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PubMed2006

Disseminated spread of recurrent oligodendroglioma (WHO grade II).

Oligodendroglioma is a relatively uncommon primary brain tumour. The occurrence of metastatic dissemination of oligodendroglioma is rare and usually occurs in patients with anaplastic oligodendroglioma. The dissemination of WHO Grade II oligodendroglioma can occur and we report a patient with an initial diagnosis of a left temporal oligodendroglioma who presented with disseminated disease in the left temporal lobe, sellar region, medulla oblongata, both frontal lobes and ventricles more than 8 years later. Histology at dissemination showed anaplastic oligodendroglioma. Similar reports of metastatic dissemination of oligodendrogliomas reveal that the tumours may remain as WHO Grade II or may progress to anaplastic oligodendroglioma at metastasis. However, regardless of the histological grade at metastasis, the prognosis of metastatic oligodendroglioma is poor.

Humans↗

PubMed2006

Dissemination of a community-based physical activity project: the case of 10,000 steps.

This paper describes the use of a web-site for the dissemination of the community-based '10,000 steps' program which was originally developed and evaluated in Rockhampton, Queensland in 2001-2003. The website provides information and interactive activities for individuals, and promotes resources and programs for health promotion professionals. The dissemination activity was assessed in terms of program adoption and implementation. In a 2-year period (May 2004-March 2006) more than 18,000 people registered as users of the web-site (logging more than 8.5 billion steps) and almost 100 workplaces and 13 communities implemented aspects of the 10,000 steps program. These data support the use of the internet as an effective means of disseminating ideas and resources beyond the geographical borders of the original project. Following this preliminary dissemination, there remains a need for the systematic study of different dissemination strategies, so that evidence-based physical activity programs can be translated into more widespread public health practice.

Adolescent↗

PubMed2004

A national dissemination of an evidence-based self-management program: a process evaluation study.

While evidence exists regarding the effectiveness of many health education interventions, few of these evidence-based programs have been systematically or widely disseminated. This paper reports on the dissemination of one such intervention, the 6-week peer-led Chronic Disease Self-Management Program, throughout a large health-care system, Kaiser Permanente. We describe the dissemination process and, using qualitative analysis of interviews and surveys, discuss the factors that aided and hindered this process and make recommendations for similar dissemination projects. Six years after the beginning of the dissemination process, the program is integrated in most of the Kaiser Permanente regions and is being offered to several thousand people a year.

Aged↗

PubMed1995

Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trial Group.

PURPOSE: Amphotericin B has been the treatment of choice for disseminated histoplasmosis in patients with acquired immunodeficiency syndrome (AIDS). Oral antifungal agents would be welcome alternatives to standard treatment of disseminated histoplasmosis in less severe cases. The purpose of this study was to assess the efficacy and safety of itraconazole therapy in patients with AIDS and disseminated histoplasmosis. PATIENTS AND METHODS: This was a multicenter, open-label, nonrandomized prospective trial conducted in university hospitals of the AIDS Clinical Trial Group. All patients had AIDS and first episodes of disseminated histoplasmosis. Patients with central nervous system involvement or with severe clinical manifestations were excluded. Patients were treated with itraconazole BID by mouth 300 mg for 3 days and then 200 mg BID for 12 weeks. Resolution of clinical findings, clearance of positive cultures, and drug tolerance were the main outcome measurements. A secondary objective was effect of therapy on Histoplasma capsulatum var capsulatum antigen levels. RESULTS: Of 59 evaluable patients, 50 (85%) responded to therapy. Five patients withdrew because of progressive infection, 1 died of a presumed pulmonary embolus within the first week of therapy without improvement, 2 withdrew because of toxicity, and 1 was lost to follow-up after week 2 of therapy. Patients with moderately severe clinical (fever > 39.5 degrees C or Karnofsky score < 60) or laboratory abnormalities (alkaline phosphatase > 5 times normal or albumin < 3 g/dL) at baseline tended to respond more poorly than did other patients. Resolution of complaints of fever and improvement in fatigue occurred after a median of 3 and 6 weeks, respectively, and weight gain after 2 weeks. Fungemia cleared after a median of 1 week. H capsulatum var capsulatum antigen cleared from the urine and serum at rates of 0.2 and 0.3 units per week, respectively. CONCLUSIONS: Itraconazole is safe and effective induction therapy for mild disseminated histoplasmosis in patients with AIDS, offering an alternative to amphotericin B in such cases. Patients with moderately severe or severe histoplasmosis should first be treated with amphotericin B and then may be switched to itraconazole after achieving clinical improvement.

