Clinical aspects of gestational trophoblastic disease: A review based partly on 25-year experience of a statewide registry

Background: Gestational trophoblastic disease is a fascinating group of pregnancy disorders characterised by abnormal proliferation of trophoblast, ranging from benign to malignant. Because the disease is uncommon, there is a need to formulate management with the assistance of collective information. Methodology: A review of available information from English written literature was undertaken especially data reported by registries around the world (Charing Cross Hospital in England, the North-western University and the New England area in the USA as well as our own experience in Queensland, Australia). Where possible, collated data from relevant studies were analysed to answer some of the questions posed in clinical practice, with reference to metastatic disease to liver and brain, twinning of molar gestation and coexisting fetus, and placental-site tumour. Results: We found that molar gestation can be classified according to its clinical presentation which influences the time taken to reach human chorionic gonadotropin (HCG) 'negativity' and the risk of persisting disease. Categorisation of risk is the basis for choice of chemotherapy to achieve good outcomes. Metastases to liver and brain remain problems in management; the development of 'new' metastases during chemotherapy is a very poor prognostic factor. In the variant of twinning with molar gestation and coexisting fetus, it is important to elucidate the fetal karyotype in planning management: a 69XXX fetus is not salvageable but a normal 46XX or 46XY fetus faces the prospect of early preterm delivery. The placental-site tumour is very rare; localised disease is curable by surgery; chemotherapy is less effective in disseminated disease. From collated worldwide data, the recurrence rate after one mole is 1.3% and after two or more is 20%. Reproductive outcome in subsequent pregnancies, even after multidrug chemotherapy, is not different from the general population. Because of the increased risk long-term of second tumours after multidrug chemotherapy a closer surveillance of these patients is necessary Conclusion: In general, the disease in its persisting or malignant form is 'a cancer model par excellence' because of an identifiable precursor condition, a reliable HCG marker, and sensitivity of the disease to cytotoxic drugs. With current management, retention of fertility is possible and normal reproductive outcome assured.

Laparoscopic Swenson procedure - An optimal approach for both primary and secondary pull-through for Hirschsprung's disease

Background/Purpose: Several pull-through procedures are available for the surgical management of Hirschsprung's disease (HD) in children. The authors have adopted a laparoscopic approach since 1995, including laparoscopic Swenson procedure (LSw), both for one-stage primary and 2-stage secondary procedures. The aim of this study was to examine the role of LSw in children with HD in both primary and secondary procedures. Methods: From January 1995 to December 2001, 42 children with biopsy-proven HD underwent laparoscopic pull-through procedure for HD. This group included 29 children who underwent LSw, a detailed analysis of which forms the basis of this report. Results: Sixteen children underwent a single-stage neonatal LSw; the median weight of this group at the time of surgery was 3.2 kg and the median age was 5 days. Secondary LSw was performed in the remaining 13 children, which included 3 children with total colonic HD who underwent laparoscopic total colectomy and LSw. The median operating time was 105 minutes (range, 66 to 175 minutes). The median time to commence full diet was 48 hours (range, 24 to 86 hours), and median time to return to normal play and activity was 72 hours (range, 48 hours to 5 days). There was no difference in operating time between primary and secondary pull-through procedures. There were no intraoperative complications, and no patient required open conversion. Postoperative ileus was noted in 3 children and enterocolitis in 2. The median hospital stay was 4 days (range, 2 to 6 days). Follow-up was between 6 months to 7 years with a median follow-up of 2.2 years. At follow-up, 2 children required laparoscopic antegrade continence enema procedure. A satisfactory continence was noted in 15 of the 19 children who were older than 3 years at the time of last follow-up. Conclusions: LSw seems to be a suitable procedure for laparoscopic management of HD in children. LSw is safe and effective, both for primary and secondary type of pull-through procedures, with good short-term results.

