bluuebunny/crossref_metadata_2025 huggingface dataset:
Autologous stem cell transplantation for patients with chronic myeloid leukemia
Authors: Koziner Benjamín , Dengra Cristina , Lucero Graciela , Klein Graciela , Cánepa Carlos , Milovic Vera , Milone Gustavo , Robinson Anibal , Cerutti Ider , Saporito Graciela , Kusminsky Gustavo , Milone Jorge , Bordone Javier , Lastiri Francisco
Published: November 2002

BACKGROUND

The objective of this analysis was to evaluate the role of autologous stem cell transplantation (ASCT) in prolonging disease free survival (DFS) and overall survival (OS) in patients with chronic myeloid leukemia (CML) who received autografts of Philadelphia chromosome (Ph) positive or Ph negative cell harvests.

METHODS

Over a 4‐year period (1994–1999), 53 patients who underwent ASCT for CML were reported to the Argentine Group of Bone Marrow Transplantation (GATMO) Registry.

RESULTS

Ph negative cell products were harvested in only 18 patients (34%). Comparison of disease status at the time of autograft, duration of neutropenia, thrombocytopenia, days of antibiotics, and transfusional requirements of red blood cells and platelets did not reveal statistical significant differences between the Ph positive group and the Ph negative group. Only days of hospitalization were increased significantly in patients who received Ph positive autografts. Although DFS at 36 months was significantly longer after infusion of Ph negative cell products (54% vs. 14%; P ≤ 0.005), OS differences between the Ph negative group and the Ph positive group (68% vs. 53%; P ≤ 0.134) were not significant.

CONCLUSIONS

ASCT with Ph negative cell harvests after myeloablative chemotherapy resulted in prolonged periods of hematologic and cytogenetic remission or stable disease after cytogenetic/molecular recurrence in some patients with CML. A superior DFS was observed without any benefit observed for OS. Cancer 2002;95:2339–45. © 2002 American Cancer Society.

DOI 10.1002/cncr.10931
Incidence patterns of invasive and borderline ovarian tumors among white women and black women in the United States
Authors: Mink Pamela J. , Sherman Mark E. , Devesa Susan S.
Published: November 2002

BACKGROUND

Malignant tumors of the ovary are the leading cause of death from gynecologic malignancies in the United States. Population‐based incidence data for these neoplasms by histopathologic type and race are limited. Variation in rates may provide clues for future etiologic studies.

METHODS

The authors performed a detailed, population‐based analysis of U.S. incidence rates by histologic type, race, and age for invasive ovarian tumors that were diagnosed during 1978–1998 and for borderline ovarian tumors that were diagnosed during 1992–1998 using data from the U.S. Surveillance, Epidemiology, and End Results (SEER) Program.

RESULTS

White women had significantly higher rates compared with black women of all types of epithelial tumors, with the white:black rate ratios ranging from 1.23 to 2.56. Black women had higher rates of gonadal stromal tumors. Among both white women and black women, total carcinoma rates did not change greatly from 1978–1982 to 1995–1998. Among white women, the reported incidence rates for invasive serous, endometrioid, and clear cell tumors increased during 1978–1998, whereas the rates of mucinous; papillary, not otherwise specified (NOS); and other epithelial tumors declined. Among black women, the reported rates of papillary, NOS tumors decreased significantly, whereas the rates of other tumor types fluctuated. Incidence rates of borderline ovarian tumors were higher among white women compared with black women and did not change significantly during 1992–1998. Serous and mucinous tumors were the predominant tumors reported for women age < 45 years, whereas serous; papillary, NOS; and other epithelial tumors predominated among older women.

CONCLUSIONS

Incidence rates for malignant ovarian tumors have remained relatively stable, with higher rates for white women compared with black women. The reported rates for some specific histopathologic tumor types have changed over time, in part reflecting more specific pathologic classification. The possible effect of shifting exposure prevalence on incidence patterns warrants further study. Cancer 2002;95:2380–9. Published 2002 by the American Cancer Society.

DOI 10.1002/cncr.10935
Nitric oxide pathways in human bladder carcinoma
Authors: Ehsan Amgad , Sommer Frank , Schmidt Annette , Klotz Theodor , Koslowski Jolanta , Niggemann Sandra , Jacobs Georg , Engelmann Udo , Addicks Klaus , Bloch Wilhelm
Published: November 2002

BACKGROUND

Nitric oxide (NO) is produced by a group of synthase enzymes (NOS). By means of different pathways, NO exerts several functions in benign and malignant human bladder tissues. The current paper describes the NO/guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) and the NO/oxidative pathways in human bladder tissues.

METHODS

Bladder carcinoma tissues were collected from 18 patients by transurethral resection procedures. Normal benign vesical tissue specimens from a further eight patients with benign diseases served as controls. Immunohistochemistry was conducted for localization of sGC, cGMP, and nitrotyrosine in benign and malignant vesical tissues, evaluating two–three tissue sections per patient.

RESULTS

Positive immunolabeling for sGC and cGMP was detected in vascular endothelial cells of normal and malignant vesical tissues. Those signals were most intense in bladder carcinoma tissues. Immunolabeling for sGC and cGMP was also detected in normal urothelial cells. In bladder carcinoma cells, a heterogeneous immunolabeling for sGC and cGMP was seen, with a wide spectrum of signal intensity. Positive immunostaining for sGC and cGMP was also observed in stromal round cells in benign and malignant bladder tissues. Immunolabeling for nitrotyrosine was mainly observed in endothelial cells, with a much stronger immunolabeling in bladder carcinoma tissues compared to normal benign controls. A weak immunolabeling for nitrotyrosine was also observed in bladder carcinoma cells. Normal urothelial cells did not show such nitrotyrosine expression.

