Equivocal Reports Research Articles

Body mass index as a prognostic feature in operable breast cancer: the International Breast Cancer Study Group experience

BackgroundCurrent information on the prognostic importance of body mass index (BMI) for patients with early breast cancer is based on a variety of equivocal reports. Few have data on BMI in relationship to systemic treatment. Patients and methodsPatients (6792) were randomized to International Breast Cancer Study Group trials from 1978 to 1993, studying chemotherapy and endocrine therapy. BMI was evaluated with eight other factors: menopausal status, nodal status, estrogen receptor status, progesterone receptor status, tumor size, vessel invasion, tumor grade and treatment. BMI was categorized as normal (≤24.9), intermediate (25.0–29.9) or obese (≥30.0). ResultsPatients with normal BMI had significantly longer overall survival (OS) and disease-free survival (DFS) than patients with intermediate or obese BMI in pairwise comparisons adjusted for other factors. Subset analyses showed the same effect in pre- and perimenopausal patients and in those receiving chemotherapy alone. When assessed globally and adjusted for other factors, BMI significantly influenced OS (P = 0.03) but not DFS (P = 0.12). ConclusionsBMI is an independent prognostic factor for OS in patients with breast cancer, especially among pre-/perimenopausal patients treated with chemotherapy without endocrine therapy.

Individual submission and embedding of prostate biopsies decreases rates of equivocal pathology reports

Objectives To determine whether the use of biopsy kits with 6 to 12 containers in which biopsies of the prostate are individually submitted and processed reduces the monthly rates of equivocal diagnoses. Methods We searched our computer records for prostate needle biopsies submitted in 1 to 2 containers between July 1998 and June 2000 (group 1, 515 patients) and biopsies submitted individually in 6 to 12 containers between January 2001 and December 2002 (group 2, 933 patients). We analyzed the patient demographics and pathologic diagnoses between the two groups, including the rates of equivocal diagnoses, which included atypical gland suspicious for adenocarcinoma (ATYP) and high-grade prostatic intraepithelial neoplasia (PIN) with adjacent ATYP. Results Group 2 had statistically significant reductions in the monthly rates of equivocal diagnosis (2.8% versus 6.0%, P = 0.003), ATYP diagnosis (1.8% versus 3.5%, P = 0.042), and PIN with adjacent ATYP diagnosis (1.0% versus 2.5%, P = 0.038). The differences in the monthly prostatic adenocarcinoma rates (36.9% versus 35.9%, P = 0.388) and high-grade PIN rates (13.5% versus 12.3%, P = 0.311) between the two study groups were not statistically significant. Conclusions Multiple needle biopsies submitted in 1 to 2 containers tend to entangle and fragment and are difficult to embed in a single plane during processing. The resulting loss of tissue surface area makes a definitive diagnosis difficult on small foci of atypical glands, resulting in equivocal pathology reports. The results of our study indicate that individual submission and processing of prostate biopsies in 6 to 12 container kits reduces the monthly rates of equivocal diagnoses.

MR imaging in the assessment of residual tumour following inadequate primary excision of soft tissue sarcomas.

The purpose of this retrospective study was twofold: firstly, to assess the ability of MR imaging in confirming/excluding the presence of residual tumour following inadequate primary excision of soft tissue sarcomas; and secondly, to assess the accuracy of the original radiologists report as compared with a retrospective review of the scan hard copy in confirming/excluding. A total of 111 cases were identified that fulfilled the inclusion criteria of inadequate primary surgery followed by a MR scan and subsequent wide re-excision of the surgical field. The gold standard for the assessment of the MR imaging studies was histological examination of the re-excision specimens. Histological examination revealed residual tumour in 63 (56.7%) cases. In 48 cases the residual tumour was classified macroscopic (maximum diameter >10 mm) and 15 cases microscopic (maximum diameter </=10 mm). The original radiologists reports failed to indicate the presence or absence of tumour in 7 (6.3%) cases. In the remaining 104 cases the diagnostic performance of MR imaging gave a sensitivity of 0.64, specificity of 0.93, positive predictive value of 0.93 and negative predictive value of 0.67. In 12 of the 21 false-negative scans the residual tumour was microscopic. Subjective assessment of the radiologist's reports indicated that the proportion of equivocal reports was much higher in both the false-negative and false-positive groups as compared with the true groups. An unblinded retrospective review of the scan hard copies only differed from the original radiologists report in 8 (7.2%) cases. Contrast-enhanced sequences were not routinely obtained in this series. The results suggest that the poor negative predictive value can be attributed more to limitations of the MR scan and not to failures in observation or interpretation by the radiologists. Despite the low negative predictive value, MR imaging remains useful in planning the re-excision surgery by identifying the site and extent of the original operation and size of major residual tumour.

