bluuebunny/crossref_metadata_2025 huggingface dataset:
Tailored messages, external barriers, and women's utilization of professional breast cancer screening over time
Authors: Lauver Diane Ruth , Settersten Lori , Kane Janet H. , Henriques Jeffrey B.
Published: May 2003

BACKGROUND

The efficacy of tailored messages on women's utilization of professional breast screening over time has not been examined often or in combination with external barriers (e.g., costs and access). The objectives of this study were to test the effects of alternative messages on mammography and clinical breast examination (CBE) utilization over time and to examine the combined effects of such messages and external barriers.

METHODS

In a randomized, controlled trial, three message conditions were compared: no message (control group), recommendations about screening, or recommendations plus tailored discussion (on beliefs, feelings, costs, and access). Messages were delivered by advanced practice nurses over the telephone. Participants were women ages 51–80 years who had not had mammography in the prior 13 months. Outcome measures were women's mammography and CBE utilization 3–6 months postintervention (short‐term follow‐up) and 13–16 months after short‐term follow‐up (long‐term follow‐up).

RESULTS

Both messages promoted mammography and CBE utilization at short‐term follow‐up. Utilization increased over time in all groups. Mammography utilization was greater for the tailored‐message group compared with the recommendations‐only group at long‐term follow‐up. Messages and external barriers had combined effects (Ps < 0.01). Among participants with high external barriers, participants in the message conditions—especially the tailored message—had the highest screening rates; among participants with low barriers, screening rates were similar across conditions.

CONCLUSIONS

Clinicians can tailor discussions on beliefs, feelings, cost, and access about screening to promote professional breast screening over time, especially with women who have not had mammograms as recommended and who have external barriers to screening. Cancer 2003;97:2724–35. © 2003 American Cancer Society.

DOI 10.1002/cncr.11397
Elevated serum endostatin is associated with poor outcome in patients with non‐Hodgkin lymphoma
Authors: Bono Petri , Teerenhovi Lasse , Joensuu Heikki
Published: May 2003

BACKGROUND

Endostatin is a cleaved fragment of collagen Type XVIII and has antiangiogenic activity. The clinical significance of circulating, soluble endostatin (S‐endostatin) is not known.

METHODS

Pretreatment S‐endostatin and serum vascular endothelial growth factor (S‐VEGF) levels were measured in 143 patients with non‐Hodgkin lymphoma (NHL) using competitive enzyme immunoassays and were compared with the levels from a control group (n = 24 participants).

RESULTS

S‐endostatin levels varied widely from 4.5 ng/mL to 116 ng/mL (median, 29.6 ng/mL), and the median level was higher in patients with NHL compared with patients in the control group (16.4 ng/mL; P = 0.05). High S‐endostatin levels were associated with advanced disease stage (P < 0.0001) and high serum VEGF levels at diagnosis (P = 0.017). The median 5‐year survival rate for patients who had S‐endostatin concentrations within the highest tertile (> 36.0 ng/mL) was only 34% compared with 57% in patients who had lower S‐endostatin levels (P = 0.019). A high S‐endostatin level also was associated with a poor outcome in patients with large cell diffuse and immunoblastic lymphoma, which was the largest subgroup within the series (n = 60 patients). Patients who had high pretreatment levels of both S‐VEGF and S‐endostatin had particularly poor outcomes. High S‐endostatin levels had an independent, adverse influence on survival it was entered as a factor into a multivariate analysis together with the factors included in the International Prognostic Index (relative risk, 1.80; 95% confidence interval, 1.08–2.98; P = 0.0024).

CONCLUSIONS

High pretreatment levels of S‐endostatin are associated with high serum VEGF levels and poor survival in patients with NHL. Prospective studies are warranted to establish the clinical value of longitudinal S‐endostatin measurements. Cancer 2003;97:2767–75. © 2003 American Cancer Society.

DOI 10.1002/cncr.11399
A pilot study of transcatheter arterial interferon embolization for patients with hepatocellular carcinoma
Authors: Yuen Man‐Fung , Ooi Clara Gaik‐Cheng , Hui Chee‐Kin , Wong Wai‐Man , Wong Benjamin Chun‐Yu , Chan Annie On‐On , Lai Ching‐Lung
Published: May 2003

BACKGROUND

Systemic, high–dose interferon‐α treatment given three times per week subcutaneously induces tumor regression in approximately 30% of patients with inoperable hepatocellular carcinoma (HCC). The objective of the current study was to determine the efficacy and safety of transcatheter arterial interferon embolization for the treatment of patients with inoperable HCC.

METHODS

Eighteen patients with inoperable HCC were recruited to receive 3 different doses of interferon‐α‐2b (10 megaunits [MU]/m2, 30 MU/m2, or 50 MU/m2) at intervals of 8–12 weeks. Their tumor response, adverse events, and survival were monitored.

RESULTS

In 14 patients with nondiffuse HCC, complete responses and partial responses (> 50% tumor reduction) were observed in 28.6% and 35.7% of patients, respectively. One of four patients with diffuse HCC had a partial response. Thirty‐eight percent of patients had normalization of their α‐fetoprotein level. The median ferritin level at the last follow‐up was reduced significantly (765 pmol/L; range, 457–2720 pmol/L) compared with the baseline level (1980 pmol/L; range, 1100–3300 pmol/L; P = 0.011). The median survival was 15.9 months. Transient fever and rigor were the most common side effects observed. Five patients (27.8%) developed hypothyroidism. No significant liver decompensation was observed.

