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PubMed2004

Prognostic evaluation and review of immunohistochemically detected disseminated tumor cells in peritumoral lymph nodes of patients with pN0 colorectal cancer.

BACKGROUND: The value of immunohistochemical detection of disseminated tumor cells in histopathologically tumor-free lymph nodes (pN0) of patients with colorectal cancer is still of uncertain prognostic value. We therefore evaluated the immunohistochemical detection rates and their prognostic value comparing three different monoclonal antibodies. METHODS: A total of 170 lymph nodes of 85 patients with curatively resected colorectal carcinoma at UICC stage I or II were evaluated for disseminated tumor cells. Frozen sections of each lymph node were immunohistochemically stained using three antibodies directed against CEA, CK20, and Ber-EP4. The detection rates were compared with histopathological tumor parameters and with the patient's survival. The median follow-up time was 86 months. RESULTS: CEA-, CK20-, and Ber-EP4-positive disseminated tumor cells were identified microscopically in lymph nodes of 23 patients (27%), 24 patients (28%), and 23 patients (27%), respectively. In 18 patients (21%) disseminated tumor cells were found in consecutive sections and stained positive for all three monoclonal antibodies. The lymph nodes of 10 of 18 patients (56%), which developed tumor recurrence, contained CEA- and CK20-positive disseminated tumor cells. Ber-EP4-positive cells were present in lymph nodes of 9 of 18 patients (50%) with tumor recurrence. The 5-year overall survival of the 23 patients with CEA-positive disseminated tumor cells was 72% compared to 91% of the patients without immunohistochemical evidence of tumor cells (p<0.01). While the identification of CK20-positive tumor cells was also correlated significantly with a worse overall patient survival (p<0.01), the application of Ber-EP4 failed to reach significance (p=0.057). Multivariate analysis identified the tumor site (colon versus rectal cancer) (p<0.006) and the presence of CEA-positive disseminated tumor cells (p<0.03) as independent prognostic factors. CONCLUSION: In colorectal carcinoma, the immunohistochemical detection of disseminated tumor cells in histopathologically pN0 peritumoral lymph nodes allows the identification of a subgroup with a significantly worse prognosis. Nevertheless, the prognostic value of immunohistochemically detected disseminated tumor cells remains controversial due to the nonuniform data in the literature.

Adult↗

PubMed2000

Evaluation of dissemination studies with FDG whole-body positron emission tomography in patients with suspected metastatic tumours of brain and spine.

BACKGROUND: In the preoperative diagnosis of malignant brain tumours there is often uncertainty regarding their metastatic or primary nature, requiring dissemination studies. Currently FDG-wbPET is being used for the efficient detection of systemic tumours. It therefore may become a substitute for the conventional dissemination studies if it allows an earlier diagnosis. METHOD: In this descriptive and preliminary study a population of 14 patients with suspected or proven metastatic lesions, [18F]-fluoro-2-deoxy-D-glucose whole body positron emission tomography (FDG-wbPET) was conducted and verified by additional conventional dissemination studies. FINDINGS AND THEIR INTERPRETATION: The entire series of dissemination studies required an average of 30 days with a range of 4-73 days. The FDG-wbPET was corroborated by the other dissemination studies in 10 of the 14 patients. In 7 of these 10 patients both PET and dissemination studies showed systemic abnormal findings, but in one case the presence of high pulmonary activity on the FDG-wbPET and the abnormal findings on the chest X-rays proved to be Aspergillus infection at autopsy. In the other 2 cases the negative PET findings corresponded to the absence of systemic dissemination. In 5 cases there was disagreement of the results of the FDG-wbPET with other evidence, among which there were 2 cases of glioblastoma in which systemic metastases were most unlikely, and the foci of activity on the FDG-wbPET had to be considered as false positives. In the remaining 3 cases the systemic presence of high activity on the FDG-wbPET indicated the systemic presence of tumour, whereas the other dissemination studies disclosed no tumour. CONCLUSION: The results warrant the use of FDG-wbPET as a screening method for the search of metastases, allowing other studies to be focussed on the lesion. But from the cost/benefit point of view this would make the method less suitable as a substitute for dissemination studies in general, although it may speed up the diagnostic process.

Adult↗

PubMed1998

Mycobacterium tuberculosis infection and disease are not associated with protection against subsequent disseminated M. avium complex disease.

