[Aspergillus in airway material : Ignore or treat?] / Aspergillus-Nachweis im Atemwegsmaterial : Ignorieren oder behandeln?

Fungi of the genus Aspergillus are ubiquitously present. Even though humans inhale Aspergillus spores daily under natural conditions, Aspergillus-associated pulmonary diseases only occur under special circumstances. Whether an Aspergillus-associated disease develops and which type of Aspergillus-associated disease develops depends on the constitution of the host. The spectrum of Aspergillus-associated pulmonary diseases ranges from allergic diseases, such as hypersensitivity pneumonitis to allergic infectious diseases, such as allergic bronchopulmonary aspergillosis (ABPA) and bronchocentric granulomatosis (BG) to infectious diseases, such as invasive (IA) or semi-invasive aspergillosis (SIA) and chronic pulmonary aspergillosis (CPA). Identification of Aspergillus spp. from sputum or bronchopulmonary secretions is not sufficient for a definitive diagnosis of Aspergillus-associated infections. The gold standard is the identification of Aspergillus spp. from lung tissue by culture or by histopathological methods; however, in clinical practice the decision to initiate antifungal therapy is more often based on immunological methods, such as the detection of Aspergillus-specific IgG antibodies from peripheral blood or galactomannan antigens from bronchoalveolar lavages. Acute IA or SIA infections have a high mortality and require immediate antifungal therapy. With rare exceptions CPA cannot be cured by medicinal therapy alone; however, active CPA can be brought into remission with antifungal therapy. Eradication of Aspergillus in CPA can as a rule only be successful using a combined antimycotic and surgical intervention.

Interobserver agreement and accuracy of non-invasive diagnosis of endometriosis by transvaginal sonography.

OBJECTIVES: To evaluate interobserver agreement and accuracy of transvaginal sonography (TVS) in diagnosing deep infiltrating endometriosis (DIE) and endometriomas. METHODS: A total of 67 consecutive patients referred to a pelvic pain clinic and scheduled for laparoscopy were enrolled in the study between January 2013 and January 2014. Patients were independently examined prospectively by two experienced sonographers (Observers A and B) who were blinded to the other's results. For the two observers, Gwet's first-order agreement coefficient (Gwet's AC1) was used to calculate interobserver agreement and diagnostic accuracy, as well as sensitivity, specificity, positive (PPV) and negative (NPV) predictive values using TVS, as compared to laparoscopy, for diagnosing DIE and endometriomas. RESULTS: Among the 67 patients enrolled, 65 were analyzed. For the diagnosis of DIE and endometriomas by TVS, the level of agreement (Gwet's AC1) between Observers A and B and sensitivity/specificity values for the respective Observers were, by site: vagina (Gwet's AC1, 0.933; 62%/94% and 82%/94%), bladder (Gwet's AC1, 1.00; 67%/97% and 67%/97%), uterosacral ligaments (Gwet's AC1, 0.84; 73%/83% and 53%/90%), adnexa (Gwet's AC1, 0.95; 71%/93% and 71%/93%), rectovaginal septum (Gwet's AC1, 0.95; 40%/90% and 33%/87%) and rectosigmoid (Gwet's AC1, 0.98; 93%/96% and 94%/98%) which reflected high interobserver agreement. With the exception of sensitivity of diagnosis of DIE affecting the RVS, similar results were observed when TVS was compared with laparoscopy. CONCLUSIONS: TVS is a highly accurate and reproducible method for non-invasive diagnosis of DIE by well-trained professionals.

[A 73-year-old female patient after liver and kidney transplantation with dull pain in the epigastrium and recurrent epistaxis]. / 73-jährige leber- und nierentransplantierte Patientin mit dumpfen Oberbauchschmerzen und rezidivierendem Nasenbluten.

A 73-year-old female patient who had received a liver and kidney transplantation presented with symptomatic pancytopenia and right-sided upper abdominal pain. The histological investigation of a bone marrow biopsy showed the extremely rare manifestation of a disseminated Merkel cell carcinoma with infiltration of the bone marrow and suppression of hematopoiesis. Also a Coombs test positive hemolytic anemia did not show a significant response to high-dose steroid therapy. Palliative chemotherapy with carboplatin and etoposide at reduced dosage had to be terminated due to deterioration of the patient's general condition. The patient died 2 days after initiation of chemotherapy.

Which lumen is the source of catheter-related bloodstream infection in patients with multi-lumen central venous catheters?

