Platinum disposition after intraarterial and intravenous infusion of cisplatin for osteosarcoma

Summary Preoperative chemotherapy according to the COSS 86 protocol, including two courses of cisplatin, was used for high-risk osteosarcoma. Patients were randomised to receive either intraarterial (i.a.) or intravenous (i.v.) cisplatin infusions. As measured by flameless atomic absorption spectroscopy (FAAS), platinum (Pt) levels in serum, ultrafiltrate, and urine did not show a decrease in systemic drug availability with i.a. administration. Turmors were surgically removed 3 weeks after the last cisplatin dose and analysed for Pt content and response to chemotherapy. A correlation could not be demonstrated between Pt levels in tumor tissue samples and the mode of CDDP application or extent of tumor cell destruction.This work was supported by the Hamburger Krebsgesellschaft and the Bundesministerium für Forschung und Technologie     

Dietary patterns, nutrient intake and gastric cancer in a high-risk area of Italy

Objectives: To better understand the role of overall dietary patterns and major energy-providing components in gastric cancer etiology. Methods: In a population-based case–control study conducted in a high-risk area in central Italy, 382 gastric cancer cases and 561 controls were available for analysis. Multivariate models based on energy-adjusted residuals and completely partitioned logistic models were used; dietary patterns were evaluated by factor analysis and multiple correspondence analysis. Results: Gastric cancer risk was inversely related to high energy-adjusted intakes of vegetable fat, sugar, beta-carotene, vitamin C, alpha-tocopherol, and nitrates. In contrast, significant positive associations emerged with high intake of protein, nitrite, and sodium. According to energy decomposition models, gastric cancer risk increased with increasing intake of protein and decreased with increasing intake of sugar and total fat. The pattern analysis identified four dietary profiles, overall explaining 75% of total dietary variability. Two patterns, named traditional and vitamin-rich, were strongly associated with gastric cancer risk and overall accounted for 44% of estimated gastric cancer attributable risk. The other two patterns, refined and fat-rich, were not consistently associated with gastric cancer. Conclusion: Innovative methodological approaches may contribute to better evaluation of the complex relationship between diet and cancer risk and to planning dietary interventions.     

The “portrait” of hereditary breast cancer

Summary Five to ten per cent of all breast carcinomas are of hereditary origin. Many of them have been associated to mutations in the BRCA1 and BRCA2 susceptibility genes. No BRCA3 gene has been found to account for the non-BRCA1/BRCA2 breast cancer (BRCAx) families, and BRCAx tumors are increasingly believed to originate from multiple distinct genetic events. Phenotype studies have questioned the existence of specific portraits among hereditary breast carcinomas (HBC). They have shown that most BRCA1 tumors have a basal (epithelial)-like aspect, while BRCA2 and BRCAx HBC are more heterogeneous. HBC have also been submitted to genetic analyses, notably with the objective of resolving the heterogeneity of BRCAx lesions. The present review aims to summarize recent data on BRCA1, BRCA2, and BRCAx HBC, including hypotheses on the origin of BRCA1 tumors and their paradoxical relations to estrogen-sensitivity.BreastMed Consortium: Yves-Jean Bignon, Nancy Uhrhammer, Unité dOncogénétique, Centre Jean Perrin, Clermont-Ferrand, France; Nathalie Zammatteo, José Remacle, URBC, Fondation Universitaire Notre-Dame de la Paix, Namur, Belgium; André Mégarbané, Unité de Génétique Médicale, Université Saint-Joseph, Beirut, Lebanon; Nourredine Ben Jafaar, Abdelaziz Sefiani, Institut National dOncologie, Rabat, Morocco; Lotfi Chouchane, Sami Remadi, Laboratoire dImmuno-Oncologie Moléculaire, Monastir, Tunisia; Amel Ben Ammar-El Gaaied, Laboratoire de Génétique Moléculaire, dImmunologie et de Biotechnologie, Faculté des Sciences de Tunis, Tunis, Tunisia; Denis Larsimont, Jean-Marie Nogaret, Institut Jules Bordet, Bruxelles, Belgium; Catherine Sibille, Christine Galant, Centre de Génétique Médicale, Université Catholique de Louvain, Bruxelles, Belgium; Françoise de Longueville, Eppendorf Array Technologies (EAT), Namur, Belgium Véronique Vidal, Diagnogène, Aurillac, France.     