OBJECTIVE: To determine the relationship between Mycobacterium tuberculosis infection and disease and subsequent disseminated M. avium complex (MAC) disease in HIV-infected persons. DESIGN: A prospective observational cohort study. SETTING: The AIDS Linked to the Intravenous Experience (ALIVE) cohort of injecting drug users and the Johns Hopkins Hospital Adult HIV Clinic (JHHAHC). PARTICIPANTS: HIV-infected persons aged > 18 years with CD4 lymphocytes < 100 x 10(6)/l were followed between July 1989 and 31 October 1996. There were 182 persons in the ALIVE cohort and 1129 persons in JHHAHC who met these criteria. MAIN OUTCOME MEASURE: The relative risk of disseminated MAC was determined according to a history of prior opportunistic infection, MAC prophylaxis, antiretroviral therapy, M. tuberculosis infection or disease, race, sex, and injecting drug use. RESULTS: Amongst the 30 patients with active tuberculosis, eight developed disseminated MAC, compared with 208 cases of disseminated MAC amongst 1148 patients without prior M. tuberculosis infection or disease [relative risk (RR), 1.5; 95% confidence interval (CI), 0.8-2.7; P=0.2]. Amongst the 10 patients with extrapulmonary tuberculosis, five developed disseminated MAC (RR, 2.8; 95% CI, 1.5-5.2; P=0.02). Injecting drug use was associated with a decreased risk of disseminated MAC (RR, 0.7; 95% CI, 0.6-0.9; P=0.007). In a logistic regression analysis, disseminated MAC was significantly associated with extrapulmonary tuberculosis and other opportunistic disease, whereas antibiotic prophylaxis and injecting drug use were protective. CONCLUSIONS: A history of M. tuberculosis infection or disease was not associated with protection against subsequent disseminated MAC disease in HIV-infected persons. However, persons with extrapulmonary tuberculosis were at increased risk for disseminated MAC, particularly at low CD4 cell levels.

AIDS-Related Opportunistic Infections↗

PubMed2004

Risk factors for disseminated candidiasis in children with candidemia.

OBJECTIVE: To determine the risk factors for disseminated infection in hospitalized children with candidemia. METHODS: We performed a nested case-control study within a cohort of hospitalized children with candidemia. The cohort was defined by all patients with positive blood cultures for Candida species in a large, urban, academic, tertiary care children's hospital from 1998 to 2001. Cases were patients with clinical, microbiologic or radiographic evidence of disseminated candidiasis. Controls were patients with no evidence of disseminated candidiasis. RESULTS: Among 168 total children with candidemia, the median age was 3.5 years (interquartile range, 0.6-14.3). There were 189 episodes of candidemia. Candida species included:Candida albicans (41%), Candida parapsilosis (24%), Candida glabrata (13%) and Candida tropicalis (9%). The most common underlying diagnoses were oncologic (24%), gastrointestinal (15%) and cardiac (10%) diseases. Eighty-nine patients (53%) were admitted to an intensive care unit, 46 (27%) to a general pediatric or surgical ward and 33 (20%) to the oncology ward. Of the 168 patients with candidemia, 153 were included in the analysis of risk factors for disseminated candidiasis. Of 153 (17%) patients, 26 had evidence of organ dissemination. Organ involvement was most commonly identified in the lung (58%), followed by the liver (23%), kidney (16%), brain (12%), spleen (8%), eye (8%) and heart (8%). Eight of the 26 patients had evidence of dissemination to more than 1 organ. Independent risk factors for disseminated candidiasis were persistently positive blood cultures for Candida (>3 days) with a central venous catheter in place (odds ratio, 3.0; 95% confidence interval, 1.2, 7.8; P = 0.02) and immunosuppression (odds ratio, 2.9; 95% confidence interval, 1.2, 7.0; P = 0.02). CONCLUSIONS: Prolonged duration of candidemia with a central venous catheter in place and immunosuppression were independent risk factors for disseminated candidiasis in children with candidemia. Furthermore review of the epidemiology of candidemia at our institution revealed a heterogeneous population of children at risk for candidemia and a predominance of non-albicans species as the cause of these infections. Future studies are needed to determine the extent of evaluation needed for detecting dissemination among children with candidemia and to explore interventions for its prevention.