CONCLUSIONS

This pilot study showed that transcatheter arterial interferon embolization was an effective method for the treatment of patients with inoperable HCC without significant hepatic toxicity. Cancer 2003;97:2776–82. © 2003 American Cancer Society.

DOI 10.1002/cncr.11400
Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma
Authors: Wiedmann Marcus , Caca Karel , Berr Frieder , Schiefke Ingolf , Tannapfel Andrea , Wittekind Christian , Mössner Joachim , Hauss Johann , Witzigmann Helmut
Published: May 2003

BACKGROUND

Only 20–30% of patients with hilar cholangiocarcinomas (CC) are candidates for potentially curative resection. However, even after curative (R0) resection, these patients have a disease recurrence rate of up to 76%. The current prospective Phase II study investigated photodynamic therapy (PDT) as a neoadjuvant treatment for CC.

METHODS

Seven patients with advanced proximal bile duct carcinoma were evaluated. Patients were treated with PDT at the area of tumor infiltration and 2 cm beyond and underwent surgery after a median period of 6 weeks (range, 3–44 weeks).

RESULTS

One patient had a Bismuth–Corlette Type II tumor, two patients had Type IIIa, one patient had Type IIIb, and three patients had Type IV. Cholestasis parameters after PDT decreased significantly. No relevant adverse events from PDT occurred except for minor intraoperative phototoxicity in one patient. Three patients underwent right‐sided liver resections, two patients underwent left‐sided liver resections, and one patient received a combined hilar resection with partial pancreatoduodenectomy (PD) due to tumor extension into the distal bile duct. Liver transplantation and PD were performed in another patient. In all patients, R0 resection was achieved. Four patients developed minor surgical complications, even though the bilioenteric anastomoses were sewn to PDT‐pretreated bile ducts. No viable tumor cells were found in the inner 4 mm layer of the surgical specimens. The PDT‐pretreated epithelium of the tumor‐free proximal resection margins exhibited only minimal inflammatory infiltration. Tumors recurred in 2 patients 6 and 19 months after surgery. The 1‐year recurrence free survival rate was 83%.

CONCLUSIONS

Neoadjuvant PDT for hilar CC is a low‐risk procedure with efficient selective destruction of the superficial 4 mm layer of bile duct tumor without complications exceeding series without neoadjuvant PDT. Neoadjuvant PDT should be evaluated prospectively to determine whether it reduces the rate of local disease recurrence after potentially curative resection. Cancer 2003;97:2783–90. © 2003 American Cancer Society.

DOI 10.1002/cncr.11401
Perceptions and attitudes of clinical oncologists on complementary and alternative medicine
Authors: Hyodo Ichinosuke , Eguchi Kenji , Nishina Tomohiro , Endo Hisashi , Tanimizu Masahito , Mikami Ichiro , Takashima Shigemitsu , Imanishi Jiro
Published: May 2003

BACKGROUND

The prevalence of complementary and alternative medicine (CAM) is increasing worldwide because of the growing public interest in natural or holistic therapies and because of the flow of information through the Internet. However, there is a lack of communication between cancer patients and their physicians on topics relating to CAM. The authors performed a cross‐sectional survey to evaluate the perceptions and attitudes of Japanese clinical oncologists toward cancer CAM.

METHODS

The CAM questionnaires were sent to 2118 clinical oncologists. The questionnaires gathered data on background (age, gender, years in practice, specialty, and knowledge of cancer CAM), perception (effectiveness/ineffectiveness, scientific evidence, and drug interactions), and attitude (experience with and response to CAM users). Questions about oncologists' perceptions and attitudes to CAM were limited to herbs and other natural products that were sold over the counter.

RESULTS

One hundred sixty‐six questionnaires were returned as undeliverable. Of the remaining questionnaires, 751 were returned (a response rate of 39%). Two‐thirds of the responders were surgical oncologists and most of the remaining responders were medical oncologists. The majority of oncologists (82%) believed that CAM products were ineffective against cancer. The main reason for this belief was a lack of reliable information (as cited by 85% of oncologists). Only 13% of oncologists had experienced CAM‐associated disease improvement in their cancer patients. Of all the oncologists, 84% considered the possibility of drug interactions between anticancer drugs and CAM products. The majority of oncologists (80%) replied that they could neither promote the use of CAM products nor recommend quitting the products, when they were asked about the use of CAM products by cancer patients.

CONCLUSIONS

Negative perceptions of CAM products persist among clinical oncologists. A lack of proven effectiveness of CAM products and concerns about drug interactions with anticancer treatment suggest a need for both accurate information on CAM products and clinical trials. Cancer 2003;97:2861–8. © 2003 American Cancer Society.

DOI 10.1002/cncr.11402
Reflections of a cancer survivor/research scientist
Authors: Zebrack Brad
Published: May 2003

[Our original introduction to Listen to the Patient is published again to emphasize the Journal's commitment to this important series.]

For more than 50 years, Cancer has been devoted to exploring every facet of malignant neoplasia, from morphology to therapy, from epidemiology to biology, from historical perspective to basic science. One aspect, however, needs emphasis, namely, the human being who bears the burden of the cancer. For this reason and with the encouragement of the Editor, we have undertaken to remedy this situation by directing attention to the fears and frustrations, hopes and expectations, and feelings and thoughts of all kinds of the person who has cancer, who is worried about it, and who is dependent on physicians specialized in its diagnosis and management. For doctors to be understanding of the very deep needs of patients with cancer, it is requisite that they be privy to authentic, but often unspoken, expressions of a patient's anxieties about physical and emotional pain, loss of control over personal destiny, and plain dread of dying and of the end of cherished relationships.

