Predicting postoperative complications and their impact on quality of life and functional status in older patients with breast cancer.

BACKGROUND: The percentage of older patients undergoing surgery for early-stage breast cancer has decreased over the past decade. This study aimed to develop a prediction model for postoperative complications to better inform patients about the benefits and risks of surgery, and to investigate the association between complications and functional status and quality of life (QoL). METHODS: Women aged at least 70 years who underwent surgery for Tis-3 N0 breast cancer were included between 2013 and 2018. The primary outcome was any postoperative complication within 30 days after surgery. Secondary outcomes included functional status and QoL during the first year after surgery, as assessed by the Groningen Activity Restriction Scale and the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 questionnaires. A prediction model was developed using multivariable logistic regression and validated externally using data from the British Bridging the Age Gap Study. Linear mixed models were used to assess QoL and functional status over time. RESULTS: The development and validation cohorts included 547 and 2727 women respectively. The prediction model consisted of five predictors (age, polypharmacy, BMI, and type of breast and axillary surgery) and performed well in internal (area under curve (AUC) 0.76, 95 per cent c.i. 0.72 to 0.80) and external (AUC 0.70, 0.68 to 0.72) validations. Functional status and QoL were not affected by postoperative complication after adjustment for confounders. CONCLUSION: This validated prediction model can be used to counsel older patients with breast cancer about the postoperative phase. Postoperative complications did not affect functional status nor QoL within the first year after surgery even after adjustment for predefined confounders.

Surgery remains the standard of care for the majority of older patients with breast cancer. The percentage of older patients with breast cancer receiving surgery is decreasing. The reason for this decline is unknown, but it might be due to fear of complications. To better inform patients about the benefits and risks of surgery, the aim of this study was to develop a prediction model for complications after surgery. Another important aspect, especially for older adults with breast cancer, is quality of life, functional capacity, and ability to carry out daily tasks (functional status) after therapy. This study showed that quality of life and functional status did not decline after breast surgery, irrespective of the occurrence of postoperative complications.

Health-related quality of life of breast cancer patients after accelerated partial breast irradiation using intraoperative or external beam radiotherapy technique.

PURPOSE: To compare health-related quality of life (HRQL) in elderly breast cancer patients between two types of Accelerated Partial Breast Irradiation: intraoperative radiotherapy (IORT) and external beam APBI (EB-APBI). METHODS: Between 2011 and 2016 women ≥60 years undergoing breast conserving therapy for early stage breast cancer were included in a prospective multi-centre cohort study. Patients were treated with electron IORT (1 × 23.3 Gy) or photon EB-APBI (10 × 3.85 Gy daily). HRQL was measured by the EORTC-QLQ C30 and BR23 questionnaires before surgery and at several time points until 1 year. RESULTS: HRQoL data was available of 204 IORT and 158 EB-APBI patients. In longitudinal analyses emotional functioning and future perspective were significantly, but not clinically relevantly, worse in IORT-treated patients, and improved significantly during follow-up in both groups. All other aspects of HRQL slightly worsened after treatment and recovered within 3 months with an improvement until 1 year. Cross-sectional analysis showed that postoperatively fatigue and role functioning were significantly worse in IORT patients compared to EB-APBI patients who were not yet irradiated, but the difference was not clinically relevant. At other timepoints there were no significant differences. Multivariable analysis at 1 year identified comorbidity and systemic therapy as risk factors for a worse global health score (GHS). CONCLUSIONS: EB-APBI and IORT were well tolerated. Despite a temporary deterioration after treatment, all HRQL scales recovered within 3 months resulting in no clinically relevant differences until 1 year between groups nor compared to baseline levels.

Acute toxicity of intraoperative radiotherapy and external beam-accelerated partial breast irradiation in elderly breast cancer patients.

