Trends in degenerative lumbar spinal surgery during the early COVID-19 pandemic in Republic of Korea: A national study utilizing the national health insurance database.

During the first year of the COVID-19 pandemic, the Republic of Korea (ROK) experienced three epidemic waves in February, August, and November 2020. These waves, combined with the overarching pandemic, significantly influenced trends in spinal surgery. This study aimed to investigate the trends in degenerative lumbar spinal surgery in ROK during the early COVID-19 pandemic, especially in relation to specific epidemic waves. Using the National Health Information Database in ROK, we identified all patients who underwent surgery for degenerative lumbar spinal diseases between January 1, 2019 and December 31, 2020. A joinpoint regression was used to assess temporal trends in spinal surgeries over the first year of the COVID-19 pandemic. The number of surgeries decreased following the first and second epidemic waves (p<0.01 and p = 0.34, respectively), but these were offset by compensatory increases later on (p<0.01 and p = 0.05, respectively). However, the third epidemic wave did not lead to a decrease in surgical volume, and the total number of surgeries remained comparable to the period before the pandemic. When compared to the pre-COVID-19 period, average LOH was reduced by 1 day during the COVID-19 period (p<0.01), while mean hospital costs increased significantly from 3,511 to 4,061 USD (p<0.01). Additionally, the transfer rate and the 30-day readmission rate significantly decreased (both p<0.01), while the reoperation rate remained stable (p = 0.36). Despite the impact of epidemic waves on monthly surgery numbers, a subsequent compensatory increase was observed, indicating that surgical care has adapted to the challenges of the pandemic. This adaptability, along with the stable total number of operations, highlights the potential for healthcare systems to continue elective spine surgery during public health crises with strategic resource allocation and patient triage. Policies should ensure that surgeries for degenerative spinal diseases, particularly those not requiring urgent care but crucial for patient quality of life, are not unnecessarily halted.

The significance of evaluating sphenoid sinus fluid by postmortem computed tomography in cases of drowning.

PURPOSE: In cases of drowning, the presence of sphenoid sinus fluid is a non-specific autopsy finding. However, studies have reported that fluid accumulation in the paranasal sinuses is more commonly observed in drowning victims. Furthermore, some laboratory tests, such as diatom and electrolyte analysis, can serve as supplementary diagnostic tools for diagnosing drowning. Therefore, accurate sphenoid sinus fluid sampling is an important aspect of an autopsy in suspected drowning cases. The aim of this study was to identify the significance of evaluating sphenoid sinus fluid by PMCT images in cases of drowning. METHODS: We retrospectively reviewed 54 drowning victims who underwent PMCT and forensic autopsy. Fluid volume in the sphenoid sinus was measured using a graduated syringe during autopsy and a three-dimensional (3D) workstation based on PMCT images was used for the purpose of comparison. The Mann-Whitney U test and Spearman's rank correlation coefficient was used to evaluate statistically significant differences and correlations. Additionally, a Bland-Altman plot was employed to assess the agreement between PMCT and autopsy. RESULTS: The median volume was 1.65 (range 0.00-12.4) ml and 1.55 (range 0.00-7.00) ml in the PMCT and autopsy, respectively, showing a statistically insignificant difference (p = 0.294) and a significant correlation (Rs = 0.896). In 35 cases, the PMCT overestimated the fluid volume more than the autopsy, whereas in 14 cases, the PMCT underestimated the fluid volume. No fluid was identified in seven cases during the autopsy, whereas in five patients, no fluid was found in both PMCT and autopsy. By analyzing the Bland-Altman plot, a bias of 0.73 ± 1.4 ml and limits of agreement ranging from -2.04 to 3.51 ml were observed for sphenoid sinus fluid volume measurements. CONCLUSIONS: Based on the limitations of traditional fluid volume measurement in the sphenoid sinus during autopsy, we propose the utilization of PMCT volumetric analysis prior to autopsy as a means to enhance the detection of sphenoid sinus fluid in cases of drowning.

Breast Cancer to Meningioma: A Rare Case of Tumor-to-Tumor Metastasis.

