bluuebunny/crossref_metadata_2025 huggingface dataset:
Satellite lesions in patients with small hepatocellular carcinoma with reference to clinicopathologic features
Authors: Okusaka Takuji , Okada Shuichi , Ueno Hideki , Ikeda Masafumi , Shimada Kazuaki , Yamamoto Junji , Kosuge Tomoo , Yamasaki Susumu , Fukushima Noriyoshi , Sakamoto Michiie
Published: October 2002

BACKGROUND

It is not rare to find satellite lesions in patients with small hepatocellular carcinoma (HCC). The purpose of this study was to elucidate the factors associated with satellite lesions in these patients.

METHODS

We investigated the prevalence of satellite lesions, the relationship of clinicopathologic factors to satellite lesions, and the distance from the main tumor to the satellite lesion in 149 patients. Patients, who had a solitary HCC of 3.0 cm or less in diameter but no satellite lesions on preoperative imaging procedures, underwent potentially curative resection. The main tumors were macroscopically classified into four groups: early HCC, a vaguely nodular type showing preservation of the preexisting liver structure; single nodular type; single nodular type with extranodular growth; and confluent multinodular type.

RESULTS

Of 149 resected specimens, 28 (19%) showed satellite lesions. Of the clinicopathologic factors investigated, the macroscopic type and tumor differentiation were significantly associated with the prevalence of satellite lesions. Both the single nodular type with extranodular growth and the confluent multinodular type showed satellite lesions more frequently than the early HCC and the single nodular type. A significantly higher prevalence of satellite lesions was observed in poorly differentiated HCC than in well and moderately differentiated HCC. The satellite lesions were located 0.5 cm or less from the main tumor in 8 (33%) specimens, 0.6–1.0 cm in 12 (50%), and 1.1–2.0 cm in 4 (17%). No identifiable factors were significantly related to the distance from the main tumor to the satellite lesion. However, all satellite lesions located more than 1.0 cm from the main tumor coexisted with poorly differentiated HCC, which were the single nodular type with extranodular growth or the confluent multinodular type.

CONCLUSION

In the single nodular type with extranodular growth, confluent multinodular type, and poorly differentiated HCC, extensive treatment achieving a large safety margin and/or frequent posttreatment follow‐up examinations may be needed because of the high prevalence of satellite lesions. Cancer 2002;95:1931–7. © 2002 American Cancer Society.

DOI 10.1002/cncr.10892
Helicobacter pylori and the risk of benign and malignant biliary tract disease
Authors: Bulajic Milutin , Maisonneuve Patrick , Schneider‐Brachert Wulf , Müller Petra , Reischl Udo , Stimec Bojan , Lehn Norbert , Lowenfels Albert B. , Löhr Matthias
Published: October 2002

BACKGROUND

The etiology of tumors arising in the biliary tract remains unclear. Several previous studies have detected Helicobacter pylori organisms in bile from patients with gallstones or cholecystitis. The objective of this study was to determine whether there is an association between H. pylori in bile and biliary tract carcinoma.

METHODS

The authors used polymerase chain reaction (PCR) assays to detect the presence of H. pylori in the stomach and bile from 89 patients: Sixty‐three disease free patients had biliary calculi, 15 patients had carcinoma of the biliary tract, and 11 patients had neither gallstones nor carcinoma. Bile was considered to contain H. pylori only if the results of PCR determinations were positive in two or more samples assayed independently in two separate laboratories.

RESULTS

There was a strong association between the presence of H. pylori in the stomach and in the bile (P ≤ 0.01). Biliary H. pylori was associated with age but not with gender, and it was associated strongly with the clinical diagnosis. Patients with gallstones were 3.5 times as likely to have H. pylori in the bile compared with patients in a control group (95% confidence interval [95%CI], 0.8–15.8; P = 0.100), and H. pylori was 9.9 times more frequent in patients with biliary tract carcinoma compared with patients in the control group (95%CI, 1.4–70.5; P = 0.022).

CONCLUSIONS

There is a strong association between biliary tract carcinoma and H. pylori in bile. If these results are confirmed by prospective studies, H. pylori may be responsible for a significant proportion of malignant biliary tract disease. Cancer 2002;95:1946–53. © 2002 American Cancer Society.

DOI 10.1002/cncr.10893
Quantitative analysis of apoptosis‐related gene expression in hepatocellular carcinoma
Authors: Ikeguchi Masahide , Hirooka Yasuaki , Kaibara Nobuaki
Published: October 2002

BACKGROUND

The suppression of apoptosis is an important factor in tumor progression in hepatocellular carcinoma (HCC). However, to the authors knowledge the clinicopathologic importance of the expression of apoptosis‐related genes (bcl‐2, bax, and survivin) in HCC remains unclear. In the current study, the authors investigated the correlation between expression of apoptosis‐related genes and the occurrence of spontaneous apoptosis in HCC. In addition, the prognostic significance of the expression of apoptosis‐related genes in patients with HCC was analyzed.

METHODS

Tissue samples were obtained through surgical resection of the liver in 53 patients with HCC and 5 patients without HCC. The expression levels of bcl‐2, bax, survivin, and glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) mRNA were analyzed using real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR). The bcl‐2/bax ratio and survivin/GAPDH ratio of the tumors were compared with clinicopathologic findings. In addition, apoptotic tumor cells and the proliferative activity of tumor cells were detected using immunohistochemistry.

RESULTS

The bcl‐2/bax ratios of the tumors were not different from those of noncancerous liver tissue samples obtained from regions distant from the tumors and were not found to correlate with apoptosis or with clinical importance in HCC. In contrast, the survivin/GAPDH ratios of the tumors were significantly higher than those of noncancerous liver tissue and demonstrated a negative correlation with apoptosis and a positive correlation with the proliferative activity of tumor cells. Moreover, patients who had tumors with a high survivin/GAPDH ratio were found to have a high incidence of disease recurrence.

