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Proceedings of the Waikato Clinical School Research Seminar,
Thursday 1 September 2005
Choosing the Right Radiocolloid for Breast Sentinel
Node Biopsy—A Randomised Comparison of 99mTc Antimony Trisulphide and
99mTc Rhenium Sulphur Colloid. B Allen,1 I Campbell,1 H Warren-Forward,2 J
Scarlett.1 1:Waikato Hospital, Hamilton, New Zealand; 2:University of Newcastle,
Callaghan, Australia.
Introduction: A
number of radiotracers and techniques have been proposed in lymphoscintigraphy
node mapping to assist with sentinel lymph node biopsy in breast cancer patients
with the long-term prospect of avoiding unnecessary regional node dissection.
There has been a trend towards different countries adopting a particular
radiotracer and technique based on arguments relating to particle size and
injection volumes. This study is the first randomised trial of two different
techniques used in the women.
Aim: To compare and
evaluate the tracer performance of two widely used radiocolloid preparations and
injection volumes for lymphoscintigraphy detection in patients with invasive
breast cancer.
Methods: A
prospective study was performed on 60 women diagnosed with invasive breast
cancer requiring axillary node dissection. Lymphoscintigraphy involving
peritumoral injection of 0.9ml – 1.2ml filtered 99mTechnetium Antimony
Sulphide (AS) and 2.4ml - 3.2ml unfiltered 99mTechnetium Rhenium Sulphur colloid
(SC) on separate days 15 and 90 minutes post injection was performed prior to
surgery. Sentinel lymph node biopsy was then performed using a gamma probe and
blue dye localisation. The radiotracer used first was randomly assigned.
Results: On
lymphoscintigraphy sentinel lymph nodes were identified in 98.3% of low
injection volume AS cases and demonstrated a more rapid peak lymph node uptake
compared with SC. Larger particle size and injection volume SC
lymphoscintigraphy studies demonstrated a SN in 100% of cases. A larger total
number of axillary basin lymph nodes were identified on delayed
lymphoscintigraphy using SC (179) compared with AS (137). Overall 18/60 (30.0%)
of patient SC studies demonstrated IM node radiocolloid uptake compared with
7/60 AS studies (11.6%). No patients demonstrated AS IM uptake only where as
11/60 (18.3%) of SC studies showed IM uptake only.
Conclusion: Contrary
to expectation and in spite of slower tracer uptake, the larger particle size
unfiltered SC demonstrated a greater number of nodes on lymphoscintigraphy and
appears better at identifying IM nodes than AS. This may be due to the larger
injection volume used. The clinical relevance of these findings needs further
investigation.
Management of In-Stent Restenosis in the Drug- Eluting
Stent Era. OI Omoregbe, M Menon, I Mirza, S Collins, CM Nunn, GP Devlin.
Department of Cardiology, Waikato Hospital, Hamilton, New Zealand.
Background: The
management of in stent restenosis (ISR) following percutaneous coronary
intervention is difficult. Drug–eluting stents (DES) show promise in this
clinical setting. We report on the impact of DES on the management of
symptomatic ISR at Waikato hospital New Zealand.
Methods:
Retrospective chart review of patients treated with DES for ISR from
1/7/02 until 30/6/04.Outcomes were compared with historical controls managed
percutaneously from 1/7/00 -30/6/02. The primary outcomes was further
presentation with symptomatic ISR.
Results: A total of
34 procedures in 31 patients were performed in the DES group compared to 52 in
49 patients in the controls (61% managed with balloon angioplasty, 39% further
bare metal stent insertion). The groups were well matched for predictors of
restenosis (Table 1). IIbIIIa receptor blockers were administered to 1 in 4
patients in each cohort. At follow-up (median 12.5 months DES v 16.3 months
control) one patient in each group had died. Whilst readmission with chest pain
was reduced by 30%, it was common in both groups (26%(8) DES v 37% (18) controls
(p=ns). A strong trend was however noted towards reduction in symptomatic re-ISR
with a 57% relative risk reduction (13%(5) DES v 26% (14) control (p=0.12).
