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).

Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201.

BACKGROUND: It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC. METHODS: Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. RESULTS: We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11). CONCLUSION: Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. TRIAL REGISTRATION: Unique ID issued by UMIN: UMIN000007819 (Date of registration: Apr 25, 2012) https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009128. Trial ID issued by jRCT: jRCTs061180089 (Date of registration: Mar 22, 2019, for a shift toward a "specified clinical trial" based on Clinical Trials Act in Japan) https://jrct.niph.go.jp/en-latest-detail/jRCTs061180089.

Cephalic Vein Cut-down for Totally Implantable Central Venous Access Devices With Preoperative Ultrasonography by Surgical Residents.

BACKGROUND/AIM: Cephalic vein (CV) cut-down for totally implantable central venous access devices (TICVADs) is not frequently used due to its low success rate. We compared the outcomes of CV cut-down using preoperative ultrasonography (US) performed by experienced surgeons versus surgical residents. PATIENTS AND METHODS: From December 2015 to December 2017, 10 surgeons implanted 212 TICVADs using CV cut-down with preoperative US. The surgeons were divided into two groups of five each: surgical residents (Group A, n=124 procedures) and experienced surgeons (Group B, n=88 procedures). Duration of operation time, completion rate, and complications were retrospectively analyzed. RESULTS: The completion rate was significantly higher in Group A (98.4% versus 92.0%, p=0.04). Duration of operation time (45.2±14.5 versus 42.0±13.1 minutes, p=0.22), rates of early complications (1.6% versus 1.1%, p=0.77) and late complications (3.2% versus 2.3%, p=0.68) were equivalent between the two groups. No fatal complications occurred in either group. CONCLUSION: CV cut-down can be safely performed by surgical residents under the use of preoperative US.

Concurrent chemoradiotherapy using cisplatin and S-1, followed by surgery for stage II/IIIA non-small cell lung cancer.

OBJECTIVES: Because chemoradiotherapy using cisplatin and S-1, an oral fluoropyrimidine, is effective for unresectable non-small cell lung cancer (NSCLC), an induction setting was used in a multicenter phase II study (Clinical trial number: UMIN000008205). The correlations of relapse and clinicopathological factors were analyzed. METHODS: We defined locally advanced NSCLC as pathologically proven chest wall invasion or hilar and/or mediastinal lymph node metastases by endobronchial ultrasound-guided transbronchial needle aspiration. The patients received two courses of S-1 administration for 14 days and intravenous cisplatin injection on day 8. A total dose of 40 Gy radiotherapy was concurrently received. Surgical resection was performed after completion of the treatment. RESULTS: Of the 23 eligible patients, 18 had stage IIIA and 5 had stage IIB NSCLC. Twenty of the eligible patients (87.0%) completed the regimen. Six (26.1%) complete responses were identified and 12 cases (52.2%) were histopathologically downstaged by induction chemoradiotherapy (ICRT). The 3-year overall survival rate was 58.1% and relapse-free survival (RFS) rate was 52.0%, respectively. Among several clinicopathological parameters, univariate RFS analysis identified that only downstaging was significantly associated with longer RFS times (p = 0.003). The radiological response did not reflect pathological response. When the variables of preoperative pathologically proven N2 metastasis, pathological ICRT effectiveness, and downstaging were included in the Cox proportional hazard modes, only the parameter of downstaging displayed significant hazard ratio (hazard ratio 0.13, p = 0.010). CONCLUSION: This protocol is considered an option among preoperative therapies and has obvious benefits for pathologically downstaged cases. CLINICAL TRIAL NUMBER: UMIN000008205. TRIAL REGISTRATION DATE: June 19, 2012.

Prognostic Impact of the ABCC11/MRP8 Polymorphism in Adjuvant Oral Chemotherapy with S-1 for Non-Small Cell Lung Cancer.