CONCLUSIONS

The real‐time RT‐PCR method appears to be a useful technique with which to detect reliable gene expression in tissues, and the detection of survivin mRNA expression by this method may be a useful marker for identifying patients with HCC who have a high risk of disease recurrence. Cancer 2002;95:1938–45. © 2002 American Cancer Society.

DOI 10.1002/cncr.10898
Expression and immunogenicity of a tumor‐associated antigen, 90K/Mac‐2 binding protein, in lung carcinoma
Authors: Ozaki Yoshitomo , Kontani Keiichi , Hanaoka Jun , Chano Tokuhiro , Teramoto Koji , Tezuka Noriaki , Sawai Satoru , Fujino Shozo , Yoshiki Tatsuhiro , Okabe Hidetoshi , Ohkubo Iwao
Published: October 2002

BACKGROUND

The authors attempted to obtain shared proteins among lung carcinoma cells by column chromatographies. A glycoprotein with approximately 500 kDa isolated from QG56 cells showed an identical amino acid sequence to 90K/Mac‐2 binding protein (M2BP). This protein has been reported to be highly expressed and to modulate the expression of surface molecules involved in immune responses on cultured cancer cells. Therefore, it would be beneficial for M2BP to be targeted in cancer immunotherapy.

METHODS

The authors analyzed the expression of M2BP in lung carcinoma cells and M2BP's immunogenicity as a tumor antigen. Eight cultured lung carcinoma cell lines and 28 tumor tissues from patients with lung carcinoma were examined for the expression of M2BP mRNA and protein. Sera from cancer patients (n = 23) and healthy donors (n = 19) were studied for their reactivity to M2BP peptides by enzyme–linked immunosorbent assay.

RESULTS

Seven of the 8 (87.5%) lung carcinoma cell lines and 17 of the 28 (60.7%) tumor tissues expressed high levels of M2BP mRNA. Most of the M2BP mRNA‐positive cancer cell lines and tumors also showed M2BP protein expression. The serum levels of antibodies to M2BP were elevated in 30.4% of the patients. In addition, M2BP‐specific immunoglobulin G was observed in all patients with anti‐M2BP antibodies.

CONCLUSIONS

M2BP is highly expressed in lung carcinoma cells and is sufficiently immunogenic to elicit specific immunity to this molecule in patients with lung carcinoma. M2BP is expected to be useful as a tumor marker and a target antigen in cancer immunotherapy. Cancer 2002;95:1954–62. © 2002 American Cancer Society.

DOI 10.1002/cncr.10899
Plasma vascular endothelial growth factor levels have prognostic significance in patients with acute myeloid leukemia but not in patients with myelodysplastic syndromes
Authors: Aguayo Alvaro , Kantarjian Hagop M. , Estey Elihu H. , Giles Francis J. , Verstovsek Srdan , Manshouri Taghi , Gidel Christy , O'Brien Susan , Keating Michael J. , Albitar Maher
Published: October 2002

BACKGROUND

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are positive regulators of angiogenesis. Increased levels in urine, serum, plasma, or malignant tissue have been associated with an adverse prognosis in patients with solid tumors.

METHODS

The authors used an enzyme‐linked immunosorbent assay to measure VEGF and bFGF levels in plasma samples from 99 patients with previously untreated myelodysplastic syndromes (MDS) (n = 41 patients; 42%) or acute myeloid leukemia (AML) (n = 58 patients; 58%) and compared the results with the results from a group of normal control participants.

RESULTS

Increased expression levels of VEGF and bFGF were found in the plasma from patients with AML and MDS (P < 0.01) compared with the levels found in the control group. Plasma levels of VEGF in patients with AML or MDS were similar (median, 30.63 pg/mL and 34.41 pg/mL, respectively). There was no significant difference in bFGF levels between patients with AML and patients with MDS (median, 6.38 pg/mL and 6.98 pg/mL, respectively). Elevated levels of VEGF were associated with reduced survival (P = 0.02) in patients with AML as well as lower complete remission (CR) rates (P = 0.004). Elevated VEGF levels were not associated with reduced remission duration (CRD) in patients with AML. There was no correlation between VEGF levels and survival, CRD, or CR rates in patients with MDS. There was no correlation between bFGF levels and CR rates or survival in patients with either AML or MDS.

CONCLUSIONS

Plasma VEGF levels have prognostic significance in patients with AML. The lack of clinical relevance of VEGF levels in patients with MDS suggests some biologic difference between AML and MDS. Cancer 2002;95:1923–30. © 2002 American Cancer Society.

DOI 10.1002/cncr.10900
Metastatic renal cell carcinoma to the thyroid gland
Authors: Heffess Clara S. , Wenig Bruce M. , Thompson Lester D.
Published: October 2002

BACKGROUND

Clear cell tumors of the thyroid gland in general are uncommon. Metastatic renal cell carcinoma (RCC) to the thyroid gland is a rare occurrence but must be considered in the differential diagnosis of a thyroid gland clear cell neoplasm to prevent misclassification, potentially resulting in inappropriate clinical management.

METHODS

Thirty‐six cases of metastatic RCC to the thyroid were retrospectively retrieved from the files of the Endocrine Registry of the Armed Forces Institute of Pathology.