AIDS-Related Opportunistic Infections↗

PubMed2002

Fatal hemorrhage after radiochemotherapy for leptomeningeal dissemination of glioma: report of two cases.

BACKGROUND: Dissemination of malignant gliomas is often observed, but the treatment of choice for leptomeningeal dissemination has not been established. CASE DESCRIPTIONS: A 55-year-old man suffered fatal hemorrhage 1 day after whole brain irradiation (2 Gy) along with intravenous administration of 150 mg of nitrosourea (ACNU) for leptomeningeal dissemination of glioblastoma. A 14-year-old boy suffered hemorrhage after intrathecal administration of 10 mg of methotrexate for recurrence of leptomeningeal dissemination of anaplastic astrocytoma 4 months after local brain irradiation and ACNU administration, and died 19 days later. CONCLUSION: Massive fatal hemorrhage is an unusual but possible acute complication after radiochemotherapy for leptomeningeal dissemination of gliomas.

Adolescent↗

PubMed2002

Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer.

BACKGROUND: Because cancer patients with small tumours often relapse despite local and systemic treatment, we investigated the genetic variation of the precursors of distant metastasis at the stage of minimal residual disease. Disseminated tumour cells can be detected by epithelial markers in mesenchymal tissues and represent targets for adjuvant therapies. METHODS: We screened 525 bone-marrow, blood, and lymph-node samples from 474 patients with breast, prostate, and gastrointestinal cancers for single disseminated cancer cells by immunocytochemistry with epithelial-specific markers. 71 (14%) of the samples contained two or more tumour cells whose genomic organisation we studied by single cell genomic hybridisation. In addition, we tested whether TP53 was mutated. Hierarchical clustering algorithms were used to determine the degree of clonal relatedness of sister cells that were isolated from individual patients. FINDINGS: Irrespective of cancer type, we saw an unexpectedly high genetic divergence in minimal residual cancer, particularly at the level of chromosomal imbalances. Although few disseminated cells harboured TP53 mutations at this stage of disease, we also saw microheterogeneity of the TP53 genotype. The genetic heterogeneity was strikingly reduced with the emergence of clinically evident metastasis. INTERPRETATION: Although the heterogeneity of primary tumours has long been known, we show here that early disseminated cancer cells are genomically very unstable as well. Selection of clonally expanding cells leading to metastasis seems to occur after dissemination has taken place. Therefore, adjuvant therapies are confronted with an extremely large reservoir of variant cells from which resistant tumour cells can be selected.

Bone Marrow↗

PubMed1989

Disseminated superficial actinic porokeratosis: a clinical study.

Disseminated superficial actinic porokeratosis is an autosomal dominant condition that requires sun exposure for full expression. It affects only sun-exposed areas, with relative sparing of the face. In sun-damaged skin of Australians disseminated superficial actinic porokeratosis is commonly mistaken for solar keratosis. Twenty-nine subjects with disseminated superficial actinic porokeratosis were involved in an extensive questionnaire and clinical study. The distribution of lesions was charted on all subjects, with a mean count of 268 lesions per subject. We found no evidence that skin cancer had arisen in disseminated superficial actinic porokeratosis lesions. A review of the etiologic and clinical features of disseminated superficial actinic porokeratosis also is presented.

Adolescent↗

PubMed2000

Role of E-cadherin in peritoneal dissemination of the pancreatic cancer cell line, panc-1, through regulation of cell to cell contact.