Adolescent↗

PubMed2006

Borrelia burgdorferi genetic markers and disseminated disease in patients with early Lyme disease.

Three genetic markers of Borrelia burgdorferi have been associated with disseminated disease: the OspC type, the 16S-23S rRNA intergenic spacer type (RST), and vlsE. Here, we modified previous methods so as to identify the three markers by PCR and restriction fragment length polymorphism in parallel, analyzed B. burgdorferi isolates from erythema migrans (EM) skin lesions in 91 patients, and correlated the results with evidence of dissemination. OspC type A was found approximately twice as frequently in patients with disseminated disease, whereas type K was identified approximately twice as often in those without evidence of dissemination, but these trends were not statistically significant. The remaining seven types identified were found nearly equally in patients with or without evidence of dissemination. RST 1 strains were significantly associated with dissemination (P=0.03), whereas RST 2 and RST 3 strains tended to have an inverse association with this outcome. The vlsE gene was identified in all 91 cases, using primer sets specific for an N-terminal sequence of B. burgdorferi strain B31 (vlsEB31) or strain 297 (vlsE297), but neither marker was associated with dissemination. Specific combinations of the three genetic markers usually occurred together. OspC type A was always found with RST 1 and vlsEB31, type K was always identified with RST 2 and more often with vlsE297, and types E and I were almost always found with RST 3 and equally often with vlsEB31 and vlsE297. We conclude that B. burgdorferi strains vary in their capacity to disseminate, but almost all strains isolated from EM lesions sometimes caused disseminated disease.

Antigens, Bacterial↗

PubMed1992

Dissemination of supratentorial malignant gliomas via the cerebrospinal fluid in children.

Of 100 children with supratentorial gliomas (excluding gliomas of the anterior visual pathways) treated at the Children's Hospital of Pittsburgh from 1980 to 1990, 34 had malignant gliomas. Follow-up was adequate in 33 of these patients, and an antemortem diagnosis of dissemination of the malignant glioma via the cerebrospinal fluid (CSF) was made in 11. Of these 11, 8 were boys and 3 were girls; they ranged in age from 17 months to 16 years at the time of diagnosis of the primary glioma. The distribution of histological types was as follows: glioblastoma multiforme, 4; malignant oligodendroglioma, 3; anaplastic astrocytoma, 2; malignant mixed glioma, 1; and malignant ependymoma, 1. The interval between diagnosis and CSF dissemination ranged from 1 week to 59 months (median, 8 months). Survival after dissemination ranged from 3 weeks to 11 months (median, 4 months). Two patients were alive 5 and 3 months after diagnosis of dissemination, respectively. These 11 patients were compared with the other 22 patients who did not have CSF dissemination. The risk factors for dissemination suggested by our data were male sex, ventricular operative entry, multiple resections, and malignant oligodendroglioma. Because of the high incidence (33%) of CSF dissemination, postoperative evaluation of the craniospinal axis with gadolinium-enhanced magnetic resonance imaging should be performed on all children with supratentorial malignant gliomas. Moreover, since the mortality is extremely high once dissemination has occurred, craniospinal irradiation should be considered in children with one or more of the above risk factors, even before symptoms or definite radiological evidence of CSF dissemination emerge.

Adolescent↗

PubMed2005

Prognostic significance of intracranial dissemination of glioblastoma multiforme in adults.

OBJECT: The clinical outcome and treatment of adult patients with disseminated intracranial glioblastoma multiforme (GBM) is unclear. The objective in the present study was to assess the prognostic significance of disseminated intracranial GBM in adults at presentation and at the time of tumor progression. METHODS: Clinical data from 1491 patients older than 17 years and harboring a GBM that had been diagnosed between 1988 and 1998 at the University of California at San Francisco neurooncology clinic were retrospectively reviewed. Dissemination of the GBM (126 patients) was determined based on Gd-enhanced magnetic resonance images. Classification of dissemination was as follows: Type I, single lesion with subependymal or subarachnoid spread; Type II, multifocal lesions without subependymal or subarachnoid spread; and Type III, multifocal lesions with subependymal or subarachnoid spread. Subgroups of patients were compared using Kaplan-Meier curves that depicted survival probability. The median postprogression survival (PPS), defined according to neuroimaging demonstrated dissemination, was 37 weeks for Type I (23 patients), 25 weeks for Type II (50 patients), and 10 weeks for Type III spread (19 patients). Patients with dissemination at first tumor progression (52 patients) overall had a shorter PPS than those in a control group with local progression, after adjusting for age, Kamofsky Performance Scale score, and time from tumor diagnosis to its progression (311 patients). When analyzed according to tumor dissemination type, PPS was significantly shorter in patients with Type II (33 patients, p < 0.01) and Type III spread (11 patients, p < 0.01) but not in those with Type I spread (eight patients, p = 0.18). CONCLUSIONS: Apparently, the presence of intracranial tumor dissemination on initial diagnosis does not in itself preclude aggressive treatment if a patient is otherwise well. A single focus of GBM that later demonstrates Type I dissemination on progression does not have a worse prognosis than a lesion that exhibits only local recurrence.

