Efficacy and safety of add-on mirogabalin to conventional therapy for the treatment of peripheral neuropathic pain after thoracic surgery: the multicenter, randomized, open-label ADMIT-NeP study.

BACKGROUND: For chronic pain after thoracic surgery, optimal timing of its diagnosis and effective treatment remains unresolved, although several treatment options are currently available. We examined the efficacy and safety of mirogabalin, in combination with conventional pain therapy (nonsteroidal anti-inflammatory drugs and/or acetaminophen), for treating peripheral neuropathic pain (NeP) after thoracic surgery. METHODS: In this multicenter, randomized, open-label, parallel-group study, patients with peripheral NeP were randomly assigned 1:1 to mirogabalin as add-on to conventional therapy or conventional treatment alone. RESULTS: Of 131 patients of consent obtained, 128 were randomized (mirogabalin add-on group, 63 patients; conventional treatment group, 65 patients). The least squares mean changes (95% confidence interval [CI]) in Visual Analogue Scale (VAS) score for pain intensity at rest from baseline to Week 8 (primary endpoint) were - 51.3 (- 54.9, - 47.7) mm in the mirogabalin add-on group and - 47.7 (- 51.2, - 44.2) mm in the conventional group (between-group difference: - 3.6 [95% CI: - 8.7, 1.5], P = 0.161). However, in patients with Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) score (used for the screening of NeP) ≥ 12 at baseline, the greater the S-LANSS score at baseline, the greater the decrease in VAS score in the mirogabalin add-on group, while no such trend was observed in the conventional treatment group (post hoc analysis). This between-group difference in trends was statistically significant (interaction P value = 0.014). Chronic pain was recorded in 7.9% vs. 16.9% of patients (P = 0.171) at Week 12 in the mirogabalin add-on vs. conventional treatment groups, respectively. Regarding activities of daily living (ADL) and quality of life (QOL), changes in Pain Disability Assessment Scale score and the EQ-5D-5L index value from baseline to Week 8 showed significant improvement in the mirogabalin add-on group vs. conventional treatment group (P < 0.001). The most common adverse events (AEs) in the mirogabalin add-on group were dizziness (12.7%), somnolence (7.9%), and urticaria (3.2%). Most AEs were mild or moderate in severity. CONCLUSIONS: Addition of mirogabalin to conventional therapy did not result in significant improvement in pain intensity based on VAS scores, but did result in significant improvement in ADL and QOL in patients with peripheral NeP after thoracic surgery. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs071200053 (registered 17/11/2020).

Chemotherapy effects on bone mineral density and microstructure in women with breast cancer.

INTRODUCTION: Chemotherapy involves the administration of steroids to prevent nausea and vomiting; however, its effect on bone microstructure remains unknown. This study aimed to evaluate the changes in bone mineral density (BMD) and bone microstructure associated with chemotherapy using high-resolution peripheral quantitative computed tomography (HR-pQCT) in women with early breast cancer. MATERIALS AND METHODS: This prospective single-arm observational study included non-osteoporotic, postmenopausal women with breast cancer. The patients underwent dual-energy X-ray absorptiometry (DXA), HR-pQCT, and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide (P1NP) measurements at baseline, end of chemotherapy, and 6 months after chemotherapy. The primary endpoint was the change in total volumetric BMD at the distal tibia and radius. RESULTS: Eighteen women were included in the study (median age: 57 years; range: 55-62 years). At 6 months after chemotherapy, HR-pQCT indicated a significant decrease in total volumetric BMD (median: distal tibia -4.5%, p < 0.01; distal radius -2.3%, p < 0.01), cortical volumetric BMD (-1.9%, p < 0.01; -0.8%, p = 0.07, respectively), and trabecular volumetric BMD (-1.1%, p = 0.09; -3.0%, p < 0.01, respectively). The DXA BMD also showed a significant decrease in the lumbar spine (median: -4.5%, p < 0.01), total hip (-5.5%, p < 0.01), and femoral neck (-4.2%, p < 0.01). TRACP-5b and P1NP levels were significantly increased at the end of chemotherapy compared to baseline. CONCLUSION: Postmenopausal women undergoing chemotherapy for early breast cancer experienced significant BMD deterioration in weight-bearing bone, which was further reduced 6 months after chemotherapy.