The present study was designed to clarify the molecules responsible for peritoneal dissemination of cancer cells. We established sublines with high (HP cells) and low (LP cells) passing activity through the membrane of a transwell chamber. The cell lines were established from the human pancreatic cancer cell line, Panc-1. LP cells demonstrated an octagonal shape and tight adhesion, whereas HP cells exhibited a spindle shape and grew with less cell-cell contact in vitro. It was found that HP cells demonstrated a high degree of peritoneal dissemination in nude mice following peritoneal injection of these cells compared to LP cells. We subsequently investigated the expression of certain adhesion molecules. Consequently, we found that LP cells exhibited a stronger expression of E-cadherin than HP cells. On the other hand, there was no difference in the expression of CD44H and beta1 integrin between these two sublines. Passing activity of LP cells through the membrane of the invasion chamber increased to nearly equal levels with HP cells following treatment with anti-human E-cadherin antibody. Moreover, transfection of mouse E-cadherin cDNA into HP cells reduced both passing activity through the membrane of the invasion chamber and peritoneal dissemination in nude mice to levels similar to that of LP cells. In conclusion, these results indicated that loss of E-cadherin facilitates both passing activity in an invasion chamber and peritoneal dissemination, playing a causative role in peritoneal dissemination of cancer cells.

Animals↗

PubMed2003

Whole abdomen radiotherapy for patients with peritoneal dissemination of endometrial adenocarcinoma.

PURPOSE: No standard, universally accepted therapy exists for patients with adenocarcinoma of the endometrium with peritoneal dissemination. We report mature outcomes of selected patients with this uncommon pattern of spread treated with whole abdomen radiotherapy (RT). METHODS AND MATERIALS: A retrospective review was undertaken of all patients with a diagnosis of endometrial cancer referred to the Radiologic Associates of Sacramento Medical Group between January 1, 1988 and October 1, 1999. Eleven patients were identified who had surgically proven peritoneal dissemination (peritoneal seeding) treated with whole abdomen RT as the sole cytotoxic therapy after operative cytoreduction. Ten patients had International Federation of Obstetrics and Gynecology (1988) Stage IV disease at diagnosis, and one had peritoneal dissemination at the time of initial recurrence after hysterectomy for Stage I disease. RT was administered to the whole abdomen using 10-MV photons in fractions of 1.0 or 1.5 Gy. A cumulative dose of 30 Gy was given in all patients, with shielding used to reduce the dose to the liver and kidneys. Partial abdominal volumes (pelvis plus paraaortic nodes) received supplementary dose at 1.5-1.8 Gy/fraction to bring the cumulative dose within the limited volumes to 46.2-54 Gy. RESULTS: Four patients developed progressive cancer within 13 months of completion of whole abdomen RT. One additional patient died of hepatic venoocclusive disease (radiation hepatitis) 15 months after RT without evidence of cancer recurrence. Five patients were alive and clinically cancer free 55, 129, 131, 134, and 178 months after RT completion. One patient died of unrelated causes 79 months after treatment completion. CONCLUSION: Abdominal RT, in doses compatible with the acute and late tolerance of normal tissues, can eradicate small deposits of disseminated, intraperitoneal endometrial cancer. Currently, our patient selection criteria include limited peritoneal dissemination at diagnosis permitting complete surgical clearance (<1 mm residual) of visible and palpable disease, Grade 1 or 2 histologic features, lack of demonstrable extraabdominal metastasis, and absence of major medical contraindications.

Abdomen↗

PubMed1995

Immunohistochemical expression of sialyl Tn and sialyl Lewis(a) antigens in stromal tissue correlates with peritoneal dissemination in stage IV human gastric cancer.

Immunohistochemical expression of sialyl Tn antigen (TKH2 and B72.3), sialyl Lewis(a) antigen (CA19-9) and CEA was examined in 52 cases with Stage IV gastric cancer, the objective being to examine whether or not these tumour-associated antigens show different expression between peritoneal dissemination and liver metastasis. Stromal type for TKH2, B72.3, CA19-9 and CEA were seen in 14 (50%), 13 (46%), 18 (64%) and nine (32%) cases with peritoneal dissemination, respectively, and in four (17%), three (13%), four (17%) and four (17%) cases with liver metastasis, respectively. The stromal type correlated to peritoneal dissemination in TKH2 (P < 0.05) B72.3 (P < 0.05) and CA19-9 (P < 0.05). In other clinicopathological factors, the stromal type for TKH2, B72.3 and CA19-9 correlated to the undifferentiated type. However, even in the undifferentiated type group, the stromal type correlated to peritoneal dissemination in TKH2 (P < 0.05), B72.3 (P < 0.05) and CA19-9 (P < 0.05). Based on these results, the spread of sialyl-rich tumour-associated antigens into the surrounding stroma in the undifferentiated type of gastric cancer may be associated with peritoneal dissemination.

