Anti-Inflammatory Effects of Adiponectin Receptor Agonist AdipoRon against Intervertebral Disc Degeneration.

Adiponectin, a hormone secreted by adipocytes, has anti-inflammatory effects and is involved in various physiological and pathological processes such as obesity, inflammatory diseases, and cartilage diseases. However, the function of adiponectin in intervertebral disc (IVD) degeneration is not well understood. This study aimed to elucidate the effects of AdipoRon, an agonist of adiponectin receptor, on human IVD nucleus pulposus (NP) cells, using a three-dimensional in vitro culturing system. This study also aimed to elucidate the effects of AdipoRon on rat tail IVD tissues using an in vivo puncture-induced IVD degeneration model. Analysis using quantitative polymerase chain reaction demonstrated the downregulation of gene expression of proinflammatory and catabolic factors by interleukin (IL)-1ß (10 ng/mL) in human IVD NP cells treated with AdipoRon (2 µM). Furthermore, western blotting showed AdipoRon-induced suppression of p65 phosphorylation (p < 0.01) under IL-1ß stimulation in the adenosine monophosphate-activated protein kinase (AMPK) pathway. Intradiscal administration of AdipoRon was effective in alleviating the radiologic height loss induced by annular puncture of rat tail IVD, histomorphological degeneration, production of extracellular matrix catabolic factors, and expression of proinflammatory cytokines. Therefore, AdipoRon could be a new therapeutic candidate for alleviating the early stage of IVD degeneration.

Effect of Bone Metastasis Cancer Board on Spinal Surgery Outcomes: A Retrospective Study.

Background and Objectives: Bone metastasis cancer boards (BMCBs) focusing on the management of bone metastases have been gathering much attention. However, the association of BMCBs with spinal surgery in patients with spinal metastases remains unclear. In this retrospective single-center observational study, we aimed to clarify the effect of a BMCB on spinal metastasis treatment. Materials and Methods: We reviewed consecutive cases of posterior decompression and/or instrumentation surgery for metastatic spinal tumors from 2008 to 2019. The BMCB involved a team of specialists in orthopedics, rehabilitation medicine, radiation oncology, radiology, palliative supportive care, oncology, and hematology. We compared demographics, eastern cooperative oncology group performance status (ECOGPS), Barthel index (BI), number of overall versus emergency surgeries, and primary tumors between patients before (2008-2012) and after (2013-2019) BMCB establishment. Results: A total of 226 patients including 33 patients before BMCB started were enrolled; lung cancer was the most common primary tumor. After BMCB establishment, the mean patient age was 5 years older (p = 0.028), the mean operating time was 34 min shorter (p = 0.025), the mean hospital stay was 34.5 days shorter (p < 0.001), and the mean BI before surgery was 12 points higher (p = 0.049) than before. Moreover, the mean number of surgeries per year increased more than fourfold to 27.6 per year (p < 0.01) and emergency surgery rates decreased from 48.5% to 29.0% (p = 0.041). Patients with an unknown primary tumor before surgery decreased from 24.2% to 9.3% (p = 0.033). Postoperative deterioration rates from 1 to 6 months after surgery of ECOGPS and BI after BMCB started were lower than before (p = 0.045 and p = 0.027, respectively). Conclusion: The BMCB decreased the emergency surgery and unknown primary tumor rate despite an increase in the overall number of spinal surgeries. The BMCB also contributed to shorter operation times, shorter hospital stays, and lower postoperative deterioration rates of ECOGPS and BI.

Cluster analysis of deterioration sites after first-line epidermal growth factor receptor-tyrosine kinase inhibitor in epidermal growth factor receptor mutated non-small cell lung cancer.

Introduction: For epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC), no studies have treated the site of recurrence after first-line tyrosine kinase inhibitor (TKI) treatment as a "metastasis pattern". This study aims to assess whether these patients have a specific "metastasis pattern" at the site of recurrence after the treatment. Material and methods: Data were collected from all consecutive EGFR mutated NSCLC patients between 2009 and 2021. Metastatic patterns were analyzed using cluster analysis in patients with EGFR mutated NSCLC. Results: During the study period, 83 EGFR mutated NSCLC patients were treated with EGFR-TKI. Patients who had no metastases at the time of diagnosis were divided into two groups according to the presence or absence of recurrence of metastases after TKI administration. Patients with metastases at diagnosis were divided into 4 groups by cluster analysis. A statistically significant difference in metastasis frequency was confirmed among these 6 groups (χ2 test, p = 0.0001). Furthermore, when the frequency of metastasis recurrence after TKI administration in these 6 groups was examined, a statistically significant difference was confirmed (χ2 test, p = 0.0001). Conclusions: Even in EGFR mutation-positive patients, the knowledge of the recurrent patterns might be useful for clinical practice in the foreseeable future, as it enables more efficient detection of metastatic disease through imaging, and more effective treatment at predicted metastatic sites.

