Young Uk Kim

Effect of transforaminal epidural polydeoxyribonucleotide injections on lumbosacral radiculopathy: A case report

Rationale: Transforaminal epidural glucocorticoids administration is widely performed for the management of lumbosacral radiculopathy. However, it may worsen the condition of patients with type 2 diabetes mellitus (DM). Polydeoxyribonucleotide (PDRN) was recently noted as a substitute for glucocorticoids. Patient concerns: A 44-year-old male patient was admitted to our pain clinic with symptoms of low back pain with severe pain and tingling sensation of left posterolateral leg. He had type 2 DM medicated with Glimepiride and Metformin. Blood glucose level was 367 mg/dL. He declined to use glucocorticoid. Diagnoses: He was diagnosed as left foraminal disc protrusion at L4–5, left subarticular disc protrusion at L5-S1. Interventions: Fluoroscopically guided transforaminal epidural PDRN injections were carried out. Outcomes: The patient was followed up for more than 6 months and demonstrated good improvement in lumbosacral radiculopathy without any complications. Lessons: This is the first successful report on epidural injection of PDRN.

The prolongation of pulse transit time after a stellate ganglion block: An objective indicator of successful block.

The relationship between the change of pulse transit time and the presence of clinical signs after stallate ganglion block (SGB) was investigated in patients with disorders mediated by the sympathetic nervous system. SGB is used for the treatment and diagnosis of these disorders; however, a successful objective marker does not exist. Therefore, identifying increased blood flow following SGB and determining whether pulse transit time could be used to verify the success of SBG would be a helpful resource.

Prospective Analysis of Adoptive TIL Therapy in Patients with Metastatic Melanoma: Response, Impact of Anti-CTLA4, and Biomarkers to Predict Clinical Outcome

Purpose: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has consistently demonstrated clinical efficacy in metastatic melanoma. Recent widespread use of checkpoint blockade has shifted the treatment landscape, raising questions regarding impact of these therapies on response to TIL and appropriate immunotherapy sequence. Patients and Methods: Seventy-four metastatic melanoma patients were treated with autologous TIL and evaluated for clinical response according to irRC, overall survival, and progression-free survival. Immunologic factors associated with response were also evaluated. Results: Best overall response for the entire cohort was 42%; 47% in 43 checkpoint-naïve patients, 38% when patients were exposed to anti-CTLA4 alone (21 patients) and 33% if also exposed to anti-PD1 (9 patients) prior to TIL ACT. Median overall survival was 17.3 months; 24.6 months in CTLA4-naïve patients and 8.6 months in patients with prior CTLA4 blockade. The latter patients were infused with fewer TIL and experienced a shorter duration of response. Infusion of higher numbers of TIL with CD8 predominance and expression of BTLA correlated with improved response in anti-CTLA4 naïve patients, but not in anti-CTLA4 refractory patients. Baseline serum levels of IL9 predicted response to TIL ACT, while TIL persistence, tumor recognition, and mutation burden did not correlate with outcome. Conclusions: This study demonstrates the deleterious effects of prior exposure to anti-CTLA4 on TIL ACT response and shows that baseline IL9 levels can potentially serve as a predictive tool to select the appropriate sequence of immunotherapies. Clin Cancer Res; 24(18); 4416–28. ©2018 AACR.

Effect of multiple intra-articular injections of polynucleotides on treatment of intractable knee osteoarthritis: A case report

Rationale: Knee osteoarthritis (KOA) is a chronic joint degenerative disease. Intra-articular injection (IAI) of hyaluronic acid (HA) is widely used to treat KOA. However, some HA injections have no effect at all. Polynucleotides (PN) are recently noted as a valid substitute for HA. Patient concerns: A 61-year-old female was admitted to the pain center with symptoms of pain over the knee and warmth feeling with stiffness in the left knee. The patient reported chronic severe pain in the left knee area despite 6 times IAI of HA. She had past medical history of breast cancer and thyroid cancer. Diagnoses: She was diagnosed as having KOA. Interventions: Ultrasound-guided IAI of PN was carried out 3 times in 3 weeks. Outcomes: She was followed-up for more than 5 months with good improvement in intractable knee pain without any adverse event. Lessons: IAI of PN is an efficient therapeutic option for KOA treatment if HA injection is unsuccessful.

