Incidence, prevalence, and survival trends for neuroendocrine neoplasms in Victoria, Australia, from 1982 to 2019: Based on site, grade, and region.

AIMS: Neuroendorcine neoplasms (NENs) are rare tumors characterised by variable biology and delayed diagnosis. Several population studies have reported a marked increased incidence over time. The objectives of this analysis were to describe within Victoria (the second largest Australian state, 6.4 Million) the trends for NENs incidence/survival over nearly 38 years (1982-2019), and regional differences in survival. METHODS: All NEN cases were identified from the Victorian Cancer Registry over four time periods: 1982-1989, 1990-1999, 2000-2009, and 2010-2019. Data collected included primary tumor site, histological grade, gender, overall survival (OS), and place of residence. Incidence data were analyzed with the generation of annual standardized rates (ASR). OS was assessed for the entire cohort and between geographical regions. RESULTS: The overall NEN population (1982-2019) included 8,106 patients: over 60% grade 1/2 NENs, especially small bowel and colorectal. The number of new diagnoses increased over three-fold over time for the overall cohort and by tumoral categories. The ASR increased similarly, especially pancreatic NENs (4.3-fold) and differed between genders. The 5-year OS rates and median OS increased over time for the overall cohort: from 52% to 67% (p < 0.001). OS was greater for NEN patients residing in major cities relative to regional/remote areas (p = 0.01). CONCLUSION: This population-wide analysis with over 38 years of data has confirmed the international trends of the increased incidence, prevalence, and OS of NEN patients regardless of primary site or histological grade. The analysis also observed a difference in survival outcome in rural/remote versus urban areas.

The rate of abdominoperineal resections for rectal cancer in the state of Victoria, Australia: a population-based study.

PURPOSE: The aim of this study was to document a population-based rate of abdominoperineal resections for adenocarcinoma of the rectum in the state of Victoria, Australia. It also determined whether surgeon caseload or specialist colorectal training affects this rate. METHODS: All resections for adenocarcinoma of the rectum (International Classification of Diseases for Oncology, 3rd edition C20) that were performed in Victoria in the year 2005 were included. Procedures for rectosigmoid or colon cancer were excluded. The sample was taken from the Victorian Cancer Registry. The rate of abdominoperineal resections was calculated by dividing the total number of abdominoperineal resections by the total number of procedures for rectal cancer. Mixed-effects logistic regression was used to estimate the odds ratio for surgeon caseload and specialist colorectal training. RESULTS: There were 582 resections available for analysis. Patients were mostly males (66%) and over 60 years of age (67.7%). The overall rate of abdominoperineal resection was 23.4%. The rate of abdominoperineal resections for low rectal cancers was lower (42.8%) among surgeons who had specialist colorectal training compared with those who did not (60.6%) (OR = 2.06; 95% CI, 1.24-3.42). CONCLUSION: The rate of abdominoperineal resection in Victoria for 2005 was 23.4%. Patients with low rectal cancer operated on by surgeons who had had specialist colorectal training were significantly less likely to undergo an abdominoperineal resection compared with patients undergoing an operation by surgeons who did not have specialist colorectal training.

Radiotherapy management of patients diagnosed with glioma in Victoria (1998-2000): a retrospective cohort study.

This study aimed to describe the radiotherapy (RT) management and subsequent outcome in a cohort of patients with newly diagnosed glioma. Treatment details were obtained via a questionnaire completed by neurosurgeons, radiation and medical oncologists who treated patients diagnosed with glioma in Victoria during 1998-2000. Patients were identified by using the population-based Victorian Cancer Registry. Over the study period, data on 828 patients were obtained, of whom 612 (74%) were referred for consideration of RT. Radiotherapy was given to 496 patients as part of their initial treatment and to an additional 10 patients at the time of tumour recurrence or progression. The median age was 72 (16-85) years. Median overall survival (OS) was 9.2 (standard error (SE) 0.6) months for the entire group. Median OS was 29.1 (SE 8.0) and 7.4 (SE 0.4) months for all patients with histological confirmation of World Health Organization Grades III (anaplastic astrocytoma) and IV (glioblastoma multiforme) histology, respectively. A total of 47 different RT dose fractionation schedules were identified. This is the largest survey detailing management of glioma with RT, published to date. A marked variation in dose fractionation schemes was evident. While current best practice involves the use of chemotherapy in conjunction with RT for glioblastoma multiforme, advances in patient care may be undermined by this variation in the use of RT. Clinical trials relevant to an ageing population and evidence-based national clinical guidelines are required to define best practice.