Adult↗

PubMed2000

Postoperative evaluation for disseminated medulloblastoma involving the spine: contrast-enhanced MR findings, CSF cytologic analysis, timing of disease occurrence, and patient outcomes.

BACKGROUND AND PURPOSE: Postoperative MR imaging is routinely performed for staging of medulloblastoma because of frequent tumor dissemination along CSF pathways. The goals of this study were to: 1) determine the timing of disease occurrence and contrast-enhanced MR imaging features of disseminated medulloblastoma involving the spine and their relationship to patient outcomes; and 2) compare the diagnostic accuracy of MR imaging findings with CSF cytologic analysis. METHODS: Medical records, pathologic reports, and unenhanced and contrast-enhanced postoperative MR images of the spine and head from 112 patients who had resection of medulloblastoma were retrospectively reviewed. MR images of the spine were evaluated for abnormal contrast enhancement in the meninges and vertebral bone marrow. MR images of the head were evaluated for recurrent or residual intracranial tumor. Imaging data were correlated with available CSF cytologic results and patient outcomes. RESULTS: Twelve patients (11%) had tumor within the spinal leptomeninges depicted on MR images at the time of diagnosis. Twenty-five patients (22%) had disseminated disease in the spine (leptomeninges, n = 22; vertebral marrow, n = 1; or both locations, n = 2) on MR images 2 months to 5.5 years (mean, 2 years) after initial surgery and earlier negative imaging examinations. Eleven other patients (10%) had recurrent intracranial medulloblastoma without spinal involvement seen with MR imaging. Spinal MR imaging had a sensitivity of 83% in the detection of disseminated tumor, whereas contemporaneous CSF cytologic analysis had a sensitivity of 60%. The sensitivity of CSF cytologic analysis increased to 78% with acquisition of multiple subsequent samples, although diagnosis would have been delayed by more than 6 months compared with diagnosis by spinal MR imaging in six patients. Spinal MR imaging was found to have greater overall diagnostic accuracy than CSF cytologic analysis in the early detection of disseminated tumor (P = .03). Spinal MR imaging confirmed disseminated tumor when contemporaneous CSF cytologic findings were negative in 13 patients, whereas the opposite situation occurred in only two patients. False-positive results for spinal MR imaging and CSF cytologic analysis occurred when these examinations were obtained earlier than 2 weeks after surgery. The 5-year survival probability for patients with spinal tumor was 0.24 +/- 0.08 versus 0.68 +/- 0.05 for the entire study group. CONCLUSION: Spinal MR imaging was found to have greater diagnostic accuracy than CSF cytologic analysis in the early detection of disseminated medulloblastoma. CSF cytologic analysis infrequently confirmed disseminated tumor when spinal MR imaging results were negative. Delaying spinal MR imaging and CSF cytologic analysis by more than 2 weeks after surgery can reduce false-positive results for both methods. The presence of disseminated medulloblastoma in the spine seen with MR imaging is associated with a poor prognosis.

Adolescent↗

PubMed1986

[Mechanism by which peritoneal disseminated metastasis develops in gastric cancer].

