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Cancer

Cover image for Cancer

15 July 2003

Volume 98, Issue 2

Pages 215–435

  1. Ethics and Law in Oncology

    1. Top of page
    2. Ethics and Law in Oncology
    3. Editorial
    4. Original Articles
    5. Correspondence
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      Potential conflict between fundamental ethical principles and requirements of the oncology drug approval process : Ethical conflict in drug approval (pages 215–218)

      Maurie Markman and Joseph DeMarco

      Article first published online: 10 JUN 2003 | DOI: 10.1002/cncr.11566

      The process required to achieve federal regulatory approval of new anticancer agents has the potential to be in serious conflict with fundamental principles inherent in the ethical design of randomized controlled clinical trials.

  2. Editorial

    1. Top of page
    2. Ethics and Law in Oncology
    3. Editorial
    4. Original Articles
    5. Correspondence
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      Hyperthermia and its modern use in cancer treatment (pages 219–221)

      H. Richard Alexander Jr.

      Article first published online: 20 MAY 2003 | DOI: 10.1002/cncr.11471

      In the current issue, Jones et al. have demonstrated that treatment of advanced cervical carcinoma with concurrent hyperthermia, chemotherapy, and radiotherapy is well tolerated and associated with significant efficacy. Although Jones et al. rightly speculate on the connection between experimental and clinical data regarding the antineoplastic role of hyperthermia, it is not clear that the experimental results are relevant to the clinical findings. More than 100 years after the discovery of hyperthermia's activity against advanced cervical carcinoma, the mechanism of this activity and the optimal strategy for harnessing it have yet to be uncovered.

  3. Original Articles

    1. Top of page
    2. Ethics and Law in Oncology
    3. Editorial
    4. Original Articles
    5. Correspondence
    1. Disease Site

      Breast Disease
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      Targeted filgrastim support in patients with early-stage breast carcinoma : Toward the implementation of a risk model (pages 222–228)

      Edgardo Rivera, M. Haim Erder, Timothy D. Moore, Thomas L. Shiftan, Chris A. Knight, Moshe Fridman, Carol Brannan, Laurence Danel-Moore, Gabriel N. Hortobagyi and for the Risk Model Study Group

      Article first published online: 2 JUN 2003 | DOI: 10.1002/cncr.11516

      Breast carcinoma is reportedly the most common cancer diagnosed in women in the U.S. Early-stage breast carcinoma accounts for nearly two-thirds of all new diagnoses. The current standard of care for patients with early-stage breast carcinoma comprises of breast-conserving surgery, local radiation therapy, hormonal therapy, and systemic adjuvant chemotherapy. To the authors' knowledge, the current study is the first large prospective validation of a risk model performed in patients with early-stage breast carcinoma to examine the utility of filgrastim.

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      Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women : A prospective combined analysis of two multicenter trials (pages 229–238)

      John F. R. Robertson, C. Kent Osborne, Anthony Howell, Stephen E. Jones, Louis Mauriac, Matthew Ellis, Ulrich R. Kleeberg, Steven E. Come, Ignace Vergote, Stan Gertler, Aman Buzdar, Alan Webster and Charles Morris

      Article first published online: 2 JUN 2003 | DOI: 10.1002/cncr.11468

      A prospectively designed combined analysis of data from two Phase III trials demonstrated that the estrogen receptor antagonist fulvestrant was at least as effective as the aromatase inhibitor anastrozole in the treatment of advanced breast carcinoma in postmenopausal women who had progressed on prior antiestrogen therapy. Fulvestrant and anastrozole were similarly well tolerated. Fulvestrant therefore provides an additional option in the treatment of patients with advanced breast carcinoma.