CONCLUSIONS

The current report provides evidences that NO play several roles through different pathways in benign and malignant vesical tissues. The influences generated by NO molecules can be divided into cGMP‐mediated effects (those resulting from the NO/sGC/cGMP pathway) and non‐cGMP‐mediated effects (those resulting from the NO/oxidative pathway). Increased angiogenesis is a cGMP‐mediated effect, while nitrotyrosine production is a non cGMP‐mediated oxidative effect. Such an NO/oxidative pathway is observed more often in bladder carcinoma. Cancer 2002;95:2293–301. © 2002 American Cancer Society.

DOI 10.1002/cncr.10942
Prognostic significance of c‐myc and AIB1 amplification in hepatocellular carcinoma
Authors: Wang Yi , Wu Meng‐Chao , Sham Jonathan S. T. , Zhang Weigou , Wu Wei‐Qing , Guan Xin‐Yuan
Published: November 2002

BACKGROUND

Amplifications of 1q21, c‐myc at 8q24.1, and AIB1 at 20q12 are genetic alterations that are detected frequently in hepatocellular carcinoma (HCC). The authors evaluated the association of these amplifications with the prognosis of patients with HCC.

METHODS

In the current study, amplification of 1q21, c‐myc, and AIB1 was analyzed in 560 specimens from 400 patients with HCC and 20 patients with benign liver lesions using fluorescence in situ hybridization with high‐throughput tissue microarray. Differences of amplification patterns were compared between small and large HCC, single nodular and multiple nodular HCC, primary and metastatic HCC, and primary and recurrent HCC.

RESULTS

Significant differences between single nodular and multiple nodular HCC were detected in c‐myc amplification (12% vs. 38%; P < 0.01) and AIB1 amplification (16% vs. 30%; P < 0.05). More frequent c‐myc amplification was detected in metastatic HCC (45%) compared with primary HCC (29%) and in recurrent HCC (60%) compared with primary HCC (38%). Similarly, more frequent AIB1 amplification was observed in metastatic HCC (41%) compared with primary HCC (23%) and in recurrent HCC (60%) compared with primary HCC (29%). However, no significant differences in 1q21 amplification were observed.

CONCLUSIONS

The current results strongly suggest that amplifications of the c‐myc and AIB1 oncogenes are late genetic alterations in the progression of HCC and are correlated with a poor prognosis. Cancer 2002;95:2346–52. © 2002 American Cancer Society.

DOI 10.1002/cncr.10963
Disparities in breast carcinoma treatment in Asian/Pacific Islander women
Authors: Chui Stephen Y. , Lyerly H. Kim
Published: November 2002

A comprehensive epidemiologic survey raises issues as to why differences occur between Asian/Pacific Islander and non‐Hispanic white women in the treatment of localized breast carcinoma.

See also pages 2268‐75, this issue.
Differences in treatment patterns for localized breast carcinoma among Asian/Pacific islander women
Authors: Prehn Angela W. , Topol Barbara , Stewart Susan , Glaser Sally L. , O'Connor Lilia , West Dee W.
Published: November 2002

BACKGROUND

Many studies have examined racial/ethnic differences in treatment for localized breast carcinoma, but to the authors' knowledge few have included Asian/Pacific Islander (API) women.

METHODS

The population‐based study included API and non‐Hispanic white women diagnosed with localized invasive breast carcinoma in the Greater San Francisco Bay Area during 1994 (n = 1772). Multiple logistic regression was used to assess the association between race/ethnicity and type of surgery, radiation therapy following breast‐conserving surgery (BCS), and hormone therapy for estrogen receptor‐positive tumors while adjusting for demographic, medical, and census block‐group socioeconomic characteristics.

RESULTS

API women were significantly more likely to undergo mastectomies than white women (58% vs. 42%). This difference remained for Chinese and Filipino women after multivariate adjustment (odds ratio vs. whites [OR] = 2.4, 95% confidence interval [95% CI] = 1.4–4.2; OR [95%CI] = 1.8[1.0–3.1], respectively). Chinese women were also more likely than white women to not receive adjuvant therapy, be it radiation after BCS or hormone therapy for estrogen receptor‐positive disease. Other API women did not differ from white women in adjuvant therapy use.

CONCLUSIONS

This population‐based study identified differences in treatment for localized breast carcinoma by race/ethnicity that were not explained by differences in demographic, medical, or socioeconomic characteristics. These results underscore the importance of looking at treatment patterns separately for API subgroups and support the need for research into cultural differences that may influence breast carcinoma treatment choices. Cancer 2002;95:2268–75. © 2002 American Cancer Society.

DOI 10.1002/cncr.10965
Percutaneous radiofrequency ablation therapy for patients with hepatocellular carcinoma during occlusion of hepatic blood flow
Authors: Yamasaki Takahiro , Kurokawa Fumie , Shirahashi Hitoshi , Kusano Noriyoshi , Hironaka Kouji , Okita Kiwamu
Published: November 2002

BACKGROUND

The therapeutic efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is limited by the small volume of coagulation necrosis obtained at each activation of the RF system and the sometimes irregular burn shape due to the proximity of large vessels that have a cooling effect. To improve the efficacy of RFA, the authors designed RFA with balloon occlusion of the hepatic artery (balloon‐occluded RFA). In this study, we investigated the efficacy of balloon‐occluded RFA and compared the coagulation diameters obtained with balloon‐occluded RFA and standard RFA.