Conclusion: Despite
the limitations of small sample size, DES appear to have impacted positively on
the management of ISR in clinical practice. However representation to hospital
still occurs in 1 in 4 cases with further restenosis noted in 1 in 10 patients.
Suture Versus Staple for Fixation of Mesh in Incisional
Hernia Repair—An Experimental Study in Rats. RS Dhillon, RM van Dalen;
Waikato Hospital, Hamilton, New Zealand.
The incidence of incisional hernia has been reported to be
between 11 and 20% in patients post laparotomy. While some incisional hernias
remain asymptomatic, others are associated with pain, and are at risk of hernia
incarceration and strangulation. Prosthetic mesh is now commonly used to repair
incisional hernias and has been shown to be superior to suture repair techniques
in a large prospective multi-centre trial. Despite this, the recurrence rate of
primary mesh repair of incisional hernias has been reported to be as high as
38%.
Mesh migration as a result of inadequate fixation is a
commonly cited reason for failure of mesh repair of incisional hernias. The
fixation of mesh using either sutures or surgical staples has been studied in
mesh repair of inguinal hernias, however the difference in strength of mesh
fixation using these two methods has not been established for incisional hernia
repair. This experimental study in euthanased rats aims to compare the fixation
strength of mesh using sutures and surgical staples.
A midline laparotomy incision was made in twenty euthanased
adult male Sprague-Dawley rats. Mesh was placed over the incision with at least
1.5 cm overlap from each incision edge. The mesh was anchored in place at a
fixed distance from each incision edge using either four 3.5mm Ethicon staples
or four 3/0 interrupted Prolene sutures in each group. A modified 3.5mm Hasson
port device with a surgical glove attached to the end was introduced into the
abdomen from a lateral abdominal wall puncture. Fluid was infused into the
device for measuring the pressure required to disrupt the mesh. The Hasson port
was attached to an IVAC syringe pump for infusion and a VT Gas Flow Analyzer via
a three way connector, which was attached to a computer interface to measure and
graph the pressure required for mesh disruption. The time to place and secure
mesh in the suture and staple groups were also recorded.
There was no statistically significant difference (p=0.83)
in the pressure required to disrupt the mesh between the two groups, 101±12
mmHg in the suture group compared with 102±14 mmHg in the staple group.
Staple fixation was 9.7 times faster compared with suture fixation, 291±42
sec for suture versus 30±8 sec for staples (p<0.001). In the suture
group, 17/20 sutures disrupted laterally and 16/20 in the staple group. The
study had a calculated power of 94% assuming 15 mmHg pressure difference at a 5%
significance level. This study concludes that the early strength of fixation of
mesh for incisional is equal using both sutures and staples however staple
fixation is much faster. The reason for early failure of mesh fixation may
relate to other factors such as inadequate mesh size, inadequate hernia
reduction, patient comorbid factors as well as possible suture and staple
“cut out” during movement. Early mesh migration due to inadequate
fixation of mesh using either method is probably not the major reason for early
failure.
Systolic Murmurs in Adults: Beware the Guidelines! The
Waikato Asymptomatic Murmur Study. R A Fisher, L Rademaker, G P Devlin.
Departments of Cardiology and GP Liaison, Waikato Hospital, Hamilton, New
Zealand.
Introduction: In New
Zealand, Ministry of Health guidelines, based on established ACC/AHA criteria
exist for assessment of asymptomatic systolic murmurs by primary care
physicians. They recommend that adults with normal chest X-ray (CXR) and
electrocardiogram (ECG) can be reassured without further need for investigation.
A large number of these patients are, however, referred for specialist
opinion.
The Waikato Asymptomatic Murmur Study assessed the
applicability of these guidelines prospectively to patients with systolic
murmurs referred for cardiology assessment.