To clarify the peritoneal dissemination of gastric cancer 270 resected specimens were analyzed by methylene blue formalin fixation staining method. As a result, not only metastasis to lymph nodes but also very small disseminated metastatic lesions which had been overlooked before were observed in the greater omentum and lesser omentum. The relationship among this disseminated lesion, macroscopic peritoneal disseminated metastatic lesion, degree of serosal infiltration, area of infiltration and tissue type of the tumor was studied. The very small disseminated metastatic lesion was judged to be Po, accounting for 15.3 percent and 28.1 percent of 270 resected cases were positive for disseminated metastasis. Disseminated metastasis developed relatively early. The incidence of disseminated metastasis was higher in the poorly differentiated type than in the well-differentiated one. The case which showed break of the capsule of lymph node and infiltration into the area around lymph node accounted for 45.0 percent of the positive cases of lymphatic metastasis. Since very small disseminated lesions are present in the greater omentum, lesser omentum and the area around lymph node as described above, radical operation should been bloc resection of these lesions in gastric cancer.

Humans↗

PubMed1984

[Clinico-pathological features of intracranial germ cell tumors with dissemination or metastasis in childhood].

Recently reports of the cases with intracranial germ cell tumor associated with dissemination to the central nervous system are increased since the introduction of CT scan. The authors experienced 8 cases with the dissemination among 19 cases of intracranial germ cell tumor in childhood, and discussed their clinico-pathological features. Before the CT scan era, the authors experienced only one case with dissemination, who was a 11 years-old boy (Case 1) and revealed two cell pattern pinealoma disseminating on the subependymal layer of all ventricles and in the basal cisterns at autopsy. Since the introduction of CT scan, 4 cases were found, who showed periventricular dissemination already at the first admission. Among them three cases revealed tumors in the pineal or suprasellar region and also dissemination of tumors on the wall of the lateral ventricles. The other one (Case 3) did not reveal any tumor at pineal or suprasellar region, but disseminated tumors on the wall of the third and lateral ventricles. Histological appearances of all 4 cases were two cell pattern pinealoma by examination of surgical or CSF materials. Only one case (Case 5) was found spinal dissemination later. All 4 cases were good prognosis. The authors considered that there might be diffuse primary ependymal germ cell tumor besides diffuse metastatic one. In the CT scan era, there were three cases who showed dissemination or metastasis along their clinical courses, but had not showed at the first administration. One (Case 6) of 3 cases showed a tumor at the right thalamus at the first administration. Five years later, the tumor metastasized to the cervical cord and he died.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2006

Dissemination of physical activity evidence, programs, policies, and surveillance in the international public health arena.

The concepts of dissemination can be applied to the international challenges of promoting physical activity. With the 2004 release of the World Health Organization Global Strategy for Diet and Physical Activity, risk factor reduction and noncommunicable disease control are of global health interest. A six-step framework is proposed for understanding the attributes of successful international dissemination. These include the development of clear and evidence based resources or innovations, defining the target audience, selecting communication channels, engaging decision makers, and developing evaluation frameworks around dissemination. Four case studies to illustrate aspects of the framework are presented: (1) learning from dissemination of effective tobacco control initiatives, (2) the experience of developing global measures and surveillance systems for physical activity, (3) case study of disseminating the Agita program-an effective community wide intervention, and (4) disseminating the World Health Organization Global Strategy on Diet and Physical Activity. Substantial similarities across the experiences described in these case studies suggest underlying common themes for international dissemination, but developing a stronger evidence base for dissemination efforts remains a research priority.

Diffusion of Innovation↗

PubMed2004

Effectiveness and efficiency of guideline dissemination and implementation strategies.

