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.

Breast-conserving surgery with intraoperative radiotherapy in recurrent breast cancer: the patient's perspective.

PURPOSE: When ipsilateral breast-tumor recurrence (IBTR) following breast-conserving surgery (BCS) occurs, the cure of a potentially life-threatening disease is the main goal. If, however, this is diagnosed early, prognosis is still good and patient-reported outcomes become more important. Despite the fact that many patients would prefer a further BCS, international breast cancer guidelines still recommend mastectomy, mainly because previous radiation implies limited options. Our comparative study evaluates the long-term quality-of-life and outcome in patients with IBTR who received BCS plus intraoperative radiotherapy (IORT) versus mastectomy. METHODS: Patients with IBTR were retrospectively divided into three groups according to the local treatment: group 1 (n = 26) was treated with BCS + IORT; group 2 (n = 35) received a standard mastectomy; group 3 (n = 52) had a mastectomy with subsequent reconstruction. Outcomes were analyzed after a mean follow-up of 5 years after IBTR. Quality-of-life was evaluated by the validated questionnaire BREAST-Q in 50 patients who fulfilled the inclusion criteria. RESULTS: Quality-of-life scores varied within the groups, ranging from 51.4 to 91.3 (out of 100 points). We observed satisfactory scores in all items, with no statistical difference within the groups. Disease-free survival of all groups did not statistically differ, and overall mortality was very low (0.9%). The postinterventional complication rate was lower after BCS (19.2% versus 34.3% after mastectomy and 30.8% after mastectomy with reconstruction). CONCLUSION: For patients with previous surgery and radiation who demand a second BCS in the recurrent situation, this surgical technique can be offered in combination with IORT. Our long-term results imply oncological safety, lower complication rate, and good patient satisfaction.

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.

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.

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.

Disease-related surgery in patients with distant metastatic breast cancer.

INTRODUCTION: This study evaluates the frequency of and indications for disease-related surgical procedures in the palliative breast cancer (BC) situation. PATIENTS & METHODS: Based on a cohort of women who were treated for newly diagnosed BC during a 20-year period (1990-2009), we analyzed 340 patients who developed distant metastatic disease (DMD) until 2011 and died (i.e. still ongoing palliative disease courses were not included). RESULTS: One hundred and twenty-seven surgical procedures were performed in 100 patients (29.4% of all patients with metastatic disease). The most common site for surgery was breast (n = 60, 47.2%). The primary tumor was removed at first diagnosis of DMD in 43 patients (33.9%); sixteen operations (12.6%) were performed for local recurrence. In 37 patients, 50 surgical procedures (39.4%) were necessary to stabilize osseous structures due to metastases. Procedures were rarely performed on other common metastatic sites: lung: n = 1 (0.8%); liver: n = 1 (0.8%), brain: n = 4 (3.1%). When excluding surgery for primary breast tumors at initial diagnosis of DMD from analysis, 34 of 84 surgeries (40.4%) were performed in the first third of survival follow-up (i.e. period of metastatic disease survival); operations in the last two-thirds each totaled 29.8% (n = 25). The median survival after surgery was 16 months (range: 0.5-89 months). CONCLUSIONS: In a cohort of BC patients who had primary or developed secondary DMD, nearly one third of the patients received disease-related surgical procedures during their palliative disease course. This high rate of operations shows that surgery has a clearly established role in the palliative therapy concept.

The option of delayed reconstructive surgery following mastectomy for invasive breast cancer: why do so few patients embrace this offer?