Barrie R. Cassileth, Ph.D. Integrative Medicine Service, Memorial Sloan‐Kettering Cancer Center, New York, New York.

A. Bernard Ackerman, M.D. Ackerman Academy of Dermatopathology, New York, New York. Cancer 2003;97:2707–9. © 2003 American Cancer Society.

DOI 10.1002/cncr.11404
Gemcitabine combined with carboplatin in patients with malignant pleural mesothelioma
Authors: Favaretto Adolfo G. , Aversa Savina M. L. , Paccagnella Adriano , Manzini Vincenzo De Pangher , Palmisano Valentina , Oniga Francesco , Stefani Micaela , Rea Federico , Bortolotti Luigi , Loreggian Lucio , Monfardini Silvio
Published: May 2003

BACKGROUND

Malignant pleural mesothelioma (MPM) is increasing rapidly worldwide. Currently, pemetrexed plus cisplatin chemotherapy showed a survival advantage versus cisplatin alone. No impact on patient survival of surgery, radiotherapy, or their combination has been demonstrated.

METHODS

Eight centers in northeastern Italy participated in a Phase II multicenter study. Chemotherapy was comprised of carboplatin area under the concentration‐time curve 5 on Day 1 and gemcitabine 1000 mg/m2 on Days 1, 8, and 15. This cycle was repeated every 4 weeks.

RESULTS

Between July 1996 and September 2000, 50 patients were treated. Of the sample, 68% were males, 88% had a Eastern Cooperative Oncology Group performance status score of 0–1, 56% had Stage I–II disease, 68% had epithelioid histology, and 62% had no previous treatments. The delivered dose intensity of gemcitabine was 617 mg/m2 per week, which was 82% of the planned dose (750 mg/m2 per week). For carboplatin, the delivered dose intensity was 80 mg/m2 per week. Overall, 44% of 15th day doses were omitted or reduced. Twenty‐six percent of the patients had partial responses (95% confidence interval: 15–40%) and 24% had disease progression. None of the patients had complete responses. The median response duration was 55 weeks (range, 13–113 weeks). Patients had good clinical benefit. For example, 46% had improved dyspnea, 40% improved in weight, and 26% experienced pain reduction. Patients developed Grade 3–4 leukopenia during 18 cycles (11%) of chemotherapy. Grade 3–4 thrombocytopenia occurred more frequently, i.e., there were 24 episodes (15%) among 17 patients. Grade 3 anemia developed among patients during eight cycles (5%). None of the patients developed Grade 3–4 nonhematologic toxicity. The median survival of this sample of patients was 66 weeks with 53%, 30%, and 20% of patients alive at 1, 2, and 3 years, respectively. The median progression‐free survival period was 40 weeks.

CONCLUSIONS

The gemcitabine/carboplatin combination is a valid option in the treatment of MPM due to its acceptable toxicity profile, the good response rate, and the clinical benefit to patients. Minor adjustments in schedule (3‐week cycles instead of 4‐week cycles) would permit a more optimal treatment administration. Cancer 2003;97:2791–7. © 2003 American Cancer Society.

DOI 10.1002/cncr.11405
cDNA microarray analysis of gene expression in pathologic stage IA nonsmall cell lung carcinomas
Authors: Nakamura Haruhiko , Saji Hisashi , Ogata Akihiko , Hosaka Makoto , Hagiwara Masaru , Saijo Takamoto , Kawasaki Norihito , Kato Harubumi
Published: May 2003

BACKGROUND

The relationship between altered gene expression and tumor progression in lung carcinoma has yet to be characterized. Gene expression in pathologic Stage IA nonsmall cell lung carcinoma specimens was analyzed using a cDNA microarray.

METHODS

Surgical specimens were used for the current study. The pathologic stage was IA (AJCC) in five tumors, IB in two, IIA in one, IIIA in one, and IIIB in one. Seven tumor specimens were adenocarcinomas and three were squamous cell carcinomas. Paired mRNAs from carcinoma cells and normal lung tissue specimens from the same lobe were labeled with different fluorochromes during cDNA probe synthesis in a reverse‐transcription reaction. Both synthesized, labeled cDNA probes were mixed and hybridized to the microarray. The signal intensity of each spot was measured by laser scanner and gene expression was quantified as the tumor‐to–normal fluorescence ratio (T:N ratio). The gene was overexpressed when the T:N ratio was greater than 2.0 and underexpressed when the ratio was less than 0.5.

RESULTS

Overall, 40 (9.4%) of the 425 genes evaluated were overexpressed, and 74 genes (17.4%) were underexpressed. In the 5 Stage IA tumor specimens, 31 (7.3%) genes were overexpressed and 76 (17.9%) were underexpressed. For 30 genes (7.1%), expression was different in Stage IA tumor specimens compared with more advanced tumor specimens.

CONCLUSIONS

The cDNA microarray system showed that numerous alterations of gene expression were present in early‐stage nonsmall cell lung carcinoma specimens. Cancer 2003;97:2798–805. © 2003 American Cancer Society.

DOI 10.1002/cncr.11406
Congestive heart failure in patients treated with doxorubicin
Authors: Swain Sandra M. , Whaley Fredrick S. , Ewer Michael S.
Published: May 2003

BACKGROUND

Doxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug. A large‐scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7% of patients developed doxorubicin‐related congestive heart failure (CHF) after a cumulative dose of 550 mg/m2. To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting, the authors evaluated data from three prospective studies to determine both the incidence of doxorubicin‐related CHF and the accumulated dose of doxorubicin at which CHF occurs.

