Incisional negative pressure wound therapy in reconstructive surgery of poststernotomy mediastinitis

The efficacy of negative pressure wound therapy in the treatment of poststernotomy mediastinitis has been revealed in many reports. The present retrospective observational study examined the efficacy of incisional negative pressure wound therapy in the reconstructive surgery of poststernotomy mediastinitis. We retrospectively examined 1034 consecutive patients, who underwent median sternotomy in the period between October 2013 and September 2015. Mediastinitis developed in 21 patients (2%), who subsequently underwent surgical reconstruction. We applied incisional negative pressure wound therapy (iNPWT) after primary closure of the wound over redon drains in ten patients (iNPWT + redon group). In 11 patients, only redons were used (redons only group). We observed the time between the introduction and removal of redon drains, hospital stay until final wound closure and the rate of failure of treatment. Failure of treatment is defined as the need for further surgical reconstruction. In the iNPWT + redon group, the duration of redon drainage therapy was 6·9 ± 5·2 days versus 13·36 ± 11·58 in the redons only group. Hospital stay was 11·4 ± 8·6 versus 101·64 ± 89·2, and failure of treatment was 10% versus 45·5%, respectively. The primary results of this study appear to support the beneficial effect of iNPWT after radical wound reconstruction.     

Effect of a cytotoxic analog of LH-RH (T-98) on the growth of estrogendependent MXT mouse mammary cancers: Correlations between growth characteristics and EGF receptor content of tumors

Summary Female BDF mice bearing estrogen-dependent MXT mouse mammary cancers were treated for 4 weeks with a cytotoxic analog of luteinizing hormone-releasing hormone (LH-RH), T-98 (agonist [D-Lys⁶]LH-RH linked to glutaryl-2(hydroxymethyl)anthraquinone). The effects of T-98 were compared to those of equimolar amounts of the cytotoxic moiety 2-(hydroxymethyl)anthraquinone hemiglutarate (G-HMAQ) and carrier LH-RH agonist [D-Lys⁶]LH-RH. Both T-98 and [D-Lys⁶]LH-RH significantly inhibited the growth of MXT cancers, but G-HMAQ had only a minor non-significant effect. Cytotoxic analog T-98 and the carrier [D-Lys⁶]LH-RH had similar inhibitory hormonal activities on the pituitary-gonadal axis, but T-98 caused a larger reduction in tumor volume and decreased proliferation characteristics such as mitotic activity and AgNOR numbers in tumor cells to a greater extent than the carrier. Tumor inhibition by T-98, [D-Lys⁶]LH-RH, and ovariectomy was connected with a significant decrease in binding capacity of EGF receptors in tumor cell membranes. The concentration of EGF receptors remained high in tumors that continued to enlarge in spite of treatment and in all control untreated tumors, even those of small size. Thus, the changes in EGF receptors are likely to be the result of the therapy. Treatment with T-98 caused a greater reduction in the binding capacity of EGF receptors in tumors than [D-Lys⁶]LH-RH. This could explain the higher inhibitory effect of the cytotoxic analog on tumor growth. Since radiolabeled T-98 was shown to accumulate in MXT cancers 3 hours after a subcutaneous injection, this indicates that specific targeting might play a role in the antitumor effect exerted by this cytotoxic analog.Abbreviations LH luteinizing hormone - LH-RH LH-releasing hormone - EGF epidermal growth factor - EGF-R EGF receptor - TGF transforming growth factor - NOR nucleolar organizing region - AgNOR argyrophilic NOR - G-HMAQ 2(hydroxymethyl)anthraquinone-hemiglutarate - HPLC high performance liquid chromatography - TNF tumor necrosis factor - 5-FU 5-fluorouracil - PBS phosphate-buffered saline     

Adenovirus replication-competent vectors (KD1, KD3) complement the cytotoxicity and transgene expression from replication-defective vectors (Ad-GFP,Ad-Luc)

The successful clinical application of adenovirus (Ad) in cancer control has been of limited success because of the current inability to infect the majority of cancer cells with a large amount of vector. In this study, we show that when human lung tumors growing in immunodeficient nude mice were coinfected with a replication-defective (RD) Ad vector expressing green fluorescent protein and a replication-competent (RC) Ad vector named KD3, KD3 enhanced the expression of green fluorescent protein throughout the tumor. Also, KD3 and another RC vector named KD1 complemented the expression of luciferase from a RD vector in a human liver tumor xenotransplant in nude mice. Altogether, these results suggest that the combination of a RD vector with a RC vector might be a more effective treatment for cancer than either vector alone due to more widespread dissemination of the virus.     

