Prevalence and associations of psychological distress in Australian junior medical officers.

BACKGROUND/AIMS: To determine the prevalence of psychological distress in Australian junior medical officers (JMO) and investigate the determinants associated with psychological distress over a 3-year (2014-2016) period. METHODS: JMO were surveyed using the 2014-2016 JMO Census (n = 220, 399 and 466 each year; response rate approximately 15%). Levels of psychological distress were assessed using the Kessler Psychological Distress Scale (K10). A K10 ≥ 25 was chosen to indicate high psychological distress, and this determinant was compared to various demographic and work-related factors. RESULTS: Australian JMO experience a high level of psychological distress (mean: 18.1, median 16.0). There were no differences in demographical variables, such as age, gender, marital status, dependants and between postgraduate years 1 and 2. Increasing hours worked per week was associated with a higher K10, with every hour worked increasing odds by 3%. Attitudinal items, including feeling unwilling to study medicine again, feeling poorly trained and experiences of bullying, were related to high psychological distress. Coping strategies like exercise and spending time with friends correlated positively with lower distress, while time off work, frequent alcohol use, smoking and drug use were associated with increased distress levels. Of those with a high K10, 54.5% indicated that they did not use any form of professional support; 17.83% expressed that given their time again, they would not choose to study medicine. CONCLUSION: A focused approach to JMO support and education regarding significant risk factors identified is likely to assist health policies that aim to improve the mental well-being of Australian JMO.

Difficulty in Diagnosing Rare Cardiac Tumors: A Case Series.

Primary cardiac tumors are rare because metastatic lesions from distant sites account for most masses. We are reporting two cases of malignant intracardiac masses with their diagnostic dilemma. Our first patient is a 72-year-old male with a pertinent history of desmoplastic and spindle cell melanoma who presented after his surveillance positron emission tomography (PET) scan showed a hypermetabolic lesion in the inferior pericardium. The initial impression for this mass is recurrent malignant melanoma. After an initial negative endometrial biopsy, the patient underwent debulking surgery, and pathology revealed high-grade spindle cell sarcoma. The patient underwent chemotherapy but had a disease progression and ultimately elected hospice care. Our second patient is a 75-year-old male with a history of stage IB adenocarcinoma of the lung who presented with progressive dyspnea. An echocardiogram revealed a moderate-sized left ventricular mass. Initial assessment based on tumor morphology and location suggested possible cardiac sarcoma. However, the patient's subsequent cardiac biopsy revealed small cell carcinoma, likely of primary cardiac origin, as no other primary nidus of the tumor was seen. Based on this result, the patient has been started on carboplatin, etoposide, and atezolizumab and responded well as of the writing of this manuscript. Given the rarity of malignant primary cardiac tumors and their variable clinical presentation, intracardiac masses are often diagnosed incidentally. In addition, given the high risk of biopsy for intracardiac masses, a presumptive diagnosis is rendered via imaging techniques. However, most of these tumors have no pathognomonic imaging findings, and their diagnosis relies heavily on physician interpretation and experience. Our case series illustrated the unpredictable nature of noninvasive methods and that even endometrial biopsy can return a false negative. Therefore, it is essential to be persistent in obtaining a pathological diagnosis, especially if the clinical picture is unclear. While these more invasive methods present the challenge of identifying whether the procedure is truly needed and locating a skilled operator, it could change the diagnosis entirely and open the patient up to new therapies.

Metastatic Pancreatic Cancer: ASCO Guideline Update.

PURPOSE: The aim of this work was to provide an update to the ASCO guideline on metastatic pancreatic cancer pertaining to recommendations for therapy options after first-line treatment. METHODS: ASCO convened an Expert Panel and conducted a systematic review to update guideline recommendations for second-line therapy for metastatic pancreatic cancer. RESULTS: One randomized controlled trial of olaparib versus placebo, one report on phase I and II studies of larotrectinib, and one report on phase I and II studies of entrectinib met the inclusion criteria and inform the guideline update. RECOMMENDATIONS: New or updated recommendations for germline and somatic testing for microsatellite instability high/mismatch repair deficiency, BRCA mutations, and TRK alterations are provided for all treatment-eligible patients to select patients for recommended therapies, including pembrolizumab, olaparib, larotrectinib, or entrectinib, or potential clinical trials. The Expert Panel continues to endorse the remaining recommendations for second-line chemotherapy, as well as other recommendations related to treatment, follow-up, and palliative care from the 2018 version of this guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update.