METHODS

We retrospectively studied 31 patients with 42 HCC lesions measuring less than 4 cm in the greatest dimension. We performed balloon‐occluded RFA for 12 patients (n = 15 nodules) and standard RFA for 19 patients (n = 27 nodules). Initial therapeutic efficacy was evaluated with dynamic computed tomography scan performed 2 weeks after one treatment.

RESULTS

There were no significant differences in the ablation conditions such as the frequency of a fully expanded electrode, the number of needle insertions, application cycles, or treatment times between the two groups. However, the greatest dimension of the area coagulated by balloon‐occluded RFA was significantly larger (greatest long‐axis dimension, 36.6 ± 3.8 mm; greatest short‐axis dimension, 30.1 ± 6.0 mm; n = 15 lesions) than that coagulated by standard RFA (greatest long‐axis dimension, 26.7 ± 6.4 mm; greatest short‐axis dimension, 23.1 ± 5.0 mm; n = 27 lesions; greatest long‐axis dimension, P < 0.001; greatest short‐axis dimension, P < 0.001).

CONCLUSIONS

Balloon‐occluded RFA is superior to standard RFA for the treatment of many hepatocellular lesions, especially when larger volumes of coagulation are required. Cancer 2002;95:2353–60. © 2002 American Cancer Society.

DOI 10.1002/cncr.10966
Subcutaneous interleukin‐2 and interferon α in the treatment of patients with metastatic renal cell carcinoma—Less efficacy compared with intravenous interleukin‐2 and interferon α
Authors: Ravaud Alain , Delva Rémy , Gomez Fréderic , Chevreau Christine , Douillard Jean‐Yves , Peny Jean , Coudert Bruno , Négrier Sylvie
Published: November 2002

BACKGROUND

The main objective of this trial was to evaluate the combination of subcutaneous (SC) interleukin‐2 (IL‐2) with interferon α‐2a (IFN‐α) in the treatment of patients with metastatic renal cell carcinoma (MRCC) compared with a previous trial that used continuous‐infusion IL‐2 and IFN‐α with identical schedules and dosages.

METHODS

Between April, 1997 and January, 1998, 66 patients with MRCC received SC IL‐2 at a dose of 9 × 106 IU/m2 twice daily for 5 days during 2 induction cycles and during 4 additional cycles, with a 3‐week rest between cycles. Each induction cycle consisted of two 5‐day courses of IL‐2 separated by a 9‐day break. IFN‐α at a dose of 6 × 106 IU per day three times per week was given during induction cycles and additional cycles.

RESULTS

All patients were assessable for response and toxicity. The median follow‐up was 43 months. Thirty‐five patients (51%) and 43 patients (63%) received ≥ 80% of the planned induction doses of IL‐2 and IFN‐α, respectively. Five patients achieved objective responses (7.6%; 95% confidence interval [95%CI], 2.5–16.8%), with two complete responses. The median survival was 14 months (95%CI, 11.3–16.7 months). Fifty‐three patients (80%) had at least one episode of Grade 3 toxicity related to treatment. Twenty‐two patients developed Grade 4 toxicities, which included hypotension (24% of patients), decreased performance status (6% of patients), dyspnea (3% of patients), and mucositis (3% patients) as well as fever, ventricular tachycardia, and anemia.

CONCLUSIONS

The current results seem to indicate reduced efficacy and higher toxicity rates with SC IL‐2 plus IFN‐α compared with the results from a previous trial that used an identical regimen with IV IL‐2 administration. Although SC IL‐2 regimens are used widely, their interest remains to be determined. Cancer 2002;95:2324–30. © 2002 American Cancer Society.

DOI 10.1002/cncr.10968
Vulvar carcinoma
Authors: de Hullu Joanne A. , Hollema Harry , Lolkema Sietske , Boezen Marike , Boonstra Henk , Burger Matthe P. M. , Aalders Jan G. , Mourits Marian J. E. , van der Zee Ate G. J.
Published: November 2002

BACKGROUND

The objective of this study was to determine whether modifications in the treatment of patients with vulvar carcinoma influence the rates of recurrence and survival.

METHODS

Between 1982 and 1997, 253 patients with T1 and T2 invasive squamous cell carcinoma of the vulva were treated by essentially the same team of gynecologic oncologists, and 168 patients (Group I) underwent radical vulvectomy with en bloc inguinofemoral lymphadenectomy. Standard therapy was changed in 1993, and 85 patients (Group II) underwent wide local excision with inguinofemoral lymphadenectomy through separate incisions. The rates of recurrence and survival were compared between both groups.

RESULTS

In Group II, the overall recurrence rate (33.3%) within 4 years was increased compared with Group I (19.9%; P = 0.03). In Group II, 5 of 79 patients (6.3%) developed fatal groin or skin bridge recurrences compared with 2 of 159 patients (1.3%) in Group I (P = 0.029); this did not result in a difference in overall survival. In Group II, 40 of 79 patients had tumor free margins measuring ≤ 8 mm, resulting in 9 local recurrences; whereas 39 of 79 patients had tumor free margins measuring > 8 mm, resulting in no local recurrences (P = 0.002).

CONCLUSIONS

The current study showed that fatal recurrences in either the groin or the skin bridge were more frequent after wide local excision and inguinofemoral lymphadenectomy through separate incisions; however, probably due to lack of power, this did not result in shorter survival. In 40 of 79 patients, the histologic margins measured ≤ 8 mm, resulting in a high risk of local recurrences. Therefore, the authors recommend obtaining surgical margins of 2 cm for the local treatment of patients with vulvar carcinoma. Cancer 2002;95:2331–8. © 2002 American Cancer Society.

