Desmoid Fibromatosis of the Anterior Abdominal Wall in Pregnancy: A Case Report and Review of the Literature.

A desmoid tumor (DT) is a rare benign neoplasm arising from muscle aponeurosis, associated mostly with trauma or pregnancy. DT has an infiltrative and locally aggressive growth pattern and usually does not metastasize. However, it has a high recurrence and complication rate. When it occurs in pregnancy, the pregnancy and delivery is taken as an individual case for optimal management by physicians and midwifes, who need to be cautious in finding the optimal delivery mode for the patient, which depends on the tumor size, location, behavior, and past history. The authors report a case of 29-year-old pregnant woman who previously underwent systemic oncological treatment for a large abdominal wall desmoid tumor and became pregnant afterwards. The history of DT presented a follow-up and delivery challenge. Observational management was chosen with an elective cesarean section at week 38 + 4 of pregnancy with uncomplicated postpartum follow-up. The authors detail the clinical management and chosen therapeutic approach; chemotherapy can be a choice in the treatment options for patients with DTs, although the majority of DTs are treated surgically with subsequent mesh plastic. Moreover, the authors provide a systematic review of the literature focused on the treatment management of DTs in pregnant women during pregnancy and the postpartum period, as pregnancy-associated desmoid tumors are a specific condition, where the optimal management is not well established, despite some guidelines for non-pregnant patients.

Intrasinusoidal HHV8-EBV-Positive Large B-Cell Lymphoma With Features of Germinotropic Lymphoproliferative Disorder.

Germinotropic lymphoproliferative disorder (GLPD) is a poorly characterized lymphoproliferative entity, recently included in the World Health Organization classification of hematolymphoid neoplasms. The histological pattern of this disease comprises monotypic plasmablasts that involve the germinal centers of the lymphoid follicles (germinotrophism), forming confluent aggregates positive for both human herpes virus type 8 (HHV8) and Epstein-Barr virus. Currently, after 17 years of its first description, only 18 cases have been reported. In this article, we describe a case of a GLPD presenting in an immunocompetent 79-year-old woman with localized axillary lymphadenopathy, showing a prominent sinusoidal growth pattern, with no evidence of germinotrophism or extrasinusoidal spread. Stinking pleomorphism in tumor cells was also noted. An extension study has not revealed involvement of other groups of lymph nodes or extralymphoid sites. The patient is alive and has shown no relapse after 8 years follow-up (the longest follow-up reported period for this entity). This previously unrecognized pure sinusoidal growth pattern along with the striking pleomorphism in neoplastic cells closely mimics the appearance of an anaplastic large cell lymphoma. GLPD is not usually considered in such a setting, but it should be included in the differential diagnosis of sinusoidal proliferations. Our findings contribute to the expansion of the morphological spectrum of HHV8-associated lymphoproliferative lesions and aids in the characterization of the very infrequent GLPD entity.

SYK Inhibition Potentiates the Effect of Chemotherapeutic Drugs on Neuroblastoma Cells in Vitro.

Neuroblastoma is a malignancy arising from the developing sympathetic nervous system and the most common and deadly cancer of infancy. New therapies are needed to improve the prognosis for high-risk patients and to reduce toxicity and late effects. Spleen tyrosine kinase (SYK) has previously been identified as a promising drug target in various inflammatory diseases and cancers but has so far not been extensively studied as a potential therapeutic target in neuroblastoma. In this study, we observed elevated SYK gene expression in neuroblastoma compared to neural crest and benign neurofibroma. While SYK protein was detected in the majority of examined neuroblastoma tissues it was less frequently observed in neuroblastoma cell lines. Depletion of SYK by siRNA and the use of small molecule SYK inhibitors significantly reduced the cell viability of neuroblastoma cell lines expressing SYK protein. Moreover, SYK inhibition decreased ERK1/2 and Akt phosphorylation. The SYK inhibitor BAY 613606 enhanced the effect of different chemotherapeutic drugs. Transient expression of a constitutive active SYK variant increased the viability of neuroblastoma cells independent of endogenous SYK levels. Collectively, our findings suggest that targeting SYK in combination with conventional chemotherapy should be further evaluated as a treatment option in neuroblastoma.

Inhibitor of neuronal nitric oxide synthase improves gas exchange in ventilator-induced lung injury after pneumonectomy.

BACKGROUND: Mechanical ventilation with high tidal volumes may cause ventilator-induced lung injury (VILI) and enhanced generation of nitric oxide (NO). We demonstrated in sheep that pneumonectomy followed by injurious ventilation promotes pulmonary edema. We wished both to test the hypothesis that neuronal NOS (nNOS), which is distributed in airway epithelial and neuronal tissues, could be involved in the pathogenesis of VILI and we also aimed at investigating the influence of an inhibitor of nNOS on the course of VILI after pneumonectomy. METHODS: Anesthetized sheep underwent right pneumonectomy, mechanical ventilation with tidal volumes (VT) of 6 mL/kg and FiO2 0.5, and were subsequently randomized to a protectively ventilated group (PROTV; n = 8) keeping VT and FiO2 unchanged, respiratory rate (RR) 25 inflations/min and PEEP 4 cm H2O for the following 8 hrs; an injuriously ventilated group with VT of 12 mL/kg, zero end-expiratory pressure, and FiO2 and RR unchanged (INJV; n = 8) and a group, which additionally received the inhibitor of nNOS, 7-nitroindazole (NI) 1.0 mg/kg/h intravenously from 2 hours after the commencement of injurious ventilation (INJV + NI; n = 8). We assessed respiratory, hemodynamic and volumetric variables, including both the extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI). We measured plasma nitrite/nitrate (NOx) levels and examined lung biopsies for lung injury score (LIS). RESULTS: Both the injuriously ventilated groups demonstrated a 2-3-fold rise in EVLWI and PVPI, with no significant effects of NI. In the INJV group, gas exchange deteriorated in parallel with emerging respiratory acidosis, but administration of NI antagonized the derangement of oxygenation and the respiratory acidosis significantly. NOx displayed no significant changes and NI exerted no significant effect on LIS in the INJV group. CONCLUSION: Inhibition of nNOS improved gas exchange, but did not reduce lung water extravasation following injurious ventilation after pneumonectomy in sheep.