PURPOSE: Paired blood cultures, drawn from the catheter and a peripheral vein, used for calculation of the differential time to positivity (DTP), have been proposed for the detection of catheter-related bloodstream infections (CRBSIs). The most relevant catheter lumen to be sampled in multi-lumen central venous catheters (CVCs) has not been recommended. METHODS: Forty-four febrile neutropaenic patients, following haematopoietic stem cell transplantation (HSCT) and with multi-lumen CVCs in place, were investigated using the DTP method of blood samples drawn from every lumen of the CVC and a peripheral vein. RESULTS: Twelve of 44 patients (27 %) had CRBSIs, as determined by the DTP method. In 10 of 12 (83 %) febrile neutropaenic patients, after HSCT, CRBSIs originated from the CVC lumen used for parenteral nutrition and blood products only. 17 % had CRBSI originating from the other CVC lumen (p = 0.039). CONCLUSION: In most patients, CRBSIs originated from the CVC lumen used for parenteral nutrition and blood products, indicating that this lumen is the main source of CRBSI. However, since 17 % of patients had CRBSIs originating from another lumen, each lumen of multi-lumen CVCs has to be considered as a potential source of CRBSI and should, ideally, be sampled in order to avoid failure in diagnostic procedures.

Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.

STUDY QUESTION: What is the length of the diagnostic delay for endometriosis in Austria and Germany, and what are the reasons for the delay? SUMMARY ANSWER: The diagnostic delay for endometriosis in Austria and Germany is surprisingly long, due to both medical and psychosocial reasons. WHAT IS KNOWN ALREADY: Diagnostic delay of endometriosis is a problematic phenomenon which has been evaluated in several European countries and in the USA, but has not been reported for Germany and Austria. STUDY DESIGN, SIZE, DURATION: A cross-sectional, questionnaire-based multicentre study was conducted in tertiary referral centers in Austria and Germany. From September 2010 to February 2012, 171 patients with histologically confirmed endometriosis were included. PARTICIPANTS, SETTING, METHODS: Patients with a previous history of surgically proven endometriosis, internal diseases such as rheumatic disorders, pain symptoms of other origin, gynecological malignancy or post-menopausal status were excluded from the analysis. Patients with histologically confirmed endometriosis completed a questionnaire about their psychosocial and clinical characteristics and experiences. Of 173 patients, two did not provide informed consent and were excluded from the study. MAIN RESULTS AND THE ROLE OF CHANCE: The median interval from the first onset of symptoms to diagnosis was 10.4 (SD: 7.9) years, and 74% of patients received at least one false diagnosis. Factors such as misdiagnosis, mothers considering menstruation as a negative event and normalization of dysmenorrhea by patients significantly prolonged the diagnostic delay. No association was found between either superficial and deep infiltrating endometriosis or oral contraceptive use and the prolongation of diagnosis. LIMITATIONS AND REASONS FOR CAUTION: There was a possible selection bias due to inclusion of surgically treated patients only. WIDER IMPLICATIONS OF THE FINDINGS: Several factors causing prolongation of diagnosis of endometriosis have been reported to date. The principal factors observed in the present study are false diagnosis and normalization of symptoms. Teaching programs for doctors and public awareness campaigns might reduce diagnostic delay in Central Europe. STUDY FUNDING/COMPETING INTEREST(S): No competing interests exist.

[Statement of the Austrian Society of Pneumology (ASP)]. / Stellungnahme der Österreichischen Gesellschaft für Pneumologie (ÖGP): Management von Patienten mit SARS-CoV-2-Infektionen und von Patienten mit chronischen Lungenerkrankungen während der COVID-19-Pandemie (Stand 27.04.2020).

The COVID-19 pandemic is currently a challenge worldwide. In Austria, a crisis within the health care system has so far been avoided. The treatment of patients with community-acquired pneumonia (CAP), including SARS-CoV­2 infections, should continue to be based on evidence-based CAP guidelines during the pandemic. However, COVID-19-specific adjustments are useful. The treatment of patients with chronic lung diseases must be adapted during the pandemic, but must still be guaranteed.

Cigarette smoking and culture conversion in patients with susceptible and M/XDR-TB.