Angiotensin-(1-7) in normal and preeclamptic pregnancy

Angiotensin-(1–7) (Ang-[1–7]) is a bioactive component of the renin-angiotensin system, which has depressor, vasodilatory, and antihypertensive actions. In normal pregnancy, we questioned whether the known rise in plasma angiotensin II (Ang II) is counterbalanced by an increase in plasma Ang-(1–7) and whether Ang-(1–7) levels are decreased in preeclampsia and may thus be a factor involved in the development of hypertension. Nulliparous preeclamptic subjects, third-trimester normotensive pregnant subjects, and a nonpregnant group were enrolled (n=15/group). Preeclamptic subjects had no previous history of hypertension or renal, connective-tissue, or metabolic disease, but at the time of delivery had significant hypertension (159±3/98±3 mmHg) and ≥3+ proteinuria. Plasma Ang-(1–7) was increased by 51% in normal pregnancy (p<0.05). Plasma Ang I, Ang II, and renin activity were also significantly elevated in normal pregnancy. In preeclamptic subjects, Ang-(1–7) was significantly decreased (p<0.01) compared with normal pregnant subjects. All other components of the renin-angiotensin-aldosterone system, except serum angiotensin-converting enzyme, were reduced in preeclamptic subjects compared with normal pregnant subjects; only plasma Ang II remained elevated in preeclamptic compared with nonpregnant subjects. These studies demonstrate, for the first time, increased plasma Ang-(1–7) in normal pregnant subjects compared with nonpregnant subjects and decreased Ang-(1–7) in preeclamptic subjects compared with normal pregnant subjects. In preeclampsia the decreased plasma Ang-(1–7) in the presence of elevated Ang II is consistent with the development of hypertension.     

Rare presentations of delayed radiation injury: a lobar hematoma and a cystic space-occupying lesion appearing more than 15 years after cranial radiotherapy: report of two cases

OBJECTIVE AND IMPORTANCE: Radiation vasculopathy and radionecrosis, constituting delayed radiation injury, are rare but recognized complications of radiation therapy occurring at a peak incidence of 3 years after treatment. Little information is available about these complications occurring more than 15 years after radiotherapy and presenting as other than solid intracranial masses. CLINICAL PRESENTATION: We describe two patients who presented with space-occupying cerebral lesions. Patient 1 presented as an emergency with a sudden loss of consciousness. Computed tomography revealed a large left intracerebral hemorrhage; cerebral angiography disclosed nothing abnormal, and a primary spontaneous hemorrhage was presumed. Twenty-seven years earlier, this patient had received adjuvant whole-brain and spine radiotherapy and concomitant chemotherapy after excision of a vermis medulloblastoma. Patient 2 presented with a left frontal cystic lesion (presumed malignant glioma) as the cause of personality and behavioral changes for some months. She had previously received external beam radiation for a basal cell epithelioma, which had been excised from her left forehead 19 years earlier. INTERVENTION: Both patients recovered well after undergoing craniotomies and removal of their lesions; they were discharged home with no neurological deficit. CONCLUSION: Even after long intervals after radiotherapy, it is important to consider radiation vasculopathy and radionecrosis as differential diagnoses of more common conditions. Histological confirmation of a delayed radiation injury in the absence of any evidence of neoplasia or vascular abnormality has allowed appropriate prognosis and management to be formulated with confidence in each of these patients.     

Receptor protein tyrosine phosphatase zeta as a therapeutic target for glioblastoma therapy

Astrocytomas are the most frequent brain tumour type in adults. The most common astrocytoma is the glioblastoma (GBM), which is also the most malignant and refractory to treatment--ultimately leading to the patient's death within a year of diagnosis. Neither the classical nor more experimental therapeutic approaches have significantly improved the clinical outcome of this disease. Expression profile analysis of primary tumours has provided recent insight into the identification of new GBM therapeutic targets. These proteins serve as excellent candidates to either inhibit the target molecule's functions (e.g., angiogenesis, migration or proliferation) or, coupled with a toxin or radionucleotide, to bind and exterminate the tumour cells. The receptor protein tyrosine phosphatase zeta (RPTPzeta) and one of its main ligands, pleiotropin (Ptn), are overexpressed in GBMs, thus making them potentially very good targets for the development of new immunotherapeutics. This review will summarise recent advances in GBM therapies focusing on RPTPzeta as a target for immunotherapeutics.