BACKGROUND:The formation of sandwiched vertebrae (SDVs) after percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) has become a common phenomenon. Whether SDVs are more likely to fracture is still controversial. Therefore, we conducted a meta-analysis to provide medical evidence for whether SDVs are more prone to refracture than non-SDVs (NSDVs) after PVP or PKP. METHODS:This study was conducted in accordance with the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Several databases, including PubMed, Embase, Medline databases, China National Knowledge Infrastructure, Wanfang, and Weipu, were thoroughly searched for relevant studies included from any point up until June 2022. Statistical analyses were performed using Revman 5.4. RESULTS:A total of 4052 individuals from 9 studies were enrolled. Overall, patients with SDV presented more risk to have refracture than patients with NSDV (OR = 1.57, P = 0.04). The incidences of refracture were comparable between the 2 cohorts in studies with a follow-up time less than 3 years (OR = 1.28, P = 0.49). However, patients with SDV were more prone to have refracture than patients with NSDV in studies with a follow-up time longer than 3 years (OR = 1.92, P = 0.009). Moreover, patients with SDV were more likely to have refracture than patients with NSDV in studies that involved both PVP and PKP (OR = 1.62, P = 0.002). In addition, age, low bone density, and postoperative kyphosis angle of sandwich fracture segments >10° were independent factors to predict refracture. CONCLUSIONS:Patients with SDV were more likely to have refracture after PVP or PKP, especially when the follow-up time was longer than 3 years. LEVEL OF EVIDENCE: 3:
Secondary neuroinflammation caused by proinflammatory microglia exacerbates the disability of patients with spinal cord injury (SCI), while low drug delivery efficiency reduces the therapeutic effect of conventional drugs on promoting functional recovery. Nowadays, resorting to nanocomposites has been regarded as a promising approach to overcome such an obstacle. Herein, neutrophil membrane-coated quercetin-loaded nanoparticles (denoted NQNPs) were developed to improve drug delivery efficiency and repolarize microglia thereby inhibiting secondary neuroinflammation in SCI. Quercetin-loaded nanoparticles (QNPs), which have the capacity to reprogram proinflammatory microglia toward anti-inflammatory microglia, act as the inner core of NQNPs. The neutrophil membrane was further coated onto the inner core for targeted drug delivery and co-neutralizing inflammatory factors. In vitro and in vivo studies demonstrated that NQNPs could controllably release quercetin under the reactive oxygen species (ROS) abundant environment, reprogram microglia polarization toward M2 phenotype via nuclear factor kappa-B (NK-κB) pathway, thereby inhibiting excessive neuroinflammation, increasing the density and functional status of neurons, and finally promoting motor recovery of SCI with outstanding biocompatibility. We believe that the current research brings a novel strategy and sheds new light on the treatment of SCI.