Phenotypic analysis of 1-B-d-arabinofuranosylcytosine deamination in patients treated with high doses and correlation with response

Summary Two phenotypes for 1-B-d-arabinofuranosylcytosine (ara-C) deamination corresponding to a ratio of distribution for slow (ratio, 14) vs fast (ratio, >14) deaminators of 70%30%, have been determined on the basis of studies on plasma ratios of 1-B-d-arabinofuranosyluracil/ara-C (ara-U/ara-C) in 56 subjects treated with high-dose ara-C (3 g/m² infused i.v. over 3 h). A positive correlation of age with the concentration of ara-U was observed. In a subgroup of 36 patients with leukemia, the ara-U/ara-C pattern was similar to that observed for all 56 subjects. In these leukemic patients, who were treated with combinations of ara-C plus other conventional agents, a tendency toward a positive response (complete response +partial response) was found for those showing low ara-U/ara-C ratios (slow deaminators). The phenotypic effect of deamination in acute leukemia needs to be evaluated prospectively.This work was supported by the Don Monti Memorial Research Foundation     

Influence of truth disclosure on quality of life in cancer patients

Background Whether truth disclosure may harm patients may be critical for the promotion of truth disclosure in patients with cancer. We used the Functional Living Index-Cancer (FLIC) to study the influence of truth disclosure on quality of life (QOL) in cancer patients. Methods. Twenty-three truth-disclosed patients with cancer (TD group) and 21 truth-concealed patients (TC group) were asked to answer 22 FLIC questions at the outpatient clinic. Results were compared with those in 18 patients with irritable bowel syndrome (IBS group) and in 37 patients with other gastrointestinal diseases (OGD group). Results. Average FLIC scores were the same in the TD and IBS groups and in the TC and OGD groups. There were significant differences among the four groups for four FLIC items: Discouraged about life (P = 0.04), Uncomfortable today (P = 0.03), Pain disrupts activity, (P = 0.0003) and How much nausea (P = 0.04). The IBS group had the worst FLIC scores for the former three of these items. Truth disclosure influenced only one FLIC item, in that the TD group was more likely to think that their daily activities were disrupted by pain or discomfort than the TC group (P = 0.01). However, incurability of cancer worsened the score for ten FLIC items, among which incurability was independently associated with the deterioration of FLIC-QOL in terms of Family disruption (P = 0.03) and Cancer-related pain (P = 0.02). Conclusion. Incurability of cancer, not truth disclosure, negatively affects patients' QOL. Thus, if sufficient supportive care is provided particularly to patients with incurable cancer, the truth could be disclosed without fear of being cruel or harming patients.     

Stage-specific incidence of breast cancer before the beginning of organized screening programs in Italy

Objective: To measure stage-specific geographic and time variability of breast cancer in seven Italian areas before the onset of organized screening programs. Methods: All invasive cancers (8689 cases) arising in women aged 40–79 years during the pre-screening period 1985–1997, were considered. Multiple Poisson regression analysis was performed. Results: About 39% of the cases were classified as early, 52% as advanced, and 9% as unspecified stage. Age-adjusted incidence rates showed a significant geographic variation for early but not for advanced cancers (range: 58–103 cases/100,000 and 104–125 cases/100,000, respectively). The result was confirmed in the multiple regression analysis after adjustment for year of diagnosis and age. Early breast cancer risk adjusted for age and registry showed a significant increase over time (+ 3.9% per year for all ages, and + 6.2% per year for age category 50–79). In contrast, a decreasing time trend was observed for advanced cancer of 3 cm or over in women aged less than 60. Conclusions: In our study, early breast cancer incidence varied both by geographic area and time before the commencement of screening. The differences in early-stage incidence may well be related to differences in availability of spontaneous mammography. Late-stage incidence decreased over time in younger women and for very advanced cases, but not in the older ones, nor for cancers less than 3 cm. Early detection outside organized screening was only partially efficient in reducing advanced breast cancer incidence. The trend of incidence of advanced disease, as previously proposed, is confirmed to be a valid early indicator of effectiveness of screening.     

