Long-term experience on assisted suicide in Switzerland: dementia, mental disorders, age-related polymorbidity and the slippery slope argument.

OBJECTIVES: According to the Swiss medico-ethical guidelines valid between 2004 and 2018, the key criterion for assisted suicide (AS) was that the patients who wished to die suffered with a disease leading to death in the foreseeable future. Critics of AS fears that broadening of the medical indications will lead to an uncontrolled expansion to persons who are not terminally ill (slippery slope argument). We evaluated to what extent this broadening took place in practice over time. STUDY DESIGN: Retrospective national cohort study. METHODS: By using data of the Swiss Federal Statistical Office, we analyzed the long-term development of AS in Switzerland over a 20-year period (1999-2018; n = 8738 cases). We classified the cases into one of three categories regarding the aforementioned key criterion for AS. RESULTS: In 43.6% of AS cases, the criterion 'end of life is near' was met. In 5.3% of cases, this criterion was not met (4.7%: mental disorders; 0.6%: dementia). In 51.1% of cases, the reason underlying AS comprised several, mostly age-related diseases and/or functional impairments; the aforementioned key criterion, however, was probably not met in most of the cases. Over time, the number of cases doubled over each 5-year period; this increase occurred similarly for the three categories. CONCLUSION: The fact that many AS cases took place outside the valid medico-ethical guidelines might be interpreted as a development in the idea of the slippery slope argument. The fact that the percentage distribution of these cases remained unchanged over time argues against it.

Assisted suicide in patients with cancer.

BACKGROUND: There are limited data on the long-term development and trends of assisted suicide (AS) among cancer patients. PATIENTS AND METHODS: Using data of the Swiss Federal Statistical Office, we analyzed AS trends over an 18-year period (1999-2016; total number of cases = 6553). RESULTS: Among patients who underwent AS, cancer was the most common underlying disease (n = 2704, 41.3% of all AS cases). The most common cancer types were lung (14.0% of cancer-related AS cases), breast (11.0%) and prostate (10.1%). There was a slight preponderance of men compared with women (51.5% versus 48.5%). The proportion of AS cases within cancer types did not change over time. The ratio of cancer-related AS cases in relationship with all cancer-related deaths increased from 0.3% at the beginning of the study period (1999-2003) to 2.1% from 2014 to 2016 (change of age-standardized rates for men: +488%; for women: +417%). At the end of the study period (2014-2016), there were only minor differences between cancer-specific ratios, highest and lowest range: 1.1% (liver cancer) and 2.8% (breast, esophageal and lip/oral cavity/oropharynx cancer). Individuals who underwent AS because of cancer were considerably younger than those who choose AS on account of other diseases (73 years versus 80 years). The median age of people with cancer-related AS was similar to that of all cancer-related deaths (74 years): for women, the median age of cancer-related AS was 72, whereas for men it was 75. The median age at which AS took place increased over time. CONCLUSIONS: During the study period, the proportion of people who chose cancer-related AS has approximately sextupled. However, AS among cancer patients remains rare and represents only ∼2% of all cancer-related deaths.

Correction to: Comparative analysis of confocal microscopy on fresh breast core needle biopsies and conventional histology.

Following publication of the original article [1], the authors reported an added data on Table 1 in their paper. The original article [1] has been updated.

Prognostic impact of PIK3CA protein expression in triple negative breast cancer and its subtypes.

