A Risk Score Model for Locoregional Recurrence Following Upfront Surgery for Pancreatic Adenocarcinoma: Implications for Adjuvant Therapy.

AIMS: The aims of the study were to identify predictors of locoregional failure (LRF) following surgery for pancreatic adenocarcinoma, develop a prediction risk score model of LRF and evaluate the impact of postoperative radiation therapy (PORT) on LRF. MATERIALS AND METHODS: A retrospective review was conducted on patients with stages I-III pancreatic adenocarcinoma who underwent surgery at our institution (2005-2016). Univariable and then multivariable analyses were used to evaluate clinicopathological factors associated with LRF for patients who did not receive PORT. The risk score of LRF was calculated based on the sum of coefficients of the predictors of LRF. The model was applied to the entire cohort to evaluate the impact of PORT on the high- and low-risk groups for LRF. RESULTS: In total, 467 patients were identified (median follow-up 22 months). Among patients who did not receive PORT (n = 440), predictors of LRF were pN+, involved or close ≤1 mm margin(s), moderately and poorly differentiated tumour grade and lymphovascular invasion. After adding patients who received PORT, the 2-year LRF in the high-risk group was 57% for patients who did not receive PORT (n = 242) and 32% among patients who received PORT (n = 22), with an absolute benefit to LRF of 25% (95% confidence interval 5-52%, P = 0.07). The 2-year overall survival for the high-versus the low-risk group was 36% versus 67% (P < 0.001). CONCLUSION: This risk group classification could be used to identify pancreatic adenocarcinoma patients with higher risk of LRF who may benefit from PORT. However, validation and prospective evaluation are warranted.

Non-immunotherapy options for the first-line management of hepatocellular carcinoma: exploring the evolving role of sorafenib and lenvatinib in advanced disease.

The results of the sharp trial established sorafenib, a tyrosine kinase inhibitor (tki), as the sole first-line treatment option in advanced hepatocellular carcinoma (hcc) for more than a decade. In 2020, there has been a surge in new therapies for hcc, including immunotherapeutic strategies and the approval of a number of novel tkis. In addition to sorafenib, lenvatinib and combination atezolizumab-bevacizumab now represent standard first-line treatment options. As those systemic therapy options begin to be better utilized, assurance of adequate liver function and optimal timing are required to improve patient outcomes. Furthermore, sequencing of the agents will have to be carefully tailored, given the increasing armamentarium of choices. Here, we discuss the role of lenvatinib and sorafenib in the first-line management of hcc.

Longitudinal health utilities, symptoms and toxicities in patients with ALK-rearranged lung cancer treated with tyrosine kinase inhibitors: a prospective real-world assessment.

Background: Tyrosine kinase inhibitors (tkis) have dramatically improved the survival of patients with ALK-rearranged (ALK+) non-small-cell lung cancer (nsclc). Clinical trial data can generally compare drugs in a pair-wise fashion. Real-world collection of health utility data, symptoms, and toxicities allows for the direct comparison between multiple tki therapies in the population with ALK+ nsclc. Methods: In a prospective cohort study, outpatients with ALK+ recruited between 2014 and 2018, treated with a variety of tkis, were assessed every 3 months for clinico-demographic, patient-reported symptom and toxicity data and EQ-5D-derived health utility scores (hus). Results: In 499 longitudinal encounters of 76 patients with ALK+ nsclc, each tki had stable longitudinal hus when disease was controlled, even after months to years: the mean overall hus for each tki ranged from 0.805 to 0.858, and longitudinally from 0.774 to 0.912, with higher values associated with second- or third-generation tkis of alectinib, brigatinib, and lorlatinib. Disease progression was associated with a mean hus decrease of 0.065 (95% confidence interval: 0.02 to 0.11). Health utility scores were inversely correlated to multiple symptoms or toxicities: rho values ranged from -0.094 to -0.557. Fewer symptoms and toxicities were associated with the second- and third-generation tkis compared with crizotinib. In multivariable analysis, only stable disease state and baseline Eastern Cooperative Oncology Group performance status were associated with improved hus. Conclusions: There was no significant decrease in hus when patients with ALK+ disease were treated longitudinally with each tki, as long as patients were clinically stable. Alectinib, brigatinib, and lorlatinib had the best toxicity profiles and exhibited high mean hus longitudinally in the real-world setting.