Distant organ metastasis patterns in lung cancer patients with pancreatic metastasis - a cluster analysis.

Introduction: Pancreatic metastasis of lung cancer is rare, but the narrowing or obstruction of the biliary tract from pancreatic metastases limits the choice of antitumour agents. Lung cancer patients with pancreatic metastasis often have metastasis of other organs. For these patients, however, no studies have been conducted to evaluate distant metastasis sites as metastasis patterns. This study aims to assess whether these patients have specific metastasis patterns at the time of diagnosis of lung cancer. Material and methods: Data were collected from consecutive lung cancer patients with pancreatic metastasis between April 2012 and March 2022. Metastatic patterns were analysed using cluster analysis in patients with lung cancer. Results: During the study period, 33 (2.0%) of 1659 patients were diagnosed as having pancreatic metastasis. Of the 33 patients, 28 (84.8%) were male. Eighteen, 14, and one patient had small cell lung cancer (SCLC), lung adenocarcinoma, and large cell neuroendocrine carcinoma, respectively. They were divided into 3 groups by cluster analysis. A statistically significant difference in metastasis frequency was confirmed among these 3 groups (χ2 test, p = 0.001). Conclusions: In lung cancer patients with pancreatic metastasis, knowledge of the metastatic patterns might be useful for clinical practice in the foreseeable future because it enables more efficient detection of metastatic disease through imaging, and more effective treatment at predicted metastatic sites.

An autopsied NSCLC patient with huge adrenal gland metastasis with rapid growth and local invasion.

The adrenal gland is a common site for metastasis from non-small-cell lung cancer (NSCLC). Adrenal metastases are usually solitary, asymptomatic and diagnosed incidentally during staging of patients with lung adenocarcinoma. Huge but sole adrenal gland metastasis with rapid growth and local invasion is extremely rare and those occurring in the setting of NSCLC have not been reported previously. Herein we describe a 66 year old male patient with NSCLC who had huge but sole adrenal gland metastasis with rapid growth and local invasion and extension into stomach, pancreas and left kidney. Interestingly there was no increase in the primary lesion of NSCLC. These findings were confirmed by autopsy. Despite the occurrence of an adrenal gland metastasis with considerable size being rare, it should be considered in the differential diagnosis, even if there is no involvement of the other organ and the primary lesion is of a small size.

Skin metastasis from small cell lung cancer.

Patients with skin metastasis always had disseminated metastases in many organs. We herein report an unusual case with skin metastasis from small cell lung cancer (SCLC). The patient was treated with platinum-containing chemotherapy, and the response to the therapy was evaluated as partial response. The patient had slowly progressive disease and died of SCLC 16 months after the diagnosis of the diseases. If skin lesions, whether it may be typical or not, are found in SCLC patients, biopsy from the lesion would be considered to perform. Although trunk may be the most common sites, it is important to suspect such metastasis occurs in patients with SCLC.

Predictors of Persistent Postoperative Numbness Following Lumbar Fusion in Patients Older Than 75 Years: A Minimum 2-Year Follow-up.

OBJECTIVE: To evaluate the preoperative and perioperative predictors of persistent leg numbness following lumbar fusion in patients aged ≥ 75 years. METHODS: This single-center retrospective study examined 304 patients aged ≥ 75 years who underwent lumbar fusion for lumbar degenerative disease (102 men, 202 women; mean age, 79.2 [75-90] years). The visual analogue scale (VAS) score for leg numbness was examined preoperatively and at 2 years postoperatively. The persistent leg numbness group included patients with a 2-year postoperative VAS score for leg numbness ≥ 5 points. The demographic data were also reviewed. A multivariate stepwise logistic regression analysis was performed for variables with univariate analysis values of p < 0.2 on univariate analysis. RESULTS: In total, 71 patients (23.4%) experienced persistent postoperative leg numbness. Multivariate logistic regression analysis revealed that a history of lumbar decompression, longer symptom duration, and a preoperative VAS score for leg numbness ≥ 5 points were associated with greater postoperative persistent leg numbness following lumbar fusion. In contrast, other factors, such as sex, body mass index, vertebral fracture, diabetes mellitus, depression, symptom duration, dural injury, operative time, and estimated blood loss, were not. CONCLUSION: A history of preoperative lumbar decompression, longer symptom duration, and greater preoperative VAS scores for leg numbness were preoperative predictors of persistent postoperative leg numbness following lumbar fusion in older patients. Although lumbar fusion is expected to improve leg numbness, surgeons should consider the surgical history, duration, and preoperative numbness intensity and explain the potential postoperative persistent leg numbness in advance.

