We report a multilevel modified vertebral column resection (MVCR) through a single posterior approach and clinical outcomes for treatment of severe congenital rigid kyphoscoliosis in adults. Transpedicular eggshell osteotomies and vertebral column resection are two techniques for the surgical treatment of rigid severe spine deformities. The authors developed a new technique combining the two surgical methods as a MVCR, through a single posterior approach, for surgical treatment of severe congenital rigid kyphoscoliosis in adults. Thirteen adult patients with severe rigid congenital kyphoscoliosis deformity were treated by a single posterior approach using a MVCR technique. The surgery processes included a onestage posterior transpedicular eggshell technique first, and then expanded the eggshell technique to adjacent intervertebra space through abrasive reduction of the vertebral cortices from inside out. All posterior vertebral elements were removed including the cortical vertebral bone around the neural canal. Range of resection of the vertebral column at the apex of the deformity included apical vertebra and both cephalic and/or caudal adjacent wedged vertebrae. Totally, 32 vertebrae had been removed in 13 patients, with 2.42 vertebrae being removed on average in each case. The average fusion extent was 7.69 vertebrae. Mean operation time was 266 min with average blood loss of 2,411.54 ml during operation. Patients were followed up for an average duration of 2.54 years. Deformity correction was 59% in the coronal plane (from 79.7°to 32.4°) postoperatively and 33.7°(57% correction) at 2 years followup. In the sagittal plane, correction was from preoperative 85.9°to 27.5°immediately after operation, and 32.0°at 2 years follow-up. Postoperative pain was reduced from preoperative 1.77 to 0.54 at 2 years follow-up in visual analog scale. SRS-24 scale was from 38.2 preoperatively to 76.9 at 2 years follow-up postoperative. Complications were encountered in four patients (30.7%) with transient neurology that spontaneously improved without further treatment within 3 months. MVCR technique through a single posterior approach is an effective procedure for the surgical treatment of severe congenital rigid kyphoscoliosis in adults.

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Survival of KRAS mutant pancreatic cancer is critically dependent on reprogrammed metabolism including elevated macropinocytosis, autophagy, and lysosomal degradation of proteins. Lysosomal acidification is indispensable to protein catabolism, which makes it an exploitable metabolic target for KRAS mutant pancreatic cancer. Herein we investigated ultra-pH-sensitive micelles (UPSM) with pH-specific buffering of organelle pH and rapid drug release as a promising therapy against pancreatic cancer. UPSM undergo micelle–unimer phase transition at their apparent pK a, with dramatically increased buffer capacity in a narrow pH range (<0.3 pH). Cell studies including amino acid profiling showed that UPSM inhibited lysosomal catabolism more efficiently than conventional lysosomotropic agents (e.g., chloroquine) and induced cell apoptosis under starved condition. Moreover, pH-triggered rapid drug release from triptolide prodrug-loaded UPSM (T-UPSM) significantly enhanced cytotoxicity over non-pH-sensitive micelles (T-NPSM). Importantly, T-UPSM demonstrated superior safety and antitumor efficacy over triptolide and T-NPSM in KRAS mutant pancreatic cancer mouse models. Our findings suggest that the ultra-pH-sensitive nanoparticles are a promising therapeutic platform to treat KRAS mutant pancreatic cancer through simultaneous lysosomal pH buffering and rapid drug release.

Surgical treatment of complex severe spinal deformity, involving a scoliosis Cobb angle of more than 90 degrees and kyphosis or vertebral and rib deformity, is challenging. Preoperative two-dimensional images resulting from plain film radiography, computed tomography (CT) and magnetic resonance imaging provide limited morphometric information. Although the three-dimensional (3D) reconstruction CT with special software can view the stereo and rotate the spinal image on the screen, it cannot show the full-scale spine and cannot directly be used on the operation table. This study was conducted to investigate the application of computer-designed polystyrene models in the treatment of complex severe spinal deformity. The study involved 16 cases of complex severe spinal deformity treated in our hospital between 1 May 2004 and 31 December 2007; the mean +/- SD preoperative scoliosis Cobb angle was 118 degrees +/- 27 degrees. The CT scanning digital imaging and communication in medicine (DICOM) data sets of the affected spinal segments were collected for 3D digital reconstruction and rapid prototyping to prepare computer-designed polystyrene models, which were applied in the treatment of these cases. The computer-designed polystyrene models allowed 3D observation and measurement of the deformities directly, which helped the surgeon to perform morphological assessment and communicate with the patient and colleagues. Furthermore, the models also guided the choice and placement of pedicle screws. Moreover, the models were used to aid in virtual surgery and guide the actual surgical procedure. The mean +/- SD postoperative scoliosis Cobb angle was 42 degrees +/- 32 degrees, and no serious complications such as spinal cord or major vascular injury occurred. The use of computer-designed polystyrene models could provide more accurate morphometric information and facilitate surgical correction of complex severe spinal deformity.