Prognostic Importance of Pathological Fractures in Osteosarcomas.

Aims To investigate whether pathological fractures impact on osteosarcoma patient prognosis in Ireland. Methods This was a retrospective study over 22 years in a National Orthopaedic Oncology Centre. There were 117 nonfracture cases and 15 fracture cases. Outcome measures included 5 and 10 year event-free (EFS) and overall survival (OS). Kaplan-Meier curves assessed length of survival and time to death. Results Pathological fracture has no significant effect on 10 year EFS or 10 year OS. 3 factors strongly associate with 10 year OS rates: American Joint Committee on Cancer (AJCC) classification (p<0.001), Metastases site (p<0.001) and Distant recurrence (p<0.001). Fractures had poorer post-chemotherapeutic necrosis rates (p=0.005). Conclusion Pathological fractures have no significant effect on survival rates or length of survival in an Irish population. The effect of pathological fractures on necrosis rates must be explored in future research.

Resistance to epidermal growth factor receptor tyrosine kinase inhibitors, T790M, and clinical trials.

Tumours with sensitizing mutations in the EGFR gene constitute a distinct molecular subgroup of non-small-cell lung cancers (nsclcs) that benefit from precision medicine. First- and second-generation epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are recommended as upfront therapy for EGFR-mutated advanced nsclc and, compared with chemotherapy, have resulted in superior progression-free survival, improved tumour response rates, and improved quality of life. However, resistance inevitably develops, and the third-generation tki osimertinib has been approved to target the gatekeeper EGFR mutation T790M, which is responsible for resistance in 60% of cases. Multiple drivers of tki resistance have now been identified, and many new drugs are in development. With respect to this rapidly evolving field, our review highlights the current status of treatment options for patients with EGFR-mutated advanced nsclc, focusing especially on identified causes of resistance, challenges, and clinical trials aiming to improve outcomes in this patient population.

Is chemotherapy always required for cancer in pregnancy? An observational study.

BACKGROUND: Cancer in pregnancy is relatively rare, but the incidence is increasing. Several studies show that cytotoxic agents are safe to use in pregnancy from the second trimester onwards. AIMS: This study assesses the maternal and foetal outcomes of cancers diagnosed during pregnancy. In particular, it focuses on a subset of women who elected to defer systemic chemotherapy until after delivery. This study examines if all cancers need to be treated during pregnancy or if, in certain cases, treatment can be safely deferred until after full-term delivery. METHODS: This is a retrospective observational study of women diagnosed with cancer during pregnancy in an Irish cancer centre over a 27-year period. All women diagnosed with cancer during pregnancy who were referred to the medical oncology department for consideration of chemotherapy were included in this study. Medical and pharmacy records were extensively reviewed. RESULTS: Twenty-five women were diagnosed with cancer in pregnancy and referred to medical oncology for consideration of systemic chemotherapy. Sixteen women (64%) commenced chemotherapy during pregnancy, seven women (28%) did not receive chemotherapy while pregnant, but commenced treatment immediately after delivery, and two (8%) did not receive any systemic chemotherapy at all. Of the seven women who commenced chemotherapy after delivery, six (85.7%) were diagnosed before 30/40 gestation. There were three cases of Hodgkin's lymphoma, two breast cancers and one ovarian cancer. After a median follow-up of 12 years, all six mothers remain disease-free. CONCLUSIONS: This study identified a select cohort of patients that did not receive chemotherapy during pregnancy. There were no adverse outcomes to mothers due to delayed treatment.

Osteosarcoma in a Patient Receiving Long-Term TNF Inhibitor Therapy.

Patients with inflammatory bowel disease (IBD) have an increased risk of developing malignancy. The use of immunosuppressive therapies and tumour necrosis factor (TNF) inhibitors in these patients may provide a further risk for the development of malignancy. We report the clinical and pathological findings of a high grade osteosarcoma in a patient with Crohns disease receiving TNF inhibitor therapy. In this case, a 32-year old female presented with a painful right knee after receiving maintenance adalimumab for Crohns disease for a period of six years. There is a substantial hypothetical link between TNF inhibitor regimens such as adalimumab and an increased risk of malignancy. TNF inhibitor therapy should be ceased and chemotherapy and surgery is an effective combined modality approach in these patients. The role of TNF inhibitors in patients after cancer diagnosis is uncertain and further research is required to assess efficacy and safety.

