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Introduction: Third-line chemotherapy has been suggested to improve survival in patients with gastric cancer. This study aimed to identify factors associated with the induction of third-line chemotherapy for advanced gastric cancer, focusing on patient eligibility for clinical trial. Methods: We retrospectively analyzed 335 patients treated for unresectable or recurrent gastric cancer between April 2009 and May 2020. The patients were grouped into those that met the key eligibility criteria for clinical trial (136 patients, 40.6%) and those that did not (199 patients, 59.4%) before receiving first-line chemotherapy. Results: The overall survival (OS) was 16.8 months (95% CI: 14.0–19.6) and 9.3 months (95% CI: 7.8–11.0) in the eligible and ineligible group, respectively. Multivariate analyses to identify the risk factors associated with the induction of third-line chemotherapy revealed ineligibility of clinical trial (OR 1.95; 95% CI: 1.15–3.31), number of metastatic sites (OR 1.99; 95% CI: 1.23–3.22), low albumin concentration (OR 2.24; 95% CI: 1.14–4.38), and a lack of complete or partial response to first-line treatment (OR 1.85; 95% CI: 1.05–3.26). Indeed, in responders to first-line treatment for ineligible patients, the median OS was 17.7 months (95% CI: 10.6–27.9), respectively. Conclusions: Treatment outcomes were different for those eligible for clinical trials and those who were not. However, this study suggested that patients who responded to first-line treatment have more favorable prognosis when treated with salvage chemotherapy, even if they were deemed ineligible for clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: This study was conducted to develop and validate a nomogram for predicting the risk of neutropenia or febrile neutropenia (FN) in tumor patients in the first cycle of etoposide-based chemotherapy. Methods: This retrospective cohort study used an information system to monitor patients with non-Hodgkin's lymphoma or solid tumors receiving an etoposide regimen in the first chemotherapy cycle in our hospital from 2009 to 2020. Binary logistic regression analysis was used to identify the influencing factors of patients with neutropenia or FN. Those factors were then used to develop a nomogram. Results: A total of 1,554 patients were divided into the development group (n = 1,072) and validation group (n = 482). Variables used to predict neutropenia or FN were Karnofsky performance status (odds ratio [OR] = 0.85, 95% confidence interval [CI] = 0.81–0.89, p < 0.01), metastatic sites ≥3 (OR = 6.33, 95% CI = 2.66–15.11, p < 0.01), comorbidity of heart disease (OR = 4.88, 95% CI = 1.74–13.67, p < 0.01), recent surgery (OR = 7.96, 95% CI = 1.96–32.36, p < 0.01), administration of alkylating agents (OR = 4.50, 95% CI = 1.10–18.48, p < 0.01), total bilirubin ≥25 μmol/L (OR = 11.42, 95% CI = 4.00–32.61, p < 0.01), and lymphocyte count <0.7 × 109/L (OR = 4.22, 95% CI = 2.00–9.75, p < 0.01). Conclusion: This model can aid the early identification and screening of the potential risk of neutropenia or FN in the first cycle of treatment for patients using etoposide-based chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Female carriers of a BRCA1 or 2 germline mutation face a high lifetime risk to develop breast and ovarian cancer. Risk-reducing surgery, such as prophylactic bilateral mastectomy and prophylactic bilateral salpingo-oophorectomy, are proven strategies to prevent breast and ovarian cancer. These procedures are, however, associated with considerable side effects, and the uptake of these highly effective interventions is therefore low in many countries. This highlights the need for alternative and noninvasive strategies for risk reduction in mutation carriers. Summary: While endocrine treatments with tamoxifen and aromatase inhibitors (AI) have been shown to be effective in secondary prevention, their benefit in primary prevention has never been prospectively evaluated. Moreover, their side effect profile makes them inappropriate candidates for chemoprevention in healthy premenopausal women. Recently, denosumab, a well-tolerated osteoprotective drug, has been shown to have an antitumoral effect on RANK+, BRCA1-deficient luminal progenitor cells in vitro, and has been demonstrated to abrogate tumors in BRCA1-deficient mouse models. Key Message: The prospectively randomized, double-blind BRCA-P trial is currently investigating the preventative effect of denosumab in healthy BRCA1 germline mutation carriers. [ABSTRACT FROM AUTHOR]

Background: Prophylactic mastectomies in carriers of mutations in BRCA1 or BRCA2 are becoming increasingly more accepted. We investigated the outcome after prophylactic mastectomy, especially regarding satisfaction with the procedure, in a monocenter study. Methods:BRCA1/2 mutation carriers and non-carriers with elevated pedigree-based cancer risk were followed prospectively in a structured surveillance program between 2000 and 2017. A retrospective telephone survey was conducted among all patients with documented prophylactic mastectomy. Complications and satisfaction with the decision for prophylactic mastectomy were recorded. Results: 39 patients who opted for a prophylactic mastectomy (38 BRCA1/2 mutation carriers and 1 non-carrier) were interviewed. Mostly nipple-sparing mastectomy with reconstruction was performed (87%). Half of the patients (22/39; 56.4%) had a history of unilateral breast cancer. The median time since prophylactic mastectomy was 5.6 years. While 61.5% did not report any complications, flap loss was seen in 15% (3/20) and moderate limitations in everyday life were present