Positive Biopsy Results Research Articles

Correlations among prostatic biopsy results, transrectal ultrasound findings and PSA levels in diagnosing prostate adenocarcinoma

Objective: The objective of this study was to evaluate transrectal ultrasound (TRUS) findings and prostate-specific antigen (PSA) levels in relation to prostatic biopsy results and to analyze their individual and combined performances in diagnosing prostate adenocarcinoma (PAC). Methods: Men ( n=143) with PSA levels above 4 ng/ml underwent TRUS and randomized ultrasound-guided prostatic biopsy through the peripheral zone, including additional hypoechoic nodules biopsies, if they were noted on TRUS. Data related to TRUS, biopsy, and PSA level results were then correlated. Results: A significant correlation between TRUS images suspicious for PAC and a biopsy-confirmed diagnosis of PAC, or between the lack of such images and a negative biopsy result, was not found. However, a significant correlation was found between positive biopsy results and PSA levels greater or equal to 10 ng/ml. The sensitivity of transrectal ultrasound in making a diagnosis of PAC was 63%, whereas its specificity was 73%. Conclusion: We conclude that while the separate performances of these examinations were not effective in diagnosing PAC, the integrated use of these methods was more adequate for making the diagnosis.

Low diagnostic yield with second biopsies in suspected giant cell arteritis.

The clinical diagnosis of giant cell arteritis may be confirmed with a biopsy of the superficial temporal artery. Because of "skip lesions," a histologic diagnosis of giant cell arteritis may be missed with a unilateral biopsy. The authors report a study that investigates whether a biopsy of the contralateral superficial temporal artery provides any additional information for confirmation of a diagnosis of giant cell arteritis. Available medical records of 91 consecutive patients who underwent bilateral superficial temporal artery biopsy procedures were reviewed. Information that was abstracted included sequence of biopsy procedures, length specimens, and histologic diagnosis. Microslides from all biopsy specimens were retrieved and reexamined in a masked fashion by the ocular pathologist (RCE) who had made the original diagnoses. Seventy-two bilateral simultaneous superficial temporal artery biopsies and 19 bilateral sequential biopsies were performed. The mean length of biopsy specimens was 23 mm, and the mean length of the total artery removed from each patient was 33 mm. The pathologist's original diagnosis and the diagnosis at reexamination were in 100% agreement. In 90 (99%) of the 91 patients, the histologic diagnoses in the left and right superficial temporal arteries were the same. This is a concordance rate of 98.9% (38 of 39 positive biopsy results) among the positive biopsy results. There is a low yield of information from a second temporal artery biopsy in patients with suspected giant cell arteritis. This suggests that patients who present to the ophthalmologist with possible giant cell arteritis will, in most cases, have a similar diagnosis on both temporal artery biopsies if the specimens are adequate.

