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PubMed2004

Characterization of amplifiable, circulating RNA in plasma and its potential as a tool for cancer diagnostics.

BACKGROUND: Several recent reports have described the detection of circulating, cancer-related RNA molecules in serum or plasma from cancer patients, but little is known about the biology of this extracellular RNA. We aimed to determine how RNA is protected against degradation in serum, to optimize RNA isolation from large volumes of serum, and to test our optimized assays for serum-based cancer detection. METHODS: We used quantitative reverse transcription-PCR (QRT-PCR) analysis to investigate the isolation and biology of extracellular plasma RNA. We then examined the presence of amplifiable RNA transcripts in plasma and serum from controls and from patients with esophageal cancer and malignant melanoma. RESULTS: We found that extracellular RNA in plasma is highly degraded and can be isolated most efficiently by guanidinium-phenol extraction followed by precipitation. Extracellular RNA is stable in serum for up to 3 h but is destroyed immediately by addition of detergents. Extracellular RNA can be captured on 0.2 microm filters, allowing concentration of RNA from several milliliters of plasma. When we concentrated RNA from up to 4 mL of serum, detection of cancer-related transcripts in serum from cancer patients and controls was infrequent and inconsistent. CONCLUSIONS: Extracellular RNA is most likely protected within protein or lipid vesicles, possibly apoptotic bodies, which can be disrupted by detergents. Despite optimizing many aspects of plasma RNA detection, we were unable to reproducibly detect cancer-related transcripts. Our data suggest that measurement of circulating RNA may not be a good approach to early cancer diagnosis.

Animals↗

PubMed1997

Colorectal cancer: diagnostic potential of CT measurements of hepatic perfusion and implications for contrast enhancement protocols.

PURPOSE: To assess changes in hepatic perfusion in patients with colorectal cancer with computed tomography (CT), diagnostic potential of CT perfusion measurements, and implications for design of contrast enhancement protocols. MATERIALS AND METHODS: In 27 patients with colorectal cancer, arterial and portal perfusion were calculated from temporal changes in attenuation after intravenous administration of contrast material. RESULTS: Arterial perfusion greater than 0.25 mL/min/mL was seen in nine (82%) of the 11 patients with overt metastases versus six (38%) of the 16 patients with no overt metastases (P < .05). Portal perfusion of 0.25 mL/min/mL or less was found in five (46%) of the patients with overt metastases versus three (19%) of the patients with no overt metastases. Follow-up imaging showed progressive metastatic disease in three patients, all of whom had decreased portal perfusion. CONCLUSION: Increased arterial perfusion appears to be an indicator of liver metastases, whereas reduced portal perfusion may indicate progressive disease. Contrast enhancement protocols that are based on experience with normal livers may not be optimal for patients with metastases.

Aged↗

PubMed1988

Early prostate cancer: diagnostic costs of screening transrectal US and digital rectal examination.

A screening study with transrectal ultrasound (US) and digital rectal examination to diagnose early prostate cancer was performed to calculate diagnostic costs. The total costs of screening 784 men were $130,400 with transrectal US and $41,080 with digital rectal examination. Per diagnosed cancer, the costs were $6,520 for transrectal US and $4,108 for digital rectal examination, a difference of 37%. The costs per early diagnosed cancer (stage A or B) were $7,671 and $5,869 for transrectal US and digital rectal examination, respectively--a difference of 23%. The costs per early cancer that would have been advanced if diagnosed without screening were $22,177 for transrectal US and $28,528 for digital rectal examination--a difference of 22% in favor of transrectal US. Equations for these relative costs were generated for transrectal US and digital rectal examination. Costs are related to changes in prevalences and to changes in the stages of prostate cancer when diagnosed without screening.

Cost-Benefit Analysis↗

PubMedDate not supplied

Tumor-reactive immunoglobulins in ovarian cancer: diagnostic and therapeutic significance? (review).

