Toward a Flexible Variable Stiffness Endoport for Single-Site Partial Nephrectomy.

Laparoscopic partial nephrectomy for localized renal tumors is an upcoming standard minimally invasive surgical procedure. However, a single-site laparoscopic approach would be even more preferable in terms of invasiveness. While the manual approach offers rigid curved tools, robotic single-site systems provide high degrees of freedom manipulators. However, they either provide only a straight deployment port, lack of instrument integration, or cannot be reconfigured. Therefore, the current main shortcomings of single-site surgery approaches include limited tool dexterity, visualization, and intuitive use by the surgeons. For partial nephrectomy in particular, the accessibility of the tumors remains limited and requires invasive kidney mobilization (separation of the kidney from the surrounding tissue), resulting in patient stress and prolonged surgery. We address these limitations by introducing a flexible, robotic, variable stiffness port with several working channels, which consists of a two-segment tendon-driven continuum robot with integrated granular and layer jamming for stabilizing the pose and shape. We investigate biocompatible granules for granular jamming and demonstrate the stiffening capabilities in terms of pose and shape accuracy with experimental evaluations. Additionally, we conduct in vitro experiments on a phantom and prove that the visualization of tumors at various sites is increased up to 38% in comparison to straight endoscopes.

Adjuvant sequential chemoradiation therapy in high-risk endometrial cancer: results of a prospective, multicenter phase-II study of the NOGGO (North-Eastern German Society of Gynaecological Oncology).

PURPOSE: The management of high-risk endometrial cancer (HREC) remains controversial. We conducted a prospective multicenter phase-II clinical trial to evaluate an adjuvant chemotherapy (CT) with sequential radiotherapy (RT) in patients with HREC. METHODS: Patients with HREC from 8 institutions in Germany were enrolled. After surgery, patients received four cycles of paclitaxel 175 mg/m² (P) and carboplatin AUC5 (C) (d1, q21d) and subsequent external pelvic radiation therapy (1.8 Gy/d, d1-5) at a total dose of 45 Gy with vaginal brachytherapy (3 × 5 Gy). Quality of life (QoL) was assessed using the EORTC-QLQ-C30 questionnaire. Primary endpoints were tolerability, toxicity and QoL. Progression-free survival (PFS) was defined as secondary endpoint. RESULTS: Thirty-five patients were enrolled from 2004 through 2008. Median follow-up was 24 months (range 3-24 months). All patients received 4 cycles of P and C and completed RT. Overall, grade 3/4 haematological toxicity was 25.6 %. Three cycles were delayed because of leukopenia. Grade 3/4 non-haematologic toxicities were rare (≤3 %). No overall change in QoL occurred during treatment. Two-year median PFS and OS rates were both 75.8 %. CONCLUSIONS: Adjuvant combination CT with P + C and sequential RT is well tolerated and a feasible regimen in patients with HREC. Subsequent phase-III trials are warranted.

The 21-gene recurrence score assay impacts adjuvant therapy recommendations for ER-positive, node-negative and node-positive early breast cancer resulting in a risk-adapted change in chemotherapy use.

BACKGROUND: We carried out a prospective clinical study to evaluate the impact of the Recurrence Score (RS) on treatment decisions in early breast cancer (EBC). PATIENTS AND METHODS: A total of 379 eligible women with estrogen receptor positive (ER+), HER2-negative EBC and 0-3 positive lymph nodes were enrolled. Treatment recommendations, patients' decisional conflict, physicians' confidence before and after knowledge of the RS and actual treatment data were recorded. RESULTS: Of the 366 assessable patients 244 were node negative (N0) and 122 node positive (N+). Treatment recommendations changed in 33% of all patients (N0 30%, N+ 39%). In 38% of all patients (N0 39%, N+ 37%) with an initial recommendation for chemoendocrine therapy, the post-RS recommendation changed to endocrine therapy, in 25% (N0 22%, N+ 39%) with an initial recommendation for endocrine therapy only to combined chemoendocrine therapy, respectively. A patients' decisional conflict score improved by 6% (P = 0.028) and physicians' confidence increased in 45% (P < 0.001) of all cases. Overall, 33% (N0 29%, N+ 38%) of fewer patients actually received chemotherapy as compared with patients recommended chemotherapy pre-test. Using the test was cost-saving versus current clinical practice. CONCLUSION: RS-guided chemotherapy decision-making resulted in a substantial modification of adjuvant chemotherapy usage in node-negative and node-positive ER+ EBC.