4-1BB Agonist Focuses CD8+ Tumor-Infiltrating T-Cell Growth into a Distinct Repertoire Capable of Tumor Recognition in Pancreatic Cancer

Purpose: Survival for pancreatic ductal adenocarcinoma (PDAC) patients is extremely poor and improved therapies are urgently needed. Tumor-infiltrating lymphocyte (TIL) adoptive cell therapy (ACT) has shown great promise in other tumor types, such as metastatic melanoma where overall response rates of 50% have been seen. Given this success and the evidence showing that T-cell presence positively correlates with overall survival in PDAC, we sought to enrich for CD8+ TILs capable of autologous tumor recognition. In addition, we explored the phenotype and T-cell receptor repertoire of the CD8+ TILs in the tumor microenvironment. Experimental Design: We used an agonistic 4-1BB mAb during the initial tumor fragment culture to provide 4-1BB costimulation and assessed changes in TIL growth, phenotype, repertoire, and antitumor function. Results: Increased CD8+ TIL growth from PDAC tumors was achieved with the aid of an agonistic 4-1BB mAb. Expanded TILs were characterized by an activated but not terminally differentiated phenotype. Moreover, 4-1BB stimulation expanded a more clonal and distinct CD8+ TIL repertoire than IL2 alone. TILs from both culture conditions displayed MHC class I-restricted recognition of autologous tumor targets. Conclusions: Costimulation with an anti-4-1BB mAb increases the feasibility of TIL therapy by producing greater numbers of these tumor-reactive T cells. These results suggest that TIL ACT for PDAC is a potential treatment avenue worth further investigation for a patient population in dire need of improved therapy. Clin Cancer Res; 23(23); 7263–75. ©2017 AACR.

Optimal cut-off points of lumbar pedicle thickness as a morphological parameter to predict lumbar spinal stenosis syndrome: a retrospective study

Purpose Lumbar spinal stenosis syndrome (LSSS) is induced by factors such as ligamentum flavum hypertrophy, facet joint hypertrophy and disc degeneration. However, the role of lumbar pedicle (LP) in LSSS has yet to be evaluated. We devised a new morphological parameter called the lumbar pedicle thickness (LPT) to evaluate the connection between LSSS and the LP. We hypothesized that the LPT is a major morphological parameter in the diagnosis of LSSS. Patients and methods The LPT data were collected from 136 patients diagnosed with LSSS. A total of 99 control subjects underwent lumbar spine magnetic resonance imaging (MRI) as part of a detailed medical assessment. Axial T2-weighted magnetic resonance (MR) images were acquired from all the participants. Using our picture archiving and communication system, we analyzed the thickness of the LP at the level of L5 vertebra on MRI. Results The average LPT was 9.46±1.81 mm in the control group and 13.26±1.98 mm in the LSSS group. LSSS patients showed a significantly greater LPT (P<0.001) than the control group. The receiver operating characteristic (ROC) curve analysis showed an optimal cutoff point of 11.33 mm for the LPT, with 83.8% sensitivity, 83.8% specificity and area under the curve of 0.92 (95% confidence interval [CI], 0.89–0.96). Conclusion A higher LPT was associated with a higher possibility of LSSS, suggesting its importance in the evaluation of patients with LSSS.

Combining Immune Checkpoint Blockade and Tumor-Specific Vaccine for Patients With Incurable Human Papillomavirus 16–Related Cancer: A Phase 2 Clinical Trial

Importance In recurrent human papilloma virus (HPV)–driven cancer, immune checkpoint blockade with anti–programmed cell death 1 (PD-1) antibodies produces tumor regression in only a minority of patients. Therapeutic HPV vaccines have produced strong immune responses to HPV-16, but vaccination alone has been ineffective for invasive cancer. Objective To determine whether the efficacy of nivolumab, an anti–PD-1 immune checkpoint antibody, is amplified through treatment with ISA 101, a synthetic long-peptide HPV-16 vaccine inducing HPV-specific T cells, in patients with incurable HPV-16–positive cancer. Design, Setting, and Participants In this single-arm, single-center phase 2 clinical trial, 24 patients with incurable HPV-16–positive cancer were enrolled from December 23, 2015, to December 12, 2016. Duration of follow-up for censored patients was 12.2 months through August 31, 2017. Interventions The vaccine ISA101, 100 &mgr;g/peptide, was given subcutaneously on days 1, 22, and 50. Nivolumab, 3 mg/kg, was given intravenously every 2 weeks beginning day 8 for up to 1 year. Main Outcomes and Measures Assessment of efficacy reflected in the overall response rate (per Response Evaluation Criteria in Solid Tumors, version 1.1). Results Of the 24 patients (4 women and 20 men; 22 with oropharyngeal cancer; median age, 60 years [range, 36-73 years]), the overall response rate was 33% (8 patients; 90% CI, 19%-50%). Median duration of response was 10.3 months (95% CI, 10.3 months to inestimable). Five of 8 patients remain in response. Median progression-free survival was 2.7 months (95% CI, 2.5-9.4 months). Median overall survival was 17.5 months (95% CI, 17.5 months to inestimable). Grades 3 to 4 toxicity occurred in 2 patients (asymptomatic grade 3 transaminase level elevation in 1 patient and grade 4 lipase elevation in 1 patient), requiring discontinuation of nivolumab therapy. Conclusions and Relevance The overall response rate of 33% and median overall survival of 17.5 months is promising compared with PD-1 inhibition alone in similar patients. A randomized clinical trial to confirm the contribution of HPV-16 vaccination to tumoricidal effects of PD-1 inhibition is warranted for further study. Trial Registration ClinicalTrials.gov identifier: NCT02426892