BACKGROUND AND PURPOSE: We investigated the acute toxicity of accelerated partial breast irradiation using external beam (EB-APBI) or intraoperative radiotherapy (IORT) techniques in elderly breast cancer patients. MATERIALS AND METHODS: Women ≥ 60 years with unifocal breast tumors of ≤ 30 mm were eligible for this prospective multi-center cohort study. IORT was applied with electrons following lumpectomy (23.3 Gy). EB-APBI was delivered using 3D-CRT or IMRT in 10 daily fractions of 3.85 Gy within 6 weeks after surgery. Acute toxicity was scored using the CTCAE v3.0 at 3 months after treatment. Patient-reported symptoms were analyzed using visual analogue scales (VAS) for pain and fatigue (scale 0-10), and single items from the EORTC QLQ-C30 and Breast Cancer questionnaires. RESULTS: In total, 267 (IORT) and 206 (EB-APBI) patients were available for toxicity analysis. More patients experienced ≥ grade 2 CTCAE acute toxicity in the IORT group (10.4% IORT and 4.9% EB-APBI; p = 0.03); grade 3 toxicity was low (3.3% IORT and 1.5% EB-APBI; ns); and no grade 4 toxicity occurred. EB-APBI patients experienced less fatigue direct postoperatively (EORTC p < 0.00, VAS p < 0.00). After 3 months only pain, according to the VAS scale, was significantly worse in the EB-APBI group (p < 0.00). CONCLUSION: Acute toxicity after IORT and EB-APBI treatment is acceptable.

Contralateral breast cancer risk in relation to tumor morphology and age-in which patients is preoperative MRI justified?

Identification of patients who are at increased risk for contralateral breast cancer is essential to determine which patients should be routinely screened for contralateral breast cancer using MRI. The aim of this study was to assess the association of age and tumor morphology with contralateral breast cancer incidence in a large, nationwide population-based study in the Netherlands. All patients with breast cancer stage I-III, diagnosed between 1989 and 2009, were selected from the Netherlands Cancer Registry. The association between contralateral breast cancer risk with tumor morphology and age was assessed using competing-risk regression according to Fine & Gray. Overall, 194,898 patients were included. In multivariable analyses, lobular tumors were significantly associated with an increased risk of contralateral breast cancer within 6 months (cumulative incidence 1.9 %, subdistribution hazard ratio (SHR) 1.17, 95 % confidence interval (CI) 1.06-1.30 compared with 1.3 % in ductal tumors, p = 0.002). Age was also associated with an increased risk of contralateral breast cancer within 6 months (SHR 2.34, 95 % CI 2.08-2.62, p < 0.002 for patients over the age of 75 as compared to patients younger than 50 years). The absolute risk of contralateral breast cancer within 6 months is only slightly increased in patients with a lobular tumor and older patients. In our view, this small increased risk does not justify standard use of preoperative MRI based on tumor morphology or age alone. We propose a more personalized strategy in which additional risk factors (family history, prognosis of primary tumor, and others) may play a role.

Clinical differentiation between acute appendicitis and acute mesenteric lymphadenitis in children.

INTRODUCTION: Acute mesenteric lymphadenitis in children has a clinical presentation very similar to that of acute appendicitis. The aim of this study was to evaluate whether it is possible to clinically differentiate between acute appendicitis and acute mesenteric lymphadenitis in children. METHODS: A prospective cohort analysis was performed for all children (<17 years) presenting to the emergency department of our institution with acute abdominal pain between June 2005 and July 2006. The relevant clinical parameters, clinical and radiological diagnoses and all management decisions were scored prospectively. Ultrasound was the primary imaging modality for the majority of patients. All patients were re-evaluated until a final diagnosis was attained. The Alvarado score was calculated retrospectively, and a logistic regression model was used to analyze the diagnostic potential of clinical parameters. RESULTS: 289 patients were eligible for analysis. 38 patients had acute mesenteric lymphadenitis, and 69 patients had acute appendicitis as a final diagnosis. The positive predictive values of the clinical diagnosis, the Alvarado score and the logistic regression model were 0.62, 0.81 and 0.79 respectively. Ultrasound had a positive predictive value of 96% for acute appendicitis. CONCLUSION: It is not possible to accurately distinguish acute mesenteric lymphadenitis from acute appendicitis in children using clinical evaluation alone. Ultrasound should be performed in equivocal cases.

Colonic diverticulitis: a prospective analysis of diagnostic accuracy and clinical decision-making.

