Clinical Experience of Axillary Radiotherapy for Node-positive Breast Cancer.

AIMS: Patients with breast cancer who have positive lymph nodes are currently recommended axillary node clearance (ANC) or regional nodal irradiation (RNI). ANC is associated with complications such as lymphoedema, brachial plexopathy and shoulder stiffness. The AMAROS Group showed RNI to be non-inferior to ANC with regards to survival and recurrence, and with a better quality of life. We conducted a large real-world population study to show our centre's experience with the use of RNI and to contribute to the current discussion around the management of node-positive breast cancer. MATERIALS AND METHODS: We evaluated patients who received RNI as opposed to ANC between 2006 and 2009 (n = 190). Patients had a range of cancer subtypes/grades. All had positive axillary disease, identified by axillary node sampling or sentinel lymph node biopsy. Systemic therapy was given as per standard protocol. Our data were compared with those of patients who had RNI (n = 681) in AMAROS. Patients were followed up retrospectively and overall survival, breast cancer-specific survival, distant metastasis-free survival, locoregional recurrence and toxicity were recorded, including lymphoedema, brachial plexopathy and shoulder stiffness. Survival analysis was performed on R via the Kaplan-Meier method. Univariate and multivariate analyses were also performed. Toxicity data were reported as percentages. Patients meeting POSNOC trial criteria (one to two positive sentinel lymph nodes, macrometastasis, receiving adjuvant chemotherapy) including if oestrogen receptor-positive (stratified POSNOC) were identified for subgroup analysis in the regression model. RESULTS: Locoregional recurrence was 3.16% versus AMAROS RNI of 1.82%. Overall survival was slightly lower in our population, but cancer-specific survival was higher than AMAROS. Lymphoedema rates were 5.8% versus AMAROS 11% in RNI and 23% in ANC arms, respectively. Brachial plexopathy was 1.6% and arm/shoulder stiffness 7.4%. AMAROS conducted a quality of life survey pertaining to arm/shoulder stiffness, mobility and function, which seemed to affect about 18% in the RNI arm. Univariate analysis revealed POSNOC status, especially if also oestrogen receptor-positive, to be a low risk group with hazard ratio 0.42 (0.20-0.83, P = 0.015). Extracapsular extension of lymph node metastasis was a poor prognostic factor; hazard ratio 4.39 (1.45-14.0, P = 0.009). CONCLUSION: We support the conclusion of the AMAROS trial with survival and recurrence following RNI being non-inferior to ANC, and with similarly favourable toxicity data. We support the continuing use of RNI as a treatment option for patients with node-positive breast cancer. Further research is required to answer the key questions regarding personalised management for node-positive breast cancer, with regards to de-escalation and also intensification for the patients exhibiting adverse tumour biology.

Enhancing clinical decision support with genomic tools in breast cancer: A Scottish perspective.

INTRODUCTION: The Oncotype DX Breast RS test has been adopted in Scotland and has been the subject of a large population-based study by a Scottish Consensus Group to assess the uptake of the recurrence score (RS), evaluate co-variates associated with the RS and to analyse the effect it may have had on clinical practice. MATERIALS & METHODS: Pan-Scotland study between August 2018-August 2021 evaluating 833 patients who had a RS test performed as part of their diagnostic pathway. Data was extracted retrospectively from electronic records and analysis conducted to describe change in chemotherapy administration (by direct comparison with conventional risk assessment tools), and univariate/multivariate analysis to assess relationship between covariates and the RS. RESULTS: Chemotherapy treatment was strongly influenced by the RS (p < 0.001). Only 30 % of patients received chemotherapy treatment in the intermediate and high risk PREDICT groups, where chemotherapy is considered. Additionally, 55.5 % of patients with a high risk PREDICT had a low RS and did not receive chemotherapy. There were 17 % of patients with a low risk PREDICT but high RS who received chemotherapy. Multivariate regression analysis showed the progesterone receptor Allred score (PR score) to be a strong independent predictor of the RS, with a negative PR score being associated with high RS (OR 4.49, p < 0.001). Increasing grade was also associated with high RS (OR 3.81, p < 0.001). Classic lobular pathology was associated with a low RS in comparison to other tumour pathology (p < 0.01). Nodal disease was associated with a lower RS (p = 0.012) on univariate analysis, with menopausal status (p = 0.43) not influencing the RS on univariate or multivariate analysis. CONCLUSIONS: Genomic assays offer the potential for risk-stratified decision making regarding the use of chemotherapy. They can help reduce unnecessary chemotherapy treatment and identify a subgroup of patients with more adverse genomic tumour biology. A recent publication by Health Improvement Scotland (HIS) has updated guidance on use of the RS test for NHS Scotland. It suggests to limit its use to the intermediate risk PREDICT group. Our study shows the impact of the RS test in the low and high risk PREDICT groups. The implementation across Scotland has resulted in a notable shift in practice, leading to a significant reduction in chemotherapy administration in the setting of high risk PREDICT scores returning low risk RS. There has also been utility for the test in the low risk PREDICT group to detect a small subgroup with a high RS. We have found the PR score to have a strong independent association with high risk RS. This finding was not evaluated by the key RS test papers, and the potential prognostic information provided by the PR score as a surrogate biomarker is an outstanding question that requires more research to validate.