BACKGROUND: Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Active cigarette smoking may have a significant impact on treatment responses to anti-tuberculosis treatment. OBJECTIVE: To ascertain the effect of smoking on Mycobacterium tuberculosis sputum culture conversion rates following treatment initiation in patients with susceptible, multidrug-resistant and extensively drug-resistant TB (M/XDR-TB). METHOD: Sputum cultures of smoking and non-smoking patients with pulmonary TB (PTB) treated at a referral centre in Germany were evaluated. RESULTS: Between January 2012 and March 2017, 247 patients with PTB treated at the Medical Clinic of Research Center Borstel, Borstel, Germany, were included in the study. Of 247 patients, 65 (26.3%) were infected with multidrug-resistant strains of M. tuberculosis (MDR-TB). Sputum culture examinations were performed on a weekly basis. Active smoking (n = 111; time to culture conversion [TCC] 50.7 days, interquartile range [IQR] 26.5-73.0) and former smoking (n = 72; TCC 43.1 days, IQR 19.8-56.0) significantly delayed culture conversion rates (P < 0.001) when compared with never smoking (n = 64; TCC 33.2 days, IQR 8.0-50.3). Delay in TCC among smoking, non-MDR-TB patients (n = 138; TCC 47.3 days, IQR 19.0-89.0) was comparable with non-smoking, MDR-TB patients (n = 20; TCC 53.0 days, IQR 18.0-71.0). The shortest TCC was observed in non-smoking, non-MDR-TB patients (n = 44; TCC 33.0 days, IQR 10.0-48.5), whereas the longest was seen in smoking, MDR-TB patients (n = 45; TCC 60.7 days, IQR 33.3-89.0); P < 0.001). CONCLUSION: Active cigarette smoking and, to a lesser extent, former cigarette smoking, substantially delayed culture conversion in PTB.

Treatment responses in multidrug-resistant tuberculosis in Germany.

BACKGROUND: Excellent treatment outcomes have recently been reported for patients with multi/extensively drug-resistant tuberculosis (M/XDR-TB) in settings where optimal resources for individualised therapy are available. OBJECTIVE: To ascertain whether differences remain in treatment responses between patients with M/XDR-TB and those with non-M/XDR-TB. METHOD: Patients with TB were prospectively enrolled between March 2013 and March 2016 at five hospitals in Germany. Treatment was conducted following current guidelines and individualised on the basis of drug susceptibility testing. Two-month and 6-month sputum smear and sputum culture conversion rates were assessed. A clinical and radiological score were used to assess response to anti-tuberculosis treatment. RESULTS: Non-M/XDR-TB (n = 29) and M/XDR-TB (n = 46) patients showed similar rates of microbiological conversion: 2-month smear conversion rate, 90% vs. 78%; culture conversion rate, 67% vs. 61%; time to smear conversion, 19 days (IQR 10-32) vs. 31 days (IQR 14-56) (P = 0.066); time to culture conversion, 39 days (IQR 17-67) vs. 39 days (IQR 6-85) (P = 0.191). Both clinical and radiological scores decreased after the introduction of anti-tuberculosis treatment. CONCLUSION: There were no significant differences in scores between the two groups until 6 months of treatment. Under optimal clinical conditions, with the availability of novel diagnostics and a wide range of therapeutic options for individualised treatment, patients with M/XDR-TB achieved 6-month culture conversion rates that were compatible with those in patients with non-M/XDR-TB.

Enzyme immunoassay and Scatchard plot estimation of estrogen receptor in gynecological tumors.

Tissue samples of three endometrial carcinomas, seven ovarian carcinomas, and 24 mammary carcinomas were analyzed for estrogen receptor (ER) by enzyme immunoassay (EIA) and a conventional dextran-coated charcoal (DCC) method. In addition, ER and progesterone receptor were assayed by DCC only in 68 ovarian carcinoma specimens. All three endometrial cancer specimens showed elevated ER values by both assays. As with mammary cancers the ER-EIA values tend to be higher than DCC values. It was intriguing to note that negative Scatchard plot data resulted in residual ER levels in the EIA system. Also four ovarian cancer specimens with negative ER values by the DCC assay had detectable levels by ER-EIA, and three of these four had ER-EIA values less than or equal to 10 fmol/mg of protein. Of the ten breast cancers with negative DCC values, seven were less than or equal to 10 fmol/mg of protein by the ER-EIA. Good correlation (r = 0.88) between EIA and Scatchard plot data was calculated from ER data of 24 mammary carcinoma tissue samples. Receptor assays in 68 ovarian cancer patients indicate that ER determinations should become a useful tool in the management of patients bearing this carcinoma. In addition, receptor determinations may improve the possibility of predicting which well differentiated Stage I ovarian carcinomas are likely to recur. Present data combine to suggest that ER-EIA may become a useful diagnostic laboratory tool.

