of a series of patients homogeneously treated with adjuvant anthracyclines.

Neoadjuvante Therapie beim lokal fortgeschrittenen Magenkarzinom

Zusammenfassung  Die Prognose des lokal fortgeschrittenen Magenkarzinoms ist ungünstig. Das Fünfjahresüberleben für Patienten in den Stadien II und III liegt nach alleiniger Resektion bei nur 14–57%. Prognostisch limitierend sind die begrenzte Rate an R0-Resektionen und die hohe systemische Rezidivrate. Beide Probleme könnten durch neoadjuvante Therapie verbessert werden. Neoadjuvante Chemotherapie wurde in mehreren Phase-II-Studien als effektiv und sicher charakterisiert und gilt für lokal irresektabel einzuschätzende Tumoren als Verfahren der Wahl. Bei Ansprechen sollte eine sekundäre Resektion überlegt werden. In wenigen Studien wurde auch neoadjuvante Radiochemotherapie untersucht. Aus den ersten Ergebnissen einer randomisierten Phase-III-Studie (MAGIC) wird ein prognostischer Gewinn für neoadjuvant chemotherapierte Patienten mit Magenkarzinomen in den Stadien II und III sichtbar. Ergebnisse weiterer Studiengruppen werden in Kürze folgen. Somit ist die neoadjuvante Chemotherapie eine Behandlungsmodalität mit wachsender Evidenz und Bedeutung für die klinische Routineversorgung von Patienten mit lokal fortgeschrittenen Magenkarzinomen.

The current status of perioperative chemotherapy for invasive bladder cancer: a multiinstitutional retrospective study in Japan

AbstractBackground  We conducted a multiinstitutional analysis to clarify the clinical significance of perioperative chemotherapy, in invasive bladder cancers in Japan, and to identify the patient subpopulations who could benefit from perioperative chemotherapy.

Indications, contre–indications, résultats attendus et choix de la chimiothérapie néo–adjuvante du cancer du sein opérable

Résumé:   La chimiothérapie néoadjuvantedu cancer du sein correspondà lutilisation dun traitementcytostatique systémique avant letraitement locorégional (chirurgieet/ou radiothérapie). Initiée dans lesannées 1970 pour le traitement desformes localement avancées et/ouinflammatoires, la chimiothérapiedinduction sest étendue au débutdes années 1980 aux cancers ditsopérables, de taille supérieure à3 cm et/ou de position centrale afinde permettre une chirurgie conservatriceplus fréquente. Cet objectifest obtenu dans environ 75 % descas sans augmentation du risquede rechute locale et sans effet délétèresur la survie globale, malgré leretard du traitement locorégional.La chimiothérapie néo–adjuvante abien sûr évolué au fur et à mesurede lavènement des droguesmajeures du cancer du sein quesont les anthracyclines, la vinorelbineet les taxanes. Mais à ce jour,aucun protocole ne sest imposécomme un standard incontesté.Toutefois, il semble que lobtentiondune réponse complète cliniquesoit le meilleur garant pour éviter larechute. Et cela semble ne pouvoirsobserver quaprès 6 cycles, voire8 cycles de chimiothérapie combinantau minimum 2 des 3 droguesmajeures du traitement du cancerdu sein dont le docétaxel qui paraît,aujourdhui, avoir une place incontournablesurtout lorsquil estutilisé en séquentiel après un traitementà base danthracyclines endehors de toute contre–indicationcardiaque.

Sputumscreening auf Lungenkrebs ehemals asbestexponierter Arbeitnehmer

Zusammenfassung  Die Korrelation zwischen semiautomatisierter Sputumzytometrie (ASC), konventioneller Zytologie (CY) und Lungenkrebs wurde an 640 ehemals asbestexponierten Arbeitnehmern als Vorbereitung für ein Lungenkrebsscreeningprogramm untersucht (867 Untersuchungen). Nach konventioneller Röntgenuntersuchung des Thorax in 2 Ebenen wurde Sputum gesammelt. Es wurden jeweils 2 Objektträger für die ASC (saure Hydrolyse, Thionin) und die CY (Papanicolaou) gefärbt. ASC-suspekte Proben wurden mittels CY überprüft. 791 Proben waren ASC-benigne, 7 inadäquat und 69 (7,8%) ASC-suspekt. Davon wurden 4 durch CY als tumorverdächtig klassifiziert, 16 als CIS/schwere Dysplasie. 14 Proben zeigten mittelgradige/leichte dysplastische Veränderungen, 34 waren normal, inflammatorisch oder wiesen Plattenepithelmetaplasien auf, 1 war inadäquat. In einer Untergruppe von 143 Patienten mit tumorsuspekten anamnestischen Angaben bei ASC-unauffälligen Proben ergab eine CY-Überprüfung 1 schwere und 13 leichte oder mittelgradige Dysplasien, 124 normale oder inflammatorische Befunde und 4 inadäquate Proben. Vorläufig konnten 7 Patienten mit Lungenkrebs identifiziert werden (Prävalenz 0,81%), 4 Plattenepithelkarzinome (CY: high grade lesions), 3 Pleuramesotheliome, 6 Proben waren ASC-positiv. Bei 1 Pleuramesotheliompatienten war das Sputum schwergradig dysplastisch verändert. Der Einsatz von ASC und CY sollte in einer kontrollierten prospektiven randomisierten Studie mit gemeinsam radiologischen und molekularbiologischen Verfahren überprüft werden.

