PR05POST‐OPERATIVE HAEMATOMAS IN MICROVASCULAR FREE FLAP RECONSTRUCTION OF THE HEAD AND NECK: THE INCIDENCE,AETIOLOGY AND OUTCOME MODIFICATIONS

Background Free tissue transfer using microvascular surgery has become a safe a reliable means to repair soft tissue and/or bony defects of the head and neck. Operative success reaches 98%, however the incidence of significant post‐operative complication is also relatively high (32%). One common and often severe complication is haematoma formation at either donor or recipient sites. The incidence of recipient site haematoma is reported at 6%, however the causes and outcomes of haematomas have not been well investigated. A retrospective historical analysis of both donor and recipient site wound haematoma was performed to identify causative factors and the effect on patient outcome. Methodology A five year review was conducted for microvascular free tissue transfer to defects in the head and neck at The Royal Melbourne Hospital, for the period from February 2001 until February 2006. The medical records of these 150 patients were reviewed for donor and recipient site wound haematoma and outcomes. Results Significant factors for the development of post‐operative haematomas included lood pressure control during the first post‐operative, correlating with the likelihood of developing either a donor or recipient site haematoma (p value < 0.001), drain‐tube outputs (both high and low), smoking and the use of pre‐operative NSAIDs. Conclusion There are significant reversible factors that contribute to the development of post‐operative haematomas in head and neck surgery. Close monitoring of patient blood pressure by theatre and recovery nursing staff, close monitoring of drain outputs, and pre‐operative counselling on the use of NSAIDs and smoking may all be useful in the prevention of haematoma formation.     

Co-administration of Salvia miltiorrhiza and verapamil inhibits detrimental effects of torsion/detorsion on testicular tissue in rats

Testicular torsion/detorsion is one of the important emergencies that requires fast surgical intervention. This study aimed to investigate the effects of Salvia miltiorrhiza hydroalcoholic extract combined with verapamil on testicular ischaemia/reperfusion damage in Wistar albino rats. All animals were distributed in 3 groups (n = 8), including the sham-operated group, torsion/detorsion (TD) group and torsion/detorsion + pretreatment with 200 mg/kg Salvia miltiorrhiza extract combined with 0.3 mg/kg verapamil (SMV) group. Oxidative stress biomarkers (MDA, GPx, CAT and TAC) both in plasma and testicular tissue, sperm parameters (motility, vitality, concentration and morphology) and histopathological parameters (MSTD, GECT, Johnson's score, Cosentino's score and testicular cell thickness) were assessed in all groups. Ischaemia/reperfusion significantly increased MDA and decreased GPx, CAT and TAC levels (p < .05). Pretreatment with SMV significantly increased GPx, CAT and TAC levels (p < .05). SMV group increased progressive sperm motility and vitality and reduced non-progressive motility of spermatozoon (p < .05). Testicular torsion significantly decreased all histopathological parameters compared to the sham group (p < .05). SMV pretreatment remarkably increased MSTD, GECT and Cosentino's score in comparison with the TD group (p < .05). A combination of Salvia miltiorrhiza with verapamil could reduce damages triggered by testicular torsion detorsion and improve sperm functionality parameters and oxidative stress defence systems.     

Long-term efficacy and safety of interferon α-2a therapy in severe refractory ophthalmic Behcet’s disease

Ophthalmic involvement is the most debilitating complication of Behcet’s disease (BD). The aim of the current study is to report on the efficacy and safety of a long-term use of interferon alpha-2a (IFNα-2a) in the treatment of refractory ophthalmic BD in the Azari population of Iran. We retrospectively analyzed the clinical data of 12 patients with ophthalmic BD who were under IFNα-2a therapy. All these patients had previously been treated unsuccessfully with corticosteroid and at least one conventional immunosuppressive drug. IFNα-2a was administered at a daily dose of 6 million IU (MIU). After controlling the symptoms, a dose of 6 MIU three times per week was applied for 8–12 weeks, and then, a dose of 3 MIU was administered three times per week as a subcutaneous injection. Visual acuity and total inflammatory activity index (TIAI) were used in order to assess the response to the treatment. Response to the treatment and complete eye remission were obtained in 10 (83.3 %) and 7 (58.3 %) patients, irrespectively. Improvement or stabilization of visual acuity was observed in 18 (81.8 %) out of 22 eyes. After a mean period of 29.6 months, the use of IFNa-2a was discontinued in eight (66.7 %) patients. Unaltered vision for 2 years after IFNa-2a discontinuation happened in eight (100 %) patients. IFNa-2a is probably effective and safe in the treatment of refractory sight-threatening ophthalmic BD in the Azari population of Iran.     