Determination of HER-2/neu amplification and expression in tumor tissue and cultured cells using a simple, phenol free method for nucleic acid isolation.

A rapid, simple and non-toxic procedure for the simultaneous isolation of DNA and RNA from tumor tissue and cells grown in vitro is described. Guanidinium isothiocyanate was used for homogenization of tumor tissue and for cell lysis. Separation of proteins, DNA and RNA was carried out by isopycnic centrifugation in cesium trifluoroacetate. DNA was further purified by salting out residual protein. Nucleic acids prepared by this method from 47 primary human carcinomas and 17 human cell lines were analysed for amplification and expression of the HER-2/neu proto-oncogene. 2- to 10-fold amplification of HER-2/neu was noted in 7/22 mammary carcinomas (32%) and in 4/14 ovarian carcinomas (28%). No amplification of the proto-oncogene was found in 4 laryngeal carcinomas, 1 pharyngeal carcinoma, 2 retrolingual carcinomas, 3 gastric carcinomas and 1 kidney carcinoma. HER-2/neu overexpression was observed in 6/22 of mammary carcinomas (27%) and 7/14 of ovarian carcinomas (50%). No overexpression was found in all other carcinomas studied. Concordance between amplification and overexpression was noted in 3 mammary and 4 ovarian carcinomas, respectively. 3 mammary and 3 ovarian carcinomas showed overexpression without amplification. 5 human mammary carcinoma cell lines showed both amplification and overexpression of HER-2/neu. In two mammary carcinoma cell lines (MDA MB-453 and ZR 75-1) overexpression was noted without amplification of the proto-oncogene. These data combine to suggest that mechanisms other than gene amplification may also lead to overexpression of the HER-2/neu protooncogene in cancer cells.

Clonogenic growth in vitro: an independent biologic prognostic factor in ovarian carcinoma.

A retrospective analysis was performed to investigate the prognostic value of growth in a human tumor clonogenic assay system for 84 ovarian cancer patients. A significant difference in survival probability (determined by the method of Kaplan-Meier) was found by univariate analysis between patients with ovarian carcinoma whose tumors manifested clonogenic growth (defined as growth of greater than or equal to five colonies per plate) and patients whose tumors did not grow. Clonogenic growth in vitro was associated with worse prognosis (P = .007, log-rank test). A number of generally accepted prognostic factors, International Federation of Gynecology and Obstetrics (FIGO) stage (P = .003), residual tumor mass (P less than .001), and grade (P = .011), were also of prognostic importance in our patient population. Multivariate analysis, based on the Cox regression model, identified clonogenic growth as a significant independent prognostic parameter in ovarian carcinoma (P = .031), in addition to the conventional risk factors. Estimation of survival of individual patients was best accomplished by combining the factors of residual tumor mass (P less than .05), age (P less than .01), and clonogenic growth (P less than .05) (in sequence of decreasing potential of risk).

Lack of impact of platinum dose intensity on the outcome of ovarian cancer patients. 10-year results of a prospective randomised phase III study comparing carboplatin-cisplatin with cyclophosphamide-cisplatin.