Prognostic Evaluation of the New American Joint Committee on Cancer/International Union Against Cancer Staging System for Hepatocellular Carcinoma: Analysis of 112 Cirrhotic Patients Resected for Hepatocellular Carcinoma

AbstractBackground  In 2002, the American Joint Committee on Cancer and the International Union Against Cancer redefined the T-classification for hepatocellular carcinoma, shifting the cutoff value for tumor size from 2 to 5 cm and giving more emphasis to vascular invasion.

Die Bedeutung von Information für Krebspatienten und Erfahrungen aus der Arbeit des Krebsinformationsdienstes in Heidelberg

Zusammenfassung   Krebspatienten haben einen ausgeprägten Informationsbedarf. Neben dem Arzt als wichtigstem Ansprechpartner nutzen sie zahlreiche andere Quellen. Aus der breiten Verfügbarkeit von Informationen ergibt sich jedoch der Bedarf nach Metainformation, nach Erklärung, Wertung und Integration in den individuellen Kontext. Ein qualitätsgesicherter telefonischer Informationsdienst kann hier wesentliche Unterstützung leisten und verbindet die Vorteile eines Massenmediums mit denen inter-personaler Kommunikation. Der Krebsinformationsdienstes (KID), mit Förderung durch das Bundesgesundheitsministerium im Jahr 1986 am Deutschen Krebsforschungszentrum etabliert, hat dieses Konzept der Gesundheitsinformation erstmals als bundesweites Angebot implementiert. Der KID vermittelt entsprechend dem aktuellen Stand des Wissens und auf den individuellen Bedarf zugeschnittene qualitäts-gesicherte Informationen zu allen onkologischen Fragen und Themen sowie Adressen und Angebote von Versorgungseinrichtungen bundesweit. Rund 40% der KID-Klientel sind Patienten. Wesentliche Anliegen sind der Wunsch nach Rückversicherung, nach Erklärung, Wertung und Einordnung vorhandener Informationen, nach einem Wegweiser in der Versorgungslandschaft und nach einem unterstützenden Gespräch. Die Telefoninformation kann Defizite ausgleichen und die Arzt-Patienten-Beziehung durch die Möglichkeit vertiefender Gespräche stützen. Entsprechend dem Bedarf und neuen Informationspräferenzen wird das Angebot durch umfangreiche Internet-Informationen, einen E-Mail-Service und die Herausgabe von Broschüren ergänzt. Der KID ist eingebunden in ein Netzwerk der Versorgungsangebote und leistet durch Auswertung der Anfragen einen Beitrag zur bedarfsorientierten Gesundheitsinformation.

Les besoins psychosociaux et le soutien apporté aux patients atteints d’un cancer: une étude nationale belge

Résumé:  Dans le cadre d’une étude Belge multicentrique, cet article rapporte l’évaluation qualitative et quantitative des besoins psychosociaux des patients atteints d’un cancer ainsi que les aides qu’ils souhaitent et re?oivent de la part de médecins spécialistes et d’infirmiers (ières). De janvier à novembre 2004, l’ensemble des patients atteints d’un cancer et hospitalisés au sein de sept unités de soins en oncologie, ainsi qu’un patient sur deux consultant au sein de ces mêmes unités ont été invités à prendre part à l’étude. Ces patients ont rempli un questionnaire sociodémographique ainsi qu’une adaptation fran?aise du Cancer Rehabilitation Evaluation System (CARES) investigant, à l’aide de 138 items, 38 types de difficultés potentiellement rencontrées au cours du dernier mois. De plus, pour chaque type de difficulté rencontrée, les patients ont signalé s’ils ont souhaité et re?u de l’aide de la part de médecins spécialistes et d’infirmiers (ières). Les informations médicales relatives à ces patients ont été récoltées auprès de leurs oncologues. Parmi les 382 patients inclus, une grande majorité a rencontré au cours du dernier mois une à plusieurs difficultés physiques, psychosociales, sexuelles ainsi que des difficultés liées aux conséquences des traitements. L’intensité des difficultés vécues est la plus élevée au niveau des difficultés physiques dans le cadre professionnel, des difficultés sexuelles et des difficultés liées aux traitements. Les patients ont attendu et re?u de l’aide de la part de médecin(s) spécialistes(s) et d’infirmiers (ières) pour faire face à de très nombreuses difficultés médicales mais également psychosociales. Les seules difficultés pour lesquelles ils rapportent avoir re?u moins d’aide qu’ils n’en ont souhaitée sont les difficultés à obtenir des informations concernant leur maladie. Cette étude souligne la diversité des difficultés rencontrées par les patients atteints d’un cancer et la nécessité d’informer les patients sur les aides que d’autres professionnels que les médecins spécialistes et les infirmiers (ières) peuvent leur apporter pour faire face à ces difficultés.

Okkulte lymphatische Tumorzelldisseminierung beim Pankreaskarzinom

ZusammenfassungZielsetzung  Ziel der Untersuchung war es, die relative Häufigkeit und prognostische Relevanz von okkulten Tumorzellen in lokoregionären Lymphknoten des Pankreaskarzinoms zu bestimmen.

Gene expression studies in prostate cancer tissue: which reference gene should be selected for normalization?