OBJECTIVE: To evaluate the diagnostic accuracy of clinical evaluation and cross-sectional imaging modalities such as ultrasound and computed tomography for patients with suspected colonic diverticulitis and to determine the value of these examinations in clinical decision-making. METHOD: A prospective analysis was conducted of 802 consecutive patients that presented with abdominal pain at the emergency department. Initial clinical diagnoses and management proposals were compared to the final diagnoses and therapeutic strategies for all patients. RESULTS: Fifty-seven patients were identified with colonic diverticulitis as the final diagnosis. The positive and negative predictive values for the clinical diagnosis of colonic diverticulitis were 0.65 and 0.98 respectively. Additional cross-sectional imaging had a positive and negative predictive value of respectively 0.95 and 0.99 or higher. These additional examinations led to a correct change of the initial clinical diagnosis in 37% of the patients, and a change in management in only 7%. CONCLUSION: The accuracy of the clinical diagnosis for colonic diverticulitis is low. Ultrasound and computed tomography have superior diagnostic accuracy but these examinations rarely change the initial management proposal.

[Sensible family planning: pitfalls and dilemmas]. / Verstandige gezinsplanning: valkuilen en dilemma's.

In a recent article in this journal it was stated that Dutch women were sensible in having their first child between the ages of 25 and 35 years. One of the conclusions was that associated health risks increase after the age of 35 but are still acceptable even at the age of 40. We demonstrate that these conclusions were based on flawed assumptions. Postponing pregnancy until after the age of 30 increases the risks of infertility and breast cancer. Motherhood at a later age is associated with an increase in obstetrical complications, miscarriage and other adverse effects on the child. Therefore, for couples planning a family with 2 children or more, it would be sensible to have the first pregnancy not long after the mother reaches the age of 30 years, or even earlier. Couples should be informed on the risks of late parenthood in order to be able to take the right decisions concerning family planning.

[Perinatal mortality in The Netherlands: an audit is now more necessary than ever]. / Perinatale sterfte in Nederland: audit dringend nodig.

In 1999, The Netherlands was found to have the highest perinatal mortality rate (11.4 per thousand), according to the WHO definition, in comparison with 14 other European countries. Many explanations were given, amounting essentially to a higher percentage of women with one or more risk factors (higher age at delivery, more non-western immigrants, and more multiple pregnancies). Furthermore, screening for congenital anomalies was not yet an issue at that time in The Netherlands. Finally, Dutch obstetricians and paediatricians have a restrictive policy regarding the treatment of newborns with a very poor prognosis. There are, however, also doubts about the quality of the delivered perinatal care. In an audit feasibility study in 2004 in a representative part of The Netherlands, it was found that in 9% of the cases of perinatal mortality, substandard care was (very) probably related to the mortality. In The Netherlands, a nationwide perinatal audit programme will start this year. The Netherlands, with its specific obstetric care system, has the obligation to look for the causes of perinatal mortality and to introduce improvements based on the results of a perinatal audit. Hasty conclusions are a threat to a careful audit.

Supracondylar fractures of the humerus in children. Comparison of results in two treatment periods.

Displaced supracondylar fractures of the humerus in children may be managed with or without Kirschner-wire fixation. The results of treatment of displaced supracondylar fractures of the humerus in children were analyzed, comparing the period before and after an audit of our results in 1997. From 1998 onward a more active policy regarding the use of percutaneous Kirschner-wire fixation was adopted. We treated 33 children between 1991 and 1997 (Period 1) and 49 children between 1998 and 2004 (Period 2). In Period 1, closed reduction and plaster immobilisation was performed in 29 patients. Four received initial Kirschner-wire fixation with plaster immobilisation. Secondary dislocation necessitating re-reduction occurred in 14 patients. In Period 2 initial Kirschner-wire fixation was performed in 41 patients, of whom 23 had open reduction. The other eight had conservative treatment consisting of closed reduction and plaster immobilization, two of them needing re-reduction. This evaluation indicates that a more active policy with regard to (open) reduction with Kirschner-wire fixation in displaced supracondylar humeral fractures in children, results in less need for secondary intervention with comparable functional and cosmetic outcome.

[Obstetric care in The Netherlands under assessment again]. / De verloskundige zorg in Nederland opnieuw de maat genomen.

