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[Obstruction of the extrahepatic bile ducts by tumor debris and/or clots in primary cancer of the liver. Diagnostic and therapeutic problems. Apropos of 9 personal cases and review of the literature].

The onset of jaundice in patients with primary liver cancer is sometimes caused by intra ductal biliary system tumor casts, free floating debris or hemobilia. The diagnosis of this complication is now possible by E.R.C.P. or P.T.C. We report 9 cases of unrecognized primary liver tumor revealed by intra biliary system migration of tumor casts or free floating debris. In three patients the diagnosis was operative, but for the last six cases the E.R.C.P. data in addition with U.S., C.A.T. Scan and/or hepatic angiography were helpful in determining the nature of the hepatic and biliary changes, the operability (size, location, extent). A curative surgery was not indicated in our 8 operated patients: liver resection and biliary decompression. With the palliative procedures, bilio enteric by pass (2 cases) T tube (1 case) trans hepatic uni or bilateral tubes. The survey was not longer than 11 months. Three patients died in post operative course. Only 56 patients among 117 observations of the literature have been operated: 10 liver resections including the main hepatic junction in two cases were performed with one hospital death, two patients were alive over 2 years with recurrence and three patients were disease free with a follow up less than one year. The operative mortality with palliative procedures was 34.4%; the one-two years survival was 23%; the two longest survivors lived 41 and 61 months.

Adenoma, Bile Duct↗

A novel diagnostic test for prostate cancer emerges from the determination of alpha-methylacyl-coenzyme a racemase in prostatic secretions.

PURPOSE: With the recent discovery that alpha-methlyacly-coenzyme A racemase (AMACR) is over expressed in a majority of prostate cancer (CaP) specimens we developed a novel polymerase chain reaction (PCR) based approach that would predict the presence of CaP from prostatic secretions. MATERIALS AND METHODS: A total of 21 patients were enlisted in this study, including 10 with CaP, 2 with high grade PIN and 9 cancer-free individuals (7 healthy men and 2 with benign hyperplasia). Total cellular RNA was extracted from prostatic secretions obtained from post-massage urine specimens. Levels of AMCAR transcripts and prostate specific antigen (PSA) transcripts in these samples were determined by quantitative reverse transcriptase-PCR analyses. Relative AMACR value scores (RAVSs) were calculated by normalizing the AMACR transcript level to that of PSA for each sample and multiplying by 100. An experimentally defined diagnostic cutoff RAVS value was determined in the cancer-free control group. RESULTS: Neither AMACR nor PSA mRNA levels were predictive of CaP when used alone. However, using RAVS values and imposing a diagnostic cutoff value of 2 SDs above the mean RAVS in the cancer-free control group all 9 (100%) cancer-free individuals, including those with benign prostatic hyperplasia, were below the cutoff and 7 of 10 (70%) with CaP had RAVS above the cutoff. Furthermore, 2 of the 3 false-negative cases showed clinically insignificant disease. The 2 patients with high grade PIN were above the cutoff in this test. CONCLUSIONS: In this study the quantification of AMACR transcripts normalized to PSA transcripts in prostatic secretions was shown to be predictive of CaP. Therefore, our novel approach using quantitative reverse transcriptase-PCR to detect the AMACR-to-PSA transcript ratio shows promise as a noninvasive screening test for CaP. Furthermore, early results demonstrate a trend toward excluding patients with clinically insignificant disease that may not yet require aggressive treatment due to a low cancer burden.

Biomarkers, Tumor↗

Analysis of the diagnostic performance in breast cancer screening by relative operating characteristics.

In medical usage, relative operating characteristics (ROC) refer to the symptoms, signs, and laboratory values used for making a diagnosis. Diagnosis analysis by ROC measures diagnosis performance independently of the diagnostic criteria used, thus revealing the arbitrary character of diagnosis. In order to carry out ROC analysis, the diagnosis has to be graded in levels of certainty of the presence of disease (or suspicion of a lesion). When both the graded diagnosis decisions and the ultimate proof of presence or absence of disease are available, ROC analysis can easily be carried out. Analysis of 50,102 successive examinations of 19,400 women in the Utrecht breast cancer screening projects presents a remarkably good fit of the observed data with the calculated values. In the medical context even small deviations of the actual sensitivity and specificity values from the ROC curve values must be considered as signs of differences in the diagnosis procedure and should lead to further analysis of the diagnostic criteria and the examined population. Consequently the separate effect of diagnosis impairment by the mammographic risk patterns (Wolfe) on diagnostic accuracy could be isolated. The effect of age on the detection capability of breast cancer by mammography appeared to operate in narrow age groups.

