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PurposeTo examine the risk factors of proximal junctional kyphosis (PJK) after surgery for adult spinal deformity (ASD) focusing on rod contour.MethodsSixty-three patients with ASD who underwent surgery using lateral lumbar interbody fusion and percutaneous pedicle screws were analyzed. Fixation range was from the lower thoracic spine to the pelvis in all cases. Patients were divided into two groups. The PJK group consisted of 16 patients with PJK. The non-PJK group had 47 patients without PJK. We examined various spinopelvic parameters and parameters related to rod contour.ResultsAmong the various spinal and pelvic parameters, those in the PJK group were significantly larger in terms of preoperative SVA and were significantly smaller in terms of postoperative “PI-LL.” For parameters related to rod contour, the rod kyphotic curve at the thoracic spine in the PJK group was significantly less than that in the non-PJK group. The inclination of the pedicle screw at the upper instrumented vertebra (UIV) was significantly more cranial in the PJK group than in the non-PJK group. The kyphotic curve of the rod at the UIV was more parallel in the PJK group than in the non-PJK group.On logistic regression analysis, insufficient kyphotic curve at the thoracic spine along with UIV and overcorrection of the lumbar spine were identified as significant risk factors.ConclusionsInsufficient kyphotic curve of the rod in the thoracic spine along with UIV and overcorrection of the lumbar spine were noted as significant risk factors of PJK.

Background and Objectives: Proximal junctional kyphosis (PJK) and failure (PJF), the most prevalent complications following long-segment thoracolumbar fusions for adult spinal deformity (ASD), remain lacking in defined preventive measures. We studied whether one of the previously reported strategies with successful results—a prophylactic augmentation of the uppermost instrumented vertebra (UIV) and supra-adjacent vertebra to the UIV (UIV + 1) with polymethylmethacrylate (PMMA)—could also serve as a preventive measure of PJK/PJF in minimally invasive surgery (MIS). Materials and Methods: The study included 29 ASD patients who underwent a combination of minimally invasive lateral lumbar interbody fusion (MIS-LLIF) at L1-2 through L4-5, all-pedicle-screw instrumentation from the lower thoracic spine to the sacrum, S2-alar-iliac fixation, and two-level balloon-assisted PMMA vertebroplasty at the UIV and UIV + 1. Results: With a minimum 3-year follow-up, non-PJK/PJF group accounted for fifteen patients (52%), PJK for eight patients (28%), and PJF requiring surgical revision for six patients (21%). We had a total of seven patients with proximal junctional fracture, even though no patients showed implant/bone interface failure with screw pullout, probably through the effect of PMMA. In contrast to the PJK cohort, six PJF patients all had varying degrees of neurologic deficits from modified Frankel grade C to D3, which recovered to grades D3 and to grade D2 in three patients each, after a revision operation of proximal extension of instrumented fusion with or without neural decompression. None of the possible demographic and radiologic risk factors showed statistical differences between the non-PJK/PJF, PJK, and PJF groups. Conclusions: Compared with the traditional open surgical approach used in the previous studies with a positive result for the prophylactic two-level cement augmentation, the MIS procedures with substantial benefits to patients in terms of less access-related morbidity and less blood loss also provide a greater segmental stability, which, however, may have a negative effect on the development of PJK/PJF.