According to the Peristat II study, based on data from 2004, The Netherlands has almost the highest perinatal mortality rate in Europe. In 2006 perinatal mortality in The Netherlands was also higher than in the Flemish part of its neighbouring country Belgium (10.40 per thousand versus 7.76 per thousand). The difference in perinatal mortality between Flanders and The Netherlands cannot be explained by the risk factors analysed in the Peristat study, nor by the Dutch system of home deliveries. It is more likely that the attitude of Dutch professionals is too expectative, based on too much confidence in a non-intervention policy. Since the Peristat I publication many measures have been taken in The Netherlands in order to improve the quality of perinatal care. The most important are the start of the perinatal audit preparations, better prenatal screening and the introduction of preconception care.

Primary retroperitoneal mucinous cystadenoma with sarcoma-like mural nodule : a case report and review of the literature.

Primary retroperitoneal cystadenomas are extremely rare. This is the first report in literature to describe a primary retroperitoneal cystadenoma with a sarcoma-like mural nodule. A 45-year-old woman complained of a left-sided abdominal mass. A computed tomography scan revealed a cystic mass with a mural nodule, which seemed to originate from the tail of the pancreas. At laparotomy the cyst was not adhered to the pancreas but localized retroperitoneally. Histologic examination showed a mucinous cystadenoma with only foci of borderline malignancy with a mural "sarcoma-like" nodule. In view of the surgical and histopathological findings, the mucinous cystadenoma was regarded as primary retroperitoneal. This case demonstrates that in the era of radiological preoperative refinement, pathological diagnosis remains of utmost importance, especially for rare cases.

[The consequences of postponing pregnancy]. / Gevolgen van uitstel van zwangerschap.

The postponement of childbearing is determined by societal factors and is related to the fact that it is often difficult for women to combine an education, a job or a career with having children and taking care of a family. Especially gynaecologists are increasingly confronted with women who undergo the medical consequences of such postponement. Postponing the first pregnancy is accompanied by an increased risk of unwanted infertility. If women do succeed in becoming pregnant later in life, there is an increased risk of complications during pregnancy and delivery. The child runs a greater risk of chromosomal aberrations and of mental and physical handicaps related to increased numbers of premature births and fertility treatments. All these problems begin to increase after age 30, but especially after age 35. Finally, the risk of breast cancer is also increased if a woman delays the birth of her first child or remains childless.

[Fertility treatments: possibilities for fewer multiple births and lower costs--the 'Umbrella' study]. / Vruchtbaarheidsbehandelingen: mogelijkheden voor minder meerlingen en lagere kosten--de 'Paraplustudie'.

Since the 1980s, increasingly more fertility treatments have been performed in the Netherlands. The use of ovarian hyperstimulation during in vitro fertilisation (IVF) and intrauterine insemination (IUI) has contributed to an explosive increase in the number of multiple births. To control the costs of treatment and outcomes, the Minister of Health, Welfare and Sport commissioned research on possible improvements in the performance of fertility treatments in 1999. The results of this research ('Umbrella study'), reported in 2005, suggested that costs and the incidence of multiple births could be reduced if (a) IUI is only performed if the chance of spontaneous pregnancy is less than 30%; (b) the guideline 'Intrauterine insemination' is followed more closely regarding hormonal stimulation; (c) stimulation is used less frequently during IVF; and (d) no more than 1 embryo is placed in the uterus at a time. To achieve these results, all parties involved must revise their policies. In particular, current reimbursement regulations inhibit the implementation of the research results in practice.

Stress and outcome success in IVF: the role of self-reports and endocrine variables.

BACKGROUND: The aim of this study was to examine the associations between urinary levels of the stress hormones adrenaline, noradrenaline and cortisol during treatment with self reported stress, in order to investigate the mechanism for the previously observed negative association of anxiety and depression with the outcome of IVF/ICSI. METHODS: In a multicentre prospective cohort study, women entering their first cycle of IVF/ICSI treatment were asked to participate. From each participant nocturnal urine samples were collected; pre-treatment, before oocyte retrieval and before embryo-transfer (ET), to assess hormonal concentrations. Additionally, two questionnaires were administered before the start of the treatment to measure anxiety and depression. RESULTS: 168 women completed the questionnaires and collected at least two urine specimens. A significant positive correlation between urinary adrenaline concentrations at baseline and ET and the scores on depression at baseline were found. In women with successful treatment, lower concentrations of adrenaline at oocyte retrieval and lower concentrations of adrenaline and noradrenaline at ET, compared with unsuccessful women, were found. CONCLUSIONS: The significant positive association of adrenaline concentration with pregnancy and with depression suggested that this adrenal hormone could be one of the links in the complex relationship between psychosocial stress and outcome after IVF/ICSI.