Aged↗

CEA, CA 19-9 and CA 72-4 improve the diagnostic accuracy in gastrointestinal cancers.

BACKGROUND: CEA, CA 19-9, CA 242 and CA 72-4 are commonly used tumour markers for gastrointestinal malignancies. The advantage of the concomitant use of these markers is under debate. MATERIALS AND METHODS: Serum concentrations of the markers were measured at the time of diagnosis in 161 patients with benign and 125 with malignant gastrointestinal diseases. Concomitant use of the markers was evaluated in a logistic regression model. RESULTS: CA 19-9, CA 242 or CA 72-4 showed similar sensitivity of 44% for gastric cancer, whereas CEA was elevated in 25% of the cases. In patients with colorectal cancer, CEA was most frequently elevated (54%), followed by CA 242 (46%), CA 19-9 (36%) and CA 72-4 (25%). High CA 19-9 and CA 242 serum levels were frequent in patients with cholangiocarcinoma (86% and 68%, respectively) and pancreatic cancer (80% and 63%, respectively). In the benign disease group, serum CA 19-9 was most frequently elevated, i.e. in 24%, 25% and 38% of patients with pancreatic, biliary and liver disorders, respectively. The overall accuracy of CEA, CA 19-9, CA 242 and CA 72-4 was 66%, 71%, 71% and 66%, respectively (p > 0.18). When combined in a logistic regression model, CA 72-4, CA 19-9 and CEA provided independent diagnostic information, whereas CA 242 contributed with independent diagnostic information only on excluding CA 19-9. The probability of cancer for each patient, calculated with the model, was applied as a diagnostic test and was compared with the single markers by ROC-curve analysis. The AUC value of the probability index was significantly higher than the values of the different tumour markers. CONCLUSION: An algorithm based on the combination of CEA, CA 19-9 and CA 72-4 improved the diagnostic accuracy in gastrointestinal tract malignancies compared with these markers alone.

Antigens, Tumor-Associated, Carbohydrate↗

Diagnostic assessment of laryngeal cancer.

Laryngeal carcinoma must be diagnosed expeditiously to maximize curative efforts. Our approach combines useful aspects of the patient's presentation with application of appropriate diagnostic modalities. Newer methods of assessment and follow-up are being scientifically validated and will likely enhance the diagnostic efforts of the head and neck surgical oncologist.

Alcohol Drinking↗

Breast cancer and pregnancy: a diagnostic and management dilemma.

BACKGROUND: The purpose of the present paper was to review the current knowledge of pregnancy concurrent with a diagnosis of breast cancer, and how best to manage this group of women and those breast cancer survivors who may subsequently conceive. RESULTS: Pregnancy-associated breast cancer or gestational breast cancer is defined as breast cancer diagnosed during pregnancy or in the 12 months post-partum. A review of the current literature on breast cancer-related pregnancy suggests an incidence of between 0.7 and 3.9%. The prognosis is thought not to be significantly different from non-pregnancy-associated breast cancer, except in cases where a delay in diagnosis is associated with more advanced disease. The treatment is similar to non-pregnant cases, with the exception of radiotherapy, which is contraindicated throughout pregnancy; and chemotherapy, which is contraindicated during the first trimester. Few breast cancer survivors go on to conceive, but those who do have no worse breast cancer or pregnancy outcomes. CONCLUSION: Most of the research in this field has come from small, specialized institutions and may not reflect what occurs in the wider community. Further population-based research in this area is needed, and is currently being undertaken in Western Australia.

Antineoplastic Agents↗

SELDI-TOF serum profiling for prognostic and diagnostic classification of breast cancers.

Surface enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry has emerged as a successful tool for serum based detection and differentiation of many cancer types, including breast cancers. In this study, we have applied the SELDI technology to evaluate three potential applications that could extend the effectiveness of established procedures and biomarkers used for prognostication of breast cancers. Paired serum samples obtained from women with breast cancers prior to surgery and post-surgery (6-9 mos.) were examined. In 14/16 post-treatment patients, serum protein profiles could be used to distinguish these samples from the pre-treatment cancer samples. When compared to serum samples from normal healthy women, 11 of these post-treatment samples retained global protein profiles not found in healthy women, including five low-mass proteins that remained elevated in both pre-treatment and post-treatment serum groups. In another pilot study, serum profiles were compared for a group of 30 women who were known BRCA-1 mutation carriers, half of whom subsequently developed breast cancer within three years of the sample procurement. SELDI protein profiling accurately classified 13/15 women with BRCA-1 breast cancers from the 15 non-cancer BRCA-1 carriers. Additionally, the ability of SELDI to distinguish between the serum profiles from sentinel lymph node positive and sentinel lymph node negative patients was evaluated. In sentinel lymph node positive samples, 22/27 samples were correctly classified, in comparison to the correct classification of 55/71 sentinel lymph node negative samples. These initial results indicate the utility of protein profiling approaches for developing new diagnostic and prognostic assays for breast cancers.