Fatal pneumothorax associated with bleomycin-induced pulmonary fibrosis

Summary A patient developed fatal pneumothorax associated with bleomycin-induced interstitial fibrosis. Pneumothorax may be a complication of bleomycin lung.     

Birth weight,ethnicity, and occurrence of cancer in children: a population-based,incident case-control study in the State of Texas,USA

Objective: To investigate the relationship between birth weight and risk of early age childhood cancer and whether racial differences in birth weight distribution could explain differences in the incidence of cancer in white, Hispanic, and black children. Methods: We compared birth weights of 268 children younger than five years old and diagnosed with cancer in the State of Texas in 1995 to the birth weights of 2680 randomly selected, age-matched population-based controls. Birth weight, sex, race/ethnicity, maternal age, smoking status, parity, and gestational age information was ascertained from the birth certificates. Logistic regression analyses were performed to evaluate the association between high birth weight (> 4000 g) and occurrence of childhood cancer. Results: Increased odds ratios (OR) were found for total cancer cases (OR 1.4, 95% CI 0.9–2.1), leukemia cases (OR 1.7, 95% CI 0.9–3.0) and acute lymphoblastic leukemia (ALL) cases (OR 2.2, 95% CI 1.2–4.1). Increased ORs in the former two groups were shown to be due to ALL cases. Including the race/ethnicity variable in the regression model did not affect the ORs. Conclusion: Compared to newborns who weighed between 2500 and 4000 g at birth, children who weighed > 4000 g had an increased risk of developing childhood ALL during the first five years of life. Birth weight differences does not explain the sequence of childhood cancer incidence by race/ethnicity.     

Alcohol and colorectal cancer: a case-control study from northern Italy

The role of alcohol consumption in the etiology of colorectal cancer has been investigated in a case-control study conducted from 1985 to 1990 in the northern part of Italy, on 889 cases of colon cancer, 581 cases of rectal cancer, and 2,475 controls admitted to hospital for acute, non-neoplastic, nodigestive disordes. After allowance for age, education, study center, body mass index, and approximate total energy intake, no significant associations between alcohol intake and the risk of cancer of the colon or rectum were found (odds ratios [OR] for 42 drinks/week cf none =1.0 (95 percent confidence interval [CI]=0.8–1.4) and 0.7 (CI=0.5–1.0) for cancer of the colon and rectum, respectively). A significant increase in the risk of colon cancer with increasing alcohol consumption was, however, observed in females (OR for 28 drinks/week cf none = 1.8 (CI=1.1–3.0)). While the results of the present case-control study do not suggest that alcohol plays a role in the etiology of colon or rectum cancer overall, they provide a hint for a weak association between alcohol consumption and colon cancer among females which, because of the similarities with breast cancer, should be evaluated in the context of the possible relationship between colon cancer, alcohol intake, and female hormones.Drs Barra, Franceschi, and Guarneri, are with the Epidemiology Unit, Aviano Cancer Center Aviano, Italy. Dr Franceschi is also with the European Cancer Prevention Organisation (ECP), Epidemiology and Cancer Working Group, Brussels, Belgium. Drs Negri and La Vecchia are with the Mario Negri Institute for Pharmacological Research, Milan, Italy. Dr La Vecchia is also with the Institute of Social and Preventive Medecine, University of Lausanne, Lausanne, Switzerland. Address correspondence to Dr Barra, Epidemiology Unit, Aviano Cancer Center, Via Pedemontana Occ., 33081 Aviano (PN) Italy. Support for this project was contributed by the Italian Association for Research on Cancer and the Italian League against Tumors, Milan and the Italian National Research Council (CNR Applied Project Clinical Applications of Oncological Research).     