The management of testicular cancer in Victoria, 1988-1993. Urology Study Committee of the Victorian Co-operative Oncology Group.

OBJECTIVES: To evaluate the patterns of care and management of testicular cancer in Victoria. DESIGN AND SETTING: Retrospective analysis of all cases of testicular cancer in Victoria from 1988 to 1993 identified through the Victorian Cancer Registry. MAIN OUTCOME MEASURES: Description of patient characteristics, staging investigations, initial management, and outcome. RESULTS: 667 eligible cases of testicular cancer were identified and questionnaires were returned for 633 of these patients (94.9% response rate). There were 357 (56.4%) patients with pure seminoma; 271 (42.8%) with non-seminomatous germ cell tumours, 3 (0.5%) with stromal tumours, and 2 (0.3%) with other tumours. The median age was 32 years (range, 0-80 years). Preoperative marker levels were not available for 8% of patients, and initial staging was considered inadequate in 6%. Surveillance programs used for patients with Stage I disease were considered inadequate in most. Relative survival at five years was 99% for patients with seminoma and 91% for non-seminoma. CONCLUSIONS: There was considerable variation in the investigation, treatment, and follow-up of these patients, which is likely to have resulted in unnecessary morbidity. Clinical practice guidelines should be developed and implemented to promote optimal management.

Prostate cancer in Victoria in 1993: patterns of reported management.

OBJECTIVE: To describe the management of newly diagnosed prostate cancer in 1993 during the early prostate specific antigen (PSA) era. DESIGN: Survey of medical practitioners involved in the management of a total sample of incident prostate cancer cases selected from a population-based cancer registry. The survey was conducted in 1996, and the sample was followed up until 1998, to obtain five-year survival data on all patients. SETTING: The State of Victoria, including both public and private health sectors. PATIENTS: All men who were newly diagnosed with prostate cancer in the six months January-June 1993. MAIN OUTCOME MEASURES: Reported management by method of diagnosis; staging investigations; and treatment by observation, hormonal therapy, radical radiotherapy or radical prostatectomy. RESULTS: 1048 of 1117 (94%) cases diagnosed were surveyed. Most of the men (858 [82%]) were older than 65 years: 117 (11%) cancers were detected by screening asymptomatic men, and a further 269 (26%) were found by testing of men with symptoms ("case-found"). The 259 (25%) men treated with definitive local therapies (prostatectomy and curative radiotherapy) were younger (< 75 years), and their disease was clinically more localised (clinical stage, T1-2) and they were often found by screening or case-finding. Men given hormonal therapy (407; 39%) or managed without treatment (373; 36%) tended to be older and more likely to have been diagnosed by transurethral resection of the prostate (TURP). The overall relative survival at five years was 86% and was decreased in men with cancers of higher histological grade or more advanced clinical stage, or who had higher PSA levels. CONCLUSIONS: Although a third of patients were detected by screening or case-finding early in the PSA era, definitive local therapies were used infrequently (25% of the total sample). Most received appropriate treatment.

Reported management of lung cancer in Victoria in 1993: comparison with best practice. Anti-Cancer Council of Victoria Lung Cancer Study Group.