Adult↗

Diagnostic and treatment procedures induced by cervical cancer screening.

The amount of diagnostic and treatment procedures induced by cervical cancer screening has been assessed prospectively and related to mortality reduction. Assumptions are based on data from Dutch screening programmes and on a scenario for future developments. With 5 invitations for screening, between ages 37-70 every eight years, 13 deaths are avoided per million women per screening year. Each death avoided is balanced by 2800 preventive smears, 9 women referred to a gynaecology department and 4 minor treatment procedures (conserving treatment or exconisation). 25 invitations in a life-time avoids 27 deaths per million women per screening year but with 7300 preventive smears, 22 referrals and 8 small treatment procedures. Thus intensifying screening will not only result in diminishing returns of extra screening efforts, but also in increasing risk for women to undergo unnecessary (no invasive disease or death avoided) diagnostic and treatment procedures. The balance between beneficial and adverse effects deteriorates strongly when hysterectomies play an important part in the management of cervical intraepithelial neoplasia.

Adult↗

Identification by proteomic analysis of calreticulin as a marker for bladder cancer and evaluation of the diagnostic accuracy of its detection in urine.

BACKGROUND: New methods for detection of bladder cancer are needed because cystoscopy is both invasive and expensive and urine cytology has low sensitivity. We screened proteins as tumor markers for bladder cancer by proteomic analysis of cancerous and healthy tissues and investigated the diagnostic accuracy of one such marker in urine. METHODS: Three specimens of bladder cancer and healthy urothelium, respectively, were used for proteome differential display using narrow-pH-range two-dimensional electrophoresis. To evaluate the presence of calreticulin (CRT) as detected by Western blotting, we obtained 22 cancerous and 10 noncancerous surgical specimens from transurethral resection or radical cystectomy. To evaluate urinary CRT, we collected 70 and 181 urine samples from patients with and without bladder cancer, respectively. Anti-CRT COOH-terminus antibody was used to detect CRT in tissue and urine. RESULTS: Proteomic analysis revealed increased CRT (55 kDa; pI 4.3) in cancer tissue. Quantitative Western blot analysis showed that CRT was increased in cancer tissue (P = 0.0003). Urinary CRT had a sensitivity of 73% (95% confidence interval, 62-83%) at a specificity of 86% (80-91%) for bladder cancer in the samples tested. CONCLUSIONS: Proteomic analysis is useful in searching for candidate proteins as biomarkers and led to the identification of urinary CRT. The diagnostic accuracy of urinary CRT for bladder cancer appears comparable to that of Food and Drug Administration-cleared urinary markers, but further studies are needed to determine its diagnostic role.

Aged↗

Non-invasive diagnostic tests for bladder cancer: a review of the literature.

Transitional cell carcinoma of the bladder is the second most common malignancy of the genitourinary tract. Cystoscopy and urine cytology are the traditional most used techniques for diagnosis and surveillance of superficial bladder cancer. Urine cytology is specific for diagnosis of bladder cancer but sensitivity results not high, particularly in low-grade disease. Voided urine can be easily obtained and therefore additional diagnostic urine tests would be ideal for screening or follow-up of transitional cell carcinoma. A number of studies have focused on the evaluation of urinary markers that hold promise as non-invasive adjuncts to conventional diagnostic or surveillance techniques. In this review we discuss several new urinary markers (test for bladder tumor antigen, NMP22, fibrin degradation products, telomerase, fluorescence in situ hybridization test, flow cytometry) and their role in detection and follow-up of bladder cancer. Most of these markers have higher sensitivity than urine cytology, but voided urine cytology has the highest specificity.

Antigens, Neoplasm↗

Circulating IL-8 and anti-IL-8 autoantibody in patients with ovarian cancer.