Background: Neuroinflammation plays a crucial role in the repair of spinal cord injury (SCI), with microglia, pivotal in neuroinflammation, driving either degeneration or recovery in this pathological process. Recently, plasma-derived exosomes (denoted Exos) have presented a high capacity for promoting functional recovery of SCI through the anti-inflammatory effects, and pretreated exosomes are associated with better outcomes. Thus, we aimed to explore whether melatonin-pretreated plasma-derived exosomes (denoted MExo) could exert superior effects on SCI, and attempted to elucidate the potential mechanisms. Methods: Electron microscopy, nanoparticle tracking analysis, and western blot were applied to delineate the distinctions between Exos and MExos. To assess their therapeutic potentials, we established a contusion SCI rat model, complemented by a battery of in vitro experiments comparing both groups. Subsequently, a miRNA microarray analysis was conducted, followed by a series of rescue experiments to elucidate the specific role of miRNAs in MExos. To further delve into the molecular mechanisms involved, we employed western blot analysis and the luciferase reporter gene assay. Results: Melatonin promoted the release of exosome from plasma, concurrently amplifying their antiinflammatory properties. Furthermore, it was discerned that MExos facilitated a transition in microglia polarization from M1 to M2 phenotype, a phenomenon more pronounced than that observed with Exos. In an endeavor to elucidate this variance, we scrutinized miRNAs exhibiting elevated expression levels in MExos, pinpointing miR-138-5p as a pivotal element in this dynamic. Following this, an in-depth investigation into the role of miR138-5p was undertaken, which uncovered its efficacy in driving phenotypic alterations within microglia. The analysis of downstream genes targeted by miR-138-5p revealed that it exerted a negative regulatory influence on SOX4, which was found to obstruct the generation of M2-type microglia and the secretion of anti-inflammatory cytokines, thereby partially elucidating the mechanism behind miR-138-5p ' s regulation of microglia polarization. Conclusions: We innovatively observed that melatonin enhanced the anti-inflammatory function of Exos, which further decreased the expression of SOX4 by delivering miR-138-5p. This inhibition promoted the conversion of M1 microglia to M2 microglia, thus offering a viable option for the treatment of SCI. The translational potential of this article: This study highlights that melatonin enhances the anti-inflammatory function of Exos through delivery of miR-138-5p. Activation of miR-138-5p/SOX4 axis by engineered melatonin-pretreated plasma exosomes may be a potential target for SCI treatment.
Study Design: A meta-analysis. Objective: This study aimed to analyze the incidence of spontaneous resorption of lumbar disk herniation (LDH) after conservative treatment. Summary of Background Data: The resorption of intervertebral disks has been more frequently reported, but there is a lack of reference to the probability of resorption. Methods: We strictly refer to the standard established in the PRISMA (Preferred Reporting Items for a Systematic Review and Meta-analysis) statement, comprehensively searched electronic databases using the terms related to the spontaneous resorption of LDH. Two reviewers independently evaluated the potential studies, extracted, and analyzed the enrolled data. Results: Thirty-one studies with 2233 patients who received conservative treatment were included for this analysis. We found that the pooled overall incidence of disk resorption was 70.39%, 87.77% for disk sequestration, 66.91% for disk extrusion, 37.53% for disk protrusion, and 13.33% for disk bugle, respectively. The resorption incidence in of 25%≤ reduction of disk herniation (RDH) 50%, RDH≥50%, and RDH=100% were 40.19%, 43.62, and 36.89%. The resorption incidence was 66.98% in Japan, 61.66% in the United States, 83.52% in Korea, 60.68% in China, 78.30% in the UK, 56.70% in Italy, and 83.68% in Turkey, respectively. Subgroup analysis showed that there was no significant difference in resorption incidence among prospective, retrospective studies and randomized controlled trials ( P =0.77), and there was no significant difference in evaluation method among qualitative and quantitative studies ( P =0.05). Conclusions: The existing evidence shows that the overall resorption incidence of LDH was 70.39%, the resorption incidence of ruptured LDH is higher than that of contained LDH. There are significant differences in the resorption incidence among countries. The resorption process mainly occurred within 6 months of conservative treatment.
Intervertebral disc (IVD) degeneration is the common cause of lumbar degenerative diseases, causing severe social and economic burden. The process of IVD degeneration involves a complex of pathologic changes on both extracellular matrix degradation and resident cell apoptosis. In recent years, there is increasing evidence that macrophages play vital roles during the damage and repair process of IVD degeneration. Nevertheless, the interactions between macrophages and IVD are not well understood, even if the IVD has long been regarded as the immune privileged site. Therefore, this review mainly focuses on the progress and obstacles of studies investigating the blood supply, immune response and especially macrophages during the IVD degeneration process.
