Non-solid Tumors Research Articles

A clinicopathological study of resected adenocarcinoma 2 cm or less in diameter

Background The biological behavior of small adenocarcinoma is different in each patient and these are especially enormous differences when evaluating solid tumors and nonsolid tumors. Methods A total of 159 adenocarcinomas 2 cm or less in diameter were studied. Several clinicopathological factors were retrospectively analyzed. Results The diameter of the primary tumors was less than 1 cm in 47 patients, 1–1.5 cm in 49 patients, and 1.5–2 cm in 63 patients, respectively. Almost all patients (147) were pathologic N0 and there were 12 node-positive patients (7.5%). Lymph-node involvement was observed in 1 patient with a tumor diameter measuring less than 1 cm and in 11 patients with a tumor diameter measuring 1–2 cm. According to Noguchi' s classification, 33 patients belonged to class A or B, 71 patients belonged to class C, and 55 patients belonged to class D, E, or F. The ratio of ground-glass opacity (GGO) area in the main tumor in high resolution computed tomography was classified into two groups with a threshold of 50%. There were 44 patients with a GGO ratio of equal to or greater than 50%, none of which indicated lymph-node metastasis or tumor recurrence during follow-up (5-year survival = 100%). On the contrary among 115 patients with a GGO ratio less than 50%, lymph-node involvement was indicated in 12 patients (10.4%) and the 5-year survival rate was 83.9%. Conclusions The biological malignancy of small adenocarcinomas might be accurately evaluated by the proportion of GGO area as well as the Noguchi classification.

Long-term risk of second malignancy after treatment of Hodgkin’s disease: the influence of treatment, age andfollow-up time

BackgroundTo quantify the long-term risk of second cancers (SCs) up to 30 years after primary treatment for Hodgkin’s disease (HD) Material and methodsIn the period 1968 to 1985, an unselected population of 1024 patients started treatment for HD at the Norwegian Radium Hospital (NRH) and were followed for SC from 1969 through 1998 by The Norwegian Cancer Registry. The median age at diagnosis of HD was 40 years, and the median time at follow-up was 14 years. ResultsOf 197 SCs, 14 were acute non-lymphocytic leukemia (ANLL), 31 non-Hodgkin’s lymphoma (NHL) and 152 solid cancers. The standardized incidence ratio (SIR) was significantly increased for SCs as a group, and for the subgroups ANLL, NHL, lung cancer, breast cancer, stomach cancer and melanoma. ANLL was related to heavy treatment with chemotherapy (CT) and combined CT and radiotherapy (RT), NHL was not treatment related, and solid tumors were related to radiotherapy only or combined RT and CT. The SIR of ANLL and NHL reached a peak between 5 and10 years after treatment. Solid and non-solid tumors increased with young age at diagnosis of HD and solid tumors increased with follow-up time up to 28 years ConclusionIn a long-term follow-up study of HD patients of all ages, the SIR of solid tumors was high in patients treated at young age and decreased with increasing age. Most solid tumors had started within or at the edge of the irradiated field, and SIR of solid tumors increased even 20–30 years after diagnosis.

Recurrent growth factor starvation promotes drug resistance in human leukaemic cells.

Multi-drug resistance can be induced by various environmental stresses including an exposure to chemical drugs and X-ray irradiation. In addition, hypo-nutritive conditions are known to promote multi-drug resistance in solid tumours. To understand the importance of nutritive conditions in the development of drug resistance in non-solid tumours and to know whether a transient malnutrition could induce a permanent reduction in drug sensitivity, leukaemic cells were transiently cultured under growth factor-starved conditions. Granulocyte-macrophage colony-stimulating factor-dependent human leukaemic MO7e cells were cultured in the absence of granulocyte-macrophage colon-stimulating factor for 2 weeks, during which the majority of the cells died, and the minor viable cells were expanded in the presence of granulocyte-macrophage colon-stimulating factor for following 1 week. This procedure was repeated three times, and the surviving cells were cloned by limiting dilution. These clones underwent G1 arrest in the absence of granulocyte-macrophage colon-stimulating factor, while parental cells underwent apoptosis. Interestingly, activities of the downstream targets of granulocyte-macrophage colon-stimulating factor receptor were regulated in a granulocyte-macrophage colon-stimulating factor-independent manner, indicating that the ligand-independent activation of granulocyte-macrophage colon-stimulating factor receptor had not taken place. Moreover, the 4–7-fold increases in IC50 for etoposide and the 2–6-fold increase in IC90 for doxorubicin was observed. Furthermore, Bcl-2 protein expression was significantly up-regulated in the clones while no significant changes in Bax, Bcl-xL, P-glycoprotein and Hsp70 protein expression and no consistent changes in p53 expression were detected. We propose that recurrent growth factor starvation, which may occur in vivo when stromal function is damaged after intensive chemotherapy or bone marrow occupation by malignant cells, causes selection of drug resistant leukaemia cells that will expand when the growth factor supply recovers.British Journal of Cancer (2002) 86, 292–300. DOI: 10.1038/sj/bjc/6600036 www.bjcancer.com© 2002 The Cancer Research Campaign

MR imaging of liver metastases at 1.5 T: similar contrast discrimination with T1- and T2-weighted pulse sequences.