Tumor-to-tumor metastasis (TTM) is defined as the hematogenous metastasis within a primary host tumor from a donor neoplasm. Since there is insufficient evidence regarding the pathophysiology, clinical course, and management of TTM, there are no precise guidelines for its management. A 73-year-old female patient diagnosed with breast cancer was found to have convexity meningioma. Since the size of tumor and peritumoral brain edema increased during follow-up period, the meningioma was treated with surgical resection. Postoperatively, histopathologic examination confirmed metastasis of invasive ductal carcinoma within a secretory meningioma. The final diagnosis was TTM of breast cancer in meningioma. Here, we report a rare case of intra-meningioma metastasis and a review of literature to provide a better understanding of this rare phenomenon.

Efficacy of 3D-printed simulation models of unruptured intracranial aneurysms in patient education and surgical simulation.

OBJECTIVE: The purpose of this study was to determine the efficacy of a 3D-printed aneurysm simulation model (3DPM) in educating patients and improving physicians' comprehension and performance. METHODS: This prospective study involved 40 patients who were diagnosed with unruptured intracranial aneurysms (UIAs) and scheduled for surgical clipping or endovascular coiling and randomly divided into two groups (the 3DPM group and the non-3DPM group). The 3DPM was used in preoperative consultation with patients and intraoperatively referenced by surgeons. The patients, 7 neurosurgical residents, and 10 surgeons completed questionnaires (5-point Likert scale) to determine the usefulness of the 3DPM. RESULTS: Patients in the 3DPM group had significantly higher scores in terms of their understanding of the disease (mean 4.85 vs. 3.95, p<0.001) and the treatment plan (mean 4.85 vs. 4.20, p=0.005) and reported higher satisfaction during consultation (5.0 vs. 4.60, p=0.036) than patients in the non-3DPM group. During patient consultation, 3DPMs were most useful in improving doctor-patient communication (mean 4.57, range 4-5). During clipping surgery, the models were most useful in assessing adjacent arteries (mean 4.9, range 4-5); during endovascular coiling, they were especially helpful in microcatheter shaping (mean 4.7, range 4-5). CONCLUSIONS: In general, 3DPMs are beneficial in educating patients and improving the physician's performance in terms of surgical clipping and endovascular coiling of UIAs.

Does the Surgical Approach Matter in Treating Odontoid Fractures? A Comparison of Mechanical Complication Rates Between Anterior Versus Posterior Surgical Approaches: A Meta-Analysis and Systematic Review.

Objective: Odontoid fractures are treated surgically through the anterior or posterior approach. Each surgical approach has its advantages and disadvantages, so the preferred approach remains debatable. There are few meta-analyses or systemic reviews on the mechanical complications of surgical treatment for odontoid fractures. This meta-analysis aimed to compare the operation-related morbidity, including mechanical complications, and mortality of patients with odontoid fractures, treated via the anterior or posterior approach. Methods: A systematic search was performed on PubMed/Medline, Embase, and the Cochrane Library for the studies up to October 2023 on the complication rate of the surgical treatment of odontoid fractures, related to the surgical approach. The risk ratios (RR) with the 95% confidence intervals (CIs) were pooled to assess the mechanical complication rates, other complications, revision surgery, and mortality, depending on the surgical approach. Results: A total of 1,519 studies were retrieved using the search strategy, and 782 patients from 15 articles were included in this meta-analysis. Mechanical complications were significantly more frequent in the anterior surgical group with low heterogeneity. The incidences of fracture nonunion and revision surgery were also higher in the anterior surgery group. However, there was no significant difference in systemic complications and mortality rates between the two groups. Conclusion: The posterior approach was more advantageous than the anterior approach in terms of mechanical complications, fusion rates, and incidence of revision surgery. However, further studies, should be performed to strengthen these results.

Fusion Assessment of Oblique Lumbar Interbody Fusion Using Demineralized Bone Matrix: A 2-Year Prospective Study.