METHODS

A group of 630 patients who were randomized to a doxorubicin‐plus‐placebo arm of three Phase III studies, two studies in patients with breast carcinoma and one study in patients with small cell lung carcinoma, were included in the analysis.

RESULTS

Thirty‐two of 630 patients had a diagnosis of CHF. Analysis indicated that an estimated cumulative 26% of patients would experience doxorubicin‐related CHF at a cumulative dose of 550 mg/m2. Age appeared to be an important risk factor for doxorubicin‐related CHF after a cumulative dose of 400 mg/m2, with older patients (age > 65 years) showing a greater incidence of CHF compared with younger patients (age ≤ 65 years). In addition, > 50% of the patients who experienced doxorubicin‐related CHF had a reduction < 30% in left ventricular ejection fraction (LVEF) while they were on study.

CONCLUSIONS

Doxorubicin‐related CHF occurs with greater frequency and at a lower cumulative dose than previously reported. These findings further indicate that LVEF is not an accurate predictor of CHF in patients who receive doxorubicin. Cancer 2003;97:2869–79. © 2003 American Cancer Society.

DOI 10.1002/cncr.11407
Nausea and emesis remain significant problems of chemotherapy despite prophylaxis with 5‐hydroxytryptamine‐3 antiemetics
Authors: Hickok Jane T. , Roscoe Joseph A. , Morrow Gary R. , King David K. , Atkins James N. , Fitch Tom R.
Published: May 2003

BACKGROUND

Clinical reports suggest that nausea remains a side effect of chemotherapy despite widespread use of serotonin receptor antagonists. This study summarized the frequency, timing, and intensity of postchemotherapy nausea for patients receiving doxorubicin, cisplatin, or carboplatin.

METHODS

Three hundred sixty chemotherapy‐naïve patients (73% female) were enrolled in a study testing the ability of an information intervention to reduce nausea. Of these, 322 subjects completed the Morrow Assessment of Nausea and Emesis (MANE), as well as a 5‐day self‐report diary, at Cycle 1 (300 subjects completed the MANE and self‐report diary at Cycle 2). All patients received a 5‐hydroxytryptamine‐3 receptor antagonist (ondansetron) with dexamethasone on the day of treatment.

RESULTS

Seventy‐six percent of the patients developed nausea during the 5‐day period, beginning with the Cycle 1 infusion, and 73% of patients reported delayed nausea (DN) during Days 2–5. The proportions were similar during Cycle 2. Fifty‐five percent of patients described their DN as being of moderate or greater intensity compared with 28% of patients who described acute nausea. Carboplatin was less likely to cause DN than either of the other agents (56% of 106 patients compared with 75% of 47 receiving cisplatin and 83% of 169 taking doxorubicin). The mean peak DN severity was 4.34 (range, 1–7) for doxorubicin, which was significantly higher than the mean peak value for carboplatin (3.66) but was not significantly different from the mean peak value for cisplatin (4.26). Eighteen percent of patients did not experience nausea until Day 3 or later.

CONCLUSIONS

Despite prophylaxis with ondansetron, the majority of patients receiving one of these common chemotherapy agents experienced nausea. The frequency of DN was nearly twice that of acute nausea. Results show the need for continued development of antiemetics that are effective against DN. Cancer 2003;97:2880–6. © 2003 American Cancer Society.

DOI 10.1002/cncr.11408
Serum S100β
Authors: Kanner Andrew A. , Marchi Nicola , Fazio Vincent , Mayberg Marc R. , Koltz Michael T. , Siomin Vitaly , Stevens Glen H. J. , Masaryk Thomas , Ayumar Barbara , Vogelbaum Michael A. , Barnett Gene H. , Janigro Damir
Published: May 2003

BACKGROUND

S100β protein is expressed constitutively by brain astrocytes. Elevated S100β levels in cerebrospinal fluid and serum reported after head trauma, subarachnoid hemorrhage, and stroke were correlated with the extent of brain damage. Because elevated serum S100β also was shown to indicate blood‐brain barrier (BBB) dysfunction in the absence of apparent brain injury, it remains unclear whether elevation of serum levels of S100β reflect BBB dysfunction, parenchymal damage, or both.

METHODS

The authors conducted a prospective study of serum S100β levels in six patients who underwent hyperosmotic BBB disruption (BBBD) with intraarterial chemotherapy for primary central nervous system lymphoma. In addition, 53 serum S100β samples were measured in 51 patients who had a variety of primary or metastatic brain lesions at the time of neuroimaging.

RESULTS

S100β was correlated directly with the degree of clinical and radiologic signs of BBBD in patients who were enrolled in the hyperosmotic study. In patients with neoplastic brain lesions, gadolinium enhancement on a magnetic resonance image was correlated with elevated S100β levels (n = 45 patients; 0.16 ± 0.1 μg/L; mean ± standard error of the mean) versus nonenhancing scans (n = 8 patients; 0.069 ± 0.04 μg/L). Primary brain tumors (n = 8 patients; 0.12 ± 0.08) or central nervous system metastases also presented with elevated serum S100β levels (n = 27 patients; 0.14 ± 0.34). Tumor volume was correlated with serum S100β levels only in patients with vestibular schwannoma (n = 6 patients; 0.13 ± 0.10 μg/L) but not in patients with other brain lesions.

