Negative Biopsy Results Research Articles

Routine prostate biopsies following radiotherapy for prostate cancer: Results for 226 patients

Objectives To determine the time course of histologic resolution of prostate cancer following radiotherapy (RTj and to correlate biopsy results with clinical outcome. Methods Since July 1990, all patients treated with radical external beam RT for prostate cancer at the General Division of the Ottawa Regional Cancer Centre have had systematic transrectal ultrasound (TRUS) and TRUS-guided biopsies beginning 12 months after RT and then every 6 months until negative or until clinical failure. Thus, 226 patients have had 375 TRUS with four to seven specimens per examination. Stage distribution was T1b: 32, T1c: 11, T2a: 45, T2b: 82, T3: 50, and T4: 6. Median follow-up was 33 months. Results Biopsy results were negative in 69.5% of patients by 30 months of follow-up. Thirty-two (14%) had local failure (T1b: 12.5%, T1c: 0%, T2a: 11 %, T2b: 15%, T3: 18%, T4: 33%). Seven (3%) had chemical failure, and 47 (21%) had biopsy-only failure. Median follow-up for the biopsy-only failure group is only 19.5 months and mean prostate-specific antigen (PSA) is 1.0 ng/mL Thirty-nine patients, initially with biopsyonly failure, have converted to negative biopsies at a median of 26 months. Nadir PSA for patients with local failure was 3.9 ng/mL at 14 months versus 0.7 ng/mL at 23 months for those without failure. Patients with late conversion to negative biopsy results had a later nadir PSA of 1.3 ng/mL at 27.3 months. Conclusions Routine prostate biopsy specimens after RT in an unselected population show tumor clearance that is in agreement with long-term clinical follow-up, although tumor may take more than 30 months to resolve. Nadir PSA can be used to predict outcome.

Distinguishing tumor recurrence from irradiation sequelae with positron emission tomography in patients treated for larynx cancer

Purpose : Distinguishing persistent or recurrent tumor from postradiation edema, or soft tissue/cartilage necrosis in patients treated for carcinoma of the larynx can be difficult. Because recurrent tumor is often submucosal, multiple deep biopsies may be necessary before a diagnosis can be established. Positron emission tomography with 18F-2fluoro-2deoxyglucose (FDG) was studied for its ability to aid in this problem. Methods and Materials : Positron emission tomography (18FDG) scans were performed on 11 patients who were suspected of having persistent or recurrent tumor after radiation treatment for carcinoma of the larynx. Patients underwent thorough history and physical examinations, scans with computerized tomography, and pathologic evaluation when indicated. Standard uptake values were used to quantitate the FDG uptake in the larynx. Results : The time between completion of radiation treatment and positron emission tomography examination ranged from 2 to 26 months with a median of 6 months. Ten patients underwent computed tomography (CT) of the larynx, which revealed edema of the larynx (six patients), glottic mass (four patients), and cervical nodes (one patient). Positron emission tomography scans revealed increased FDG uptake in the larynx in five patients and laryngectomy confirmed the presence of carcinoma in these patients. Five patients had positron emission tomography results consistent with normal tissue changes in the larynx, and one patient had increased FDG uptake in neck nodes. This patient underwent laryngectomy, and no cancer was found in the primary site, but nodes were pathologically positive. One patient had slightly elevated FDG uptake and negative biopsy results. The remaining patients have been followed for 11 to 14 months since their positron emission studies and their examinations have remained stable. In patients without tumor, average standard uptake values of the larynx ranged from 2.4 to 4.7, and in patients with tumor, the range was 4.9 to 10.7. Conclusion : Positron emission tomography with labeled FDG appears to be useful in distinguishing benign from malignant changes in the larynx after radiation treatment. This noninvasive technique may be preferable to biopsy, which could traumatize radiation-damaged tissues and precipitate necrosis.