Methods:
Asymptomatic adults with a systolic murmur present for longer than one month
with normal CXR and ECG were eligible for inclusion. Patients underwent
echocardiography (echo), with cardiologist review of the study. Studies were
categorized as normal, abnormal but not requiring cardiologist clinical review
or abnormal requiring cardiologist clinical review.
Results: A total of
253 consecutive patients were referred for a first specialist assessment of an
asymptomatic systolic murmur to Waikato hospital from 01-01-01 to 31-10-03.
78/253 (31%) patients fulfilled entry criteria with 77 undergoing echo. The mean
patient age was 59 years, with 64% female
. 48% (37) had a normal echo, 35% (27) had
an abnormal echo but did not require cardiologist review. Findings in this group
were predominately mild valve lesions or left ventricular hypertrophy. However,
one in six patients (17%,13/71) had findings felt to require cardiologist
review, mostly moderate-severe valve lesions. These results were independent of
advanced age, gender or ethnicity.
Conclusion: The
Waikato Asymptomatic Murmur study suggests that current guidelines for murmur
assessment may underestimate the potential for valve disease. In particular
normal CXR and ECG cannot confidently exclude important valve disease.
Conversely, 83% referred with asymptomatic murmurs could be
“triaged” with echo and avoid cardiologist review; an important
observation for countries with limited public access to specialist opinion
similar to New Zealand.
Honey Stimulates Proliferation of Fibroblasts in an
In Vitro Model. NR Harcourt, P C Molan.
Honey Research Unit, University of Waikato, Hamilton, New Zealand.
Clinical trials have shown that honey is an effective
broad-spectrum antibacterial agent that has no adverse effects on wound tissues,
and also provides anti-inflammatory activity which minimizes hypertrophic
scarring. Honey may offer significant advantages to other available treatments
for the management of scarring in wound healing. This is an analysis of a
laboratory study conducted to examine the effectiveness of honey on stimulating
proliferation of a fibroblast culture in
vitro culture. Fibroblasts from the Swiss 3T3-L1 cell-line were incubated
with diluted honey (0.25%) from two different floral sources and an artificial
honey solution for 48 h. The cell density of fibroblast cultures was then
determined by the 3 (4,5-dimethylthiazolyl-2)-2,5-diphenyl tetrazolium bromide
(MTT) assay. It showed that exposure of cultures to natural honeys (0.25%)
increased proliferation levels above those obtained for cultures exposed to
culture medium alone. Artificial honey at the same concentration had no effect
on proliferation, indicating that sugars alone in honey could not account for
stimulation. Manuka honey only had a stimulatory effect on fibroblast
proliferation in a 0.25% v/v solution, and not outside of this optimal
concentration.
The Profile of Diabetic Patients in a Rural Town in New
Zealand and the Extent of Aspirin Use. G Joshy, M Devers, D Simmons, Waikato
Clinical School, University of Auckland, Hamilton, New Zealand.
Background: The risk
of a cardiovascular event in those with diabetes has been shown to be as high as
those post myocardial infarction. Aspirin is of major benefit in the prevention
of cardiovascular disease (CVD) in those with diabetes. There is disagreement
over the use of aspirin in diabetes to those with a 15% risk calculated on the
Framingham data, to those who recommend use in all of those with diabetes aged
over 40 years. The aim of this study was to assess aspirin use among those with
diabetes.
Methods: The Waikato
DHB has introduced a new, integrated approach for diabetes services management
in one rural area in New Zealand. Data has been linked from multiple data
sources including the “Get Checked” database and the Waikato
Regional Diabetes Service database. As part of this program, data on aspirin use
has been collected through a mail survey starting from March 2004.