OBJECTIVES: In an ongoing effort to identify diagnostic ovarian cancer biomarkers, SEREX (serological analysis of recombinant cDNA expression libraries) technique was employed resulting in detection of 20 known genes, nine ESTs and one novel sequence. Interleukin-8 (IL-8) was one of ovarian cancer-associated antigens identified by SEREX screening. The objective of this study was, therefore, to evaluate the potential importance of circulating anti-IL-8 antibody as ovarian cancer biomarker. METHODS: We developed and optimized a new immunofluorescent bead-based assay for detection of anti-IL-8 antibody in blood serum. Circulating IL-8 and anti-IL-8 IgG concentrations were measured in blood sera from 44 patients with early stage (I-II) ovarian cancer, 50 patients with late stage (III-IV) ovarian cancer, 37 patients with benign pelvic masses, and 80 healthy women using the bead-based assay. RESULTS: Our data indicate that serum contains IL-8 cytokine, anti-IL-8 antibody, and IL-8:anti-IL-8 complexes. We found that concentrations of IL-8 and anti-IL-8 antibody were elevated in sera of patients with ovarian cancer as compared with healthy controls. Logistic regression analysis of circulating concentrations of anti-IL-8 IgG in patients with stages I-II ovarian cancer versus healthy controls allowed for prediction of early ovarian cancer with 98% specificity, 65.5% sensitivity, 80.3% of patients correctly classified. Combining IL-8 and anti-IL-8 IgG with CA 125 resulted in increased classification power as compared to individual markers analyzed separately. CONCLUSION: Thus, IL-8 and anti-IL-8 autoantibody might potentially serve as additional biomarkers for ovarian cancer.

Autoantibodies↗

Lung cancer: an update on current diagnostic techniques and treatment.

National Clinical published Lung cancer is the second most commonly diagnosed cancer in the UK. In 2000 there were 38,410 new cases, accounting for 14 per cent of all cancers diagnosed (Cancer Research UK, 2004). While the incidence of lung cancer is less than that for breast cancer, lung cancer deaths account for more than one-fifth of all cancer deaths. In 2002 this amounted to 33,600 lung cancer deaths, or 22 per cent of all cancer deaths (Cancer Research UK, 2004).

Female↗

The pathology of lung cancer--changing concepts and newer diagnostic techniques.

While the basic classification of lung cancer has not altered drastically over the course of the last several years, histologic criteria have undergone a slow, progressive evolution. Input from biological studies has aided the subtyping of some tumors, especially SCLC, and helped delineate the importance of the accurate typing of NSCLC. Newer technological advances, especially in molecular biology, and application of established immunohistochemical techniques using newly generated antibodies are beginning to impact on diagnosis and typing. The evolution and application of clinical protocols directed to specific types or subtypes of lung cancer will provide an even greater impetus to these studies.

Adenocarcinoma↗

The salivary microbiota as a diagnostic indicator of oral cancer: a descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects.

BACKGROUND: The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls. METHODS: Unstimulated saliva samples were collected from 229 OSCC-free and 45 OSCC subjects and evaluated for their content of 40 common oral bacteria using checkerboard DNA-DNA hybridization. DNA counts per ml saliva were determined for each species, averaged across subjects in the 2 subject groups, and significance of differences between groups determined using the Mann-Whitney test and adjusted for multiple comparisons. Diagnostic sensitivity and specificity in detection of OSCC by levels of salivary organisms were computed and comparisons made separately between a non-matched group of 45 OSCC subjects and 229 controls and a group of 45 OSCC subjects and 45 controls matched by age, gender and smoking history. RESULTS: Counts of 3 of the 40 species tested, Capnocytophaga gingivalis, Prevotella melaninogenica and Streptococcus mitis, were elevated in the saliva of individuals with OSCC (p < 0.001). When tested as diagnostic markers the 3 species were found to predict 80% of cancer cases (sensitivity) while excluding 83% of controls (specificity) in the non-matched group. Diagnostic sensitivity and specificity in the matched group were 80% and 82% respectively. CONCLUSION: High salivary counts of C. gingivalis, P. melaninogenica and S. mitis may be diagnostic indicators of OSCC.

Adolescent↗

Human Wings Apart-Like Protein as a Serum Diagnostic Biomarker in Cervical Cancer: An Integrative Bioinformatics Analysis with Serum Validation.