Serial Prostatic Biopsies in Men with Persistently Elevated Serum Prostate Specific Antigen Values

The objective of this study was to determine the need for repeat prostatic biopsies in men whose initial biopsy results revealed no evidence of cancer or atypia. We evaluated 1,136 men who underwent 1 or more prostatic biopsies in a longitudinal prostate specific antigen (PSA) based prostate cancer screening study that called for biopsy if the serum PSA level was greater than 4.0ng./ml. (Hybritech assay) and findings on rectal examination or ultrasonography were abnormal or suspicious for cancer. Of the 1,136 men who underwent prostatic biopsy 391 (34%) had prostate cancer on the initial biopsy. Of 427 men who had negative initial biopsy results, a persistent serum PSA level of greater than 4.0ng./ml. and abnormal rectal or ultrasound examination findings 82 (19%) had cancer on biopsy 2. Of 203 men with persistent abnormalities 16 (8%) had cancer on biopsy 3 and 6 of 91 (7%) had cancer on biopsy 4 or later. Thus, 96% of the cancers were detected through either biopsy 1 or 2. The median initial PSA level, followup PSA levels and the yearly rate of change in PSA were significantly greater in men whose cancer was detected compared with those of men whose cancer was not detected (6.4 versus 5.4ng./ml., 7.4 versus 6.6ng./ml. and 1.1 versus 0.7ng./ml. per year, respectively). There was a trend for a higher percentage of tumors detected through serial screening to be pathologically organ confined compared with those detected through initial screening (73% versus 62%, p = 0.07). We conclude that men with a persistently elevated serum PSA value after an initial negative prostatic biopsy should routinely undergo at least 1 repeat biopsy to exclude adequately the presence of detectable prostate cancer.

Direct immunofluorescence of detached gingival epithelium for diagnosis of cicatricial pemphigoid: Report of five cases

The diagnosis of mucosal cicatricial pemphigoid is often problematic because of frequent false negative or equivocal biopsy results. We describe an immunofluorescent technique that uses detached gingival epithelium for diagnostic purposes when oral manifestations of cicatricial pemphigoid are suspected. Erythematous mucosa that is gently rubbed produces detached epithelium that is then submitted for direct immunofluorescence studies along with tissue acquired via conventional techniques. In the five cases reported, the detached gingival epithelium stained intensely for immunoglobulins and complement on the basilar pole of the basal epithelial cells. The donor sites healed without a resultant periodontal defect. This adjunctive biopsy technique offers the advantage of easily procuring gingival tissue with deposition of immunoreactants that are quite specific for the diagnosis of cicatricial pemphigoid.

Prostate ultrasonography

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.

Temporal arteritis with low erythrocyte sedimentation rate: A review of five cases

We compared 5 patients who had biopsy-proven temporal arteritis and erythrocyte sedimentation rates (ESR) less than 50 mm/hour with 25 patients who had temporal arteritis and high ESR and with 10 patients who had negative temporal artery biopsy results and low ESR. Patients with low-ESR temporal arteritis were similar to the other groups, except that they had a higher mean hemoglobin level than the high-ESR group and a significant increase in the percentage of patients (4 of 5) who had a previous diagnosis of polymyalgia rheumatica or had received steroid therapy compared with either of the other groups. The latter finding suggests that even low-dose steroid therapy can lower the ESR in patients with temporal arteritis. We conclude that the ESR is low in only a small percentage of patients with temporal arteritis, and that most of these patients have a history of polymyalgia rheumatica or steroid therapy.

Cancer surveillance in ulcerative colitis

During a 13-year period, 213 patients with ulcerative colitis who had no clinical or endoscopic evidence of colonic carcinoma were enrolled in a biopsy surveillance program for dysplasia and carcinoma. The aims of the study were to determine whether such a program could decrease the cancer risk in this group of patients, to determine whether patients with a low risk of carcinoma could be identified, thus enabling them to retain their colon, and to accomplish these goals with a reasonable expenditure of resources. Eighteen patients had dysplasia detected in the initial biopsy specimens; 15 of these patients underwent colectomy, and 7 had unsuspected carcinoma (1 Dukes' stage A, 2 stage B, and 4 stage C). Eleven patients had dysplasia detected during follow-up; 7 of these patients had colectomy, and only 1 patient had carcinoma (Dukes' B). Dysplasia developed in 5 of 20 patients with indefinite changes on initial biopsy samples; 3 of these patients underwent colectomy, and 1 patient had carcinoma (Dukes' B). There was no difference in the prevalence of dysplasia between patients with left-sided disease and patients with extensive disease. With the exception of 2 patients with inadequate surveillance, there has been no clinical evidence of carcinoma in any of the 148 patients whose biopsy results remained negative throughout the study; carcinoma has not developed in any of 175 patients without dysplasia on initial biopsy sample. All 4 patients who died of carcinoma had high-grade dysplasia in their initial colonoscopic biopsy samples. It is concluded that a biopsy surveillance program can be an effective aid in helping control the risk of carcinoma in patients with long-standing ulcerative colitis, that the short-term risk of carcinoma for patients with negative biopsy results is low and colectomy for risk of carcinoma can be deferred in this group, and that patients with extensive and left-sided disease share the same risk of the development of dysplasia.