OBJECTIVE: Although several studies have reported successful fusion rates after oblique lumbar interbody fusion (OLIF) using allografts or dimerized bone matrix (DBM) instead of autografts, whether OLIF can achieve satisfactory solid fusion without the use of autografts remains unclear. This study investigated the real fusion rates after OLIF using allografts and DBM, which were evaluated using both dynamic radiographs and computed tomography scans. METHODS: We enrolled 79 consecutive patients who underwent minimally invasive OLIF followed by percutaneous pedicle screw fixation. All patients were treated with OLIF between L2 and L5 and underwent radiographic and clinical follow-ups at 12, 18, and 24 months after surgery. Radiographic assessment of fusion was performed using the modified BrantigaSteffee-Fraser (mBSF) scale, which was categorized as follows: grades I (radiographic pseudoarthrosis), II (indeterminate fusion), and III (solid radiographic fusion). Other radiologic and clinical outcomes were evaluated using the following parameters: vertebral slippage distance, disc height, subsidence, Oswestry Disability Index (ODI), and visual analogue scale (VAS). RESULTS: Clinical outcomes demonstrated significant improvements in the VAS scores for back pain, leg pain, and ODI after surgery. Subsidence was present in 34 cases (35.4%) at 12 months postoperatively, which increased to 47.9% and reached 50.0% at 1.5 years and 2 years after surgery, respectively. The solid fusion rate after OLIF was 32.3% at 1 year, increased to 58.3% at 1.5 years, and reached 72.9% at 2 years. Radiographic pseudoarthrosis was 24.0% at 1 year, which decreased to 6.3% at 1.5 years and 3.1% at 2 years. CONCLUSION: OLIF is a safe and effective surgical procedure for the treatment of degenerative lumbar diseases. The mBSF scale, which simultaneously evaluates both dynamic angles and bone bridge formation, offers great reliability for the radiological assessment of fusion. Moreover, OLIF using allografts and DBM, which is performed on one or 2 levels at L2-5, can achieve satisfactory fusion rates within 2 years after surgery.

Roles of NF-κB activation in benign prostatic hyperplasia and association between NF-κB and HIF-1α.

OBJECTIVE: The aim of this study was to elucidate the role of NF-κB activation in benign prostatic hyperplasia (BPH) using immunohistochemistry. METHODS: Immunohistochemical staining for NF-κB was performed and evaluated, dividing into glands and stroma in 101 human BPH tissues. To evaluate the impacts of NF-κB activation on BPH progression, correlations between NF-κB expression and clinical findings, hormone receptors, and HIF-1α were evaluated. RESULTS: NF-κB expression was found in 37.6% and 30.7% in glands and stroma of BPH, respectively. Total and T-zone volumes in transrectal ultrasonography were significantly higher in patients with NF-κB activation than those without NF-κB activation in the stroma. However, NF-κB activation of stroma was not correlated with HIF-1α expression and microvessel density. In subgroup analysis based on NF-κB activation, androgen and progesterone receptors of stroma were highly expressed in HIF-1α negative cases than in HIF-1α positive cases. In cases without NF-κB activation, patients with HIF-1α positivity showed a high frequency of diffuse fibrosis than those with HIF-1α negativity (P = 0.001). CONCLUSION: Taken together, our result showed that NF-κB activation of stroma was significantly correlated with low total and T-zone volumes in transrectal ultrasonography. Diffuse fibrosis was frequently found in patients with NF-κB inactivation and HIF-1α positivity.

Rapid-Growing Intracranial Immature Teratoma Presenting Obstructive Hydrocephalus and Abducens Nerve Palsy: A Case Report and Literature Review.

Intracranial immature teratoma is an extremely rare disease with poor prognosis and requires complicated treatment. Owing to the deep midline location of the tumor, total surgical resection of the tumor is challenging. We present our experience with a fast-growing pineal gland immature teratoma in a 4-year-old boy, who presented with obstructive hydrocephalus and abducens nerve palsy, which was treated with total surgical resection of the tumor. In addition, we aimed to determine the appropriate treatment modality for intracranial immature teratomas by reviewing the literature and investigating the prognosis.