Superior articular process cross-sectional area is a new sensitive parameter for the diagnosis of lumbar central canal spinal stenosis

Purpose Previous studies reported that hypertrophied superior articular process (SAP) was associated with an increased risk of lumbar foraminal stenosis. However, no study investigated the effect of SAP hypertrophy in lumbar central canal spinal stenosis (LCCSS). We hypothesized that the SAP cross-sectional area (SAPCSA) is the main morphologic feature in the diagnosis of LCCSS. Patients and methods Data regarding the SAPCSA were collected from 109 patients with LCCSS. All patients were enrolled after the LCCSS diagnosis was confirmed by an experienced, board-certified neuroradiologist. All patients had clinical manifestations compatible with LCCSS. A total of 120 subjects in the control group underwent lumbar spine MRI as part of non-symptomatic medical examination. T2-weighted axial images were obtained from the 2 groups. Using a picture archiving and communications system, we analyzed the CSA of the bone margin of SAP at the level of L4–L5 facet joint on MRI. Results The average SAPCSA was 96.63±13.37 mm2 in the control group, and 123.59±14.18 mm2 in the LCCSS. The LCCSS group showed significantly higher levels of the SAPCSA (P<0.001) compared with the control one. Receiver operator characteristic (ROC) curve analysis was performed to determine the validity of the SAPCSA as a predictor of LCCSS. In the LCCSS group, the optimal cut-off-point was 110.71 mm2, with 83.5% sensitivity, 83.3% specificity, and area under the curve of 0.92 (95% CI: 0.88–0.95). Conclusion Higher SAPCSA values were associated with a higher possibility of LCCSS. These results are important in the evaluation of patients with LCCSS.

Optimal Cut-Off Value of the Superior Articular Process Area as a Morphological Parameter to Predict Lumbar Foraminal Stenosis

Background. We devised a new morphological parameter called the superior articular process area (SAPA) to evaluate the connection between lumbar foraminal stenosis (LFS) and the superior articular process. Objective. We hypothesized that the SAPA is an important morphologic parameter in the diagnosis of LFS. Methods. All patients over 60 years of age were included. Data regarding the SAPA were collected from 137 patients with LFS. A total of 167 control subjects underwent lumbar magnetic resonance imaging (MRI) as part of a routine medical examination. We analyzed the cross-sectional area of the bone margin of the superior articular process at the level of L4-L5 facet joint in the axial plane. Results. The average SAPA was 96.3 ± 13.6 mm2 in the control group and 128.1 ± 17.2 mm2 in the LFS group. The LFS group was found to have significantly higher levels of SAPA (p < 0.001) in comparison to the control group. In the LFS group, the optimal cut-off value was 112.1 mm2, with 84.4% sensitivity, 83.9% specificity, and AUC of 0.94 (95% CI: 0.91–0.96). Conclusions. Higher SAPA values were associated with a higher possibility of LFS. These results are important in the evaluation of patients with LFS.

Effect of polydeoxyribonucleotide injection on pes anserine bursitis: A case report

Rationale: Pes anserine (PA) bursitis is an inflammatory condition of the medial knee. The PA bursa becomes more painful when infected, damaged, or irritated. Although various treatment options have been attempted to treat PA bursitis, optimal treatments are still debated. This study aims to investigate the effect of polydeoxyribonucleotide (PDRN) injection on reducing pain and inflammation in a patient presenting with PA bursitis. Patient concerns: A 50-year-old female patient was admitted to our pain clinic with symptoms of tenderness and pain over the medial knee. Physical examination revealed the pain to be located over the proximal medial tibia at the insertion of the conjoined tendons of the PA. The knee had lost its range of movement and strength, and resisted knee flexion. Diagnoses: She was diagnosed as having PA bursitis. Interventions: Ultrasound guided PA bursa injection was carried out. Outcomes: Follow-up for the patient was more than eight months. She showed good improvement in PA bursitis without any complications. Lessons: This is the first successful report of successful PDRN injection for PA bursa.