Abstract  Using quantitative reverse transcription–polymerase chain reaction (RT-PCR), reference genes are utilized as endogenous controls for relative quantification of target genes in gene profiling studies. The suitability of housekeeping genes for that purpose in prostate cancer tissue has not been sufficiently investigated so far. The objective of this study was to select from a panel of 16 potential candidate reference genes the most stable genes for gene normalization. Expression of mRNA encoding ACTB, ALAS1, ALB, B2M, G6PD, GAPD, HMBS, HPRT1, K-ALPHA-1, POLR2A, PPIA, RPL13A, SDHA, TBP, UBC, and YWHAZ was examined in matched, microdissected malignant and nonmalignant tissue specimens obtained from 17 nontreated prostate carcinomas after radical prostatectomy by real-time RT-PCR. The genes studied displayed a wide expression range with cycle threshold values between 16 and 37. The expression was not different between samples from pT2 and pT3 tumors or between samples with Gleason scores <7 and 7 (P>0.05). ACTB, RPL13A, and HMBS showed significant differences (P<0.02 at least) in expressions between malignant and nonmalignant pairs. All other genes did not differ between the matched pairs, and the software programs geNorm and NormFinder were used to ascertain the most suitable reference genes from these candidates. HPRT1, ALAS1, and K-ALPHA-1 were calculated by both programs to be the most stable genes covering a broad range of expression. The expression of the target gene RECK normalized with HRPT1 alone and with the normalization factors generated by the combination of these three reference genes as well as with the unstable genes ACTB or RPL13A is given. That example shows the significance of using suitable reference genes to avoid erroneous normalizations in gene profiling studies for prostate cancer. The use of HPRT1 alone as a reference gene shown in our study was sufficient, but the normalization factors generated from two (HRPT1, ALAS1) or all three genes (HRPT1, ALAS1, K-ALPHA-1) should be considered for an improved reliability of normalization in gene profiling studies of prostate cancer.

Clinical relevance of sentinel lymph nodes in the internal mammary chain in breast cancer patients

AbstractPurpose  Despite the widespread use of sentinel lymph node (SLN) biopsy in breast cancer patients, some controversy exists about the correct management of extra-axillary nodes, especially those located in the internal mammary chain. The aim of this study was to evaluate the incidence of SLNs in this region, calculate the lymphoscintigraphic and surgical detection rates and evaluate the clinical impact on staging and therapeutic decisions.

Vakzinierungen in der Therapie des Mammakarzinoms

Zusammenfassung  Für Brustkrebspatientinnen wurden therapeutische Vakzinierungen bisher selten und dann in Pilot- bzw. Phase-I-Studien beim metastasiertem Mammakarzinom erprobt. Dabei kam international ein breites Spektrum verschiedener Strategien zum Einsatz: tumorzellbasierte Vakzinen, antigenspezifische Impfungen (definierte Peptid-, RNA- und DNA-Vakzinen) sowie Vakzinierungen gegen Karbohydrate. Allen Ansätzen ist gemeinsam, dass sie ein tolerierbares Nebenwirkungsprofil hatten und in der palliativen Situation zumindest vereinzelt zur Stabilisierung der Erkrankung beitrugen. In aktuelleren Studien wurde anhand diverser immunologischer Parameter gezeigt, dass die Induktion tumorspezifischer T-Zellen und/oder Antikörper in Mammakarzinompatientinnen prinzipiell möglich ist. Da es für die Validierung antitumoraler Immunreaktionen jedoch keine verbindlichen Standards gibt und da klinische Endpunkte meist nur als sekundäre Zielkriterien erfasst wurden, ist es derzeit noch nicht möglich, induzierte Immunreaktionen als Surrogatparameter für die therapeutische Wirksamkeit verschiedener Impfstrategien zu werten. In der metastasierten Situation führte die Zusammensetzung, Ausprägung und Persistenz der induzierten Immunrantwort noch nicht zu einem dauerhaften klinischen Benefit. Jedoch zeigte eine erste prospektiv kontrollierte Vakzinierungsstudie mit insgesamt 53 Patientinnen in der Adjuvanz, dass nodalpositive, Her-2/neu+ Hochrisikopatientinnen von der Vakzination mit Her-2/neu-abgeleiteten Peptiden profitierten und die Rückfallrate reduziert wurde. Zur Optimierung immuntherapeutischer Strategien sollen Kombinationen verschiedener Ansätze führen, die multiple Targetstrukturen erreichen und multiple immunologische Effektorarme aktivieren können. Zudem müssen Patientenkollektive definiert werden, die tatsächlich von Immuntherapien profitieren können.

Jüngste Fortschritte in der Therapie des Kolonkarzinoms

Zusammenfassung Hintergrund:  In der Therapie des kolorektalen Karzinoms wurden in den letzten Jahren bedeutende Fortschritte erzielt, von denen viele bei der Jahrestagung der American Society of Clinical Oncology (ASCO) im Mai 2005 in Orlando, FL, USA, vorgestellt wurden.

Der Bochumer Nachsorgepass ?Tumorerkrankungen HNO“

ZusammenfassungHintergrund  Die Krebserkrankung ist ein mehrdimensionaler Prozess, der die körperliche, psychische und geistige Verfassung eines Patienten betrifft. In der Krebsnachsorge ist ein Dokumentationssystem notwendig, welches die Anforderungen an eine umfassende psychosoziale Nachsorge berücksichtigt. Mit dieser Zielsetzung wurde der Nachsorgepass Tumorerkrankungen HNO in der HNO-Klinik der Ruhr-Universität Bochum entwickelt.

Patientenkontrollierte Analgesie (PCA) bei ambulanten Tumorschmerzpatienten

ZusammenfassungHintergrund  Benötigen Patienten mit starken Tumorschmerzen eine parenterale Schmerztherapie, stehen für den Einsatz im häuslichen Umfeld portable PCA- (patientenkontrollierte Analgesie-)Pumpen zur Verfügung. Aussagekräftige Daten über die Logistik und den Erfolg dieser kosten- und betreuungsintensiven Therapie spezialisierter ambulanter Dienste sind rar.