Background. The mechanisms underlying M2 macrophage polarization induced by nucleus pulposus (NP) cells are unclear. The effects that M2-polarized macrophages have on NP cells are also controversial. Methods. Transcriptome sequencing was performed to detect the gene change profiles between NP cells from ruptured intervertebral disc (IVD) and normal IVD. The main difference on biological activities between the two cell groups were analyzed by GO analysis and KEGG analysis. Virus transduction, flow cytometry, immunofluorescence, RT-PCR, western blot, CCK-8, TUNEL staining, and AO/EB staining were performed to explore the interactions between NP cells and RAW264.7 macrophages. Statistics were performed using SPSS26. Results. 801 upregulated and 276 downregulated genes were identified in NP cells from ruptured IVD in mouse models. According to GO and KEGG analysis, we found that the differentially expressed genes (DEG) were dominantly enriched in inflammatory response, extracellular matrix degradation, blood vessel morphogenesis, immune effector process, ossification, chemokine signaling pathway, macrophage activation, etc. CX3CL1 was one of the top 20% DEG, and we confirmed that both NP tissue and cells expressed remarkably higher level of CX3CL1 in mouse models (p<0.001∗). Besides, we further revealed that both the recombinant CX3CL1 and NP cells remarkably induced M2 polarization of RAW264.7 (p<0.001∗), respectively, while this effect was significantly reversed by si-CX3CL1 or JMS-17-2 (p<0.001∗). Furthermore, we found that M2 macrophages significantly decreased the apoptosis rate (p<0.001∗) and the catabolic gene levels (p<0.001∗) of NP cells, while increased the viability, proliferation as well as the anabolic gene levels of NP cells (p<0.01∗). Conclusions. Via regulating CX3CL1/CX3CR1 pathway, NP cells can induce the M2 macrophage polarization. M2 polarized macrophages can further promote NP cell viability, proliferation, and anabolism, while inhibit NP cell apoptosis and catabolism.
Background The purpose of this study is to evaluate the change patterns of leg numbness (LN) after lumbar decompression surgery (LDS), and to find the predictive factors that affect the recovery of numbness. Methods Patients who underwent LDS in our institution between August 2020 and July 2021 were prospectively enrolled in this study, and were followed by a 12-month follow-up. The degree of LN, leg pain (LP) and the disability were assessed using the visual analog scale (VAS) and oswestry disability index (ODI). Results A total of 314 patients finished the 12-month follow-up. The preoperative mean VAS-LN score was 3.49 ± 2.44, which decreased to 1.91 ± 1.30 at 3 months, to 1.29 ± 0.97 at 6 months and to 1.26 ± 0.96 at 12 months after surgery. The preoperative mean VAS-LP score was 6.05 ± 1.30, which decreased to 2.00 ± 0.86 at 3 months, to 1.02 ± 0.80 at 6 months, and to 0.49 ± 0.71 at 12 months after surgery. The preoperative mean ODI score was 27.90 ± 7.08, which decreased to 9.73 ± 3.09 at 3 months, to 6.72 ± 2.98 at 6 months, and to 4.57 ± 2.76 at 12 months after surgery. Via multivariate logistic regression analysis, only preoperative VAS-LN score (p < 0.001*) was identified as a significantly independent predictive factor for residual LN after operation. Conclusion Clinically significant improvement in LN was observed in the majority of patients within 6 months after LDS, and the improvement of VAS-LN was slower than the VAS-LP. High pre-operative VAS-LN score can independently predict the presence of residual LN after surgery at 12-month follow up.
With the recent development of minimally invasive techniques, minimally invasive posterior cervical foraminotomy (MIS-PCF) has become increasingly popular as a minimally invasive method to treat cervical radiculopathy. However, there are still controversies about whether MIS-PCF is superior to anterior cervical discectomy and fusion (ACDF). The purpose of this study is to evaluate the therapeutic effects of MIS-PCF and ACDF on unilateral cervical radiculopathy without myelopathy. We searched PubMed, Embase, the Cochrane Library, and Scopus comprehensively using the terms related to MIS-PCF. Two reviewers independently evaluated the potential studies, and extracted and analyzed the data of operation time, hospital stay, neck disability index (NDI) score, visual analog scale for neck pain (VAS-neck) and arm pain (VAS-arm) scores, reoperation rate, and complications. Seven studies with 1175 patients were included. The study population was 53.5% male, with a mean age of 48.9. MIS-PCF presented a significantly shorter postoperative hospitalization time compared to ACDF, while the operation time, complication/reoperation rate, and VAS-arm, VAS-neck, and NDI scores were comparable between the two cohorts. In North America, the average cost of MIS-PCF is lower than ACDF. Thus, we suggest that MIS-PCF is an alternative to ACDF for selected patients.