Liposomes for Topical Use: A Physico-Chemical Comparison of Vesicles Prepared from Egg or Soy Lecithin

Developments in nanotechnology and in the formulation of liposomal systems provide the opportunity for cosmetic dermatology to design novel delivery systems. Determination of their physico-chemical parameters has importance when developing a nano-delivery system. The present study highlights some technological aspects/characteristics of liposomes formulated from egg or soy lecithins for topical use. Alterations in the pH, viscosity, surface tension, and microscopic/macroscopic appearance of these vesicular systems were investigated. The chemical composition of the two types of lecithin was checked by mass spectrometry. Caffeine, as a model molecule, was encapsulated into multilamellar vesicles prepared from the two types of lecithin: then zeta potential, membrane fluidity, and encapsulation efficiency were compared. According to our observations, samples prepared from the two lecithins altered the pH in opposite directions: egg lecithin increased it while soy lecithin decreased it with increased lipid concentration. Our EPR spectroscopic results showed that the binding of caffeine did not change the membrane fluidity in the temperature range of possible topical use (measured between 2 and 50 °C). Combining our results on encapsulation efficiency for caffeine (about 30% for both lecithins) with those on membrane fluidity data, we concluded that the interaction of caffeine with the liposomal membrane does not change the rotational motion of the lipid molecules close to the head group region. In conclusion, topical use of egg lecithin for liposomal formulations can be preferred if there are no differences in the physico-chemical properties due to the encapsulated drugs, because the physiological effects of egg lecithin vesicles on skin are significantly better than that of soy lecithin liposomes.     

A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia in solid tumor s and hematologic malignancies

Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy treatment delays, dose reductions, and discontinuation. There is no US Food and Drug Administration (FDA)-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at four US centers. The primary outcome was achievement of a romiplostim response (median on-romiplostim platelet count ≥75x10⁹/L and ≥30x10⁹/L above baseline). Secondary outcomes included time to platelet count ≥100x10⁹/L and rates of the following: platelet count <100×10⁹/L, platelet count <75x10⁹/L, platelet count <50x10⁹/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare weekly dosing with intracycle/intermittent dosing. A total of 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of four (range: 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays, and 89% avoided platelet transfusions. Median per-patient platelet count on romiplostim was significantly higher than baseline (116x10⁹/L vs. 60x10⁹/L; P<0.001). Bone marrow (BM) tumor invasion, prior pelvic irradiation, and prior temozolomide exposure predicted romiplostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays/bleeding; intracycle dosing had an incidence rate ratio (IRR) for dose reduction/treatment delay of 3.00 (95%CI: 1.30-6.91; P=0.010) and an IRR for bleeding of 4.84 (95%CI: 1.18-19.89, P=0.029) compared with weekly dosing. Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with BM involvement. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients.     

Tumor location and nature of lymphatic vessels are key determinants of cancer metastasis

Tumor metastasis to lymph nodes is a key indicator of patient survival, and is enhanced by the neo-lymphatics induced by tumor-secreted VEGF-C or VEGF-D, acting via VEGFR-3 signalling. These targets constitute important avenues for anti-metastatic treatment. Despite this new understanding, clinical observations linking metastasis with tumor depth or location suggest that lymphangiogenic growth factors are not the sole determinants of metastasis. Here we explored the influence of tumor proximity to lymphatics capable of responding to growth factors on nodal metastasis in a murine VEGF-D over-expression tumor model. We found that primary tumor location profoundly influenced VEGF-D-mediated lymph node metastasis: 89 % of tumors associated with the flank skin metastasised, in contrast with only 19 % of tumors located more deeply on the body wall (p < 0.01). Lymphatics in metastatic tumors arose from small lymphatics, and displayed distinct molecular and morphological profiles compared with those found in normal lymphatics. Smaller lymphatic subtypes were more abundant in skin (2.5-fold, p < 0.01) than in body wall, providing a richer source of lymphatics for VEGF-D⁺ skin tumors, a phenomenon also confirmed in human samples. This study shows that the proximity of a VEGF-D⁺ primary tumor to small lymphatics is an important determinant of metastasis. These observations may explain why tumor location relative to the lymphatic network is prognostically important for some human cancers.