OBJECTIVE: To determine recent patterns of management of lung cancer in Victoria in order to stimulate interest in the development of Australian consensus guidelines. DESIGN: A cross-sectional survey of doctors responsible for the care of an incident series of lung cancer patients in 1996-1997. PARTICIPANTS: 1054 people diagnosed with primary lung cancer in the State of Victoria between 1 January 1993 and 31 July 1993 and notified to the Victorian Cancer Registry. MAIN OUTCOME MEASURES: Method of diagnosis; tumour characteristics; factors affecting management plan; first-line and subsequent treatment; outcome; and patients' current status. RESULTS: Questionnaires were completed for 868 eligible patients (82%): 635 (73%) diagnosed with non-small-cell lung cancer, 124 (14%) diagnosed with small-cell lung cancer, and 109 (13%) with no histological diagnosis. Chest x-ray (814 patients; 94%) and computed tomography (CT) of the chest and abdomen (589 patients; 68%) were the most common investigations, and was the only diagnostic procedure in 48 patients (6%). Treatments were radiotherapy alone or in combination (385 patients; 44%), surgery alone or in combination (196 patients; 23%), chemotherapy alone or in combination (152 patients; 18%); 215 patients (25%) received no antitumour therapy. 243 patients (28%) were treated initially with curative intent. A further 399 (46%) were treated initially with palliative intent, and in 219 (55%) of these good symptom control was achieved. For 427 patients (49%) tumour size was not recorded. While 23% of non-small-cell patients had limited disease, only 8% were investigated with mediastinoscopy. Only four patients (13%) with limited-stage, small-cell lung cancer had combined-modality treatment. There was little use of adjuvant chemotherapy or neoadjuvant therapy. The five-year crude survival rate was 11%. CONCLUSIONS: The demographics of lung cancer in Victoria are similar to other population-based studies. Patterns of management are not uniform, and are inconsistent with current published guidelines.

A case-control study of melanomas of the soles and palms (Australia and Scotland).

OBJECTIVES: Because the factors that influence risk of acral melanomas on the soles and palms in White populations are unknown, we investigated these in a multi-center case-control study. METHODS: Cases of melanoma of the feet and hands diagnosed from 1987-93 in persons aged over 18 years were ascertained in eastern Australia and western Scotland. There were 275 cases of melanoma on the soles and palms matched to 496 controls (selected from the electoral roll) in Australia, and 36 cases matched to 72 controls (nominated by general practitioners) in Scotland. RESULTS: Acral melanoma was strongly associated with high total body nevus counts (adjusted relative risk [RR] = 6.3, 95% confidence interval [CI] = 2.5-15.6), and with nevi on the soles (RR = 7.5, CI = 3.0-18.6). There were also significant positive associations with a penetrative injury of the feet or hands (RR = 5.0, CI = 3.0-8.6) and with heavy exposure to agricultural chemicals (RR = 3.6, CI = 1.5-8.3). Sun-sensitive complexions, cumulative sun exposure and a past history of nonmelanoma skin cancer were also associated with increased risk of acral melanoma. Current cigarette smoking was inversely related to acral melanoma (RR = 0.6, CI = 0.4-0.9). CONCLUSIONS: Melanomas of the soles and palms resemble other cutaneous melanomas in their association with sun exposure, but are distinguished from them by their strong positive associations with nevi on the soles, previous penetrative injury, and exposure to agricultural chemicals, and by their inverse association with smoking.

General practitioner screening for melanoma: sensitivity, specificity, and effect of training.

OBJECTIVE: To measure the performance of trained and untrained general practitioners (GPs) in screening men and women aged 50 or more for melanomas. METHODS: GPs trained in melanoma diagnosis, untrained GPs, and skin cancer specialists examined groups of volunteers, each of which included a small number of subjects with prediagnosed suspicious pigmented lesions (SPLs) that were subsequently excised for histopathological examination. RESULTS: Trained and untrained GPs achieved mean sensitivities of 0.73 and 0.71, and mean predictive values of 0.40 and 0.37, respectively, for the detection of prediagnosed SPLs. When the SPLs had been excised and examined histopathologically, reanalysis showed mean sensitivities of 0.98 and 0.95, mean specificities of 0.52 and 0.49, and mean positive predictive values of 0.24 and 0.22 for the detection of subjects with melanomas by trained and untrained GPs respectively. Trained GPs were significantly better than untrained GPs at diagnosing as melanomas SPLs that subsequently proved to be melanomas (p = 0.04). CONCLUSIONS: GPs in this study achieved high sensitivities in screening older Australian men and women for melanomas, but at the cost of low specificities and positive predictive values. Training in melanoma diagnosis had no significant effect on sensitivity, specificity, and positive predictive value for screening. Data from the study were tested in a model of population screening for melanomas, and costs per life year saved for men aged 50-70 ranged from $A11,852 to $A40,259 depending upon the screening interval and whether the GPs excised the SPLs diagnosed, or referred all patients to skin cancer specialists; this would be as cost effective as cervical cancer screening.