This prospective multicentre phase III trial was conducted to assess whether increased platinum dose intensity (DI) by combining carboplatin with cisplatin has an impact on overall survival (OS) and progression-free interval (PFI) compared with the standard combination of cyclophosphamide and cisplatin in patients with epithelial ovarian cancer. A total of 253 patients with epithelial ovarian cancer of stages International Federation of Gynecology and Obstetrics (FIGO) IC-IV were randomised to receive either cyclophosphamide (600 mg/m(2), intravenously (i.v.), day 1) and cisplatin (100 mg/m(2), i.v., day 2) (n=125) as the standard regimen or carboplatin (300 mg/m(2), i.v., day 1) and cisplatin (100 mg/m(2), i.v., day 2) (n=128), every 28 days for six courses. The median follow-up was 6.0 years. 124 patients randomised to the platinum dose-intensified arm and 123 patients randomised to the standard arm met all of the eligibility criteria. Patient characteristics were well balanced between the two treatment groups. All eligible patients randomised were included in the analysis of OS and PFI. The median OS of the standard and platinum dose-intensified arms were 41.2 (95% Confidence Interval (CI): 29.2-50.7) and 43.0 months (95% CI: 34.3-63.2), respectively (P=Non-significant (N.S.). The median PFI in the standard arm was 29.7 (95% CI: 17.4-41.7) versus 23.1 months (95% CI: 17.8-35.4) in the platinum dose-intensified arm, respectively (P=N.S.). Toxicity, comprising leucopenia, granulocytopenia, thrombocytopenia, anaemia, emesis and nausea, was statistically significantly higher in the platinum dose-intensified arm than in the standard arm. Unexpectedly, no statistically significant differences were found between the 2 arms' overall neuro- and ototoxicity. When converting carboplatin-platinum into cisplatin-platinum on the basis of an equivalence ratio of 4:1, patients in the platinum dose-intensified arm received a total platinum dose 1.58 times the platinum dose of the standard arm. With 35.0 mg/m(2)/week being administered, the total platinum DI of the dose-intensified arm was statistically significantly (P<0.0001) higher than that of the standard regimen (with 22.0 mg/m(2) being administered). Calculating the average administered relative dose intensities of the regimens yielded almost identical results with 0.56 and 0.58 for the standard and experimental arms, respectively. Thus, by conventional means, a 1.6-fold increase in the platinum DI could be reached by combining carboplatin and cisplatin without unacceptable morbidity. Nevertheless, this did not translate into any therapeutic benefit for the patient, even in the optimally debulked group of patients for whom dose-intensification would have been expected to be of benefit.

Analysis of factors influencing clonogenic growth in vitro of cells from ovarian carcinoma patients.

Clonogenic growth (defined as the formation of greater than or equal to 5 colonies per 5 x 10(5) viable nucleated cells per plate) of ovarian cancer specimens assessed in our clonogenic assay system was significantly associated with the proportion of tumor cells in the suspensions plated (N = 87; P = 0.0006), although there was no quantitative relationship with the corresponding plating efficiencies. An inverse correlation was observed between monocytes/macrophages/mesothelial cells (M) proportion and clonogenic growth (P = 0.013). These associations were most evident when only effusions were considered. Univariate analyses identified tumor cell content, M proportion and, to a lesser degree, granulocyte content as the only factors out of 12 examined to be correlated with colony formation. Multivariate analysis using a logistic regression model identified the proportion of tumor cells as the only significant factor predicting clonogenic growth in vitro (P = 0.0006). The overall accuracy of prediction for growth or non-growth was 63.2%.

Prediction of toxicity but not of clinical course by determining carboplatin exposure in patients with epithelial ovarian cancer treated with a combination of carboplatin and cisplatin.

We present the data from 105 patients with primary epithelial ovarian cancer, who received up to 6 cycles of carboplatin (300 mg/m2) and cisplatin (100 mg/m2) as one treatment arm of a prospective randomized trial. Values for first-course carboplatin area-under-the-curve (AUC) were determined retrospectively. WHO grade 3-4 thrombocytopenia was found in 10% of patients with low AUC (AUC <4 mg/ml x min), but in 44.6% of patients with high AUC (AUC 4 mg/ml x min) (chi-square p<0.0001). No single case of ototoxicity was found in the low AUC group but in 12% of patients in the high AUC group (chi-square p=0.003). Determination of carboplatin AUC may prevent ototoxicity and severe thrombocytopenia for the first cycle of combined treatment with carboplatin and cisplatin.

The role of chemotherapy including ifosfamide for ovarian carcinoma. Austrian Collab. Ovarian Cancer Study Group.

On the basis of the results of earlier studies, 30 departments of gynecology have been cooperating nationwide in Austria since 1980 to promote the use of adjuvant chemotherapy after surgery for cure of ovarian carcinoma in early stages and the role of lymph node dissection and of second-look operation. Results recorded in more than 160 patients treated with adjuvant chemotherapy after so-called radical surgery performed in disease stages I and II demonstrate that only highly differentiated tumours in stage Ia can be cured by surgery only with no further adjuvant treatment. This underlines the necessity for staging. More than 200 patients with TNM stages III and IV were randomized after debulking surgery to receive treatment with different kinds of drug combinations to compare the therapeutic efficacy of a sequential alternating drug regimen consisting of Adriamycin-cisplatin + vincristine-cyclophosphamide + high-dose methotrexate with that of the combination of Adriamycin-cyclophosphamide and that of Adriamycin-cisplatin. High-dosed ifosfamide was also used in pilot studies.

Oral contraceptives that contain ethinyl estradiol (0.035 mg) and cyproterone acetate (2 mg) inhibit leukocyte transmigration through endothelial cell monolayers.