Antibodies, Monoclonal↗

PubMed2003

Effective therapy for peritoneal dissemination in gastric cancer.

Peritoneal dissemination is the most frequent cause of death from gastric cancer, accounting for death in 20% to 40% of patients. Preoperative intraperitoneal chemotherapy, peritonectomy, intraoperative chemohyperthermic perfusion, and early postoperative intraperitoneal chemotherapy are treatment modalities specifically designed to eliminate peritoneal dissemination and progression. Preoperative intraperitoneal chemotherapy is for containment of peritoneal free cancer cells, and also may facilitate complete eradication of visible peritoneal dissemination by peritonectomy. Further, complete cytoreduction can be achieved more often when peritonectomy is included in the surgical treatment of gastric cancer with peritoneal dissemination. Phase III data shows prolonged survival attributed to complete cytoreduction. Aggressive cytoreduction of peritoneal dissemination by peritonectomy can reduce residual tumor burden to micrometastases on the peritoneal surface that can be treated by intraoperative intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy. Among all these modalities, surgical cytoreduction is probably the most important for survival benefit. If the surgical cytoreduction is visibly incomplete, prolonged survival cannot be expected, despite subsequent treatment. The surgeon's goal is to reduce the cancer cell burden to a microscopic level. Continued refinement of phase II studies is needed for maximal benefit and to standardize the technical and chemotherapeutic options of each modality.

Adult↗

PubMed2003

Central neurocytoma with craniospinal dissemination.

Central neurocytoma was first described by Hassoun et al. in 1982. The tumor is a rare benign tumor of the central nervous system, usually located in the lateral ventricles. Most reported cases are histologically and clinically benign. Several cases with recurrence have been described. Including the case presented here, only seven cases with craniospinal dissemination have been reported. None of the previous cases with dissemination had histological atypia but most did have a high MIB-1 labeling index (MIB-1 LI). Our patient had a high MIB-1 LI (4.6%) and dissemination was found to have advanced through the anterior horns of the lateral ventricles and to the spinal cord at the T4 level. The patient underwent partial resection of the tumor with follow-up radiation treatments for the residual tumor and dissemination. After the radiation, the size of the tumor decreased. The report of this casewill be helpful in the treatment of disseminated central neurocytoma.

Adult↗

PubMed2003

Leptomeningeal dissemination of cerebellar malignant astrocytomas.

Primary malignant astrocytomas of the cerebellum are extremely rare, and the dissemination patterns and effectiveness of postoperative radiation therapy are unclear. Five consecutive cases of histologically proven cerebellar malignant astrocytoma, two anaplastic astrocytomas, one anaplastic pilocytic astrocytoma, and two glioblastomas, were treated between 1997 and 2001. Four patients underwent surgical removal, local irradiation, and chemotherapy, and one patient with anaplastic pilocytic astrocytoma received subtotal removal followed by gamma knife radiosurgery for the residual tumor. Two patients had no recurrence at the primary site. All patients developed leptomeningeal dissemination. Four patients had supratentorial dissemination and two patients had spinal metastases. The time interval between the diagnosis of the primary cerebellar tumor and the diagnosis of leptomeningeal dissemination was 5-29 months (mean 14.6 +/- 10.4 months). All patients died at 10-38 months (mean survival 22.2 +/- 13.6 months). Intensive treatment including chemotherapy and radiotherapy may be required in cerebellar malignant astrocytomas, considering the high incidence of symptomatic leptomeningeal dissemination.

Adult↗

PubMed2001

Early dissemination of Borrelia burgdorferi without generalized symptoms in patients with erythema migrans.