Objective:Through TTC staining, immunohistochemical analysis, RT-PCR and hind limb motor function evaluation and other experimental methods, to explore the regulatory mechanism of metformin on anti-apoptosis in rats with spinal cord injury (SCI).Methods:Establish a rat spinal cord injury model. Through Basso-Beattie -Bresnahan locomotor rating scale (BBB) and cant test to evaluate the recovery of hindlimb motor function in rats. The changes of necrotic area of spinal cord tissue were compared by TTC staining. Extraction of rat spinal cord tissue, by Dot blot analysis and immunohistochemical detection of the hydroxyl of DNA methylation level. By qPCR, Western Blot detection TET2mRNA and protein expression level, and the changes in the scope of spinal cord injury were detected by inhibiting the expression of TET2. The interaction between TET2 and Foxo3a was detected by immunoblotting and immunoprecipitation. Through RT-PCR assay Foxo3a downstream related changes in the level of gene expression.Results:Compared with the SCI+NS group, the necrotic area of the spinal cord tissue was reduced after metformin treatment, and the BBB score and the incline test score were higher ( P<0.05). At the same time, we found that the levels of TET2mRNA and protein increased significantly after SCI at 24 h, and the 5-hmC level of DNA increased. The levels of TET2mRNA and protein and 5-hmC increased further after the use of metformin. After using SC-1, compared with the SCI+MET group, the level of 5-hmC decreased and the area of infarction increased. After SCI, the mRNA levels of downstream genes Bim, P27kip, Bax increased significantly. After metformin treatment, the mRNA levels of Bim and Bax were lower than those in the SCI+NS group ( P<0.05). After SCI, the 5-hmC levels of downstream genes Bim, P27kip, Bax increased significantly. After metformin treatment, the 5-hmC levels of Bim and Bax were lower than those in the SCI+NS group ( P<0.05). Conclusion:Metformin can promote the interaction between TET2 and Foxo3a, increase the 5-hmC level of the overall DNA, and inhibit the activation of related apoptosis genes, thereby improving tissue damage and nerve function recovery after spinal cord injury.
BACKGROUND: Allicin can suppress liver and cardiac fibrosis; thus, we hypothesized that it might prevent scar tissue from extensive epidural fibrosis after laminectomy. METHODS: Human epidural scar fibroblasts were isolated from surgical specimens and treated with allicin at a gradient of concentrations. Morphology, viability, migration rate, cell cycle, and apoptosis rate were measured by fluorescence microscope, Cell Counting Kit-8 assay, scratch assay, and flow cytometry. Western blot was used to measure the expression level of proliferation-related proteins. - RESULTS: After treatment by allicin, cell viability (P = 0.042) and migration rate (P = 0.010 in scratch assay and P = 0.025 in transwell assay) decreased significantly in a dose-dependent manner. The percentage of G(1) phase cells significantly decreased (P = 0.017), whereas the percentage of S phase cells (P = 0.096) and G(2) phase cells (P = 0.038) significantly increased in a dose-dependent manner. Similarly, the percentage of apoptotic cells increased significantly in a dose-dependent manner (P = 0.036). Compared with the control group, the expression level of proliferating cell nuclear antigen protein (P = 0.081) and Bcl-2 protein (P = 0.029) significantly decreased, whereas the BAX protein level significantly increased (P = 0.017). - CONCLUSIONS: Allicin can suppress human epidural scar fibroblast migration, induce cell apoptosis, and block cell proliferation at S phase and G(2) phase.