OBJECTIVES: To undertake a systematic review of the effectiveness and costs of different guideline development, dissemination and implementation strategies. To estimate the resource implications of these strategies. To develop a framework for deciding when it is efficient to develop and introduce clinical guidelines. DATA SOURCES: MEDLINE, Healthstar, Cochrane Controlled Trial Register, EMBASE, SIGLE and the specialised register of the Cochrane Effective Practice and Organisation of Care (EPOC) group. REVIEW METHODS: Single estimates of dichotomous process variables were derived for each study comparison based upon the primary end-point or the median measure across several reported end-points. Separate analyses were undertaken for comparisons of different types of intervention. The study also explored whether the effects of multifaceted interventions increased with the number of intervention components. Studies reporting economic data were also critically appraised. A survey to estimate the feasibility and likely resource requirements of guideline dissemination and implementation strategies in UK settings was carried out with key informants from primary and secondary care. RESULTS: In total, 235 studies reporting 309 comparisons met the inclusion criteria; of these 73% of comparisons evaluated multifaceted interventions, although the maximum number of replications of a specific multifaceted intervention was 11 comparisons. Overall, the majority of comparisons reporting dichotomous process data observed improvements in care; however, there was considerable variation in the observed effects both within and across interventions. Commonly evaluated single interventions were reminders, dissemination of educational materials, and audit and feedback. There were 23 comparisons of multifaceted interventions involving educational outreach. The majority of interventions observed modest to moderate improvements in care. No relationship was found between the number of component interventions and the effects of multifaceted interventions. Only 29.4% of comparisons reported any economic data. The majority of studies only reported costs of treatment; only 25 studies reported data on the costs of guideline development or guideline dissemination and implementation. The majority of studies used process measures for their primary end-point, despite the fact that only three guidelines were explicitly evidence based (and may not have been efficient). Respondents to the key informant survey rarely identified existing budgets to support guideline dissemination and implementation strategies. In general, the respondents thought that only dissemination of educational materials and short (lunchtime) educational meetings were generally feasible within current resources. CONCLUSIONS: There is an imperfect evidence base to support decisions about which guideline dissemination and implementation strategies are likely to be efficient under different circumstances. Decision makers need to use considerable judgement about how best to use the limited resources they have for clinical governance and related activities to maximise population benefits. They need to consider the potential clinical areas for clinical effectiveness activities, the likely benefits and costs required to introduce guidelines and the likely benefits and costs as a result of any changes in provider behaviour. Further research is required to: develop and validate a coherent theoretical framework of health professional and organisational behaviour and behaviour change to inform better the choice of interventions in research and service settings, and to estimate the efficiency of dissemination and implementation strategies in the presence of different barriers and effect modifiers.

Cost-Benefit Analysis↗

PubMed1998

Trypsinogen expression and early detection for peritoneal dissemination in gastric cancer.

BACKGROUND AND OBJECTIVES: The most reliable method for the diagnosis of peritoneal dissemination of gastric cancer at the present time is cytological examination of ascitic fluid, which is unavailable to patients without ascites or may be inadequate for those with ascites containing few cancer cells. It has been reported recently that human gastric cancer immunoreacted with a monoclonal antibody against pancreatic trypsinogen. We therefore examined the expression of trypsinogen as a new marker for the early diagnosis of peritoneal dissemination of gastric cancer. METHODS: Pancreatic trypsinogen protein was immunohistochemically stained with a three-step indirect immunoperoxidase method and cationic trypsinogen (trypsinogen-1) mRNA expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in gastric cancer. Twenty-nine of 30 primary tumors (97%) and all 12 tumors (100%) of the peritoneal seedings immunohistochemically reacted with trypsinogen. Preliminary study for early diagnosis of peritoneal dissemination was carried out for eight more recent patients who showed positive immunoreactivity to trypsinogen protein and expressed trypsinogen- mRNA in the primary tumor. The expression of trypsinogen-1 mRNA was detected by using peritoneal lavage fluid preoperatively collected in these patients. RESULTS: All three patients in whom peritoneal dissemination was diagnosed at the time of their operation(s) expressed trypsinogen-1 mRNA. One patient, who did not show peritoneal dissemination at the operation but was positive for trypsinogen-1 mRNA detection, later died of the recurrence of peritoneal dissemination. CONCLUSIONS: These results indicated that trypsinogen protein and trypsinogen-1 mRNA frequently expressed in peritoneal dissemination as well as primary tumors in gastric cancer and detection of trypsinogen-1 mRNA expression was a useful method for early diagnosis in peritoneal dissemination of gastric cancer.

Adenocarcinoma↗

PubMed2003

Detection of hematogenic and lymphogenic tumor cell dissemination in patients with medullary thyroid carcinoma by cytokeratin 20 and preprogastrin-releasing peptide RT-PCR.