Risk factors for pulmonary complications after colorectal cancer surgery: a Japanese multicenter study.

PURPOSE: Pulmonary complications (PC) are a serious condition with a 20% mortality rate. However, few reports have examined risk factors for PC after colorectal surgery. This study investigated the frequency, characteristics, and risk factors for PC after colorectal cancer surgery. METHODS: Between January 2016 and December 2022, we retrospectively reviewed 3979 consecutive patients who underwent colorectal cancer surgery in seven participating hospitals. Patients were divided into patients who experienced PC (PC group, n = 54) and patients who did not (non-PC group, n = 3925). Clinical and pathological features were compared between groups. RESULTS: Fifty-four patients (1.5%) developed PC, of whom 2 patients (3.7%) died due to PC. Age was greater (80 years vs 71 years; p < 0.001), frequency of chronic obstructive pulmonary distress was greater (9.3% vs 3.2%; p = 0.029), performance status was poorer (p < 0.001), the proportion of underweight was higher (42.6% vs 13.4%, p < 0.001), frequency of open surgery was greater (24.1% vs 9.3%; p < 0.001), and blood loss was greater (40 mL vs 22 mL; p < 0.001) in the PC group. Multivariate analysis revealed male sex (odds ratio (OR) 2.165, 95% confidence interval (CI) 1.176-3.986; p = 0.013), greater age (OR 3.180, 95%CI 1.798-5.624; p < 0.001), underweight (OR 3.961, 95%CI 2.210-7.100; p < 0.001), and poorer ASA-PS (OR 3.828, 95%CI 2.144-6.834; p < 0.001) as independent predictors of PC. CONCLUSION: Our study revealed male sex, greater age, underweight, and poorer ASA-PS as factors associated with development of PC, and suggested that pre- and postoperative rehabilitation and pneumonia control measures should be implemented for patients at high risk of PC.

Effect of the lymphocyte-to-monocyte ratio on the prognosis of patients with obstructive colorectal cancer with a colonic stent: a retrospective multicenter study in Japan.

PURPOSE: The prognostic value of the lymphocyte-to-monocyte (LMR) ratio has been reported for various cancers, including colorectal cancer (CRC). The insertion of colonic stents is considered effective for patients with surgically indicated obstructive CRC, but their LMR can vary depending on factors such as inflammation associated with stent dilation and improvement of obstructive colitis. However, the usefulness of the LMR in patients with obstructive CRC and colonic stents and the optimal timing for its measurement remain unclear. We conducted this study to investigate the relationship between the pre-stent LMR and the mid-term prognosis of patients with obstructive CRC and stents as a bridge to surgery (BTS). METHODS: The subjects of this retrospective multicenter study were 175 patients with pathological stage 2 or 3 CRC. Patients were divided into a low pre-stent LMR group (n = 87) and a high pre-stent LMR group (n = 83). RESULTS: Only 3-year relapse-free survival differed significantly between the low and high pre-stent LMR groups (39.9% vs. 63.6%, respectively; p = 0.015). The pre-stent LMR represented a prognostic factor for relapse-free survival in multivariate analyses (hazard ratio 2.052, 95% confidence interval 1.242-3.389; p = 0.005), but not for overall survival. CONCLUSIONS: A low pre-stent LMR is a prognostic factor for postoperative recurrence in patients with obstructive CRC and a colonic stent as a BTS.

The C-reactive protein-albumin-lymphocyte (CALLY) index is a useful predictor of postoperative complications in patients with a colonic stent for obstructive colorectal cancer: a Japanese multicenter study.

