Composite tissue transfer in limb-salvage surgery.

After extensive resection due to extremity sarcoma, the inability to cover the defect for satisfactory healing and limb function has been an indication for amputation rather than limb salvage. We report herein our experience with seven limb-salvage cases in which we closed difficult and complex defects with composite tissue transfers utilizing microvascular techniques. Free-flap transfers were used to cover soft-tissue defects after extensive resection of primary and locally recurrent tumor and to manage radiation-induced complications. The grafts healed well when infected irradiated tissue was covered, and the grafts tolerated postoperative irradiation. Composite tissue transfer also provided soft-tissue coverage around distal joints that would not have been adequately protected with a skin graft. Complications were minimal, and all patients maintained good extremity function. No patient who underwent composite tissue transfer has had a local recurrence. A free-flap composite tissue transfer can extend the indications for limb-salvage surgery and offers an alternative to amputation in selected patients.     

Exercising with blocked muscle glycogenolysis: Adaptation in the McArdle mouse

Background

McArdle disease (glycogen storage disease type V) is an inborn error of skeletal muscle metabolism, which affects glycogen phosphorylase (myophosphorylase) activity leading to an inability to break down glycogen. Patients with McArdle disease are exercise intolerant, as muscle glycogen-derived glucose is unavailable during exercise. Metabolic adaptation to blocked muscle glycogenolysis occurs at rest in the McArdle mouse model, but only in highly glycolytic muscle. However, it is unknown what compensatory metabolic adaptations occur during exercise in McArdle disease.

The recent reduction in mortality from bleeding oesophageal varices is primarily observed from Days 1 to 5

Background: Several new treatments of bleeding oesophageal varices (BOV) have been introduced during the last 25 years; among these are vasoactive drugs, improved endoscopic techniques and prophylactic antibiotics. Aims: The aim was to compare clinical outcomes based on Baveno IV criteria in two patient‐cohorts (1983–1987, n=56 and 2000–2007, n=111) with respect to control of bleeding, rebleeding and mortality after a first episode of BOV. Further, we wanted to assess whether an eventual reduction in bleeding‐related mortality occurred within the first 5 days or between Days 6 and 42 after the bleeding episode. Methods: Data from medical records were collected, according to the Baveno IV criteria, on key events: type of treatment, failure to control bleeding, failure to prevent rebleeding, 5‐day and 6‐week mortality. Results: Six‐week mortality decreased from 30.4 to 17.1% [odds ratio (OR) 0.44; 0.21–0.95] with a reduction in 5‐day mortality from 17.9 to 6.3% (OR 0.31; 0.11–0.86). A non‐significant reduction was seen in the 5‐day failure rate to control bleeding from 35.7 to 26.1%. Mortality and failure to prevent rebleeding Days 6–42 decreased from 15.2 to 11.5% (NS) and 22.2 to 10.7% (NS) respectively. Mean length of hospital stay decreased from 14.6 ± 12.5 to 9.1 ± 9.0 days (P<0.01) and mean number of cumulated blood transfusions within the first 5 days decreased from 5.0 ± 4.8 to 3.6 ± 3.9 (P=0.05). Conclusions: In this retrospective study on individual patient records, we observed a decrease in mortality from BOV over the last 20 years, which seems mainly owing to a reduction in 5‐day mortality; mortality at Days 6–42 remained unaffected.     

OCT2, SSX and SAGE1 reveal the phenotypic heterogeneity of spermatocytic seminoma reflecting distinct subpopulations of spermatogonia

Spermatocytic seminoma (SS) is a rare testicular neoplasm that occurs predominantly in older men. In this study, we aimed to shed light on the histogenesis of SS by investigating the developmental expression of protein markers that identify distinct subpopulations of human spermatogonia in the normal adult testis. We analysed the expression pattern of OCT2, SSX2-4, and SAGE1 in 36 SS cases and four intratubular SS (ISS) as well as a series of normal testis samples throughout development. We describe for the first time two different types of SS characterized by OCT2 or SSX2-4 immunoexpression. These findings are consistent with the mutually exclusive antigenic profile of these markers during different stages of testicular development and in the normal adult testis. OCT2 was expressed predominantly in A(dark) spermatogonia, SSX2-4 was present in A(pale) and B spermatogonia and leptotene spermatocytes, whilst SAGE1 was exclusively present in a subset of post-pubertal germ cells, most likely B spermatogonia. The presence of OCT2 and SSX2-4 in distinct subsets of germ cells implies that these markers represent germ cells at different maturation stages. Analysis of SAGE1 and SSX2-4 in ISS showed spatial differences suggesting ongoing maturation of germ cells during progression of SS tumourigenesis. We conclude that the expression pattern of OCT2, SSX2-4, and SAGE1 supports the origin of SS from spermatogonia and provides new evidence for heterogeneity of this tumour, potentially linked either to the cellular origin of SS or to partial differentiation during tumour progression, including a hitherto unknown OCT2-positive variant of the tumour likely derived from A(dark) spermatogonia.     

Mature autologous dendritic cell vaccines in advanced non-small cell lung cancer: a phase I pilot study

Background

Overall therapeutic outcomes of advanced non-small-cell lung cancer (NSCLC) are poor. The dendritic cell (DC) immunotherapy has been developed as a new strategy for the treatment of lung cancer. The purpose of this study was to evaluate the feasibility, safety and immunologic responses in use in mature, antigen-pulsed autologous DC vaccine in NSCLC patients.

Methods

Five HLA-A2 patients with inoperable stage III or IV NSCLC were selected to receive two doses of 5 × 10⁷ DC cells administered subcutaneous and intravenously two times at two week intervals. The immunologic response, safety and tolerability to the vaccine were evaluated by the lymphoproliferation assay and clinical and laboratorial evolution, respectively.

Results

The dose of the vaccine has shown to be safe and well tolerated. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization, with a significant response after the second dose (p = 0.005). This response was not long lasting and a tendency to reduction two weeks after the second dose of the vaccine was observed. Two patients had a survival almost twice greater than the expected average and were the only ones that expressed HER-2 and CEA together.

Conclusion

Despite the small sample size, the results on the immune response, safety and tolerability, combined with the results of other studies, are encouraging to the conduction of a large clinical trial with multiples doses in patients with early lung cancer who underwent surgical treatment.

Trial Registration

Current Controlled Trials: ISRCTN45563569