Results: All 365
people with diabetes were invited to participate. Non response 132 (36%), no
consent 17 (5%), returned mail 19 (5%). Among 180 (49%) people with diabetes who
participated in the survey to date, 5 were aged below 40, mean age 64.8 years
(12.3), 45.6% male. European 66%, Maori 31%. 107 patients had year of diagnosis
in their medical records. Age at diagnosis mean(sd) of 56.1 (12.1), duration of
diabetes 9.1 (7.1). Europeans were diagnosed about 8 years later than Maori.
Metabolic and other clinical data is still being collected. Most patients (91%)
were registered with the Waikato Regional Diabetes Service database. Only 56%
had annual review under Get Checked program (64% Europeans and 50% Maori). Among
respondents, 46.9% of patients aged above 40 use aspirin including 49.5%
Europeans and 41.6% Maori. Only 3% use 300mg and 30.9% use 100mg or lesser.
Among the 166 patients who had the clinical data to calculate cardiovascular
risk (CVR), 45 (27.1%) had >15% CVR. Only 19 (42.2%) of the high risk
patients were taking aspirin. But 59 (48.7%) of the low-risk patients were
taking aspirin. There was no significant association between aspirin intake and
CVR. (Chi-square test, p=0.4531).
Conclusion: We
conclude that the aspirin usage in diabetes is not in relation to CVR.
Diagnosis of Pulmonary Embolism: CTPA as a Stand-alone
Investigation.
K McAnulty,1 R Heath,1 D Blair,1 K Gilbert,1 G Coltman,1 F Tawse,1 K Cox,1 N Karalus,2 R Subramaniam.1 1:Department of Radiology, Waikato Hospital, Hamilton, New Zealand; 2:Respiratory Department, Waikato Hospital, Hamilton, New Zealand. Objectives: To test
the clinical outcome accuracy of a negative CTPA as a stand alone investigation
to exclude Pulmonary Embolism.
Materials and
Methods: 535 consecutive patients (Emergency Department and Hospital in
patients) who had CTPA (Single Slice, GE Helical Scan) were recruited
prospectively from March 2003 to
September 2004. 48 patients were excluded from the study for incomplete data
(12) or had a lower limb ultrasound examination subsequent to a negative CTPA
(36). Hence the study population was 487 patients. Each CTPA examination was
read by two consultant radiologists independently. A 3 month post CTPA follow up
was done in all patients by telephone interview, interview with General
Practitioners and hospital records to establish the clinical outcome accuracy of
a negative CTPA.
Results: There were
383 (78.6%) negative and 104 (21.4%) positive CTPA examinations. Among those
with a negative CTPA, 2 patients had DVT and 343 patients had no evidence of an
episode of venous thromboembolism or pulmonary embolism. At 3 month follow up,
38 patients died within the three month follow up period and one patient’s
death was attributed to suspected PE. All patients with positive CTPA were
treated with anticoagulation.
The negative predictive value is 99.1% (95% CI 97.5% -
99.7%)
Conclusion: A single
slice helical negative CTPA examination excludes clinically significant PE. No
further additional imaging examination such as lower limb ultrasound is
unnecessary.
Mechano-Growth Factor (MGF) Stimulates Expression and
Secretion of Brain Natriuretic Peptide (BNP) and Improves Ejection Fraction
after Myocardial Infarct. V Carpenter, GP Devlin,2 KG Matthews,1 J Jensen,2 SP
Stuart,1 PH Goldspink,4 SY Yang,3 JV Conaglen,2 JJ Bass,1 G Goldspink,3 CD
McMahon.1 1:AgResearch Ltd, Hamilton, New Zealand; 2:Waikato Clinical School,
University of Auckland, Hamilton, New Zealand; 3:Royal Free and University
College Medical School, London, UK; 4:University of Illinois (Chicago),
USA.