    3. Endocrine Disease
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      High-dose 131I-metaiodobenzylguanidine therapy for 12 patients with malignant pheochromocytoma (pages 239–248)

      Brian Rose, Katherine K. Matthay, David Price, John Huberty, Barbara Klencke, Jeffrey A. Norton and Paul A. Fitzgerald

      Article first published online: 17 JUN 2003 | DOI: 10.1002/cncr.11518

      Twelve patients with malignant pheochromocytoma or paraganglioma were treated with median single and cumulative 131I-Metaiodobenzylguanidine (131I-MIBG) doses of 800 millicuries (mCi; range, 386–866 mCi) and 1015 mCi (range, 386–1690 mCi), respectively. Complete or partial responses were seen in 10 of 12 patients. Eight patients are alive at a median follow-up of 45 months (range, 23–101 months), including 4 with stable disease, 1 with progressive disease, and 3 with complete responses. Grade 3 thrombocytopenia and Grade 4 neutropenia followed 79% (15 of 19 patients) and 19% (4 of 19 patients) of 131I-MIBG treatments, respectively. Of 12 patients, 3 have sustained complete responses. Therefore, further efforts are warranted to improve the effectiveness of 131I-MIBG therapy for patients with malignant pheochromocytoma.

    4. Gastrointestinal Tract
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      Prospective study of the ability of serial measurements of serum chromogranin A and gastrin to detect changes in tumor burden in patients with gastrinomas (pages 249–261)

      Alaa Abou-Saif, Fathia Gibril, Jeremiah V. Ojeaburu, Showkat Bashir, Laurence K. Entsuah, Behnam Asgharian and Robert T. Jensen

      Article first published online: 28 MAY 2003 | DOI: 10.1002/cncr.11473

      Few studies have assessed the value of serial chromogranin A (CgA) levels in assessing changes in tumor burden in patients with neuroendocrine tumors. This study of 72 patients with gastrinomas showed that both serial CgA levels and gastrin levels were relatively insensitive markers of smaller, clinically important changes in tumor burden.

    5. Genitourinary Disease
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      High expression of cathepsin B in transitional bladder carcinoma correlates with tumor invasion (pages 262–268)

      Ana M. Eiján, Eduardo O. Sandes, María D. Riveros, Sebastián Thompson, Leonardo Pasik, Hector Mallagrino, Francisco Celeste and Alberto R. Casabé

      Article first published online: 5 JUN 2003 | DOI: 10.1002/cncr.11493

      In the current study, the authors demonstrated that cathepsin B (CB)—a lysosomal cysteine proteinase—is involved in the progression of transitional bladder carcinoma progression. No changes in CB localization, as determined by immunohistochemical staining, were observed between tumor and nontumor tissue. However, higher expression of CB was observed in bladder tumors. Furthermore, whereas normal bladder tissue only expressed the 29-kilodalton (kD) CB form, tumor and nontumor bladder tissue from transitional bladder tumor patients expressed CB forms of 27 kD and 29 kD.

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      Phase II trial of paclitaxel, estramustine, etoposide, and carboplatin in the treatment of patients with hormone-refractory prostate carcinoma (pages 269–276)

      David C. Smith, Christopher H. Chay, Rodney L. Dunn, Jude Fardig, Peg Esper, Karin Olson and Kenneth J. Pienta

      Article first published online: 5 JUN 2003 | DOI: 10.1002/cncr.11494

      In this clinical trial, the authors studied the effect of adding carboplatin to the combination of paclitaxel, estramustine, and etoposide (TEE) in the treatment of patients with hormone-refractory prostate carcinoma. Although carboplatin did not appear to add to the efficacy of TEE, the combination was tolerated well.

    7. Gynecologic Oncology
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      A pilot Phase II trial of concurrent radiotherapy, chemotherapy, and hyperthermia for locally advanced cervical carcinoma (pages 277–282)

      Ellen L. Jones, Thaddeus V. Samulski, Mark W. Dewhirst, Angeles Alvarez-Secord, Andrew Berchuck, Daniel Clarke-Pearson, Laura J. Havrilesky, John Soper and Leonard R. Prosnitz

      Article first published online: 10 JUN 2003 | DOI: 10.1002/cncr.11475

      Twelve patients with either locally advanced cervical carcinoma (LACC; n = 10) or locally recurrent cervical carcinoma following hysterectomy (n = 2) were treated with concurrent hyperthermia, chemotherapy, and radiotherapy. All 10 patients with LACC achieved clinical complete responses and local control; 2 eventually developed extrapelvic recurrences. For the entire study group, the initial complete response and local control rates were 92% and 83%, respectively, and treatment was well tolerated. This thermochemoradiotherapeutic treatment strategy shows considerable promise and warrants additional study to verify its efficacy.