Rising incidence of oesophageal adenocarcinoma in men in Australia.

Adenocarcinomas of the oesophagus and of the gastric cardia have been reported to be increasing in incidence in many countries, while the incidence of squamous cell carcinoma of the oesophagus is stable and non-cardia gastric cancers are decreasing in incidence. Age-standardized incidence rates for the years 1982-1993 for oesophageal adenocarcinoma and non-adenocarcinoma, and gastric cardia and non-cardia cancers were calculated based on state cancer registry incidence data. Time trends in the age-standardized rates were assessed using linear regression. A consistent increasing trend in the incidence of oesophageal adenocarcinoma in men was seen in all states of Australia and was statistically significant in all states except South Australia. There were no consistent nationwide trends in the incidence of oesophageal adenocarcinoma in women, although a trend towards an increase in the incidence of this cancer reached statistical significance (P < 0.05) in three states (New South Wales, Victoria, Queensland). There were no important trends in the incidence of oesophageal non-adenocarcinoma in either men or women. There were no consistent nationwide changes in the incidence of gastric cardia cancer in either men or women, although this cancer was significantly increasing in Tasmania in both men and women. The incidence of cancer of the stomach not arising at the gastric cardia was significantly decreasing in men in all states and was also decreasing in women in all states, although in women this decrease was statistically significant only in New South Wales, Victoria and Western Australia. There has been a dramatic increase in the incidence of oesophageal adenocarcinoma in men in Australia. The incidence of this cancer in men is now approximately equal with that of non-adenocarcinoma of the oesophagus. The incidence of non-cardia stomach cancer continues to fall.

Has mortality from melanoma stopped rising in Australia? Analysis of trends between 1931 and 1994.

OBJECTIVE: To describe recent trends in mortality from melanoma in Australia. DESIGN: An analysis of trends in age standardised and age and sex specific mortalities by year of death and median year of birth (cohort). SETTING: Australia. SUBJECTS: All deaths from melanoma registered in Australia between 1931 and 1994. RESULTS: Melanoma mortality rose steadily from 1931 to 1985. From 1959 the annual rate of increase was 6.3% in men and 2.9% in women, resulting in mortalities of 4.82 and 2.51 per 100,000 person years in 1985 and 1989, respectively. Mortalities for both sexes seem to have plateaued from June 1985 onwards. In 1990-4 the rate rose by 3.7% in men to 5.00 per 100,000 and in women it fell by 5.2% to 2.38 per 100,000. The non-significant increase after 1985 in mortality in men was restricted to those aged over 70 years of age, whereas the fall in rates in women was mostly in those aged under 55 years. This pattern was generally reflected in the state trends, though with some variation: rates for women in Queensland had peaked in the late 1970s; while rates for men in New South Wales continued to rise in 1990-4, placing them above those for Queensland. Examination of mortalities specific for age, period, and cohort for Australia as a whole showed several salient features. Rates in men rose steeply in cohorts born before about 1930; were stable in cohorts born between 1930 and 1950; and fell in more recent cohorts. Rates in women showed similar changes but about five years earlier. CONCLUSION: Melanoma mortality in Australia peaked in about 1985 and has now plateaued. On the basis of trends in cohorts it can be expected to fall in coming years.

Incidence trends in oesophageal and proximal gastric carcinoma in Victoria.

BACKGROUND: There is clinical evidence that adenocarcinoma of the lower oesophagus is increasing in the Australian society. The population-based cancer registry of Victoria was used to describe the incidence of adenocarcinoma of the oesophagus and gastric cardia. METHODS: Data were obtained from 1982 to 1991 and were analysed using the Poisson regression techniques. RESULTS: In men, a statistically significant annual increase of 9.5% in oesophageal adenocarcinoma and a non-significant increase of 1.6% in adenocarcinoma of the gastric cardia was observed. These increases were balanced by decreases in other histological types found in the oesophagus in men resulting in little change in the overall rate. No significant trends by age or histological type were observed in women. CONCLUSIONS: There is evidence for a rise in adenocarcinoma in men in Victoria. Possible risk factors include Barrett's oesophagus.

Childhood cancer in Victoria, Australia, 1970-1989.

