First repeated bone scan in the observation of patients with operable breast cancer.

Data on 1,601 patients with node-positive operable breast cancer who were randomized in four different prospective adjuvant therapy trials were analyzed to evaluate the role of routine bone scans and the alkaline phosphatase value at regular intervals in screening for bone involvement. Bone scan was a prerequisite for randomization and was repeated within the first 12 months in 90% (1,441) of the patients. Abnormal or doubtful scan findings had to be verified by x-ray examination. The repeated scan results were normal in 1,263 (87.8%) patients, doubtful but with no radiologic evidence of bone metastasis in 161 (11%), and abnormal (radiologically confirmed) in 17 (1.2%). After a median observation of 4 years bone metastases as the first relapse developed in 136 (8.5%) patients. This occurred in 87 of 1,263 (6.9%) of the patients with normal repeated scan results and in 18 of 161 (11.2%) of those with doubtful repeated scan findings. Based on the results of the first repeated scan, early detection of a first recurrence in bone might have been possible for 2.4% of the population. Serum alkaline phosphatase levels were also without clinical use. Bone scan in the observation of patients with operable breast cancer should be performed only as dictated by the clinical situation.

Quality of life measures for patients receiving adjuvant therapy for breast cancer: an international trial. The International Breast Cancer Study Group.

Serial quality of life (QL) assessments are being obtained every 3 months for 2 years from patients with operable breast cancer in two ongoing International Breast Cancer Study Group (IBCSG) randomised clinical trials of adjuvant treatment. The QL-assessments include patient-derived perceived coping (PACIS, personal adjustment to chronic illness scale), well-being (Bf-S, Befindlichkeitsskala von Zerssen), mood, physical well-being and appetite (LASA, linear analogue self assessments). The first assessment within 6 weeks of surgery was performed by 70% of the patients. The analysis of serial assessments for 265 patients with each of the first four assessments completed showed that all measures improved with increasing time from study entry; that the degrees of improvement for the four major language groups were similar; and that measures were sensitive to treatment difference. In conclusion, measurement of QL related aspects in a multicultural clinical trial is feasible and possibly relevant for the evaluation of treatment results.

Retreating recurrent breast cancer with the same CMF-containing regimen used as adjuvant therapy. The International Breast Cancer Study Group.

Breast cancer metastases appearing soon after adjuvant chemotherapy (within 12 months of its completion) are usually resistant to retreatment with the same cytotoxic agents, while relapses occurring later (beyond 12 months) regress when rechallenged with the same agents, showing similar response rates observed in non-pretreated patients with advanced disease. The International Breast Cancer Study Group (IBCSG) prospectively explored the efficacy of retreatment for patients upon relapse using the same therapy administered during the adjuvant programme. 87 patients previously treated with an adjuvant CMF (cyclophosphamide, methotrexate, 5-fluorouracil) combination chemotherapy (with or without the addition of low-dose prednisone and tamoxifen), who had measurable first breast cancer relapse, usually after at least 6 months of completion of the adjuvant treatment, were treated with CMF. Pretreatment consisted of 1-3 CMF courses in 27 patients and 4 or more courses in 60 patients. 17 patients were retreated with additional tamoxifen or had tamoxifen stopped at relapse. The data of these patients are shown separately. 47 of the 86 fully evaluable patients (55%) had an objective response, which was complete in 25 (29%). The dominant metastatic type and the number of involved sites were the most important factors influencing response to retreatment. Patients with soft tissue metastases had a high response rate (36/52, 69%) compared with those who had visceral involvement (9/24, 38%) or those with bony disease (2/10, 20%) (P = 0.002). In conclusion, response rates to retreatment with CMF were similar to those expected in a non-pretreated population. The patterns of relapse and the number of metastatic sites were the most important factors predicting response to retreatment, while treatment-free interval (usually longer than 6 months due to the study design) did not influence response rates. This study supports the hypothetic effectiveness of late reintroduction of adjuvant cytotoxic therapy (prior to evidence of systemic relapse), upon which several current trials are based.

Newer laboratory approaches for assessing visual dysfunction.

The crucial point that will be emphasized throughout this report is the potential utility of analyzing visual cortical receptive field (RF) properties of the single-cell level as a sensitive and reliable neurotoxicity screening tool. Numerous studies employing exposure of kittens to altered visual environments during the critical period have demonstrated that particular classes of RFs can be selectively affected while sparing others. There has been a rapid proliferation of new methods used to investigate such effects. An important current trend involves the development of multidisciplinary combinations of approaches. The various maneuvers reviewed here seem adaptable to studying neurotoxic insult of the sensitive properties of cortical visual neurons, particularly in the cat or monkey. Conceivably, a general disruption of cortical RF properties might be expected following toxic exposure since individual RF properties are generally not determined by completely independent mechanisms. In fact, some toxicants might produce a general degradation of RF properties akin to the electrophysiological results reported for long-term dark rearing or binocular deprivation.