Evidence for an Osmoregulatory Role of Thyroid Hormones in the Freshwater Mozambique Tilapia Oreochromis mossambicus

The existing equivocal reports on the osmoregulatory role of triiodothyronine (T3) and thyroxine (T4) in teleosts prompted a reinvestigation of their osmoregulatory function in the euryhaline teleost Oreochromis mossambicus. Evidence is presented for thyroidal involvement in hydromineral balance in freshwater tilapia. Dose- and tissue-related responses to various T3 and T4 concentrations were observed in the branchial and renal tissues. The branchial Na+,K+-ATPase activity, known to reflect sodium pump dynamics, increased significantly after the administration of low doses of T3 (20 and 40 ng · g−1) or T4 (40 and 80 ng · g−1). Higher doses of T3 and T4 (>160 ng · g−1) did not change the enzyme activity, compared to sham-injected fish. Conversely, the specific activity of renal Na+,K+-ATPase decreased significantly at all doses of T3 or T4. Further, immunoreactive Na+,K+-ATPase in T4-treated fish increased in branchial chloride cells and this was coupled with a significant increase in the size of chloride cells. T4 treatment, however, did not change branchial chloride cell density. Plasma osmolality, [Na+], and [Cl−] increased, whereas [K+] decreased following low doses of T3 or T4. As expected, plasma levels of T3 and T4 increased significantly in a dose-dependent manner after a single injection of either T3 or T4. The basal levels of T3 and T4 were 4.45 ± 0.49 and 1.25 ± 0.26 nmol · L−1, respectively. This study shows that physiological concentrations of T3 (<10.57 nmol · L−1) and T4 (<6.64 nmol · L−1) enhance branchial Na+ pump activity and chloride cell morphometric dynamics, favoring hyperosmoregulatory capacity in freshwater tilapia. These data are consistent with the hypothesis that thyroid hormones perform a role in hydromineral regulation in freshwater teleosts.

Low‐dose recombinant interferon therapy in anti‐HBe‐positive chronic hepatitis B in Asian Indians*

Approximately 15% of Indian patients with hepatitis B virus (HBV)-related chronic liver disease (CLD) have infection with precore mutant forms. These patients are likely to have an aggressive course. There are equivocal reports of success with interferon therapy of mutant infection in the West. This therapy has not been evaluated in precore mutant-related CLD in Asian Indians. Eighteen patients (mean age 38.2 +/- 12 years, M:F: 17:1) with biopsy proven CLD and precore mutant HBV infection (hepatitis B surface antige (HBsAg) positive, hepatitis B e antigen (HBeAg) negative, anti-HBe positive, HBV-DNA positive) were included. Interferon alpha 2b was given at 3 mIU on alternate days for 4 months. Serology, determination of HBV-DNA (both by dot-blot hybridization and polymerase chain reaction) and liver biopsy were repeated after completion of the therapy. Response to interferon therapy was defined as loss of HBV-DNA by dot-blot hybridization. Thirteen (72.2%) patients responded to the treatment (responders). Mean alanine aminotransferase levels (83 +/- 12 vs 55 +/- 29 IU/L, P < 0.01) and the histological activity index (15 +/- 1.4 vs 12 +/- 1.3, P < 0.01) significantly decreased in the responders compared with initial values. Serum albumin levels also improved at the end of the therapy (3.5 +/- 0.4 g/dL vs 3.8 +/- 0.4 g/dL, P = 0.07). During follow up, seven of the 13 (54%) responders relapsed; cirrhotics relapsed more often than chronic hepatitis patients (P < 0.05). All 18 patients, however, continued to be HBV-DNA positive at the end of follow up. This study concluded that: 1. Interferon therapy is beneficial, albeit to a limited extent, in HBV precore mutant-related chronic liver disease in Asian Indians. 2. It is ineffective in eliminating the mutant HBV infection, which explains the high relapse rate. 3. Prolonged low-dose interferon therapy alone or in combination with newer nucleoside analogues should be evaluated in these patients.