PSA-BASED SCREENING FOR PROSTATE CANCER AFTER RENAL TRANSPLANTATION

Immunosuppressive treatment after organ transplantation is associated with an increased incidence of malignancy. In addition, increased graft survival rates will result in a larger number of patients reaching the age group at risk for prostate cancer, the most frequent cancer in men. However, in the absence of a screening procedure, a rather low incidence of prostate cancer (1.8%) was reported among 389 renal transplant recipients (1). In the largest series of prostate cancer in renal transplant recipients published to date, only 16 cases were reported, underestimation in diagnosis was suggested and screening was strongly advocated (2). We report our 1998 experience of PSA screening (Hybritech Tandem-R assay) in 120 consecutive male renal transplant recipients >50 years (median 61, range 50–74), receiving transplants between 1986 and 1996 and receiving cyclosporine A-based immunosuppressive therapy in addition to steroids and azathioprine (Fig. 1Figure 1: Distribution of PSA values in the serum of 120 male renal transplant recipients, according to age. The horizontal line (4 ng/ml) represents the threshold used for indicating sextant biopsies. o : patients with PSA values <4 ng/ml who were not submitted to further investigations; ⋄ : patients who declined further investigations; ▪ : patients presenting with prostate cancer on sextant transrectal biopsies; □ : patients with negative sextant biopsy results.). All patients had induction therapy with polyclonal antilymphocytes antibodies. Eleven patients (9.2%) for whom PSA values exceeded the threshold value (4 ng/ml) were proposed for digital rectal examination and sextant transrectal biopsies, that is, transrectal ultrasound-guided biopsies. Two patients declined examination and a biopsy. When one of them was reviewed 6 months later, the PSA had increased from 24 to 116 ng/ml, which was evocative of advanced cancer, and later biopsies confirmed this diagnosis. Among the nine patients who accepted biopsies, inflammatory lesions were evidenced in one, benign prostatic hyperplasia in one, and prostate cancer in seven. In the latter, the mean Gleason score was 6 (range : 5 - 7). The resulting detection rate was 5.8% (7 of 120 patients). Median time since transplantation was 84 months (range 14–156 months) in cancer patients. Digital rectal examination was abnormal in four patients and unremarkable in three patients, bone scan was normal in all seven. One patient declined any surgical procedure and was clinically classified as T2b according to the joint TNM-AJCC classification (3). In four patients, lymphadenectomy opposite the graft was performed for staging and proved to be negative (pNO), clinical staging was T1c in 1 patient, T2a in 2 patients, and T2b in 1 patient. All five patients were then submitted to 3D-conformal radiotherapy after adjuvant hormonal deprivation. In two patients, radical prostatectomy with lymphadenectomy (pNO) was performed; pathologic staging was pT2a with negative margins in both cases. In all seven patients graft function, as evidenced by creatinine clearance, was unchanged by cancer treatment and immunosuppressive therapy regimens were not modified. PSA values were above the threshold in roughly 10% of the patients, in line with the results observed in other screened populations of similar ages, such as in the European Randomized Study of Screening for Prostate Cancer (age selection 55–74) (4). In the Belgium and Netherlands arms of this study, the sextant biopsies performed in patients with PSA > 4 ng/ml were of moderate diagnostic yield and detected cancer in 65 of 206 patients (31.5%) and 131 of 472 (27.8%) patients, respectively (4). It is surprising that in our series, biopsy results were positive in seven of nine renal transplant recipients (77.7%). The Fisher exact chi-square test showed that this percentage of positive biopsy results was significantly higher than those reported in the above mentioned arms (P =0.007 and P =0.002, respectively). In conclusion, the detection rate in this series showed a high incidence of prostate cancer (5.8%), supporting the fact that prostate cancer prevalence in renal transplant recipients is underestimated in the absence of screening. Moreover, in this particular population, this experience highlighted, the high diagnostic efficacy of sextant biopsies after PSA screening. Whereas prostate cancer screening is still debated for the general population, we recommend its use in the follow-up of patients after renal transplantation. Bernard Malavaud Madeleine Hoff Marcel Miédouge Lionel Rostaing

Surveillance transbronchial lung biopsies: Implication for survival after lung transplantation

Objectives: We wished to determine whether early rejection after lung transplantation as assessed by surveillance transbronchial biopsy predicts for survival. Methods: Between 1990 and 1997, 96 consecutive patients had lung transplantation: 89 had a minimum 1-month follow-up. For 71 consecutive patients we have 1-year follow-up and for 69 patients we have the results of the first 3 biopsies. Cytomegalovirus status, bronchiolitis obliterans prevalence, and use of total lymphoid irradiation are noted. Biopsies were done at 1 week and 1, 3, and 6 months. Standard immunosuppression consisted of induction antilymphocyte globulin and high-dose methylprednisolone induction for 1 week and standard maintenance triple therapy. Acute rejection treatment was with pulse methylprednisolone. Bronchiolitis obliterans syndrome was treated with total lymphoid irradiation and a change to tacrolimus and mycophenolate. Blinded grading using International Society for Heart and Lung Transplantation classification was done retrospectively. Results: Survival at 1 month and 1, 2, and 3 years for the 96-patient cohort with 1-year follow-up was 93%, 74%, 62%, and 56%. Survival was not significantly different for subsets with rejection on any combination of the first 3 biopsies (1/3, 2/3, 3/3) or absence of rejection on the first 3 biopsies. Ninety-one positive biopsy results were graded. Eighteen of 71 patients had one or more moderate or severe rejection episodes without survival difference relative to the others. There was no statistically significant association between acute rejection on the first 3 surveillance biopsy results and bronchiolitis obliterans. Conclusions: Intensive induction and maintenance immunotherapy with surveillance transbronchial biopsies and aggressive treatment of acute rejection is associated with a survival similar to that of patients without early acute rejection. This regimen appears to uncouple the association between early acute rejection and bronchiolitis obliterans. Further study may elucidate this mechanism. (J Thorac Cardiovasc Surg 2000;119:27-38)