Cancer Surveillance in Ulcerative Colitis

During a 13-year period, 213 patients with ulcerative colitis who had no clinical or endoscopic evidence of colonic carcinoma were enrolled in a biopsy surveillance program for dysplasia and carcinoma. The aims of the study were to determine whether such a program could decrease the cancer risk in this group of patients, to determine whether patients with a low risk of carcinoma could be identified, thus enabling them to retain their colon, and to accomplish these goals with a reasonable expenditure of resources. Eighteen patients had dysplasia detected in the initial biopsy specimens; 15 of these patients underwent colectomy, and 7 had unsuspected carcinoma (1 Dukes' stage A, 2 stage B, and 4 stage C). Eleven patients had dysplasia detected during follow-up; 7 of these patients had colectomy, and only 1 patient had carcinoma (Dukes' B). Dysplasia developed in 5 of 20 patients with indefinite changes on initial biopsy samples; 3 of these patients underwent colectomy, and 1 patient had carcinoma (Dukes' B). There was no difference in the prevalence of dysplasia between patients with left-sided disease and patients with extensive disease. With the exception of 2 patients with inadequate surveillance, there has been no clinical evidence of carcinoma in any of the 148 patients whose biopsy results remained negative throughout the study; carcinoma has not developed in any of 175 patients without dysplasia on initial biopsy sample. All 4 patients who died of carcinoma had high-grade dysplasia in their initial colonoscopic biopsy samples. It is concluded that a biopsy surveillance program can be an effective aid in helping control the risk of carcinoma in patients with long-standing ulcerative colitis, that the short-term risk of carcinoma for patients with negative biopsy results is low and colectomy for risk of carcinoma can be deferred in this group, and that patients with extensive and left-sided disease share the same risk of the development of dysplasia.

Determination of prostate volume with transrectal US for cancer screening. Part I. Comparison with prostate-specific antigen assays.

To investigate whether radiologists can objectively define a high-risk group for prostate cancer, the researchers measured gland volume and compared it with results of a screening blood test, prostate-specific antigen (PSA) assay. A total of 768 men, aged 55-71 years, were self-referred to two prostate cancer screening programs using transrectal ultrasound (US) and digital rectal examination. In patients with no evidence of cancer, statistically significant increases in mean PSA values were noted with increasing gland volume ranges (P less than .05). PSA values in patients with cancer were more likely to exceed the volume-adjusted 95th percentile (mean + [1.65.standard deviation]) than those in patients with negative biopsy results (P less than .005). Patients with PSA values above the volume-adjusted 95th percentile have an estimated risk for prostate cancer up to nine times that of the general screening population. The researchers conclude that knowledge of transrectal US gland volume and prostate-specific antigen assay type are important objective variables for future prostate cancer screening programs. The volume-adjusted 95th percentiles presented may help guide cost-effective management of current early detection efforts.

Helicobacter pylori infection in pernicious anemia: A prospective controlled study

Although some authors believe that Helicobacter pylori is the etiologic agent in chronic nonspecific gastritis, it has also been suggested that the bacterium colonizes inflamed mucosa as a secondary event. This study documents the prevalence of H. pylori in 28 patients with pernicious anemia and compares the findings with those of a group of 28 age-, race-, and sex-matched asymptomatic control subjects. All subjects underwent endoscopy with biopsy of the gastric antrum and corpus. A sample of serum was obtained before endoscopy for determination of antibodies (immunoglobulin A and immunoglobulin G) to H. pylori. The prevalence of H. pylori (by biopsy) in patients with pernicious anemia was significantly less than that in controls (11% vs. 71%, P < 0.0001). All patients with pernicious anemia had abnormalities of corpus histology (inflammation and/or atrophy). In addition, 50% of patients with pernicious anemia had a lymphocytic infiltration of the antrum. All controls with H. pylori had gastritis, 50% having active chronic gastritis. Atrophie changes of the corpus were more commonly found in patients with pernicious anemia (75% vs. 7%, P < 0.0001). Serology and biopsy results correlated poorly in the patients with pernicious anemia: all 5 patients with positive serology results had negative biopsy results, whereas all 3 patients with positive cultures on biopsy had negative serological studies. In conclusion, patients with pernicious anemia are protected from infection with H. pylori, and H. pylori does not passively colonize mucosa inflamed by an unrelated process.

