Long-term follow-up of free vascularized fibular head graft for reconstruction of the proximal humerus after wide resection for bone sarcoma

Purpose: This study investigated the shape of bone grafts and associations with upper limb function over the long term after free vascularized fibular head graft (FVFHG) for reconstruction of the proximal humerus after wide resection for bone sarcoma. Methods: Patients comprised 3 women who had undergone FVFHG at least 5 years previously. Age at surgery was 12 years in 2 cases and 76 years in one. The mean follow-up periods were 10 years 4 months. Evaluated parameters comprised: 1) graft hypertrophy, and 2) shape of the fibular head as changes in shape of the bone graft; and 3) ISOLS score, and 4) DASH score as indicators of upper limb function. Results: Rates of graft hypertrophy of the fibular shaft were -14%, -17%, and -20%, respectively, with transverse diameter decreasing in all cases. In terms of changes in shape of the grafted fibular head, transverse diameter had diminished in 2 patients (-5 mm and -2 mm), and the head had been completely resorbed in the remaining patient. Both patients in whom the fibular head remained were young, and both had good ISOLS scores >80% and good DASH scores of 5.0 and 8.3. The patient in whom the fibular head had been resorbed was elderly, with ISOLS and DASH scores of 73.3% and 34.2, respectively; comparatively poor compared with the other two. A comparison of ISOLS and DASH scores before and after fibular head resorption, however, showed no deterioration in either score. Conclusions: Long-term follow-up of humerus reconstruction by FVFHG showed no deterioration in upper limb function despite the risk of fibular head resorption. FVFHG of the proximal humerus is a reconstruction technique that can provide good long-term upper limb function

Effects of several caspase inhibitors (Z-VAD-FMK, a broad caspase inhibitor; Ac-LEHD-CHO, a caspase-8 inhibitor; Ac-IETD-CHO, a caspase-9 inhibitor; Ac-DMQD-CHO, a caspase-3 inhibitor) on etodolac treatment (48 h) (n = 5).

<p>Each of these caspase inhibitors inhibited etodolac-induced apoptosis of FMS-1 cells incompletely but significantly. On the other hand, in FPS-1 cells, only Z-VAD-FMK and Ac-LEHD-CHO significantly inhibited etodolac-induced apoptosis. P-values of each analysis were calculated based on Student’s t-test (**, P<0.01; NS, not significant).</p

Univariate and multivariate analysis of overall survival (Cox proportional hazards model).

<p>*including the cases in which only a biopsy was performed; CI, confidence interval.</p

Effect of etodolac treatment on FPS-1 and FMS-1 cells (n = 5).

<p>Etodolac significantly reduced cell viability of FMS-1 cells in a dose-dependent manner. P-values compared with the control were calculated based on Student’s t-test (*, P<0.05; **, P<0.01).</p

Diffuse, strong, and cytoplasmic-positive immunoreactivity for COX-2 in MPNST (immunohistochemical score, 4+) (immune-peroxidase stain, ×400).

<p>Diffuse, strong, and cytoplasmic-positive immunoreactivity for COX-2 in MPNST (immunohistochemical score, 4+) (immune-peroxidase stain, ×400).</p

Morphology of FPS-1 (A) and FMS-1 (D) cells after etodolac treatment for 72 h.

<p>Nuclear fragmentations were observed only in FMS-1 cells (D, arrow). Both in FPS-1 (B) and FMS-1 (E) without etodolac treatment, cells were viable and no apoptotic cells were observed (May-Giemsa staining, ×400). Evaluation of apoptosis using agarose gel electrophoresis (C, FPS-1; F, FMS-1). Only DNA samples from the FMS-1 cells (F) after etodolac treatment for 72 h revealed the DNA ladder, indicating apoptosis. M, marker, 100-bp DNA ladder; E, etodolac treatment; C, control (without etodolac treatment).</p

Activities of caspase-8, -9, and -3 with etodolac treatment (24 and 48 h) (n = 3).

<p>Both in FPS-1 and FMS-1 cells, etodolac significantly activated caspase-8, -9, and -3 at both 24 and 48 h compared with the control group. However, the differences of caspase-activities were much smaller in FPS-1 cells than those in FMS-1 cells. P-values were calculated based on Student’s t-test (*, P<0.05; **, P<0.01).</p

Kaplan-Meier curve of overall survival evaluated for COX-2 overexpression.

<p>Overexpression of COX-2 was significantly associated with a decreased probability of overall survival (P = 0.0495).</p

Statistical relationship between immunohistochemical result of COX-2 and other variables.

<p>*Percentage of positive cases; NA, not available.</p