Inhibition of the immune system has been observed in association with most stages of ovarian cancer; however, the mechanisms involved in the induction and maintenance of this chronic immune unresponsiveness associated with cancer progression are poorly understood. This immunosuppressed state is primarily defined as the failure to eradicate the tumor. This immunosuppressed state is generally associated with decreased numbers and reactivity of lymphoid cells in women with ovarian cancer. The degree of immune dysfunction in ovarian cancer patients has been demonstrated to correlate with patient survival. While ovarian cancer patients generally fail to exhibit effective immunosurveillance, as manifested by continued tumor growth and progression, the presence of tumor-reactive immunoglobulins can be demonstrated in these women, indicating the continued presence of immune recognition. We have not only demonstrated the presence of tumor-reactive antibodies in ovarian cancer patients, but have also shown that the levels of these antibodies increase as the disease progresses. The antigens recognized by the patients' humoral response have been identified as either membrane-associated or intra-cellular. In general, the localization of these antigens tend to be linked to the patient's prognosis. The presence of a humoral response against intracellular proteins are correlated with poor prognosis, while autoantibodies reactive with surface components appear to have a better prognosis. In addition to general antigen recognition, these reactive antibodies have been utilized to define specific epitopes on tumor-associated proteins. Certain specific antigenic epitopes exhibit common recognition among patients with the same tumor type. The specific recognition of certain epitopes can provide early evidence of aberrant protein expression and this aberrant expression of certain proteins, such as procathepsin D, appear to be linked to the tumor's acquisition of specific malignant characteristics, including metastasis formation and chemoresistance. Despite the existence of circulating tumor-reactive immunoglobulins, their presence correlates, in general, with poor prognosis and poor host survival. Since tumor-reactive immunoglobulins are elicited and can be detected early in the development of tumors and their enhanced synthesis is induced prior to the clinical manifestation of recurrence, the assessment of the tumor-reactive immune response against specific antigenic epitopes should represent an early significant diagnostic and prognostic marker in ovarian cancer.

Antibodies, Neoplasm↗

PubMed1993

[Clinical preventive medicine in cancer diagnosis--proposal for a new cancer diagnostic system in an aging society].

To enroll a large percentage of the cancer high-risk group and to simultaneously screen for various kinds of cancer, a modified combination assay of tumor markers and risk factors in serum was devised. A pilot study using 5 tumor markers, AFP, CEA, CA19-9, CA125, Dupan-2, as well as 3 risk factors of pepsinogen, PGI, PGII, PGI/II, showed 87.0% sensitivity and 58.8% specificity in 54 patients with various cancers and 163 healthy subjects. Eighty percent of stage I or II cases were detected except for one stage I case of right lung cancer and one stage II case of oral cavity cancer. Field work is now under way to detect various cancers among approximately 1000 inhabitants above 50 years of age in a particular town using 11 tumor markers and 3 risk factors. One hundred fifty three of 967 cases (male 372, female 595) showed various abnormal values and some were examined further as higher risk cases to detect particular cancers suspected from the results of the modified combination assay. At present, 5 PAP positive cases were referred to urological clinic for examination and 3 were confirmed histologically as prostatic cancer. This corresponds to approximately a 0.8% of detection rate which is more than 40 times the prostatic cancer mortality. Other kinds of cancer are still under investigation at various specified clinics. If cancer is not detected in these higher risk cases, they will be followed year to year. Further, the most suspicious cases will be examined at a chromosome or DNA level.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed2004

Brain metastases in renal cell cancer: diagnostic and therapeutic aspects.

A 67-year-old patient with metastatic renal cell cancer was treated with fractionated stereotactic radiotherapy to a hemorrhagic pons metastasis. He then developed multiple cystic brain lesions, suggestive of diffuse metastatic spread. However, further work-up revealed abscesses from bronchopneumonia. Diagnostic and therapeutic aspects as well as potential pitfalls in the management of patients with brain metastases are discussed.

Aged↗

PubMed1978

The bone marrow examination in breast cancer: diagnostic considerations and clinical usefulness.

Bone marrow examinations were performed on 116 women with primary and metastatic breast cancer and were correlated with the clinical status of the patient and other specific diagnostic modalities. The relative diagnostic efficacy of the marrow biopsy, aspirate smear and clot section was examined, as was the value of serial marrow examinations. A marrow positive for tumor was found in 40% of those with metastatic disease, 55% with positive x-rays, 56% with positive bone scans, but only 4% (1/24) with both scan and x-ray normal. Routine hematologic parameters were of limited usefulness in predicting the finding of a positive marrow. The biopsy was superior to the smear and clot section but aspirated material also had to be analyzed to maximize diagnostic yield. When analyzed qualitatively, i.e., positive or negative for tumor, serial marrow examinations were not useful in assessing the efficacy of antitumor treatment. The potential usefulness of bone marrow examination in patients with breast cancer is discussed.

Biopsy, Needle↗

PubMed2005

Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications.