Laparoscopic Medial-to-lateral Approach for the Curative Resection of Right-Sided Colon Cancer

Abstract Introduction  Our previous randomized clinical trial comparing the laparoscopic medial-to-lateral dissection with the more classic lateral-to-medial approach for resection of rectosigmoid cancer showed that the medial approach reduces the operative time and the postoperative proinflammatory response. Besides the oncologic advantages of an early vessel division and a “no-touch” dissection, we feel that the longer the lateral abdominal wall attachments of the colon are preserved, the better the exposure and the easier the dissection. Encouraged by the above-mentioned positive findings, we therefore further conduct this phase II clinical trial to examine the feasibility and surgical outcomes regarding the utilization of this medial-to-lateral laparoscopic dissection approach for the curative resection of right-sided colon cancer.

Comparative study on cancer cell apoptosis between gastric and intestinal-type human gastric carcinoma

Summary  Apoptosis of cancer cells between the gastric and intestinal-type human gastric carcinoma were compared in terms of the expression of oncogene MDM2 and CD68, the histological types, the infiltration depth, and lymph node metastasis. Terminal deoxynucleotidyl trans-ferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay was employed to stain apoptotic cells. Histochemical method(AB-PAS) was applied to stain mucus that is neutral or acidic in nature. Immunohistochemical method (SABC) was used to detect expression of MDM2 and CD6. The results showed that the mean apoptosis index (AI) of total 48 cases was 8.60±2.60. AI in the 30 intestinal type cases was significantly higher than that in the 18 gastric type cases (t=4.67, P<0.01). In the 30 intestinal type cases, the spontaneous apoptosis index of MDM2 negative cases was significantly higher than that of the positive cases (t=7.16, P<0.01). And in the 18 gastric type cases, the same result was found. (t=11.39, P<0.01). The MDM2 positive ratio in gastric type cases was higher than that in intestinal type cases (x 2=4.68, P<0.05). There is no significant difference in AI between cases of lymph node metastasis and non-metastasis cases in intestinal type cases (t=0.26, P>0.05). But in the gastric type cases, a significant difference existed (t=5.87, P<0.01). A significant difference in lymph node metastasis ratio was found between the two gastric carcinoma types (x 2=4.48, P<0.05). The CD68 expression ratio in the 30 intestinal type cases was much lower than that in the 18 gastric type cases (t=4.29, P<0.01). AI of 25 MDM2-positive cases was much lower than that of the 23 MDM2-negative cases (t=7.80, P<0.01). CD68 positive ratio in the 25 MDM2-negative cases was much lower than that in the 23 negative cases. The difference was statistically significant (t=10.90, P<0.01). Except for few cells scattering within the cancer nest, most CD68 positive cells infiltrated in the interstitium around the cancer tissue. In the high-AI cases, CD68-positive cells increased. And the CD68-positive cells decreased in low-AI cases (r=0.96, P<0.01). Logistic regression analysis suggested that among the control variables, only AI was a statistically significant factor in the regression model (x 2=9.64, P<0.01). We concluded that (1) the spontaneous apoptosis index in gastric-type cases of gastric carcinoma was significantly lower than that in intestinal type cases; (2) AI in the two types was influenced by the expression of MDM2 and lymph node metastasis, but no visible connection was found between AI and the infiltration depth or histological types; (3) in the intestinal type cases, AI and the CD68-positive cells increased in MDM2-negative cases.

Pr?operatives Staging bei Patienten mit nichtkleinzelligem Bronchialkarzinom

Zusammenfassung   Das Bronchialkarzinom ist weltweit der am h?ufigsten zum Tode führende Tumor. Allein in Deutschland erkranken pro Jahr mehr als 40.000 Menschen, über die H?lfte kann keiner prim?r kurativen Therapie zugeführt werden. Angesichts dessen ist ein exaktes Staging für Patienten mit nichtkleinzelligem Bronchialkarzinom von entscheidender Wichtigkeit, da sowohl Prognose als auch therapeutische Optionen sich in den verschiedenen Stadien signifikant unterscheiden. In den letzten Jahren sind zur pr?operativen Diagnostik eine Reihe von weiteren Untersuchungen hinzugekommen, deren Ergebnisse Vorbereitung und Therapie des Patienten grundlegend beeinflussen. Heute liefert die CT zwar durch nochmals verfeinerte Aufl?sung eine optimale anatomische Orientierung, deren Sensitivit?t zur Vorhersage eines mediastinalen Lymphknotenbefalls hat sich allerdings nicht verbessert und verbleibt mit ca. 50 % schlecht. Die mittlerweile auch in Deutschland in der pr?operativen Diagnostik vergütete PET-CT zeitigt einen deutlich verbesserten negativ-pr?diktiven Wert, positive Befunde sind jedoch weiterhin generell histologisch oder aber zytologisch zu sichern. Mit der endobronchialen oder aber trans?sophagealen ultraschallgesteuerten Nadelaspiration haben hier zwei minimalinvasive Methoden Einzug in die Diagnostik gefunden. Diesen Verfahren kann zwar eine hohe Spezifit?t, jedoch nur ein geringer negativ-pr?diktiver Wert attestiert werden. Insofern bedarf es bei negativem Ergebnis der Hinzunahme st?rker invasiver Techniken (als Goldstandard die Mediastinoskopie), insofern sich in der PET-CT-Untersuchung ein grenzwertiger oder aber positiver Befund gezeigt hat. Ist hingegen der zytologische Befund per Feinnadelaspiration positiv, so gilt eine N2- oder aber N3-Erkrankung als gesichert und die stadienadaptierte Therapie kann eingeleitet werden.