The Modified 11-Item Frailty Index and Postoperative Outcomes in Patients Undergoing Lateral Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of this study was to analyze postoperative complications and recovery patterns in different modified 11-item frailty index (mFI-11) groups after lateral lumbar interbody fusion (LLIF) surgery. SUMMARY OF BACKGROUND DATA: The relationship between the mFI-11 score and LLIF surgery has not been previously reported. METHODS: A single-center, consecutive series of patients who underwent LLIF with at least two years of follow-up were retrospectively reviewed. Complications after LLIF surgery were recorded. Clinical outcomes, including the visual analog scale (VAS) for back/leg pain and the Oswestry Disability Index (ODI), were evaluated preoperatively and at 1 and 2 years postoperatively. The proportions of patients who achieved substantial clinical benefit (SCB) for the VAS-B, VAS-L, and ODI were also analyzed. RESULTS: One hundred fifty-two patients included in the present study were grouped according to their mFI-11 score: 0 (n = 39), 0.09 (n = 69), 0.18 (n = 31), and ≥0.27 (n = 13). An mFI-11 score ≥0.27 was a significant predictor of urinary complications (adjusted odds ratio: 3.829, P = 0.013). At 2 years postoperatively, patients in all frailty categories experienced improvements in the VAS for back pain, VAS for leg pain, and ODI, without significant differences between the four groups (p = 0.182, 0.121, and 0.804, respectively). There were also no significant differences in the proportions of patients achieving SCB for back/leg pain and the ODI between the four groups (P = 0.843, 0.957, and 0.915, respectively). CONCLUSION: An mFI-11 score was found to be independently associated with urologic complications in patients who underwent LLIF. Patients in all frailty categories experienced significant improvements in back pain, leg pain, and the ODI at 1 year and 2 years postoperatively. LLIF surgery may be useful for patients with high frailty index.Level of Evidence: 4.

C7 Fracture as a Complication of C7 Dome-Like Laminectomy : Impact on Clinical and Radiological Outcomes and Evaluation of the Risk Factors.

OBJECTIVE: Cervical expansive laminoplasty is an effective surgical method to address multilevel cervical spinal stenosis. During surgery, the spinous processes of C2 and C7 are usually preserved to keep the insertion points of the cervical musculature and nuchal ligament intact. In this regard, dome-like laminectomy (undercutting of C7 lamina) instead of laminoplasty is performed on C7 in selected cases. However, resection of the lamina can weaken the C7 lamina, and stress fractures may occur, but this complication has not been characterized in the literature. The objective of the present study was to investigate the incidence and risk factors for C7 laminar fracture after C7 dome-like laminectomy and its impact on clinical and radiological outcomes. METHODS: Patients who underwent cervical open-door laminoplasty combined with C7 dome-like laminectomy (n=123) were classified according to the presence of C7 laminar fracture. Clinical parameters (neck/arm pain score and neck disability index) and radiologic parameters (C2-7 angle, C2-7 sagittal vertical axis, and C7-T1 angle) were compared between the groups preoperatively and at postoperatively at 3, 6, 12, and 24 months. Risk factors for complications were evaluated, and a formula estimating C7 fracture risk was suggested. RESULTS: C7 lamina fracture occurred in 32/123 (26%) patients and occurred at the bilateral isthmus in 29 patients and at the spinolaminar junction in three patients. All fractures appeared on X-ray within 3 months postoperatively, but patients did not present any neurological deterioration. The fracture spontaneously healed in 27/32 (84%) patients at 1 year and in 29/32 (91%) at 2 years. During follow-up, clinical outcomes were not significantly different between the groups. However, patients with C7 fractures showed a more lordotic C2-7 angle and kyphotic C7-T1 angle than patients without C7 fractures. C7 fracture was significantly associated with the extent of bone removal. By incorporating significant factors, the probability of C7 laminar fracture could be assessed with the formula 'Risk score = 1.08 × depth (%) + 1.03 × length (%, of the posterior height of C7 vertebral body)', and a cut-off value of 167.9% demonstrated a sensitivity of 90.3% and a specificity of 65.1% (area under the curve, 0.81). CONCLUSION: C7 laminar fracture can occur after C7 dome-like laminectomy when a substantial amount of lamina is resected. Although C7 fractures may not cause deleterious clinical outcomes, they can lead to an unharmonized cervical curvature. The chance of C7 fracture should be discussed in the shared decision-making process.