The diagnosis of erythema migrans (EM) is not always easy, and reports of culture- or PCR-confirmed diagnosis as well as reports of EM with simultaneous disseminated disease are few. Characteristics and incidence of EM in addition to frequency of early dissemination of B. burgdorferi were studied in the archipelago of South-Western Finland prospectively using questionnaires, skin biopsies and blood samples. Clinical EM was recognized in 82 patients (incidence 148/100,000 inhabitants/year). Of skin biopsy samples, 35.5% were positive by PCR (the majority B. garinii), and 21.5% by cultivation (all B. garinii). Of blood samples, 3.8% were positive by PCR, and 7.7% by cultivation. Of the patients, 30.9% were seropositive at the first visit, and 52.9% 3 weeks later. Of the patients with laboratory confirmed diagnosis, the EM lesion was ring-like in 31.8% and homogeneous in 65.9%. Dissemination of B. burgdorferi, based on culture or PCR positivity of blood samples, was detected in 11.0% of the patients. The frequency of generalized symptoms was nearly the same in patients with as in those without dissemination (22.2% vs 27.4%). Only 21.4% of the patients with culture-positive EM recalled a previous tick bite at the site of the EM lesion. We conclude that EM lesions are more often homogeneous than ring-like. B. burgdorferi may disseminate early without generalized symptoms.

Antibodies, Bacterial↗

PubMed1995

Establishment of two new scirrhous gastric cancer cell lines: analysis of factors associated with disseminated metastasis.

Determination of the differences between cell lines which are derived from a primary tumour and a disseminated metastatic lesion from the same patient may aid in elucidating the factors associated with disseminated metastases. We report on the establishment and characterisation of two new scirrhous gastric cancer cell lines, designated OCUM-2M and OCUM-2D, derived from a 49-year-old female. OCUM-2M was derived from a primary gastric tumour, and OCUM-2D was derived from a sample of disseminated metastasis. The two cell lines were derived from the same patient. We investigated biological differences between the two cell lines to study mechanisms involved in disseminated metastasis. The growth activity of OCUM-2D cells as determined by doubling time and tumorigenicity was greater than that of OCUM-2M cells. The level of epidermal growth factor receptor (EGFR) expression in OCUM-2D cells was about twice that of OCUM-2M cells and the growth of OCUM-2D cells was stimulated more by epidermal growth factor (EGF) than that of OCUM-2M cells. The invasive activity of OCUM-2D cells was higher than that of OCUM-2M cells and was increased after addition of transforming growth factor-beta 1 (TGF-beta 1). An increase in the number of attached and spreading cells was found following the addition of 10 ng ml-1 TGF-beta 1. These findings suggest that high growth and invasive activity may play an important role in disseminated metastasis and that EGF and TGF-beta 1, which affect the growth and invasive activity of OCUM-2D cells, might be factors associated with metastasis in scirrhous gastric carcinoma. The two cell lines OCUM-2M and OCUM-2D should be beneficial for analysing mechanisms of tumour progression.

Adenocarcinoma, Scirrhous↗

PubMed1999

HGF/SF and its receptor c-MET play a minor role in the dissemination of human B-lymphoma cells in SCID mice.