Perioperative chemotherapy in the treatment of osteosarcoma: a 26-year single institution review.

BACKGROUND: Chemotherapy in the multimodality treatment of osteosarcoma has improved survival. Reported outcomes on adult patients are limited. Poor necrosis rates post neoadjuvant chemotherapy (NAC) is considered an adverse prognostic factor and attempts have been made to improve survival in this group. PATIENTS AND METHODS: Adult and young adult patients diagnosed with osteosarcoma between January 1986 and August 2012 were retrospectively reviewed. Patients identified were stratified according to stage (localised or metastatic) and age (≤40 and >40 years). Event free survival (EFS) and overall survival (OS) outcomes were determined. In patients with localised disease ≤40 years, survival was assessed according to necrosis rates post NAC (<90 and ≥90%). NAC consisted of two cycles of methotrexate alternating with doxorubicin/cisplatin (MAP) followed by definitive surgery. Those with ≥90% tumour necrosis continued on MAP. Patients with <90% necrosis received ifosfamide and etoposide (IE) post operatively. RESULTS: A total of 108 patients were reviewed and 97 were included. Median age was 23 years (range 16-75) and 70% of patients were male. Five year EFS and OS across all groups was 57% and 63% respectively. Of the patients with localised disease (N = 81), 5-year overall survival (OS), with a median follow up of 7 years (2-26) was 70% (p < 0.0001). Patients aged 16-40 (N = 68) with localised osteosarcoma had a significantly improved 5-year OS (74%) compared to those >40 years (N = 13) (42%) (p = 0.004). Of the 68 patients with localised osteosarcoma ≤40 years, 62 were evaluated according to necrosis rates post MAP. In 33 patients who achieved ≥90% necrosis and continued MAP, 5-year OS was 82%. In 29 patients who had <90% tumour necrosis and received adjuvant IE, 5-year OS was 68% (p = 0.15). Multivariate analysis confirmed age and stage as prognostic factors but not poor necrosis rates in our treated population. CONCLUSIONS: Long-term survival outcomes in a predominantly adult Irish population are similar to large reported trials. Age and stage at diagnosis are prognostic. Postoperative ifosfamide/etoposide alone in patients with poor necrosis rates is a feasible regimen, but its role in the adjuvant setting remains uncertain.

Vismodegib in the treatment of advanced BCC.

Basal-cell carcinoma (BCC) is the most commonly diagnosed malignancy, comprising over 80 per thousand of non-melanoma skin cancers. Surgical excision is adequate treatment for most BCC's. Options are however limited for the minority of patients presenting with locally advanced inoperable or metastatic BCC. The Hedgehog signalling pathway is a critical driver in the pathogenesis of both sporadic and hereditary BCC. On 31st January 2012, based on a phase II clinical trial the US Food and Drug Administration approved Vismodegib (Erivedge, Roche) a first-in-class, small-molecule oral Hedgehog-inhibitor for the treatment of locally advanced inoperable and metastatic BCC. We present our experience treating the first Irish patient with this agent.

Riverina men's study: a preliminary exploration of the diet, alcohol use and physical activity behaviours and attitudes of rural men in two Australian New South Wales electorates.