Prognosis of Symptomatic Pseudarthrosis Observed at 1 Year After Lateral Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of this study was to investigate the prognosis of symptomatic pseudarthrosis observed at 1 year after lateral lumbar interbody fusion (LLIF) surgery and to analyze the risk factors for persistent pseudarthrosis for 2 years postoperatively. SUMMARY OF BACKGROUND DATA: Few articles have evaluated the prognosis of symptomatic pseudarthrosis following LLIF surgery. METHODS: One hundred fifty-two patients with a minimum follow-up of 2 years were screened. Fusion status was assessed at 1 year postoperatively, and unfused segments were reevaluated at 2 years postoperatively. Dynamic x-rays and computed tomography images were acquired to evaluate the fusion status. Demographic data were evaluated to identify the risk factors associated with persistent pseudarthrosis. Clinical outcomes, including the visual analog scale (VAS) for back/leg pain and the Oswestry disability index (ODI), were evaluated preoperatively and at 1 and 2 years postoperatively. RESULTS: Symptomatic pseudarthrosis was detected in 42 patients at 1 year postoperatively. Among them, 23 patients (54.8%) exhibited solid bony fusion 2 years postoperatively without further intervention. Fourteen patients (33.3%) showed asymptomatic pseudarthrosis, and the remaining five patients (11.9%) showed symptomatic pseudarthrosis. Multivariable analysis showed that diabetes (adjusted odds ratio [OR]: 2.817, P = 0.007), smoking (adjusted OR: 6.497, P = 0.008), and fusion at more than three levels (adjusted OR: 2.525, P = 0.031) were risk factors for persistent pseudarthrosis. Improvements in the VAS scores for back pain and ODI scores were significantly lower in the persistent pseudarthrosis group than in the final solid fusion group at 2 years postoperatively. CONCLUSION: It is not necessary to intervene for all patients in whom symptomatic pseudarthrosis is detected at 1 year postoperatively because only 11.9% of them will show persistent symptomatic pseudarthrosis. However, early revision surgery should be considered when severe symptomatic pseudarthrosis associated with diabetes, smoking, and fusion at more than three levels is present.Level of Evidence: 4.

The Efficacy of Lumbar Hybrid Fusion for the Prevention of Adjacent Segment Disease: Fact or Artifact? A Meta-analysis.

STUDY DESIGN: A systematic literature review and meta-analysis. OBJECTIVE: The aim of this study is to compare hybrid constructs with traditional fusion-only constructs for the incidence of adjacent segment degeneration (ASDeg) and clinical outcomes in patients with degenerative lumbar diseases. SUMMARY OF BACKGROUND DATA: Spinal fusion is a standard surgery for various pathologies of the lumbar spine, which results in changes to the biomechanics of the spine, potentially leading to ASDeg. Although ASDeg can occur slowly as a natural course, early-onset ASDeg is regarded to be related to fusion surgery. MATERIALS AND METHODS: A systematic search was conducted to identify studies that match the purpose. Included studies were compared using the incidence of ASDeg, Oswestry Disability Index, Visual Analog Score, and perioperative outcomes. We calculated the Peto odds ratio and mean difference (MD) for the continuous variables, respectively. In the hybrid group, subgroup analysis was also performed among devices. RESULTS: Among 10 papers involving 767 patients, 372 patients underwent hybrid fusion and 395 patients underwent fusion-only. ASDeg occurred in 10.2% in the hybrid and 21.5% in the fusion-only group [Peto odds ratio, 0.39; 95% confidence interval (CI), 0.23-0.64]. The MD for Visual Analog Score were 0.45 (95% CI, 0.05-0.85) between 2 groups, which was statistically significant but was too small to have clinical significance. The MD for Oswestry Disability Index was 0.93 (95% CI, -1.016 to 2.872), which was not statistically different between 2 groups. The hybrid is superior for 18 minutes (95% CI, 5.78-30.72) shorter than typical surgery. CONCLUSIONS: Hybrid lumbar surgery decreased the incidence of early-onset ASDeg for about 2 years of follow-up. Among the hybrid constructs, the interspinous devices group accomplished favorable results with a lower risk. Adjacent segment disease was not as statistically significant as ASDeg, but adjacent segment disease may show a substantial difference for >2-year follow-up.

Intraoperative Radiographs in Single-level Lateral Lumbar Interbody Fusion Can Predict Radiographic and Clinical Outcomes of Follow-up 2 Years After Surgery.

MINI: Some of the improvements in DH, FH, and SLL achieved intraoperatively during lateral lumbar interbody fusion surgery were lost by the postoperative 1-week follow-up. An intraoperative radiograph can predict radiographic and clinical outcomes of the 2-year follow-up. The difference between preoperative DH and intraoperative DH should be >4.18 mm.