in 20% (7/35). An improvement in quality of life was noticed by 82% after prophylactic mastectomy and no patient expressed regret with regard to the decision. Conclusions: Prophylactic mastectomy is a procedure with risk for long-term complications in some cases. Our results confirm high satisfaction with the decision and improved quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Public willingness to collect personal family health history (FHH) assessments is integral to implement population screening to identify those at high cancer risk who could benefit most from lifesaving interventions. Yet, surprisingly little consideration has been given to factors associated with the public's perceived importance of FHH in the context of cancer. Methods: Using data from the 2013 Health Information National Trends survey, we assessed the association of intrapersonal (e.g., cancer worry), sociodemographic (e.g., education), and interpersonal-level factors (e.g., family trust) associated with not perceiving FHH assessment to be very important for personal health. Associations were tested with bivariate analyses and hierarchical logistic regression. Results: Of the 3,007 respondents, 32.7% reported perceiving FHH as not very important to their health. Whites (p < 0.001), males (p = 0.003), and those born in the United States (p = 0.004) were most likely to perceive FHH as not very important. Those who were least worried about cancer and perceived that cancer risk could not be lowered also viewed FHH as not very important (p = 0.002, p = 0.018, respectively). In hierarchical regression analyses, the association of low cancer worry remained significant after accounting for sociodemographic and interpersonal factors. The addition of sociodemographic factors modestly improved the model; the addition of interpersonal factors did not improve the model. Conclusions: A sizable proportion of the public does not perceive FHH to be very important, may be hard to reach, and impede implementation of population screening guidelines for inherited cancers. Campaigns to increase the perceived value of FHH assessment may need to be tailored to demographic subgroups, emphasize cancer prevention, and encourage family communication. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignant diseases and brings about serious damage to the human body. Presently, the incidence of CRC ranks third among the malignant tumors, and its 5-year survival rate is only about 50%. In recent years, more and more studies have focused on the application of transgenic technology in CRC research in vivo, which involves a great number of genes significantly related to the occurrence and development of CRC. The core of transgenic technology refers to the host chromosome gene accepting exogenous genes, which integrate into the host chromosome expressing it stably, followed by transmission to the next generations. Here, we will present a brief review of the related technologies used in transgenic animal models and provide an overview of the application of transgenic animal models in CRC research. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aim: Enforced expression of the connexin (Cx) 32 gene, a member of the gap junction gene family and a tumor suppressor gene in human renal cell carcinoma (RCC), enhanced vinblastine (VBL)-induced cytotoxicity in RCC cells due to suppression of multidrug resistance 1 (MDR1) expression. Furthermore, in RCC the Cx32 gene is silenced by hypermethylation of CpG islands in a promoter region of the Cx gene. In this study, we investigated if the green tea polyphenol epigallocatechin-3-gallate (EGCG) could enhance susceptibility of RCC cells (Caki-1, a human metastatic RCC cell) to VBL. Methods: The effects of EGCG on Caki-1 cells were estimated by WST-1 (cell viability), real-time RT-PCR (mRNA level) and immunoblotting (protein level). We estimated the methylation status in the promoter region of the Cx32 gene in RCC cells by methylation-specific PCR. Each protein function was inhibited by small interfering RNA (siRNA) and specific inhibitors. Results: The EGCG treatment elicited significant upregulation of Cx32 in Caki-1 cells, and the induction of the Cx led to the suppression of MDR1 mRNA expression through inactivation of Src and subsequent activation of c-Jun NH2-terminal kinase (JNK). Chemical sensitivity to VBL in Caki-1 cells was increased by EGCG pretreatment, and this effect was abrogated by siRNA-mediated knockdown of Cx32. Conclusion: This study suggests that the restoration of Cx32 by EGCG pretreatment improves chemical tolerance on VBL in Caki-1 cells via the inactivation of Src and the activation of JNK. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Identification of conserved pathways regulating longevity holds out the eventual possibility of pharmacologic health- and lifespan extension in humans. Members of the sirtuin deacetylase/ADP-ribosyltransferase/deacylase family extend longevity in invertebrates and promote various aspects of mammalian healthspan. The mitochondrial sirtuin SIRT3 deacetylates numerous proteins in this organelle, regulating mitochondrial functions and suppressing diverse age-associated pathologies. However, recent findings raise the possibility that SIRT3 may regulate some mitochondrial functions indirectly, rather than by direct deacetylation of specific mitochondrial substrates. Specifically, it has been found that SIRT3 promotes activities of the upstream mitochondrial regulators adenosine monophosphate-activated protein kinase and PGC1α. In addition, studies of tissue-specific SIRT3 knockouts suggest non-tissue-autonomous roles for SIRT3. Thus, mitochondrial regulation by SIRT3 is likely much more complex than initially appreciated, potentially involving both direct and indirect mechanisms. Unraveling these may reveal novel aspects of how the functional status of the mitochondria is communicated to the rest of the cell, and to the organism overall. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess whether the neutrophil to lymphocyte ratio (NLR) and other laboratory markers may predict the prognosis of advanced colorectal cancer (CRC) patients receiving palliative chemotherapy. Methods: The study population included50 patients with far advanced or recurrent unresectable CRC who received oxaliplatin-based combination chemotherapy as first-line treatment in our hospital between June 2005 and November 2010. Seven clinical variables and 7 laboratory indices before chemotherapy were evaluated retrospectively as the possible prognostic factors of overall and progression-free survival. Results: During the study period, 27 patients (54%) died of CRC. Elevated NLR (≥4.0) was observed in 15 patients (30%). By univariate analysis, elevated NLR, performance status and hypoalbuminemia were significantly associated with both poor overall and progression-free survivals. Multivariate analysis showed that elevated NLR (hazard ratio 4.39, 95% confidence interval 1.82-10.7; p = 0.0013) and thrombocytosis (hazard ratio 5.02, 95% confidence interval 1.69-13.4; p = 0.0066) were independently associated with overall survival. Conclusion: Elevated NLR is a powerful predictor of poor response to oxaliplatin-based chemotherapy in patients with unresectable CRC. The ratio is a simply accessible and inexpensive but useful biomarker in CRC patients receiving chemotherapy. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: We aimed to describe the efficacy and safety of sunitinib in unselected Korean advanced renal cell carcinoma (RCC) patients. Patients and Methods: From November 2005 to August 2008, 132 histologically confirmed advanced RCC patients (100 in the global expanded access program) were enrolled. Response and toxicity were assessed regularly according to the protocol. Results: Within this population, 82.6% had clear cell RCC, and 28.8% were treatment naïve. Patients received a median of 5 cycles of sunitinib (range 1-30), and the mean relative dose intensity was 82.0 ± 14.20 (SD). The progression-free survival (PFS) and overall survival rates were 8.2 and 23.1 months, respectively. For the 130 evaluable patients, the objective response rate was 34.1% (n = 45); 44.7% (n = 59) exhibited stable disease. Reasons for discontinuation were disease progression (75.0%) and toxicity (7.6%). The most frequent adverse events were thrombocytopenia (75.0%), neutropenia (70.5%), and anemia (69.7%). Low body surface area (OR = 4.2, 95% CI 1.2-13.8, p = 0.02) and previously treated status (OR = 3.1, 95% CI 1.3-7.4, p = 0.01) were highly predictive of grade 3-4 toxicities. Based on these findings, a nomogram predicting the probability of 12-month PFS was constructed, giving a concordance index of 0.675. Conclusions: Despite the different toxicity profiles, maintaining adequate dose modifications and a careful follow-up enables comparable treatment outcomes for unselected Korean advanced RCC patients. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: In first-line management for small-cell lung cancer (SCLC), the combination of a platinum salt and etoposide is recommended, with thoracic radiotherapy and prophylactic cranial irradiation in selected patients. Anticoagulants, including heparin, are rarely used. We analyzed the results of these different treatments in a comprehensive population of patients with SCLC. Patients and Methods: We retrospectively analyzed clinical and therapeutic characteristics of SCLC patients managed in our center during the period 1990-2002. Results: First-, second- and third-line chemotherapy was received by 98.3, 47.3 and 11.7%, respectively; 55% received curative heparin. The 2-year survival rates were 31 and 7% among patients with localized and metastatic disease, 33 and 15% among patients treated with the PCDE (cisplatin-cyclophosphamide-doxorubicin-etoposide) regimen with and without heparin, and 27 and 12% among patients treated with the PE (cisplatin or carboplatin-etoposide) regimen with and without heparin, respectively. The 2-year survival rate among the 27 patients who received an optimal combination of PCDE, heparin, thoracic radiotherapy and prophylactic cranial irradiation was 44.2%. In multivariate analysis, localized disease, younger age, use of heparin and inclusion in a clinical trial were independently associated with a better outcome. Conclusion: Despite the bias inherent in a retrospective, single-center study, these results support chemotherapy optimization for SCLC patients and confirm the value of heparin in this setting. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