      See also pages 219–21.

    8. Head and Neck Disease
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      18-Fluoro-2-deoxyglucose positron emission tomography in detecting residual/recurrent nasopharyngeal carcinomas and comparison with magnetic resonance imaging (pages 283–287)

      Ruoh-Fang Yen, Rey-Long Hung, Mei-Hsiu Pan, Yao-Hung Wang, Kou-Mou Huang, Louis T. Lui and Chia-Hung Kao

      Article first published online: 12 JUN 2003 | DOI: 10.1002/cncr.11519

      The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) images were 100%, 93.4%, 95.5%, 87.5%, and 100%, respectively. The results of the current study suggest that FDG-PET is much more effective in detecting residual/recurrent nasopharyngeal carctinomas than magnetic resonance imaging.

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      Pretherapy quantitative measurement of circulating Epstein–Barr virus DNA is predictive of posttherapy distant failure in patients with early-stage nasopharyngeal carcinoma of undifferentiated type (pages 288–291)

      Sing-fai Leung, Anthony T. C. Chan, Benny Zee, Brigette Ma, Lisa Y. S. Chan, Philip J. Johnson and Y. M. Dennis Lo

      Article first published online: 28 MAY 2003 | DOI: 10.1002/cncr.11496

      Within the group of patients with International Union Against Cancer Stage I–II nasopharyngeal carcinoma, the pretherapy quantification of circulating Epstein–Barr virus DNA identifies a poor risk group with a probability of distant failure similar to that of patients with advanced stage disease. This group of patients may require management considerations that currently are applicable only to Stage III–IV disease.

    10. Hematologic Malignancies
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      Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies (pages 292–299)

      Dimitrios P. Kontoyiannis, Ray Hachem, Russell E. Lewis, Gustavo A. Rivero, Harrys A. Torres, John Thornby, Richard Champlin, Hagop Kantarjian, Gerald P. Bodey and Issam I. Raad

      Article first published online: 27 MAY 2003 | DOI: 10.1002/cncr.11479

      Caspofungin as salvage therapy for refractory invasive aspergillosis (IA) (CAS) had a 45% response rate among a heterogeneous group of patients. The use of CAS with other agents is appealing given its unique mechanism of action. The CAS/ liposomal amphotericin B combination is a promising preemptive therapy for IA and might have limited benefit as a salvage therapy for documented IA.

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      Population-based patterns of human immunodeficiency virus-related Hodgkin lymphoma in the Greater San Francisco Bay Area, 1988–1998 (pages 300–309)

      Sally L. Glaser, Christina A. Clarke, Margaret L. Gulley, Fiona E. Craig, Joseph A. DiGiuseppe, Ronald F. Dorfman, Risa B. Mann and Richard F. Ambinder

      Article first published online: 28 MAY 2003 | DOI: 10.1002/cncr.11459

      In population-based data from 1988–1998 for the Greater San Francisco Bay Area, patients with human immunodeficiency virus (HIV)-related Hodgkin lymphoma (n = 128 patients) had distinctive demographic features (male gender, black race/ethnicity, young-adult age, San Francisco residence), clinical and histologic characteristics of more aggressive disease, greater association with Epstein–Barr virus, and poorer survival, contributing to elevations in regional Hodgkin lymphoma incidence rates, particularly among young adults. With the availability of antiretroviral therapies, patients with HIV-related Hodgkin lymphoma appear to have clinically less aggressive disease and have better survival.