Despite an extensive surgical approach only 50% of the patients with medullary thyroid carcinoma (MTC) are biochemically cured. The failure to cure a larger number of patients is a result of the early dissemination of MTC. The present study evaluates two RT-PCR based assays for the detection of disseminated tumor cells in blood, bone marrow and lymph node samples of patients with MTC. Frozen tissue and blood samples of 19 patients with MTC and 61 cervical lymph nodes of these patients were obtained intraoperatively during thyroidectomy and lymphadenectomy. Preoperative bone marrow samples were obtained from 8 patients with MTC. An expression of CK20 and preproGRP was found in all MTC tissue samples. Using CK20-PCR, disseminated MTC cells were detected in 67% of the cervical lymph nodes of patients with MTC, compared to 72% involved lymph nodes, detected by preproGRP-PCR. In 16 of 61 nodes (26%) each PCR-system detected disseminated tumor cells in histologically tumor-free lymph nodes. Disseminated tumor cells were detected with CK20-PCR and preproGRP in 5 of 18 (28%) preoperative blood samples, each. The detection of a hematogenic tumor cell dissemination by preproGRP correlated significantly with the tumor stages (p = 0.019). Circulating MTC cells were found in 3 of 8 bone marrow samples with CK20-PCR, compared to 1 of 8 samples with preproGRP-PCR. Both PCR assays are highly sensitive to detect disseminated MTC cells in blood, bone marrow and lymph node samples. Our results of disseminated MTC cells in 26% of histologically tumor-free cervical lymph nodes and in 28% of the blood samples of patients with MTC might therefore explain the low biochemical cure rates.

Adult↗

PubMed2000

Integrin alpha6beta4 as a suppressor and a predictive marker for peritoneal dissemination in human gastric cancer.

BACKGROUND & AIMS: Because alterations of integrin expression in cancers contribute to cancer cell biology, we analyzed the association between the potential for peritoneal dissemination and integrin expression. METHODS: The dissemination potential of 10 human gastric cancer cell lines in mice with severe combined immunodeficiency (SCID) was compared with the expression of various integrins. The relationship between integrin expression and peritoneal dissemination was also investigated in surgically resected gastric cancer cases. RESULTS: The level of integrin beta4 subunit expression was inversely correlated with dissemination potential. Introduction of a full-length complementary DNA (cDNA) for beta4 subunit into cancer cells showing negligible beta4 subunit expression markedly suppressed peritoneal dissemination and inhibition of endogenous integrin alpha6beta4 by introduction of a cytoplasmic domain-deleted beta4 subunit cDNA into cells showing high expression of beta4 subunit promoted peritoneal dissemination. Apoptosis, which was histologically evident in peritoneal nodules of SCID mice, was induced in the cells with high beta4 subunit expression by attachment to laminin and stimulation with growth factors in vitro. An immunohistochemical study of specimens from 120 cases of primary gastric cancer showed that patients with beta4 subunit-positive tumors exhibited peritoneal dissemination only infrequently (P < 0.0001) and had a better outcome (P < 0.01). CONCLUSIONS: These results indicate that integrin alpha6beta4 is both a suppressor and a predictive marker for peritoneal dissemination in gastric cancer.

Animals↗

PubMed2001

Recommendations of the Canadian Consensus Conference on Dementia--dissemination, implementation, and evaluation of impact.

BACKGROUND: Subsequent to the development of consensus statements on a clinical topic, it is vital to establish a plan for dissemination, implementation and evaluation of impact. Consensus statements can be used for both guiding continuing medical education (CME) and producing clinical practice guidelines (CPGs). Insufficient attention to dissemination can lead to a failure to change physician behaviour and improve patient outcomes. METHODS: A plan to disseminate the conclusions of the Canadian Consensus Conference on Dementia (CCCD) was developed. This plan was based on a literature review of CME and CPGs. A Medline search was performed on the dissemination and evaluation of the 1989 Canadian Consensus Conference on the Assessment of Dementia (CCCAD) and other published guides for physicians on dementia care. CCCD dissemination that has occurred to date (June, 2000) was reviewed in this paper. RESULTS: Lectures and unsolicited printed material are weak forms of CME. Small-group interactive CME that provides practice opportunities appears to be the most effective way to change physician behaviour. The ability of CPGs to change physician behaviour is uncertain. It appears that inadequate attention has been placed on CPG dissemination and implementation. The CCCAD had a modest impact on clinical practice in Canada. While dissemination of the conclusions of the CCCD has taken place, evaluation of the impact of the CCCD has yet to be done. Local initiatives utilizing the conclusions of the CCCD are on-going. CONCLUSIONS: Further work is needed on how to optimize the impact of consensus statements and CPGs. While dissemination of the CCCD has occurred, it is currently unknown whether it has led to any change in physician practices.

Canada↗

PubMed2003

Some new aspects of the pathology, pathogenesis, and aetiology of disseminated lung lesions in slaughter pigs.