INTRODUCTION: Discourses around men's health refer to greater risk-taking behaviour, the social construct of masculinity and differences between men's and women's rates of death and disease. These ways of describing 'men's health' may be inadequate, but many men, particularly rural men, experience health disadvantage. OBJECTIVE: To determine the reported eating, drinking and exercise behaviours of rural men and relationships between reported behaviours and attitudes to health and body image, age and occupation. METHOD: A written postal survey was used to collect demographic data, eating behaviours using the Food Habit Score, alcohol use, physical activity behaviours using an adaptation of the Pilot Study of the Fitness of Australians and attitudes to health and body image. SUBJECTS AND SETTING: The survey was sent to 2000 randomly selected men in two New South Wales Riverina federal electorates in June 2004, with 529 returns (27% response). MAIN OUTCOME MEASURES: Food Habit Scores; regularity of physical activity; frequency and amount of alcohol use; degree of agreement with statements about attitudes to health and body image. STATISTICAL ANALYSES: Descriptive statistics using frequencies and cross tabulations were performed with further univariate analyses conducted at a level of significance of 5%. RESULTS: Approximately one-third of the men achieved a poor Food Habit Score (< or =10 out of 20). Age was not significantly associated with diet quality, but those in higher skilled occupations had a better diet, compared with those in less skilled occupations (p<0.01). Eighty-seven percent of the respondents drank alcohol and of those, almost half consumed only one or two alcoholic drinks at each session. Nearly a quarter of the men reported that they had more than four drinks on each drinking occasion. Almost half the men did no 'vigorous' exercise, but 42% did heavy labouring/gardening at least three times a week. The men with poor dietary habits were more likely to agree with less desirable attitudes to health, such as needing a health scare before changing lifestyle behaviours (p<0.001). The low response rate (27%) limits the ability to generalise these results to the whole male population in the Farrer and Riverina federal electorates. CONCLUSION: This study describes the eating and physical activity behaviours of a sample of rural men and highlights the attitudes that are associated with poor lifestyle behaviours among this hard to reach group. IMPLICATIONS: Health promotion programs targeting men, especially rural men, should address existing attitudes to health which may impact on lifestyle behaviours.

Community acquisition of gentamicin-sensitive methicillin-resistant Staphylococcus aureus in southeast Queensland, Australia.

Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) susceptible to gentamicin has been reported in a number of countries in the 1990s. To study the acquisition of gentamicin-sensitive MRSA (GS-MRSA) in southeast Queensland and the relatedness of GS-MRSA to other strains of MRSA, 35 cases of infection due to GS-MRSA from October 1997 through September 1998 were examined retrospectively to determine the mode of acquisition and risk factors for MRSA acquisition. Thirty-one isolates from the cases were examined using a variety of methods (antibiotyping, phage typing, pulsed-field gel electrophoresis [PFGE] fingerprinting, and coagulase typing by restriction analysis of PCR products) and were compared with strains of local hospital-acquired gentamicin-resistant MRSA (GR-MRSA) and of Western Australian MRSA (WA-MRSA). Only 6 of 23 cases of community-acquired GS-MRSA had risk factors for MRSA acquisition. Twenty of 21 isolates from cases of community-acquired infection were found to be related by PFGE and coagulase typing and had similar phage typing patterns. Hospital- and nursing home-acquired GS-MRSA strains were genetically and phenotypically diverse. Community-acquired GS-MRSA strains were not related to nosocomial GR-MRSA or WA-MRSA, but phage typing results suggest that they are related to GS-MRSA previously reported in New Zealand.

Candidaemia in an Australian teaching hospital: relationship to central line and TPN use.

We performed a retrospective review of patient case records to identify risk factors for candidaemia and to assess incidence, management and outcome of candidaemia in an Australian teaching hospital. Between January 1994 and June 1996, 38 cases of candidaemia were identified. The incidence was 0.74 per 1000 admissions of 24 h duration, and 1.54 per 1000 admissions of 5 days or more. The mortality rate was 34%, with eight of 13 (62%) of these deaths attributable to candidaemia. Risk factors included underlying gastrointestinal disease (66%) and recent abdominal surgery (61%), while recent broad spectrum antibiotic use was a contributing factor in 95%. Twenty-nine patients (76%) had a vascular access device in situ at time of detection. This was the apparent source of candidaemia in 28 (97%). Twenty-six (90%) were being used for TPN administration. Of patients receiving TPN, 5.2% developed candidaemia. Standard central venous catheters (CVC) were present in 21 patients (55%), having been in situ for an average of 12.7 days. Eighteen (86%) had been in situ for 7 days or more. Management involved removal of any implicated intravascular device. Thirty of 33 early survivors received antifungal chemotherapy. Therapy with amphotericin B, fluconazole alone or amphotericin B followed by fluconazole was equally effective. Concurrent corticosteroid use and neutropaenia contributed to increased mortality. Candidaemia is not benign. Policies regarding regular changing of central lines, especially in the setting of TPN administration and control of broad spectrum antibiotic use are appropriate measures aimed to reduce incidence. Management involves removal of implicated lines and antifungal chemotherapy. Pre-emptive therapy for candida infection should be considered in selected patients with the likelihood of TPN-related central line sepsis. Fluconazole is an effective alternative to amphotericin B in non-neutropenic patients.