Immunhistochemie als Prognoseindikator bei Speicheldrüsenkarzinomen

Zusammenfassung Hintergrund  Die Vielfalt maligner Tumoren der Speicheldrüsen (Spd) macht die Etablierung prognostischer Faktoren schwierig. Ziel der Studie war es u. a., neue immunhistochemische Marker und ihre Korrelation (Korr.) zum Langzeit-überleben (ü) zu evaluieren.

Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients

AbstractBackground  Aprepitant is a selective neurokinin-1 receptor antagonist that is effective for the prevention of nausea and vomiting caused by highly emetogenic chemotherapy. In vitro, aprepitant is a moderate inhibitor of the CYP3A4 enzyme, which is involved in the clearance of several chemotherapeutic agents. In this study we examined the potential for aprepitant to affect the pharmacokinetics and toxicity of intravenously administered docetaxel, a chemotherapeutic agent that is primarily metabolized by CYP3A4.

Reversal of multidrug resistance of cancer through inhibition of P-glycoprotein by 5-bromotetrandrine

AbstractPurpose  The present study aimed to evaluate the MDR reversal activity of bromotetrandrine (BrTet), a bromized derivative of tetrandrine (Tet), in vitro and in vivo.

An orally active Amazonian plant extract (BIRM) inhibits prostate cancer growth and metastasis

Pharmacokinetics of capecitabine (Xeloda) in Japanese and Caucasian patients with breast cancer

Shared decision-making—Results from an interdisciplinary consulting service for prostate cancer

Abstract  Locally confined prostate cancer (PCa) can be treated by various treatment options (e.g. radical prostatectomy or radiation therapy) with comparable results but different possible side effects. Therefore, treatment recommendations can vary between urologists and radiation oncologists. In 2001 the Charité-Campus Benjamin Franklin (CBF, Berlin), established the first interdisciplinary consulting service for prostate cancer patients in Germany. The aim was to offer a comprehensive and neutral consultation on all treatment options and to make treatment recommendations. The study examines what benefits may be derived from this type of consultation. A total of 362 patients presented to the consulting service between May 2001 and April 2003. Two questionnaires were used. The first one contained epidemiological questions as well as questions covering information already available on PCa. It also examined feelings and fears about the disease and possible treatment options. The second questionnaire was completed 2 weeks after the consultation to evaluate the treatment decision, determine the patients satisfaction with the consultation and trace the development of feelings and fears. Of the patients, 334 (92.2%) were completely assessable. All patients had already obtained information about the disease and possible treatment options and wished to be involved in the decision-making process through objective and neutral consultation. Nearly all of them had a great fear of the possible side effects of therapy. Such a comprehensive consultation is time-consuming (average of 35 min) but largely received a very positive assessment in that a total of 66% found it either helpful (n=74, 22%) or very helpful (n=147, 44%). Patients felt they had been completely informed in 92% of the cases. Only 22 (9.7%) had still failed to make a decision after 2 weeks, 115 patients had stage T1c, PSA <10 ng/ml and a Gleason score 7. In these cases an equivalent recommendation for radical prostatectomy, percutaneous radiotherapy or permanent seed implantation was given. Of these, 49 (43.4%) decided on the surgical intervention, 48 (42.5%) on a type of radiotherapy and only 18 (15.6%) remained undecided. The histological examination of prostatectomy specimens from patients who had decided to undergo radical surgery at CBF showed a significant decrease in the rate of extracapsular disease extension (T3) from 38% to 20% during the observation period. The interdisciplinary approach has made the process of deciding on an appropriate treatment much easier for the patient. The time-consuming consultation enables better selection of individual treatment modalities and their possible side effects from the point of view of both the patients and the attending physicians. In this study, patients chose either radical surgery or radiotherapy with equal frequency.

Awareness of diagnosis, and information-seeking behavior of hospitalized cancer patients in Greece

AbstractPurpose  The goal of our study was to evaluate the extent of disease-related knowledge and the need for further information of cancer patients in Greece.

Kinetics of [ 11C]choline uptake in prostate cancer: a PET stydy

Abstract  Carbon-11 choline has recently been introduced as a potential tracer for tumour imaging with positron emission tomography (PET). We evaluated the kinetics of the uptake of [11C]choline in prostate cancer and benign prostatic hyperplasia. We also evaluated the association between the uptake of [11C]choline and the histological grade of malignancy, Gleason score, volume of the prostate and prostate-specific antigen (PSA). Fourteen patients with histologically confirmed prostate cancer and five patients with benign prostatic hyperplasia were studied with [11C]choline PET. A mean dose of 430±31 MBq of [11C]choline was injected intravenously and a dynamic emission acquisition of prostate was performed for 30 min. The uptake of [11C]choline was measured as a standardised uptake value (SUV) and as a kinetic influx constant (K i) obtained from graphical analysis. Both cancerous and hyperplastic prostate were well visualised with [11C]choline against low or moderate tracer accumulation in the bladder and rectal wall. The measured radioactivity in urine was invariably low. In the graphical analysis, linear plots were achieved. The mean K i of the untreated tumour was 0.205±0.089 min–1 (range 0.128–0.351; n=7) and the mean SUV was 5.6±3.2 (range 1.9–15.5; n=15). K i values and SUVs correlated closely (r=0.964, P=0.0005), whereas no correlation could be demonstrated between the tumour uptake of [11C]choline and the histological grade, Gleason score, volume of the prostate or PSA . The mean SUV and the mean K i of benign hyperplastic prostate were 3.5±1.0 (range 2.0–4.5; n=4) and 0.119±0.076 min–1 (range 0.065–0.173; n=2). In conclusion, a high uptake of [11C]choline characterises not only carcinomatous but also hyperplastic prostatic tissue. Dynamic imaging of the uptake of [11C]choline in the prostate shows a good applicability of the graphical analysis model with an irreversible compartment. A close correlation between the K i values and semiquantitative SUVs of tumours supports the use of the simpler SUV in the clinical setting.