Recent trends of in situ carcinoma of the breast and mammographic screening in the Florence area, Italy

Objectives: The study analyzes the relationship between the incidence trends of breast carcinoma in situ (CIS) and the spread of mammography screening in the Italian area of Florence (about 608,000 female residents).Setting: In this area, since the seventies, a mammographic screening by personal invitation was performed by the Center for Cancer Prevention (CSPO) in some rural municipalities. After 1990, the municipality of Florence and other municipalities were involved in the screening.Methods: The study included all cases of female breast carcinomas in situ reported to the population-based Tuscany Cancer Registry between 1985 and 1995. On the basis of information from the CSPO files, the cases were categorized into: screen-detected, self-referrals, and other (CSPO cases diagnosed in symptomatic women or at periodic check up after breast cancer plus hospital cases).Results: Overall, 332 women with breast carcinoma in situ (CIS) were registered between 1985 and 1995. The CIS incidence rate increased from 2.39/100,000 women in 1985–87 to 6.22/100,000 in 1994–95. The largest increase was observed for the ductal carcinoma in situ (2.9 times) and in women aged 50–69 years (3.8 times). In this age group, cases diagnosed at the screening by personal invitation accounted for 69% of the rise in CIS incidence. The proportion of mastectomy lowered from 41% before 1990 to 25% after 1990.Conclusion: In the Florence area the CIS incidence trend, showing a marked increase beginning in 1991, was mainly explained by the spread of the mammographic screening by personal invitation. The period during which mammographic screening became widespread coincided with a change in the treatment policy of breast cancer, with a high proportion of breast conserving surgery also for CIS. Therefore, the rise in CIS incidence rates correlated with the widespread use of mammographic screening did not substantially increase the number of women treated by mastectomy.     

Malignant melanoma of pleura in a patient with giant congenital “bathing suit” hairy nevus

An unusual case of malignant melanoma of the pleura in a patient with bathing-suit type of giant congenital hairy nevus is presented. The treatment advocated and the outcome are discussed.     

Molecular genetic studies of early breast cancer evolution

Summary In the past few years there has been an explosion in the number of patients diagnosed with hyperplastic breast disease andin situ breast cancer. Based on epidemiological data, these morphologically defined lesions may be categorized as those with little malignant potential (e.g. typical hyperplasia or proliferative disease without atypia [PDWA]), those with significant malignant potential which may already be initiated (e.g. atypical ductal hyperplasia [ADH]), and early transformed lesions which are malignant but not yet invasive (e.g. ductal carcinomain situ [DCIS]). They may represent sequential evolutionary stages in the ontogeny of invasive breast cancer, with each morphologically defined stage resulting from accumulating genetic changes culminating in a transformed clonal lineage capable of invasion and metastasis. Using loss-of-heterozygosity (LOH) analysis, we are studying the genetic changes associated with these lesions in archival tissue samples. 50% (6/12) of the proliferative lesions (PDWA and ADH) and 80% of the DCIS shared their LOH patterns with more advanced lesions from the same breast, strongly supporting a precursor/product relationship between these lesions and the cancers they accompany.     

Reduced sun exposure and tanning in children after 2 years of a school-based intervention (Australia)

Objective: This paper presents the results of the evaluation of measured suntan and parent-reported sun exposure in participating children after 2 years of the Kidskin study, a 5-year school-based sun protection intervention undertaken in Perth, Western Australia (1995–1999). Methods: The study involves three groups: a control, a moderate, and a high intervention group. Participants were 5 or 6 years of age at the beginning of the study. Control schools received the standard Health Education curriculum, while intervention schools received a multicomponent intervention including a specially designed curriculum. Children in the high intervention group also received program materials over the summer vacation and were offered sun-protective swimwear at low cost. At the end of the second summer, suntan was measured and parents completed a questionnaire about their child's sun-related behavior. Results: Children in the intervention groups – especially the high group – were less tanned at the end of the summer; this effect was greater for the back than for the forearms. These children were also reported to have received less sun exposure and made greater use of sun protection measures. Conclusion: Intensive school-based interventions can reduce tanning and reported sun exposure in children.     