CONCLUSIONS

S100β was correlated directly with the extent and temporal sequence of hyperosmotic BBBD, further suggesting that S100β is a marker of BBB function. Elevated S100β levels may indicate the presence of radiologically detectable BBB leakage. Larger prospective studies may better determine the true specificity of S100β as a marker for BBB function and as an early detection or follow‐up marker of brain tumors. Cancer 2003;97:2806–13. © 2003 American Cancer Society.

DOI 10.1002/cncr.11409
Long‐term results in elderly patients with differentiated thyroid carcinoma
Authors: Vini Louiza , Hyer Stephen L. , Marshall Jennifer , A'Hern Roger , Harmer Clive
Published: May 2003

BACKGROUND

The authors assessed the biologic behavior of differentiated thyroid carcinoma in patients age 70 years or older and evaluated factors that influenced long‐term survival.

METHODS

Among 1448 patients with differentiated thyroid carcinoma who were treated at the authors' institution over the past 60 years, 111 patients were identified who were age 70 years or older at the time of their initial diagnosis (range, 70–93 years). The authors conducted a retrospective analysis of the outcome of these 111 patients, who had a median follow‐up of 9 years (range, 2–9 years).

RESULTS

There were 83 female patients and 28 male patients (female to male ratio, 3:1). Fifty‐eight tumors were papillary, 46 tumors were follicular, and 7 tumors were Hürthle cell carcinoma. Eighty percent of patients presented with a thyroid mass, and 70% of tumors were pathologic stage T3 (pT3) or pT4. Lymph node disease was evident at presentation in 44% of patients, and distant metastases were documented at diagnosis in 23% of patients. Forty‐six patients underwent total thyroidectomy, and the remaining patients underwent subtotal thyroidectomy or biopsy only. Radioiodine was administered to 80 patients, and external beam radiotherapy was administered to 19 patients. The cause specific survival rates were 75%, 50%, and 50% at 5 years, 10 years, and 15 years, respectively. Multivariate analysis showed that the presence of metastases was the most important independent prognostic factor for survival. External beam radiotherapy was associated with a poorer prognosis, in that it was reserved for patients with either inoperable disease or residual disease after surgery and patients with no uptake of radioiodine.

CONCLUSIONS

A large proportion of thyroid tumors showed extrathyroid spread and distant metastases, which frequently were not iodine‐avid. The prevalent histologic type was papillary, often with features of poor differentiation. Thyroid carcinoma in the elderly appears to behave more aggressively, and they have a less favorable prognosis compared with younger adults. Cancer 2003;97:2736–42. © 2003 American Cancer Society.

DOI 10.1002/cncr.11410
Racial disparities in breast carcinoma survival rates
Authors: Chu Kenneth C. , Lamar Charisee A. , Freeman Harold P.
Published: May 2003

BACKGROUND

Black females have lower breast carcinoma survival rates compared with white females. One possible reason is that black females have more advanced‐stage breast disease. Another factor may be racial differences in the utilization of cancer treatments.

METHODS

The authors determined racial differences in 6‐year stage specific survival rates, adjusting for age and treatments (using estrogen receptor [ER] status), to determine whether there were racial differences in treatment. Racial differences in the stage distributions of breast disease were used to examine the impact of racial factors on breast carcinoma diagnosis.

RESULTS

For all breast carcinoma cases, the stage specific 6‐year survival rates, in general, were significantly lower for black females for all stages combined and for Stages I–III in every age group. However, examination by different treatments, as measured by ER status, revealed some different results. Only black women younger than age 50 years with ER‐positive tumors and women younger than age 65 years with ER‐negative tumors had significantly lower stage‐specific survival rates. In addition, the stage distribution analyses showed that black females of every age group had less Stage I breast disease.

CONCLUSIONS

For younger black women (younger than age 50 years), there was evidence of racial differences in treatment for both women with ER‐positive tumors and women with ER‐negative tumors, as indicated by their lower stage‐specific survival rates. In contrast, for black females age 65 years or older with ER‐positive or ER‐negative tumors, the lack of a significant difference in the stage‐specific survival rate suggests that Medicare may help to alleviate racial disparities in cancer treatment. Furthermore, racial differences in the stage distributions indicated the need for earlier diagnosis for black females of every age. cancer 2003;97:2853–60. Published 2003 American Cancer Society.

DOI 10.1002/cncr.11411
Phase II trial of gemcitabine and docetaxel in patients with advanced carcinoma of the urothelium
Authors: Dreicer Robert , Manola Judith , Schneider Daniel J. , Schwerkoske John F. , George Christopher S. , Roth Bruce J. , Wilding George
Published: May 2003

BACKGROUND

Gemcitabine and docetaxel are active agents in advanced urothelial carcinoma. A Phase II trial of this combination was performed to determine the activity and toxicity of these agents in a multiinstitutional setting in patients previously treated with one prior chemotherapy regimen.

METHODS

Twenty‐nine eligible patients with advanced urothelial carcinoma were treated with docetaxel at a dose of 40 mg/m2 over 1 hour followed by gemcitabine, 800 mg/m2, over 30 minutes, both intravenously (i.v.) on Days 1 and 8. Cycles were repeated every 21 days until disease progression or a maximum of 6 cycles.

RESULTS

Five patients obtained an objective response for an overall response rate of 17% (90% confidence interval, 7–33%). One patient achieved a complete clinical response. The median overall survival of the group was 7.7 months. Toxicity was moderate with granulocytopenia, anorexia, and fatigue being the most commonly noted side effects.