The potential clinical utility of serum α-protryptase levels

Background: Because biopsy criteria for diagnosing systemic mastocytosis are not precise, the value of serum α-protryptase levels in the work-up of suspected systemic mastocytosis should be considered. Objective: A retrospective analysis was performed on subjects with total tryptase serum levels that were high (≥20 ng/mL), while β-tryptase serum levels were normal (<1 ng/mL) or modestly elevated (1 to 5 ng/mL). Methods: Over a 3.5-year period, 52 qualifying specimens were identified from 1369 consecutive samples. The corresponding subjects were divided into those with suspected mastocytosis and those with suspected anaphylaxis. Subjects with suspected mastocytosis were subdivided into 3 subgroups on the basis of biopsy results (positive, negative, or not available). Subjects with suspected anaphylaxis were subdivided into living and deceased subgroups. Results: Among the 15 subjects who underwent biopsy, α-protryptase serum levels (the difference between directly-measured levels of serum total tryptase and β-tryptase), when greater than 75 ng/mL (n = 9), were always associated with a positive biopsy result for systemic mastocytosis; levels from 20 to 75 ng/mL (n = 6) were associated with a positive biopsy result in 50% of subjects. α-Protryptase serum levels may be a more sensitive screening test than a bone marrow biopsy for this disorder. Also, elevated α-protryptase serum levels in some adult patients return to normal over time, suggesting that mast cell hyperplasia resolved in these patients. Finally, a high α-protryptase level may reveal anaphylaxis to be a presenting manifestation of systemic mastocytosis or mast cell hyperplasia. Conclusion: Levels of serum α-protryptase, relative to those of β-tryptase, appear to be useful in the diagnostic work-up and follow-up of subjects with suspected systemic mastocytosis. (J Allergy Clin Immunol 1999;103:1092-9.)

Indocyanine green angiographic features in ocular sarcoidosis

Objective To determine indocyanine green (ICG) angiographic features and evaluate the extent of choroidal involvement in proven cases of posterior ocular sarcoidosis. Design Nonrandomized controlled trial. Participants Nineteen patients (14 females, 5 males; average age, 56 ± 4 years) with clinically typical posterior sarcoidosis (biopsy-proven in 6 cases and fulfilling the other diagnostic criteria in 13 cases) participated, with 10 control subjects (average age, 48 ± 7 years). Criteria for the diagnosis of sarcoidosis were a positive biopsy result or the presence of at least three of the following four criteria: elevated serum angiotensin-converting enzyme, elevated lysozyme, cutaneous anergy, and hilar lymph node enlargement. Intervention Indocyanine green angiography was performed according to a standard angiographic protocol used in inflammatory disorders. Main outcome measures Indocyanine green angiographic features and proportion of choroidal inflammatory involvement were measured. Results Indocyanine green angiographic features could be classified into four main patterns. The first pattern is hypofluorescent choroidal lesions in the early and intermediate phases, irregularly distributed, invisible on funduscopy or fluorescein angiography, and localized in the midperiphery (63% of patients), in the macula (11%) or in both regions (26%) with an average dot diameter of 0.31 ± 0.03 disc diameters. These lesions either became isofluorescent in the late phase of the angiogram (Type 1, present in all patients) or remained hypofluorescent (Type 2, present in 84% of patients). The second pattern is focal hyperfluorescent pinpoints visible in the intermediate and late phases (in 89% of patients). The third pattern is fuzzy choroidal vessels with leakage in the intermediate phase of the angiogram, and the fourth pattern is diffuse late zonal choroidal hyperfluorescence with staining in the late phase of the angiogram, both features being present in all patients. Conclusions Indocyanine green angiography allowed the authors to assess and quantify the hitherto unknown extent of choroidal involvement in ocular sarcoidosis. Furthermore, characteristic ICG findings might represent an additional valuable tool for diagnosing and monitoring this disease.