BACKGROUND: Only a minority of patients who had undergone mastectomy for invasive breast cancer (BC) chose the option for delayed breast reconstruction (BR). We hypothesized that this might partly be (a) due to a lack of information, or (b) because many women cope well with their altered body. METHODS: A cross-sectional survey was completed by 101 early-stage BC survivors who had primary mastectomy. Twenty-six patients had delayed BR. The survey included measures to attitudes to BR and experiences/expectations about information related to BR. RESULTS: The percentage of patients who was informed regarding BR was high (97%). For 39.5% such information was not considered important, neither before mastectomy, nor during follow-up; advanced age was an important factor for the disinterest in information (odds ratio 1.81; 95% CI: 1.04-3.16; p = 0.033). For women without BR, the perception that mastectomy caused a serious damage to their body image changed over time to perceiving the operation as an acceptable alteration of the body (-1.10; 95% CI, -1.52, -0.64; p < 0.001); this process was similar to that in patients who had BR (paired t-test: -2.12; 95% CI, -2.82, -1.41; p > 0.001). From 63 patients who reported no intention to have a BR in the future, 28 (44.4%) responded with answers that showed a high satisfaction with their mastectomies without BR; 30 patients (47.6%) reported reasons, which might potentially be dispelled by information by an experienced reconstructive surgeon. CONCLUSIONS: We did not find any evidence that the low number of patients who chose delayed BR results from a lack of information regarding this procedure. The majority of patients overcome negative attitudes towards their mastectomy quickly and are uninterested in BR. Patients who are ambivalent must be identified; these women require particular attention and should receive intensive counseling.

The post ACOSOG Z0011 era: does our new understanding of breast cancer really change clinical practice?

BACKGROUND: The ACOSOG Z0011 trial (Z0011) expanded our thinking about breast cancer (BC) and showed that limited metastatic disease left behind in the axilla did not compromise oncological safety in a selected group of patients. The aim of the current study was to assess the potential impact of Z0011 on clinical practice by testing the applicability of its criteria to a European patient population. METHODS: We reviewed a consecutive series of 389 sentinel lymph node biopsies (SLNB) performed for invasive BC at the University Hospital Basel between 2003 and 2009 (65.6% of all surgically treated patients, n = 593). RESULTS: When compared to the axillary lymph node dissection (ALND) arm of Z0011, our patients had significantly less advanced LN involvement (≥ 3 LN: 8.5% vs. 21.0%, p = 0.048). Thirty-five patients (9.0%) met the Z0011 inclusion criteria and had 1-2 SLNs with macrometastases (5.9% of all surgically treated BC patients). If the inclusion criteria of Z0011 had been applied, a considerable number of LNs would have been missed in two cases (0.5% of all SLNBs). CONCLUSIONS: The application of the Z0011 led to the omission of completion ALND in less than 10% of all SLNB procedures (<6% of all surgically treated BC patients); therefore, we do not think that the perception of Z0011 as "practice changing" is justified. On the other side, skeptics of the routine implementation of the Z0011 protocol may overestimate its potential hazards. When performing a thorough preoperative clinical axillary staging, the number of patients who would have been undertreated is minimal.

Increasing rates of contralateral prophylactic mastectomy - a trend made in USA?

BACKGROUND: Numerous recent studies conducted in the USA reported a considerable rise in the rates of contralateral prophylactic mastectomy (CPM) in early-stage breast cancer (BC). However, this aggressive surgical approach only showed an evidence-based improvement in prognosis for a small subgroup of high-risk BC patients. We present the first European study reporting CPM rates in an unselected cohort of patients with BC. PATIENTS & METHODS: The data of 881 patients (≤ 80 years) who underwent surgery for stage I-III BC from 1995 to 2009 at the University of Basel Breast Center was analyzed. RESULTS: CPM was performed in 23 of 881 patients (2.6%). Of the entire patient population, 37.5% underwent ipsilateral mastectomy and of those, only 7.0% chose to undergo CPM. Importantly, there was no trend over time in the rate of CPM. Women who chose CPM were significantly younger (54 vs. 60 years, p < 0.001), had more often a positive family history (39.1% vs. 24.4%, p = 0.032) and tumors of lobular histology (30.5% vs. 13.9%, p = 0.035). CONCLUSIONS: Our analysis of CPM rates in BC patients, conducted at a European University breast center, does not show the considerably rising CPM rates observed in the USA. We hypothesize that different medico-social and cultural factors, which are highlighted by a different public perception of BC and a different attitude toward plastic surgery, determine the varying CPM rates between the USA and Europe.

