Effect of renin-angiotensin system inhibitors on pemetrexed plus platinum-induced hematological toxicities: a multicenter retrospective study using three propensity score analyses.

Hematological toxicities induced by pemetrexed plus platinum therapy remain a critical issue in clinical practice. We hypothesized that inhibition of the renin-angiotensin system (RAS) can ameliorate pemetrexed-induced hematological toxicities through drug-drug interactions involving organic anion transporters. Thus, this study aimed to clarify whether RAS inhibitors (RASIs) could prevent pemetrexed plus platinum-induced hematological toxicities. We retrospectively analyzed data from 305 consecutive patients with non-small cell lung cancer or malignant pleural mesothelioma who received their first cycle of a pemetrexed plus platinum regimen and were treated with or without RASIs. The primary endpoint was the incidence of severe myelosuppression after the first cycle. Propensity score (PS)-matched, PS-adjusted, and inverse probability of treatment weighting (IPTW) analyses were used. The number of patients with grade ≥3 hematological toxicities was 27 (8.9%). PS-matched analyses revealed that the concomitant use of RASIs was slightly associated with a lower risk of grade ≥3 hematological toxicities (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.20-2.32; p = 0.536). Additionally, sensitivity analyses using PS-adjusted and IPTW methods demonstrated similar results (OR, 0.63; 95% CI, 0.19-2.15; p = 0.463 and OR, 0.37; 95% CI, 0.11-1.29; p = 0.117, respectively). These findings suggest that RASIs might prevent pemetrexed plus platinum-induced hematological toxicities.

Long-term outcome of transtrochanteric anterior rotational osteotomy for osteonecrosis of the femoral head in patients with systemic lupus erythematosus.

This study sought to examine the long-term outcomes of transtrochanteric anterior rotational osteotomy (ARO) as treatment for osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE). Twenty-one patients (33 hips), aged 20-40 years, underwent ARO between 1980 and 1988. We examined 16 patients (25 hips), a 76% follow-up rate. A Kaplan-Meier curve was used for survivorship analysis. Patients with surviving hips were evaluated by the modified Oxford hip score and Short Form 36 (SF-36). Twelve hips in eight patients had survived at the final follow-up. The average length of hip survival was 24.6 years (range: 20.1-27.2 years). Three patients (six hips) had died of unrelated causes without any subsequent operation. Based on Kaplan-Meier analysis with the endpoint defined as the need for a subsequent operation, the hip survival rate at 25 years was 73.7% (95% confidence interval, +/-19.8%). Based on classification by the modified Oxford hip score, five hips were classified as excellent, two hips were good, and the remaining five hips were fair. The average SF-36 summary score for the physical and mental components was 38.7 and 47.2 points, respectively. The physical component summary scores for three patients exceeded the normal level of the Japanese population. Lupus (2010) 19, 860-865.

Leg-length discrepancy after transtrochanteric curved varus osteotomy for osteonecrosis of the femoral head.

Transtrochanteric curved varus osteotomy was designed to avoid some of the disadvantages of varus wedge osteotomy, such as post-operative leg-length discrepancy. In this retrospective study we investigated the leg-length discrepancy and clinical outcome after transtrochanteric curved varus osteotomy undertaken in patients with osteonecrosis of the femoral head. Between January 1993 and March 2004, this osteotomy was performed in 42 hips of 36 patients with osteonecrosis of the femoral head. There were 15 males and 21 females with a mean age at surgery of 34 years (15 to 68). The mean follow-up was 5.9 years (2.0 to 12.5). The mean pre-operative Harris hip score was 64.0 (43 to 85) points, which improved to a mean of 88.7 (58 to 100) points at final follow-up. The mean varus angulation post-operatively was 25 degrees (12 degrees to 38 degrees ) and the post-operative mean leg-length discrepancy was 13 mm (4 to 25). The post-operative leg-length discrepancy showed a strong correlation with varus angulation (Pearson's correlation coefficient; r = 0.9530, p < 0.0001), which may be useful for predicting the leg-length discrepancy which can occur even after transtrochanteric curved varus osteotomy.

Effects of intertrochanteric osteotomy plane and preoperative femoral anteversion on the postoperative morphology of the proximal femur in transtrochanteric anterior rotational osteotomy: 3D CT-based simulation study.