Enhanced Bladder Cancer Detection with the Lewis X Antigen as a Marker of Neoplastic Transformation

Recent evidence indicates that the Lewis X determinant is a tumor-associated antigen in the urothelium. Immunohistochemical analyses on frozen and deparaffinized, formalin-fixed tissue sections have demonstrated that the Lewis X antigen is not detected in normal adult urothelium except for occasional umbrella cells. However, papillomas and transitional cell carcinomas express this blood group-related antigen in more than 90% of the cases regardless of the grade or stage of the tumor, or the blood type or secretor status of the individual. To determine the presence of Lewis X antigen on exfoliated bladder epithelial cells we used an anti-Lewis X monoclonal antibody (P-12) and the avidin-biotin-peroxidase technique on 129 bladder barbotage specimens. Of 40 controls 34 were negative for Lewis X antigen, for a specificity of 85%. The 89 bladder tumor patients consisted of 14 with papilloma, 13 with flat carcinoma in situ, 49 with transitional cell carcinoma, and 13 with a positive cytology and negative biopsy results. Of these 89 patients 76 were considered positive for Lewis X antigen, for an over-all sensitivity 85.4%. The sensitivity for cytology alone was 61.2%. However, the combination of a positive cytology and/or positive Lewis X antigen result yielded a sensitivity of 93.2%. The data suggest that immunocytological detection of the Lewis X antigen on exfoliated bladder cells enhances the detection of urothelial tumor cells, particularly from low grade and low stage neoplasms.

Retrospective analysis of the efficacy of open lung biopsy in acquired immunodeficiency syndrome

Open lung biopsy (OLB) was performed on 66 patients with acquired immunodeficiency syndrome from November 1981 through December 1987. Twenty-two patients with severe respiratory failure died within a month, 3 during operation. Fourteen patients with negative transbronchial biopsy and 19 with failure of treatment based on transbronchial biopsy died within a year. Six were alive and 5 were lost to follow-up. The most common organism found in patients with severe respiratory failure was Pneumocystis carinii alone or with other pathogens. Successful therapeutic change based on OLB findings was possible in only 1 (1.5%) of the 66 patients. Open lung biopsy has limited application in the management of acquired immunodeficiency syndrome. In patients with overt pulmonary failure, OLB is invariably fatal. Those seen with suspicious lung infiltrates without risk factors or with known risk factors and negative transbronchial biopsy results might benefit from OLB. In our institution, 18 of 64 acquired immunodeficiency syndrome admissions underwent OLB in 1983, whereas in 1987, only 2 of 302 patients admitted with acquired immunodeficiency syndrome had OLB.

Diagnostic Value of Surgical Testicular Biopsy After Therapy for Acute Lymphocytic Leukemia

Inasmuch as several cooperative research groups currently require routine testicular biopsy in boys with acute lymphocytic leukemia before cessation of therapy, we performed bilateral open wedge biopsies in 38 boys aged 4 1/2 to 18 years, all of whom were completing 3 years of therapy, were apparently in complete remission, and had palpably normal testes. Biopsy specimens from two other patients were examined during therapy for specific clinical indications. Among the 40 patients, one biopsy revealed leukemia bilaterally; 39 patients had negative biopsy results, three of whom had overt, biopsy-proved testicular relapse 6 weeks to 17 months after normal biopsy. All four patients with testicular relapse are in complete remission six to 50 months after testicular irradiation. We conclude that random sampling during routine testicular biopsies may fail to demonstrate occult leukemia. and that the high rate of complete remissions following retrieval therapy after overt testicular relapse makes routine biopsies before cessation of therapy unnecessary.