RESULTS

The tumors occurred in 22 women and 14 men, ages 53–80 years (mean, 64.9 years). Symptoms were present for a mean of 13.0 months. The tumors generally affected a single lobe of the thyroid gland as a solitary mass (n = 30; 83%), measuring 1.0–15.0 cm in diameter (mean, 3.8 cm). Histologically, the tumors were composed of polygonal cells with clear cytoplasm, distinct cell membranes, and small compact eccentric nuclei within a rich vascular network. Diastase‐sensitive, periodic acid–Schiff‐positive material (n = 22; 61%) and/or Oil Red O‐positive material (n = 5; 14%) were noted. Thyroglobulin immunohistochemistry was negative in the foci of metastatic RCC. Although the majority of the patients had documented previous evidence of an RCC (n = 23; 64%) as remotely as 21.8 years before the thyroid metastases (mean, 9.4 years), the metastatic tumor to the thyroid gland was the initial manifestation of RCC in 13 patients. The majority of patients (n = 23; 64%) died with disseminated disease (mean, 4.9 years), but 13 patients (36%) were alive or had died without evidence of disease (mean, 9.1 years).

CONCLUSIONS

In the presence of a clear cell tumor of the thyroid gland, the diagnostic considerations must include metastatic RCC. The light microscopic features may suggest this possibility and the diagnosis can be established by supplemental histochemical and immunohistochemical studies. Surgical treatment of the metastatic disease is suggested, as this may result in prolonged patient survival. Cancer 2002;95:1869–78. Published 2002 by the American Cancer Society.

DOI 10.1002/cncr.10901
A phase I study of a weekly schedule of paclitaxel and carboplatin in patients with advanced carcinoma
Authors: Akerley Wallace , Rathore Ritesh , Ready Neil , Leone Louis , Sikov William , Safran Howard , Kennedy Teresa
Published: October 2002

BACKGROUND

We conducted a Phase I study of weekly paclitaxel (P) and carboplatin (C) in patients with advanced malignancies to determine the maximum tolerated dose (MTD) of this combination.

METHODS

Dose levels were escalated independently for patients with and without previous chemotherapy exposure and advanced malignancies. Both agents were administered weekly for 6 weeks followed by a 2‐week break per cycle. P, escalated to tolerance starting at 135 mg/m2 per week, and C, fixed dose at area under the curve (AUC) = 2 mg/mL/min, were administered to groups of three or six patients. Doses were modified for granulocyte counts less than 1800/μL or for neurotoxicity greater than Grade 1. MTD was defined as the highest dose level at which less than 50% of patients developed unacceptable toxicity and received more than 80% of the intended dose during the first cycle. Dose levels were escalated until these conditions were exceeded.

RESULTS

Twenty‐seven patients (12 patients with previous chemotherapy exposure and 15 chemotherapy‐naive patients) were examined for toxicity. Dose escalation was halted due to neutropenia and/or Grade 2/3 neuropathy in both arms. The MTD was P = 135/C = 2 for patients with previous chemotherapy exposure and P = 150/C = 2 for chemotherapy‐naive patients.

CONCLUSIONS

The combination of P and C administered on a weekly schedule permits a two to threefoldenhancement of P dose intensity with full doses of C. Phase II trials of this regimen in patients with various malignancies are being evaluated to determine efficacy and tolerance. Cancer 2002;95:2000–5. © 2002 American Cancer Society.

DOI 10.1002/cncr.10902
Testicular carcinoma and HLA Class II genes
Authors: Sonneveld Dirk J. A. , Holzik Martijn F. Lutke , Nolte Ilja M. , Sleijfer Dirk Th. , van der Graaf Winette T. A. , Bruinenberg Marcel , Sijmons Rolf H. , Hoekstra Harald J. , Te Meerman Gerard J.
Published: October 2002

BACKGROUND

The association with histocompatibility antigens (HLA), in particular Class II genes (DQB1, DRB1), has recently been suggested to be one of the genetic factors involved in testicular germ cell tumor (TGCT) development. The current study, which uses genotyping of microsatellite markers, was designed to replicate previous associations.

METHODS

In 151 patients, along with controls comprising parents or spouses, the HLA region (particularly Class II) on chromosome 6p21 was genotyped for a set of 15 closely linked microsatellite markers.

RESULTS

In both patients and controls, strong linkage disequilibrium was observed in the genotyped region, indicating that similar haplotypes are likely to be identical by descent. However, association analysis and the transmission disequilibrium test did not show significant results. Haplotype sharing statistics, a haplotype method that derives extra information from phase and single marker tests, did not show differences in haplotype sharing between patients and controls.

CONCLUSION

The current genotyping study did not confirm the previously reported association between HLA Class II genes and TGCT. As the HLA alleles for which associations were reported are also prevalent in the Dutch populations, these associations are likely to be nonexistent or much weaker than previously reported. Cancer 2002;95:1857–63. © 2002 American Cancer Society.

DOI 10.1002/cncr.10903
Association of proline‐directed protein kinase FA with tumorigenesis, invasion, and poor prognosis of human colon carcinoma
Authors: Chung Yuan‐Chiang , Chang King‐Jen , Yang Chuan‐Ching , Lai Ming‐Tsung , Hsu Chih‐Ping , Hsueh Sheng‐Feng , Peng Chien‐Chung , Fu Hsiao‐Hui , Chang Ya‐Fen , Yang Shiaw‐Der
Published: October 2002

BACKGROUND

Initial studies revealed that the multisubstrate proline‐directed protein kinase FA (PDPK FA) is overexpressed in various types of human carcinomas relative to normal controls. Suppression of overexpressed PDPK FA inhibits the growth of cancer cells, suggesting a role of this PDPK in human malignancy. In this study, we combine immunohistologic, molecular, cellular, animal, and clinicopathologic studies to demonstrate an essential and critical role of PDPK FA in progression and poor prognosis of human colon carcinoma.