Prognosis of early-stage synchronous bilateral invasive breast cancer.

BACKGROUND: Contradictory data exists concerning the prognosis of patients with synchronous bilateral breast cancer (SBBC). Most authors report a worse prognosis for SBBC patients compared to unilateral breast cancer (UBC) patients. There are a few studies that did not support these findings. This study gives a comprehensive picture of SBBC and tests the hypothesis that outcome of this entity is based on the tumor with the worse prognosis (reference lesion). PATIENTS & METHODS: The data of two prospective Swiss breast cancer databases covering a 20-year period (1990-2009) was reviewed. Forty-six cases of SBBC were identified. In 34 patients with early-stage SBBC, the reference lesions (defined as the tumor with the more advanced stage or, in cases where both tumors had the same stage, the larger tumor) were compared in a case-control approach with 100 patients having UBC (SBBC/UBC ratio = 1/3). The controls were matched for age, time of diagnosis, tumor size, axillary node status, histological grade and estrogen-receptor status. Differences in terms of survival curves were analyzed using the log rank test; the possible correlation between matched groups was evaluated by a frailty Cox model. RESULTS: There were no significant differences in disease-specific survival between SBBC and its unilateral controls (HR, 0.932; 95% CI, 0.322-1.07; p = 0.90). CONCLUSIONS: The prognosis of SBBC was determined by the reference lesion; the contralateral second tumor had no additional impact on outcome.

[Successful methotrexate therapy of tubal pregnancy]. / Erfolgreiche Methotrexattherapie bei Tubargravidität.

Pathologists are well acquainted with the histopathologic features of a vital tubal pregnancy; however, tubal pregnancy successfully treated with medication is seen much less often, since these patients do not usually undergo surgery. We report a rare case of this type, in which no trophoblast tissue was found at histopathologic examination. Intratubal granulation tissue represented the remaining non-vital pregnancy tissue.

Sentinel lymph node biopsy in primary breast cancer: trust the radiolabeled colloid method and avoid unnecessary procedures.

BACKGROUND: With regard to the sentinel lymph node (SLN) procedure in breast cancer, the study analyzed the impact of discrepancies between the number of clinically and histologically identified SLN, the impact of removing additional non-hot/non-blue but clinically conspicuous lymph nodes (LN), and whether the application of blue dye for mapping is necessary. METHODS: We analyzed 391 SLN procedures in which 928 SLN were removed. In all cases, radiolabeled colloid and blue dye were used for SLN mapping. RESULTS: In 60 cases (15.3%), additional LN that were not identified by the surgeon were found by histological examination. In 22 cases (5.3%), tissue which clinically resembled an SLN but was histologically connective tissue, was removed. In 76 cases (19.4%), 133 non-hot/non-blue but clinically conspicuous LN were removed. These additionally removed LN, however, did not alter the axillary staging. In 50.8% of the cases (n = 471), the SLN were marked only by radiolabeled colloid. In 27 cases (2.9%), the surgeon identified the LN through blue coloration alone; however, in all of the latter cases, these SLN were not deciding for axillary staging. CONCLUSION: The mapping agents may accumulate in axillary tissue and mimic the existence of an SLN. The radiolabeled colloid method alone gives excellent mapping results. The additional application of blue dye is avoidable. Exact surgical preparation enables removal of the SLN only and avoids removal of LN-containing adjacent tissue. The removal of further clinically identifiable enlarged non-hot LN should only be done if there is strong suspicion of metastatic involvement.

Metastatic involvement of the urinary tract in patients with advanced ovarian carcinoma: lessons from the autopsy for an interdisciplinary treatment approach.