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      A pilot study of rituximab in patients with recurrent, classic Hodgkin disease (pages 310–314)

      Anas Younes, Jorge Romaguera, Frederick Hagemeister, Peter McLaughlin, Maria Alma Rodriguez, Paolo Fiumara, Andre Goy, Sima Jeha, John T. Manning Jr., Dan Jones, Lynne V. Abruzzo and L. Jeffrey Medeiros

      Article first published online: 5 JUN 2003 | DOI: 10.1002/cncr.11511

      The authors investigated the role of benign B cells in Hodgkin disease lesions in supporting the survival of malignant Reed–Sternberg cells. The results of this pilot study showed that rituximab induced clinical remissions in patients with recurrent, classic Hodgkin disease, presumably by depleting benign B cells.

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      Outcome predictors of 84 patients with hematologic malignancies and Fusarium infection (pages 315–319)

      Marcio Nucci, Elias J. Anaissie, Flavio Queiroz-Telles, Carlos A. Martins, Plínio Trabasso, Cristiana Solza, Claudia Mangini, Belinda P. Simões, Arnaldo L. Colombo, Jorge Vaz, Carlos E. Levy, Silvia Costa, Vaneusa A. Moreira, José Salvador Oliveira, Nestor Paraguay, Gisele Duboc, Julio C. Voltarelli, Angelo Maiolino, Ricardo Pasquini and Cármino A. Souza

      Article first published online: 12 JUN 2003 | DOI: 10.1002/cncr.11510

      The authors assessed prognostic factors in 84 patients with hematologic diseases and invasive fusariosis. Multivariate predictors of poor outcome were persistent neutropenia and use of corticosteroids. Measures to reduce the duration of neutropenia, as well as the judicious use of corticosteroids, may reduce the high mortality rate of fusariosis in patients with hematologic carcinoma.

    14. Hepatobiliary Disease
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      Hepatic cryotherapy and regional chemotherapy with or without resection for liver metastases from colorectal carcinoma : How many are too many? (pages 320–330)

      Dong Bo Yan, Philip Clingan and David L. Morris

      Article first published online: 12 JUN 2003 | DOI: 10.1002/cncr.11498

      In patients with hepatic metastases from colorectal carcinoma, the numbers of metastases were not prognostic of survival when all hepatic lesions were resected or ablated.

    15. Lung Disease
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      High-dose ifosfamide with mesna and granuloctye–colony-stimulating factor (recombinant human G-CSF) in patients with unresectable malignant mesothelioma : A Southwest Oncology Group study (pages 331–336)

      Susan M. Talbot, Cathryn Rankin, Robert N. Taub, Stanley P. Balcerzak Jr., Nirmala Bhoopalam, Robert A. Chapman, Laurence H. Baker, Edward L. Middleman and Karen H. Antman

      Article first published online: 2 JUN 2003 | DOI: 10.1002/cncr.11512

      A study of the activity and toxicity of high-dose ifosfamide and mesna with recombinant human granulocyte–colony-stimulating factor in patients with unresectable malignant mesothelioma, given in an outpatient setting, was performed. This regimen demonstrated a low overall objective response rate with substantial toxicity, and in the authors' opinion does not warrant further investigation in the treatment of unresectable malignant mesothelioma.

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      Prolonged gemcitabine infusion in advanced non–small cell lung carcinoma : A randomized Phase II study of two different schedules in combination with cisplatin (pages 337–343)

      Anna Ceribelli, Cesare Gridelli, Filippo De Marinis, Alessandra Fabi, Teresa Gamucci, Enrico Cortesi, Maria Barduagni, Mauro Antimi, Paolo Maione, Maria R. Migliorino, Diana Giannarelli and Francesco Cognetti

      Article first published online: 5 JUN 2003 | DOI: 10.1002/cncr.11501

      This randomized Phase II trial showed that cisplatin plus gemcitabine with gemcitabine at fixed infusion rate (10 mg/m2 per minute) is active and well tolerated in advanced non–small cell lung carcinoma.

    17. Melanoma
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      Symptoms and signs of primary melanoma : Important indicators of Breslow depth (pages 344–348)

      Benjamin P. Negin, Elyn Riedel, Susan A. Oliveria, Marianne Berwick, Daniel G. Coit and Mary S. Brady

      Article first published online: 16 JUN 2003 | DOI: 10.1002/cncr.11513

      Understanding the signs and symptoms of primary melanoma can be valuable in guiding therapy, especially when pathologic data are confusing or incomplete. In a prospective study, the authors found a strong association between the presence and number of signs/symptoms and increasing Breslow depth of the primary melanoma.