Introduced mammals in Australian rangelands: Future threats and the role of monitoring programmes in management strategies

In the present paper, we have provided an initial assessment of the current and future threats to biodiversity posed by introduced mammals (predators and herbivores) inhabiting the Australian rangelands, exploring trends in populations and options for management. Notably, rabbits have declined in recent years in the wake of rabbit haemorrhagic disease, populations of feral camels have increased dramatically and foxes appear to have moved northwards, thereby threatening native fauna within an expanded range. Following on, we developed a framework for monitoring the impacts of introduced mammals in the Australian rangelands. In doing so, we considered the key issues that needed to be considered in designing a monitoring programme for this purpose and critically evaluated the role of monitoring in pest animal management. Finally we have provided a brief inventory of current best-practice methods of estimating the abundance of introduced mammal populations in the Australian rangelands with some comments on new approaches and their potential applications.

Achieving better in-hospital and after-hospital care of patients with acute cardiac disease

In patients hospitalised with acute coronary syndromes (ACS) and congestive heart failure (CHF), evidence suggests opportunities for improving in-hospital and after hospital care, patient self-care, and hospital-community integration. A multidisciplinary quality improvement program was designed and instigated in Brisbane in October 2000 involving 250 clinicians at three teaching hospitals, 1080 general practitioners (GPs) from five Divisions of General Practice, 1594 patients with ACS and 904 patients with CHF. Quality improvement interventions were implemented over 17 months after a 6-month baseline period and included: clinical decision support (clinical practice guidelines, reminders, checklists, clinical pathways); educational interventions (seminars, academic detailing); regular performance feedback; patient self-management strategies; and hospital-community integration (discharge referral summaries; community pharmacist liaison; patient prompts to attend GPs). Using a before-after study design to assess program impact, significantly more program patients compared with historical controls received: ACS: Angiotensin-converting enzyme (ACE) inhibitors and lipid-lowering agents at discharge, aspirin and beta-blockers at 3 months after discharge, inpatient cardiac counselling, and referral to outpatient cardiac rehabilitation. CHF. Assessment for reversible precipitants, use of prophylaxis for deep-venous thrombosis, beta-blockers at discharge, ACE inhibitors at 6 months after discharge, imaging of left ventricular function, and optimal management of blood pressure levels. Risk-adjusted mortality rates at 6 and 12 months decreased, respectively, from 9.8% to 7.4% (P=0.06) and from 13.4% to 10.1% (P= 0.06) for patients with ACS and from 22.8% to 15.2% (P < 0.001) and from 32.8% to 22.4% (P= 0.005) for patients with CHF. Quality improvement programs that feature multifaceted interventions across the continuum of care can change clinical culture, optimise care and improve clinical outcomes.

C-reactive protein, cardiovascular risk, and renal disease in a remote Australian Aboriginal community

Rates of cardiovascular and renal disease in Australian Aboriginal communities are high, but we do not know the contribution of inflammation to these diseases in this setting. In the present study, we sought to examine the distribution of C-reactive protein (CRP) and other markers of inflammation and their relationships with cardiovascular risk markers and renal disease in a remote Australian Aboriginal community. The study included 237 adults (58% of the adult population) in a remote Aboriginal community in the Northern Territory of Australia. Main outcome measures were CRP, fibrinogen and lgG concentrations, blood pressure (BP), presence of diabetes, lipids, albuminuria, seropositivity to three common micro-organisms, as well as carotid intima-media thickness (IMT). Serum concentrations of CRP [7 (5-13) mg/l; median (inter-quartile range)] were markedly increased and were significantly correlated with fibrinogen and lgG concentrations and inversely correlated with serum albumin concentration. Higher CRP concentrations were associated with lgG seropositivity to Helicobacter pylori and Chlamydia pneumoniae and higher lgG titre for cytomegalovirus. Higher CRP concentrations were associated with the following: the 45-54-year age group, female subjects, the presence of skin sores, higher body mass index, waist circumference, BP, glycated haemoglobin and greater albuminuria. CRP concentrations increased with the number of cardiovascular risk factors, carotid IMT and albuminuria independently of other risk factors. These CRP concentrations were markedly higher than described in other community settings and are probably related, in a large part, to chronic and repeated infections. Their association with markers of cardiovascular risk and renal disease are compatible with the high rates of cardiovascular and renal disease in this community, and provide more evidence of strong links between these conditions, through a shared background of infection/inflammation. This suggests that a strong focus on prevention and management of infections will be important in reducing these conditions, in addition to interventions directed at more traditional risk factors.

Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life

Background and aim: Obesity is a risk factor for progression of fibrosis in chronic liver diseases such as non-alcoholic fatty liver disease and hepatitis C. The aim of this study was to investigate the longer term effect of weight loss on liver biochemistry, serum insulin levels, and quality of life in overweight patients with liver disease and the effect of subsequent weight maintenance or regain. Patients: Thirty one patients completed a 15 month diet and exercise intervention. Results: On completion of the intervention, 21 patients (68%) had achieved and maintained weight loss with a mean reduction of 9.4 (4.0)% body weight. Improvements in serum alanine aminotransferase (ALT) levels were correlated with the amount of weight loss (r=0.35, p=0.04). In patients who maintained weight loss, mean ALT levels at 15 months remained significantly lower than values at enrolment (p=0.004), while in regainers (n=10), mean ALT levels at 15 months were no different to values at enrolment (p=0.79). Improvements in fasting serum insulin levels were also correlated with weight loss (r=0.46, p=0.04), and subsequent weight maintenance sustained this improvement. Quality of life was significantly improved after weight loss. Weight maintainers sustained recommended levels of physical activity and had higher fasting insulin levels (p=0.03) at enrolment than weight regainers. Conclusion: In summary, these findings demonstrate that maintenance of weight loss and exercise in overweight patients with liver disease results in a sustained improvement in liver enzymes, serum insulin levels, and quality of life. Treatment of overweight patients should form an important component of the management of those with chronic liver disease.

Nonalcoholic fatty liver disease: is all the fat bad?

Nonalcoholic fatty liver disease is now a major cause of liver disease in developed countries, largely as a result of an epidemic of obesity, diabetes and sedentary lifestyles. This has resulted in raised clinical awareness and diagnostic refinement. The entity encompasses several histologic patterns from benign steatosis to nonalcoholic steatohepatitis, the latter having a significant risk of progressive fibrosis and the development of cirrhosis. Labor-atory tests and imaging are not able to distinguish steatosis from steatohepatitis, which requires liver biopsy. However following an assessment of several risk factors, patients can be stratified for the potential risk of fibrosis, allowing the rational use of liver biopsy. This review will describe the various patterns of nonalcoholic fatty liver disease and relate this to disease pathogenesis and progression. Strategies for management, including experimental interventions, will be discussed.

The management of extra-abdominal desmoid tumours

We performed a retrospective analysis of 35 cases of desmoid tumours (aggressive fibromatoses) that underwent treatment at our institutions between 1987 and 2002. The purpose was to evaluate the rate of local recurrence of desmoid tumours treated with surgical excision, to assess the impact of surgical margins on local recurrence and to define the role of radiotherapy in the treatment. Nine patients experienced a recurrence at an average of 16 months after initial treatment. Seven of the 15 patients with a less-than-wide margin had a local recurrence. Comparatively, only two of the 20 patients with a wide margin had a local recurrence. Thirty-three of the 35 patients were disease free at the last follow-up. We recommend wide excision with clear margins whenever possible. Marginal resections are appropriate when wide excision would severely compromise the function of the limb. Surgical resections and selective supplementation of adjuvant radiotherapy give excellent control rates.

