Clinical management of borderline tumours of the ovary: results of a multicentre survey of 323 clinics in Germany

The aim of this survey was to analyse the standard of care in diagnostic, surgery, chemotherapy and aftercare management for patients with borderline tumours of the ovary (BOTs) in Germany. A structured questionnaire comprising different dimensions was sent to all 1114 gynaecological departments. The questionnaire could be returned anonymously. The overall response rate was 29.0% (323 departments). Most departments were on secondary care (71.8%), tertiary care (23.2%) or university hospital (5.0%) level. Most clinicians performed not more than five BOT operations (89.2%) per year. Most departments (93.2%) used in addition to classical bimanual examination and vaginal ultrasound, tumour marker CA-125 detection, CT scan, MRI or PET-CT techniques. Departments in university and tertiary care hospitals performed more often a fresh frozen section (87 vs 64%). In young women, clinicians performed much seldom unilateral salpingo-oophorectomy (92%) and only in 53% biopsies of the contralateral ovary. Generally, biopsies of the contralateral ovary were performed in 4–53% of the patients. Chemotherapy was mostly favoured in ‘high-risk' patients with tumour residual, microinvasion or invasive implants. Thus, a high grade of insecurity in diagnostic and therapy of BOT exists in some gynaecological departments and underlines the need for more educational and study activities

The patient experience

The impact of improved treatments for the management of hormone-sensitive breast cancer extends beyond clinical responses. Thanks to appropriate literature and access to the internet, patient awareness of treatment options has grown and patients are now, in many cases, able to engage their oncologists in informed conversations regarding treatment and what to expect in terms of efficacy and safety. Indeed, patients realize that although there is no cure for metastatic disease, treatment can greatly reduce the risk of progression and in the adjuvant setting, where treatment is administered with a curative intent, current treatment options reduce the risk of relapse. The approval of letrozole throughout the breast cancer continuum has provided patients with many reassuring options. The improvement in outcome with letrozole is achieved without a detrimental effect on overall quality of life. Adverse events such as hot flushes, arthralgia, vaginal dryness, and potential osteoporosis are most significant from the patient’s perspective, and it is important that caregivers pay attention to patients experiencing these events, as they can impact compliance unless effectively explained and managed. The major benefits of letrozole are to improve prospects for long-term survivorship in the adjuvant setting and to delay progression and the need for chemotherapy in the metastatic setting

A Controversy That Has Been Tough to Swallow: Is the Treatment of Achalasia Now Digested?

Esophageal achalasia is a rare neurodegenerative disease of the esophagus and the lower esophageal sphincter that presents within a spectrum of disease severity related to progressive pathological changes, most commonly resulting in dysphagia. The pathophysiology of achalasia is still incompletely understood, but recent evidence suggests that degeneration of the postganglionic inhibitory nerves of the myenteric plexus could be due to an infectious or autoimmune mechanism, and nitric oxide is the neurotransmitter affected. Current treatment of achalasia is directed at palliation of symptoms. Therapies include pharmacological therapy, endoscopic injection of botulinum toxin, endoscopic dilation, and surgery. Until the late 1980s, endoscopic dilation was the first line of therapy. The advent of safe and effective minimally invasive surgical techniques in the early 1990s paved the way for the introduction of laparoscopic myotomy. This review will discuss the most up-to-date information regarding the pathophysiology, diagnosis, and treatment of achalasia, including a historical perspective. The laparoscopic Heller myotomy with partial fundoplication performed at an experienced center is currently the first line of therapy because it offers a low complication rate, the most durable symptom relief, and the lowest incidence of postoperative gastroesophageal reflux

Living Donor Liver Transplantation in Patients 70 Years or Older

PubMed ID: 25606791Previous published studies have shown that age is not a contraindication for deceased donor liver transplantation. The data about elderly recipient after living donor liver transplantation (LDLT) is unsatisfactory. The aim of this study was to evaluate the outcome of the LDLT with recipients aged 70 years or older. Patients and Methods Between 2005 and 2013, 469 patients underwent LDLTs. The clinical characteristics, preoperative, intraoperative, and postoperative data, graft, and patients' survival of these patients were retrospectively analyzed. All recipients who were 70 years or older at the time of liver transplantation were indentified. The results were compared to the results of the patients younger than 70 years. Results There were 12 patients (2%) 70 years or older. All patients received the right lobe of their donor in a standard technique. One patient died postoperatively because of pulmonary infection, and one patient died 6 months after the operation because of graft failure after cardiac infarction. The comorbidity score of these two patients were significantly higher compared to the other ten patients without any complications (8.5 vs. 4.6, P = 0.01). The 1-year and 3-year patient and graft survival was 84%. There were no significant differences in complications, hospital stay, perioperative mortality, or median survival compared to the younger group. Conclusion Although the number of the patients is small, our study emphasizes that LDLT of patients 70 years or older can be performed safely in patients without major comorbidities. Elderly patients with increased risk for postoperative complications should be excluded from LDLT. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved

Mutations in the EGF-CFC gene Cryptic are an infrequent cause of congenital heart disease

Cryptic (CFC1), a member of the epidermal growth factor-Cripto/FRL-1/Cryptic (EGF-CFC) gene family, is involved in the evolutionarily conserved establishment of left-right lateral asymmetry. Inactivation of Cfc1 in mice results in laterality defects and complex cardiac malformations. Similarly, mutations in the human CFC1 gene have been identified in patients with heterotaxy syndrome. The cardiac defects in humans resemble those in mice lacking Cfc1. We postulated that some patients with isolated cardiac malformations could also have mutations in the CFC1 gene. Our analysis of the CFC1 gene in 167 patients with congenital heart disease revealed a novel A145T missense variant in 3 patients with type II atrial septal defect. Furthermore, we found the previously characterized R78W polymorphism in another patient with type II atrial septal defect. However, the A145T sequence alteration was also identified in 3 controls, suggesting that this variant is a polymorphism. We conclude that CFC1 variants could be a rare cause of congenital heart disease in patients without laterality defects

Sequence analysis of myozenin 2 in 438 European patients with familial hypertrophic cardiomyopathy

Background: Familial hypertrophic cardiomyopathy (HCM) is an allelic cardiac disorder characterized by increased ventricular wall mass and sudden cardiac death. A variety of dominant single-gene mutations in sarcomeric genes have been identified, indicating a highly heterogeneous genetic etiology. MYOZ2 encodes for sarcomeric calsarcin-1 located in the myocardial z-disc, a focal point of HCM disease genes. Very recently mutations in MYOZ2 were reported as a cause for HCM. To assess the prevalence of MYOZ2 mutations among European HCM patients, coding exons weree analyzed for genetic variants in 438 patients. Material/Methods: Four hundred thirty-eight patients with HCM in four European cardiovascular centers were recruited. The coding region of MYOZ2 was directly sequenced in all the HCM subjects. Results: Two non-synonymous polymorphisms in exon 2 (rs17851524) and exon 5 (rs7687613) of MYOZ2 were identified in eight and twenty-two patients, respectively. However, no disease-causing mutations could be identified in this large cohort of HCM patients. Conclusions: Although a large cohort of more than 400 patients with familial HCM was screened, a disease-associated mutation in MYOZ2 was not identified. When these results are combined with previous reports, it can be concluded that MYOZ2 mutations are rare causes of familial HCM

Dysfunction of dysferlin-deficient hearts

Mutations in the gene encoding dysferlin cause limb-girdle muscular dystrophy 2B (LGMD2B), a disorder that is believed to spare the heart. We observed dilated cardiomyopathy in two out of seven LGMD2B patients and cardiac abnormalities in three others. Cardiac biopsies showed that dysferlin was completely absent from the sarcolemma and appeared to be trapped within the cardiomyocytes. SJL/J mice (33-week-old) had diminished end-systolic pressure and reduced dP/dt; however, the hearts were histologically normal. Gene expression profiles of cardiac tissue were obtained and later confirmed by quantitative RT-PCR. Dysferlin-deficient and control mice had different gene expression patterns in terms of cardiomyocyte Z-disc and signal transduction proteins. CapZ, LIM-domain-binding protein 3 (LDB3, MLP), cypher (ZASP), desmin, and the cardiac ankyrin-repeated protein (CARP) were differentially expressed, compared to controls. Mechanical stress induced by the nonselective beta-adrenergic agonist isoproterenol (5 mg/kg body weight) given daily for 10 days resulted in reduced fractional shortening and increased cardiac fibrosis in SJL/J mice as compared to controls. Isoproterenol also caused metalloproteinase-2 upregulation in SJL/J mice. In A/J mice, the effect of isoproterenol injection was even more dramatic and lead to premature death as well as marked sarcolemmal injury as demonstrated by Evans blue dye penetration. Our data suggest that disturbances in dysferlin as well as Z-line proteins and transcription factors particularly under mechanical stress cause cardiomyopathy