Cervical cancer remains a major threat to women's health worldwide, and reliable serum biomarkers for early detection and therapeutic stratification remain limited. Human wings-apart-like (hWAPL) protein has been implicated in cervical carcinogenesis, but its diagnostic and clinical value has not been fully elucidated. To address this gap, this study integrated public multi-omics datasets, including The Cancer Genome Atlas, GEPIA2, the Human Protein Atlas, and single-cell transcriptomic data, to characterize hWAPL expression, clinicopathological associations, immune infiltration, co-expression networks, post-translational modifications, and drug sensitivity predictions. These findings were evaluated in an independent single-center serum cohort comprising 89 patients with histologically confirmed cervical squamous cell carcinoma and 89 healthy female controls. Serum hWAPL and squamous cell carcinoma antigen (SCC) levels were measured, and diagnostic performance was assessed by receiver operating characteristic curve analysis. In silico, hWAPL was broadly upregulated across multiple malignancies, particularly cervical cancer, enriched in malignant epithelial cells and monocytes/macrophages, and associated with shorter progression-free interval, predicted reduced sensitivity to cisplatin, paclitaxel, and 5-fluorouracil, and predicted sensitivity to MCL-1 and Wee1 inhibitors. In the serum cohort, hWAPL levels were significantly higher in patients than controls and discriminated cervical cancer with an area under the curve of 0.961, exceeding SCC alone. Combining hWAPL with SCC further improved diagnostic performance (area under the curve, 0.974; sensitivity, 93.3%; specificity, 95.5%). These findings suggest that serum hWAPL is a potential novel diagnostic biomarker for cervical squamous cell carcinoma whose performance is enhanced by SCC, whereas the observed associations with chemoresistance and immune microenvironment remodeling are hypothesis-generating and require experimental confirmation.

Humans↗

Evaluation of 111In-DTPA-folate as a receptor-targeted diagnostic agent for ovarian cancer: initial clinical results.

UNLABELLED: The cell-membrane folate receptor is a potential molecular target for tumor-selective drug delivery, including radiolabeled folate-chelate conjugates for diagnostic imaging. We report here the initial clinical study of such an agent, (111)In-diethylenetriaminepentaacetic acid (DTPA)-folate, evaluated for diagnosis of ovarian malignancy. METHODS: Thirty-five women were enrolled in a phase I/II clinical study, with 33 completing the surgical follow-up required by the study protocol for definition of disease status. Patients either had a pathologically proven malignancy or were scheduled for surgery for suspected new ovarian cancer (n = 26), recurrent ovarian cancer (n = 5), or endometrial cancer (n = 2). (111)In-DTPA-folate was administered as an intravenous bolus, and whole-body images were obtained at 30 min, 4 h, and (for the first 19 patients) 24 h after injection; SPECT also was done at the delayed imaging times. For 19 of the patients, unlabeled free folic acid was injected before administration of (111)In-DTPA-folate to also assess the impact of folate loading on tracer biodistribution. Masked and unmasked readings of the images by 2 nuclear medicine physicians were compared with the pathologic findings after surgery. RESULTS: Among 33 patients who had surgical intervention, 14 had new or recurrent malignant tumors. All of 7 newly diagnosed ovarian carcinomas were identified by both masked readers (sensitivity, 100%). The sensitivity for detection of 7 recurrent malignancies was 38% for masked readings and 85% for unmasked readings, indicating that correlation with anatomic imaging studies (CT) was highly important in diagnosis of these lesions. Eighteen of the studied patients were found to have benign masses; for this limited population, the specificity of (111)In-DTPA-folate scintigraphy was 76% and 82% for the masked and unmasked analyses, respectively. CONCLUSION: (111)In-DTPA-folate is safe, and possibly effective, for scintigraphy differentiating between malignant and benign ovarian masses.

Adult↗

[Genitourinary cancer incidence in a health geographic area of 300,000 people].

OBJECTIVE: To provide descriptive information on site-specific urological cancer occurrence we computed 10-year cancer incidence rates in the geographic area of Getafe (Madrid, Spain, 300,000 people). MATERIALS AND METHODS: Only histologically confirmed genitourinary cancer (bladder, prostate, kidney, testicle and penis) throughout 1992-2001 was considered. Cancers were classified according to the international rules. 10 years age-standardized population-adjusted incidence rates per 100,000 people (or per 100,000 men when appropriate) were calculated. Overall and cancer-specific yearly increments were also evaluated. The most recent release of National Statistics (2001) was used for population adjusting. RESULTS: Prostate cancer (PC) accounted for the majority of diagnostics. A strong correlation was detected between the total number of new cancer diagnostics and the overall population. While the correlation was frail between the number of new cancer diagnostics in females and the female population, the association remained significant in males. Nevertheless, only the number of new prostate cancer diagnostics was firmly and significantly associated with the population. CONCLUSIONS: Incidence rates of every cancer type increased throughout the last decade. Nevertheless, this increases didn't parallel the population increment perhaps translating environmental factors.

Female↗