脊髓损伤(spinal cord injury,SCI)是脊柱骨折的严重并发症之一.SCI不仅导致肢体活动和功能的障碍、社会和职业角色的受损,还可以导致患者心理状态的改变,从而增加患抑郁症的几率,严重影响患者与家属的日常生活[1].严重的SCI几乎可以导致损伤部位的神经细胞完全丧失活性,造成神经回路的不可逆破坏.神经干细胞或前体细胞(neural stem or precursor cells,NS/PCs)可分化为神经元和胶质细胞(星形胶质细胞和少突胶质细胞),从而替补损伤部位失活的神经细胞,因此NS/PCs移植被认为是治疗SCI的潜在有效方法[2].了解NS/PCs及其子代增殖与分化的分子机制,有助于制定更好的SCI后再生治疗策略.
Background: The use of 3D-printed scaffolds in repairing bone defects remains unexplored. We aimed to determine whether the duration of electrochemical deposition (ECD) affects the properties of hydroxyapatite (HA) coatings on 3D-printed titanium (TI) scaffolds as well as the corresponding phenotype of MC3T3-E1 cells seeded on these surfaces. Methods: Five groups of HA-coated TI scaffolds were produced using different durations of ECD (0, 5, 10, 20, and 30 min) and examined under scanning electron microscopy (SEM). MC3T3-E1 cell adhesion to the HA-coated scaffolds and subsequent proliferation and viability were assessed using SEM, DAPI staining, EdU staining, and Alamar Blue assay, respectively. MC3T3-E1 cell expression of osteogenic genes was analyzed by fluorescence RT-PCR. Results: On SEM, longer ECD durations resulted in more compact HA crystals of differing morphology coated onto the TI scaffolds. MC3T3-E1 cell adhesion differed among the five groups (p < 0.05), with the largest number of cells adhered to the scaffolds prepared with 30 min of ECD, followed by the group prepared with 20 min of ECD. However, the ECD duration of 20 min was associated with the highest cell viability and proliferation rate (both p < 0.05) as well as the highest mRNA expression levels of alkaline phosphatase, collagen I, osteocalcin and runt-related transcription factor 2 among the five groups (p < 0.05). Conclusions: In the fabrication of HA-coated 3D printed TI scaffolds, an ECD duration of 20 min resulted in scaffolds that best promoted MC3T3- E1 cell viability, proliferation and osteogenic gene expression. (C) 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.
Whether allicin can suppress the angiogenesis via inhibiting the activity of vascular endothelial cells (VECs) in preventing epidural hypertrophic scars remains unknown. VECs were treated by allicin at a gradient of concentrations. Cell activity was measured by CCK-8 assay, scratch assay and flow cytometry. Reverse-transcription PCR and Western Blot were used to measure the expression levels of relevant genes and proteins. After treated with allicin at concentrations of 0, 25, 50 and 100 mg/L, the viability of VECs significantly decreased at 24 h (p < 0.001*) and 48 h (p < 0.001*), and migration rate significantly decreased in scratch assay (p = 0.017*) and in Transwell assay (p = 0.021*). As the concentrations of allicin increased, the apoptosis rate of VECs rose up (p = 0.018*). There was no significant difference on cell numbers at S phase (p = 0.25), but cell numbers at G1 phase decreased (p = 0.039*) and at G2 phase increased (p = 0.047*). With the increase of allicin concentrations, the ability of tube formation for VECs significantly decreased (p < 0.001*). Comparing with control group, the expression of PCNA and BCL-2 decreased (p < 0.001*), while the expression of BAX increased significantly (p < 0.001*). Regarding to JAK2/STAT3 pathway, the expression levels of JAK3 and STAT3 decreased significantly with the increase of allicin concentrations (p < 0.001*). Allicin can suppress the activity of VECs probably by regulating JAK2/STAT3 pathway.