The Utility and Feasibility of Smart Glasses in Spine Surgery: Minimizing Radiation Exposure During Percutaneous Pedicle Screw Insertion.

OBJECTIVE: Spine surgeons are often at risk of radiation exposure due to intraoperative fluoroscopy, leading to health concerns such as carcinogenesis. This is due to the increasing use of percutaneous pedicle screw (PPS) in spinal surgeries, resulting from the widespread adoption of minimally invasive spine stabilization. This study aimed to elucidate the effectiveness of smart glasses (SG) in PPS insertion under fluoroscopy. METHODS: SG were used as an alternative screen for fluoroscopic images. Operators A (2-year experience in spine surgery) and B (9-year experience) inserted the PPS into the bilateral L1-5 pedicles of the lumbar model bone under fluoroscopic guidance, repeating this procedure twice with and without SG (groups SG and N-SG, respectively). Each vertebral body's insertion time, radiation dose, and radiation exposure time were measured, and the deviation in screw trajectories was evaluated. RESULTS: The groups SG and N-SG showed no significant difference in insertion time for the overall procedure and each operator. However, group SG had a significantly shorter radiation exposure time than group N-SG for the overall procedure (109.1 ± 43.5 seconds vs. 150.9 ± 38.7 seconds; p = 0.003) and operator A (100.0 ± 29.0 seconds vs. 157.9 ± 42.8 seconds; p = 0.003). The radiation dose was also significantly lower in group SG than in group N-SG for the overall procedure (1.3 ± 0.6 mGy vs. 1.7 ± 0.5 mGy; p = 0.023) and operator A (1.2 ± 0.4 mGy vs. 1.8 ± 0.5 mGy; p = 0.013). The 2 groups showed no significant difference in screw deviation. CONCLUSION: The application of SG in fluoroscopic imaging for PPS insertion holds potential as a useful method for reducing radiation exposure.

Clinical Characteristics, Surgical Outcomes, and Risk Factors for Emergency Surgery in Patients With Spinal Metastases: A Prospective Cohort Study.

OBJECTIVE: To elucidate the patient characteristics and outcomes of emergency surgery for spinal metastases and identify risk factors for emergency surgery. METHODS: We prospectively analyzed 216 patients with spinal metastases who underwent palliative surgery from 2015 to 2020. The Eastern Cooperative Oncology Group performance status, Barthel index, EuroQol-5 dimension (EQ5D), and neurological function were assessed at surgery and at 1, 3, and 6 months postoperatively. Multivariate analysis was performed to identify risk factors for emergency surgery. RESULTS: In total, 146 patients underwent nonemergency surgery and 70 patients underwent emergency surgery within 48 hours of diagnosis of a surgical indication. After propensity score matching, we compared 61 patients each who underwent nonemergency and emergency surgery. Regardless of matching, the median performance status and the mean Barthel index and EQ5D score showed a tendency toward worse outcomes in the emergency than nonemergency group both preoperatively and 1 month postoperatively, although the surgery greatly improved these values in both groups. The median survival time tended to be shorter in the emergency than nonemergency group. The multivariate analysis showed that lesions located at T3-10 (p = 0.002; odds ratio [OR], 2.92; 95% confidence interval [CI], 1.48-5.75) and Frankel grades A-C (p < 0.001; OR, 4.91; 95% CI, 2.45-9.86) were independent risk factors for emergency surgery. CONCLUSION: Among patients with spinal metastases, preoperative and postoperative subjective health values and postoperative survival are poorer in emergency than nonemergency surgery. Close attention to patients with T3-10 metastases is required to avoid poor outcomes after emergency surgery.

Patient Age and EGFR-positive Non-small Cell Lung Cancer: A Multicenter Retrospective Study.