Retrospective cohort study The aim of this study was to evaluate whether the intraoperatively estimated parameters, as calculated on a cross-table lateral radiograph, are maintained in an upright position at discharge and at 2 years postoperatively and to identify the appropriate disc height (DH) to achieve substantial clinical benefit. The amount of correction retained following lateral lumbar interbody fusion (LLIF) surgery had not been reported. A single-center, consecutive series of patients who underwent single-level LLIF with at least 2 years of follow-up were retrospectively reviewed. Upright standardized preoperative, 1-week, and 2-year postoperative radiographs, as well as intraoperative lateral radiographs, were analyzed for DH, foraminal height (FH), and segmental lumbar lordosis (SLL) at the index level. Clinical outcomes were compared between preoperatively and 1 week and 2 years postoperatively. In total, 89 patients were evaluated (mean follow-up, 42.8 months [range, 24­83 months]). DH decreased from 12.5 ±â€Š2.7 mm intraoperatively to 11.7 ±â€Š3.1 mm at 1 week postoperatively, FH decreased from 15.9 ±â€Š3.6 mm to 15.1 ±â€Š3.6 mm, and SLL decreased from 13.6°â€Š±â€Š1.7° to 12.4°â€Š±â€Š1.7°. A linear correlation between intraoperative and 2-year postoperative parameters was found ( R2  = 0.552, 0.518, and 0.616, respectively). Clinical outcomes, including back pain, leg pain, and Oswestry Disability Index (ODI), significantly improved 2 years postoperatively. The optimal cutoff point for substantial clinical benefit thresholds for the ODI was a 4.18 mm increase in DH (sensitivity, 64.3%; specificity, 80.3%; area under the curve, 0.793; 95% confidence interval, 0.642­0.855). Some of the improvements in DH, FH, and SLL achieved intraoperatively during LLIF surgery were lost by the postoperative 1-week follow-up. An intraoperative radiograph can predict radiographic and clinical outcomes of the 2-year follow-up. The difference between preoperative DH and intraoperative DH should be >4.18 mm. Level of Evidence: 4.

Clinicopathological significance and angiogenic role of the constitutive phosphorylation of the FOXO1 transcription factor in colorectal cancer.

PURPOSE: This study aimed to evaluate the clinicopathological significance of phospho-forkhead box O1 (pFOXO1) expression and its impact on the angiogenesis of colorectal cancer (CRC). METHODS: We performed immunohistochemistry in 266 human CRC tissues for pFOXO1, and evaluated its cytoplasmic expression, regardless of its nuclear expression. We also investigated the correlation between pFOXO1 expression and clinicopathological characteristics, survival, microvessel density (MVD), and angiogenesis-related molecules in CRC. RESULTS: pFOXO1 was expressed in the cytoplasm of 100 (37.6 %) of the 266 CRC tissues. Furthermore, pFOXO1 expression was significantly correlated with the left colon and rectum, and with vascular invasion, lymph node metastasis, distant metastasis, and higher pTNM stage. However, there was no significant correlation between pFOXO1 expression and other clinicopathological parameters. MVD was significantly higher in pFOXO1-positive tumors than in pFOXO1-negative tumors (P = 0.025). Among the angiogenesis-related molecules examined, pFOXO1 expression was significantly correlated with SIRT1 (P = 0.002) and VEGF expression (P < 0.001), but not with HIF-1α expression. pFOXO1 expression was significantly correlated with poor overall and recurrence-free survival rates (P = 0.001 and P < 0.001, respectively). CONCLUSIONS: Taken together, our results showed that the pFOXO1 expression was significantly correlated with aggressive tumor behavior and poor survival rates. Moreover, pFOXO1 expression may affect tumor progression through SIRT1- and VEGF-induced angiogenesis.

Clinicopathological significance of PD-L1 expression in colorectal cancer: Impact of PD-L1 expression on pFOXO1 expression.

OBJECTIVE: This study aimed to evaluate the clinicopathological significance of PD-L1 expression and its impact on phospho-Forkhead box O 1 (pFOXO1) expression in colorectal cancer (CRC). METHODS: Immunohistochemical analysis for PD-L1 and pFOXO1 was performed on 265 human CRC tissues. PD-L1 expression was evaluated in the tumor and immune cells. The impact of PD-L1 expression on survival was investigated in relation to the pattern of pFOXO1 expression. RESULTS: PD-L1 was expressed in 25 (9.4%) and 41 (17.7%) patients in the tumor and immune cells of the 265 CRC tissues, respectively. PD-L1 expression in immune cells (I-PD-L1) was significantly correlated with less lymphatic invasion, lymph node metastasis, and distant metastasis and lower pT and pTNM stages. Additionally, there was a significant correlation between PD-L1 expression in tumor cells (T-PD-L1) and tumor location (right colon), but not the other clinicopathological characteristics. pFOXO1 expression was significantly lower in CRC with high I-PD-L1 expression than in CRC with low or negative I-PD-L1 expression. However, there was no significant correlation between pFOXO1 and T-PD-L1 expression in CRC. Patients with positive pFOXO1 and low or negative I-PD-L1 expression exhibited the worst survival among patients with CRC. CONCLUSION: Collectively, our results indicate that I-PD-L1 expression was significantly correlated with favorable tumor behaviors and better survival. In addition, patients with high I-PD-L1 and low pFOXO1 expressions had a favorable prognosis than those with other I-PD-L1 and pFOXO1 expression patterns.