Staphylococcal bacteraemia: the hospital or the home? A review of Staphylococcus aureus bacteraemia at Concord Hospital in 1993.

AIMS: To examine the risk factors for, and the complications and mortality of, Staphylococcus aureus bacteraemia. METHODS: A retrospective case review of patients with S. aureus bacteraemia in 1993 diagnosed at the Concord Repatriation General Hospital, Sydney. RESULTS: Of 104 cases reviewed, 32 were due to methicillin resistant S. aureus (MRSA), 73 were due to methicillin sensitive S. aureus (MSSA) and one was a dual infection. Twenty-eight of the bacteraemias were community-acquired, including one case of MRSA, and 76 were hospital-acquired; 38% had an implanted prosthetic device or graft. The average age (68 years), incidence of underlying diseases and hospitalisation in the past month (26%) did not differ between MRSA and MSSA groups. MRSA was more likely in patients with recent broad-spectrum antibiotic use (53% vs 0, p < .01). Vascular access was the commonest source of sepsis (61%) but in community-acquired cases the source was unknown in 50%. Use of central line access was more predictive of MRSA infection (75% vs 49%, p = .018). In hospital-acquired infection, MRSA sepsis occurred later in the course of the admission (26 days vs eight days, p < .01). Directly attributable mortality was highest in MRSA and community-acquired MSSA infection (9% and 11%) compared with hospital-acquired MSSA infection (1%). CONCLUSIONS: Nosocomial S. aureus bacteraemia, particularly MRSA, is a major source of preventable morbidity, which could be addressed by improved infection control of MRSA, antibiotic use and attention to central line catheter use.

Chromoblastomycosis: a retrospective study of six cases at the Royal Darwin Hospital from 1989 to 1994.

Chromoblastomycosis, a localized chronic cutaneous and subcutaneous infection of the skin caused by pigmented fungi, is most common in the world's tropical and subtropical zones. The condition rarely occurs in Australia. We present 6 cases of chromoblastomycosis seen at the Royal Darwin Hospital, Northern Territory, from 1989 to 1994 and affecting predominantly male Caucasians ranging from 38 to 71 yrs of age. Clinically the lesions were verrucous or nodular. They mimicked basal or squamous cell carcinoma, nevi or solar keratoses. Histopathologic findings were nonspecific. The only pathognomonic finding was the presence of brown spores or sclerotic bodies within granulomata or within microabscesses in the skin.

Intensive care in an Irish district general hospital--a three year review.

The International Missionary Training Hospital is a 340-bed acute general hospital with maternity and paediatric units. It serves a population of 120,000 people within the North Eastern Health Board Area and has approximately 14,000 admissions each year. This report retrospectively reviews the activity of a three bedded, Intensive Therapy Unit (ITU) over the three year period July 1987-June 1990. 805 patients (1.9% of hospital admissions) with an average age of 55 +/- 22 years (mean +/- SD, range 14-94 years) were admitted to the unit. There were 458 males (57%) and 347 females (43%). 68% of the patients were admitted from the general wards and the remainder from the accident unit. 59% of the admissions were immediate postoperative cases. 82% of patients had APACHE scores less than 20. There was a wide diversity of medical and surgical diagnoses requiring treatment. 219 cases required one or more systems to be supported and 586 (73%) were admitted as high dependency cases. For those requiring ventilation, the average ventilation time was 3.2 days (range 0.5-23 days). The average length of stay within in the unit was 2.3 days (range 1-23 days). 86% of the patients were discharged to the wards, 11% died and 3% were transferred to external specialist care facilities. ITU's in district general hospitals serve as both critical care areas and high dependency units. In our opinion they produce a positive contribution to progressive patient care for high risk medical and surgical patients.

Near-fatal septicaemia with Chromobacterium violaceum.

Chromobacterium violaceum is a Gram-negative organism which normally inhabits water and soil. Human infection is unusual and is associated with a high mortality rate. We describe a typical case of disseminated infection with Chr. violaceum in a male carpet cleaner. The possible origin and treatment of the infection is discussed.