Outcome and Safety of Transrectal US-guided Percutaneous Cryotherapy for Localized Prostate Cancer

To assess the effectiveness and safety of ultrasound (US)-guided cryotherapy as a primary treatment for localized prostate cancer. A prospective study of percutaneous transrectal US (TRUS)-guided cryotherapy was performed on 71 patients with T1-T3, N0, M0 prostatic cancer: 10 patients underwent two or more procedures. All cases were newly diagnosed and patients had no previous treatment for cancer. For all patients, TRUS biopsies were performed at 5-6 months. Patients were monitored at 6 weeks; 3, 6, 9, and 12 months; and twice yearly thereafter for prostate specific antigen (PSA) levels, complications, and clinical evidence of residual disease. Follow-up from 10 to 36 months was available for 70 of 71 patients; one patient died of unrelated disease. Initially, 10 of 69 patients had positive postcryotherapy biopsy results. After repeated treatment, nine of these 10 patients had negative biopsy results and one patient had no follow-up. Overall, 68 of 69 patients had negative biopsy results. At 1 year, 43 of 64 (67%) had an undetectable PSA level. Two patients had proven metastases. Complications include three cases with urethral sloughing requiring transurethral resection of the prostate (TURP). One patient had orchitis. Two patients had persistent incontinence, one as the result of a TURP. There was no death, acute serious morbidity, or fistula formation. Impotence was universal at 6 months, but many patients demonstrated late recovery. Cryoablation is an imaging-guided percutaneous intervention for prostate cancer that can safely yield disease-free status in a high percentage of patients with localized disease.

Bone marrow scintigraphy using Technetium-99m antigranulocyte antibody in malignant lymphomas

The purpose of this study was to elucidate the clinical reliability of immunoscintigraphy (IS) to detect infiltration of the bone marrow in patients with malignant lymphoma. Whole body IS was performed in 103 patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) using Tc-99m labelled anti-NCA-95 which allows visualization of the granulopoietic bone marrow. Of these, 52% were studied prior to any therapy. Findings were compared to posterior iliac crest biopsy as well as MRI and/or follow-up examination. Criteria of marrow infiltration were a positive biopsy, positive follow-up, or positive results of MRI. Comparison of IS and biospy revealed concordant findings in 69 and discordant findings in 34 of 103 patients. Of the 34 patients with discordant results, IS showed lesions suspicious of bone marrow infiltration in 29 patients despite normal biopsy findings. When follow-up and additional examinations were taken into consideration, 10 patients remained with probably false positive and five with false negative IS findings. IS proved to be highly sensitive and specific in patients with HD (100% and 84%, respectively) and high-grade NHL (93% and 84%, respectively). Moderate sensitivity (60%) was found in low-grade NHL. This was possibly due to false negative IS in three to five patients with chemotherapy in contrast to one of five false negative results in patients without chemotherapy. Bone marrow scintigraphy using antigranulocyte antibodies is highly sensitive in HD and high-grade NHL. Positive findings in IS subsequent to a negative biopsy should be followed by guided re-biopsy or MRI.

Preselected Biopsy for Normal-Appearing Mucosa of Superficial Bladder Carcinoma

Objectives: We examined the incidence of positive findings (concomitant carcinoma in situ (CIS), frank carcinoma and dysplasia) for normal-appearing mucosal biopsies in superficial bladder carcinoma and the clinical outcome of patients with positive biopsy results. Methods: Eighty-four cases of newly diagnosed superficial bladder carcinoma, from whom biopsies of preselected cystoscopically normal-appearing mucosal tissue were taken at the time of initial treatment, were studied. Multivariate analysis by Cox’s proportional hazards model was applied. Results: Twenty-seven percent of the patients with superficial bladder carcinoma showed positive biopsy results. Positive biopsy results independently influenced intravesical recurrence by Cox’s proportional hazards model. Conclusions: Positive mucosal biopsy results are a significant indicator of intravesical recurrence in patients with superficial bladder carcinoma.