Heat shock proteins (Hsps) are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion, metastasis, death, and recognition by the immune system. We review the current status of the role of Hsp expression in cancer with special emphasis on the clinical setting. Although Hsp levels are not informative at the diagnostic level, they are useful biomarkers for carcinogenesis in some tissues and signal the degree of differentiation and the aggressiveness of some cancers. In addition, the circulating levels of Hsp and anti-Hsp antibodies in cancer patients may be useful in tumor diagnosis. Furthermore, several Hsp are implicated with the prognosis of specific cancers, most notably Hsp27, whose expression is associated with poor prognosis in gastric, liver, and prostate carcinoma, and osteosarcomas, and Hsp70, which is correlated with poor prognosis in breast, endometrial, uterine cervical, and bladder carcinomas. Increased Hsp expression may also predict the response to some anticancer treatments. For example, Hsp27 and Hsp70 are implicated in resistance to chemotherapy in breast cancer, Hsp27 predicts a poor response to chemotherapy in leukemia patients, whereas Hsp70 expression predicts a better response to chemotherapy in osteosarcomas. Implication of Hsp in tumor progression and response to therapy has led to its successful targeting in therapy by 2 main strategies, including: (1) pharmacological modification of Hsp expression or molecular chaperone activity and (2) use of Hsps in anticancer vaccines, exploiting their ability to act as immunological adjuvants. In conclusion, the present times are of importance for the field of Hsps in cancer, with great contributions to both basic and clinical cancer research.

Adjuvants, Immunologic↗

PubMed1988

[Peripheral bronchopulmonary cancers. Diagnostic efficiency of fibroscopic samples. Prospective study on 561 patients].

The purpose of this french multicentric study was to evaluate the diagnostic accuracy of samples collected by fibroscopy in peripheral lung cancer with normal endoscopy. Five hundred and sixty-one patients entered the study; a tumour had been diagnosed in 350 of them (62 p. 100). Among these 350 patients, 147 were examined with the help of a light-amplifier screen, and a positive diagnosis was made in 97 (66 p. 100). Guided sample collection in the pathological area (biopsy, brushing, transcatheter aspiration) proved much more rewarding than unguided sample collection (biopsy of the bronchus, simple aspiration or cytology of 3-day sputum): 45 p. 100 positive results versus 18 p. 100 (P less than 0.001). However, sputum cytology still had good diagnostic value since it provided by itself the diagnosis in 14 p. 100 of the cases. Results were significantly inferior in tumours less than 3 cm in diameter.

Adult↗

PubMed2006

Molecular advances in medullary thyroid cancer diagnostics.

Germline activating mutations in the RET proto-oncogene cause inherited medullary thyroid cancer (MTC) and the multiple endocrine neoplasia type 2 (MEN2) syndrome. Identification of a RET mutation in an individual with MEN2 allows pre-symptomatic genetic testing of other at-risk family members, and guides early intervention to prevent death and serious morbidity from MTC. Developments in the understanding of downstream RET receptor signalling pathways and how activating mutations disturb receptor function has led to insights into the possible molecular mechanisms underlying the different MEN2 phenotypes. Mutation analysis of RET in individuals with MEN2 has identified a number of different mutations, and correlation with cancer biology and clinical outcome has led to tailoring of management according to the mutation detected.

Animals↗

PubMed2002

[Breast metastasis of kidney cancer. Diagnostic and therapeutic features].

The breast is a rare site of metastasis from renal cancer and the preoperative diagnosis is often difficult. The treatment recommended for this type of metastasis is tumourectomy associated with frozen section examination, while mastectomy and lymph node dissection are unnecessary. The prognosis is often poor with a life expectancy rarely exceeding one year. The authors report a case of isolated right breast metastasis occurring two and a half years after left radical nephrectomy for renal cell carcinoma. Tumourectomy and frozen section examination were performed. The patient died four years later in a context of disseminated metastases despite immunotherapy.

Adenocarcinoma, Clear Cell↗

PubMed2005

[Lymphadenectomy for bladder cancer. Diagnostic and prognostic significance as well as therapeutic benefit].

BACKGROUND: Pelvic lymphadenectomy for invasive bladder cancer is not a standardized procedure and its relevance for staging and prognoses is still under discussion. A number of retrospective studies have demonstrated a positive correlation between extent of lymphadenectomy and prognosis after radical cystectomy. MATERIALS AND METHODS: In a retrospective study, we correlated the extent of lymphadenectomy with survival after radical cystectomy. Thereafter, we conducted a prospective study to investigate the limits of pelvic lymphadenectomy and the pattern of lymphatic spread. RESULTS: Retrospectively, we found a significantly better survival for patients when 15 and more lymph nodes were removed. The individual surgeon was also evaluated as an important prognostic factor. CONCLUSIONS: Based on retrospective data, an extended and complete pelvic lymphadenectomy improves the prognosis. The cranial border should be at least at the level of the aortic bifurcation. A prospective randomized study will have to clarify the effect of lymphadenectomy on the prognosis of patients after radical cystectomy.

Germany↗

PubMed2005

The pregnant mother with breast cancer: diagnostic and therapeutic management.