For many years, therapy for metastatic renal cell carcinoma (mRCC) was limited to a single line of cytokine therapy with either interferon or interleukin-2. Relatively recently, the novel targeted agents bevacizumab, sorafenib, sunitinib and temsirolimus have each demonstrated activity in patients with mRCC that is refractory to cytokine therapy. Based on phase III trial data of patients who have received no prior therapy for mRCC, targeted agents have now rapidly replaced cytokines or, in the case of bevacizumab, are used in combination with interferon as first-line therapy for mRCC. Thus, second-line therapy for mRCC needs to be re-evaluated. Available data indicate that patients whose disease is refractory to a targeted agent may obtain, in some cases, benefit from a different agent, inhibiting either the same or a different pathway. With the availability of relatively few drugs for the treatment of mRCC, it is important to consider how to ensure that patients are obtaining maximum benefit through optimal use of the agents available. The definition of whether second-line therapy is active and tolerable and which therapy should be used in this setting in individual patients, particularly taking into account prior therapy, will therefore be important in defining the general therapeutic strategy in patients with mRCC. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: We report the results obtained using an original immunotherapy schedule featuring chronically administered low-dose interleukin-2 (IL-2) and interferon-α (IFN-α) in patients with metastatic renal cell carcinoma (mRCC), and we assess treatment efficacy according to the patients’ prognostic profiles. Methods: 138 consecutive patients were enrolled, and received IL-2 (1 million IU/m2) subcutaneously twice daily on days 1 and 2, and once daily on days 3–5 of each week, and IFN-α (1.8 million IU/m2) intramuscularly once daily on days 3 and 5. Each cycle consisted of 4 consecutive weeks and was repeated indefinitely at 4-month intervals regardless of response. The patients’ baseline risk profile was assessed using Negrier’s stratification system. Results: The overall response rate was 10.9% (95% CI 6.7–17.2), and median overall survival was 19.6 months (95% CI 14.2–28.2). Treatment-related toxicity was mostly WHO grade 2 or below. Survival in the low-, intermediate- and high-risk groups was significantly different (p for trend <0.001), with low-risk patients having a median survival of 65.1 months (95% CI 42.7–84.2). Conclusion: Chronically administered low-dose IL-2 and IFN-α may be a safe and effective option for low-risk mRCC patients. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Choroid plexus carcinoma (CPC) has been associated with TP53 germline mutations and Li-Fraumeni syndrome (LFS). We describe our finding of a novel germline mutation in the TP53 gene in a family with multiple malignancies and in association with a child presenting with CPC. Method: An 8-month-old male presented with seizure-like activity; imaging disclosed a 1.5-cm left ventricular mass confirmed to be CPC intra- and postoperatively. Family history was significant for a half-sister who died of a primary CNS sarcoma and a paternal grandmother negative for BRCA1, BRCA2, MLH1, and MSH2 mutations with multiple (>6) LFS spectrum malignancies. Results: Familial TP53 testing revealed an A→T substitution at DNA position 13071, creating a deleterious Asn→Ile substitution at amino acid 131 in exon 5. Conclusion: Physicians treating patients with CPC should be attuned to reviewing family history for risk factors suggestive of genetic cancer syndromes such as LFS. These syndromes markedly influence both the patient and family members and may alter postoperative treatment regimens. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: To investigate pre- and postoperative expression and alterations in the indices of peripheral blood lymphocytes (PBL) CD25 and Ki67 in 32 patients with renal cell carcinoma (RCC) who underwent unilateral radical nephrectomy. We investigated the relationship between the above parameters in PBL and CD8+Ki67+ T cells infiltrated in tumor cells. Patients and Methods: Blood samples were collected preoperatively and on postoperative day 7 (POD7). The PBL CD25 and Ki67 indices were detected by flow cytometry in 32 patients with RCC and in 16 healthy individuals. We conducted double immunohistochemistry for CD8 and Ki67 in tumoral, peritumoral and normal kidney tissues. Results: The PBL CD25 and Ki67 indices on POD7 were higher than their preoperative levels (CD25: 21.37 ± 4.66 vs. 20.30 ± 6.23%; Ki67: 21.92 ± 16.08 vs. 17.05 ± 9.87%), with no significance (p = 0.397 and 0.076, respectively). The pre- and postoperative PBL CD25 and Ki67 indices were significantly higher in patients than in the control group (where they were 14.72 ± 5.40 and 7.50 ± 5.25, respectively, p < 0.01). A negative correlation was observed between the level of the PBL CD25 index on POD7 and the expression of CD8+Ki67+ T cells infiltrated in tumor cells (r = –0.417 and –0.657, p = 0.017 and 0.000, respectively). Conclusions: The PBL CD25 and Ki67 indices could be useful parameters to evaluate performance status in RCC patients. The data we obtained seemed controversial and puzzling and further investigation is required. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Since 2002, hereditary cancer gene testing has been funded at the national level in France. Here we report on the impact of this funding on the number of tests carried out and specify the genes/syndromes on which these tests focus. Methods: All French laboratory facilities funded had to submit a report on their activities to the French Health Ministry in March 2004. Results: Funding has led to an increase of >344% in the number of tests carried out between the years 2000 and 2003. For every 100,000 inhabitants, 16.02 cases with a familial cancer syndrome (index cases subjected to ‘diagnostic genetic testing’) and 4.44 relatives of an index case with a proven mutation were tested. The overall mutation detection rate was 15.2% in the case of breast cancer genes and 17.2% in that of mismatch repair genes. Conclusion: In France, the current mutation detection rate is high in comparison with the 10% benchmark level. A further increase can be expected to occur in the number of tests carried out in the future. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Topotecan is indicated in the treatment of advanced-stage ovarian cancers refractory to prior platinum-based regimen. The aim of this study was to compare the standard therapeutic strategy with a novel strategy of weekly administration of topotecan. The primary endpoints were dose density and overall tolerance. This retrospective cohort study included patients with ovarian cancer in relapse. During a first period (1998–2001), 24 patients received the standard topotecan dose of 1.5 mg/m2/day for 5 consecutive days with a 3-week interval between each treatment course. During a second period (2003–2006), 21 patients received a weekly topotecan dose of 4 mg/m2 for 3 weeks out of every 4. Grades III and IV haematological toxicities were more frequent with the standard strategy (p < 0.05), even after adjustment of the prescription of erythropoietin and G-CSF. With the weekly strategy, an increase in dose density and a reduction in the number of delayed doses were observed. No significant difference between the 2 strategies was found in terms of response to the treatment and specific survival. This study suggests that the weekly administration of topotecan 4 mg/m2, for 3 weeks out of every 4, results in a better maintenance of dose density and a reduction in haematological toxicity. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to evaluate the efficacy and safety in unresectable or advanced renal carcinoma treated with sorafenib, in a situation closely similar to the everyday medical practice. Patients and Methods: One hundred and thirty-six patients have been treated with 400 mg b.i.d. of sorafenib administered orally until disease progression or unacceptable toxicity. They were either previously untreated or relapsed after one or more previous treatments with systemic therapy. Most of them had clear cell renal carcinoma (RCC), but other histological types such as papillary, chromophobe, Bellini ducts, sarcomatoid and mixed forms were also represented. Results: Overall disease control of 70.6% was achieved with 7.9% of partial remissions. Response was observed in the majority of patients with RCC, but also in some patients with non-clear cell RCC. Safety was acceptable, with the most common adverse events consisting of hand-foot skin reaction, cutaneous rash, diarrhoea, fatigue and hypertension. Conclusions: The results confirm previous ones reported in the literature concerning the efficacy and the safety of sorafenib as second-line treatment in patients with RCC. In addition, they disclose the hypothesis that sorafenib could be effective also in patients who underwent multiple previous treatments and in those with histology different from clear cells. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Therapeutic decision-making in metastatic renal cell carcinoma (MRCC) is based on conventional radiological evaluation. Fluorodeoxyglucose positron emission tomography (FDG-PET) scans may modify this strategy. Methods: Patients with MRCC for whom a therapeutic decision had been made underwent an FDG-PET scan in order to complete the standard radiological evaluation. Results: Twenty-four patients and 26 FDG-PET scans were eligible. In 18 patients, metastatic disease was evaluable on the computed tomography (CT) scan; the FDG-PET scan was positive in 16 patients and negative in 10. In 2 patients, the FDG-PET scan was positive while they were considered disease free on radiological evaluation. In 5 patients (20.8%), the previous therapeutic decision was changed. Thirteen patients had a pathological evaluation for 19 sites. One patient out of 13 had a false-positive FDG-PET scan, while 4 sites out of 6 were false-negative. The sensitivity was 75% (95% CI: 47.6–92.7) and the predictive positive value was 92.3% (95% CI: 64–99.8). With a median follow-up of 24 months, 3 patients developed new metastatic sites. Conclusion: Our data suggest that, when positive, an FDG-PET scan may modify the decision made; when negative, it should not modify decision-making especially for surgery, owing to its sensitivity. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: We reviewed our experiences in performing cytoreductive metastatectomy before initiating systemic immunochemotherapy and tried to investigate potential prognostic factors for such an approach. Patients and Methods: A retrospective analysis of 57 patients who received interleukin-2, interferon-α, and 5-fluorouracil immunochemotherapy for metastatic renal cell carcinoma was conducted. Before undergoing immunochemotherapy, 20 of the 57 patients had received metastatectomy along with nephrectomy (metastatectomy group) and the other 37 nephrectomy alone (non-metastatectomy group). Results: The metastatectomy group demonstrated median disease-specific and progression-free survival of 23 and 13 months, respectively. The patients in the metastatectomy group were identified as having a better performance status and primarily demonstrating pulmonary metastasis compared with those in the non-metastatectomy group. As assessed in the metastatectomy group, factors such as the number of metastatic lesions, completeness of metastatectomy, and location of metastatic lesions (lung only vs. others) were observed to be significantly associated with overall survivals on univariate analysis. Conclusions: Metastatectomy may still play a significant therapeutic role for metastatic renal cell carcinoma even in the era of immunochemotherapy as part of a multidisciplinary treatment approach in a selected group of patients in adequate general condition who have pulmonary-limited metastasis that can be completely resected. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate patient and tumor characteristics in 102 patients with unknown primary tumors (UPT) prospectively treated with a combination of carboplatin, doxorubicin, and etoposide, to identify clinical variables predictive of response and survival. Patients and Methods: The association between clinical characteristics and outcome was evaluated by univariate and multivariate analysis: χ2 test and logistic regression analysis were used to study variables predictive of response, and survival analysis, comparison of survival curves and Cox multiple regression analysis to study variables predictive of survival. Results: We obtained 26.5% objective responses (95% confidence interval: 18.2–36.1%) and a median survival of 9 months (95% confidence interval: 7–11 months). Several variables were associated with response to treatment and survival at univariate analysis. At multivariate analysis the number of tumor sites, bone/visceral involvement and epithelial tumor markers were significantly predictive of response; presence of pain, serum alkaline phosphatase, carboplatin AUC and response to treatment were significantly associated with survival. Conclusions: The identification of variables that can predict prognosis and response to treatment in patients with UPT may be useful to offer aggressive treatment to sensitive subsets of patients and provide therapeutic alternatives to those with a low probability of benefiting from standard treatment. In our patients the use of carboplatin AUC higher than 6 and response to treatment were the most important factors associated with prognosis, together with presence of pain and serum alkaline phosphatase. However, larger series and identification of new disease markers are necessary to better define predictive and prognostic variables in UPT patients. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A case of high-grade endometrial stromal sarcoma, confined into an intrauterine polypoid growth, in a woman with a history of breast cancer who was treated with adjuvant tamoxifen. Based on the findings, a high-grade endometrial stromal sarcoma was diagnosed. The patient underwent a total hysterectomy and bilateral salpingo-oophorectomy with multiple omental biopsies. Pathological examination on multiple uterine sections showed the absence of residual tumor cells in the uterus. The endometrium showed patterns of glandular cystic hyperplasia. After 14 months of follow-up, the patient is well and free of disease. In deciding if tamoxifen therapy is warranted, all potentially life-threatening adverse events associated with tamoxifen should be considered, including endometrial adenocarcinoma or uterine sarcoma. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: To explore parental attitudes and beliefs about genetic testing of children for conditions that present throughout the life cycle. Methods: Twelve semi-structured focus groups with black and white parents were conducted. Results: Across racial groups, most respondents want access to genetic testing and believe that parents should be the final decision-makers. While most respondents believe it is important to share genetic information with relatives, white respondents want physicians to respect confidentiality absolutely, whereas some black respondents accept physician disclosures in specific situations. Conclusions: Professional policy statements are restrictive about access to predictive genetic testing of children. This conflicts with parental attitudes about who should have decisional authority. While there is consensus among respondents that genetic information should be shared with relatives, respondents disagree as to who should be responsible for disclosure, and when professionals should breach patient confidentiality. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: This retrospective study was undertaken to analyze the profile of patients presenting with renal cell carcinoma (RCC) and treatment outcomes. Subjects and Methods: Records of 49 patients (36 male, 16 female, 21–75 years) treated at the Kuwait Cancer Control Center, Kuwait for RCC during the period 1993–1998 were analyzed. Forty-one patients had a nephrectomy, 18 postoperative radiotherapy and 1 patient also received adjuvant immunotherapy with interferon. Patients with metastatic disease were treated with a variety of agents including interferon, chemotherapy (vinblastine) or a hormonal agent (megestrol acetate). Data analysis was performed using SPSS statistical software package. Overall survival and disease-free survival were calculated using the Kaplan-Meier method. Results: Twenty-nine patients presented with symptoms classically associated with RCC. Metastases at diagnosis were seen in 9 patients (18%), with lung being the most frequent site. The commonest tumor subtype was clear cell carcinoma (32.6%). Thirty-nine patients (80%) achieved a complete response to treatment and relapse was documented in 10 patients (26%). The majority of failures were distant, with lung metastases being the most common. Response to salvage treatment was poor. Overall survival was 83% at 2 years. The disease-free survival was 68 and 45% at 2 and 5 years, respectively. Conclusions: Although many patients presented with advanced local disease, a majority achieved complete response after radical surgery with or without postoperative radiation therapy. Salvage of metastatic disease proved difficult with interferon, chemotherapy.Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Conventional preclinical investigations have strongly recommended to combine interferon-α (IFN-α) with 13-cis retinoic acid (13-cRA, isotretinoin) for treatment of renal cell carcinoma (RCC). However, a recent randomized controlled trial on the drug combination ultimately failed to demonstrate an increased tumor-specific survival of patients with metastatic RCC (MRCC). All-trans retinoic acid (ATRA, tretinoin) was suggested to provide stronger antineoplastic properties than 13-cRA in different other tumors. Materials and Methods: The present study aimed to compare ATRA with 13-cRA (0.1, 1, 10, 100 nM) alone or in combination with IFN-α (5, 400, 5,000, 25,000, 250,000 IU/ml) or 5-fluorouracil (5-FU; 0.1, 1, 10, 100 μg/ml). Multicellular tumor spheroids of human RCC cells (SN12C) were treated in order to facilitate the predictions of the model system. Results: ATRA decreased the mean volume of SN12C spheroids 10–20% more than 13-cRA. Both retinoids led to a super-additive growth inhibition in combination with IFN-α, but not with 5-FU. However, in this scenario the superior effect of ATRA compared to 13-cRA, although statistically significant, was not impressive (<10%). Conclusions: ATRA provides a slightly stronger direct antineoplastic effect on human renal cancer cells than 13-cRA, and acts synergistically with IFN-α. However, ATRA, if at all, does not seem to be more suitable for treatment of patients with MRCC than 13-cRA. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The present study reports on the important issue of how family communication and support regarding breast cancer risk affects interest in genetic testing and mental health. Methods: Participants (n = 221) were women aged 18-74 who had at least one relative of Ashkenazi Jewish descent, no personal history of breast or ovarian cancer, and lived within 60 miles of Seattle, Wash. Results: Communication about breast cancer risk was reported with very low frequency across all types of relatives. Women talked with their mothers and sisters more often than their fathers, brothers, or children. The only significant predictor of interest in genetic testing was the individual level variable of seeking social support. Conclusion: Social support needs might be a part of the genetic testing process. [ABSTRACT FROM AUTHOR]

Background: In order to promote safe and effective testing for BRCA1 and BRCA2 mutations in clinical practice, a network of expert centres in hereditary breast and ovarian cancer ('Verbundprojekt familiärer Brust- und Eierstockkrebs'; German Consortium on Hereditary Breast and Ovarian Cancer) has been established by the Deutsche Krebshilfe (German Cancer Aid). To improve practice, evaluations based upon the views of patients who have undergone testing concerning the impact of the genetic diagnosis and the quality of the services they receive and require are undertaken. Methods: Herein, we first describe the protocols for interdisciplinary pre- and post-test counselling and for molecular diagnostics, then the feedback from the patients undergoing testing. Women and men who had obtained their test results at least 6 months earlier were interviewed using a questionnaire including open and standardised questions at 11 participating centres in 2002-2003. Reported here are the survey protocol and preliminary data from interviews with women conducted by the centre based at the University of Münster's Medical School in 2002 (n = 46). Results: Compared to international guidelines, the Consortium's protocols provide more specifically outlined indications based on the mutation frequencies observed in the German population for families that should be offered interdisciplinary counselling and genetic testing. The data from the Münster survey suggest that there is little regret regarding the decision to undergo testing and that the vast majority of women would undergo the test again. However, women with positive findings experienced more problems than women with negative results. They were less prone to recommend the test and to communicate the tests results in their family compared to women with negative test results. Communication of test results within the family was characterised by preferential information of female family members. Conclusion: BRCA1/2 testing should be provided within a framework that ensures harmonisation and standardisation of services and that protects users. Women and men with positive test results may need special support from counsellors on how to handle test results in their families. Strategies need to be developed and evaluated on how to help stimulate and facilitate the dissemination of information within families without potentially 'overstraining' the 'messenger patient', at least when a mutation has been identified. [ABSTRACT FROM AUTHOR]

Objectives: To examine whether being a BRCA1/2 mutation carrier affects a wide array of aspects of life, and if so, how. Methods: Participants were grouped according to their carrier status (carrier and noncarrier status), health status (affected or unaffected by cancer), and their enrollment at the counseling service (probands and other family members). One hundred and sixty-five women completed a self-administered questionnaire following their genetic consultation session. Results: Probands/ nonprobands and carriers/noncarriers did not differ with regard to demographic characteristics, health behaviors including medical checkups, the distress they experience or their resources (sense of coherence, social integration, religiosity). Individuals affected by cancer did differ on some of these aspects from participants without cancer. Conclusions: From the results of this study, being a carrier could not be considered a psychosocial risk factor, nor does it seem to have an effect on carriers' resources and lifestyle. [ABSTRACT FROM AUTHOR]