Lysosomal dysfunction causes neurodegeneration in mucolipidosis II 'knock-in' mice.

Mucolipidosis II is a neurometabolic lysosomal trafficking disorder of infancy caused by loss of mannose 6-phosphate targeting signals on lysosomal proteins, leading to lysosomal dysfunction and accumulation of non-degraded material. However, the identity of storage material and mechanisms of neurodegeneration in mucolipidosis II are unknown. We have generated 'knock-in' mice with a common mucolipidosis II patient mutation that show growth retardation, progressive brain atrophy, skeletal abnormalities, elevated lysosomal enzyme activities in serum, lysosomal storage in fibroblasts and brain and premature death, closely mimicking the mucolipidosis II disease in humans. The examination of affected mouse brains at different ages by immunohistochemistry, ultrastructural analysis, immunoblotting and mass spectrometric analyses of glycans and anionic lipids revealed that the expression and proteolytic processing of distinct lysosomal proteins such as α-l-fucosidase, ß-hexosaminidase, α-mannosidase or Niemann-Pick C2 protein are more significantly impacted by the loss of mannose 6-phosphate residues than enzymes reaching lysosomes independently of this targeting mechanism. As a consequence, fucosylated N-glycans, GM2 and GM3 gangliosides, cholesterol and bis(monoacylglycero)phosphate accumulate progressively in the brain of mucolipidosis II mice. Prominent astrogliosis and the accumulation of organelles and storage material in focally swollen axons were observed in the cerebellum and were accompanied by a loss of Purkinje cells. Moreover, an increased neuronal level of the microtubule-associated protein 1 light chain 3 and the formation of p62-positive neuronal aggregates indicate an impairment of constitutive autophagy in the mucolipidosis II brain. Our findings demonstrate the essential role of mannose 6-phosphate for selected lysosomal proteins to maintain the capability for degradation of sequestered components in lysosomes and autophagolysosomes and prevent neurodegeneration. These lysosomal proteins might be a potential target for a valid therapeutic approach for mucolipidosis II disease.

WITHDRAWN: The safety of synthetic paclitaxel by intralesional delivery with OncoGeltrade mark into skin breast cancer metastases: method and results of a clinical pilot trial.

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Unilateral ovarian agenesis: report of three cases and review of the literature.

INTRODUCTION: Unilateral ovarian agenesis is a rare event and only a few case have been reported. CASE REPORT: We present three additional cases, where patients presented with diffuse lower abdominal pain. During laparoscopy, an unilateral ovarian agenesis was observed in the three cases. DISCUSSION: There are two possible explanations of a unilateral ovarian absence, involving an asymptomatic adnexal torsion or congenital absence. Unknown environmental factors or genetic predisposition could contribute to this kind of anomaly.

Effectiveness of Trastuzumab (Herceptin) in a patient with locally recurrent breast cancer after cardiac failure caused by severe cytotoxic pretreatment.

In HER2-positive breast cancer patients, the humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) may improve overall survival. No reports exist regarding the application of trastuzumab in patients with cytotoxically induced cardiac failure and decreased left ventricular ejection fraction or about locally recurrent and advanced disease. In this case report, trastuzumab resulted in a complete and long-lasting response of recurrent and locally advanced breast cancer and was well tolerated in a severely cytotoxically pretreated patient with cardiac failure. We encourage other oncologists to offer trastuzumab also to severely cytotoxically pretreated patients with conditions after cardiac insufficiency or with locally advanced breast cancer.