BACKGROUND/AIM: The median age of subjects in many clinical trials of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor conducted to date has been approximately 60 years. However, it is not uncommon to encounter EGFR gene-positive patients in their 70s or 80s. Based on information obtained from these clinical trials, EGFR gene-positive non-small cell lung cancer (NSCLC) patients are considered to be younger than EGFR-negative patients. In this study, we analyzed clinical data to identify whether this assumption is true. PATIENTS AND METHODS: We retrospectively reviewed the medical records of NSCLC patients diagnosed in a multicenter clinical practice from 2009 to 2023. Patients included all cases of non-advanced and advanced NSCLC. RESULTS: Information on 2,540 patients, including 605 EGFR gene-positive patients, was collected. The median age of EGFR-positive and EGFR-negative patients was 72 years and 71 years, respectively, and there was no significant difference in the age of patients between these two groups (p=0.7887). The most common age in these two groups was 70 years. Among the EGFR gene subtypes, the frequency of exon 19 deletion decreased with age, whereas that of EGFR L858R increased. CONCLUSION: Patients in their 70s and 80s with non-small cell lung cancer were relatively frequently EGFR gene-positive. To avoid missing out on treatment opportunities, EGFR gene testing should also be performed on patients in this age group.

Investigation of age and smoking in NSCLC patients with uncommon EGFR mutations.

Introduction: In addition to the two common epidermal growth factor receptor (EGFR) mutations, there are many uncommon mutations. Due to the high number of uncommon types, as well as the rarity of patients, there is lack of information regarding patient demographics, especially age distribution and smoking status. Against this background, we conducted an analysis to clarify the background of patients with uncommon EGFR mutations, especially considering their age distribution and smoking status. Materials and Methods: We retrospectively reviewed the medical records of non-small cell lung cancer (NSCLC) patients diagnosed in a multicenter clinical practice from 2002 to 2023. Patients included all cases of non-advanced and advanced NSCLC with uncommon EGFR mutations. Result: Information on 158 patients with uncommon EGFR mutation was collected. Median age was 72 years, with the age distribution showing that most patients were in their 70s. There was a significant difference between the proportion of patients aged up to 59 years and the proportion aged 75 years or older. In 88 patients with a smoking habit history, a significant correlation was found between smoking index and age. Among non-smokers, there was a peak between ages 70 and 74, which was older than the peak among smokers. Conclusions: Even in elderly patients and NSCLC patients with a history of smoking, although it is unclear whether EGFR mutation is common or uncommon, EGFR gene testing should be performed considering the possibility of these patients being EGFR-positive.

Real Clinical Practice of Combined Atezolizumab Plus Chemotherapy in Patients With Small Cell Lung Cancer.

BACKGROUND/AIM: Atezolizumab, an anti-PD-L1 antibody, has been increasingly administered in combination with chemotherapy to patients with small cell lung cancer (SCLC). This study aimed to determine how patients with extensive disease (ED) -SCLC responded to atezolizumab with chemotherapy and found factors affecting long-term response and survival. PATIENTS AND METHODS: This study focused on patients with SCLC who were treated with a combination of atezolizumab and chemotherapy in Japan between 2019 and 2023. Patient information and tumor response were analyzed, along with adverse events. We compared data and estimated survival probabilities. RESULTS: In our clinical trial, 95 patients with SCLC who received this treatment had a median progression-free survival of 6.0 months and a median overall survival of 15.0 months. Immune-related adverse events were observed in 13.7% of the patients, with grade 3 or higher in 5.3%. The efficacy and immune-related adverse events associated with this treatment regimen were comparable to those reported in previous clinical trials. Progression-free survival >2 years was observed in a small number of patients (5.3%). CONCLUSION: Our research will offer important insights for the future care of patients with extensive-stage SCLC by utilizing atezolizumab in combination with chemotherapy. Accumulation and confirmation of clinical practice results will have important implications for the future implementation of this therapy.

Relationship Between TTF-1 Expression and PFS of Pemetrexed-containing Chemotherapy in Non-squamous-NSCLC Patients With and Without Driver Genes.