CONCLUSIONS

Gemcitabine and docetaxel is an active second‐line combination in patients with advanced urothelial carcinoma. Responses in visceral, lymph node, and soft tissues sites were observed. Granulocytopenia without fever, fatigue, and anorexia was common. Thromboembolic symptoms were reported and are of concern. The combination of gemcitabine and docetaxel has the potential to palliate a subset of previously treated patients with an adequate performance status. Cancer 2003;97:2743–7. © 2003 American Cancer Society.

DOI 10.1002/cncr.11413
Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high‐risk myelodysplastic syndrome, and myeloproliferative disorders
Authors: Cortes Jorge , Giles Francis , O'Brien Susan , Thomas Deborah , Albitar Maher , Rios Mary Beth , Talpaz Moshe , Garcia‐Manero Guillermo , Faderl Stefan , Letvak Laurie , Salvado August , Kantarjian Hagop
Published: May 2003

BACKGROUND

Imatinib mesylate is a selective tyrosine kinase inhibitor of c‐abl, bcr/abl, c‐kit, and platelet‐derived growth factor‐receptor (PDGF‐R). c‐kit is expressed in most patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) and PDGF has been implicated in the pathogenesis of myeloproliferative disorders (MPD).

METHODS

The authors investigated the efficacy of imatinib in patients with these disorders. Forty‐eight patients with AML (n = 10), MDS (n = 8), myelofibrosis (n = 18), atypical chronic myeloid leukemia (CML; n = 7), chronic myelomonocytic leukemia (CMML; n = 3), or polycythemia vera (n = 2) were treated with imatinib 400 mg daily.

RESULTS

None of the patients with AML or MDS responded. Among patients with myelofibrosis, 10 of 14 patients with splenomegaly (71%) had a 30% or greater reduction in spleen size, 1 patient had trilineage hematologic improvement, 2 had erythroid hematologic improvement, and 1 had improvement in platelet count. One patient with atypical CML had erythroid hematologic improvement. Both patients with polycythemia vera needed fewer phlebotomies (from 2–3 per year to none during the 8 months of therapy and from 3–6 per year to 1 during 9 months of therapy). None of the three patients with CMML responded. Treatment was well tolerated. The side effects were similar to those observed in patients with CML.

CONCLUSIONS

Within these small subgroups of disease types, single‐agent imatinib did not achieve a significant clinical response among patients with AML, MDS, atypical CML, or CMML without PDGF‐R fusion genes. Preliminary data on polycythemia vera are promising and deserve further investigation. Responses among myelofibrosis patients were minor. Therefore, a combination treatment regimen including imatinib may be more effective. Cancer 2003;97:2760–6. © 2003 American Cancer Society.

DOI 10.1002/cncr.0000
Analysis of P‐glycoprotein–mediated membrane transport in human peripheral blood lymphocytes using the UIC2 shift assay
Authors: Park Suk W. , Lomri Noureddine , Simeoni Luiz A. , Fruehauf John P. , Mechetner Eugene
Published: May 2003

Background

During transport‐associated adenosine triphosphate hydrolysis, P‐glycoprotein (Pgp) undergoes conformation transitions detected by UIC2, a functional anti‐Pgp monoclonal antibody. A newly developed UIC2 shift assay is based on increased UIC2 reactivity in the presence of Pgp substrates. All peripheral blood leukocytes express low Pgp levels. The existing antibody‐based detection methods are limited in their sensitivity and require additional techniques to simultaneously analyze Pgp expression and efflux, making it difficult to ascertain the physiologic role of Pgp‐mediated transport.

Methods

We validated the UIC2 shift assay against UIC2 immunostaining and DiOC2 efflux. The UIC2 shift assay was then used to characterize Pgp functional expression and its physiologic substrates in peripheral blood leukocytes.

Results

A strong correlation was observed between the UIC2 shift assay versus immunostaining and dye efflux tests. The UIC2 shift assay showed improved sensitivity (compared with conventional UIC2 staining) and allowed for simultaneous detection of Pgp expression and function. Using this assay, we identified several new Pgp substrates, including monensin and retinol, and confirmed that interleukin‐2 and interferon‐γ can be transported by Pgp.

Conclusions

Our findings validate the use of the UIC2 shift assay in MDR1 detection and support the idea that Pgp plays a physiologic role in immunoregulation. Cytometry Part A 53A:67–78, 2003. © 2003 Wiley‐Liss, Inc.
Serodiagnosis of human plague by a combination of immunomagnetic separation and flow cytometry
Authors: Splettstoesser W.D. , Grunow R. , Rahalison L. , Brooks T.J. , Chanteau S. , Neubauer H.
Published: May 2003

Background

Plague is a severe, highly communicable bacterial disease caused by Yersinia pestis. It is still endemic in more than 20 countries worldwide. Although known as a devastating disease for centuries, laboratory confirmation of clinical suspected cases is still problematic. No standardized and internationally approved test system is commercially available. The aim of this study was the introduction and evaluation of a combination of immunomagnetic separation and flow cytometry for the serodiagnosis of human plague.

Methods

Paramagnetic polystyrene beads were coated with purified F1 capsular antigen (F1 CA) and reacted with sera from plague patients, from 26 laboratory personnel vaccinated against plague and from 102 healthy blood donors (HBD). After incubation with fluorescein isothiocyanate–conjugated anti‐human rabbit IgG, particle‐associated fluorescence was detected by flow cytometry.

Results

Anti‐F1 CA antibodies could be demonstrated in all patients with bacteriologically confirmed plague and in 22 sera (84.6%) from vaccinees. Only one serum in the HBD group showed a weakly positive reaction. The total assay time was less than 2 h.