The iCT navigation system provides desirable accuracy of posterior spinal instrumentation for patients during surgical correction of spinal deformity without radiation exposure to the medical staff, especially in thoracic spine instrumentation. Meanwhile, the iCT in itself is an effective means of assessing complex instrumentation of the spinal deformity.

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Objective This study aimed at reporting the results of a transthoracic approach in the treatment of patients with calcified giant herniated thoracic discs (HTDs). Methods Fifteen consecutive patients, 11 males and 4 females with a mean age of 46 years (range 33-61), with calcified giant HTDs underwent transthoracic decompression and segmental instrumentation with interbody fusion from November 2004 to September 2010. Clinical data retrospectively examined and compared were levels and types of disc herniation, operative time, blood loss, preand postoperative Frankel grades and Japanese Orthopedic Association (JOA) score, and complications. Results Of the 15 patients, 2 had HTDs at two levels and affected discs were primarily at the T11/12 level (60 %). Presenting symptoms included myelopathy, axial back pain, urinary symptoms, and radiculopathy. Disc herniations were classified as central (40 %) or paracentral (60 %). All discs were successfully removed without dural tears or cerebral spinal fluid leakage. The mean operation time was 179 ± 27 min (range 140-210 min), and the mean estimated blood loss was 840 ± 470 ml (range 300-2,000 ml). Frankel grades improved in 9 patients postoperatively and 12 patients at the last follow-up. The mean JOA score improved from 4.9 to 7.7. All patients reported improvement in symptoms. The average duration of follow-up was 45 ± 24 months (range 7-77 months). Conclusions Transthoracic decompression combined with reconstruction, fusion, and fixation is an effective method for the treatment of these lesions and is associated with a low rate of complications, morbidity, and neurological impairment.

Itraconazole (ITA), an old and widely prescribed antifungal drug with excellent safety profile, has more recently been demonstrated to be a multitarget antiangiogenesis agent affecting multiple angiogenic stimulatory signals and pathways, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, and mammalian target of rapamycin (mTOR). In this study, we developed two nanoparticle formulations, i.e., polymer micelles (IP2K) and albumin nanoparticles (IBSA), to solubilize the extremely hydrophobic and insoluble ITA to allow intravenous administration and pharmacokinetics (PK)/pharmacodynamics (PD) comparisons. Although none of the formulations showed strong antiproliferation potency against non-small cell lung cancer (NSCLC) cells in vitro, when administrated at the equivalent ITA dose to a NSCLC patient-derived xenograft (PDX) model, IBSA retarded while IP2K accelerated the tumor growth. We attributed the cause of this paradox to formulation-dependent PK and vascular manipulation: IBSA demonstrated a more sustained PK with a C of 60-70% and an AUC ∼2 times of those of IP2K, and alleviated the tumor hypoxia presumably through vascular normalization. In contrast, the high C of IP2K elevated tumor hypoxia through a strong angiogenesis inhibition, which could have aggravated cancer aggressiveness and accelerated tumor growth. Furthermore, IBSA induced minimal hepatic and hematologic toxicities compared to IP2K and significantly enhanced the in vivo tumor inhibition activity of paclitaxel albumin nanoparticles when used in combination. These findings suggest that formulation and pharmacokinetics are critical aspects to be considered when designing the ITA angiogenesis therapy, and IBSA could potentially be assessed as a novel and safe multitarget angiogenesis therapy to be used in combination with other anticancer agents.