PURPOSE: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel score that offers a good reflection of nutritional status, inflammatory response, and immune system status. The CALLY index is reported to correlate with the prognosis of various carcinomas. The purpose of the present study was to investigate the association between the CALLY index and the short-term prognosis of obstructive colorectal cancer managed with a colonic stent. METHODS: The subjects of this retrospective study were 263 patients who underwent colorectal resection after colonic stenting for obstructive colorectal cancer between 2016 and 2023. Patients were classified into a group with a low CALLY index (CALLY-L group, n = 85) and a group with a high (CALLY-H group, n = 178) CALLY index. RESULTS: The CALLY-L group had greater blood loss (53 mL vs 20 mL, p = 0.002) and higher poor performance status (PS3; 20% vs 10.1%, p = 0.033), open surgery (21.2% vs 7.3%, p = 0.001), distant metastases (41.2% vs 20.8%, p = 0.01), and postoperative complications (30.6% vs. 18.5%, p = 0.039) than the CALLY-H group. Multivariate analysis identified a prolonged operative time (odds ratio 1.983, 95% confidence interval 1.013-3.881; p = 0.045), greater blood loss (odds ratio 2.572, 95% confidence interval 1.291-5.129; p = 0.007) and a low CALLY index (odds ratio 1.961, 95% confidence interval 1.013-3.795; p = 0.045) as independent predictors of complications. CONCLUSION: The CALLY index may be a useful predictor of postoperative complications of obstructive colorectal cancer.

Effect of revised organ transplant law in Japan on lung transplantation.

PURPOSE: To investigate how revision of the organ transplant law in Japan affected lung transplantation in this country. METHODS: Lung transplant candidates registered between January, 2000 and December, 2009 were designated as the pre-revision group (n = 396) and those registered between January, 2011 and December, 2020, as the post-revision group (n = 1326). Both groups were analyzed retrospectively using data collected by the Japanese Society of Lung and Heart-Lung Transplantation. RESULTS: The number of patients who underwent brain-dead donor lung transplantation (BDLT) increased significantly after the law amendment (32.2 vs. 13.8%, p < 0.01). The median waiting time for BDLT was significantly reduced (708 days vs. 1163 days, p < 0.01) and the mortality rate while waiting for BDLT improved significantly after the law amendment (33.1 vs. 42.6%, p < 0.01). In the post-revision group, 18 pediatric patients underwent BDLT. The 5-year survival rates after BDLT were comparable between the groups (73.5% in the pre-revision group vs. 73.2% in the post-revision group, p = 0.32). CONCLUSIONS: The organ transplant law revision shortened the waiting time for BDLT significantly and decreased the mortality rate while waiting for BDLT. The posttransplant outcomes in Japan remained favorable throughout the study period.

Long-term outcomes and early recurrence after resection for metachronous pulmonary metastases from colorectal cancer.

PURPOSE: Properly selecting patients for aggressive curative resection for pulmonary metastases (PMs) from colorectal cancer (CRC) is desirable. We purposed to clarify prognostic factors and risk factors for early recurrence after metachronous PM resection. METHODS: Clinical data of 151 patients who underwent R0 resection for metachronous PMs from CRC at two institutions between 2008 and 2021 were reviewed. RESULTS: Seventy-six patients (50.3%) were male, and the median age was 71 (42-91) years. The numbers of colon/rectal cancers were 76/75, with pStage I/II/III/IV/unknown in 15/34/86/13/3. The duration from primary surgery to PM was 19.7 (1.0-106.4) months. The follow-up period was 41.9 (0.3-156.2) months. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 75.1%, 53.7%, and 51.1%, and the 1-, 3-, and 5-year overall survival (OS) rates were 97.7%, 87.5%, and 68.2%. On multivariate analysis, lymph node metastasis of the primary lesion (HR 1.683, 95%CI 1.003-2.824, p = 0.049) was an independent predictor of poor RFS, and history of resection for extrapulmonary metastasis (e-PM) (HR 2.328, 95%CI 1.139-4.761, p = 0.021) was an independent predictor of poor OS. Patients who experienced early recurrence (< 6 months) after PM resection showed poorer OS than others (3-year OS 50.8% vs. 90.2%, p = 0.002). On multivariate analysis, e-PM was an independent predictor of early recurrence after PM resection (OR 3.989, 95%CI 1.002-15.885, p = 0.049). CONCLUSION: Since a history of e-PM was a predictor of early recurrence and poor OS after R0 resection for PM, surgical treatment of patients with a history of e-PM should be considered carefully.