Objective: To investigate the reactions of general practitioners (GPs), nurses and midwives concerning the cancer risks in a high-risk family. Methods: Questionnaires were sent to 356 GPs, 881 nurses and 119 midwives. Results: The response rate was 60% for GPs, 58% for midwives and 33% for nurses. The breast cancer risk of an unaffected patient from a high-risk family as well as the risk of her daughter were mostly (180%) correctly evaluated as increased. The percentage answering 'increased risk' dropped to 40% for the daughters of the patient's brother. Half of the GPs and nurses/midwives explicitly mentioned that a predictive DNA test was available. Less than one third would recommend such a test for a young child. Reluctance was also observed regarding prophylactic mastectomy. Conclusion: These results should be taken into account in genetic education initiatives for GPs, nurses and midwives. [ABSTRACT FROM AUTHOR]

Objective: To conduct a survey in seven European cancer genetics centres to compare service provision, organisation and practices for familial breast and colon cancer consultations and testing. Information was obtained on aspects of services both nationally and locally. Methods: A detailed survey questionnaire was adapted collaboratively to obtain the required information. Initial survey data were collected within each centre and interim results were discussed at two European Workshops. Where differences in practice existed, details were clarified to ensure accuracy and adequacy of information. Participating centres were Haifa (Israel), Hannover (Germany), Leiden (The Netherlands), Leuven (Belgium), Manchester (UK), Marseille (France) and Milan (Italy), representing countries with populations ranging from 6.5 to 80 million. Results: The European countries diverged in regard to the number of cancer genetics centres nationally (from 8 in Belgium to 37 in France), and the average population served by each centre (from 0.59 million in Israel to 3.32 million in Italy). All centres offered free care at the point of access, but referral to specialist care varied according to national health care provision. At a centre level, staff roles varied due to differences in training and health care provision. The annual number of counsellees seen in each participating centre ranged from 200 to over 1,700. Access to breast surveillance or bowel screening varied between countries, again reflecting differences in medical care pathways. These countries converged in regard to the wide availability of professional bodies and published guidelines promoting aspects of service provision. Similarities between centres included provision of a multidisciplinary team, with access to psychological support, albeit with varying degrees of integration. All services were dominated (70-90%) by referrals from families with an increased risk of breast cancer despite wide variation in referral patterns. Collection of pedigree data and risk assessment strategies were broadly similar, and centres used comparable genetic testing protocols. Average consultation times ranged between 45 and 90 min. All centres had access to a laboratory offering DNA testing for breast and bowel cancer-predisposing genes, although testing rates varied, reflecting the stage of service development and the type of population. Israel offered the highest number of genetic tests for breast cancer susceptibility because of the existence of specific founder mutations, in part explaining why the cancer genetics service in Haifa differed most from the other six. Conclusion: Despite considerable differences in service organisation, there were broad similarities in the provision of cancer genetic services in the centres surveyed. [ABSTRACT FROM AUTHOR]

Objective: Investigate attitudes of midwives and nurses regarding predictive testing for hereditary breast cancer and Huntington’s disease. Methods: Mail questionnaires were sent to 119 midwives and 881 nurses. Results: The response rate was 58% for midwives, but only 33% for nurses. The attitude toward predictive testing in an asymptomatic adult was more favourable in case of hereditary breast cancer than in case of Huntington’s disease, mostly because prevention or therapy is unavailable for the latter condition. Prevention of breast cancer through prophylactic mastectomy elicited adverse reactions among 40% of the participants. Predictive testing for these diseases in an adolescent at the own request was also rated favourably while testing in children at the parents’ request was less acceptable. For both diseases, concealing carrier status information from the employer or the insurance company was judged as acceptable by the majority. Conclusion: Our findings contribute to the understanding of nurses’ and especially midwives’ attitudes to predictive testing, which may in turn serve as a basis for genetic education for these groups of health care professionals.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We report a pediatric patient with a posterior fossa ependymoma in whom the second of two magnetic resonance imaging (MRI) scans obtained preoperatively within a 10-day span showed intense but transient disseminated enhancement. However, following posterior fossa craniotomy for near total tumor resection, neither three MRI exams nor two craniospinal fluid samplings revealed evidence of disseminated disease. Concerned that the one MRI with disseminated enhancement indicated an elevated risk of leptomeningeal metastasis, we initiated craniospinal irradiation. However, we terminated this treatment after realizing that the bulk of the clinical evidence refuted the diagnosis of metastatic disease.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]