METHODS

The stable antisense clones of human colon carcinoma cells with specific suppression of PDPK FA were established for tumorigenesis and invasion studies. In immunohistologic and clinicopathologic studies, the expression and localization of PDPK FA were analyzed by immunohistochemical staining of the specimens obtained from human colon carcinoma patients with Dukes Stage B/C.

RESULTS

Initial molecular and cellular studies revealed that the antisense clone of colon carcinoma cells (COLO‐205) with specific suppression of PDPK FA dramatically lost capabilities of adhesion, chemotaxis, and invasion when compared with the parental or control‐transfected colon carcinoma cells. This is the first indication of an association of overexpressed PDPK FA with colon carcinoma progression. In agreement with this notion, the in vivo study also revealed that the mice injected with the antisense clone with low‐level PDPK FA only developed very small tumors (< 0.5 cm3) even after a 6‐week observation. This is in contrast to the parental or control‐transfected cells that developed large tumors (> 5 cm3) under identical conditions. Pathologic evaluation revealed invasion to the muscle layer in all tumors formed by the parental cells. In contrast, there was no sign of invasion in mice injected with the antisense clone, confirming an essential role of PDPK FA in colon carcinoma progression. Clinicopathologic study also revealed that PDPK FA is preferentially overexpressed in the invasive area of colon carcinomatous tissues and overexpression of PDPK FA is statistically and closely correlated with venous/lymphatic infiltration, lymph node metastasis, and poor prognosis of colon carcinoma patients with Dukes Stage B/C.

CONCLUSIONS

The results demonstrate an essential and critical role of overexpressed PDPK FA in progression and poor prognosis of colon carcinoma patients. Suppression of overexpressed PDPK FA may provide a new powerful adjuvant approach to prevent human colon carcinoma progression and poor prognosis after surgery and chemotherapy. Cancer 2002;95:1840–7. © 2002 American Cancer Society.

DOI 10.1002/cncr.10904
Intravenous gamma globulin inhibits the production of matrix metalloproteinase‐9 in macrophages
Authors: Shapiro Sarah , Shoenfeld Yehuda , Gilburd Boris , Sobel Esther , Lahat Nitza
Published: October 2002

BACKGROUND

Degradation of the extracellular matrix (ECM) is essential for progression and metastasis of cancer cells. The ECM‐degrading enzymes, matrix metalloproteinases (MMPs), are produced mainly by intratumor monocytes/macrophages. MMPs, particularly MMP‐9, are reported to be of crucial significance for both growth and tumor invasiveness. Inhibition of the expression of MMP‐9 may prevent tumor development. High‐dose intravenous gamma globulins (IVIG) effectively inhibit metastatic spread of tumors in mice and humans and a variety of mechanisms have been suggested to explain this effect.

METHODS

We studied the effect of purified IVIG on MMP‐9 secretion and mRNA expression by in vitro differentiated human monocytic cells (cell lines and peripheral blood monocytes). Zymography was employed to measure gelatinase secretion and Northern blot analysis was used to detect mRNA expression. Involvement of F(ab)2 and Fc components in IVIG activity was also evaluated.

RESULTS

IVIG dose dependently and significantly reduced the amount of secreted MMP‐9 and its mRNA expression. F(ab)2, but not Fc fragments, led to suppressed MMP‐9 activity. However, competitive experiments demonstrated that Fc, but not F(ab)2 fragments, reversed the IVIG‐induced inhibitory effects.

CONCLUSIONS

These results suggest that the whole IgG molecule may be needed for pertinent IVIG‐induced MMP‐9 down‐regulation. This study points to an additional new mechanism whereby IVIG may play a beneficial role in the prevention of tumor spread in humans. Cancer 2002;95:2032–7. © 2002 American Cancer Society.

DOI 10.1002/cncr.10905
Classical Kaposi sarcoma
Authors: Brenner Baruch , Weissmann‐Brenner Alina , Rakowsky Erica , Weltfriend Sara , Fenig Eyal , Friedman‐Birnbaum Rachel , Sulkes Aaron , Linn Shai
Published: October 2002

BACKGROUND

Classical Kaposi sarcoma (CKS) is a rare indolent neoplasm that is particularly prevalent among Jews of Ashkenazi and Mediterranean origin. Data regarding prognostic factors for CKS are scarce. The aim of the current retrospective analysis was to better define prognostic subgroups among patients with CKS.

METHODS

Between 1960 and 1995, 248 consecutive patients with CKS were treated at the Rambam and Rabin Medical Centers in Israel. Although treatment options included local excision, radiotherapy, and chemotherapy, observation alone was used for 31% of patients. For prognostic factor analysis, disease progression was classified as any progression and dissemination, and progression‐free survival was calculated for each.

RESULTS

At a median follow‐up of 20 months, four patients (1.6%) died of CKS. Of the patients eligible for analysis, 94 of 220 (39%) had any progression and 23 of 120 (18%) had dissemination. Only 8 of 202 (4%) had visceral spread. On univariate analysis, age was a statistically significant prognostic factor for any progression (P= 0.04), whereas immunosuppression and visceral involvement at presentation had only borderline significance. Immunosuppression was the only prognostic factor for dissemination (P= 0.003). On multivariate analysis, both age and immunosuppression were significant prognostic factors for any progression (P= 0.001 and 0.01, respectively). Immunosuppression was also predictive of dissemination (P= 0.006).

CONCLUSIONS

Immunosuppression and older age (50 years and older) are strongly associated with poorer outcome among CKS patients. The two end points used in this study may be used for future prognostic factor analyses. Cancer 2002;95:1982–7. © 2002 American Cancer Society.