Kelp detritus: Unutilized productivity or an unacknowledged trophic resource?

Kelp beds are one of the most productive marine systems and, while little of this production is directly consumed, there is growing evidence that kelp detritus is an essential food source for many detrital and suspension feeders, and forms an important component of offshore sedimentary carbon pools. However, the extent of the contribution of kelp detritus to the nutrition of coastal fauna is not well resolved. In this study, we compare the contribution of phytoplankton, kelp detritus, and waste from fish cages to the diet of a sentinel suspension feeder, the blue mussel (Mytilus edulis) using stable isotopes. We found a significant depletion in both 13C and 15N in kelp tissue with age (distance from stipe to the deteriorating distal end of the kelp frond) which may have biased dietary estimates in previous studies which have applied isotopic source values derived from fresh kelp. Our mixing models indicate that macroalgal detritus formed 59% of the diet of the mussels in Berehaven, Bantry Bay, Ireland. We support the isotopic mixing model results by modelling the relative production of phytoplankton, kelp, and salmon farm waste, and found the supply of C and N from kelp and phytoplankton far exceeded the requirements of the mussels with much less coming from the nearby fish cages. Monthly chlorophyll measurements indicated there was only sufficient phytoplankton density to support mussel growth during the spring and autumn, explaining our observation of patterns in the relative importance of utilization of kelp detritus. Where there is pressure to harvest kelp beds, this study highlights the supporting ecosystem service they provide as an important dietary source in coastal food webs and emphasises the need for appropriate management measures for this resource.

Ocean Tides for and from TOPEX/POSEIDON.

Comparisons of TOPEX/POSEIDON tidal solutions derived from the data of the first year of this altimetric mission with the best previous models and with in situ data show very substantial improvements. Typically, the gain in accuracy for the major lunar tidal component M(2) is 30 percent in root-mean-square differences with reference to a standard ground truth data set from 78 stations distributed over the world ocean. This is a major step, obtained because of the high quality of these altimetric data. The combination of these data with recent numerical models through assimilation methods is pointing toward solutions at the ultimate limits of practical accuracy.

Diurnal and Semidiurnal Variations in the Earth's Rotation Rate Induced by Oceanic Tides.

Recent space-geodetic observations have revealed daily and subdaily variations in the Earth's rotation rate. Although spectral analysis suggests that the variations are primarily of tidal origin, comparisons to previous theoretical predictions based on various ocean models have been less than satisfactory. This disagreement is partly caused by deficiencies in physical modeling. Rotation predictions based on a reliable tidal-height model, with corresponding tidal currents inferred from a modified form of Laplace's momentum equations, yield predictions of tidal variations in Universal Time that agree with very long baseline interferometer observations to 2 microseconds. This agreement resolves a major discrepancy between theory and observation and establishes the dominant role of oceanic tides for inducing variation in the Earth's rotation at these frequencies.

The effect of pasteurization on trace elements in donor breast milk.

OBJECTIVE: Premature infants often receive pasteurized donor human milk when mothers are unable to provide their own milk. This study aims to establish the effect of the pasteurization process on a range of trace elements in donor milk. STUDY DESIGN: Breast milk was collected from 16 mothers donating to the milk bank at the Royal Brisbane and Women's Hospital. Samples were divided into pre- and post-pasteurization aliquots and were Holder pasteurized. Inductively coupled plasma mass spectrometry was used to analyze the trace elements zinc (Zn), copper (Cu), selenium (Se), manganese (Mn), iodine (I), iron (Fe), molybdenum (Mo) and bromine (Br). Differences in trace elements pre- and post-pasteurization were analyzed. RESULTS: No significant differences were found between the trace elements tested pre- and post-pasteurization, except for Fe (P<0.05). The median (interquartile range, 25 to 75%; µg l(-1)) of trace elements for pre- and post- pasteurization aliquots were-Zn: 1639 (888-4508), 1743 (878-4143), Cu: 360 (258-571), 367 (253-531), Se: 12.34 (11.73-17.60), 12.62 (11.94-16.64), Mn: (1.48 (1.01-1.75), 1.49 (1.11-1.75), I (153 (94-189), 158 (93-183), Fe (211 (171-277), 194 (153-253), Mo (1.46 (0.37-2.99), 1.42 (0.29-3.73) and Br (1066 (834-1443), 989 (902-1396). CONCLUSIONS: Pasteurization had minimal effect on several trace elements in donor breast milk but high levels of inter-donor variability of trace elements were observed. The observed decrease in the iron content of pasteurized donor milk is, however, unlikely to be clinically relevant.