Conclusions

Compared with a recently published combination of an anti‐F1 CA enzyme‐linked immunosorbent assay (ELISA) and immunoblot, the new assay showed the same sensitivity as the ELISA and almost the same specificity (99.0 versus 100%) as the immunoblot. Allowing a rapid, reliable, and quantitative analysis, immunomagnetic separation combined with flow cytometry might replace both conventional immunoassays. Cytometry Part A 53A:88–96, 2003. © 2003 Wiley‐Liss, Inc.
Human peripheral B cells: A different cytometric point of view
Authors: Carbonari Maurizio , Tedesco Tiziana , Fiorilli Massimo
Published: May 2003

Background

Human peripheral B lymphocytes, analyzed by current flow cytometers, frequently show complex patterns of morphological and fluorescence signals. However, fluorescence intensity values are commonly reported without any correlation to the cell surface area. We propose a different approach, based on the evaluation of the ratio of phenotype fluorescence intensity to forward scatter intensity, to determine the apparent fluorescence density of surface molecules.

Methods

Starting from list mode acquired data, and after logical gating of live B cells, the analytical procedure suggests a serial scanning of the FSC versus SSC plot to obtain apparent fluorescence density of progressively larger cells.

Results

This method, applied to normal human peripheral B lymphocytes, was able to detect the presence of steady and modulated (with respect to cell size) fluorescence densities for a variety of surface molecules. B cells from patients with B cell disorders displayed interesting alterations of the phenotype density values and distributions.

Conclusions

Our preliminary data show that, in human B cell cytometry, the apparent fluorescence density based method allows one to recognize variations in fluorescence intensities solely due to cell size differences and to disclose patterns of expression not detectable by the conventional intensity based approach. Cytometry Part A 53A:97–102, 2003. © 2003 Wiley‐Liss, Inc.
New flow cytometric method to quantify the inhibition of enteropathogenic Escherichia coli adhesion by anti‐adhesin antibodies
Authors: Boullier Séverine , Tasca Christian , Milon Alain
Published: May 2003

Background

Pathogenesis of enteropathogenic Escherichia coli (EPEC) infections can be divided in three stages. The first one is the intestinal colonization mediated by bacterial adhesins. The second and third stages are characterized by an intimate attachment of bacteria to the enterocytes. Little information is available on the specific immune response against EPEC. Here, we describe and validate a new approach to quantify the function of anti‐EPEC adhesin antibodies (Abs).

Methods

We developed a new method to quantify the function of anti‐adhesin Abs by flow cytometry. We used pEGFP‐E22 (a rabbit EPEC E22 strain expressing the GFP protein) and HeLa cells. The adhesion of E22 bacteria to HeLa cells is mediated by AF/R2, the specific E22 adhesin. We performed short‐time interaction (30 min) between pEGFP‐E22 and HeLa cells. After extensive washes, 10,000 HeLa cells were acquired by flow cytometry and bacterial adhesion was quantified. Different sera were used to inhibit bacterial adhesion and recombinant MPB‐Afr2G (Afr2G is the main AF/R2 subunit) was also tested in this system.

Results

We first verified that GFP expression by E22 did not modify bacterial adhesion. We then showed that this flow cytometry approach allowed easy quantification of bacterial adhesion and inhibition mediated by a specific anti‐AF/R2 serum. Moreover, recombinant AF/R2 protein reversed the effect of the anti‐AF/R2 serum. Finally, we validated our method using sera from E22 orally infected rabbits. We detected and quantified with this method functional specific anti‐AF/R2 Abs in their sera. In addition, we correlated our results with an anti‐AF/R2 enzyme‐linked immunosorbent assay.

Conclusions

We have developed a new method to detect and quantify specific anti‐EPEC adhesin Abs by flow cytometry. This method is easy to use and highly reproducible. Its development could be extended to the search of specific anti‐adhesin Abs in human EPEC infections. Cytometry Part A 53A:79–87, 2003. © 2003 Wiley‐Liss, Inc.
Effects of resolution reduction on data analysis
Authors: Hunsberger B. , Bagwell C. B. , Herbert D. , Bray C. , Langweiler M.
Published: May 2003

Background

There is often a need in flow cytometry to display and analyze histograms at resolutions lower than those native to the data. It is common, for example, to analyze DNA histograms at 256‐channel resolution, even though the data were acquired at 1,024 channels or more. The most common method for reducing resolution, referred to as the consecutive summation (CS) method, can introduce distortions into the shape of histograms. Peaks that were symmetric in the original data can become skewed in the reduced‐resolution histogram. Data analysis can be negatively affected by the distortions produced by reducing the histogram resolution. An alternative technique for reducing histogram resolution, the unbiased summation (US) method, minimizes shape distortion. This paper describes the US method and examines the benefits it provides in the analysis of DNA histograms.

Methods

Reduced chi‐square (RCS) was used to measure the response to three experimental variables in the least‐squares analysis of simulated DNA histograms. For each variable (the percentage of coefficient of variation [%CV], number of events, and mean position of the G1 distribution), a test data set of 1,000 histograms was generated at 1,024‐channel resolution. Histogram resolutions were reduced with each method and then analyzed with ModFit LT cell‐cycle analysis software (Verity Software House, Topsham, ME). S‐phase error and processor computation time of each method also were evaluated. A Monte Carlo experiment was performed to compare CS and US methods to theoretically correct reductions.