Value of integrated PET/CT for lesion localisation in cancer patients: a comparative study

Abstract  The aim of this study was to retrospectively compare the value of integrated PET/CT and separate PET plus morphological imaging studies for lesion localisation in cancer patients. Two different series of consecutive patients who had previously been treated for neoplastic disease were considered. One series consisted of 105 patients who had undergone [18F]fluorodeoxyglucose (FDG) PET/CT (n=70) or [11C]choline PET/CT (n=35) studies (PET/CT group). The other series comprised 105 patients who had undergone FDG PET scan (n=70) or [11C]choline PET scan (n=35) alone; in this series, PET findings were correlated with the results of morphological imaging (MI) studies, i.e. CT (n=92) or MR imaging (n=13) (PET+MI group). Regions of abnormal tracer uptake at PET scanning were classified as ambiguous or unambiguous depending on their precise anatomical localisation. A total of 207 and 196 lesions were found in the PET/CT and PET+MI groups, respectively. The difference in terms of number of lesions per patient detected with the two imaging protocols was not statistically significant (P=0.718). When analysis of lesion localisation was performed, there were 7/207 (3.4%) and 30/196 (15.3%) ambiguous lesions in the PET/CT and PET+MI groups, respectively. The number of ambiguous lesions was significantly higher in the PET+MI group than in the PET/CT group (2=15.768, P<0.0001). Comparison of the effect of use of the different tracers on reporting of PET/CT versus PET+MI revealed that the improvement in the final report in [11C]choline PET/CT studies was similar to that observed in [18F]FDG studies. In cancer patients, PET/CT shows higher diagnostic accuracy for lesion localisation than PET plus morphological imaging studies performed independently. This result does not seem to be affected by the type of tracer used.

Apoptosis Rate and Objective Diagnosis of Drug Resistance ofOvarian Cancer Cell Lines

Abstract  Objective: To investigate whether the change of drug resistance degree could be evaluated by apoptotic rate in ovarian cancer cell lines. Methods: Human epithelia ovarian cancer cell line A2780 and its platinum (DDP) resistance cell line AD4 were used. They were divided into 4 groups respectively (A2780-DDP group, A2780-DDP+VRM group, AD4-DDP group and AD4-DDP+VRM group). 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) was used to measure the multiple of drug resistance. The expression of drug-resistance genes (mdrl, TopoIIα and GSTπ) was detected by using reverse transcription polymerase chain reaction (RT-PCR). Semi-quantity assay was proceed by rate the of multidrug resistance genes to G3 PDH gene. Apoptosis was measured by DNA gel electrophoresis and flow cytometry respectively. The advantages and disadvantage of evaluating drug-resistance with these three methods were analyzed. Results: The 50% inhibition concentration (IC50) of A2780 and AD4 was 19.2 μg/mL and 66 μg/mL respectively, and the resistance fold of the AD4 was 3.4. Some drug-resistance genes could be detected by RT-PCR in A2780 and AD4 cell lines. The expression of mdr1 was only (0.09±0.03)×10-2:1 and (0.10±0.02)×10-2:1 respectively (rate to G3 PDH gene) with the difference being not significant between them. The expression of TopoIIα in the A2780 cells was (2.60±0.12)×10-2:1 and (0.11±0.03)×10-2:1 in the AD4 cells respectively with the difference between them being significant. On the contrary, the expression of GSTπ in A2780 cells was lower than in AD4 cells, and the ratio was (0.11±0.03)×10-2:1 and (3.13±0.14)×10-2:1 respectively with the difference being significant between them. There was no significant difference among the genes expression after the drugs were given for 6 h, 12 h and 24 h. couldn't reflect the change of drug-resistance timely. DNA gel electrophoresis used to detect apoptosis was only a qualitative analysis. Different drug resistance degrees may be detected by flow cytometry as early as few hours after drugs were given, which realized the earlier and quantities detection of drug resistance. Conclusion: Detection of apoptosis with flow cytometry may not be affected by the variety of drug-resistance genes, suggested this was a general, quantitative and objective method to reflect drug resistance.

Indicators for Surgical Resection and Intraoperative Radiation Therapy for Pelvic Recurrence of Colorectal Cancer

Abstract  PURPOSE: We retrospectively analyzed prognostic factors for surgical resection and intraoperative radiation therapy to identify indicators for this treatment strategy. METHODS: Thirty-nine consecutive patients with locally recurrent colorectal cancer who underwent surgical resection with intraoperative radiation therapy from January 1, 1987, to June 30, 1999, were analyzed. The mean electron energy was 10.5 MeV and the mean intraoperative radiation dose was 22.6 Gy. Kaplan-Meier survival estimates were obtained for the 37 patients who recovered postoperatively. Prognostic factors were analyzed univariately by log-rank test and multivariately by Coxs proportional hazards model. RESULTS: Three-year cumulative survival was 44 percent (standard error = 11) for 26 patients free of unresectable distant metastasis who underwent surgical resection and intraoperative radiation therapy for pelvic recurrence of colorectal cancer, but none of the 11 patients with unresectable distant metastasis survived 3 years. Preoperative prognostic factors which were significant on univariate and multivariate analysis were unresectable distant metastasis (P = 0.001) and elevated preoperative serum CA 19–9 (P = 0.02). Patients with synchronous resection of local recurrence and distant metastasis had a significant survival advantage over those without resection of metastases (P = 0.02). Univariate analysis in a subgroup of 26 patients without unresectable distant metastasis revealed pain (P = 0.0003) to be a useful preoperative prognostic indicator, whereas tumor fixation (P = 0.01) and amount of residual tumor after surgical resection (P = 0.01) were significant intraoperative and postoperative factors, respectively. Fluorouracil-based postoperative systemic chemotherapy produced a significant survival benefit (P = 0.04). CONCLUSIONS: Patients with unresectable distant metastasis are not suitable candidates for surgical resection and intraoperative radiation therapy, whereas those with resectable metastasis are potential candidates. Intraoperative radiation therapy may be less useful for patients with pain, elevated preoperative CA19–9, fixed tumors, or gross residual tumor after surgical resection. Multimodal treatment strategies combining preoperative and/or postoperative external beam radiation therapy and intraoperative radiation therapy with fluorouracil-based systemic chemotherapy are recommended for patients with these indicators.