Purpose In 2016, ASCO published a guideline to assist in clinical decision making in metastatic pancreatic cancer for initial assessment after diagnosis, first- and second-line treatment options, palliative and supportive care, and follow-up. The purpose of this update is to incorporate new evidence related to second-line therapy for patients who have experienced disease progression or intolerable toxicity during first-line therapy. Methods ASCO convened an Expert Panel to conduct a systematic review of the literature on second-line therapy published between June 2015 and January 2018. Recommendations on other topics covered in the 2016 Metastatic Pancreatic Cancer Guideline were endorsed by the Expert Panel. Results Two new studies were found that met the inclusion criteria. Recommendations For second-line therapy, gemcitabine plus nanoparticle albumin-bound paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin), an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1, and a favorable comorbidity profile; fluorouracil plus nanoliposomal irinotecan can be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, an ECOG PS of 0 to 1, and a favorable comorbidity profile; fluorouracil plus irinotecan or fluorouracil plus oxaliplatin may be offered when there is a lack of availability of fluorouracil plus nanoliposomal irinotecan; gemcitabine or fluorouracil should be offered to patients with either an ECOG PS of 2 or a comorbidity profile that precludes other regimens. Testing select patients for mismatch repair deficiency or microsatellite instability is recommended, and pembrolizumab is recommended for patients with mismatch repair deficiency or high microsatellite instability tumors. Endorsed recommendations from the 2016 version of this guideline for computed tomography, baseline performance status and comorbidity profile, defining goals of care, first-line therapy, and palliative care are also contained within the full guideline text. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

Shoulder arthroplasty in sickle cell patients with humeral head avascular necrosis.

The purpose of this study was to evaluate the results of shoulder arthroplasty for the treatment of avascular necrosis in patients with sickle cell disease. Medical records, radiographs, operative reports, and outcome scores of 8 adult patients with sickle cell disease were evaluated. The mean follow-up was 51 months (range, 2-10 years). Seven patients had a hemiarthroplasty, and one had a total shoulder arthroplasty. One patient had an intraoperative rotator cuff tear. Two had sickle cell crises in the immediate postoperative period. In one patient, stiffness developed that required arthroscopic capsular release 22 months after her arthroplasty. Another patient with a hemiarthroplasty underwent revision to a total shoulder arthroplasty 5 years after the index procedure. The mean American Shoulder and Elbow Surgeons score improved by 31.9 points. However, only 2 patients reported improvement in pain as assessed with a visual analog scale. Although shoulder arthroplasty provides improvements in range of motion and function in the majority of patients, pain relief is less predictable.

Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations.

PURPOSE: The tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib are effective in non-small cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) gene mutations. The usual clinical dose of gefitinib (250 mg/d) is only one third of its maximum tolerated dose, whereas the dose of erlotinib (150 mg/d) is at its maximum tolerated dose. In NSCLC cell lines, both TKIs have similar micromolar inhibitory concentrations. We explored whether erlotinib at 25 mg/d (trough serum concentration similar to gefitinib 250 mg/d) would be efficacious in EGFR-mutated NSCLC. METHODS: To study the inhibitory concentrations of gefitinib and erlotinib, we exposed EGFR-mutated cell lines (HCC827, H3255, PC-9, and H1975) to increasing concentrations of these TKIs. Further on, we performed a retrospective evaluation of seven patients with advanced EGFR-mutated (exon 19 deletions and L858R) NSCLC that were given erlotinib at 25 mg/d as their first EGFR TKI. RESULTS: Gefitinib and erlotinib generated similar inhibitory curves across our panel of EGFR-mutated NSCLC cell lines with overlapping mean 50% inhibitory concentration 95% confidence intervals for HCC827, PC-9, and H1975. Both drugs also displayed a high degree of correlation in mean 50% inhibitory concentration (Pearson's r = 0.99, p = 0.0417). Of the seven patients, five patients (71.5%) had partial responses to erlotinib 25 mg/d. Median progression-free survival was 17 months (95% confidence interval, 6-35 months). Toxicities were minimal, with only two (28.5%) patients having a rash and none experiencing (0%) diarrhea. CONCLUSIONS: In NSCLC cell lines, gefitinib and erlotinib have similar inhibitory profiles. In patients with NSCLC and EGFR-activating mutations, a dose of erlotinib 25 mg/d (equivalent to gefitinib 250 mg/d) leads to impressive response rates and progression-free survival similar to the growing experience with the approved doses of gefitinib (250 mg/d) and erlotinib (150 mg/d). Identifying prospectively the lowest and clinically active dose ranges of erlotinib and gefitinib will help further to personalize care for patients with tumors harboring EGFR mutations.