Concentrations of BNP are acutely increased after myocardial
infarction (MI) and are believed to protect the infarcted heart. The stimulus
for secretion of BNP is not known, but expression is induced by mechanical
stretch. Interestingly, expression of MGF, a splice-variant of IGF-I, is also
induced by mechanical stretch. We have previously shown that MGF improves the
ventricular ejection fraction after MI. Therefore, we hypothesise that MGF
induces expression and secretion of BNP, which, in turn, improves cardiac
performance.
In experiment 1, MI was induced by occluding the left
circumflex coronary artery of sheep. Ewes received one of four protein
treatments (n=6 per group) delivered into the circumflex artery: vehicle
(saline), 200 nM mature IGF-I, 200 nM MGF E domain, or 200 nM of full MGF
(domains B, C, A and D of mature IGF-I plus the E domain of MGF). Left
ventricular function was assessed with echocardiography before MI (baseline),
and at days 1, 2 and 6 post-MI. Blood samples were collected at days 0, 1, 2,
and 6 for assay of BNP. In experiment 2, H9C2 rat cardiomyocytes were treated
with 100 and 300 ng of MGF for 30, 60, 120 and 180 min. After treatment, mRNA
was extracted and reverse transcribed. RT-PCR was used to semi-quantify
expression of BNP.
Cardiac ejection fraction was reduced by 40% (P<0.001) at
d 1 in all sheep, but was increased by 4% at d 6 only in sheep treated with MGF
peptide (E or full peptide; at least P<0.05). Concentrations of BNP were
increased in ewes treated with the E domain of MGF (P<0.05). Furthermore, BNP
mRNA was increased after 30 min compared with controls. We speculate that the E
domain of MGF, but not mature IGF-I, stimulates expression and secretion of BNP,
which, in turn, acts to improve the ejection fraction after MI.
Procalcitonin—A Valuable Diagnostic Marker in
Meningococcal Disease.
GD Mills,1 HM Lala,1 MR Oehley,1 AB Craig,1 K Barratt,1
D Hood,1 CN Thornley,2 A Nesdale,3 NE Manikkam,1 P Reeve.1 1:Waikato,
2:Auckland, 3:Hutt Valley District Health Boards, New Zealand.
Background: Some
patients with meningococcal disease (MCD) seeking medical attention create a
diagnostic dilemma for clinicians due to the non-specific nature of their
presentation. We have assessed the diagnostic accuracy of procalcitonin within
the emergency department (ED), to clarify its role in the evaluation of
MCD.
Methods: Two
overlapping cohorts have been studied. Procalcitonin levels were measured in a
cohort of patients with confirmed MCD diagnosed within the current New Zealand
serogroup B epidemic, to assess the sensitivity of procalcitonin. In the second
cohort, a large consecutively recruited ED population of febrile patients,
enabled specificity and likelihood ratios of procalcitonin to be
evaluated.
Results: There were
193 patients in the MCD cohort (92 children, 101 adults). The procalcitonin
geometric mean was 10.9ng/ml with higher childhood than adult values (22.9ng/ml
vs 5.5ng/mL, p=0.01). The overall sensitivity of procalcitonin, using a 2.0ng/ml
cut-off in children and 0.5ng/ml for adults, was 94% (95% CI 89-97%). Despite
the higher paediatric cut-off, a trend towards greater procalcitonin sensitivity
existed in children (96% vs 92%, p=0.30). Procalcitonin was correlated with
whole blood meningococcal load (r=0.50) and Glasgow Meningococcal Septicaemia
Prognostic Score (r=0.40). Within the cohort of
1521 febrile ED
presentations, 28 patients were confirmed to have MCD. We showed a procalcitonin
specificity in MCD of 85% (95% CI 83-87%), positive and negative likelihood
ratios of 6.1 and 0.08, and corroborated the sensitivity of procalcitonin (93%;
95% CI 76-99%).
Conclusions:
Procalcitonin can
provide an important tool in the diagnosis of patients with MCD who
present with non-specific febrile illnesses. The diagnostic accuracy surpasses
current early laboratory markers and can be used to guide patient management
decisions.
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