This review describes the epidemiology, pathology, clinical picture and therapeutic management of pregnant women with breast cancer. In addition, it covers other important issues like the safety of both diagnostic and treatment procedures, the indications for pregnancy termination, the mother and fetal outcome as well as the metastatic potential to the placenta and/or fetus. Several recommendations are also provided.

Breast Neoplasms↗

PubMed1981

Hepatic metastases in gastrointestinal cancer: diagnostic value of biochemical investigations.

The results of biochemical estimations in 116 patients with known gastrointestinal cancer but no clinically detectable metastatic hepatic disease have been analyzed statistically. The most sensitive and the most specific tests for the presence or absence of hepatic metastasis were measurements of alkaline phosphatase and gamma-glutamyl transpeptidase. The predictive value for the absence of hepatic metastasis when the test results were normal was about 90% for alkaline phosphatase, gamma-glutamyl transpeptidase, lactate dehydrogenase, and serum aspartate aminotransferase. The best predictive value for the presence of hepatic metastasis (80%) was given by abnormal results of combined estimations of gamma-glutamyl transpeptidase and lactate dehydrogenase, and of gamma-glutamyl transpeptidase and serum aspartate aminotransferase.

Alkaline Phosphatase↗

PubMed2005

[Local recurrence following radical cystectomy for bladder cancer. Diagnostic and therapeutic options].

The prognosis for patients with local recurrence following cystectomy for urothelial bladder cancer is poor. Only a small proportion of patients with good performance status are candidates for any form of therapy at all. Clinical experience shows that local recurrence is often accompanied or followed by systemic tumor spread. Therefore, palliative systemic chemotherapy is the cornerstone of treatment. Local radiotherapy or local tumor resection is reserved for subgroups of patients and to ease local symptoms or complications. Only a few patients are candidates for multimodal therapeutic approaches with curative intent. Despite such efforts, the survival of patients with local recurrence is limited in nearly all cases.

Antineoplastic Agents↗

PubMed1993

Fever and neutropenia in children with cancer: diagnostic parameters at presentation.

We evaluated 91 episodes of fever in 46 profoundly neutropenic children with cancer, in a search for any symptom, sign or laboratory test that would serve to identify patients with septicemia and differentiate them from those in no immediate need of prompt antimicrobial therapy. Seventeen episodes (19%) were bacteremias, 59 (64%) were suspected septic infections, 9 (10%) were focal bacterial infections and 6 (7%) proved not to be bacterial infections. We were unable to detect any parameter, either on admission or after two days of antimicrobial therapy (except for blood culture findings), that would be helpful in differentiating bacteremia from an episode not of bacterial origin. We focused on serum levels of C reactive protein and found them unreliable on an individual level. Prompt institution of antimicrobial therapy at the occurrence of fever results in low mortality, but does not allow assignment of cases to different categories.

Adolescent↗

PubMed2005

[Lymphadenectomy for testicular cancer. Diagnostic and prognostic significance as well as therapeutic benefit].

The rationale to perform retroperitoneal lymph node dissection (RPLND) in testicular cancer depends on the clinical stage and previous therapy. Thus, it can be performed either with diagnostic, prognostic, or therapeutic intention. In verified clinical stage I nonseminoma, RPLND provides one of three adjuvant options. To verify the clinical stage pathologically, surgery is done for diagnostic reasons, since CT scanning provides a false-negative staging in up to 30%. In higher stage lesions RPLND is a therapeutic procedure. The importance, however, of RPLND in clinical stage I nonseminoma is decreasing, since prognostic factors are available to stratify patients with either low or high risk for recurrence. Thus, these patients are selected for surveillance (low risk) or adjuvant chemotherapy (high risk). RPLND after chemotherapy is done for resection of residual tumor with a therapeutic intention. The histology of the residual mass is of prognostic importance and may help define further therapy. Resection of retroperitoneal metastases in patients with chemorefractory tumors is curative in about 25%.

Clinical Trials as Topic↗

PubMed2004

Oral cancer: diagnostic options as an aid to histology in order to predict patients at high risk for malignant transformation.

Oral cancer continues to afflict the general population in growing numbers with a relatively low survival rate. Today, through histology, the potential danger of a pre-cancerous lesion can be detected, yet it does not reflect with certainty its biologic behavior. Recent studies have shown that some pre-cancerous lesions with mild dysplasia may undergo malignant transformation and lesions with severe dysplasia may remain quiet. Our goal is to locate the relatively small population of patients that are at high risk for malignant transformation at an early stage of carcinogenesis so they can be treated effectively. Methods that can identify the molecular and DNA changes may provide the data needed to predict the true malignant potential of a pre-cancerous lesion and its potential for transformation with a higher degree of certainty. The purpose of this article was to review some of the diagnostic options that are being studied and their link to carcinogenesis.

Aneuploidy↗