Oral contraceptives and venous thromboembolism

In October, 1995, the United Kingdom Committee on Safety of Medicines recommended that women should use oral contraceptives containing desogestrel or gestodene only if prepared to accept an increased risk of thromboembolism. This action was based on observational studies that indicated a 2–3-fold increase in the risk of thromboembolism when desogestrel and gestodene-containing contraceptives were compared to products with levonorgestrel. The fact that these studies point in the same direction is concerning, but it is possible that these observational studies, somewhat similar in design, are influenced by the same unrecognized biases. Furthermore, the case numbers are relatively small (20–40 cases), and, for example, preferential prescribing to women at greater risk could affect the results. It is difficult to reconcile the conclusions with the strong belief supported by good evidence that thrombosis is an estrogen dose-related complication, and that progestational agents have no impact on clotting parameters. In my view, these equivocal reports are not of sufficient strength to escape biases and to change our prescribing of oral contraceptives.

Fine needle aspiration cytology of the breast: improving the predictive value of equivocal cytologic reports by monoclonal antibody B72.3

<h2>Abstract</h2> The monoclonal antibody B72.3 was tested on 77 consecutive patients with masses where cytology was reported as equivocal; all patients had been examined by palpation, sonography and mammography and underwent surgical biopsy. The positive predictive value of an equivocal cytologic report in this series was 49.3% (38 carcinomas, 39 benign lesions). B72.3 immunocytochemical assay was highly accurate (sensitivity = 94.7%, specificity=82.0%) and had a higher positive predictive value (83.7%) than conventional cytology. The B72.3 assay may be valuable in cases with equivocal cytology, as it may improve the final diagnostic judgement.

Biopsy of Occult Breast Lesions and Professional Liability-Reply

In Reply.— Dr Darios questions the advisability of not performing a biopsy of innocuous-appearing occult mammographic abnormalities on the basis of a possible malpractice judgment. Despite published and broadly accepted standards, there is unquestionably a wide variation in the criteria used by individual radiologists to support biopsy of an occult breast abnormality. This recommendation is usually based on one or more of the following factors: (1) the degree of experience and confidence of the radiologist in separating benign from malignant abnormalities, (2) the proper utilization of magnification, compression spot films, ultrasound, and/or prior comparison mammograms, and (3) the level of concern over possible litigation when recommending a 6-month follow-up rather than biopsy. Equivocal official mammographic reports diminish the value of the interpretation and almost always result in excision being performed. To orient one's practice strictly toward avoidance of litigation is unfair to our patients. We are certain that Dr Darios

Breast screening practices among primary physicians: reality and potential.

Increased use of regular screening mammograms and clinical breast examinations (CBE) among women aged 40 years and more could have a dramatic impact on mortality from breast cancer, but patient and physician barriers to mammography impede its acceptance. We conducted a survey of 300 primary care physicians to assess their knowledge, attitudes, beliefs, and breast screening practices. Our results show that only 71 percent of the respondents ordered mammograms for all women aged 50 to 75 years, which is the recommendation by the National Cancer Institute and American Cancer Society. Approximately 46 percent of respondents performed CBE on all women patients aged 50 to 75 years. Inadequate patient insurance coverage, equivocal radiology reports, patient reluctance or worry, and patient embarrassment all appear to be barriers to physicians' utilization of breast screening.