Computed tomography-guided biopsy of the spine. A review of 103 patients.

A retrospective study of 103 computed tomography-guided biopsies of the spine. These represent a consecutive series of patients with spinal lesions or disorders observed over a 32-month period. To determine the diagnostic accuracy and clinical usefulness of computed tomography-guided biopsies with respect to major influencing variables. Computer tomographic-guided biopsy of the spine is considered a safe, accurate, and relatively inexpensive examination technique. A study comparing its diagnostic accuracy with respect to all the variables of age, gender, radiographic appearance, spinal level, tissue type, or pathologic diagnosis has not been done. Biopsy specimens were sent for cytologic and histologic analysis. Bacteriologic studies were performed when clinically indicated. The biopsy results were analyzed for adequacy and diagnostic accuracy, i.e., the ability to generate a tissue sample adequate for pathologic examination and one that yields diagnostic information. The mean age of patients was 60 years, with a range of 4-91 years. The spines of 52 males and 51 females were studied. There were eight cervical, 28 thoracic, 53 lumbar, and 14 sacral lesions used as biopsy sites. The radiographic appearance of spinal lesions were lytic in 74 cases, blastic in four cases, and mixed in two cases. Tissues undergoing biopsy included bone (63 cases), soft tissue (35 cases), and mixed specimens (five cases). The pathologic examinations revealed 18 infections, 23 primary neoplasms, 34 metastases, and 19 normal tissues. An adequate specimen for pathologic examination was obtained in 90 biopsies (87%). A diagnosis was achieved in 67 of 94 patients (71%). Diagnostic rates obtained in thoracic level biopsies were lower than those from biopsies of other spinal levels (P = .007). Computed tomography-guided biopsy is an important tool in the evaluation of spinal lesions. A positive biopsy result may preclude the need for open surgical intervention. This study included one of the largest series of patients in the medical literature. In addition, it determined the diagnostic rates of this procedure with respect to the major influencing variables. Thoracic-level biopsies have a diagnostic rate that is significantly lower than that of other spinal levels. No significant correlation was found between diagnostic accuracy and age, gender, radiographic appearance, tissue type, or eventual diagnosis.

Changing to core biopsy in an NHS breast screening unit

We recently changed from using fine needle aspiration cytology to using core biopsy exclusively in the assessment of screen detected abnormalities. Two hundred and two biopsies (1% of women screened) were performed. Surgical histological confirmation was obtained in 111 patients (101 malignant and 10 benign). The remaining patients were either returned to standard 3-yearly screening or early repeat screening after 1 year. Analysis of the results was performed in accordance with the standards specified in the National Health Service Breast Screening Programme (NHSBSP) Publication Number 22. Absolute sensitivity was 89.3%, complete sensitivity was 93.2%, specificity (including patients undergoing both surgical excision and follow-up) was 88.7%. The predictive value of a positive (malignant) core biopsy result was 100%. The false negative rate was 3.9%. Twelve (5.9%) biopsies were classified inadequate for diagnosis. Core biopsy is a safe and accurate way of assessing screen detected abnormalities and can be used as a substitute for fine needle aspiration cytology with results that exceed the National Health Service Breast Screening Programme target standards, even in the learning phase.