Diagnostic value of surgical testicular biopsy after therapy for acute lymphocytic leukemia

Inasmuch as several cooperative research groups currently require routine testicular biopsy in boys with acute lymphocytic leukemia before cessation of therapy, we performed bilateral open wedge biopsies in 38 boys aged 4 1/2 to 18 years, all of whom were completing 3 years of therapy, were apparently in complete remission, and had palpably normal testes. Biopsy specimens from two other patients were examined during therapy for specific clinical indications. Among the 40 patients, one biopsy revealed leukemia bilaterally; 39 patients had negative biopsy results, three of whom had overt, biopsy-proved testicular relapse 6 weeks to 17 months after normal biopsy. All four patients with testicular relapse are in complete remission six to 50 months after testicular irradiation. We conclude that random sampling during routine testicular biopsies may fail to demonstrate occult leukemia, and that the high rate of complete remissions following retrieval therapy after overt testicular relapse makes routine biopsies before cessation of therapy unnecessary.

Stress-Coping Response to Genitourinary Carcinoma in Men

In this descriptive study of 30 men with chronic genitourinary cancer, subjects were found to have minimal emotional distress in response to a periodic diagnostic procedure (cystoscopy). State anxiety levels and critical thinking ability measured preprocedure were not significantly different from levels obtained six to eight weeks postprocedure in subjects with negative biopsy results. Routine hospitalization for diagnostic monitoring was found, during COPE interview (Weisman & Worden, 1976), to be less stressful than regular work or financial and family concerns. Subjects with higher concurrent life stress had higher state anxiety and achieved less resolution of problems. Although anxiety levels for the group were within normal limits, 33% of the sample were categorized as having high anxiety on at least one testing occasion. This high-anxiety group had more severe behavioral responses, including feelings of depression, helplessness, and inability to set priorities.

Intramyocardial Coronary Arterial Changes in Rheumatic Mitral Valve Disease

A retrospective analysis of intramyocardial coronary arterial changes was done in excised papillary muscles obtained at surgery in 46 cases with rheumatic mitral valve disease (RMVD). The findings were correlated with left ventricular function. Vessel wall thickening with obliteration of the lumen was found in 15 patients (32.6%) while adventitial and perivascular fibrosis was found in 12 cases (26%). Patients with microarteriopathy had significantly higher left ventricular and diastolic pressure (p less than 0.05), lower ejection fraction (p less than 0.001), and lower cardiac index (p less than 0.01), as compared to patients with no microarteriopathy. The incidence of left ventricular dysfunction and surgical mortality was higher in patients with microarteriopathy (80 and 47%, respectively) than in those with normal microvasculature (26 and 13%, respectively). As a test for predicting left ventricular dysfunction and surgical mortality a positive biopsy was moderately sensitive (sensitivity 60 and 64%, respectively) and highly specific (specificity 88 and 77%, respectively). Successful outcome after mitral valve replacement was correctly predicted by a negative biopsy result in 87% cases. We conclude that in RMVD, microarteriopathy is associated with left ventricular dysfunction and poor postoperative prognosis.

Diagnostic yield of transbronchoscopic biopsies.

Transbronchoscopic biopsies of lung (transbronchial) or bronchus (endobronchial) have a high diagnostic of yield when performed by a single expert bronchoscopist or a small group of expert bronchoscopists. This procedure's diagnostic yield was evaluated in a general hospital where biopsies are performed by a diverse group of individuals. One hundred fifty-one consecutive biopsies were reviewed, including 53 transbronchial biopsies and 98 endobronchial biopsies. Only 44% of endobronchial biopsies and 21% of transbronchial biopsies were diagnostic. The diagnostic yield was significantly greater in patients with suspected neoplasms (48%) than in patients with suspected infections (13%). Of 97 patients who ultimately had definitive diagnoses established, 43 (44%) had negative biopsy results, including 36% of those with cancers and 80% of those with infections. Failure to obtain alveolar parenchyma by transbronchial biopsy (probably related to the absence of fluoroscopic control) and failure to obtain multiple tissue fragments during each procedure contributed to the low diagnostic yield. The especially disappointing results of transbronchial biopsy for diagnosis of infection suggest that, in this hospital setting, open lung biopsy may be the procedure of choice when infection is suspected.