The authors evaluated soft-tissue contrast on spin-echo (SE) proton density-weighted, SE T2-weighted, SE short-echo-time (TE) T1-weighted, and gradient-echo (GRE) images of 34 patients with known hepatic tumors who underwent high-field-strength (1.5-T) magnetic resonance imaging. For solid liver tumors, the difference in the mean lesion-liver contrast-to-noise ratios (C/Ns) with T1- (GRE and SE) and T2-weighted pulse sequences was not statistically significant (P greater than .05). For nonsolid liver tumors, the T2-weighted images provided significantly greater (P less than .05) mean lesion-liver C/N than T1-weighted GRE images. Mean liver signal-to-noise ratio was significantly greater on T1-weighted GRE (P less than .0001) and T1-weighted SE (P less than .05) images than on T2- and proton density-weighted images. Qualitative analysis of T1-weighted (SE and GRE) images and proton density- plus T2-weighted images showed that lesion conspicuity was similar in 25 of 32 patients (78%). The results suggest that liver tumor imaging at high field strength can be performed with short-TE T1-weighted (SE or GRE) or conventional T2-weighted pulse sequences.

A multifaced DNA ploidy analysis to determine ovarian carcinoma aggressiveness

A microfluorometric DNA study was conducted on isolated cells from 64 fragments of ovarian epithelial tumors. Data analysis considered the DNA content of the main stemline and the prevalence of cells in the different compartments of the DNA ploidy histogram in relation to the mitotic activity index and the histologic architecture. Main stemlines were found remarkably stable in different parts of the same tumor. Peridiploid (1.8c to 2.2c) stemlines were found both in well-differentiated and in poorly differentiated tumors. However, low aneuploid (2.2c to 3.0c) stemlines were mostly found in nonsolid tumors and high ploidy (3.2 to 5.04 c) stemlines were prevalent in solid tumors. A comparative analysis between DNA ploidy parameters and mitotic activity was useful to evaluate the expanding modalities of neoplastic cell populations. This analysis revealed that several tumors accumulate an excessive amount of heteroploid cells and others an excessive amount of G2 cells. Yet, most neoplastic cell populations vary from slow to rapidly growing patterns without relevant abnormalities in their ploidy graphic profiles. No relationship was found between stemline ploidy and histologic architecture compared with expanding modalities. These findings indicate that multifaced criteria combining features such as main ploidy, graphic profile, mitotic rate, and histologic architecture measured on one or more microsamples of the same tumor may help to objectively estimate the aggressiveness reached by the neoplastic cells at the time of clinical presentation.

非固形腫瘍に於けるPhotosensitizerの腫瘍集積性と治療効果

Solid tumors can accumulate large amount of HpD and other photosensitizers. The effectiveness of PDT after administration of HpD has been demonstrated.On the other hand, almost nobody has investigated the accumulation of photosensitizers in non-solid tumors. In this study, we measured the fluorescence spectra of HpD and 13, 17-di tetra ammonium protoporphyrin (PH-1008, MW. 988. 8, Hamari Chemical Ltd.) in ascites tumors of mice by an excimer dye laser system. Large amounts of both HpD and PH-1008 were accumulated in ascites. HpD showed a rapidly increasing pattern, but PH-1008 showed a slowly increasing pattern. PH-1008 bound specifically with Meth-A cells. In pellets. PH-1008 showed maximum fluorescence at 48hrs after i.v. injection, and the maximum concentration of PH-1008 was approximately 3 times greater than that of HpD at 24hrs after. The reason may be related to the possible electric binding of PH-1008 and cell membrane. PH-1008 had excellent cytocidal effects following PDT at 48hrs after i.v. injection. The viability of Meth-A cells was 17.0%. The result shows that PH-1008 may be ideal photosensitizer for application to the treatment of non-solid tumors.

Cancer Clinical Trials: Methods and Practice.

The first complete guide to organizing and running cancer clinical trials, this book brings together in a single volume information on the fundamental concepts of trials, design, planning, conduct, and analysis that has previously ben scattered throughout medical and statistical literature. Topics covered include scientific background, ethical considerations, design and quality control, treatment toxicities and results in solid and non-solid tumors, preclinical and phase I trials, design of phase II trials, and analysis of phase III trials. The editors have updated the original 1984 text for this new paperback edition.

Chemosensitivity testing of nonsolid tumors by the subrenal-capsule implant assay

A procedure to test chemosensitivity of nonsolid tumors using the subrenal-capsule xenograft assay has been developed. This technique is applicable to the study of malignant effusions and hematopoietic tumors. The tumor cells are centrifuged to form a pellet and the pellet is resuspended in the presence of bovine fibrinogen to form a jelled clot. This clot is cut into fragments which are implanted beneath the renal capsule of normal mice. The growth of the tumor cells from ovarian adenocarcinoma obtained from ascitic fluid is better than that of tumor fragments from the solid tumors. This is probably a reflection of the greater viability of tumor cells from ascitic fluids. The sensitivity to chemotherapy was the same for the solid tumor and its malignant effusions.

Seven-drug polychemotherapy in the treatment of advanced and recurrent squamous carcinoma of the female genital tract

Single-agent chemotherapy of advanced and recurrent squamous carcinoma of the female genital tract has been largely ineffective. Combination-drug therapy which has augmented the efficacy of chemotherapy in numerous solid and nonsolid human tumors is usually attended by a degree of toxicity that has discouraged its use against malignancies exhibiting a poor response to single agents. A seven-drug regimen consisting of cyclophosphamide, 5-fluorouracil, actinomycin D, vincristine, cytosine arabinoside, methotrexate, and bleomycin administered during a 24 hour period at 4 week intervals was selected for clinical trial against squamous malignancies of the female genitalia because of its proved broad-spectrum activity among solid tumors and its low incidence of serious toxicity. Severe bone marrow depression occurred during only two of 98 drug cycles involving 23 patients. An objective tumor response was observed in nine of 18 evaluable patients. This regimen appears to be useful in the palliative management of squamous carcinoma of the female genital tract.