Prostate imaging may not be necessary in nonpalpable carcinoma of the prostate

Stage T1c carcinoma of the prostate is defined as a nonpalpable carcinoma (NPC-P) that is not visible by imaging and is identified by needle biopsy performed because of elevated prostate-specific antigen (PSA) concentrations. The purpose of this study was to define the incidence of normal findings on transrectal ultrasound (TRUS) and/or endorectal coil magnetic resonance imaging (EMRI) among patients with NPC-P, as well as to investigate the value of differentiating patients with Stage T1c disease from all other patients with NPC-P. The records of 2211 patients diagnosed with prostate carcinoma between 1988 and 1995 were reviewed to identify 291 men with NPC-P. TRUS and EMRI reports were analyzed with regard to the presence and laterality of hypoechoic nodules or low-signal areas reported on T2-weighted images, respectively. Ninety percent of patients (n = 262) had at least six prostate biopsies, 185 patients (64%) underwent both TRUS and EMRI, 224 (77%) had TRUS, and 251 (86%) had an EMRI study. Results were considered normal in 101 (47%) of 214 patients undergoing TRUS, in 58 (23%) of 249 undergoing EMRI, and in 22 (12%) of 185 undergoing both TRUS and EMRI. For the side of the prostate with positive biopsy results, correlation with imaging abnormalities was better for EMRI than for TRUS (39% versus 24%). There was no significant difference in mean PSA value, distribution of Gleason score, or unilateral versus bilateral positive biopsy results among patients with normal versus abnormal findings on both TRUS and EMRI. (1) Only 12% of men with NPC-P have no TRUS or EMRI abnormalities, fulfilling the criteria for Stage T1c prostate carcinoma. (2) Those patients with Stage T1c disease do not differ from patients with NPC-P up-staged by TRUS or EMRI, with regard to pretreatment PSA levels, Gleason scores, and the probability of having bilateral rather than unilateral positive biopsy results. (3) The value of classifying patients with NPC-P into Stage T1c versus higher stages of prostate carcinoma on the basis of imaging should be questioned.

Loss of serum HBsAg after interferon-A therapy in liver transplant patients with recurrent hepatitis-B infection

Reinfection with hepatitis B virus after orthotopic liver transplantation is nearly universal in patients who have not received posttransplant immunoprophylaxis. Recurrence almost invariably leads to chronic liver disease. Interferon has been used both prophylactically and therapeutically but has not been effective. We treated 2 liver transplant patients with recurrent hepatitis B virus (HBV) infection (serum hepatitis B surface antigen [HBsAg] and HBV DNA positive on polymerase chain reaction, and positive liver biopsy result) with interferon, 3 to 6 MU three times weekly for 6 to 22 months. A full response to therapy was manifested in both patients by normalized serum alanine aminotransferase levels and the loss of serum HBsAg and HBV DNA. The effectiveness of interferon in our patients may have been related to coinfection with hepatitis D virus in the first case and the high interferon dose (6 MU, three times weekly) and long treatment period (22 months) in the second. No episodes of rejection were noted during therapy. We conclude that interferon can induce a complete response in liver transplant patients with recurrent HBV infection. Future studies should investigate the use of interferon therapy at higher doses and/or for longer periods. (Liver Transpl Surg 1997 Jul;3(4):394-7)

The Free-To-Total Prostate Specific Antigen Ratio Improves the Specificity of Prostate Specific Antigen in Screening for Prostate Cancer in the General Population

The ratio between free and total prostate specific antigen (PSA) in serum improves the specificity of total serum PSA for the detection of prostate carcinoma in select populations. The value of the free-to-total PSA ratio for a PSA of 4.0 to 10.0 ng./ml. was analyzed in a screening population. From 4,800 participants 55 to 76 years old 977 biopsies were obtained because of an abnormal digital rectal examination, suspicious transrectal ultrasonography and total serum PSA 4.0 ng./ml. or more. Of 191 patients with prostate carcinoma detected 101 had a serum PSA of 4.0 to 10.0 ng./ml. and 54 of them underwent radical prostatectomy. A free-to-total PSA ratio of 0.20, age specific PSA reference ranges and a PSA density of 0.12 ng./ml./cc were evaluated for the ability to increase the specificity of total serum PSA in predicting positive prostate biopsy results. Receiver operating characteristics curves for the free-to-total PSA ratio showed a significant increase in specificity compared to PSA. Retrospective application of age specific PSA reference ranges, the free-to-total PSA ratio and the PSA density decreased the number of biopsies significantly by up to 40% in our study, with a decrease in cancer detection rate of 12%. When used in combination with digital rectal examination, the pathological stage of undetected carcinomas appeared favorable. The free-to-total PSA ratio may be used to decrease biopsies in patients with an intermediate PSA of 4.0 to 10.0 ng./ml.