Expression of vascular endothelial growth factor and receptor flk-1 in colon cancer liver metastases

AbstractBackground/Purpose  This study investigated vascular endothelial growth factor (VEGF) and flk-1 expression in hepatic metastases from colon carcinoma, and their associations with tumor angiogenesis, proliferation, and apoptosis.

Postoperative adjuvant chemotherapy with cisplatin, cyclophosphamide, and anthracycline (doxorubicin, epirubicin, pirarubicin) for endometrial cancer

AbstractBackground  Doxorubicin and cisplatin are the most commonly used chemotherapeutic agents in the treatment of endometrial cancer, but their clinical efficacy is still controversial. The aim of this study was to retrospectively assess the efficacy and toxicity of combination chemotherapy using cisplatin, cyclophosphamide, and anthracy-clines in patients with stage III/IV adenocarcinoma of the endometrium.

Diagnostik und Immunhistochemie des medull?ren Mammakarzinoms

Zusammenfassung  Das medulläre Mammakarzinom stellt wegen der paradoxen Assoziation von hohem Grad der Dedifferenzierung und Atypie mit einer eher günstigen Prognose eine diagnostische Herausforderung dar. Dabei sind makroskopischer und mikroskopischer Befund maßgeblich, die Haupt- und Nebenkriterien zu berücksichtigen haben. Dagegen ist die Bedeutung des Immunphänotyps noch nicht abschließend geklärt. Da die diagnostische Reproduzierbarkeit der morphologischen Kriterien eingeschränkt ist, haben wir überprüft, inwieweit die Immunhistologie zur Diagnosesicherung herangezogen werden kann. Bei 32 medullären Mammakarzinomen wurden 23 verschiedene Marker analysiert und mit wenig differenzierten duktal-invasiven Mammakarzinomen mit partiellen medullären Eigenschaften (so genannte atypische medulläre Mammakarzinome) verglichen. Dabei zeigte der sehr charakteristische, aber nicht spezifische Immunphänotyp eine starke Überlappung mit dem so genannten Basalzellphänotyp des Mammakarzinoms (Negativität für Steroidhormonrezptoren und Her2, Positivität für Basalzellzytokeratine). Mit keinem der angewandten Marker konnte eine spezifische Diskriminierung erreicht werden. Medulläre Mammakarzinome exprimierten signifikant häufiger EGF-R. Werden die charakteristischen morphologischen Kriterien, die nur am Resektat und nicht an der Stanze zu erheben sind, mit dem immunhistochemischen Nachweis des charakteristischen Immunphänotyps kombiniert, lässt sich die diagnostische Sicherheit deutlich erhöhen.

Activin A circulating levels in patients with bone metastasis from breast or prostate cancer

Abstract  Recent studies have highlighted that Activin A, a member of the transforming growth factor-β (TGF-β) superfamily, may be involved in the regulation of osteoblastic activity and in osteoclast differentiation. Therefore, we have investigated the clinical significance of its circulating levels in patients with bone metastasis. Activin A serum concentrations were determined, by a commercially available enzyme-linked immunosorbent assay kit, in 72 patients with breast cancer (BC) or prostatic cancer (PC) with (BM+) or without (BM−) bone metastases, in 15 female patients with age-related osteoporosis (OP), in 20 patients with benign prostatic hypertrophy (BPH) and in 48 registered healthy blood donors (HS) of both sex (25 female and 23 male). Activin A serum concentrations were significantly increased in BC or PC patients as compared to OP (P < 0.0001) or BPH (P = 0.045), respectively, or to sex matched HS (P < 0.0001). Additionally, these levels resulted more elevated in PC patients as compared to BC patients (P = 0.032). Interestingly, Activin A was significantly higher in BM+ patients than in BM− patients (BC, P = 0.047; PC, P = 0.016). In BC patients, a significant correlation was observed only between Activin A and number of bone metastases (P = 0.0065) while, in PC patients, Activin A levels were strongly correlated with the Gleason score (P = 0.011) or PSA levels (P = 0.0001) and, to a lessen extent, with the number of bone metastases (P = 0.056). Receiver operating characteristic curve (ROC) analysis showed a fair diagnostic accuracy of Activin A to discriminate between BM+ and BM− patients (BC: AUC = 0.71 ± 0.09, P = 0.03; PC: AUC = 0.73 ± 0.081, P = 0.005). These findings indicate that Activin A may be implicated in the pathogenesis of bone metastasis. Therefore, this cytokine may be considered a novel potential target for a more selective therapeutic approach in the treatment of skeletal metastasis and may be also useful as additional biochemical marker of metastatic bone disease.

Factors related to posttraumatic stress in adolescent survivors of childhood cancer and their parents

Abstract Goals of work  The purpose of this study was to investigate factors related to severe posttraumatic stress symptoms (PTSS) in adolescent survivors of childhood cancer and their parents.