BACKGROUND/AIM: We performed a retrospective study too clarify whether the presence or absence of driver genes affects the relationship between thyroid transcription factor-1 (TTF-1) expression and response to pemetrexed (PEM) in non-squamous non-small cell lung cancer (non-sq-NSCLC) patients. PATIENTS AND METHODS: We reviewed the medical charts of patients treated with PEM-containing chemotherapy during the period from February 2016 to February 2022 at Mito Medical Center-University of Tsukuba, Ryugasaki Saiseikai General Hospital, and University of Tsukuba Hospital. RESULTS: During the period of the study, 185 driver gene-negative patients negative, and 65 driver gene-positive patients were evaluated. Among the 165 driver gene-negative patients, progression free survival (PFS) of TTF-1-expressing patients treated with PEM-containing chemotherapy was significantly longer compared to that of TTF-1-negative patients. In the analysis of 65 driver gene-positive patients, the PFS of TTF-1-positive patients treated with PEM-containing chemotherapy did not differ significantly from that of TTF-1-negative patients. There was no significant difference in PFS between driver gene-negative and driver gene-positive patients treated with PEM-containing chemotherapy. Comparison between four groups defined according to the presence of driver gene and TTF-1 expression indicated shorter PFS only in 'driver gene-negative and TTF-1-negative' patients. CONCLUSION: In driver gene-positive non-sq NSCLC patients, expression of TTF does not affect the survival outcome of PEM-containing-chemotherapy. In other words, in these patients, second-line or later-line PEM-containing chemotherapy after development of resistance for specific-tyrosine kinase inhibitor could be expected to have the same level of efficacy as first-line PEM containing chemotherapy in driver gene-negative, TTF-1-positive non-sq NSCLC patients.

Impact of COVID-19 Pandemic on Advanced Non-small Cell Lung Cancer Treatment at a Japanese Hospital.

Background/Aim: The COVID-19 pandemic has forced medical institutions to scale back their practice. Changes in patient behavior seemed to be having an impact. We conducted a survey with the aim of reviewing lung cancer treatment during the pandemic period and identifying problems. Patients and Methods: We examined the medical records of all patients pathologically diagnosed with non-small cell lung cancer (NSCLC) in our hospital from 2017 to 2022. NSCLC patients were divided into two groups: those diagnosed between 2017 and 2019 (first period) and those diagnosed between 2020 and 2022 (second period). Results: Within the study period, 267 NSCLC patients (first period: 147 patients, second period: 121 patients) were diagnosed in our hospital. The patients in the two study periods did not differ significantly in age (p=0.613), ECOG performance status (p=0.125), and clinical stage (p=0.354). Tumor size was significantly larger in the second period with a mean of 5.88 cm ± 3.02, compared to 4.24 cm ± 1.76 in the first period (p<0.001). In the standard treatment group, the median survival time was 457 days in the first period and 313 days in the second period (p=0.063). In the best supportive care group, median survival time was 122 days in the first period and 57 days in the second period (p=0.004). Conclusion: Patients themselves refrained from seeking consultation for lung cancer treatment during the pandemic period. It is inconclusive how to reduce the delay due to the suppression of consultations, but this is an important issue for the future.

Discontinuation of Immune Checkpoint Inhibitor due to irAEs in NSCLC Patients With EGFR Mutation.

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have revolutionized advanced non-small cell lung cancer (NSCLC) treatment. Even patients with epidermal growth factor receptor (EGFR)-mutated NSCLC may choose an ICI after failure of EGFR-tyrosine kinase inhibitor treatment. ICI-mediated immune-related adverse events (irAEs) may prompt NSCLC patients to discontinue their treatment. This study evaluated the effect of ICI treatment discontinuation on the prognosis of patients with EGFR-mutated NSCLC. PATIENTS AND METHODS: We performed a retrospective study that reviewed the clinical courses of patients with EGFR-mutated NSCLC treated with ICI therapy from February 2016 to February 2022. 'Discontinuation' was defined as failure to receive at least two treatment courses of ICI due to grade 2 irAEs (grade 1 in the lung) or higher in patients responding to ICI. RESULTS: During the study period, 13 of 31 patients discontinued ICI therapy due to irAEs. Survival from the initiation of ICI therapy was significantly longer in patients who discontinued ICI therapy compared with those who did not discontinue. In uni- and multivariate analyses, 'discontinuation' was a favourable factor. There was no significant difference in survival from ICI initiation between patients with grade 3 or higher irAEs and those with grade 2 or lower irAEs. CONCLUSION: In this patient cohort, discontinuation of ICI therapy due to irAEs did not adversely affect prognosis in patients with EGFR-mutant NSCLC. Our results suggest that when treating patients with EGFR-mutant NSCLC with ICIs, chest physicians should consider discontinuing ICI with close monitoring.