The Free-To-Total Prostate Specific Antigen Ratio Improves the Specificity of Prostate Specific Antigen in Screening for Prostate Cancer in the General Population

Purpose The ratio between free and total prostate specific antigen (PSA) in serum improves the specificity of total serum PSA for the detection of prostate carcinoma in select populations. The value of the free-to-total PSA ratio for a PSA of 4.0 to 10.0 ng./ml. was analyzed in a screening population. Materials and Methods From 4,800 participants 55 to 76 years old 977 biopsies were obtained because of an abnormal digital rectal examination, suspicious transrectal ultrasonography and total serum PSA 4.0 ng./ml. or more. Of 191 patients with prostate carcinoma detected 101 had a serum PSA of 4.0 to 10.0 ng./ml. and 54 of them underwent radical prostatectomy. A free-to-total PSA ratio of 0.20, age specific PSA reference ranges and a PSA density of 0.12 ng./ml./cc were evaluated for the ability to increase the specificity of total serum PSA in predicting positive prostate biopsy results. Results Receiver operating characteristics curves for the free-to-total PSA ratio showed a significant increase in specificity compared to PSA. Retrospective application of age specific PSA reference ranges, the free-to-total PSA ratio and the PSA density decreased the number of biopsies significantly by up to 40% in our study, with a decrease in cancer detection rate of 12%. When used in combination with digital rectal examination, the pathological stage of undetected carcinomas appeared favorable. Conclusions The free-to-total PSA ratio may be used to decrease biopsies in patients with an intermediate PSA of 4.0 to 10.0 ng./ml.

Free and total prostate-specific antigen in a screened population.

To determine whether the ratio of free to total (F/T) prostate-specific antigen (PSA) can differentiate between men with prostate carcinoma or benign conditions in a screened population. Total and free serum PSA (measured using Delfia PSA assays, Abbott IMx and Hybritech Tandem E methods) were determined retrospectively in 1726 men aged 55-77 years, in whom 67 prostate carcinomas were detected by screening with a digital rectal examination, transrectal ultrasonography, and total serum PSA level. Predictors for a positive biopsy result were estimated as a function of total PSA, free PSA and the combination of both. There was an excellent correlation between the Delfia ProStatus, the Abbott IMx and the Hybritech Tandem E assays. Compared with the total serum PSA level, the F/T ratio improved the specificity significantly only in those men with a total PSA of > or = 7 ng/mL. Using the information given by the total and free PSA values, a maximum sensitivity of 75% at a specificity of 74% was obtained for the whole PSA range from 4 to 10 ng/mL; the maximum sensitivity was 79% with a specificity of 71%. The optimal mathematical combination of free and total serum PSA improves the specificity of total serum PSA level in detecting prostate carcinoma more than the does the F/T PSA ratio.

Routine contralateral breast biopsy: helpful or irrelevant? Experience in 871 patients, 1979-1993.

Is routine contralateral biopsy in the breast cancer patient justified, and by which parameters can the result be predicted in advance? Routine contralateral biopsy remains controversial, and with the possible exception of an invasive lobular primary, little used by most surgeons. Previous series are biased by small sample size, by interpreting lobular carcinoma in situ (LCIS) as a positive result, by selection on the basis of tumor type, and by the inclusion of patients with clinical or mammographic abnormalities. Among 1113 consecutive patients with breast cancer treated in the author's practice between 1979 and 1993 (excluding 77 patients who had a previous mastectomy, 131 who declined biopsy, and 34 with suspicious clinical or mammographic findings), 871 had a routine contralateral biopsy. Invasive cancers were found in 1.6%, duct carcinoma in situ in 1.4%, LCIS in 3.2%, and atypical hyperplasia in 6.9% of all random biopsies. If LCIS was excluded as a positive result, invasive lobular carcinoma was not significantly more bilateral than invasive duct (5.2% vs. 2.9%, p = 0.32), nor were in situ tumors more bilateral than invasive (2.5% vs. 3.0%, p = 0.76). Tumor size, axillary node status, and young age were not predictive of a positive result. A positive biopsy result was significantly more frequent in patients older than 50 years of age (4% vs. 1%, p = 0.016), and with a first-degree family history of breast cancer (6.3% vs. 2.2%, p = 0.004). The following conclusions can be made: 1. If LCIS was excluded as a positive biopsy result, invasive lobular was not significantly more bilateral than invasive duct cancer. 2. Family history and older age significantly predicted a positive biopsy, whereas young age, tumor size, and axillary node status did not. 3. Routine contralateral biopsy identified conditions (invasive cancer or duct carcinoma in situ) requiring immediate further management in 3.0% of patients, and markers of risk (LCIS or atypia) with the potential to influence future decisions in another 10.1%. 4. As a screening device applied in a high-risk population, with low cost and little morbidity, contralateral biopsy deserves wider consideration in an era of ever-earlier breast cancer diagnosis.