    18. Neuro-Oncology
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      Neuroblastoma in adolescents (pages 349–355)

      Nathalie Gaspar, Olivier Hartmann, Caroline Munzer, Christophe Bergeron, Frédéric Millot, Lucie Cousin-Lafay, Annie Babin-Boilletot, Pascale Blouin, Christine Pajot and Carole Coze

      Article first published online: 6 JUN 2003 | DOI: 10.1002/cncr.11521

      Adolescent patients with advanced neuroblastoma (Stage III–IV) fared worse than children, even though adolescents with Stage III disease appeared to have a longer survival time. Adolescent patients may benefit from a more intensive or innovative therapeutic approach and from larger biologic studies on tumor tissue to ascertain why their outcomes are particularly poor.

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      Management of brain metastases from thyroid carcinoma : A study of 16 pathologically confirmed cases over 25 years (pages 356–362)

      Robert R. McWilliams, Caterina Giannini, Ian D. Hay, John L. Atkinson, Scott L. Stafford and Jan C. Buckner

      Article first published online: 2 JUN 2003 | DOI: 10.1002/cncr.11488

      In the current study, the authors report what to their knowledge is the largest case series reported to date of biopsy proven thyroid carcinoma metastatic to the brain. Surgical intervention, radiosurgery, external beam radiation, and radioiodine therapy are discussed, and each appears to play a role in the management of this disease.

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      Brain metastasis from prostate carcinoma : The M. D. Anderson Cancer Center experience (pages 363–368)

      Ivo W. Tremont-Lukats, George Bobustuc, George K. Lagos, Konstantinos Lolas, Athanassios P. Kyritsis and Vinay K. Puduvalli

      Article first published online: 12 JUN 2003 | DOI: 10.1002/cncr.11522

      The authors retrospecitively reviewed their database to identify patients with prostate carcinoma who had craniospinal metastases in order to determine the clinical and radiologic features, the treatment used, and the prognosis of these patients.

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      Treatment and prognosis of patients with intracranial nongerminomatous malignant germ cell tumors : A multiinstitutional retrospective analysis of 41 patients (pages 369–376)

      Kazuhiko Ogawa, Takafumi Toita, Katsumasa Nakamura, Takashi Uno, Hiroshi Onishi, Jun Itami, Naoto Shikama, Naokatsu Saeki, Yoshihiko Yoshii and Sadayuki Murayama

      Article first published online: 6 JUN 2003 | DOI: 10.1002/cncr.11495

      Intracranial nongerminomatous malignant germ cell tumors are rare neoplasms, and, to the authors' knowledge, information regarding the results of treatment and possible prognostic factors in patients with these tumors is limited. In the current study, the authors analyzed their experience involving 41 patients with intracranial nongerminomatous malignant germ cell tumors and investigated their optimal management.

    22. Discipline

      Diagnostic Imaging
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      Probably benign lesions at breast magnetic resonance imaging : Preliminary experience in high-risk women (pages 377–388)

      Laura Liberman, Elizabeth A. Morris, Catherine L. Benton, Andrea F. Abramson and D. David Dershaw

      Article first published online: 16 JUN 2003 | DOI: 10.1002/cncr.11491

      A “probably benign” interpretation was given to 24% of high-risk women at their first breast magnetic resonance (MR) imaging screening examination. In 7–10% of women with “probably benign” interpretations, malignancy subsequently developed in an area initially judged to be probably benign; of these malignancies, more than half were ductal carcinoma in situ, and more than half were detected by MR imaging only.