The incidence of cancer between 1970 and 1989 in children aged less than 15 years and resident in the state of Victoria, Australia, was ascertained using records held by the Victorian Cancer Registry. Altogether, 1,189 children in the 1970s and 1,261 children in the 1980s were registered with new diagnoses of cancer and these were followed up until 30 June 1993. Between 1970-1979 and 1980-1989 the incidence of childhood cancer rose by 14%, but this was not statistically significant. Part of this apparent increase may have been due to improved registration of cases in the 1980s, particularly of certain tumour types, and of tumours in older children who may have been treated outside the major paediatric treatment centres. Between the 2 decades, 5-year survival increased from 49% to 67%, with improvements in almost all tumour types. Only in Ewing's sarcoma did survival proportions decrease, and this may be related to histological misclassification and to an increased proportion of Ewing's arising in the pelvis during the 1980s. There is evidence already that with new treatment regimens introduced during the 1980s survival in the 1990s will show increased gains.

Investigation, follow-up and recurrence after resection of colorectal cancer.

A study was undertaken to determine the patterns of management in the 2 years following resection of colorectal cancer by Victorian surgeons. Patients were identified by the Victorian Cancer Register as having colorectal cancer diagnosed between July 1 and December 31 1987. The surgeon of each of the 947 eligible patients who underwent surgery was sent a questionnaire seeking information about the pre-operative investigation, type of surgery and subsequent line of referral. Only 16% of colonic cancers and 39% of rectal cancers were biopsied pre-operatively and colonoscopy was undertaken in one-half and one-third respectively. Of the 737 responses, 555 patients were considered to have had curative surgery, and details of their follow-up during the four 6-month periods following surgery was analysed; this includes the effect of tumour stage and surgeon activity on the use and frequency of each test. Most patients had a clinical examination in each of the 6 month periods, but almost half did not have a colonoscopy and two-thirds did not have the serum CEA level measured at all. Only one in eight had a chest X-ray and fewer had the liver scanned during this 2 year period. Eighty-two patients (20% of those satisfactorily followed) suffered a recurrence during this period. Twenty-six were asymptomatic at the time of recurrence and were diagnosed by a routine test and of these, eight were diagnosed by tests used infrequently. Sixteen (20%) were considered surgically curable.

Comparison of indices of islet B-cell function in type 2 diabetes in relation to insulin effectiveness and clinical outcome.

The most appropriate way to estimate islet B-cell function in Type 2 diabetes is unclear, and this has led to many different techniques of measurement being used. We have examined the associations to two fasting and four glucose-stimulated indices of islet B-cell function in members of a group of 249 Type 2 patients, seeking correlations with concurrent glucose tolerance and antilipolytic effect, and with subsequent clinical outcome. The six B-cell indices were interrelated to variable degrees (rs -0.21 to +0.92). Early glucose-stimulated insulin output (incremental 1st-phase insulin area) was not significantly positively correlated with the fasting plasma concentration of immunoreactive insulin at any time. Fasting immunoreactive insulin and 'minimal model' islet B-cell parameters were poorly related to the rate constant for glucose clearance and the degree of antilipolysis (rs values between -0.13 and +0.40). Homeostatic model assessment of the fasting islet B-cell function was more consistently related to these metabolic effects. Incremental first-phase insulin area was the islet B-cell index most consistently related to metabolic abnormalities (rs up to +0.56), and to subsequent need for oral hypoglycaemic or exogenous insulin therapy. No index of islet B-cell function was consistently associated with the subsequent development of diabetic tissue damage.

The metabolic associations of intravenous glucose tolerance in the 10 years from diagnosis of type 2 diabetes.

Intravenous glucose tolerance was measured at diagnosis and during the subsequent 10 years in 103 Type 2 diabetic patients not treated with insulin. KG (the rate constant for clearance of intravenous glucose) was inversely related to fasting plasma glucose at all review times (at diagnosis being Rs = -0.77, p less than 0.001), and at times to the circulating concentrations of ketone bodies (at diagnosis being Rs = -0.52, p less than 0.001) and glycerol (Rs = -0.29, p less than 0.01). In the first year of treatment, most metabolic abnormalities improved. One to 10 years after diagnosis, fasting glucose concentration and intravenous glucose tolerance deteriorated (median glucose from 6.4 to 7.4 mmol l-1, p less than 0.001; median KG from 0.81 to 0.69% min-1, p less than 0.01). Likewise, the 'homeostatic model assessment' of insulin insensitivity deteriorated (median from 2.3 to 3.7 arbitrary units, p less than 0.001) over the same period but first-phase insulin secretion remained steady or improved. This suggests that increases in insulin insensitivity have a predominant effect on slowly deteriorating glucose tolerance from 1 to 10 years after diagnosis in Type 2 diabetes.