BACKGROUND: Transtrochanteric anterior rotational osteotomy (ARO) is joint-preserving surgery for patients with osteonecrosis of the femoral head (ONFH). During ARO, femoral neck-shaft varus angulation by changing intertrochanteric osteotomy plane is often designed to obtain a sufficient postoperative intact ratio. However, the effect of intertrochanteric osteotomy plane on postoperative femoral anteversion has not been well examined. Therefore, we performed a simulation study of ARO to determine how intertrochanteric osteotomy plane and preoperative femoral anteversion affect both femoral neck-shaft varus angle and postoperative femoral anteversion. HYPOTHESIS: Both femoral neck-shaft varus angle and postoperative femoral anteversion are predicted by intertrochanteric osteotomy plane and preoperative femoral anteversion in ARO. MATERIALS AND METHODS: Using CT-data obtained from 10 hips in 10 patients with ONFH, ARO was simulated. On anteroposterior view, basic intertrochanteric osteotomy line (AP-view line) was defined as the perpendicular line to the femoral neck axis. On lateral view, basic intertrochanteric osteotomy line (lateral-view line) made through the cut surface of greater trochanter was defined as the perpendicular line to the lateral axis of the femur. By changing either AP-view or lateral-view line, 49 ARO models/hip were produced, in which femoral neck-shaft varus angle and postoperative femoral anteversion were assessed. RESULTS: With increase in the vertically-inclined degree of AP-view line, both neck-shaft varus angle and postoperative femoral anteversion increased. With increase in the posteriorly-tilted degree of lateral-view line, neck-shaft varus angle increased, whereas postoperative femoral anteversion decreased. The approximation equations based on the multiple regression analyses were as follows: neck-shaft varus angle≈vertically-inclined degree of AP-view line×0.9+posteriorly-tilted degree of lateral-view line×0.8+preoperative femoral anteversion×0.7; postoperative femoral anteversion≈vertically-inclined degree of AP-view line×1.1-posteriorly-tilted degree of lateral-view line×0.8. DISCUSSION: The postoperative morphology of proximal femur was nearly defined by intertrochanteric osteotomy plane with preoperative femoral anteversion, which is useful for preoperative planning in terms of both achieving a sufficient postoperative intact ratio and maintaining femoral anteversion. LEVEL OF EVIDENCE: Level IV case series without control group.

Factors influencing progressive collapse of the transposed necrotic lesion after transtrochanteric anterior rotational osteotomy for osteonecrosis of the femoral head.

BACKGROUND: Transtrochanteric anterior rotational osteotomy (ARO) for osteonecrosis of the femoral head (ONFH) can preserve for a long-time collapsed femoral head. Progressive collapse of anteriorly-transposed necrotic lesion leads to secondary arthritic changes and clinical failure. Critical factors influencing collapse of the transposed necrotic lesion after ARO remain largely unknown. Therefore, we performed a retrospective study of ARO to determine: (1) if preoperative collapse influences collapse of the transposed necrotic area, (2) if any other factor may influence collapse of the transposed necrotic area. HYPOTHESIS: We hypothesized the degree of preoperative femoral head collapse influences progressive collapse of the transposed necrotic lesion after ARO. MATERIALS AND METHODS: We reviewed 47 hips in 42 patients with ONFH treated with ARO between 2000 and 2005 with a mean follow-up of 11.4 years (10-14 years). The occurrence of progressive collapse of the transposed necrotic lesion after ARO was examined using lateral radiographs taken at least once every year after ARO. The following factors were statistically analyzed: age, sex, body mass index, Harris Hip Score (HHS), preoperative level of collapse, extent of the necrotic lesion and postoperative intact ratio (ratio of the transposed intact articular surface of the femoral head). RESULTS: Progressive collapse of the transposed necrotic lesion (progressive collapse group) was seen in 17 hips (36%) during a mean period of 1.8 years (0.5-3.7 years) after ARO, which has developed within 4 years in all cases. Preoperative level of collapse in the progressive collapse group (4.4±1.4mm) was significantly larger than that in the non-progressive collapse group (2.1±1.0mm), which was independently associated with progressive collapse of the transposed necrotic lesion in multivariate analysis (P<0.0001) with cut off point of 2.98mm. In univariate analysis, lower preoperative HHS, severe extent of the necrotic lesion and the lower postoperative intact ratio were also associated with progressive collapse of the transposed necrotic lesion, but were not associated as independent factors in multivariate analysis. DISCUSSION: The current study suggests that progressive collapse of the transposed necrotic lesion after ARO depends mainly on the preoperative level of collapse (cut-off point=2.98mm). LEVEL OF EVIDENCE: IV; retrospective case series.

Enhanced surfaces for endothelial cell seeding.