DOI 10.1002/cncr.10969
The use of treatments for erectile dysfunction among survivors of prostate carcinoma
Authors: Schover Leslie R. , Fouladi Rachel T. , Warneke Carla L. , Neese Leah , Klein Eric A. , Zippe Craig , Kupelian Patrick A.
Published: November 2002

BACKGROUND

The objectives of this survey were to describe the prevalence of using a treatment for erectile dysfunction (ED) among men after therapy for localized prostate carcinoma and to construct models explaining the variance in trying a treatment, treatment success, and adherence to treatment.

METHODS

A postal survey was sent to 2636 men in The Cleveland Clinic Foundation's Prostate Cancer Registry who were treated initially with either definitive radiotherapy or prostatectomy for localized prostate carcinoma. The survey asked about demographic items, past and current sexual functioning, and the partner's sexual function. Men were asked about their current and intended use of medical treatments for ED. Standardized questionnaires included the Sexual Self‐Schema Scale‐Male Version, the International Index of Erectile Function, urinary and bowel symptom scales from the Los Angeles Prostate Cancer Index), and the Short‐Form Health Survey.

RESULTS

The return rate was 49%. Differences between men who returned the questionnaire and men who did not respond suggest that the sample was weighted toward men who were more interested in staying active sexually. ED was a problem for 85% of men, and 59% of this group used at least 1 treatment for ED. Only 38% of men found that a medical treatment was at least somewhat helpful in improving their sex lives, however, and 30% of respondents still were using at least 1 treatment at the time of the survey. Factors that were associated with the efficacy of treatments for ED and with their continued use included having a sexual partner, younger age, choosing a treatment for prostate carcinoma that was more likely to spare some sexual function, and not having had neoadjuvant or current antiandrogen therapy. Men who tried a greater number of treatments for ED were more likely to find one that worked. Men were more likely to continue using treatments for ED that produced greater improvements in sexual function.

CONCLUSIONS

The success of medical treatments for men with ED among long‐term survivors of prostate carcinoma is limited. Men prefer noninvasive treatments, although invasive treatments are more effective. Sexual counseling for men and their partners is recommended, because it may increase the use of medical therapies for ED. Creating more realistic expectations in both partners also may enhance treatment adherence. Cancer 2002;95:2397–407. © 2002 American Cancer Society.

DOI 10.1002/cncr.10970
Food groups and the risk of colorectal carcinoma in an Asian population
Authors: Seow Adeline , Quah Stella R. , Nyam Denis , Straughan Paulin T. , Chua Terrence , Aw Tar‐Choon
Published: November 2002

BACKGROUND

Singapore Chinese have experienced a rapid transition toward a pattern of disease in which lifestyle‐related, chronic, degenerative diseases are major public health concerns. The rates of colorectal carcinoma have increased 2‐fold over the last 3 decades. It has long been known that dietary factors play a role in the risk of this disease, although studies in Asian populations, with their unique dietary intake, have been few.

METHODS

The authors conducted a population‐based case‐control study that included 121 Chinese patients with colorectal carcinoma and 222 healthy control participants who provided information on usual intake of major food groups in the preceding 3 years, physical activity, family history of colorectal carcinoma, and demographic variables through an in‐person questionnaire.

RESULTS

High intake of red meat, but not other meats, indicated a predisposition to risk of colorectal carcinoma (adjusted odds ratio [OR] for the highest tertile vs. the lowest tertile, 2.2; 95% confidence interval [95%CI], 1.1–4.2). A low vegetable intake also was associated with a higher risk, and the combined effect appeared to be additive. Those in the highest tertile of meat intake and the lowest quartile of vegetable intake had an OR of 2.6 (95%CI, 1.0–6.7). The authors observed a slight, albeit nonsignificant, positive association with foods high in refined sugars. There was no association observed with fruit or soy‐legume intake in this study. Among nondietary variables, a family history of colorectal carcinoma conferred a significant increase in risk (OR, 6.7; 95% CI 2.4–18.7).

CONCLUSIONS

Meat intake and vegetable intake were associated significantly with risk of colorectal carcinoma in this Asian population, and further studies on the effects of changes in these specific types of food may shed light on how best to reduce the rapid increase in rates in similar populations. Cancer 2002;95:2390–6. © 2002 American Cancer Society.

DOI 10.1002/cncr.10971
Combination of neoadjuvant chemotherapy with cryotherapy and surgical resection for the treatment of unresectable liver metastases from colorectal carcinoma
Authors: Rivoire Michel , De Cian Franco , Meeus Pierre , Négrier Sylvie , Sebban Henri , Kaemmerlen Pierre
Published: November 2002

BACKGROUND

This retrospective study was conducted to assess the safety, efficacy, and long‐term results of neoadjuvant chemotherapy and cryotherapy as additional means for eradicating liver metastases from colorectal carcinoma when curative treatment was not possible by resection alone.

METHODS

Between January 1996 and December 1997, 131 patients with unresectable liver metastases were referred to our department and received chemotherapy. After 3–6 months of chemotherapy, curative surgery of liver metastases was considered possible in 57 patients, either by resection alone in 33 patients (25%) or cryotherapy associated with resection in 24 patients (18%). Characteristics and survival of patients in the cryotherapy plus resection group were compared with those of the 33 patients in the resection group.