The MET protooncogene, c-MET, encodes a cell surface tyrosine kinase receptor. The ligand for c-MET is hepatocyte growth factor (HGF), also known as scatter factor (SF), which is known to affect proliferation and motility of primarily epithelial cells. Recently, HGF/SF was also shown to affect haemopoiesis. Studies with epithelial and transfected NIH3T3 cells indicated that the HGF/SF-c-MET interaction promotes invasion in vitro and in vivo. We previously demonstrated that HGF/SF induces adhesion of c-MET-positive B-lymphoma cells to extracellular matrix molecules, and promoted migration and invasion in in vitro assays. Here, the effect of HGF/SF on tumorigenicity of c-MET-positive and c-MET-negative human B-lymphoma cell lines was studied in C.B-17 scid/scid (severe combined immune deficient) mice. Intravenously (i.v.) injected c-MET-positive (BJAB) as well as c-MET-negative (Daudi and Ramos cells) B-lymphoma cells formed tumours in SCID mice. The B-lymphoma cells invaded different organs, such as liver, kidney, lymph nodes, lung, gonads and the central nervous system. We assessed the effect of human HGF/SF on the dissemination of the B-lymphoma cells and found that administration of 5 microg HGF/SF to mice, injected (i.v.) with c-MET-positive lymphoma cells, significantly (P = 0.018) increased the number of metastases in lung, liver and lymph nodes. In addition, HGF/SF did not significantly influence dissemination of c-MET-negative lymphoma cells (P = 0.350 with Daudi cells and P= 0.353 with Ramos cells). Thus the effect of administration of HGF/SF on invasion of lymphoma cells is not an indirect one, e.g. via an effect on endothelial cells. Finally, we investigated the effect of HGF/SF on dissemination of c-MET-transduced Ramos cells. In response to HGF/SF, c-MET-transduced Ramos cells showed an increased migration through Matrigel in Boyden chambers compared to wild-type and control-transduced Ramos cells. The dissemination pattern of c-MET-transduced cells did not differ from control cells in in vivo experiments using SCID mice. Also no effect of HGF/SF administration could be documented, in contrast to the in vitro experiments. From our experiments can be concluded that the HGF/SF-c-MET interaction only plays a minor role in the dissemination of human B-lymphoma cells.

3T3 Cells↗

PubMed2001

Novel immunotherapy for peritoneal dissemination of murine colon cancer with macrophage inflammatory protein-1beta mediated by a tumor-specific vector, HVJ cationic liposomes.

A critical issue for cancer treatment is control of metastatic or disseminated tumors. Although immune gene therapy has been considered as a possible strategy for treatment of such tumors, successful results have not yet been obtained. To evoke antitumor immunity more efficiently, macrophage inflammatory protein-1beta (MIP-1beta) was used for gene therapy of colon cancer in mice. Injection of hemagglutinating virus of Japan (HVJ) cationic liposomes-MIP-1beta into subcutaneous tumor masses resulted in local expression of MIP-1beta and local accumulation of CD4(+) T lymphocytes. Few studies of cancer gene therapies have targeted peritoneal dissemination. In a mouse model of peritoneal dissemination of colon tumor, we used a luciferase-based assay to demonstrate that HVJ cationic liposomes had high tumor specificity and were effective vectors for transfer of genes in peritoneal dissemination. When mice were treated by intraperitoneal injection of HVJ cationic liposomes containing the MIP-1beta gene, the survival periods of the MIP-1beta-treated mice were significantly longer than those of control mice. Therefore, this HVJ cationic liposome strategy may serve as a powerful tool against peritoneal disseminated cancer.

Animals↗

PubMed2002

Intraperitoneal injection of adenovirus-mediated NK4 gene suppresses peritoneal dissemination of pancreatic cancer cell line AsPC-1 in nude mice.

NK4, composed of the N-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts not only as a competitive antagonist for HGF but also as a potent angiogenesis inhibitor. This study was designed to assess a therapeutic potential of adenovirus-mediated NK4 gene transfer for disseminated pancreatic cancer cells in the peritoneal lavage of nude mice. We constructed a recombinant adenovirus NK4 (Ad-NK4), which encodes a secretable form of human NK4. In vitro migration of AsPC-1 (human pancreatic cancer cell line) was stimulated by HGF, and it was completely inhibited by Ad-NK4 transfection. Weekly intraperitoneal injections of Ad-NK4 could suppress the development of tumor nodules in a nude mouse peritoneal dissemination model. NK4 expression was detected in the disseminated nodules, liver, pancreas, spleen, and mesenterium. Immunohistochemical study of the disseminated tumors showed a remarkable decrease in microvessel density and an increase in number of apoptotic tumor cells in the Ad-NK4-treated mice. Survival of the Ad-NK4-treated mice was significantly improved. This study indicates that the intraperitoneal transduction of adenovirus-mediated NK4 gene may be a useful therapeutic modality to prevent the development of peritoneal dissemination of pancreatic cancer.

Adenocarcinoma↗