Post-thoracotomy pain syndrome in the era of minimally invasive thoracic surgery.

Post-thoracotomy pain syndrome (PTPS) is defined as pain around the wound that persists for more than 2 months after surgery. Persistent pain not only increases the use of analgesics and their side effects but also causes many social problems, such as decreased activities of daily living, decreased quality of life, and increased medical costs. In particular, thoracic surgery is associated with a higher frequency and severity of chronic pain than is surgery for other diseases. The basic principles of postoperative pain treatment, not limited to thoracic surgery, are multimodal analgesic methods (using combinations of several drugs to minimize opioid use) and around-the-clock treatment (administering analgesics at a fixed time and in sufficient doses). Thoracic surgeons must always be aware of the following three points: acute severe postoperative pain is a major risk factor for chronic pain; neuropathic pain due to intercostal nerve injury is a major cause of postoperative pain after thoracic surgery, and its presence must not be overlooked from the acute stage; and analgesics must be administered in sufficient quantities according to dosage and volume. The frequency of PTPS has decreased compared with that in the standard thoracotomy era because of the development of analgesia and the widespread use of minimally invasive procedures such as thoracoscopic surgery and robot-assisted surgery. However, no consistently effective prevention or treatment strategies for PTPS have yet been established. In this review, we focus on PTPS in the era of minimally invasive surgery and discuss the role of thoracic surgeons in its management.

Development and validation of a high-quality simulator with exchangeable peritoneum for transabdominal preperitoneal laparoscopic inguinal hernia repair.

INTRODUCTION: Practical simulation training with proper haptic feedback and the fragility of the human body is required to overcome the long learning curve associated with laparoscopic inguinal hernia repair (LIHR). However, few hernia models accurately reflect the texture and fragility of the human body. Therefore, in this study, we developed a novel model for transabdominal preperitoneal (TAPP) LIHR training and evaluated its validity. METHODS: We developed a high-quality mock peritoneum with a hydrated polyvinyl alcohol layer and a unique two-way crossing cellulose fiber layer. To complete the simulation, the peritoneum was adhered to a urethane foam inguinal base with surgical landmarks. Participants could perform all the procedures required for the TAPP LIHR. Twenty-four surgeons performed TAPP LIHR simulation using a novel simulator. Their opinions were rated on a 5-point Likert scale. Additionally, 6 surgical residents and 10 surgical experts performed the procedure. Their performance was evaluated using the TAPP checklist score and procedure time. RESULTS: Most participants strongly agreed that the TAPP LIHR simulator with an exchangeable peritoneum model was useful. The participants agreed on the model fidelity for tactile sensation, forceps handling, and humanlike anatomy. In comparisons between surgical residents and experts, the experts had significantly higher scores (10.6 vs. 17.2, p < 0.05) and shorter procedure times (92.3 vs. 55.9 min; p < .05) than did surgical residents. CONCLUSIONS: We developed a high-quality exchangeable peritoneal model that mimics the human peritoneum's texture and fragility. This model enhances laparoscopic simulation training, potentially shortening TAPP LIHR learning curves.

Curved Axillary Incision with Video-Assisted Thoracoscopic Surgery: An Alternative Approach for Teenage Female with Large Apical Chest Wall Tumor.

Primary chest wall tumors are rare, their common clinical features are not well known, and surgical resection remains the main treatment. Apical chest wall tumors require large skin incisions and dissection of the chest wall muscles, making it difficult to maintain cosmetic appearance, respiratory function, and support of the upper extremity. There are few treatment options and no studies have reported on thoracotomy that spares muscles and preserves cosmetic superiority. However, in benign chest wall tumors in young patients, it is necessary to consider radicality, cosmetic superiority, and muscle sparing. We used a combined axillary incision and thoracoscopic approach to treat a massive myxoid neurofibroma at the apical chest wall in a 14-year-old female and were able to preserve the chest wall, upper limb function, and cosmetic aspects. This report provides a detailed description of the combined axillary incision and thoracoscopic approach for apical chest wall tumors.