RESULTS

All patients in the resection group had partial response to neoadjuvant chemotherapy. In the cryotherapy plus resection group, neoadjuvant chemotherapy resulted in 13 partial responses, 9 stable diseases, and 2 disease progressions. The rate of postoperative complications in the entire series was 14%. No major difference was seen between the two groups. After a median follow‐up of 48 months, the median survival time was 39 months. The survival rates at 1, 3, and 4 years were similar in both groups: 94, 58, and 37% in the resection group and 92, 50, and 36% in the cryotherapy plus resection group, respectively.

CONCLUSIONS

The combination of neoadjuvant chemotherapy, cryotherapy, and liver resection constitutes a promising treatment strategy for patients with extremely advanced metastatic liver involvement. Patients having more than four liver metastases from a colorectal carcinoma or patients with a poor liver reserve due to previous resection should be screened carefully to determine whether they could be candidates for this procedure. Cancer 2002;95:2283–92. © 2002 American Cancer Society.

DOI 10.1002/cncr.10973
Identification of distinct protein expression patterns in bilateral matched pair breast ductal fluid specimens from women with unilateral invasive breast carcinoma
Authors: Kuerer Henry M. , Goldknopf Ira L. , Fritsche Herbert , Krishnamurthy Savitri , Sheta Essam A. , Hunt Kelly K.
Published: November 2002

BACKGROUND

Analysis of the biochemical and cellular contents of breast ductal fluid has recently gained attention as a potential noninvasive method for studying the local microenvironment associated with the development and progression of breast carcinoma.

METHODS

Patients with unilateral primary invasive breast carcinoma were eligible for the current prospective pilot study. Nipple aspiration fluid (NAF) was obtained from the breast with cancer and the normal contralateral breast and subjected to two‐dimensional electrophoresis. Computer‐assisted image analysis was used to analyze NAF protein expression profiles.

RESULTS

The number of separate protein spots detected in NAF samples ranged from 1280 to 1649. Substantial qualitative differences were identified between NAF protein expression patterns in the breast with cancer compared with the breast without cancer. Protein spots detected in the breast with cancer and not in the breast without cancer from the same patient varied from 30 to 202 different proteins. In addition, the number of protein spots detected in the breast without cancer and not in the breast with cancer of the same patient varied from 14 to 73 different proteins. Conversely, in an individual without breast carcinoma, only three protein spots were detected in the left breast but not the right breast, and only two were detected in the right breast but not the left breast.

CONCLUSIONS

The breast is a unique organ in that its microenvironment can be readily accessed and evaluated by aspiration of fluid from the nipple. Breast ductal fluid contains a large number of proteins. As breasts are paired organs, comparisons of ductal fluid from a breast with cancer and the same patient's normal contralateral breast may reveal significant differences in protein expression associated with breast carcinoma. Recent advances in image analysis, automated mass spectrometry, and bioinformatics have provided the tools necessary to use ductal fluids from breast carcinoma patients for high‐throughput biomarker discovery. Cancer 2002;95:2276–82. © 2002 American Cancer Society.

DOI 10.1002/cncr.10974
Risk factors for urinary bladder carcinoma in postmenopausal women
Authors: Tripathi Apeksha , Folsom Aaron R. , Anderson Kristin E.
Published: November 2002

BACKGROUND

We evaluated prospectively the association of smoking and other potential risk factors with bladder carcinoma incidence in postmenopausal women.

METHODS

A total of 37,459 women participating in the Iowa Women's Health Study completed baseline questionnaires in 1986 and were followed 13 years for bladder carcinoma incidence (n = 112).

RESULTS

Adjusted for potential confounders, the relative risk (RR) of bladder carcinoma in women who were current smokers compared with those who had never smoked was 3.58 (95% confidence interval [CI] = 1.86–6.88). The RR declined as years since quitting increased. Currently, married women, compared with unmarried women, had a RR of 0.66 (95% CI = 0.44–0.99). A 2.46‐fold (95% CI = 1.32–4.59) increase in bladder carcinoma risk was identified for women who reported, versus did not report, diabetes. Regular versus no physical activity (RR = 0.66, 95% CI 0.43–1.01) and body mass index were inversely associated (P = 0.06) with bladder carcinoma incidence.

CONCLUSIONS

We confirmed that cigarette smoking is an important risk factor for bladder carcinoma in women; women who had quit smoking had a reduction of risk. We also identified diabetes as a potential risk factor, which may invite more research on its role in the development of urinary bladder carcinoma. Cancer 2002;95:2316–23. © 2002 American Cancer Society.

DOI 10.1002/cncr.10975
Decongestive lymphatic therapy for patients with breast carcinoma‐associated lymphedema
Authors: Szuba Andrzej , Achalu Radha , Rockson Stanley G.
Published: November 2002

BACKGROUND

Disruption of the lymphatic circulation through breast carcinoma‐associated axillary lymph node dissection, with or without radiation therapy, reportedly is the most common cause of lymphedema in developed countries. There is no cure for breast carcinoma‐associated lymphedema. Although intermittent pneumatic compression (IPC) has been acknowledged as a potential component of the multidisciplinary therapeutic strategy in the treatment of patients with breast carcinoma‐associated lymphedema, prospective study of its adjunctive safety and efficacy is required.