Silver negative ions (Ag-) were implanted to polystyrene (PS) and tissue culture polystyrene (TCPS) by using neutral and ionized alkaline bombardment-type heavy negative ion sources, NIABNIS. Surface property and biocompatibility of Ag(-)-implanted TCPS and PS were investigated. Enhanced growth of vascular endothelial cells was observed on Ag(-)-implanted TCPS at a dose of 10(16) ions.cm-2 at an ion energy of 10 keV and Ag(-)-implanted (at ca. 10(15) ions.cm-2 dose and 10 keV energy) PS region. As a result of Ag(-)-implantation, PS and TCPS surfaces were considered to be more hydrophobic and to be more hydrophilic, respectively.

[Surgical treatment of lung cancer complicated with liver cirrhosis, esophageal varices and pancytopenia: a case report].

Left upper lobectomy and lymph node dissection were successfully performed in a 75-year-old man with lung cancer combined with liver cirrhosis, esophageal varices and pancytopenia. No postoperative complications were encountered due to appropriate fluid transfusion, sufficient administration of fresh frozen plasma and well-chosen antibiotics. In lung operations on patients with liver cirrhosis, it is important to determine the operative indication according to natural history of liver cirrhosis and lung cancer, operative risk and prognosis. Furthermore, the management with special attention to complicated conditions of liver cirrhosis is necessary at the time of surgery.

Prognostic factors associated with a subchondral insufficiency fracture of the femoral head.

OBJECTIVE: The aim of this study was to identify the risk factors associated with the prognosis of a subchondral insufficiency fracture of the femoral head (SIF). METHODS: Between June 2002 and July 2009, 25 patients diagnosed with SIF were included in this study. Sequential radiographs were evaluated for the progression of collapse. Clinical profiles, including age, body mass index, follow-up period and Singh's index, were documented. The morphological characteristics of the low-intensity band on T(1) weighted MRI were also examined with regards to four factors: band length, band thickness, the length of the weight-bearing portion and the band length ratio (defined as the proportion of the band length to the weight-bearing portion of the femoral head in the slice through the femoral head centre). RESULTS: Radiographically, a progression of collapse was observed in 15 of 25 (60.0%) patients. The band length in patients with progression of collapse [22.5 mm; 95% confidence interval (CI) 17.7, 27.3] was significantly larger than in patients without a progression of collapse (13.4 mm; 95% CI 7.6, 19.3; p<0.05). The band length ratio in patients with progression of collapse (59.8%; 95% CI 50.8, 68.9) was also significantly higher than in patients without a progression of collapse (40.9%; 95% CI 29.8, 52.0; p<0.05). No significant differences were present in the other values. CONCLUSION: These results indicate that the band length and the band length ratio might be predictive for the progression of collapse in SIF.

Morphological analysis of collapsed regions in osteonecrosis of the femoral head.

In order to investigate the mechanisms of collapse in osteonecrosis of the femoral head, we examined which part of the femoral head was the key point of a collapse and whether a collapsed region was associated with the size of the necrotic lesion. Using 30 consecutive surgically removed femoral heads we retrospectively analysed whole serial cut sections, specimen photographs, specimen radiographs and histological sections. In all of the femoral heads, collapse consistently involved a fracture at the lateral boundary of the necrotic lesion. Histologically, the fractures occurred at the junction between the thickened trabeculae of the reparative zone and the necrotic bone trabeculae. When the medial boundary of the necrotic lesion was located lateral to the fovea of the femoral head, 18 of 19 femoral heads collapsed in the subchondral region. By contrast, when the medial boundary was located medial to the fovea, collapse in the subchondral region was observed in four of 11 femoral heads (p = 0.0011). We found that collapse began at the lateral boundary of the necrotic lesion and that the size of the necrotic lesion seemed to contribute to its distribution.

Radiological outcome analysis of transtrochanteric curved varus osteotomy for osteonecrosis of the femoral head at a mean follow-up of 12.4 years.

We investigated the factors related to the radiological outcome of a transtrochanteric curved varus osteotomy in patients with osteonecrosis of the hip. We reviewed 73 hips in 62 patients with a mean follow-up of 12.4 years (5 to 31.1). There were 28 men and 34 women, with a mean age of 33.3 years (15 to 68) at the time of surgery. The 73 hips were divided into two groups according to their radiological findings: group 1 showed progression of collapse and/or joint-space narrowing; group 2 had neither progressive collapse nor joint-space narrowing. Both of these factors and the radiological outcomes were analysed by a stepwise discriminant analysis. A total of 12 hips were categorised as group 1 and 61 as group 2. Both the post-operative intact ratio and the localisation of the necrotic lesion correlated with the radiological outcome. The cut-off point of the postoperative intact ratio to prevent the progression of collapse was 33.6%, and the cut-off point to prevent both the progression of collapse and joint-space narrowing was 41.9%. The results of this study indicate that a post-operative intact ratio of 33.0% is necessary if a satisfactory outcome is to be achieved after this varus osteotomy.