The Clinical Implications and Complications of Anterior Versus Posterior Surgery for Multilevel Cervical Ossification of the Posterior Longitudinal Ligament; An Updated Systematic Review and Meta-Analysis.

OBJECTIVE: Theoretically, the optimal approach is determined by the status of ossification of the posterior longitudinal ligament (OPLL) and sagittal alignment. However, there have long been disputes about the optimum surgical approach of OPLL. This study is to compare risk-effectiveness between anterior decompression and fusion (ADF) and laminoplasty and laminectomy with fusion (LP/LF) for the patient with cervical myelopathy due to multilevel cervical OPLL. METHODS: We searched core databases, and compared complication and outcomes between ADF and LP/LF for patients with multiple OPLL for the cervical spine. The incidence of complications such as neurologic deterioration, C5 palsy, and dura tear was assessed. Changes in JOA score between baseline and final evaluations were assessed for 2 groups. The minimal clinically important difference (MCID) was utilized for evaluating clinical significance. We calculated Peto odds ratio (POR) and mean difference for the incidence and continuous variables, respectively. RESULTS: We included data from 21 articles involving 3,872 patients with cervical myelopathy with OPLL. Major neurologic deficits such as paraplegia, quadriplegia developed 2.17% in the ADF group and 1.11% in the LP/LF group, and POR was 2.16. Mean difference of JOA score improvement of 2 groups was 1.30, and the mean difference showed a statistical significance. However, 1.3 points of JOA improvement cannot reach 2.5 points of the MCID. CONCLUSION: Anterior surgery often led to rare but critical complications, and the difference of neurological improvement between 2 groups was below a clinically meaningful level. Posterior surgeries may be appropriate in the treatment of multilevel cervical myelopathy with OPLL.

Clinicopathological significance and prognostic role of tumor-infiltrating lymphocytes in colorectal cancer.

PURPOSE: This study aimed to elucidate the clinicopathological significance and prognostic role of tumor-infiltrating lymphocytes in colorectal cancer. METHODS: The immunohistochemistry of CD3 and CD8 was performed on 265 human colorectal cancer tissues to investigate the tumor-infiltrating lymphocytes using Immunoscore. The correlation between Immunoscore and clinicopathological characteristics, including survival rates, was elucidated. In addition, the impact of tumor-infiltrating lymphocytes on programmed death-ligand 1 (PD-L1) protein expression was evaluated through immunohistochemistry. RESULTS: Of the 265 colorectal cancer tissues, 40.8% had high Immunoscore, while 59.2% had low Immunoscore. A high Immunoscore was significantly correlated with favorable tumor behaviors, including lower rates of vascular, lymphatic, and perineural invasion; lymph node metastasis; and distant metastasis. PD-L1 expressions of tumor and immune cells were significantly higher in patients with high Immunoscore than in those with low Immunoscore. In addition, colorectal cancer tissues with high CD8-positive lymphocytes showed higher PD-L1 expressions of tumor and immune cells than colorectal cancer tissues with low CD8-positive lymphocytes. There was a significant correlation between high Immunoscore and better overall survival. However, there was no significant difference in survival rate according to PD-L1 expressions of tumor and immune cells in high and low Immunoscore subgroups. CONCLUSIONS: Taken together, our results showed that high tumor-infiltrating lymphocytes were significantly correlated with favorable tumor behaviors and better survival. In addition, there was a significant correlation between PD-L1 expression and tumor-infiltrating lymphocytes.

Extensive Pituitary Apoplexy after Chemotherapy in a Patient with Metastatic Breast Cancer.