PURPOSE OF INVESTIGATION: Frequency and extent of metastases in urologic organs found at autopsy of ovarian carcinoma patients were evaluated. METHODS: Autopsy reports from 170 patients who died of advanced ovarian carcinoma between 1975 and 2005 were studied. The distribution of abdominal metastatic sites with particular attention to the involvement of the urologic organs, and hydronephrosis was analyzed. RESULTS: The distribution of metastatic sites was as follows: kidney (n = 6, 3.5%), urinary bladder (n = 38, 22.4%), and ureter (n = 20, 11.8%). In 36 patients, hydronephrosis was observed (21.2%); of these patients, 20 (55.6%) also had ureteral involvement. All patients with ureteral involvement had hydronephrosis. CONCLUSION: Hydronephrosis in late stages of ovarian carcinoma, usually attributed to extrinsic compression of the ureter by an abdominal tumor, may also be explained by ureteral metastases. This fact must be considered in the clinical management of these patients, particularly in the restoration of luminal patency through an endoscopically placed internal ureteral stent.

Target and reality of adjuvant endocrine therapy in postmenopausal patients with invasive breast cancer.

Previous research evaluating the use of adjuvant endocrine therapy among postmenopausal breast cancer patients showed with 15-50% wide ranges of non-adherence rates. We evaluated this issue by analysing an unselected study group comprising of 325 postmenopausal women, diagnosed from 1997 to 2003 with hormonal receptor-positive invasive breast cancer. The different clinical situations that led to the discontinuation of adjuvant endocrine therapy were clearly defined and differentiated: non-adherence was not simply the act of stopping medication, but rather the manifestation of an intentional behaviour of the patient. Of the 287 patients who initiated endocrine therapy, 191 (66.6%) fully completed this treatment. Thirty-one patients (10.8%) showed non-adherence to therapy. Patients who had follow-up with a general practitioner, rather than in an oncologic unit, were more likely to be non-adherent (P=0.0088). Of 25 patients who changed medication due to therapy-related adverse effects, 20 (80%) patients fully completed the therapy after drug change. In adjuvant endocrine therapy, a lowering of the non-adherence rate to 10.8%, the lowest reported in the literature, is realistic when patients are cared for by a specialised oncologic unit focusing on the individual needs of the patients.

[Ectopic prostatic tissue in the uterine cervix]. / Ektopes Prostatagewebe in der Cervix uteri.

Ectopic prostate tissue is a rare occurrence in the lower female genital tract. Possible theories of histogenesis include a developmental anomaly, metaplasia of preexisting endocervical glands, and derivation from mesonephric remnants. We report an example of prostatic tissue involving the uterine cervix of an 82-year-old woman as an incidental finding in a hysterectomy specimen. This unusual lesion should be differentiated from atypical glandular lesions of the cervix. Immunohistochemical studies confirm the histological suspicion of ectopic prostatic tissue.

[Breast cancer with noninflammatory skin involvement: new data revise the traditional image of a "classical" clinicopathologic entity]. / Mammakarzinome mit nichtinflammatorischer Hautbeteiligung: Neue Daten revidieren das traditionelle Bild einer "klassischen" klinikopathologischen Entität.

Historically, the presence of skin involvement results in the classification of a breast carcinoma into the highest tumor category, or accordingly into the highest non-metastatic disease stage (current TNM classification: T4/stage III). However, probably the most important criterion of the TNM classification system is the basic rule that tumors exhibiting similar extension and prognosis should be grouped into one category. Newer studies indicate the need to revise the current TNM system, since grouping all tumors demonstrating "skin involvement" together results in the combination of tumors with widely differing prognostic and therapeutic implications into a single group. Thus, our recommendation is that breast carcinomas classified under the TNM categories T4a-c should be only grouped together according to tumor size. Only the prognostically very unfavorable inflammatory carcinomas (T4d) should be maintained in the T4 category.