Quantitative estimates of the impact of sensitivity and specificity in mammographic screening in Germany.

STUDY OBJECTIVE: To estimate quantitatively the impact of the quality of mammographic screening (in terms of sensitivity and specificity) on the effects and costs of nationwide breast cancer screening. DESIGN:...

Clinical and Prognostic Significance of Femoral Marrow Magnetic Resonance Imaging in Patients With Malignant Lymphoma

AbstractWe evaluated 56 consecutive patients with newly diagnosed lymphoma including 48 with non-Hodgkin's lymphoma (NHL) and 8 with Hodgkin's disease to determine the clinical and prognostic significance of magnetic resonance imaging (MRI) of the femoral marrow. MR images of the femoral marrow were obtained by the T1-weighted spin echo method and the short TI inversion recovery technique. Abnormal “positive” images were seen in 29 of the 56 patients (52%). All 17 patients with positive biopsy results showed abnormal images on their femoral marrow MRI. Three “positive” MRI patterns — scattered (72%), uniform (21%), and nodular (7%) — were observed. The overall survival of the patients with a positive MRI pattern was significantly poorer than that of patients with a normal pattern (P = .0129). Survival did not differ significantly according to MRI pattern. The 3-year survival rate in the patients with a normal MRI pattern was 89.9% and in the patients with a positive MRI pattern, it was 41.0%. This difference was statistically significant (P = .0279) when we evaluated only the patients with NHL. Patients with positive MRI patterns, but a normal bone marrow histology, showed a significantly shorter survival than those with a normal MRI pattern (P = .016). These results indicate that abnormal MR images of the femoral marrow are associated with a significantly poorer survival in patients with malignant lymphoma, regardless of histologic findings in the marrow.

Clinical and Prognostic Significance of Femoral Marrow Magnetic Resonance Imaging in Patients With Malignant Lymphoma

We evaluated 56 consecutive patients with newly diagnosed lymphoma including 48 with non-Hodgkin's lymphoma (NHL) and 8 with Hodgkin's disease to determine the clinical and prognostic significance of magnetic resonance imaging (MRI) of the femoral marrow. MR images of the femoral marrow were obtained by the T1-weighted spin echo method and the short TI inversion recovery technique. Abnormal “positive” images were seen in 29 of the 56 patients (52%). All 17 patients with positive biopsy results showed abnormal images on their femoral marrow MRI. Three “positive” MRI patterns — scattered (72%), uniform (21%), and nodular (7%) — were observed. The overall survival of the patients with a positive MRI pattern was significantly poorer than that of patients with a normal pattern (P = .0129). Survival did not differ significantly according to MRI pattern. The 3-year survival rate in the patients with a normal MRI pattern was 89.9% and in the patients with a positive MRI pattern, it was 41.0%. This difference was statistically significant (P = .0279) when we evaluated only the patients with NHL. Patients with positive MRI patterns, but a normal bone marrow histology, showed a significantly shorter survival than those with a normal MRI pattern (P = .016). These results indicate that abnormal MR images of the femoral marrow are associated with a significantly poorer survival in patients with malignant lymphoma, regardless of histologic findings in the marrow.