The effect of episodic anxiety on an in vitro fertilization and intracytoplasmic sperm injection treatment outcome: a pilot study.

This study examines whether the inconsistent and contradictory findings from prospective studies on the effect of psychosocial factors on treatment outcome of in vitro fertilization (IVF) can be explained by the fact that no clear distinction has been made between acute and chronic emotional stress responses. Because chronicity is difficult to measure within the context of an IVF-procedure, the focus of the present study was on episodic anxiety. We compared its predictive value on treatment outcome after the second IVF and intracytoplasmic sperm injection (ICSI) with the predictive value of trait anxiety and acute anxiety. In a prospective study with 47 women who failed to conceive after the first IVF, state anxiety was measured both before and after the first IVF treatment. Episodic anxiety was operationalized as high state anxiety both before and after the first IVF treatment Student's t-test and logistic regression analysis were used to determine the predictive value of episodic anxiety compared with acute or trait anxiety. Women with episodic anxiety, but not those with high levels of trait or acute anxiety, were less likely to become pregnant after the second IVF/ICSI. The results suggest that future studies should differentiate between acute and chronic stress, when examining the effects of psychosocial factors on treatment outcome after a fertility treatment

[Angiosarcoma following breast-conserving therapy]. / Angiosarcoom na borstsparende behandeling.

Two women with breast cancer, 59 and 72 years of age, were treated by means of breast-conserving surgery and radiotherapy. At the age of 66 and 77, respectively, discolouration of the skin was seen in the treated breast. Punch biopsy did not show secondary malignancy. Diagnostic (deeper) excisional biopsy revealed angiosarcoma. Ablation of the breast was performed in both patients. The younger woman, however, had a recurrence four months later that was treated with wide local excision and omentum-plasty. The older woman died two years after the ablation as a result of haematogenous metastases. Knowledge of the symptoms and diagnostic pitfalls of radiotherapy-induced angiosarcoma after breast-conserving treatment is important in the follow-up of breast-cancer patients. Histological diagnosis of a biopsy taken at sufficient depth is indicated when a secondary angiosarcoma is suspected.

A randomized placebo-controlled study of the effect of transdermal vs. oral estradiol with or without gestodene on homocysteine levels.

OBJECTIVE: To assess the effect of transdermal vs. oral administration of E2 on plasma homocysteine levels and to evaluate the impact of adding a progestogen to these regimens. DESIGN: Prospective, double-blind, double-dummy, placebo-controlled study. SETTING: Outpatient clinics in two university hospitals and two teaching hospitals in The Netherlands. PATIENT(S): One hundred fifty-two healthy hysterectomized postmenopausal women. INTERVENTION(S): Thirteen 28-day treatment cycles with placebo (n = 49); transdermal 17beta-E2, 50 microg (n = 33), oral E2, 1 mg (n = 37), or oral E2, 1 mg, plus gestodene, 25 microg (n = 33), followed by four cycles of placebo in each group. MAIN OUTCOME MEASURE(S): Fasting plasma total homocysteine concentrations at baseline and cycle 4, 13, and 17. RESULT(S): Mean (+/-SD) homocysteine concentrations in the oral E2 group decreased from baseline to cycle 4 (9.0 +/- 2.5 micromol/L vs. 8.2 +/- 2.0 micromol/L; mean change, -7.6%). Homocystine values in the oral E2 plus gestodene group did not change substantially from baseline to cycle 4 (8.9 +/- 1.6 micromol/L vs. 8.6 +/- 2.0 micromol/L; mean change, -4.4%). No significant changes were observed in the transdermal E2 group. After four washout cycles, the homocysteine concentration had returned to baseline values in all groups. CONCLUSION(S): Oral E2 therapy reduced the homocysteine concentration more than did therapy with transdermal E2 or oral E2 plus gestodene. This finding may indicate a role of liver metabolism and suggests that gestodene has a negative effect on these changes.