Enflurane metabolism produces covalently bound liver adducts recognized by antibodies from patients with halothane hepatitis.

The existence of a rare syndrome of "enflurane hepatitis" similar to that described for halothane and of a cross-sensitization between halothane and enflurane has been controversial, largely due to equivocal clinical case reports and a lack of a plausible molecular mechanism for the hepatotoxicity. The present study suggests a possible hypersensitivity basis for enflurane hepatitis and the apparent cross-sensitization between halothane and enflurane involving covalently bound liver microsomal adducts. Immunoblotting studies have revealed that antibodies in the sera of six patients with halothane hepatitis recognize liver microsomal antigens of Mr = 100,000, or both 100,000 and 76,000, formed in rats treated with enflurane or halothane. These antigens were not detected in microsomes from isoflurane- or sesame oil-treated rats. The recognition of these antigens could be abolished by preincubation of the sera with microsomes from halothane-treated rats. These data suggest that the difluoromethoxydifluoroacetyl halide metabolite of enflurane, as well as the trifluoroacetyl halide metabolite of halothane, covalently bind to similar hepatic proteins, and may become immunogens in susceptible patients. This mechanism may also account for the apparent cross-sensitization between halothane and enflurane anesthesia, and the development of hepatic necrosis.

Mammography of women with suspicious breast lumps.

We analyzed 342 women who had suspicious breast lumps to determine if preoperative mammography could improve the malignancy yield of biopsy procedures. The number of women with cancer of the breast and false-negative mammogram reports ranged from 11% to 25%, depending on how equivocal mammogram reports were interpreted. Therefore, women with clinically suspicious breast lumps should undergo biopsy regardless of mammographic findings. A significant difference in the mean (+/- SD) predictive value of a positive mammogram existed between women above and below the age of 50 years (80 +/- 8 vs 43 +/- 14) because of the age-specific relative prevalence of benign and malignant disease, and because mammography had difficulty distinguishing between benign and malignant lumps (specificity, 70). Preoperative mammography of women with suspicious breast lumps is indicated to screen for occult carcinoma, to prevent biopsy sampling errors, and to judge the adequacy of lumpectomy if the lesion is malignant.

Nutrition Study Design Questioned

In Reply.— We welcome the interest in our study1 and are pleased to have the opportunity to respond to Dr Wilson's letter. At the initiation of our study, there were two equivocal reports on indices of protein metabolism in full-term infants fed human milk, whey-predominant formula, or cow's milk formula.2-4 Therefore, our objective was to assess whether specific parameters of protein metabolism responded quantitatively to dietary intakes of protein, nitrogen, and amino acids. Our results did confirm that plasma aminograms are elevated with feeding either a whey-predominant or a cow's milk formula3; however, we are the first to report that total protein (total nitrogen) intake is as important as protein quality in determining plasma amino acid response in infants.