Background and Objectives: Spinal minimally invasive surgery (MIS) experts at the university hospital worked as a team to develop a new treatment algorithm for pyogenic spondylodiscitis in lumbar and thoracic spines. They modified a flow chart introduced for this condition in a pre-MIS era to incorporate MIS techniques based on their extensive experiences accumulated over the years, both in MIS for degenerative lumbar diseases and in the treatment of spine infections. The MIS procedures incorporated in this algorithm consisted of percutaneous pedicle screw (PPS)–rod fixation and transpsoas lateral lumbar interbody fusion (LLIF). The current study analyzed a series of 34 patients treated with prospective selection of the methods according to this new algorithm. Materials and Methods: The algorithm first divided the patients into those who had escaped complicated disease conditions, such as neurologic impairment, extensive bone destruction, and the need to be mobilized without delay (Group 1) (19), and those with complicated pyogenic spondylodiscitis (Group 2) (15). Group 1 had image-guided needle biopsy followed by conservative treatment alone with antibiotics and a spinal brace (12) (Group 1-A) or a subsequent addition of non-fused PPS–rod fixation (7) (Group 1-B). Group 2 underwent an immediate single-stage MIS with non-fused PPS–rod fixation followed by posterior exposure for decompression and debridement through a small midline incision (12) (Group 2-A) or an additional LLIF procedure after an interval of 3 weeks (3) (Group 2-B). Results: All patients, except four, who either died from causes unrelated to the spondylodiscitis (2) or became lost to follow up (2), were cured of infection with normalized CRP at an average follow up of 606 days (105–1522 days). A solid interbody fusion occurred at the affected vertebrae in 15 patients (50%). Of the patients in Group 2, all but two regained a nearly normal function. Despite concerns about non-fused PPS–rod instrumentation, only seven patients (21%) required implant removal or replacement. Conclusions: Non-fused PPS–rod placements into infection-free vertebrae alone or in combination with posterior debridement through a small incision worked effectively in providing local stabilization without contamination of the metal implant from the infected tissue. MIS LLIF allowed for direct access to the infected focus for bone grafting in cases of extensive vertebral body destruction.

Background and Objectives: This study aimed to investigate the process and morphology of thoracic and lumbosacral bone fusion in patients with adult spinal deformity (ASD) who underwent circumferential minimally invasive spine surgery (CMIS) by lateral lumbar interbody fusion (LLIF) and percutaneous pedicle screws (PPSs) without bone grafting in the thoracic spine and who have risk factors for bone fusion failure in the thoracic spine. Materials and Methods: This retrospective study included 61 patients with spinal deformities (46 women and 15 men) who underwent CMIS with LLIF and PPSs at our hospital after 2016 and completed a 3-year postoperative follow-up. The rate and morphology of bone fusion and rod fracture rate in the thoracic and lumbosacral vertebrae were evaluated. Patients were divided into the thoracic spine spontaneous bone fusion group and the bone fusion failure group. The data of various spinopelvic parameters and the incidence of complications were compared. The vertebral body conditions in the thoracic spine were classified as less degenerative (type N), osteophyte (type O), and diffuse idiopathic skeletal hyperostosis (DISH) (type D). Results: After three postoperative years, the bone fusion rates were 54%, 95%, and 89% for the thoracic, lumbar, and lumbosacral spine, respectively. Screw loosening in the thoracic vertebrae was significantly higher in the bone fusion failure group, while no significant differences were observed in the spinopelvic parameters, Oswestry Disability Index (ODI), and rate of proximal junctional kyphosis and rod fractures. Type N vertebral body condition and screw loosening were identified as risk factors for spontaneous bone fusion failure in the thoracic spine. Conclusion: This study indicated that spontaneous bone fusion is likely to be obtained without screw loosening, and even if bone fusion is not obtained, there is no effect on clinical results with the mid-term (3-year) results of CMIS without bone grafting in the thoracic spine.

This retrospective study aimed to evaluate the clinical outcomes of circumferential minimally invasive surgery (CMIS) using lateral lumbar interbody fusion (LLIF) and percutaneous pedicle screw (PPS) in adult spinal deformity (ASD) patients, and to clarify the conditions for achieving postoperative pelvic incidence-lumbar lordosis (PI-LL) < 10°. Demographics and other parameters of ASD patients who underwent CMIS and who were divided into groups G (achieved postoperative PI-LL < 10°) and P (PI-LL ≥ 10°) were compared. Of the 145 included ASD patients who underwent CMIS, the average fused level, bleeding volume, operative time, and number of intervertebral discs that underwent LLIF were 10.3 ± 0.5 segments, 723 ± 375 mL, 366 ± 70 min, and 4.0 segments, respectively. The rod material was titanium alloy in all the cases. The PI-LL significantly improved from 37.3 ± 17.9° to 1.2 ± 12.2° postoperatively. Pre- and postoperative PI, postoperative LL, preoperative PI-LL, PI-LL after LLIF, and postoperative PI-LL were significantly larger in group P. PI-LL after LLIF was identified as a significant risk factor of postoperative PI-LL < 10° by logistic regression, and the cut-off value on receiver operating characteristic curve analysis was 20°. Sufficient correction was achieved by CMIS. If PI-LL after LLIF was ≤20°, it was corrected to the ideal alignment by the PPS procedure.