DOI 10.1002/cncr.10907
An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane
Authors: Buzdar Aman U. , Robertson John F. R. , Eiermann Wolfgang , Nabholtz Jean‐Marc
Published: October 2002

BACKGROUND

The newer generation, nonsteroidal aromatase inhibitors (AIs) anastrozole and letrozole have shown superior efficacy compared with tamoxifen as first‐line treatments and compared with megestrol acetate as second‐line therapy in postmenopausal women with advanced breast carcinoma. In an open‐label, Phase II trial, it was reported that exemestane showed numerical superiority compared with tamoxifen for objective response and clinical benefit. Because these agents ultimately may be administered for periods of up to 5 years in the adjuvant setting, it is of increasing importance to assess their tolerability and pharmacologic profiles.

METHODS

In the absence of data from direct clinical comparisons, the published literature was reviewed for the clinical pharmacology, pharmacokinetic characteristics, and selectivity profiles of anastrozole, letrozole, and exemestane.

RESULTS

At clinically administered doses, the plasma half‐lives of anastrozole (1 mg once daily), letrozole (2.5 mg once daily), and exemestane (25 mg once daily) were 41–48 hours, 2–4 days, and 27 hours, respectively. The time to steady‐state plasma levels was 7 days for both anastrozole and exemestane and 60 days for letrozole. Androgenic side effects have been reported only with exemestane. Anastrozole treatment had no impact on plasma lipid levels, whereas both letrozole and exemestane had an unfavorable effect on plasma lipid levels. In indirect comparisons, anastrozole showed the highest degree of selectivity compared with letrozole and exemestane in terms of a lack of effect on adrenosteroidogenesis.

CONCLUSIONS

All three AIs demonstrated clinical efficacy over preexisting treatments. However, there were differences in terms of pharmacokinetics and effects on lipid levels and adrenosteroidogenesis. The long‐term clinical significance of these differences remains to be elucidated. Cancer 2002;95:2006–16. © 2002 American Cancer Society.

DOI 10.1002/cncr.10908
Gliomatosis cerebri
Authors: Elshaikh Mohamed A. , Stevens Glen H.J. , Peereboom David M. , Cohen Bruce H. , Prayson Richard A. , Lee Shih‐Yuan , Barnett Gene H. , Suh John H.
Published: October 2002

BACKGROUND

Gliomatosis cerebri (GC) is a rare primary brain tumor characterized by proliferation of neoplastic glial cells that typically involve multiple brain areas, with preservation of brain structures and sparing of neurons. The optimal therapeutic strategy is not well established. The impact of radiotherapy on survival in patients with GC remains undefined.

METHODS

Between 1980 and 2001, 12 patients with GC were identified, representing less than 1% of all patients with primary brain neoplasms treated at the Cleveland Clinic.

RESULTS

All 12 patients had brain biopsies between March 1986 and July 2001 (seven males, five females, with a median age of 53 years [range, 13–85 years]). Median Karnofsky performance status at the time of presentation was 70 (range, 40–90). Eight patients had low‐grade gliomas and four patients had anaplastic astrocytomas. Eight patients received radiation treatment to the brain as the only treatment, and four received neither radiation nor chemotherapy. The median dose of megavoltage radiation was 55.4 Gy (range, 45–61.2 Gy). Of the eight patients who received brain radiotherapy, the clinical and radiologic follow‐up findings improved in three patients, stabilized in three patients, and worsened in two patients. Median follow‐up was 10.3 months (range, 1–55 months). The median survival for the eight patients who received brain radiotherapy was 11.4 months. The one– and two‐year survival rates were 45% and 30%, respectively. Two of the eight patients who received radiotherapy were alive at the time of writing. The four patients who did not receive radiotherapy died of the disease at 0.6, 1.0, 1.9, and 2.4 months after diagnosis.

CONCLUSIONS

Gliomatosis cerebri is associated with poor survival. Although brain radiotherapy controlled or stabilized disease progression in most patients, the overall survival after brain radiotherapy alone was not satisfactory. More aggressive therapy may be needed. Cancer 2002;95:2027–31. © 2002 American Cancer Society.

DOI 10.1002/cncr.10909
Comparison of selection strategies for genetic testing of patients with hereditary nonpolyposis colorectal carcinoma
Authors: Reyes Carolina M. , Allen Brian A. , Terdiman Jonathan P. , Wilson Leslie S.
Published: October 2002

BACKGROUND

Molecular testing for hereditary nonpolyposis colorectal carcinoma (HNPCC) is becoming standard care and it is cost‐effective compared with no genetic testing. However, the best strategy for detection of HNPCC gene carriers is unknown.

METHODS

We use a decision analytic model to evaluate the effectiveness and incremental cost‐effectiveness of four commonly used testing strategies to detect HNPCC gene carriers. The model starts with a population of colorectal carcinoma (CRC) patients and measures costs, the number of gene carriers detected, and incremental costs per gene carrier detected.

RESULTS

We found that germline testing on only those CRC probands who meet the Amsterdam criteria detects the fewest gene carriers and has the lowest cost whereas tumor microsatellite instability (MSI) testing of all CRC patients and families has the highest cost and detects the most gene carriers. When cost‐effectiveness is considered, the mixed strategy (MSH2 and MLH1 testing on those who meet the Amsterdam criteria and germline testing for the remainder who meet less stringent modified criteria and are MSI‐High) seems superior. The mixed strategy detects 59.6 mutation carriers per 1000 CRC cases and costs much less than the test all strategy, which has an incremental cost‐effectiveness of $51,151. The mixed strategy often other strategies and when compared to the Amsterdam strategy, has a cost‐effectiveness of only $6441 per gene carrier detected.

CONCLUSIONS

It is not very effective to limit genetic testing to only individuals who meet the Amsterdam criteria, as many gene carriers are missed. However, testing all CRC patients for tumor MSI‐H, although effective, may be prohibitively expensive. A mixed strategy is the more cost‐effective approach. Cancer 2002;95:1848–56. © 2002 American Cancer Society.