Effect of intermittent positive pressure ventilation on diastolic ventricular filling patterns in premature infants.

Eleven preterm newborn infants had a Doppler echocardiographic examination of their ventricular filling patterns during intermittent positive pressure ventilation. Peak velocity during early ventricular filling (VE) and during atrial systole (VA) and diastolic velocity-time integral of early (IE) and late (IA) ventricular filling caused by atrial contraction were measured. The ratios of VE/VA and IE/IA were also calculated. Diastolic peak velocities, as well as the diastolic velocity-time integral of early and late ventricular filling measured through the mitral valve were significantly higher during inspiration. The peak of the wave representing the velocity during atrial systole (A) was always higher than the peak of the wave representing the velocity of early ventricular filling (E). As a result, the ratio of these two variables (E/A) was always less than 1, showing no significant variation from inspiration to expiration. The flow patterns into the right ventricle were the opposite of those observed through the mitral valve. During inspiration, a significant decrease (p less than 0.001) in peak and time integral velocities of both the early ventricular filling and atrial systole waves was observed. Heart rate did not vary with respiration. It is concluded that during positive pressure ventilation, inspiration decreases right ventricular filling and enhances left ventricular filling. Opposite changes are recorded during expiration. Early and late phases of diastolic filling are equally affected. These changes are different from those observed during spontaneous breathing and should be taken into account in the assessment of diastolic ventricular function in preterm infants requiring assisted ventilation.

Response to furosemide in chronic renal insufficiency: rationale for limited doses.

Patients with renal insufficiency often undergo therapy with large doses of loop diuretics. We tested the hypotheses that remaining nephrons respond normally to amounts of diuretic reaching them, and that more limited doses than are commonly used are sufficient to reach effective portions of the dose-response curve. In eight patients with creatinine clearance less than 20 ml/min/1.73 m2, the amount of diuretic causing half-maximal response was identical to that in normal subjects, but the maximal response expressed as fractional excretion of sodium was increased approximately 60%. The upper plateau of the dose-response curve was attained with single intravenous doses of furosemide, 120 to 160 mg. In conclusion, remnant nephrons appear to demonstrate an exaggerated response to furosemide. Because maximal response was attained with single intravenous doses of furosemide of 120 to 160 mg, there appears to be no need to administer larger single doses in such patients.

Effect of high-dose etodolac on renal function.

Previous studies from our laboratory have demonstrated transient effects on renal function by etodolac, 200 mg b.i.d. The current study assessed the effects of a larger dose of etodolac (500 mg b.i.d.) to explore the time course of its renal effects and to determine whether the transient effect would become more prolonged with a larger dose. We studied 10 normal subjects and nine patients with renal insufficiency, examining the effects of the first 500 mg dose of etodolac as well as 4 days of b.i.d. administration. In both groups, etodolac transiently decreased fractional excretions of sodium and chloride and urinary prostaglandin E2. In patients, etodolac also transiently decreased inulin and para-aminohippuric acid clearances and urinary 6-keto-prostaglandin F1 alpha. Chronic administration caused no changes in renal function in either group. In summary, in this relatively small group of patients, high-dose etodolac caused only transient, fully reversible effects on renal function, the cumulative effect of which was negligible.

Effect of etodolac in patients with moderate renal impairment compared with normal subjects.

Twenty subjects (10 with normal renal function and 10 with moderate renal insufficiency) participated in an 8-day study to assess the effects of acute and chronic etodolac dosing on renal function. Subjects and patients were hospitalized and followed a controlled diet (150 mEq sodium, 60 to 80 mEq potassium) during the study. A 3-day drug-free period was followed by 4 days of etodolac, 200 mg b.i.d. Sodium balance and body weight remained unchanged in both groups. Modest reductions in renal function as measured by clearances of inulin and p-aminohippurate occurred acutely only in the patients with renal impairment. Chronic therapy resulted in no decrements in daily creatinine clearance. In an average effective anti-inflammatory dose, etodolac did not produce a sustained effect on renal function in either normal subjects or patients with moderate renal insufficiency.