Reflecting on ethical and legal issues in wildlife disease

Disease in wildlife raises a number of issues that have not been widely considered in the bioethical literature. However, wildlife disease has major implications for human welfare. The majority of emerging human infectious diseases are zoonotic: that is, they occur in humans by cross-species transmission from animal hosts. Managing these diseases often involves balancing concerns with human health against animal welfare and conservation concerns. Many infectious diseases of domestic animals are shared with wild animals, although it is often unclear whether the infection spills over from wild animals to domestic animals or vice versa. Culling is the standard means of managing such diseases, bringing economic considerations, animal welfare and conservation into conflict. Infectious diseases are also major threatening processes in conservation biology and their appropriate management by culling, vaccination or treatment raises substantial animal ethics issues. One particular issue of great significance in Australia is an ongoing research program to develop genetically modified pathogens to control vertebrate pests including rabbits, foxes and house mice. Release of any self-replicating GMO vertebrate pathogen gives rise to a whole series of ethical questions. We briefly review current Australian legal responses to these problems. Finally, we present two unresolved problems of general importance that are exemplified by wildlife disease. First, to what extent can or should 'bioethics' be broadened beyond direct concerns with human welfare to animal welfare and environmental welfare? Second, how should the irreducible uncertainty of ecological systems be accounted for in ethical decision making?

Exposing extinction risk analysis to pathogens: Is disease just another form of density dependence?

In the United States and several other countries., the development of population viability analyses (PVA) is a legal requirement of any species survival plan developed for threatened and endangered species. Despite the importance of pathogens in natural populations, little attention has been given to host-pathogen dynamics in PVA. To study the effect of infectious pathogens on extinction risk estimates generated from PVA, we review and synthesize the relevance of host-pathogen dynamics in analyses of extinction risk. We then develop a stochastic, density-dependent host-parasite model to investigate the effects of disease on the persistence of endangered populations. We show that this model converges on a Ricker model of density dependence under a suite of limiting assumptions, including. a high probability that epidemics will arrive and occur. Using this modeling framework, we then quantify: (1) dynamic differences between time series generated by disease and Ricker processes with the same parameters; (2) observed probabilities of quasi-extinction for populations exposed to disease or self-limitation; and (3) bias in probabilities of quasi-extinction estimated by density-independent PVAs when populations experience either form of density dependence. Our results suggest two generalities about the relationships among disease, PVA, and the management of endangered species. First, disease more strongly increases variability in host abundance and, thus, the probability of quasi-extinction, than does self-limitation. This result stems from the fact that the effects and the probability of occurrence of disease are both density dependent. Second, estimates of quasi-extinction are more often overly optimistic for populations experiencing disease than for those subject to self-limitation. Thus, although the results of density-independent PVAs may be relatively robust to some particular assumptions about density dependence, they are less robust when endangered populations are known to be susceptible to disease. If potential management actions involve manipulating pathogens, then it may be useful to. model disease explicitly.

Management of recurrent epithelial ovarian carcinoma

Despite the standardisation of surgical techniques and significant progress in chemotherapeutics over the last 30 years, advanced epithelial ovarian cancer remains the most lethal gynaecological malignancy in the western world. Although the majority of women achieve a remission following primary therapy, most patients with advanced stage disease will eventually relapse and become candidates for 'salvage' therapy. The chances of a further remission depend on factors such as the 'treatment-free interval', and there are now a large number of chemotherapy agents with activity in ovarian cancer available to the oncologist. Recent randomised studies have reported on survival benefits for chemotherapy in recurrent disease, and therefore careful and appropriate selection of treatments has assumed a greater importance. This article reviews the most current data, and discusses the factors involved in making individualised treatment decisions.

Potential economic implications for regional tourism of a Foot and Mouth Disease outbreak in North Queensland

International and domestic tourism are sensitive to disastrous events which make areas inaccessible to visitors, less attractive or more dangerous. One form of tourism disaster is the outbreak of an exotic disease, of which Foot and Mouth Disease (FMD) is a prime case. It is now well documented that the 2001 FMD outbreak in the UK had a greater impact on tourism than on agriculture. It has been estimated than an FMD outbreak in Australia would impose a cost of about $13 million. The impact on tourism would be highly dependent on the extent and duration of an FMD outbreak, as well as on any management and containment restrictions imposed by the authorities in their attempt to control and eventually eradicate the disease. Public perception and thus the provision of accurate information and the way in which the media report disasters will also play an important role in determining the impact on the tourism industry. The economy of Tropical North Queensland relies heavily on international visitors, and an FMD outbreak in the region would impose a large cost to the regional economy, conservatively estimated here to be of the order of $200 million per year.