Binocular depth perception following early experience with interocular torsional disparity.

The relationship between the behavioral and physiological consequences of rearing with optically induced cyclotropia was assessed. Beginning at the age of 4 weeks, kittens wore goggles that rotated the visual field in opposite directions in each eye for several hours each day over a period of several weeks. The amounts of interocular rotation were 0 deg (control), 16 deg, and 32 deg. Subsequently, they were tested to determine their monocular and binocular depth thresholds and, in some cases, visual acuity. In several kittens recordings were also made from the visual cortex. Binocular performance of all kittens in the 0-deg condition and three out of six kittens in the 16-deg condition was comparable to, although slightly lower than, that of normally reared kittens. In contrast, none of the 32-deg kittens showed any evidence of the binocular superiority that would suggest the presence of stereopsis. Extracellular unit recordings from the visual cortex confirmed our earlier results with goggle-reared kittens. In 16-deg kittens, the distribution of the cells' preferred interocular disparities (IOD) in receptive-field orientation showed a compensating shift so that the mean matched the experienced rotational disparity. In the 32-deg kittens, binocularity was greatly disrupted and there was no compensatory shift in the IOD distribution. Two 32-deg kittens were afforded 3 years of subsequent normal visual experience. Both the behavioral and the physiological findings were unaffected by normal visual exposure in adulthood. Control measurements of acuity indicated that any deficits in depth perception were not due to reduced spatial-resolution abilities. The data indicate that the kitten visual system is able to maintain functional binocularity sufficient to subserve a moderate level of stereoacuity with interocular rotations of up to at least 16 deg.

Interocular torsional disparity and visual cortical development in the cat.

1. The present experiments were designed to assess the effects of relatively large optically induced interocular torsional disparities on the developing kitten visual cortex. Kittens were reared with restricted visual experience. Three groups viewed a normal visual environment through goggles fitted with small prisms that introduced torsional disparities between the left and right eyes' visual fields, equal but opposite in the two eyes. Kittens in the +32 degrees goggle rearing condition experienced a 16 degrees counterclockwise rotation of the left visual field and a 16 degrees clockwise rotation of the right visual field; in the -32 degrees goggle condition the rotations were clockwise in the left eye and counterclockwise in the right. In the control (0 degree) goggle condition, the prisms did not rotate the visual fields. Three additional groups viewed high-contrast square-wave gratings through Polaroid filters arranged to provide a constant 32 degrees of interocular orientation disparity. 2. Recordings were made from neurons in visual cortex around the border of areas 17 and 18 in all kittens. Development of cortical ocular dominance columns was severely disrupted in all the experimental (rotated) rearing conditions. Most cells were classified in the extreme ocular dominance categories 1, 2, 6, and 7. Development of the system of orientation columns was also affected: among the relatively few cells with oriented receptive fields in both eyes, the distributions of interocular disparities in preferred stimulus orientation were centered near 0 degree but showed significantly larger variances than in the control condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Piggyback technique and selective use of veno-venous bypass in adult orthotopic liver transplantation.