The relationship of plasma acetate with glucose and other blood intermediary metabolites in non-diabetic and diabetic subjects.

In investigating the interrelations of plasma acetate with glucose metabolism, we established that fasting plasma acetate levels (mmol/l) were greater in the diabetic than non-diabetic individuals (p less than 0.001). Plasma acetate and glucose levels correlated in all subjects (non-diabetic and diabetic) as a whole (rs 0.28, p less than 0.0001) and in the diabetics alone (rs 0.35, p less than 0.001). After i.v. glucose (20 g/m2 body surface area), plasma acetate levels increased further in the diabetic and non-diabetic individuals. Plasma acetate also increased when non-diabetic individuals consumed 75 g oral glucose. Moreover, while plasma acetate levels had returned to fasting values by 90 min in the non-diabetic subjects after oral and i.v. glucose, levels remained elevated in the diabetics after i.v. glucose. The K rate constant of glucose elimination after i.v. glucose in the diabetics correlated negatively with acetate values at many time points. In the non-diabetics, changing acetate and glucose levels after oral glucose also correlated at multiple time points. These results suggest that the plasma acetate level is influenced by variations in glycaemia and provide further evidence for an impaired rate of acetate metabolism in diabetes.

Diabetic retinopathy: different risk factors for exudates and haemorrhages.

The retinae of 137 patients were examined ophthalmologically and for visual acuity at diagnosis of non-insulin dependent diabetes and again in 1982 and 1983, approximately 7 and 8 years later, when colour photographs were also taken. In 1983, 46% were without detectable retinopathy, 32% had haemorrhages (including microaneurysms) only, 4% exudates alone and 18% both lesions. Those with haemorrhages were more hyperglycaemic than those without retinopathy and those with exudates only. Indeed, those with exudates alone had lower mean glucose levels than those without retinopathy (p less than 0.05). Patients with exudates (+/- haemorrhages) had a lower percentage of the fatty acids of plasma cholesterol esters as linoleate than those without (p less than 0.05) but this did not hold for those developing haemorrhages. Different risk factors appear to operate in different features of diabetic retinopathy. In some respects exudate formation may be more akin to macro than to micro angiopathy.

Mortal factors in type 2 (NIDDM) diabetes mellitus.

Five years after entry into a study prospective from diagnosis of non-insulin-dependent (Type 2) diabetes, 17 patients were known to be dead and 197 alive. On analysis of 136 patients (12 deaths) in whom there was complete information from clinical, metabolic and hormonal examination both before and 1 yr after start of treatment, an index of liability to death within this first 5 yr was calculated, to separate best the dead from the living. One index value correctly ascribed 83% of the dead and 90% of the living (89% of all predictions correct; Youden's "J" value = 0.73). Estimates from the less complete data on the other 78 patients (5 deaths) did not alter the predictive factors. Prediction is more successful with non-cardiac than with cardiac deaths. Five factors contributed to the predictive index for death. One was a long duration of symptoms as recalled at diagnosis. The other 4 factors all came from the 1-yr review (no death then). These were (a) greater glucose intolerance, as expressed by the KG rate constant for disappearance of i.v. injected glucose from the blood (more useful than fasting glucose concentration); (b) higher systolic blood pressure (more useful than diastolic); (c) less obesity, as expressed by the Body Mass Index, and (d) higher fasting blood glycerol concentration. As expected, hyper-glycaemia (as reflected in the KG value) is important, but adrenergic factors may contribute to (a), (b) and (d). From these results earlier diagnosis of this type of diabetes could well be associated with an improved outlook, and in addition this alone might ameliorate the other factors, but measures to normalise them post-diagnosis also require testing.