METHODS

IPC was assessed as a component of the initial therapeutic regimen for newly treated patients with breast carcinoma‐associated lymphedema. Twenty‐three patients who had not previously been treated for lymphedema were randomized to receive either decongestive lymphatic therapy (DLT) alone or DLT with daily adjunctive IPC. Patients with stable, treated, breast carcinoma‐associated lymphedema also were assessed in the maintenance phase of therapy. Twenty‐seven patients were randomized either to DLT alone or to DLT coupled with daily IPC. In both studies, objective assessment included serial measurement of volume by water displacement, tissue tonometry to assess elasticity of the skin, and goniometry to measure joint mobility.

RESULTS

During initial treatment, the addition of IPC to standard DLT yielded an additional mean volume reduction (45.3% vs. 26%; P < 0.05). During maintenance DLT alone, there was a mean increase in volume (32.7 ± 115.2 mL); with DLT and IPC, there was a mean volume reduction (89.5 ± 195.5 mL; P < 0.05). In both studies, IPC was tolerated well without detectable adverse effects on skin elasticity or joint range of motion.

CONCLUSIONS

When IPC is used adjunctively with other, established elements of DLT, it provides an enhancement of the therapeutic response. IPC is well tolerated and remarkably free of complications. Cancer 2002;95:2260–7. © 2002 American Cancer Society.

DOI 10.1002/cncr.10976
Pulmonary complications in survivors of childhood and adolescent cancer
Authors: Mertens Ann C. , Yasui Yutaka , Liu Yan , Stovall Marilyn , Hutchinson Ray , Ginsberg Jill , Sklar Charles , Robison Leslie L.
Published: November 2002

BACKGROUND

The Childhood Cancer Survivor Study is a resource that was designed to investigate long‐term effects among 5‐year survivors of childhood and adolescent malignancies. Previous studies have shown that exposure to chemotherapy and/or radiation can compromise pulmonary function in these survivors of childhood cancer.

METHODS

Using information obtained from questionnaires from 12,390 childhood cancer survivors and 3546 randomly selected siblings, the authors evaluated the rate of first occurrence of 15 selected pulmonary conditions in three periods: during therapy, from the end of therapy to 5 years postdiagnosis, and ≥ 5 years postdiagnosis. Multivariate analyses were used to determine the relative risks with 95% confidence intervals of reported pulmonary conditions by exposure to the following treatment variables: radiation therapy to the chest, bleomycin, cyclophosphamide, busulfan, lomustine (CCNU), and/or carmustine (BCNU).

RESULTS

Compared with siblings, survivors had a statistically significant increased relative risk (RR) of lung fibrosis, recurrent pneumonia, chronic cough, pleurisy, use of supplemental oxygen, abnormal chest wall, exercise‐induced shortness of breath, bronchitis, recurrent sinus infection, and tonsillitis for all three periods. During the period of ≥ 5 years postdiagnosis, statistically significant associations were present for lung fibrosis and chest radiation (RR, 4.3; P = 0 001); for supplemental oxygen use and chest radiation (RR, 1.8; P < 0.001), BCNU (RR, 1.4; P = 0.05), bleomycin (RR, 1.7; P = 0.001), busulfan (RR, 3.2; P = 0.002), CCNU (RR, 2.1; P < 0.001), and cyclophosphamide (RR, 1.5; P = 0.01); for recurrent pneumonia and chest radiation (RR, 2.2; P = 0.001) and cyclophosphamide (RR, 1.6; P = 0.04); for chronic cough and chest radiation (RR, 2.0; P < 0.001), bleomycin (RR, 1.9; P < 0.001), and cyclophosphamide (RR, 1.3; P = 0.004); and for pleurisy and chest radiation (RR, 1.4; P = 0.02) and busulfan (RR, 5.1; P = 0.02). Chest radiation was associated with a 3.5% cumulative incidence of lung fibrosis at 20 years after diagnosis.

CONCLUSIONS

For self‐report of pulmonary conditions, treatment‐related factors that continue to manifest > 5 years after diagnosis and treatment are important determinants of risk. Continued follow‐up of childhood cancer survivors is needed to evaluate the impact of pulmonary conditions on quality of life. Cancer 2002;95:2431–41. © 2002 American Cancer Society.

DOI 10.1002/cncr.10978
Antibody‐based screening for hereditary nonpolyposis colorectal carcinoma compared with microsatellite analysis and sequencing
Authors: Christensen Mariann , Katballe Niels , Wikman Friedrik , Primdahl Hanne , Sørensen Flemming B. , Laurberg Søren , Ørntoft Torben F.
Published: November 2002

BACKGROUND

Germline mutations in the DNA mismatch repair genes, MSH2, MLH1, and others are associated with hereditary nonpolyposis colorectal cancer (HNPCC). Due to the high costs of sequencing, cheaper screening methods are needed to identify HNPCC cases. Ideally, these methods should have a high sensitivity and identify all mutated cases without too many false‐positive cases.

METHODS

Sequencing was compared with microsatellite analysis and immunohistochemistry to detect the presence or absence of the mismatch repair proteins. In the current study, the authors examined 42 patients with colorectal carcinoma of whom 11 met the Amsterdam criteria and 31 were suspected to belong to HNPCC families. Thirty‐five patients were examined by microsatellite analysis, 40 by immunohistochemical staining, and in 31 patients both the MLH1 and MSH2 genes were sequenced.

RESULTS

Ninety‐two percent of patients with germ line mutations were detected by either immunohistochemistry or microsatellite instability, indicating that a combination of these methods may be suitable for HNPCC screening. Microsatellite instability and abnormal immunohistochemical staining were found in 73% of the tumors. Concordance among the three methods was found in 74 % of the tumors.