Results

CS method analysis results were negatively affected by changes in %CV, number of events, and G1 peak position. The US method produced consistently lower RCS values (more accurate results) within the tested ranges. The US method eliminated bias in S‐phase error and had negligible impact on analysis processing speed. It improved RCS values 44.50% on average (P < 0.0002) with actual DNA histograms. Whereas the CS method became less accurate (chi‐square test) as the amount of reduction increased, the US method was unaffected, producing consistently better results.

Conclusions

The US method is recommended for reducing histogram resolution in modeling applications such as DNA cell‐cycle analysis. It may have implications in other areas of flow cytometric data analysis. Cytometry Part A 53A:103–111, 2003. © 2003 Wiley‐Liss, Inc.
Is core needle biopsy superior to fine‐needle aspiration biopsy in the diagnosis of papillary breast lesions?
Authors: Masood Shahla , Loya Asif , Khalbuss Walid
Published: May 2003

Since the 1980s core needle biopsy (CNB) has gained remarkable popularity and in many institutions it has replaced fine‐needle aspiration biopsy (FNAB). However, similar to FNAB, limitation remains in the ability of this procedure to reliably diagnose a small, but prognostically significant, number of breast lesions. These include entities such as atypical ductal hyperplasia, fibro‐epithelial tumors, radial scar, papillary lesions, and lobular neoplasia. To assess the diagnostic accuracy of CNB vs. FNAB in the same breast lesions, we reviewed our cases of papillary lesions of the breast. In a retrospective study, we identified 36 cases of FNAB and 11 cases of CNB diagnosed as papillary lesions and compared the results with their corresponding surgical specimen. Interpretation ranged from papillary vs. atypical papillary lesions favoring benign vs. malignant tumors, respectively. Occasionally, definitive diagnosis of papillary carcinoma was entertained. Immunohistochemical staining with smooth muscle actin was used to evaluate the presence or absence of a myoepithelial cell layer. FNAB had benign findings in 21 lesions, atypical in 10, and malignant in five. Of the five lesions yielding malignant features, four had invasive carcinoma and one had micropapillary ductal carcinoma in situ (DCIS). Surgery revealed invasive carcinoma in three of the cases interpreted as atypical papillary lesions and invasive cancer and micropapillary DCIS in three of the cases diagnosed as benign lesions. Similar results were obtained with CNB. DCIS was found in one out of six of the cases diagnosed as papilloma. Out of the four cases that were interpreted as atypical papillary lesion, surgery revealed invasive carcinoma in one case and one case had micropapillary DCIS. Diagnosis of malignancy was confirmed by histology in one case interpreted as papillary carcinoma by CNB. This study suggested that both FNAB and CNB share similar diagnostic challenges and a follow‐up surgical excision is indicated when diagnosis of a papillary lesion is entertained by both procedures. Diagn. Cytopathol. 2003;28:329–334. © 2003 Wiley‐Liss, Inc.
Cytoplasmic vacuolation, intracytoplasmic lumina, and DPAS staining in ductal carcinoma of the breast
Authors: Nijhawan Raje , Rajwanshi Arvind , Gautam Upasana , Gupta Subhash K.
Published: May 2003

A retrospective study was carried out on 30 cases of histologically proven invasive ductal carcinoma of the breast with a prior fine‐needle aspiration (FNA) cytology. On evaluating the May‐Grünwald‐Giemsa (MGG) FNA smears, cytoplasmic vacuolation was observed in 70% cases. Positivity with periodic acid Schiff‐positive, diastase‐resistant (DPAS) staining was observed in 90% of cases. The χ2 value on a McNemar test was 4.16. Thus, DPAS staining was significantly superior to MGG staining for picking up cytoplasmic vacuoles (P < 0.05). In 56.67% cases, DPAS staining showed an improvement in score as compared to MGG smears. This was highly significant (P < 0.001) on Wilcoxon matched‐pairs signed‐ranks test. Applying the strict criteria of thick‐walled cytoplasmic vacuoles with a central darkly stained dot, none of our cases revealed true intracytoplasmic lumina. Larger studies are required to establish a role for DPAS staining in separating borderline, in situ, and invasive breast lesions, and to see if such positvity can be incorporated into the grading systems for breast carcinoma. Diagn. Cytopathol. 2003;28:291–294. © 2003 Wiley‐Liss, Inc.
Melanoma of the soft parts: Diagnosis of metastatic and recurrent tumors by aspiration cytology
Authors: Kumar Neeta , Das Partha M. , Jain Shyama , Sodhani Pushpa , Gupta Sanjay
Published: May 2003

Three cases of melanoma of the soft parts diagnosed by aspiration cytology and immunochemistry are described. Unusual clinicoradiological features, variable cytomorphology, absence of melanin, and lack of awareness due to rarity of the lesion caused diagnostic dilemma. Morphological similarity to alveolar soft part sarcoma, synovial and epithelioid sarcoma, cutaneous melanoma, poorly differentiated carcinoma, and plasmacytoma were noted. Consideration of clinical data such as age, site, and radiology was helpful in narrowing down the diagnosis. A presumptive cytologic diagnosis helped in selecting the antibody panel, which established the definitive diagnosis in all cases. This approach is valuable in preoperative management and obviates the need for an open biopsy in primary, metastatic, or recurrent tumor. Increasing experience in fine‐needle aspiration of this rare entity and correlation with immunochemistry and histopathology are valuable in narrowing down the differential diagnosis, reducing diagnostic errors, and widening its clinicocytological spectrum. Diagn. Cytopathol. 2003;28:295–300. © 2003 Wiley‐Liss, Inc.