This study aimed to devise measures and investigate their effect on coronal imbalance (CI) after circumferential minimally invasive correction surgery (CMIS) with lateral lumbar interbody fusion and percutaneous pedicle screw for adult spinal deformity (ASD). A total of 115 patients with ASD who underwent CMIS from the lower thoracic spine to the ilium were included. Patients were stratified based on the distance between the spinous process of the upper instrumented vertebra and central sacrum vertical line (UIV-CSVL) after the first intraoperative rod application into groups P (UIV-CSVL > 10 mm, n = 50) and G (UIV-CSVL < 10 mm, n = 65). Measures to correct postoperative CI introduced during surgery, preoperative and postoperative UIV-CSVL, and changes in UIV-CSVL after various measures (ΔUIV-CSVL) were investigated in group P. Rod rotation (RR), S2 alar-iliac screw distraction (SD), and kickstand-rod (KR) technique were performed in group P. Group P was further divided into group RR (n = 38), group SD (RR and SD) (n = 7), and group KR (RR and KR) (n = 5); the ΔUIV-CSVLs were 13.9 mm, 20.1 mm, and 24.4 mm in these three groups, respectively. Postoperative C7-CSVL < 10 mm was achieved in all three correction groups. In conclusion, our measures enabled sufficient correction of the UIV-CSVL and are useful for preventing CI after CMIS for ASD.

RET encodes the tyrosine kinase receptor of growth factors belonging to the glial‐derived neurotrophic factor family. Recently, RET gene rearrangements with N‐terminal of KIF5B gene were identified in lung adenocarcinomas from large‐scale sequencing. We investigated RET mRNA expression by real‐time reverse‐transcriptase polymerase chain reaction (RT‐PCR) assay using LightCycler, and KIF5B/RET gene rearrangements using newly established fluorescence in situ hybridization (FISH) analysis in surgically treated nonsmall cell lung cancer (NSCLC) cases. RET protein expression was also investigated by immunohistochemistry (IHC). This study included 157 surgically removed NSCLC cases for mRNA level analyses. The RET/β actin mRNA levels were not significantly different between lung cancer (6.359 ± 15.268) and adjacent normal lung tissues (8.205 ± 28.931, P = 0.6332). Tumor/normal (T/N) ratio of RET/β actin mRNA levels was not different within gender, stage, smoking status, and pathological subtypes. T/N ratio of RET/β actin mRNA levels was significantly higher in KIF5B/RET rearrangement samples (161.763 ± 123.488) than in wild‐type samples (5.9013 ± 17.148, P = 0.044). Although RET IHC positivity was not perfectly correlated with KIF5B/RET arrangement, we have detected the KIF5B/RET rearrangements using FISH analysis. Thus, we have successfully introduced FISH for diagnosing KIF5B/RET positive lung adenocarcinoma. This method facilitates the molecular evaluation for RET fusions and could be applicable in clinical practice to detect lung cancer that may be responsive to RET inhibitors. Original FISH probes were used for KIF5B/RET translocation in lung adenocarcinimas.