CONCLUSIONS

The authors suggest that immunohistochemistry should be used in combination with microsatellite analysis to prescreen suspected HNPCC patients for the selection of cases where sequencing of the MLH1 and MSH2 mismatch repair genes is indicated. Cancer 2002;95:2422–30. © 2002 American Cancer Society.

DOI 10.1002/cncr.10979
Response predicting factors to recombinant human erythropoietin in cancer patients undergoing platinum‐based chemotherapy
Authors: González‐Barón Manolo , Ordóñez Amdio , Franquesa Rosa , Constenla Manuel , Montalar Joaquin , Gili Frederic , Camps Carlos , Sancho José Felix , Pérez‐Cachot Pedro
Published: November 2002

BACKGROUND

The response to epoetin‐α treatment is hard to predict in cancer patients receiving chemotherapy.

METHODS

One hundred and seventeen patients were enrolled in this observational study. They had a hemoglobin (Hb) level less than or equal to 10.5 g/dL, were receiving platinum chemotherapy with three cycles pending, and they did not have an iron deficiency or hemolysis. Epoetin‐α was administered subcutaneously three times a week at a dose of 150 IU/kg. Ninety patients were examined.

RESULTS

Response was defined as an increase in Hb of at least 2 g/dL during the treatment period. The response rate was 63.3%. The following data were compared between responders and nonresponders at the onset of treatment and after 2 and 4 weeks of epoetin therapy: Hb, reticulocytes, serum iron, ferritin, transferrin, transferrin saturation index, and endogenous erythropoietin levels. At baseline, these variables were similar for responders and nonresponders; after 2 weeks, responders showed higher Hb (P = 0.001) and transferrin levels (P = 0.042) and reticulocyte counts (P = 0.003); after 4 weeks, only the Hb level showed a significant difference (P < 0.0005). Changes from baseline in Hb level after 2 and 4 weeks correlated significantly (P < 0.01) with response. The change in Hb level at Week 4 was the best predictor. A change in Hb level of less than 0.5 g/dL was associated with a lack of response (predictive power, 71%); a change in Hb greater than or equal to 0.5 g/dL was associated with response (predictive power, 89%).

CONCLUSIONS

Response to epoetin‐α treatment in cancer patients receiving platinum chemotherapy can be predicted from changes in Hb level after 4 weeks of therapy. Cancer 2002;95:2408–13. © 2002 American Cancer Society.

DOI 10.1002/cncr.10980
Ethical communication in clinical trials
Authors: Loh Winnie Y. , Butow Phyllis N. , Brown Richard F. , Boyle Frances
Published: November 2002

BACKGROUND

Informed consent has been proposed as the optimal method for ensuring the ethical entry of patients into clinical trials. However, it is known that problems with informed consent exist from the perspective of both patients and physicians. This has led to the suggestion that a third party, such as a research nurse or data manager, should be responsible for obtaining informed consent. The objective of this study was to explore the views of data managers concerning the nature, challenges, and rewards of their role and the similarities and differences between their role and that of physicians in obtaining informed consent.

METHODS

Four focus groups in three large teaching hospitals were conducted. Twenty‐one data managers who were involved in cancer or pain clinical trials participated. The focus groups were audiotaped, transcribed, and subjected to content analysis to identify themes.

RESULTS

Data managers identified three primary roles complementary to that of physicians: information provision, quality assurance of the informed consent process, and ongoing support during the trial. Despite expressed concern that medical and drug company interests may lead to subtle coercion of the patient, participants did not support the notion that they may be solely responsible for the consent process. Participants described a range of ethical dilemmas they confronted, including patients asking them for medical details they could not provide and situations in which they felt that informed consent was compromised in some way, for example, dealing with situations in which the patient appeared to be entering the trial for the wrong reasons due to misunderstanding, need, or passivity. Effective functioning of the multidisciplinary team assisted data managers in performing their role. A range of training needs were identified, particularly communication skills training and trial start‐up briefing.

CONCLUSIONS

The issues raised by these data managers have important implications for the successful conduct of clinical trials, particularly the need for an integrated, multidisciplinary approach at all levels of the informed‐consent process. Cancer 2002;95:2414–21. © 2002 American Cancer Society.

DOI 10.1002/cncr.2002;10994
Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD), and human leukocyte interferon for metastatic uveal melanoma
Authors: Pyrhönen Seppo , Hahka‐Kemppinen Marjo , Muhonen Timo , Nikkanen Väinämö , Eskelin Sebastian , Summanen Paula , Tarkkanen Ahti , Kivelä Tero
Published: November 2002

BACKGROUND

A Phase II trial comprising patients with metastatic uveal melanoma (Stage IVB) was undertaken to determine the activity of bleomycin, vincristine, lomustine, and dacarbazine (BOLD) chemotherapy with human leukocyte interferon, as well as the progression‐free and overall survival of the patients according to the substage before treatment.

METHODS

Twenty‐two patients with histologically proven metastatic uveal melanoma received 15 mg of bleomycin (Days 2 and 5), 1 mg/m2 vincristine (Days 1 and 4), 200 mg/m2 dacarbazine (Days 1 to 5), and 80 mg lomustine (Day 1) every 4 weeks together with a leukocyte interferon preparation (3 × 106 IU daily for 6 weeks followed by 6 × 106 IU three times per week).

