Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group

Annals of Surgical Oncology - Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly...     

Effectiveness of manual lymphatic drainage vs. perineal massage in secundigravida women with gestational oedema: A randomised clinical trial

Perineal trauma (PT) may be considered as a very common injury during the childbirth. The incidence of PT was estimated in 30% to 85%, with 60% to 70% requiring suture. The present study was a prospective, single‐blinded, randomised, clinical trial carried out from January 2015 to January 2016. For this study, 49 secundigravida women diagnosed with gestational oedema were recruited and randomly divided into two groups (A and B). Group A (n = 30) received the conventional treatment plus perineal massage and group B (n = 19) the conventional treatment plus manual lymphatic drainage (MLD). Visual analogue scale (VAS) and King Health's Questionnaire (KHQ) were performed to assess pain intensity and quality of life‐related with urinary incontinence (UI). Pain intensity measurements showed statistically significant differences for a decrease after 30‐weeks (P = .037), after 36‐weeks (P = .000), and at the end of puerperium (P = .014) for MLD with respect to perineal massage group. Moreover, inter‐groups repeated measures ANOVA for the values related statistically significant differences to the interaction of each applied treatment (perineal massage and MLD group, separately) over the pain intensity variable. MLD treatment reduced pain intensity with respect to perineal massage in secundigravida women with gestational oedema from 25‐weeks of gestation to the end of puerperium.     

Serum proteome of dogs at subclinical and clinical onset of canine leishmaniosis

The objective of this study was to identify changes in serum proteome in dogs that may occur after an experimental infection at subclinical and clinical stages of canine leishmaniosis (CanL). For this purpose, canine pre‐ and post‐infection with Leishmania infantum serum proteomes in the same dogs were analysed by a high‐throughput label‐based quantitative LC‐MS/MS proteomic approach. A total of 169 proteins were identified, and 74 of them including complement C8 alpha chain, adiponectin, transferrin, sphingomyelin phosphodiesterase acid‐like 3A and immunoglobulins showed different modulation between the different stages of CanL. These proteins could be considered as potential serum biomarkers of early diagnostic or disease progression in CanL. Additionally, biological pathways modulated during CanL such as blood coagulation or gonadotropin‐releasing hormone receptor were revealed, which could help to understand the pathological mechanisms of the disease.     

Long-term complete response in metastatic poorly-differentiated neuroendocrine rectal carcinoma with a multimodal approach: A case report

BACKGROUNDNeuroendocrine gastrointestinal tumors (NETs) are rare and have different natural behaviors. Surgery is the gold standard treatment for local disease while radiotherapy has been demonstrated to be ineffective. Poorly differentiated neuroendocrine carcinomas (NECs) represent only 5%-10% of digestive NETS. Due to aggressive growth and rapid metastatic diffusion, early diagnosis and a multidisciplinary approach are mandatory. The role of surgery and radiotherapy in this setting is still debated, and chemotherapy remains the treatment of choice.CASE SUMMARYA 42-year-old male with an ulcerated bleeding rectal lesion was diagnosed with a NEC G3 (Ki67 index > 90%) on May 2015 and initially treated with 3 cycles of first-line chemotherapy, but showed early local progressive disease at 3 mo and underwent sphincter-sparing open anterior low rectal resection. In September 2015, the first post-surgery total-body computed tomography (CT) scan showed an early pelvic disease relapse. Therefore, systemic chemotherapy with FOLFIRI was started and the patient obtained only a partial response. This was followed by pelvic radiotherapy (50 Gy). On April 2016, a CT scan and 18F-fluorodeoxyglucose positron emission tomography imaging showed a complete response (CR) of the pelvic lesion, but pathological abdominal inter-aortocaval lymph nodes were observed. Due to disease progression of abdominal malignant nodes, the patient received radiotherapy at 45 Gy, and finally obtained a CR. As of January 2021, the patient has no symptoms of relapse and no late toxicity after chemotherapy or radiotherapy.CONCLUSIONThis case demonstrates how a multimodal approach can be successful in obtaining long-term CR in metastatic sites in patients with high grade digestive NECs.     

Direct interaction with filamins modulates the stability and plasma membrane expression of CFTR

The role of the cystic fibrosis transmembrane conductance regulator (CFTR) as a cAMP-dependent chloride channel on the apical membrane of epithelia is well established. However, the processes by which CFTR is regulated on the cell surface are not clear. Here we report the identification of a protein-protein interaction between CFTR and the cytoskeletal filamin proteins. Using proteomic approaches, we identified filamins as proteins that associate with the extreme CFTR N terminus. Furthermore, we identified a disease-causing missense mutation in CFTR, serine 13 to phenylalanine (S13F), which disrupted this interaction. In cells, filamins tethered plasma membrane CFTR to the underlying actin network. This interaction stabilized CFTR at the cell surface and regulated the plasma membrane dynamics and confinement of the channel. In the absence of filamin binding, CFTR was internalized from the cell surface, where it prematurely accumulated in lysosomes and was ultimately degraded. Our data demonstrate what we believe to be a previously unrecognized role for the CFTR N terminus in the regulation of the plasma membrane stability and metabolic stability of CFTR. In addition, we elucidate the molecular defect associated with the S13F mutation.     

The development of a quantitative ELISA for antibodies against human platelet antigen type 1a

BACKGROUND: Severe neonatal alloimmune thrombocytopenia is often due to antibodies against human platelet antigen type 1a (HPA-1a). The aim of this study was to develop a quantitative ELISA for the measurement of antibodies against HPA-1a. STUDY DESIGN AND METHODS: HPA-1a glycoprotein (GP) IIb-IIIa was immobilized and mixed with recalcified anti-HPA-1a-positive plasma overnight at 4 degrees C. The beads were washed, the antibodies against HPA-1a were eluted, and the eluate pH level was promptly adjusted. The purified antibodies were dialyzed and used for the development of an ELISA incorporating HPA-1a-coated plates. RESULTS: Serial doubling dilutions of the purified antibodies resulted in consistent sigmoid standard curves with a sensitivity of 0.5 microg per mL. To determine the reproducibility of the ELISA, antibodies against HPA-1a in five plasma samples (Samples A-E) were measured at serial doubling dilutions in four separate assays. Three of the samples (Samples A-C) contained antibodies against HPA-1a. The mean amounts in microg per mL (+/- SD, percentage of CV) obtained in the four assays were as follows: Sample A, 133 (9.4, 7.1%); Sample B, 16.5 (1.7, 10%); and Sample C, 8 (0.8, 10%). The amounts in the two antibody-negative controls (Samples D and E) were consistently less than 0.2 microg per mL. CONCLUSION: Using immobilized HPA-1a1a, antibodies against HPA-1a has been purified, and a quick and simple quantitative assay has been developed.