BACKGROUND: The piggyback technique (PT), with preservation of the cava, is being used more frequently in adult orthotopic liver transplantation (OLT). The advantages of PT include hemodynamic stability during the anhepatic phase without a large-volume fluid infusion and obviating the need for veno-venous bypass (VVB). At our center, we changed our practice in July 1997 from the standard technique (ST) of OLT with routine use of VVB to PT and selective use of VVB. The purpose of the present study was to analyze the results with the two different practices, ST-routine VVB versus PT-selective VVB. METHODS: Forty OLTs were performed during the period July 1995 July 1997 using ST-routine VVB (group I) and 36 during August 1997-December 1998 using PT-selective VVB (group II). The etiology of liver disease was similar in the two groups, with hepatitis C and alcoholic liver disease accounting for half of the patients in each group. The UNOS status, age, sex, and percentage of patients with previous upper abdominal surgery were also similar between the two groups. RESULTS: In the PT-selective VVB era (group II), 34/36 patients (94%) underwent OLT with PT and VVB was used for 8 (22%) patients. The decision to use VVB was elective for 3 patients (fulminant hepatic failure, 2; severe portal hypertension, 1) and urgent for 5 patients (hemodynamic instability during hepatectomy). The intraoperative use of packed red blood cells (PRBC) (mean +/- SD) was 15+/-12 units for group I and 9+/-8 units for group II (p = 0.023). Anastomosis time and total operating time (mean +/- SD) were 91 + 30 min and 9.5+/-3.2 h, respectively, for group I patients compared with 52+/-28 min and 7.6+/-1.6 h, respectively, for group II patients (p<0.0001 and 0.002, respectively). Median post-operative stays in the intensive care unit (ICU) and in the hospital were 5 and 17 d, respectively, for group I and 4 and 11 d, respectively, for group II (p = NS). Mean serum creatinine on day 3 was similar in the two groups. Median hospital charges for group I patients were $105439 compared with $91779 for group II patients (p = NS). The 1-year actuarial graft and patient survival rates were 78% and 82%, respectively, for group I, and 92% and 95%, respectively, for group II. CONCLUSIONS: PT is safe and can be performed in the majority of adult patients (>90%) undergoing OLT. With the routine application of the piggyback procedure, the use of VVB has been reduced to 20% of OLTs at our center. The practice of piggyback technique with the selective use of VVB is associated with shorter anhepatic phase and total operating time, lower blood product use, a trend towards shorter hospital length of stay, and reduced hospital charges compared with standard technique of OLT with routine use of VVB.

Visual development: early experience with torsionally disparate images.

Environmental influences on the developing primary visual cortex of kittens were studied by exposing dark reared kittens to prism-induced interocular rotational disparities of 32 degrees, the visual input rotated equally and oppositely in the two eyes. The present report describes preliminary results obtained from two kittens that received this altered visual exposure during 1-6 hours each day from 4 until 12 weeks of age. Subsequent single-unit recordings from the striate cortex revealed three major changes in functional cortical visual physiology. First, there was a disruption in binocularity, with many more cells being monocularly driven in the rotated conditions compared to control conditions. Second, there was an increased variance in the distribution of cells' interocular differences in preferred stimulus orientation (interocular orientation disparity, or IOD) as compared to control conditions. Third, changes were noted in orientation tuning and in the distribution of orientation preferences: cells most selective for orientation tended to be in the extreme ocular dominance groups, and monocular cells were often the most highly selective; also, both binocular and monocular cells showed a tendency for preferred orientations for both eyes to fall near the horizontal or vertical (+/- 22.5 degrees). Thus, a large optically-induced orientation disparity between the two eyes' visual fields during the critical period can modify the characteristics of striate cortical neurons, particularly binocularity and IOD. In addition, these results indicate that an inherent cortical mechanism may ensure the encoding of horizontal and vertical orientation specificities for a subclass of primary visual cortical neurons.

Plasma adenosine changes during cardiac surgery.

Changes in plasma adenosine and inosine were measured during high-dose narcotic anesthesia and surgery for coronary artery bypass grafting (CABG), and mitral or aortic valve replacement (V). Arterial and mixed venous blood samples were obtained for measurement of adenosine and inosine at eight sampling intervals ranging from preanesthesia induction to discontinuation of cardiopulmonary bypass (CPB). Arterial but not mixed venous adenosine was markedly elevated in blood samples 10 minutes after intubation, but the fourfold elevation was significant only in the CABG patient group. Mixed venous inosine and adenosine were most consistently elevated in post-CPB samples. In a separate study of arterial adenosine changes during induction, a uniform drug administration protocol was used, and again adenosine was significantly increased immediately after intubation. It is possible that adenosine and perhaps inosine may contribute to cardiovascular responses following induction-intubation and also after discontinuing CPB.

Quality of life assessment in International Breast Cancer Study Group (IBCSG) trials: practical issues and factors associated with missing data.

We report on our experience of quality of life (QL) assessment in adjuvant clinical trials of the International Breast Cancer Study Group (IBCSG), with special emphasis on cultural and logistical aspects of international organization that are unique to this group. Data are presented regarding submission rates of assessments before and after treatment failure, and timing of assessments relative to chemotherapy administration. To identify areas where rates might be improved, we investigated the association between missing data and sociodemographic and biomedical factors, treatment assignment, institution, chemotherapy compliance and toxicity in a trial of adjuvant chemoendocrine therapy for post-menopausal patients with breast cancer (IBCSG VII). The factors most highly associated with missing data were institution and chemotherapy compliance.