Targeted Therapeutic Approaches in Vulvar Squamous Cell Cancer (VSCC): Case Series and Review of the Literature

Therapeutic options in recurrent or metastasized vulvar squamous cell cancer (VSCC) not amenable to radiotherapy or radical surgery are limited. Evidence for the use of targeted therapies is sparse. All patients with VSCC treated at the Gynecological Cancer Center Hamburg-Eppendorf 2013–2019 were retrospectively evaluated for targeted therapeutic approaches. Furthermore, a MEDLINE, EMBASE, Web of Science, Scopus, and OVID database search was performed using the terms: “vulvar cancer” AND “targeted therapy,” “erlotinib,” “EGFR,” “bevacizumab,” “VEGF,” “pembrolizumab,” or “immunotherapy.” Twelve of 291 patients (4.1%) with VSCC received at least one targeted therapy at our institution. Previously, one or more platinumbased chemotherapy was applied to all patients [median 3.5 previous lines (range 2–5)]. In the erlotinib subgroup, two of five patients (40%) achieved stable disease (SD), while two patients (2/5, 40%) experienced partial response (PR). Treatment was given as monotherapy in second/third line for a median of 3.4 months (range 2–6 months). Bevacizumab (n = 9) was given as maintenance therapy after platinum-based first-line chemotherapy (9/9); best response was complete response (CR) (n = 2/9 22.2%). Median duration of treatment was 7 months (range 4–13 months) with two patients still under ongoing treatment. Best response in the pembrolizumab (n = 3) subset was SD (n = 1/3 33%). Treatment was given as monotherapy in second/third line for a median of 3.3 months (range 3–4 months). Nine of 12 patients (75%) experienced treatment-related adverse events (TRAEs), most commonly grade 1/2. Rapidly evolving antibody treatments have proven clinical benefit especially in HPV-driven tumor entities; however, clinical investigations in VSCC are still limited. These reported cases provide evidence for the clinical utility and feasibility while ensuring an acceptable safety profile.     

Initial experience with the new type A arch dissection stent: restoration of supra-aortic vessel perfusion

Open in a separate window OBJECTIVESThe goal of the present study is to investigate changes in supra-aortic vessel perfusion after implantation of the non-covered Ascyrus Medical Dissection Stent (AMDS) for surgical treatment of acute type A aortic dissection.METHODSFrom 2017 to 2020, 16 consecutive patients treated with AMDS and involvement (dissection to total occlusion) of at least 1 supra-aortic vessel were included in the study. Centre-line based computed tomography measurements of true, false and total lumen area using Terarecon software were performed before and after surgery. Changes in the true lumen area were indexed to the entire vessel area. The paired sample t-test was used to assess the significance of the observed differences.RESULTSAnalysis of supra-aortic vessels and the descending aorta showed significant improvement in true lumen perfusion after the AMDS was implanted. The indexed true lumen area increased postoperatively by 72%, 112% and 30% in the innominate, right and left common carotid arteries, respectively. Total occlusions of both common carotid arteries recovered completely after surgical treatment. The proximal- and the mid-descending aorta showed a 78% and 48% improvement of the indexed true lumen area, respectively.CONCLUSIONSArch repair using AMDS shows promising results in the treatment of acute type A aortic dissection. Quantitative measurements of true and false lumen perfusion demonstrated a significant increase in true lumen area and a 100% regression of totally occluded supra-aortic branches. Further examination in a larger cohort of patients and comparison with isolated hemiarch repair are needed to confirm positive vascular remodelling after an AMDS implant.     

Durable mechanical circulatory support in patients with heart failure with preserved ejection fraction

Only few patients with heart failure with preserved ejection fraction undergo durable mechanical circulatory support implantation. We identified three patients with heart failure with preserved ejection fraction who needed durable mechanical circulatory support as bridge-to-transplant therapy. In two patients with hypertrophic cardiomyopathy, the hypertrophic papillary muscles and myocardium were resected to allow for subsequent left ventricular assist device implantation. In one patient, all visible parts of the mitral valve were additionally resected. The third patient with restrictive cardiomyopathy underwent Berlin Heart Excor BVAD implantation with left atrial cannulation.     

Real-time intraoperative co-registration of transesophageal echocardiography with fluoroscopy facilitates transcatheter mitral valve-in-valve implantation in cases of invisible degenerated bioprosthetic valves

 Open in a separate windowOBJECTIVESTranscatheter mitral valve-in-valve (TMViV) implantation is an alternative treatment to surgery for high-risk patients with degenerated bioprosthetic mitral valves. Some types of bioprostheses are fluoroscopically translucent, resulting in an ‘invisible’ target deployment area. In this study, we describe the feasibility and outcomes of this procedure using intraoperative fusion of transoesophageal echocardiography (TEE) and live fluoroscopy to facilitate valve deployment in cases of invisible bioprosthetic valves. METHODSWe reviewed all TMViV implantations at our centre from July 2014 to July 2019. Patient, procedure and outcome details were compared between those with a visible bioprosthesis (N = 22) to those with an invisible one (N = 12). Intra-operative TEE and live Fluoroscopy co-registration were used for real-time guidance for all invisible targets.RESULTSAll valve implantations were completed successfully in both groups without cardiovascular injury, valve migration or left ventricular outflow-tract obstruction. Technical success was 100% in both groups. One-year survival was 83% [95% confidence interval (CI) 70–96] for the entire cohort, with 79% (95% CI 63–100) survival for the visible group and 92% (95% CI 77–100) for the invisible group. Probability of 1-year survival free from mitral valve reintervention, significant valve dysfunction, stroke or myocardial infraction was 78% (95% CI 63–93) for all patients whereby the probability was 72% (95% CI 54–97) in the visible group and 80% (95% CI 59–100) for the invisible group.CONCLUSIONSThe use of intraoperative TEE and live fluoroscopy image fusion facilitates accurate TMViV among patients with a fluoroscopically invisible target-landing zone.     