    23. Pediatric Oncology
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      Improved radiation protection of the thyroid gland with thyroxine, methimazole, and potassium iodide during diagnostic and therapeutic use of radiolabeled metaiodobenzylguanidine in children with neuroblastoma (pages 389–396)

      Hanneke M. van Santen, Jan de Kraker, Berthe L. F. van Eck, Jan J. M. de Vijlder and Thomas Vulsma

      Article first published online: 5 JUN 2003 | DOI: 10.1002/cncr.11523

      A new protective regimen against radiation damage to the thyroid gland during treatment with radiolabeled metaiodobenzylguanidine in children with neuroblastoma is introduced. This regimen uses combined thyroxine, methimazole, and potassium iodide.

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      Megestrol acetate in pediatric oncology patients may lead to severe, symptomatic adrenal suppression (pages 397–405)

      Lisa M. Orme, Jodie D. Bond, Maureen S. Humphrey, Margaret R. Zacharin, Peter A. Downie, Kris M. Jamsen, Susan L. Mitchell, Jacqueline M. Robinson, Natalie A. Grapsas and David M. Ashley

      Article first published online: 6 JUN 2003 | DOI: 10.1002/cncr.11502

      Although the results of this study support the ability of megestrol acetate (MA) to improve nutritional status in pediatric oncology patients, its use was complicated by severe adrenal suppression in nearly all patients tested, and MA therapy was associated with a serious clinical adverse event in one patient. Routine hydrocortisone supplementation throughout MA treatment should be considered as well as larger doses for patients who have acute illness or who are undergoing surgery.

    25. Symptom Control and Palliative Care
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      Evaluation of pain associated with oral mucositis during the acute period after administration of high-dose chemotherapy (pages 406–412)

      David Cella, Janis Pulliam, Henry Fuchs, Carole Miller, David Hurd, John R. Wingard, Stephen T. Sonis, Paul J. Martin and Francis Giles

      Article first published online: 4 JUN 2003 | DOI: 10.1002/cncr.11505

      A separate measurement of patient-reported pain was useful for capturing the patient's perspective on oral mucositis (OM), and this measurement was correlated with the physician's objective assessment. These findings support the use of a simple, patient-reported rating of mouth pain as a clinically relevant and responsive endpoint in clinical trials and may provide a straightforward method of following OM in clinical practice.

    26. Translational Research
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      Insights into the mechanisms of lymph node metastasis (pages 413–423)

      S. David Nathanson

      Article first published online: 20 MAY 2003 | DOI: 10.1002/cncr.11464

      Metastasis of primary malignant neoplasms to regional lymph nodes is a common clinical problem that occurs in a logical, anatomic sequence. Recent molecular and functional studies have revealed mechanisms by which tumor cells gain access to lymphatic capillaries and ‘home’ to the nodes.

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      Reduced bikunin gene expression as a factor of poor prognosis in ovarian carcinoma (pages 424–430)

      Yoshiko Tanaka, Hiroshi Kobayashi, Mika Suzuki, Naohiro Kanayama, Mitsuaki Suzuki, Toru Yamakawa, Hideaki Morishita and Toshihiko Terao

      Article first published online: 6 JUN 2003 | DOI: 10.1002/cncr.11506

      Low bikunin mRNA expression in ovarian carcinoma cells may be associated with poor prognosis. Testing for bikunin mRNA may identify patients with ovarian carcinoma who are at high risk for early disease recurrence and a poor prognosis.

  4. Correspondence

    1. Top of page
    2. Ethics and Law in Oncology
    3. Editorial
    4. Original Articles
    5. Correspondence
    1. You have free access to this content
      Significance of secondary ultrasonographic endometrial thickening in postmenopausal tamoxifen-treated women (pages 431–432)

      Dirk Timmerman, Patrick Neven, Jan Deprest, Maja L. Konstantinović and Ignace Vergote

      Article first published online: 2 JUN 2003 | DOI: 10.1002/cncr.11499

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      Author reply (pages 432–433)

      Ilan Cohen, Ron Azaria, Jeremiah Shapira, Dror Yigael and Ron Tepper

      Article first published online: 17 JUN 2003 | DOI: 10.1002/cncr.11503

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      Author reply (pages 434–435)

      Takahiro Yamasaki, Fumie Kurokawa and Kiwamu Okita

      Article first published online: 2 JUN 2003 | DOI: 10.1002/cncr.11504

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