Duplication 5q(5q22----5q33): from an intrachromosomal insertion.

We report on an infant with an as yet undescribed partial duplication 5q(q22----5q33). He had a number of the already recorded manifestations of partial trisomy 5q, namely microcephaly, growth retardation, brachydactyly, long flat philtrum, thin upper lip vermilion and downturned angles of mouth and apparently low set ears. He survived only 6 months. He inherited his duplication from a maternal intrachromosomal insertion; thus he represents a pure dup(5)(q22----5q33).

Computerized measurement of Doppler flow velocity waveforms: validation of a new system.

Manual measurement of Doppler flow velocity waveforms is time-consuming and carries unavoidable and significant intraobserver and interobserver variability. Those drawbacks limit the routine use of Doppler-derived indexes of systolic and diastolic function. This report describes a system that performs automatically all relevant measurements currently obtained from mitral, tricuspid, aortic, and pulmonary waveforms. One hundred and sixty waveforms, obtained from patients whose ages ranged from a 19-week fetus to a 21-year-old adult, were measured both manually and automatically. High correlations were found for all types of measurement: r = 0.993 for velocity measurements, r = 0.995 for time interval measurements, r = 0.881 for acceleration measurements, r = 0.867 for pressure half-time measurements, and r = 0.993 for flow integral measurements. When compared with manual measurements, automatized measurements displayed significantly lower intraobserver and interobserver variabilities for all types of measurements. Finally, the automatized measurement system cuts the time spent by a factor of more than five. Such a system of computerized measurements of Doppler flow velocity waveforms should become increasingly valuable as both a clinical and a research tool.

Trait and other sources of variance in the S-R inventory of anxiousness.

The S-R Inventory of Anxiousness has a reliability of .95 but shows only 5% of its variance due to persons (traits). This strange combination of results is explored logically and empirically. A distinction is made between the Inventory as a test and as an experimental design. Some characteristics and problems of the Inventory as an experimental design are examined. These problems suggest that it is unwarranted to include variance from situations and modes of response in the total variance against which the component of variance due to individual differences is evaluated. It is such inclusions that have yielded the result of 5% of variance due to persons. It is concluded that results from the Inventory, when generalized to other omnibus inventories of anxiety, do not have the drastic implications that have been previously claimed.

Central venous lines in neonates: a study of 2186 catheters.

OBJECTIVE: To describe the use of percutaneously inserted silicone central venous lines (CVLs) in neonates at the Royal Brisbane and Women's Hospital, Australia. DESIGN: Data for all infants admitted from 1 January 1984 until 31 December 2002 who had a CVL were examined in the neonatal database, completed from paper records and patient charts where necessary. Autopsy reports of all babies who died with a catheter in place were reviewed. RESULTS: There were 18,761 admissions, 2186 catheters in 1862 babies for a total of 35,159 days (median 14 days, range 1-99 days). The tip was in the right atrium for 1282 (58.6%) of the catheters. A total of 142 babies (7.6%) died with a CVL in place, 89 (4.8%) with the catheter tip in the right atrium. Thirty two of these 89 babies had an autopsy. No autopsies reported tension in the pericardium or milky fluid resembling intralipid. One case (0.05% of catheters) of non-lethal pericardial effusion occurred in a baby whose catheter was inappropriately left coiled in the right atrium. There were no cases of pleural effusion related to CVL use. Most (1523, 69.7%) were removed electively. Septicaemia occurred during the life of 116 catheters (5.3%). CONCLUSION: This is the largest series of percutaneously inserted silicone central venous catheters reported. It illustrates the safety of these catheters in this context. It highlights the value of keeping prospective records on such catheters. Catheters with their tips in the right atrium and not coiled did not cause pericardial effusion. Strict insertion and management principles for CVLs should be adhered to.

Poor outcome of very low birthweight babies with serious congenital heart disease.

OBJECTIVE: To evaluate incidence and mortality of congenital heart disease in very low birthweight babies. METHOD: Retrospective analysis of a 12 year period. RESULTS: Forty seven babies were diagnosed with severe congenital heart disease. The most common lesions were ventricular septal defect and coarctation of the aorta. Mortality attributed to congenital heart disease was 32%. Coarctation of the aorta, the second most common lesion, was fatal in 62% of cases. Closure of a patent ductus arteriosus with indomethacin proved to be detrimental in babies with undiagnosed coarctation, causing rapid deterioration in some. CONCLUSION: Very low birthweight neonates with severe congenital heart disease have a higher mortality than babies with higher birth weight. A contributing factor is closure of a patent ductus arteriosus if an underlying lesion has not been recognised. This could be of significance if the use of prophylactic treatment with indomethacin becomes more common.