Surgery, anticoagulation therapy, pregnancy, and hormone treatments, such as bromocriptine, are well-characterized precipitating factors for pituitary apoplexy. However, whether cytotoxic chemotherapy for systemic cancer could cause pituitary apoplexy has not been investigated. Here, we present a case of a 41-year-old woman who developed a severe headache with decreased visual acuity after intravenous cytotoxic chemotherapy to treat metastatic breast cancer. Preoperative neuroimaging revealed pituitary adenoma with necrosis. Operative findings and pathologic examination concluded extensive necrosis with a small intratumoral hemorrhage in a pre-existing pituitary adenoma. We reviewed two additional previously published cases of pituitary apoplexy after systemic chemotherapy and suggest that cytotoxic chemotherapy may induce pituitary apoplexy.

Concordance analysis between HER2 immunohistochemistry and in situ hybridization in non-small cell lung cancer.

PURPOSE: This study aimed to elucidate the concordance between human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) and in situ hybridization (ISH) and the diagnostic accuracy of HER2 IHC in non-small cell lung cancer (NSCLC) through a meta-analysis and diagnostic test accuracy review. METHODS: Seven eligible studies and 1,217 patients with NSCLC were included in the review. The concordance between HER2 IHC and ISH was analyzed. To confirm the diagnostic accuracy of HER2 IHC, the sensitivity and specificity were analyzed and the area under the curve (AUC) in the summary receiver operating characteristic (SROC) curve was calculated. RESULTS: The concordance rate between HER2 IHC and ISH was 0.795 (95% confidence interval [CI] 0.534-0.929). In the HER2 IHC-negative (score 0/1+) subgroup, the concordance rate was 0.975 (95% CI 0.854-0.996). The concordance rates of the HER2 IHC score 2+ and 3+ subgroups were 0.091 (95% CI 0.039-0.197) and 0.665 (95% CI 0.446-0.830), respectively. In diagnostic test accuracy review, the pooled sensitivity and specificity were 0.67 (95% CI 0.54-0.78) and 0.89 (95% CI 0.87-0.91), respectively. The AUC in the SROC curve was 0.891 and the diagnostic odds ratio was 16.99 (95% CI 5.08-56.76). CONCLUSIONS: HER2 IHC was largely in agreement with ISH in cases of HER2 IHC score 0/1+. Because the concordance rates of HER2 IHC score 2/3+ cases were lower than that of HER2 IHC score 0/1+ cases, further studies for detailed analysis criteria for HER2 IHC score 2+ or 3+ are required.

FOXO1 Suppression is a Determinant of Acquired Lapatinib-Resistance in HER2-Positive Gastric Cancer Cells Through MET Upregulation.

PURPOSE: Lapatinib is a candidate drug for treatment of trastuzumab-resistant, human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC). Unfortunately, lapatinib resistance renders this drug ineffective. The present study investigated the implication of forkhead box O1 (FOXO1) signaling in the acquired lapatinib resistance in HER2-positive GC cells. MATERIALS AND METHODS: Lapatinib-resistant GC cell lines (SNU-216 LR2-8) were generated in vitro by chronic exposure of lapatinib-sensitive, HER2-positive SNU-216 cells to lapatinib. SNU-216 LR cells with FOXO1 overexpression were generated by stable transfection of a constitutively active FOXO1 mutant (FOXO1A3). HER2 and MET in SNU-216 LR cells were downregulated using RNA interference. The sensitivity of GC cells to lapatinib and/or cisplatin was determined by crystal violet assay. In addition, Western blot analysis, luciferase reporter assay and reverse transcription-polymerase chain reaction were performed. RESULTS: SNU-216 LR cells showed upregulations of HER2 and MET, but downregulation of FOXO1 compared to parental SNU-216 cells. FOXO1 overexpression in SNU-216 LR cells significantly suppressed resistance to lapatinib and/or cisplatin. In addition, FOXO1 negatively controlled HER2 and MET at the transcriptional level and was negatively controlled by these molecules at the post-transcriptional level. A positive crosstalk was shown between HER2 and MET, each of which increased resistance to lapatinib and/or cisplatin. CONCLUSION: FOXO1 serves as an important linker between HER2 and MET signaling pathways through negative crosstalks and is a key regulator of the acquired lapatinib resistance in HER2-positive GC cells. These findings provide a rationale for establishing a novel treatment strategy to overcome lapatinib resistance in a subtype of GC patients.