OBJECTIVE: To investigate the influence of ethinyl estradiol and cyproterone acetate in oral contraceptives on leukocyte migration through endothelial cell monolayers. DESIGN: Experimental in vitro prospective study. SETTING: An academic research laboratory. INTERVENTION(S): Endothelial cells were cultured on microporous membranes to produce monolayers. Polymorphonuclear leukocytes were used in a previously described migration assay (n = 7). The amount of untreated polymorphonuclear leukocytes that migrated through untreated endothelial cell monolayers was used as a control and set at 100%. In addition, a leukocyte adhesion assay was used. MAIN OUTCOME MEASURE(S): Leukocyte adhesion to and transmigration through endothelial cell monolayers. RESULT(S): Ethinyl estradiol and cyproterone acetate inhibited the migration of polymorphonuclear leukocytes through endothelial cell monolayers significantly (67% +/- 6.4%) when both cell types were treated to simulate in vivo conditions. The adhesion assay produced similar results. CONCLUSION(S): Ethinyl estradiol and cyproterone acetate were identified as potent inhibitors of leukocyte migration through endothelial cell monolayers.

External ventricular drainage for treatment of rapidly progressive posthemorrhagic hydrocephalus.

Twenty-seven newborn infants (birth weight, 1503 +/- 776 g; gestational age, 31 +/- 3 wk) (mean +/- standard deviation) with rapidly progressive posthemorrhagic hydrocephalus and increased intracranial pressure were treated by external ventricular drainage. The progression of hydrocephalus was arrested during the drainage period in each patient. The drainage was kept in place for 23 +/- 9 days, the longest drainage period being 48 days. In 16 of 23 surviving patients, progressive ventricular dilation recurred after removal of the drainage, requiring a definitive shunt implantation (nine ventriculoatrial, seven ventriculoperitoneal). For the remaining seven infants, no further therapy was necessary. Implantation of the permanent shunt was done days 28 to 88 (body weight, 2400 +/- 950 g). Bacterial cultures from cerebrospinal fluid and/or the tip of the ventriculostomy catheter were negative in 175 instances and positive in 11 instances (7 patients). No clinical or biochemical evidence of ventriculitis was noted. Four of the 27 patients died of causes unrelated to external ventricular drainage. Twenty-three infants survived. Seventeen of 23 survivors suffered from intraventricular hemorrhage Grade 3; in 7, neurological and developmental outcomes were classified as normal; 9 patients experienced mild to moderate paresis and/or mild to moderate developmental delay; and only 1 patient was severely retarded. Six patients with parenchymal lesions had severe motor and/or developmental handicaps. We consider external ventricular drainage an effective and safe therapy in newborn infants with rapidly progressive posthemorrhagic hydrocephalus and increased intracranial pressure. The ultimate outcome, however, depends mainly on the mode and the extent of the primary brain lesion.

Scintimammography enhances negative predictive value of non-invasive pre-operative assessment of breast lesions.

AIMS: The aim of this study was to develop a criterion with a high negative predictive value for the evaluation of breast lesions. We aimed to determine the value of combining three non-invasive tests, mammography (MM), ultrasonography (USS) and 99mTc-methoxyisobutylisonitrite (99mTc-MIBI) scintimammography (scinti-MM). METHODS: We included 94 consecutive patients with suspected lesions detected by mammography or on physical examination. MM, USS and scinti-MM were performed no more than 4 weeks prior to excisional biopsy in all patients. We then compared the biopsy results with a score calculated for each patient, derived from the results of the three tests, which we termed 'mamma malignancy index' (MMI). RESULTS: Each of the three exams yielded a score ranging from 0 to 2, with 0 representing an almost certainly benign lesion, 1 an indeterminate finding and 2 a likely malignant lesion, and hence giving a total score ranging from 0 to 6. The biopsy results showed that the lesions in 64 patients were benign. Forty-nine (77%) of these patients had received an MMI score of 0 or 1. The negative predictive value for malignancy in patients with a score less than 2 was 100%. CONCLUSIONS: Since the smallest detected lesion was 9 mm in diameter, we conclude that MMI may be a highly useful diagnostic tool in the delineation of breast lesions > or =1 cm which should not be routinely referred for biopsy but may be followed non-invasively. Although fine needle aspiration has limitations, we would recommend it as a less invasive method to evaluate suspected lesions smaller than 1 cm.