RESULTS

Of 20 evaluable patients, 3 (15%; 95% confidence interval [CI] 0–38) obtained a partial objective response in hepatic and extrahepatic sites and 11 (55%; 95% CI 32–77) showed stable disease after receiving more than two cycles. The median progression‐free survival was 4 months (95% CI 2–10) and the median overall survival was 12 months (95% CI 8–22). Eleven patients who had favorable pretreatment characteristics (Stage IVBa) survived a median of 17 months (95% CI 4–37) whereas 10 patients with less favorable characteristics (Stage IVBb) survived a median of 11 months (95% CI 1–23). Moderate toxicity occurred with this outpatient regimen.

CONCLUSIONS

The BOLD/human leukocyte interferon regimen had modest activity against metastatic uveal melanoma in hepatic and extrahepatic sites. The median overall survival approached that reported for more aggressive intrahepatic therapy regimens. Substage differences can significantly impact study outcomes. Therefore, substage information should be reported to facilitate comparisons between studies. Cancer 2002;95:2366–72. © 2002 American Cancer Society.

DOI 10.1002/cncr.10996
Response of extraabdominal desmoid tumors to therapy with imatinib mesylate
Authors: Mace Joseph , Sybil Biermann J. , Sondak Vernon , McGinn Cornelius , Hayes Curtis , Thomas Dafydd , Baker Laurence
Published: November 2002

BACKGROUND

Desmoid tumor represents a rare monoclonal neoplasm arising from deep musculoaponeurotic structures and may occur sporadically or in association with the familial adenomatous polyposis and Gardner syndromes. Desmoid tumors do not appear to demonstrate metastatic potential; however, local infiltrative growth results in significant morbidity and potential mortality. Although the delineation of optimal therapy for desmoid tumors has been confounded by several factors, surgical resection with adjuvant radiotherapy for a positive surgical margin remains the standard approach. Responses have been demonstrated to nonsteroidal antiinflammatory agents, antiestrogen compounds, and a variety of other agents in small series. Imatinib mesylate appears to demonstrate inhibitory activity against multiple class 3 receptor tyrosine kinases, including platelet‐derived growth factor receptor (PDGFR)‐α and PDGFR‐β, as well as c‐kit.

METHODS

The authors performed immunohistochemical and qualitative real‐time polymerase chain reaction analysis on nine desmoid tumor specimens that demonstrated consistent positivity for c‐kit as well as PDGFR‐α and PDGFR‐β. At the time of last follow‐up, 2 patients had received therapy with imatinib mesylate at a dose of 400 mg twice daily.

RESULTS

Both patients demonstrated ongoing radiographic and clinical responses with a duration of 9 months and 11 months, respectively.

CONCLUSIONS

Imatinib mesylate has been reported to have activity against desmoid tumor, most likely because of c‐kit and PDGFR receptor tyrosine kinase activity inhibition, and warrants further study. The relative novelty of this agent and the lack of long‐term toxicity data should prompt its use only in the salvage setting in which established local and systemic approaches fail to control disease. In addition, the use of imatinib mesylate in the treatment of this neoplasm preferably should be in the context of a formal prospective clinical trial. Cancer 2002;95:2373–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.11029
A noise reduction method based on linear prediction analysis
Authors: Kawamura Arata , Fujii Kensaku , Itoh Yoshio , Fukui Yutaka
Published: November 2002

The linear prediction method works in such a way that the difference (prediction residual) between the objective signal and the output generated by making the objective signal a linear combination of the input signals is uncorrelated. Hence, in this linear prediction method, the linear predictor generates zero for the signal without correlation and recombines the voice for that with correlation. If this characteristic is used, recombined voice with suppressed noise can be obtained as the output of the linear predictor for voice with superposed white noise without correlation. Noise suppression can be realized by using this characteristic of the linear predictor. In this paper, a noise suppression method based on this linear prediction is discussed. According to this method, a noise suppression method without process delay can be realized. Also, no a priori information on the power spectrum of the noise is needed in this method. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 86(3): 1–10, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10056
Back propagation learning with periodic chaos neurons
Authors: Onozaka Yoshio , Nakagawa Masahiro
Published: November 2002

This paper proposes a back propagation method using a periodic activation function for a hierarchical neural network and examines its learning capability. As a specific learning problem, the paper addresses the n‐bit parity problem and conducts a learning process by using a three‐layer neural network. The computer simulation results indicate an increased learning coefficient range achieving a 100% learning success rate with an improved speed of learning compared with a neural network model using a monotonic activation function. In addition, the new method lessens the influence of the initial value that is set at the beginning of a learning process, and reduces the degree of dependency on parameters. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 86(3): 11–19, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.1136
Noise‐robust speech analysis using system identification methods
Authors: Arima Yuki , Shimamura Tetsuya
Published: November 2002

This paper proposes a modified linear prediction method for speech analysis, using two system identification methods—the least‐square method and the instrument variable method—for the estimation of the coefficients of an all‐pole filter. Whereas the linear prediction method estimates the coefficients of all‐pole filters from speech signals, which are observed output signals, the system identification method estimates coefficients of all‐pole filters from observed output signals and the input signals. This paper derives a novel technique that estimates input signals from speech signals that are observed output signals with a high degree of accuracy and robustness with respect to added noise, by generating improved prediction error signals. The paper also shows that when voiced speech is to be analyzed, if input signals, which are an impulse chain, can be accurately estimated, the estimation of filter coefficients can yield a high degree of accuracy provided that the least‐square method is used, and that in this manner, the pitch period dependency can be removed. We also show that by applying the instrument variable method using an auxiliary model, the accuracy of estimation of filter coefficients in a noisy environment can be substantially improved while maintaining the properties of the least‐square method. The effectiveness of these system identification methods for speech analysis is demonstrated through computer simulations. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 86(3): 20–32, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.1137