Objectives: This study was conducted to assess the clinical outcomes of using the posterior full-endoscopic cervical discectomy (PECD) in comparison with the conventional anterior cervical decompression and fusion (ACDF) in treating patients with cervical radiculopathy. Patients and Methods: From May 2015 to January 2018, patients with single cervical radiculopathy were enrolled in this study. The operative time, blood loss, hospital stay, and perioperative complications were recorded. The Visual Analog Scale (VAS) for neck and arm pain, the Neck Disability Index (NDI), and the modified MacNab criteria were used to quantify the postoperative outcomes. Results: A total of 84 patients were initially enrolled in this study, while three patients were lost during the follow-up. The remaining 81 patients were divided into two groups. Thirty-eight patients underwent conventional ACDF, and the rest 43 patients were treated by PECD procedure. The patients in the ACDF group were slightly older than those in the PECD group (51.4 +/- 8.2 VS 46.6 +/- 8.8 years old, p = 0.012*). The blood loss and hospital stay were significantly less in patients treated with PECD compared with those undergoing ACDF (p < 0.05*). There were no significant differences in the VAS scores, the NDI, and the modified MacNab criteria between the two groups. The patients in the ACDF group obtained a better Cobb angle and had less operative time compared with those in the PECD group (p < 0.05*). Only mild complications were observed in both groups, with no significant difference (p = 0.28). Conclusion: PECD could significantly relieve pain and disability with no severe complication, and the majority of patients were satisfied with this technique. Thus, it is safe and effective to use this procedure in managing patients with cervical radiculopathy as an alternative procedure to ACDF.
BACKGROUND:Platelet-rich plasma (PRP) has been frequently used to enhance bone regeneration. A meta-analysis was conducted to systematically assess the fusion rate and pain relief of applying PRP during spinal fusion surgery. METHODS:Studies investigating spinal fusion surgery combined with PRP were retrieved from Medline and the Web of Science in accordance with the inclusion and exclusion criteria. A quality evaluation was conducted using the Cochrane collaboration tool for randomized controlled trials and the Newcastle-Ottawa scale quality assessment for cohort trials. Statistical analysis was performed using RevMan, version 5.3. RESULTS:A total of 12 studies, including 3 randomized controlled trials and 9 cohort studies, with 661 patients, were included in the present meta-analysis. The mean age was 52.3 ± 8.0 years. Overall, the pooled results demonstrated that the differences in the fusion rates between the PRP and non-PRP treatment groups were not statistically significant. The risk ratio was 1.01 (95% confidence interval, 0.95-1.06; P = 0.83). Also, no significant difference in pain relief measured using the visual analog scale was found between the 2 groups. The mean difference was -0.08 (95% confidence interval, -0.26 to 0.11; P = 0.42). CONCLUSIONS:Adding PRP did not increase the fusion rates from spinal fusion surgery. In addition, no significant difference was found in pain relief between the PRP and non-PRP treatment groups.
This paper analyzes Seoul, South Korea a city developed around three centers in the past half a century with an eye on its urban heat island (UHI). It specifically looks into how the city's eight city-wide master plans established between 1966 and 2014 have shaped the city so as to transform the spatial distribution of its UHI. Master planning of Seoul has been regulating growth of its traditional center, the central business district, while promoting growth of its two newer centers, Yeongdeungpo and Gangnam business districts. Plan effects include more new buildings, cars, roads, population, and employment in the two new centers. As a result, Seoul's UHI spatially transformed over time as its traditional center became cooler while the newer two warmed up. This study makes a case for the role of master plans in shaping a city's thermal environment in the age of climate change.