It was hypothesized that four histopathological types or subtypes of breast carcinoma were undifferentiated types characterized by bidirectional differentiation toward both luminal epithelial and myoepithelial cells and had characteristic molecular changes: invasive ductal carcinoma (IDC) with a large central acellular zone, atypical medullary carcinoma (a subgroup in Grade 3 solid‐tubular carcinoma), matrix‐producing carcinoma, and spindle‐cell carcinoma (or carcinoma with spindle‐cell metaplasia). In 32 cases of the undifferentiated type and 37 cases of the relatively differentiated types, we immunohistochemically examined the expressions of myoepithelial markers and KIT, epidermal growth factor receptor (EGFR), and c‐erbB‐2 oncoproteins. Vimentin, S‐100, and α‐smooth muscle actin were positive in 28 (88%), 22 (69%), and 15 (47%) of the undifferentiated types, but were positive in seven (19%), one (3%), and one (3%) of relatively differentiated types (P < 0.0001). KIT and EGFR overexpressions were detected more frequently in the undifferentiated types (34 and 88%, respectively) than in relatively differentiated types (3 and 3%, respectively) (P < 0.0001, for both). In 11 (85%) of 13 cases with KIT overexpression, EGFR overexpression concurred. c‐erbB‐2 overexpression was almost equally detected in both the undifferentiated and relatively differentiated types, and did not correlate with KIT or EGFR overexpression. Phosphotyrosine was detected in 16 (67%) of 24 cases with KIT, EGFR, and/or c‐erbB‐2 overexpression but only in six (18%) of 34 cases without KIT, EGFR, or c‐erbB‐2 overexpression (P = 0.0002). The undifferentiated‐type breast carcinomas appeared to show mammary epithelial stem cell‐like features, and they could be identified by KIT and/or EGFR overexpressions. (Cancer Sci 2005; 96: 333–339)

For achieving optimal cancer immunotherapy, it is anticipated that both the activation and infiltration of immune cells into tumor are indispensable. In the present study, fiber-mutant adenovirus vectors (Ad) encoding chemokine FKN, (AdRGD-FKN), and cytokine interleukin 12, (AdRGD-IL-12), were constructed. The in vivo gene expression of AdRGD was confirmed and the combination of both FKN and IL-12 encoding Ad elicited synergistic anti-tumor activity in ovarian carcinoma, which induced tumor regression in all tumor-bearing mice, while using FKN alone did not show notable tumor-suppressive effect. The treatment with both IL-12 and FKN induced long-term specific immunity against OV-HM tumors in tumor-rejected mice. The results of immunohistochemical staining for CD3 + and perforin-positive cells suggested that the failure of using FKN alone was because of the inactivation of infiltrated immune cells. In contrast, cotransduction with IL-12 and FKN could induce more activated tumor-infiltrating immune cells than that transducted with FKN or IL-12 alone. The results indicated that using both chemokine and cytokine might be a powerful tool and a promising way for effective cancer immunotherapy.

The Fas (Apo-1/CD95)/Fas ligand (L) system is involved in cell death signaling, and has been suggested to be important for the regulation of germ cell apoptosis in the testis. Mutations of the Fas gene may result in accumulation of germ cells and thus might contribute to testicular carcinogenesis. The open reading frame of Fas cDNA was examined in 24 cases of testicular germ cell tumors (TGCTs), comprised of 19 pure histological type (15 seminomas, 3 embryonal carcinomas, 1 immature teratoma) and 5 mixed-type tumors. Mutations of the Fas gene were found in nine (37.5%) of these cases. Each lesion with a homogeneous histological picture was selectively microdissected using a laser capture microdissection method: samples consisted of 18 lesions from seminomas, 7 embryonal carcinomas, 4 immature teratomas, 2 choriocarcinomas, and 1 from a yolk sac tumor. Microdissected genomic DNA was examined to determine which mutations were derived from which kind of histological lesion. Eleven mutations were detected in 10 TGCT lesions from nine cases, but none were found in benign lesions. All were point mutations, and eight missense mutations occurred in exon 9 encoding the core protein of the death domain essential for apoptotic signal transduction. Three were silent mutations. Mutations were found in the seminoma (27.8%) and embryonal carcinoma lesions (62.5%), but none were found in the one yolk sac tumor, two choriocarcinomas, or four immature teratoma lesions. Each seminoma and embryonal carcinoma lesion found in the same case had a different type of Fas mutation from the others. Mouse T-cell lymphoma cells transfected with missense mutated genes were resistant to apoptosis induced by anti-Fas antibody, indicating these to be loss-of-function mutations. These findings suggested a role of Fas gene mutations in the pathogenesis of TGCTs.