Acceptance of flexible sigmoidoscopy as a screening examination for colorectal cancer in an outpatient clinic

Abstract Background and study aim  Flexible sigmoidoscopy (FS) is a feasible examination technique and a suitable tool for population-based screening, but very little is known about determinants of endoscopic screening participation. The aim of this study was to determine the acceptance rate and the factors influencing the decision of participating in a screening program for patients in an outpatient clinic.

Life review interviews on the spiritual well-being of terminally ill cancer patients

Abstract Goals  The aims of this study were (1) to evaluate the treatment efficacy of life review interviews on the spiritual well-being of terminally ill cancer patients, and (2) to explore any differences in the responses of patients who obtained clinical benefits and those who did not.

Impact of age on postoperative outcomes in 1118 gastric cancer patients undergoing surgical treatment

Abstract Background  The purpose of the study was to evaluate the impact of age on outcomes in gastric cancer surgery.

Differential expression of hypoxia and (lymph)angiogenesis-related genes at different metastatic sites in breast cancer

Abstract Introduction  Breast cancer can metastasize via lymphatic and hematogenous pathways. Hypoxia and (lymph)angiogenesis are closely related processes that play a pivotal role in the tumor progression and metastasis. The aim of this study was to compare expression of hypoxia and (lymph)angiogenesis-related genes between primary breast tumors and metastases in different tissues.

Race/ethnicity and the receipt of watchful waiting for the initial management of prostate cancer

Abstract   INTRODUCTION: Several recent studies have noted that African Americans disproportionately receive “watchful waiting” for the initial management of their prostate cancer. To determine whether racial/ethnic differences in the receipt of watchful waiting are explained by differences in clinical presentation and life expectancy at the time of diagnosis, we examined Surveillance, Epidemiology, and End Results (SEER)-Medicare data for men diagnosed with prostate cancer in 1994 to 1996. METHODS: Race/ethnicity, comorbidity, stage, grade, age, and expected lifespan and their association with the receipt of watchful waiting were examined in multivariate logistic regression analyses. Race-stratified logistic regression analyses were also used to examine racial/ethnic variation in the association of clinical and demographic factors with the receipt of watchful waiting among African-American, Hispanic, and non-Hispanic white men.

Local recurrence after mastectomy for breast cancer: analysis of clinicopathological, biological and prognostic characteristics

Abstract Background  Despite the increasing use of breast-conserving therapy, modified radical mastectomy retains an important role in primary as well as in salvage treatment of breast cancer. Nevertheless, a significant number of patients will eventually develop a local recurrence (LR).

Die Skelettszintigraphie beim neu diagnostizierten Prostatakarzinom

ZusammenfassungHintergrund  Die Indikationsstellung zur Skelettszintigraphie beim neu diagnostizierten, unbehandelten Prostatakarzinom ist kontrovers.

Calcium-Sensing Receptor Stimulation Induces Nonselective Cation Channel Activation in Breast Cancer Cells

Abstract  The calcium-sensing receptor (CaR) is expressed in epithelial ducts of both normal human breast and breast cancer tissue, as well as in the MCF-7 cell line as assessed by immunohistochemistry and Western blot analysis. However, to date, there are no data regarding the transduction pathways of CaR in breast cancer cells. In this study, we show that a CaR agonist, spermine, and increased extracellular Ca2+ ([Ca2+]o) sequentially activate two inward currents at –80 mV. The first was highly permeable to Ca2+ and inhibited by 2-aminophenyl borate (2-APB). In contrast, the second was more sensitive to Na+ and Li+ than to Ca2+ and insensitive to 2-APB. Furthermore, intracellular dialysis with high Mg2+, flufenamic acid or amiloride perfusion was without any effect on the second current. Both currents were inhibited by La3+. Calcium imaging recordings showed that both [Ca2+]o and spermine induced an increase in intracellular calcium ([Ca2+]i) and that removal of extracellular Ca2+ or perfusion of 2-APB caused a decline in [Ca2+]i. It is well known that stimulation of CaR by an increase in [Ca2+]o or with spermine is associated with activation of phospholipase C (PLC). Inhibition of PLC reduced the [Ca2+]o-stimulated [Ca2+]i increase. Lastly, reverse-transcriptase polymerase chain reaction showed that MCF-7 cells expressed canonical transient receptor potential (TRPCs) channels. Our results suggest that, in MCF-7 cells, CaR is functionally coupled to Ca2+-permeable cationic TRPCs, for which TRPC1 and TRPC6 are the most likely candidates for the highly selective Ca2+ current. Moreover, the pharmacology of the second Na+ current excludes the involvement of the more selective Na+ transient receptor potential melastatin (TRPM4 and TRPM5) and the classical epithelial Na+ channels.

Why Do Patients of Female Physicians Have Higher Rates of Breast and Cervical Cancer Screening?

OBJECTIVE:  Women are more likely to receive breast and cervical cancer screening if they see female physicians. We studied whether this is due to differences between male and female physicians, or to differences in their patients.

Clinical Significance of Large Tenascin-C Spliced Variant as a Potential Biomarker for Colorectal Cancer

Abstract Background  Tenascin-C is an extracellular matrix protein forming various types of spliced variants. Low molecule variants are transiently present, but large spliced variants are predominantly overexpressed in proliferative processes or tumorigenesis in some varieties of cancer. However, the detection of the plasma level of large tenascin-C spliced variant (L-Tn-CSV) in colorectal cancer (CRC) has not been clarified. This study was performed to validate elevated plasma L-Tn-CSV levels as a possible biomarker for CRC.