Designer umbilical cord-stem cells induce alveolar wall regeneration in pulmonary disease models.

Background: Researchers are focusing on cellular therapy for chronic obstructive pulmonary disease (COPD) using mesenchymal stem cells (MSCs), with human bone marrow-derived MSCs (hBM-MSCs) leading the way. However, BM-MSCs may not be as optimal as therapeutic cells owing to their low growth potential, invasive harvesting, and high expression of aging-related genes with poor differentiation potential. Consequently, umbilical cord-derived MSCs (hUC-MSCs), which have many excellent features as allogeneic heterologous stem cells, have received considerable attention. Allogeneic and heterologous hUC-MSCs appear to be promising owing to their excellent therapeutic properties. However, MSCs cannot remain in the lungs for long periods after intravenous infusion. Objective: To develop designer hUC-MSCs (dUC-MSCs), which are novel therapeutic cells with modified cell-adhesion properties, to aid COPD treatment. Methods: dUC-MSCs were cultured on type-I collagen gels and laminin 411, which are extracellular matrices. Mouse models of elastase-induced COPD were treated with hUC-MSCs. Biochemical analysis of the lungs of treated and control animals was performed. Results: Increased efficiency of vascular induction was found with dUC-MSCs transplanted into COPD mouse models compared with that observed with transplanted hUC-MSCs cultured on plates. The transplanted dUC-MSCs inhibited apoptosis by downregulating pro-inflammatory cytokine production, enhancing adhesion of the extracellular matrix to alveolar tissue via integrin ß1, promoting the polarity of M2 macrophages, and contributing to the repair of collapsed alveolar walls by forming smooth muscle fibers. dUC-MSCs inhibited osteoclastogenesis in COPD-induced osteoporosis. hUC-MSCs are a promising cell source and have many advantages over BM-MSCs and adipose tissue-derived MSCs. Conclusion: We developed novel designer cells that may be involved in anti-inflammatory, homeostatic, injury repair, and disease resistance processes. dUC-MSCs repair and regenerate the alveolar wall by enhancing adhesion to the damaged site. Therefore, they can contribute to the treatment of COPD and systemic diseases such as osteoporosis.

Effects of case volume on short- and long-term outcomes following cadaveric lung transplantation in Japan.

Background: Despite the low number of lung transplantations (LTs) in Japan, 10 LT facilities are accredited and good outcomes have been reported. A database review was conducted to clarify the impact of case volume at LT facilities in Japan on short- and long-term outcomes. Methods: All cadaveric LT cases treated between 2000 and 2021 in Japan were analyzed using the database of the Japanese Society of Lung and Heart-Lung Transplantation (JSLHT). The nine institutions represented were categorized into the low-volume (LV; <80 cumulative LT cases, <8 LTs/year, n=5) and high-volume (HV; ≥80 cumulative LT cases, ≥8 LTs/year, n=4) centers. Ninety-day and 1-year mortality, as well as 5- and 10-year survival data were evaluated. Results: A total of 658 cadaveric LTs were performed at the nine institutions. The 90-day rates of mortality at the HV and LV centers were 3.5% and 3.9%, respectively (P=0.801), while the 1-year mortality rates were 9.2% and 11.5%, respectively (P=0.199). Additionally, log-rank analysis of Kaplan-Meier curves showing case volume did not reveal a significant difference in long-term survival between the HV and LV centers (P=0.272), though the LV centers had wide differences for long-term outcomes (P=0.030). Conclusions: Case volume did not have effects on short- or long-term outcomes following LT in Japan, while there were large variations in long-term outcomes among the LV centers compared to those of the HV centers.