DOI 10.1002/cncr.10910
Telomerase activity in Stage II colorectal carcinoma
Authors: Kawanishi‐Tabata Rika , Lopez Francisco , Fratantonio Sam , Kim Nam , Goldblum John , Tubbs Raymond , Elson Paul , Lavery Ian , Bukowski Ronald M. , Ganapathi Ram , Ganapathi Mahrukh K.
Published: October 2002

BACKGROUND

Telomerase is a ribonucleoprotein polymerase that adds telomeric repeats to chromosome ends. This enzyme is deficient in the majority of normal somatic cells, but often is reactivated during tumorigenesis. In the current study, the authors examined telomerase activity in human American Joint Committee on Cancer Stage II colorectal carcinomas and correlated it with traditional prognostic indicators and disease outcome.

METHODS

The telomerase repeat amplification protocol (TRAP) was employed to determine telomerase activity in 122 surgical specimens (from 77 male and 45 female patients) of human Stage II colorectal carcinoma. The primary site of the tumor was the colon in 52 cases and the rectum in 70 cases. Telomerase activity was correlated with traditional prognostic indicators such as gender, age, T classification, tumor size, tumor grade, and disease outcome (overall survival and disease‐free survival). The Median follow‐up for patients who still were alive was 5.8 years.

RESULTS

Telomerase activity was detected in 80% of the tumors (98 of 122 tumors). Telomerase‐positive patients differed from telomerase‐negative patients in that they tended to be female (41% vs. 21%; P = 0.1), presented with primary tumors of the colon more frequently (49% vs. 17%; P = 0.01), and had a higher T classification (T4) (62% vs. 38%; P = 0.04). Univariate and multivariate analyses demonstrated a correlation between telomerase activity and disease‐free survival (P = 0.05).

CONCLUSIONS

Although a large percentage of Stage II colorectal carcinoma samples were positive for telomerase activity, the prognosis for patients with telomerase‐negative tumors was found to be worse than that for patients with telomerase‐positive tumors. Cancer 2002;95:1834–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10911
Estrogen replacement therapy for menopausal women with a history of breast carcinoma
Authors: Vassilopoulou‐Sellin Rena , Cohen Deborah S. , Hortobagyi Gabriel N. , Klein Mary Jean , McNeese Marsha , Singletary S. Eva , Smith Terry L. , Theriault Richard L.
Published: October 2002

BACKGROUND

Women with a history of breast carcinoma generally have been advised to avoid estrogen replacement therapy (ERT). The validity of this approach has been scrutinized and debated in recent years, and reassessment through appropriate clinical trials has been suggested.

METHODS

The authors conducted a prospective clinical trial to assess the safety and efficacy of prolonged ERT in a group of menopausal women with localized (Stage I or Stage II) breast carcinoma and a minimum disease free interval of 2 years if estrogen receptor (ER) was negative or 10 years if ER status was unknown. For 5 years, the authors followed 77 trial participants and 222 other women with clinical and prognostic characteristics comparable to those of the trial participants. Overall, 56 women were on ERT, and 243 women were not on ERT. The association of ERT with skeletal and lipid changes was assessed in the randomized trial participants. The effect of ERT on the development of recurrent or new breast carcinoma and other carcinomas was analyzed both in the trial participants and in the overall group.

RESULTS

Patient and disease characteristics, such as tumor size, number of lymph nodes involved, ER status, menopausal status, and disease free interval were comparable for women who were on ERT and women who were not on ERT. These same parameters also were comparable for women who joined the trial and women who did not. ERT use was associated with modest lipid and skeletal benefits. The introduction of ERT did not compromise disease free survival. Two of 56 women on ERT (3.6%) developed a contralateral, new breast carcinoma. In the group that was not on ERT, 33 of 243 women (13.5%) developed new or recurrent breast carcinoma. There were no differences in the development of other carcinomas with respect to ERT.

CONCLUSIONS

ERT did not compromise disease free survival in select patients who were treated previously for localized breast carcinoma. Larger scale randomized trials are needed to confirm these findings. Cancer 2002;95:1817–26. © 2002 American Cancer Society.

DOI 10.1002/cncr.10913
Effects of cyclosporine on hematopoietic and immune functions in patients with hypoplastic myelodysplasia
Authors: Selleri Carmine , Maciejewski Jaroslaw P. , Catalano Lucio , Ricci Patrizia , Andretta Claudia , Luciano Luigiana , Rotoli Bruno
Published: October 2002

BACKGROUND

Immunosuppression may benefit some patients with hypoplastic myelodysplasia (HMDS) and refractory anemia (RA), but its mechanism of action is still obscure.

METHODS

Using flow cytometry, we studied Fas‐receptor (Fas‐R), Fas‐ligand (Fas‐L), and interferon‐γ (IFN‐γ) expression in CD34+ cells and lymphocytes obtained from 11 HMDS and 20 RA patients. In colony assays and long‐term cultures, the effects of Fas triggering, IFN‐γ blockade, or cyclosporine(CsA) on the growth of hematopoietic progenitors (colony‐forming cells [CFC]) were determined. The effects of CsA at daily doses of 1–3 mg/kg for at least 3 months in HMDS patients were also studied.