From 40 pigs rejected for human consumption at slaughter due to an apparent presence of pyemic lung lesions (defined as disseminated processes containing pus and/or necrotic material), the lungs, spleen, liver, and kidneys were subjected to an extended macroscopic examination. Several lung lesions were sampled from each animal for histological and bacteriological examination. Samples from the kidneys and spleens were also subjected to bacteriological examination. At gross level, four groups of lung lesions were identified: 1) disseminated foci with contents of pus and/or necrotic material (n=26); 2) disseminated or multifocally located ecchymoses with a central area of fibroplasia (n=9); 3) non-pneumonic lesions, i.e., disseminated areas of atelectasis (n=1) or haemorrhagic areas developing due to the process of slaughter (n=1); and 4) suppurative lesions without a disseminated distribution pattern (n=3). Histologically, the disseminated suppurative/necrotic foci were identified as: A) abscesses (n=10); B) necrotic lesions (n=6); and C) ectatic or ectatic-like bronchioles with contents of pus and necrotic material (n=10). The macroscopic observation of disseminated centres of fibroplasia with peripheral ecchymoses (n=9) was confirmed histopathologically. The livers of five pigs contained multiple areas of chronic interstitial fibrosis related to migration of Ascaris suum larvae ("milk spotted liver"). Such hepatic lesions were significantly (p<0.01) related to the simultaneous occurrence of disseminated pulmonary ecchymoses with a central area of fibroplasia. Generally, all lung lesions of each individual animal contained identical monocultures of bacteria following this pattern: Staphylococcus aureus (abscesses); Actinomyces hyovaginalis (necroses); S. aureus, A. hyovaginalis, and Arcanobacterium pyogenes (ectatic and ectatic-like bronchioles). Areas with fibrosis were sterile or contained bacteria considered to be a result of contamination. Apart from one kidney, from which S. aureus was cultured, all other organs were sterile. It is concluded that difficulties exist in differentiating pulmonary pyemic lesions from non-pyemic lesions at the gross level. Thus, it was not possible to distinguish between abscesses/necroses and ectatic bronchioles, the pathogenesis of the latter being uncertain. However, the chronic non-pyemic lesions related to the migration of A. suum larvae should be identified by the absence of pus/necrosis. S. aureus was predominantly isolated from abscesses, whereas, and most surprisingly, A. hyovaginalis was the dominant bacterium isolated from the pulmonary necroses.

Abscess↗

PubMed2000

Dissemination in cutaneous leishmaniasis due to Leishmania major in different ethnic groups in Saudi Arabia.

BACKGROUND: Dissemination in patients with cutaneous leishmaniasis has previously been recorded in human infection with Leishmania major and L. tropica. In this study, the potential for dissemination in different ethnic groups in Saudi Arabia was compared. METHODS: The data were recorded from a group of 73 patients with suspected cutaneous leishmaniasis (43 Saudi and 30 non-Saudi) attending the Dermatology Clinics at King Fahd Hospital of the University and Al-Khobar Government Hospital at Al-Khobar, Eastern Region of Saudi Arabia. The patients were of various age groups (all male) between 1 and 55 years. The diagnosis of cutaneous leishmaniasis was confirmed clinically and by smear and skin biopsy. The following data were recorded for each patient: type, number, and anatomic sites of disseminative lesions and the frequency of co-occurrence of more than one type of lesion. RESULTS: Three types of disseminative lesions due to zoonotic cutaneous leishmaniasis were recorded in 16 patients (21.92%): subcutaneous nodules, satellite papules, and subcutaneous induration. The percentage of disseminative lesions in non-Saudi patients (36.66%) was higher than in Saudi patients (11. 63%). This was also true for the number of lesions: a mean of 12.27+/- 10 and 6.4+/-3, respectively. The coexistence of more than one type of disseminative lesion was higher in non-Saudi patients (63. 63%) than in Saudi patients (20.0%), as well as the occurrence of lesions on more than one body site: 36.4% in non-Saudi patients and 20.0% in Saudi patients. CONCLUSIONS: The potential for dissemination due to cutaneous leishmaniasis was significantly higher in the nonindigenous population than in the indigenous population in Saudi Arabia. Disseminative lesions must be clinically differentiated from other skin diseases and appropriately treated by avoiding the use of intralesional drugs or physical therapy.

Adolescent↗