BACKGROUND: Triple negative breast cancer (TNBC) harbors a heterogeneous group of carcinomas with poor prognosis and high genetic variability. As a potential aim for targeted therapy, genetic mutations leading to an activation of the phosphoinositide 3-kinase pathway in a catalytic subunit (PIK3CA) in breast cancer have been analyzed currently. Little is known about the clinical impact and prognostic or predictive value of this marker in TNBC subtypes. METHODS: Samples from 119 TNBC cases were submitted to immunohistochemical PIK3CA protein expression analysis and scored semi-quantitatively as negative, weak (1 +), or strongly expressed (2 +). Expression scores were correlated to patient's characteristics, imaging features, and TNBC subtypes. TNBC subtypes were categorized into four subtypes: basal like, mesenchymal like, luminal androgen receptor (LAR), and immunomodulatory. RESULTS: We did not observe differences in clinical aspects and imaging features between TNBC with and without PIK3CA expression. PIK3CA expression was in general higher in the LAR subtype. The disease-free survival and overall survival were significantly better in TNBC with PIK3CA protein expression, independent of TNBC subtypes. CONCLUSION: Despite conflicting results in the literature, our study clearly shows a better outcome of PIK3CA-expressing TNBC, independent of TNBC subtypes. PIK3CA expression in TNBC is not associated with specific clinical or diagnostic features. Further molecular studies and meta-analysis are warranted to clarify the prognostic and predictive role of PIK3CA protein expression.

Comparative analysis of confocal microscopy on fresh breast core needle biopsies and conventional histology.

BACKGROUND: Evaluation of core needle biopsies (CNB) is a standard procedure for the diagnosis of breast cancer. However, tissue processing and image preparation is a time- consuming procedure and instant on-site availability of high-quality images could substantially improve the efficacy of the diagnostic procedure. Conventional microscopic methods, such as frozen section analysis (FSA) for detection of malignant cells still have clear disadvantages. In the present study, we tested a confocal microscopy scanner on fresh tissue from CNB with intention to develop an alternative device to FSA in clinical practice. PATIENTS AND METHODS: In 24 patients with suspicious breast lesions standard of care image-guided biopsies were performed. Confocal images have been obtained using the Histolog™ Scanner and evaluated by two independent pathologists. Hematoxylin-Eosin (H&E) histological sections of the biopsies were routinely processed in a blinded fashion with respect to the confocal images. RESULTS: In total 42 confocal images were generated from 24 biopsy specimens, and available for analysis within a few minutes of taking the biopsy. This resulted in 2 × 42 = 84 pathologic evaluations. In four cases, a pathologic diagnosis was not possible with confocal microscopy. An exact correlation based on the B-classification was reached in 41 out of 80 examinations and in another 35 cases in a broader sense of correspondence definition (i.e. malignant vs. benign). CONCLUSIONS: As a reliable on-site method, the Histolog™ Scanner provides a visualization of cellular details equivalent to the H&E standards, permitting rapid and accurate diagnosis of malignant and benign breast lesions. Furthermore, this device offers great potential for immediate margin analysis of specimen in breast conserving therapy.

The impact of distinct triple-negative breast cancer subtypes on misdiagnosis and diagnostic delay.

BACKGROUND: Triple-negative breast cancer (TNBC) includes mostly aggressive types of breast cancer with poor prognosis. Due to its growth pattern, misinterpretation in clinical imaging is more frequent than in non-TNBC. As the group of TNBC contains heterogeneous types of tumors, marker expression-based subtypes have recently been established. We analyzed clinical features and false-negative imaging findings that could potentially lead to diagnostic delay within the subtypes. METHODS: An exploratory analysis compared the imaging features across the a priori defined subtypes and related these findings to molecular subtype, disease stage, potential diagnostic delay, and patient outcome. RESULTS: TNBC cases were categorized into basal-like (BL; 38.6%), mesenchymal-like (ML; 19.9%), luminal androgen receptor (LAR; 28.3%), and immunomodulatory (IM; 13.3%) subtype. In almost every third patient, malignant classification was missed in at least one imaging method. Misclassification in mammogram was more frequent in ML, while benign ultrasound features were reported more often in the BL subtype. Diagnostic delay due to misclassification in imaging led to tumor growth and/or upgrading of the tumor stage in 8.9% of BL tumors, which had the lowest overall survivals. Despite misclassification rate was higher in the ML subtype it showed better outcomes. Misdiagnosis of axillary lymph node metastasis was higher in LAR; however, this subtype showed a higher percentage of affected axillary lymph nodes. CONCLUSION: TNBC subtypes have different clinical features, benign appearances, and diagnostic delay, which can lead to tumor stage upgrade. Future clinical studies on TNBC outcomes might consider the confounder of clinical delay in the subtypes.