RESULTS

In basal conditions, committed and immature progenitor cells were found decreased in myelodysplastic (MDS) patients. No significant differences between HMDS and RA patients were detected. IFN‐γ–expressing CD4+ cells were significantly increased in HMDS patients, whereas intracytoplasmic Fas‐L expression was only borderline elevated in CD3+ MDS cells. Increased numbers of CD34+ cells expressing Fas‐R were found in HMDS and RA patients. CFC and secondary CFC showed higher susceptibility to Fas‐L–mediated inhibition and the blockade of IFN‐γ improved marrow primary, but not secondary, CFC growth. CsA added in vitro to patient's lymphocytes significantly decreased the number of IFN‐γ–expressing CD4+ cells, but not Fas‐L production. These effects were associated with increased colony formation. Similar to IFN‐γblockade, production of secondary CFC was not enhanced by CsA. Administration of CsA to patients resulted in prolonged partial hematologic improvement in 8 of 11 HMDS patients.

CONCLUSIONS

Increased frequency of IFN‐γ producing CD4+ cells supports the involvement of lymphocyte‐mediated suppression of hematopoiesis in the development of cytopenia in MDS patients. The ability of CsA to decrease in vitro IFN‐γ production may improve hematopoietic function, explaining the beneficial effect of this agent in HMDS patients. Cancer 2002;95:1911–22. © 2002 American Cancer Society.

DOI 10.1002/cncr.10915
Expression of matrix metalloproteinase 1, matrix metalloproteinase 2, and matrix metalloproteinase 9 in carcinoma of the head and neck
Authors: Franchi Alessandro , Santucci Marco , Masini Emanuela , Sardi Iacopo , Paglierani Milena , Gallo Oreste
Published: October 2002

BACKGROUND

Numerous reports have documented a direct involvement of matrix metalloproteinase (MMP) overexpression in the development and progression of head and neck squamous cell carcinoma (HNSCC). In this study, the authors examined whether the expression of MMPs in HNSCC is correlated with other steps involved in tumor growth and metastasis, like angiogenesis, activation the nitric oxide (NO) pathway, and alteration of the p53 tumor suppressor gene.

METHODS

MMP‐1, MMP‐2, and MMP‐9 expression levels were examined immunohistochemically in samples from 43 patients with HNSCC. Microvessel density (MVD) was determined by immunostaining of endothelial cells with anti‐CD31 monoclonal antibody. Inducible nitric oxide synthase (iNOS) activity and cyclic guanosine monophosphatate (cGMP) levels were assessed in fresh tumor samples, whereas exons 5–9 of the p53 gene were analyzed by reverse transcriptase‐polymerase chain reaction, single‐strand conformation polymorphism analysis and were sequenced.

RESULTS

MMP‐1 overexpression (>10% of tumor cells) was identified in 32 tumors (74.5%), whereas elevated levels of MMP‐2 and MMP‐9 were detected in 17 tumors (39.5%) each. Tumors with MMP‐9 overexpression were characterized by significantly higher MVD (P = 0.05) and significantly higher iNOS activity and cGMP levels (P = 0.005 and P = 0.02, respectively). Moreover, p53 mutation was associated strongly with MMP‐9 overexpression (P = 0.004). Conversely, no correlation was found between MMP‐1 and MMP‐2 expression, angiogenesis, iNOS activity, cGMP levels, and p53 mutation in this series.

CONCLUSIONS

This study documents the existence of a correlation between MMP‐9 expression, activity of the iNOS pathway, p53 status, and angiogenesis in patients with HNSCC. This raises the possibility that p53 mutation, which frequently is present in HNSCC, may result in increased angiogenesis and invasiveness related to increased nitric oxide and MMP production by tumor cells, ultimately contributing to tumor progression. Cancer 2002;95:1902–10. © 2002 American Cancer Society.

DOI 10.1002/cncr.10916
Comparative analysis of CA125, tissue polypeptide specific antigen, and soluble interleukin‐2 receptor α levels in sera, cyst, and ascitic fluids from patients with ovarian carcinoma
Authors: Sedlaczek Paweł , Frydecka Irena , Gabryś Marian , van Dalen Arie , Einarsson Roland , Harłozińska Antonina
Published: October 2002

BACKGROUND

The serum markers CA125, tissue polypeptide specific antigen (TPS), and soluble interleukin‐2 receptor alpha (sIL‐2Rα) concentrations were determined in sera, cyst, and ascitic fluids from patients with malignant and benign ovarian neoplasms.

METHODS

CA125, TPS, and sIL‐2Rα concentrations were measured in sera, cyst, and ascitic fluids by immunoassays in 67 patients with carcinoma and in 32 patients with benign ovarian neoplasms.

RESULTS

CA125, TPS, and sIL‐2Rα levels were elevated significantly in sera from patients who had ovarian carcinoma compared with patients who had benign neoplasms (P < 0.001). Patients who had International Federation of Gynecology and Obstetrics (FIGO) Stage III–IV disease had significantly higher serum levels for the markers studied compared with patients who had FIGO Stage I–II disease (P < 0.001 for CA125; P = 0.02 for TPS and sIL‐2Rα). Concurrent measurement of CA125 and sIL‐2Rα in sera identified 100% of ovarian carcinomas in FIGO Stage I–II. All patients with carcinoma demonstrated markedly higher levels of CA125 and TPS for both cyst and ascites compared with corresponding sera (P < 0.001). The level of sIL‐2Rα was higher statistically in ascitic fluid compared with the level in serum (P < 0.001); however, its values in sera and cyst fluids were comparable. In ascitic fluid, the CA125 level was significantly higher in patients who had FIGO Stage III–IV disease compared with patients who had FIGO Stage I–II disease (P = 0.002), whereas such correlations were not found for TPS or sIL‐2Rα. In cyst fluids, the levels of all studied markers were independent of the FIGO stage. In cyst fluids from patients with benign ovarian neoplasms, TPS and sIL‐2Rα levels were significantly lower compared with the levels in patients with ovarian carcinoma (P < 0.001), whereas the values of CA125 were overlapping. CA125 and TPS concentrations were higher in cyst fluids compared with corresponding sera, whereas sIL‐2Rα levels were comparable and low in cyst fluids and in the circulation of patients with benign neoplasms.