Research on plants for fertility regulation in India

This present review of Indian plants investigated for fertility regulation includes published literature of the country and unpublished data of the Central Drug Research Institute (CDRI), located in Lucknow, India. Publications without supportive experimental data have not been included. It is evident from the data presented in the tables that most of the investigators have failed to include the valuable information on the time and place of collection and proper botanical authentication, if conducted, in their publications. The plants evaluated at the Institute do contain this information and their herbaria sheets are available at CDRI. The plants, with part used, type of extract, isolated compound/chromatographic fraction, dose, route and schedule of administration with animal used, and percentage activity are given in tables. The plants are classified according to their activity profile and presented accordingly. Plants for which the hormonal profile or toxicity data have been reported are dealt with under each type of activity. Most of the investigators did not develop the active plants, probably because of inconsistent results in repeat tests or lack of facilities. Major attention has been devoted to identifying plants with interceptive properties. The schedules used are more or less uniform and acceptable. On the basis of preliminary toxicity data, extracts/compounds from "Aristolochia indica," "Artemisia scoparia," "Hibiscus rosa sinensis," "Laccardia lacca," and "Plumbago zeylanica" exclude themselves from consideration for follow-up. Wherever done, the hormonal profiles revealed estrogenic activity in active extracts/fractions/compounds from "Artabotrys odoratissimus," "Datura quercifolia," "Daucus carota," "Embelia ribes," "Hibiscus rosa sinensis," "Pueraria tuberosa" and "Tabernaemontana heyneana." Thus they are not ideal for follow-up. Some more plants can be excluded initially because of low activity or equivocal reports on activity. The remaining plants, in order of priority, for follow-up should be "Ensete superbum," "Achyranthes aspera," "Lygodium flexosum," "Sapindus trifoliatus," "Polygonum hydropiper," and "Abrus precatorius." The next priority could be given to plants with weak estrogenicity. The CDRI has observed 100% anti-implantation activity by 4 plants in hamsters. These should be the potential plants for development since they appear to interfere with progesterone synthesis or utilization.

Psychosurgery

Psychosurgery emerged in the late 1930s as a powerful therapeutic tool with great promise for psychiatry. Because of initial favorable case reports and studies, some influential support, and the need to aid thousands of returning World War II veterans with mental disabilities, the prefrontal lobotomy was widely implemented. It soon fell into disrepute through unfavorable reports of personality changes and neurologic sequelae, equivocal large-scale reports, and the introduction of major ataractic drugs and other treatment modalities. Psychosurgery has persisted in the form of restricted cerebral lesions, most stereotactically placed for relatively few mental illnesses. Evidence suggests that contemporary procedures are associated with minimal side effects and greater efficacy, but more extensive, better controlled studies are necessary.

Bipedal lymphography in the management of bladder cancer

Bipedal lymphography was performed in 91 patients with transitional cell carcinoma of the bladder. Equivocal reports were submitted in 18 (19.8%) examinations. In this series 18 (19.8%) of the patients died within one year of first treatment by radical radiotherapy. The prognosis was poorer in patients with more locally advanced tumours, in whom there was a higher proportion of abnormal lymphograms. An abnormal lymphogram was also related to a poorer prognosis than if the lymphogram was normal. This difference was greater when associated with a poorly differentiated cancer. The implications for management are discussed.

Effects of Roxarsone on Pigmentation and Coccidiosis in Broilers

Roxarsone (0.005%) medicated chickens inoculated at seven weeks of age with Eimeria maxima oocysts had significantly higher pigment levels in blood plasma than did unmedicated controls. Unmedicated E. maxima infected birds had significantly lower pigment levels compared to uninoculated controls. Uninoculated roxarsone medicated controls showed no increase in pigment levels over uninoculated unmedicated birds. This experimental design demonstrates that the beneficial effect of roxarsone medication is due to anticoccidial action rather than an increase in pigmentation after feeding the yellow-colored roxarsone. Since uninoculated birds gained more rapidly if roxarsone (0.025%) was added to the diet, the drug also appears to stimulate growth as well as to protect against coccidial infection.In two floor-pen experiments roxarsone demonstrated anticoccidial activity as measured by higher pigment scores than unmedicated infected controls. The coccidial infection was induced after seeding the litter with oocysts from birds infected with E. acervulina, E. brunetti, E. hagani, E. maxima, E. mivati, E. necatrix, E. praecox, and E. tenella. Pigmentation levels were significantly higher in plasma and skin of roxarsone medicated chickens in two experiments and in shanks in one experiment. Similar protection against depigmentation was demonstrated by adding roxarsone to feed medicated with nequinate.These results involving addition of roxarsone may explain some equivocal reports on pigmentation, weight gains or feed conversion. Some previous investigators appear to have used an inadequate experimental design by omitting use of unmedicated uninoculated controls or to have made no attempt to monitor for presence or absence of coccidiosis.