Pharmacokinetic evaluation of two different formulations of megestrol acetate in patients with advanced malignancies

The bioequivalence of two megestrol acetate formulations, 160-mg tablets and 160-mg sachets, was investigated in a single-dose, open-label, balanced-for-sequence cross-over study involving 12 advanced-cancer patients. The observed plasma megestrol-acetate time course obtained with both formulations was consistent with the literature data. The main source of variability in the pharmacokinetic parameters was intersubject variability; drug formulation played only a minor (and nonsignificant) role. The width of the 90% confidence interval of the areaunder-the-curve (AUC) ratio (sachets: tablets) computed according to Schuirmann (0.9–1.4) was mainly due to the presence of a single outlier, showing an AUC ratio of 2.7. The trend to higher bioavailability of the new formulation was not significant, especially as compared with the doseresponse data reported in the literature.     

左半结肠癌急性梗阻一期切除吻合的安全保证

Objective: Thorough, prompt enteral decompression technique without contamination was developed to ensure safety for emergent colon resection and primary anastomosis. Methods: After isolating the mesentery, the to be resected colon segment was cut at its lower end, then the proximal cut end was put into a plastic bag which was adhered to one side of the operating table. After releasing the clamp, the content could flow into this bag. The operator could squeeze the bowel with two hands by turns, from proximal to farness, and from small bowel to large bowel, until the entire bowel content was fully discharged. Then the upper end of this to be resected colon segment was cut, and was removed together with the plastic bag. Results: 31 cases of left colon cancer with acute obstruction were decompressed with this technique. They all recovered smoothly, without anastomosis fistula. Another 6 cases of hepatic segmentectomy with incidental colonectomy were decompressed with this technique and had the same results. This technique was also used in different kinds of acute small intestinal obstruction and gained satisfactory results. Conclusion: This technique could be considered as the preferable choice for intraoperative enteral decompression.     

Homöopathie und die Behandlung von Geschwulstkrankheiten

Zusammenfassung Die Behandlung bösartiger Tumorerkrankungen ist zweifelsfrei eine Domäne der naturwissenschaftlich orientierten Medizin mit den drei Hauptsäulen operatives Vorgehen, Chemotherapie und Behandlung mit energiereichen Strahlen neben der palliativen Nachsorge einschließlich einer ausreichenden Schmerzbehandlung. Entscheidend ist die umfassende ärztliche Betreuung dieser Patienten nach dem Eingriff. Dieses Vorgehen wird auch von den meisten außerhalb der wissenschaftlichen Medizin stehenden Heilern akzeptiert, jedoch sehen sie Chancen für eine Mitwirkung in der gleichzeitigen unterstützenden Behandlung oder in der Nachbehandlung mit Mitteln, deren Wirkungen sich entweder eines Wirkungsnachweises entziehen oder vom wissenschaftlichen Ansatz her schon fragwürdig sind. Diese Behandlungsverfahren werden als naturheilkundlich apostrophiert und treffen damit auf ein Patientenklientel, welches sich eine nebenwirkungsfreie Behandlung erhofft. Insofern kann man davon ausgehen, dass diese Patienten mit Hilfe derartiger Mittel eine Zuwendung erfahren, die ebenfalls mit einer qualifizierten ärztlichen Betreuung erreicht werden könnte.     

Glycogen‐rich carcinomas of the breast display unique characteristics with respect to proliferation and the frequency of oligonucleosomal fragments

We determined the proliferation rate and apoptotic activity of glycogenrich carcinomas of the breast as opposed to nonclear cell tumors by means of MIB1 immunohistochemistry and in situ detection of oligonucleosomal fragments (TUNEL reaction). The retrospective biopsy series included six invasive clear cell carcinomas of the glycogenrich type as well as 15 randomly selected cases of invasive ductal carcinoma without evidence of glycogen storage. Three patients in the clear cell group and seven patients in the control cohort developed lymphnode metastasis. The MIB1 labeling index of glycogenrich carcinomas averaged 9.05%, while that of the controls was 30.03%. Apoptotic nuclei were present in a mean of 1.26% of glycogenrich carcinoma cells. The control tumors exhibited an average apoptotic frequency of 5.85%. Tumor size, hormone receptor status, and presence or absence of lymph node involvement were found not to correlate with either proliferation or apoptosis. We conclude that glycogenrich breast carcinomas are characterized by a peculiar low proliferationlow apoptosis cell kinetic profile. The aggressive clinical behavior of these neoplasms may possibly be accounted for by an ineffective apoptotic elimination of otherwise slowly proliferating tumor cells.     