Hyperactivity, neuromotor defects, and impaired learning and memory in a mouse model for metachromatic leukodystrophy

Deficiency of arylsulfatase A (ASA) causes the autosomal recessive lipidosis, metachromatic leukodystrophy (MLD). Performance on tests of activity, motor ability and learning/memory was assessed in ASA-deficient mice and normal controls at 3, 6 and 12 months-of-age. ASA-deficient mice showed consistently increased cage activity in all age groups, whereas open field activity was increased only in the 3-month-old group. Motor coordination and equilibrium, as tested in the rotarod test, was impaired in 12-month-old ASA-deficient mice. Passive avoidance learning was tested in the step-through box. Performance on this test was impaired in the 12-month-old group only. Spatial learning and memory abilities were tested in the Morris water maze. Six-month-old ASA-deficient mice displayed slightly impaired hidden-platform acquisition performance. Three-month-old animals, on the other hand, did not show any acquisition or retention defect on this task, notwithstanding significantly reduced swimming velocity. Acquisition training, both in the hidden- and visible-platform conditions of the Morris water maze, and retention performance during the probe trials were impaired in 12-month-old ASA-deficient mice. The hyperactivity, motor incoordination and slowing, and the age-related learning/memory defects, reported here in ASA-deficient mice, may relate to the decline of neuromotor and cognitive functions in MLD patients, and could be used as correlative or outcome measures in the study of MLD pathophysiology and treatment.     

AGO Algorithms for the Treatment of Breast Cancer: Update 2021

Therapy options shown in the algorithms are based on the current AGO recommendations, but cannot represent all evidence-based treatment options, since prior therapies, performance status, comorbidities, patient preference, etc. must be taken into account for the actual treatment choice. In individual cases, other evidence-based treatment options may also be appropriate and justified. Regardless of approval status, the algorithms only take into account drugs that were available in Germany at the time the algorithm was last updated. Here we present the 2021 update of AGO treatment algorithms for early and metastatic breast cancer, which are intended to intensify structured treatment decision by providing reproducible and evidence-based treatment paths and may be helpful for a broad treatment landscape.Key words: therapy algorithms, evidence-based treatment, breast cancer guidelines     

Role of Thyroid Surgery in the Obstructive Sleep Apnea Syndrome

Objectives

To study the impact of thyroid surgery on obstructive sleep apnea syndrome (OSAS) evaluated by the apnea/hypopnea index (AHI) was studied. Secondary objectives were to evaluate the impact on the positional component of OSAS and to highlight possible predictors of improvement of OSAS after thyroidectomy.

Methods

Twenty-eight patients with OSAS are included in this monocentric study: they underwent total thyroidectomy (n = 26) or left loboisthmectomy. Postoperative assessment involves a nocturnal control polysomnography as of 60 days after surgery.

Results

The mean age at the time of surgery is 61.3 years (standard deviation ±7.3) and average body mass index is 29.6 kg/m² (±7.3). Continuous positive airway pressure (CPAP) treatment is introduced preoperatively in 82 % of patients. The statistical analysis shows a significant decrease of 33 % in postoperative AHI for the total population (p = 0.001), 77 % in patients under CPAP (p = 0.05), and 27 % in patients without CPAP (p = 0.02). CPAP therapy could be released in four patients. Given the limited number of subjects studied, the surgery did not impact on the positional component of the OSAS. Statistical analysis failed to link a predictive factor to AHI reduction.

Conclusions

We propose thyroid surgery as an alternative or as a complement to CPAP treatment for the patients with goitre: it allows a significant decrease in postoperative AHI, allowing adaptation of the CPAP treatment downward, or even a release in some cases. These results need to be confirmed on a larger series of patients in a prospective study with standardized criteria for polysomnography and multivariate analysis.     

Continuous cervix measurement (author's transl)]

A new technique has been devised for high-continuity recording of cervical dilatation during labour. The measuring principle is based on Hall's effect. The sensor is superior to conventional methods by its smaller dimensions and weight and the possibility of on-line processing. The new method is used in conjunction with cardiotocography to test the action of medicaments upon cervical behaviour and labour.     

A single origin for the most frequent mutation causing late infantile metachromatic leucodystrophy.

Metachromatic leucodystrophy is an autosomal recessive degenerative disease of the nervous system caused by the deficiency of the lysosomal enzyme arylsulphatase A (ARSA). We report here on the high incidence of late infantile MLD among Muslim Arabs originating from Jerusalem, most probably because of a founder effect. All the patients were found to be homozygous for 459 + 1 G-->A, a mutation which destroys the splice donor site of exon 2 of the ARSA gene. This mutation has been reported to be the most common mutation causing MLD. We studied the ARSA haplotype defined by three intragenic polymorphic sites in DNA samples from Muslim Arab patients from Jerusalem, a Christian Arab patient originating from the region, and eight other white patients, all homozygous for the 459 + 1 G-->A mutation. All the alleles carried the same haplotype which is in complete linkage disequilibrium with the mutation. This finding indicates a common origin for the 459 + 1 G-->A mutation which may have been introduced into Jerusalem at the time of the Crusades.