This study was aimed to analyze the survival of patients with spinal chordomas. Patients’ data in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved and analyzed statistically. There were 765 patients with spinal chordomas between 1974 and 2013. The overall survival did not improve significantly over decades for patients receiving surgery and radiotherapy (SR) (P = 0.221). There were significant differences in overall survival among subgroups of patients receiving surgery (S), radiotherapy (R), and neither S nor R (NSR) (P = 0.031, 0.037, and 0.031, respectively). Cancer-specific survival did not change significantly among subgroups of patients receiving R (P = 0.411), while it increased steadily among subgroups of patients receiving S, SR, and NSR (P < 0.001, 0.001, and 0.049, respectively). In the multivariate Cox regression model, younger onset age (hazard ratio [HR] 1.052, P < 0.001), surgery (HR 0.291, P = 0.001), and tumor location of the sacrum (HR 0.401, P = 0.002) were associated with a better overall survival. Similarly, younger onset age (HR 1.036, P = 0.029), surgery (HR 0.221, P = 0.009), and tumor location of the sacrum (HR 0.287, P = 0.002) were also associated with a higher cancer-specific survival. The changes in overall and cancer-specific survival over time differ among different treatment groups. Younger onset age, surgical strategy, and tumor location of the sacrum may be correlated with a higher overall and cancer-specific survival.
BACKGROUND:Effective chemotherapy protocols are currently changing the treatment options for metastasized pancreatic cancer. Survival benefits after synchronous metastasectomy have been reported for selected patients. We set out to assess predictive factors of resectability for synchronous metastases after FOLFIRINOX. METHODS:Consecutive patients with metastatic pancreatic cancer undergoing surgery after FOLFIRINOX between 2011 and 2017 were identified from a prospectively collected database. Surgery following chemotherapy was indicated in patients with no more than six metastatic lesions, no progression detected on CT, and technically resectable disease. Patients who received synchronous metastasectomy were compared with patients who received explorative laparotomy or palliative surgery in terms of predictors of resectability and overall survival. In patients undergoing resection, prognostic factors were examined. RESULTS:Of 101 patients scheduled for surgery after FOLFIRINOX, synchronous metastasectomy was performed in 43 cases (43%) and non-resection surgery in 58 cases (57%). The shrinkage rate of the primary tumor on CT (P = 0.04) and the postchemotherapy serum CA19-9 concentration (P = 0.02) were associated with resectability. The median overall survival of the patients undergoing metastasectomy was longer than that of the patients without resection (21.9 months vs 16.4 months, P = 0.006). Postchemotherapy serum CA19-9 value (P = 0.04) and lymph node ratio (P = 0.01) were prognostic factors in the patients undergoing metastasectomy. CONCLUSIONS:In selected patients who satisfied our surgical criteria, shrinkage rate of primary tumor and postchemotherapy serum CA19-9 level, which predict resectability of metastasized pancreatic cancer, should be considered in decision making to avoid unnecessary surgery.
Background: Preoperative/Neoadjuvant treatment (NT) is increasingly used in unresectable pancreatic cancer (PDAC). However, similar to 40% of patients cannot be resected after NT and reliable preoperative response evaluation is currently lacking. We investigated CA 19-9 levels and their dynamics during NT for prediction of resectability and survival. Methods: We screened our institution's database for patients who underwent exploration or resection after NT with gemcitabine-based therapy (GEM) or FOLFIRINOX (FOL). Pre- and post-NT CA 19-9, resection rate and survival were analyzed. Results: Of 318 patients 165 (51.9%) were resected and 153 (48.1 %) received exploration. In the FOL group (n = 103; 32.4%), a post-NT CA 19-9 cutoff at 91.8 Wml had a sensitivity of 75.0% and a specificity of 76.9% for completing resection with an AUC of 0.783 in the ROC analysis (95% CI: 0.692-0.874; p < 0.001. PPV: 84.2%, NPV: 65.2%). Resected patients above the cutoff did not benefit from resection. Post-NT CA 19-9 <91.8 Wml (OR 11.63, p < 0.001) and CA 19-9 ratio of <0.4 (OR 5.77, p = 0.001) were independent predictors for resectability in FOL patients. Discussion: CA 19-9 levels after neoadjuvant treatment with FOLFIRINOX predict resectability and survival of PDAC more accurately than dynamic values and should be incorporated into response evaluation and surgical decision-making.