Treatment of refractory and relapsed non-Hodgkin's lymphoma with ifosfamide,methotrexate and etoposide

Summary The combination of ifosfamide, etoposide and methotrexate was evaluated in 22 patients with non-Hodgkin's lymphoma (NHL) whose disease had relapsed or was resistant to first-line adriamycin-containing treatment. Only 4 of the 22 patients underwent remissions, 3 of which were complete and 1, partial. Two of the complete remissions occurred in patients with high-grade histology who received IMVP-16 after first-line treatment had induced only a partial remission. Bone marrow suppression was the limiting toxicity of this regime, which may be of value in the salvage therapy of selected patients with NHL.     

A case-control study of risk factor for renal cell cancer in northern Italy

A hospital-based case-control study of renal cell cancer was conducted in northern Italy betwen 1986 and 1989, with 240 cases of renal cell cancer (150 males and 90 females), and 665 controls (445 males and 220 females) chosen on the basis of age, sex, and area of residence. No associations were found between renal cell cancer and: body mass index (BMI); number of cigarettes smoked; age at starting to smoke; years of smoking; consumption of wine, beer, spirits, coffee, decaffeinated coffee; tea; intake of animal protein, fruits, and vegetables; various resproductive factors; hormonal use; sexual habits; sexually transmitted diseases; or selected occupational exposures. The odds ratio (OR) was above unity in smokers (OR=1.34 for 15 cigarettes/day), but the trends in risk with dose or duration were not statistically significant. Significant positive associations were found between renal cell cancer and sources of fat intake, especially margarine (OR for highest vs lowest intake = 1.71), and oils (OR=1.89) whereas carrot intake showed a negative association (OR=0.62). Also, a history of nephrolithiasis and multiple episodes of cystitis showed weak positive associations (OR=2.00, 95 percent confidence interval (CI) 1.07–3.73; and OR=1.60, 95 percent CI 0.95–2.70, respectively).Address reprint requests to Dr Talamini. The work was conducted with the contribution of the Italian Association for Cancer Research, Milan, Italy and the CNR (Italian National Research Council) Applied Projects Oncology (Contract n. 85.02209.44).Drs Talamini, Barón, Barra, Bidoli, Serraino, and Franceschi are in the Epidemiology Unit, Aviano Cancer Center, Via Pedemontana Occ. 33081 Aviano (PN) Italy. At the time of this work, Dr Barón was a visiting biostatistician from the Department of Preventive Medicine and Biometrics, University of Colorado, Health Science Center, CO, funded by the National Cancer Institute (US) and the Italian National Research Council. Dr Franceschi is also chief of the Hormones and Sexual Factors and Cancer Working Group of the European Organization for Cooperation in Cancer Prevention Studies, Bruxelles, Belgium. Drs La Vecchia and Negri are in the Mario Negri Institute for Pharmacological Research, Milan, Italy. Dr La Vecchia is also in the Institute of Social and preventive Medicine, University of Lausanne, Switzerland.     

Prospective Clinical Trials of Brain Tumor Therapy: The Critical Role of Neurosurgeons

Prospective clinical trials are critical to the scientific evaluation of new treatments for brain tumors. This paper reviews basic concepts of early and late phase prospective clinical trials that are most relevant to neurosurgical oncologists, with an emphasis on the challenges associated with conducting clinical trials of brain tumor therapies. Novel clinical trial designs that meet these challenges by incorporating pretreatment molecular profiling and post-treatment molecular endpoints are described. Because of their ability to obtain brain tumor specimens from patients before and after treatment, neurosurgeons have been required to play an increasingly important role in the execution of these molecular-based clinical trials. Potential avenues for enhancing the participation of neurosurgeons in the design and development of clinical trials are discussed.