Infant to staff ratios and risk of mortality in very low birthweight infants.

OBJECTIVES: To assess the effect that infant to staff ratios, in the first three days of life, have on the survival to hospital discharge of very low birthweight infants (<1500 g), having adjusted for initial risk and unit workload. DESIGN: In a retrospective analysis of a cohort of patients, the number of infants per nurse per shift were averaged for the first three days after admission and related to risk of mortality by logistic regression analysis. Infant to staff ratio was divided into terciles of low (1.16-1.58), medium (1.59-1.70), and high (1.71-1.97) infants per staff member. SUBJECTS: 692 very low birthweight infants admitted to the Intensive Care Nursery, Royal Women's Hospital, Brisbane over a four year period from January 1996 to December 1999. MAIN OUTCOME MEASURES: Survival to hospital discharge, adjusted for initial risk using the Clinical Risk Index for Babies (CRIB) score, and adjusted for unit workload using dependency scores. RESULTS: There were 80 deaths among the 692 babies analysed for the study period. The odds of mortality, adjusted for initial risk and infant dependency scores (unit workload), were improved by 82% when an infant/staff ratio of greater than 1.71 occurred, suggesting improved survival with the highest infant/staff ratio. The low and medium staffing levels corresponded with similar odds ratios for mortality. CONCLUSIONS: Infants exposed to higher infant to staff ratios have an improved adjusted risk of survival to hospital discharge.

Reversible acute decrease in renal function by NSAIDs in cirrhosis.

The effects of sulindac were compared with those of ibuprofen or naproxen on creatinine clearance and urinary prostanoids in patients with severe alcoholic cirrhosis. Sulindac caused acute declines in all renal parameters in four of five patients. The effect occurred with serum concentrations of the active sulfide metabolite comparable to those in patients with no hepatic impairment. The patient who was not affected had less effects on urinary PGE2 and TxB2 and no effect on 6-keto PGF1 alpha. In this patient, dosing with ibuprofen caused pronounced declines in all urinary prostanoids and a decrease in creatinine clearance. Two other patients treated with ibuprofen and one treated with naproxen also suffered decrements in all parameters. In conclusion, sulindac had suppressant effects on renal prostanoids associated with declines in creatinine clearance in these patients with cirrhosis, indicating a need for similar cautions with its use as with other NSAIDs.

Comparative susceptibility of Atlantic salmon, lake trout and rainbow trout to Myxobolus cerebralis in controlled laboratory exposures.

The susceptibility of lake trout Salvelinus namaycush, rainbow trout Oncorhynchus mykiss and Atlantic salmon Salmo salar to Myxobolus cerebralis, the causative agent of whirling disease, was compared in controlled laboratory exposures. A total of 450 (225 for each dose) fry for each species were exposed to a low (200 spores per fish) or high (2000 spores per fish) dose of the infective triactinomyxon. At 22 wk post-exposure, 60 fish from each group, as well as controls for each species, were examined for clinical signs (whirling behavior, blacktail, deformed heads and skeletal deformities), microscopic lesions, and presence of spores. Rainbow trout were highly susceptible to infection, with 100% being positive for spores and with microscopic pathological changes in both exposure groups. Rainbow trout were the only species to show whirling behavior and blacktail. Atlantic salmon were less susceptible, with only 44 and 61% being positive for spores, respectively, in the low and high dose groups, while 68 and 75%, respectively, had microscopic pathology associated with cartilage damage. Rainbow trout heads contained mean spore concentrations of 2.2 (low dose) or 4.0 (high dose) x 10(6) spores g tissue(-1). The means for positive Atlantic salmon (not including zero values) were 1.7 (low) and 7.4 (high) x 10(4) spores g tissue(-1). Lake trout showed no clinical signs of infection, were negative for spores in both groups and showed no histopathological signs of M. cerebralis infection.

Fine-needle aspiration biopsy of pituitary carcinoma with cervical lymph node metastases: a report of two cases and review of the literature.

Metastases from pituitary carcinomas are rare lesions that can mimic other tumors on fine-needle aspiration biopsies. Two patients with primary pituitary neoplasms developed cervical lymph node metastases, which were sampled and diagnosed correctly using the fine-needle aspiration biopsy technique. These two cases demonstrate the varied cytologic patterns of pituitary neoplasms, ranging from uniform bland cells to cells with striking anaplastic features. The time period between the onset of symptoms and subsequent metastases is unpredictable as well, underscoring the need for an accurate clinical history before a meaningful cytologic interpretation is made.