CONCLUSIONS

In patients with ovarian carcinoma, TPS and CA125 concentrations were significantly higher in the place of their generation compared with the concentrations in blood circulation. sIL‐2Rα values were higher in ascites compared with the values in corresponding sera, and its concentrations in sera and cyst fluids were comparable. The assessment of serum sIL‐2Rα levels showed potential complementary value to CA125 for the detection of ovarian carcinoma in early FIGO stages; however, a 9% false positive rate limited the significance of cumulative value for a combination of these circulating markers. Cancer 2002;95:1886–93. © 2002 American Cancer Society.

DOI 10.1002/cncr.10917
Irinotecan plus cisplatin has substantial antitumor effect as salvage chemotherapy against germ cell tumors
Authors: Miki Tsuneharu , Mizutani Yoichi , Nonomura Norio , Nomoto Takeshi , Nakao Masahiro , Saiki Shigeru , Kotake Toshihiko , Okuyama Akihiko
Published: October 2002

BACKGROUND

Only 20–30% of patients with refractory or recurrent germ cell tumors (GCT) are cured by salvage chemotherapy. Irinotecan, a new derivative of camptothecin, is a potent anticancer agent against a variety of solid cancers. The current pilot study investigated the efficacy of salvage chemotherapy with irinotecan in combination with cisplatin (CDDP) or nedaplatin (NDP), a derivative of cisplatin, for GCT.

METHODS

The combination chemotherapy consisted of 100–150 mg/m2 irinotecan on Days 1 and 15 or 200–300 mg/m2 on Day 1 in combination with 20 mg/m2 CDDP on Days 1–5 or 100 mg/m2 NDP on Day 1 every 4 weeks. Patients with refractory GCT, ranging in age from 17 to 43 years, received 2–11 cycles of the combination chemotherapy. The median duration of follow‐up is 28 months (8–140 months).

RESULTS

Twenty patients entered this study, 18 of whom were assessed for response and toxicity. The response rate was 50 % (two complete responses and seven partial responses). Nine patients remain alive without disease. However, six patients died of the disease and one patient died of a brain glioma. The 5‐year survival rate was approximately 53%. Myelosuppression was the major toxicity, but was manageable.

CONCLUSIONS

This pilot study demonstrates that the chemotherapy with irinotecan in combination with CDDP or NDP showed significant anticancer activity for patients with refractory GCT, without serious side effects. Although this study comprised only a few patients, these findings suggest that the combination chemotherapy may be one of the options of salvage chemotherapy for patients with refractory GCT. Cancer 2002;95:1879–85. © 2002 American Cancer Society.

DOI 10.1002/cncr.10918
Analysis of survival after laparoscopy in women with endometrial carcinoma
Authors: Eltabbakh Gamal H.
Published: October 2002

BACKGROUND

The effect of the laparoscopic surgical approach on the survival of women with endometrial carcinoma remains unclear. The objectives of the current study were to assess the effect of laparoscopic surgery on the survival of women with early‐stage endometrial carcinoma and to analyze the factors that affect such survival.

METHODS

A retrospective review of women presenting with clinical stage I endometrial carcinoma (according to the 1988 International Federation of Gynecology and Obstetrics Staging System) was performed. Women treated with laparoscopy were compared with those treated with laparotomy with regard to their characteristics, surgical procedure, treatment, surgical stage, histology, tumor grade, and recurrence‐free and overall survival. Factors affecting survival (surgical approach, histology, grade, and surgical stage) were evaluated using multivariate analysis and survival curves were constructed using Kaplan–Meier analyses.

RESULTS

One hundred women underwent laparoscopy and 86 underwent laparotomy. Both groups were similar with regard to age, parity, menopausal status, lymphadenectomy, surgical stage, tumor grade, histology, and postoperative radiation therapy. Women who underwent laparoscopy and those who underwent laparotomy had similar 2‐year and 5‐year estimated recurrence‐free survival rates (93% vs. 94% and 90% vs. 92%, respectively), as well as similar 2‐year and 5‐year overall survival rates (98% vs. 96% and 92% vs. 92%, respectively). There was no apparent difference with regard to the sites of recurrence between both groups. In univariate and multivariate analyses, surgical stage, tumor grade, and histology (but not the surgical approach) were found to have a significant effect on survival.

CONCLUSIONS

Although longer follow‐up is needed, the survival of women with early‐stage endometrial carcinoma does not appear to be worsened by laparoscopy. Surgical stage, tumor histology, and tumor grade were found to significantly affect survival regardless of the surgical approach used. Cancer 2002;95:1894–901. © 2002 American Cancer Society.

DOI 10.1002/cncr.10928
Self‐image in anorexia nervosa 7.5 years after initial presentation to a specialized eating disorders service
Authors: Button Eric J. , Warren Rachel L.
Published: November 2002

Objective:

The present study examined self‐image in a group of sufferers of anorexia nervosa some years after initial presentation.

Method:

A cohort of anorectic patients was followed up 7.5 years after presentation at a specialist locally based eating disorders service for adults. All subjects were invited to take part in a semi‐structured interview, which included completion of a repertory grid (SELFGRID) and a series of questionnaires.

Results:

The group as a whole showed continuing low self‐esteem. Measures of low self‐esteem were strongly related to measures of overall well‐being and particularly highly correlated with the ‘ineffectiveness’ scale of the Eating Disorders Inventory.

Discussion:

It is argued that the results highlight the chronic nature of low self‐esteem in anorexia nervosa and that greater emphasis should be placed on therapeutic initiatives to tackle this problem. Copyright © 2002 John Wiley & Sons, Ltd and Eating Disorders Association.