BACKGROUND: Postoperative 1-year administration of S-1, an oral derivative of 5-fluorouracil (5-FU), was shown to be feasible in lung cancer. The 5-year survival rates of postoperative patients treated with S-1 adjuvant chemotherapy and the prognostic impact of clinicopathological factors were examined. METHODS: The data of 50 patients with curatively resected pathological stage IB to IIIA non-small cell lung cancer, who were treated with S-1 postoperatively, were analyzed. The prognostic impacts of 22 clinicopathological factors including expressions of the 5-FU pathway enzymes were evaluated. A single-nucleotide polymorphism (SNP), i.e. 538G>A (rs17822931), of ABCC11/MRP8, which encodes a 5-FU excretion enzyme that is known as an earwax type determinant, was also evaluated. RESULTS: The 5-year overall and relapse-free survival rates were 72.5 and 67.5%, respectively. A performance status ≥ 1, lymphatic vessel invasion, blood vessel invasion, and the A/A type of SNP538, which is responsible for the dry earwax type, were significantly associated with shorter relapse-free survivals. In 34 patients who showed a relative performance of 70% or more for chemotherapy, multivariate survival analysis indicated significant hazard ratios only for the A/A type of SNP538 (p = 0.007). CONCLUSIONS: S-1 has sufficient power as adjuvant chemotherapy. However, its effect might be small in the dry earwax type patient group in an adjuvant setting.

[Thymic sarcomatoid carcinoma; report of a case].

The case was a 35-year-old male patient. Upon visiting a local doctor with complaints of cough and pain in the left chest, he was diagnosed as having an anterior mediastinal tumor. A large tumor of 15 cm in size was found by computed tomography( CT) scanning at the anterior mediastinum extending to the left thoracic cavity. Surgical resection was considered to be feasible, and the tumor was removed combined with the left brachiocephalic vein. Partial resection of the pericardium and the left upper lobe was also necessary. The diagnosis was a sarcoma-like thymic cancer by pathology. Although adjuvant chemotherapy was planned, the patient died of cancer recurrence at the 3rd postoperative month.

Thoracoscopic surgery for lung emphysema using an infrared camera.

Localized emphysema is difficult to detect on normal thoracoscopy. Indocyanine green (ICG) was used to precisely delineate an emphysematous lesion using an infrared camera system in a 75-year-old woman with a large emphysematous lesion in the right lower lobe. Due to repeated infections of the emphysematous lesion, right basal segmentectomy for localized lung emphysema was performed. During surgery, ICG (0.5 mg/kg) was injected intravenously, and the emphysematous lesion was detected as a fluorescence defect. This method could be used for precise resection of large emphysematous lesions because it permits clear detection with a small amount of ICG.

Anterior chest wall reconstruction with titanium plate sandwiched between two polypropylene sheets.

Extensive sternal resection carries the risk of difficult reconstruction and surgical complications. A 79-year-old woman underwent sternal resection and reconstruction for sternal chondrosarcoma. However, 18 months after the first operation, she developed six metastatic tumors on the anterior chest wall. She underwent subtotal sternectomy and rib resection, leaving a defect measuring 17 × 14 cm. Reconstruction of the anterior chest wall using a titanium plate sandwiched between two polypropylene mesh sheets is described. This method is potentially applicable to extensive anterior chest resection, and its advantages compared with conventional prostheses are rigidity, flexibility, and usability.

[A case of cardiac tamponade induced by gastric cancer responding to S-1].

A 56-year-old man was admitted to our hospital for gastric cancer. He had dyspnea before admission. Chest CT scan showed massive pericardial and pleural effusion. He was treated by cardiac drainage, and cytology of the effusion showed class V. We injected mitomycin C 10 mg into the pericardiac cavity, and also administered S-1 100 mg per day. His dyspnea improved and he was discharged. Afterward the dyspnea re-appeared, and he died 9 months after the diagnosis. We report this rare case of cardiac tamponade induced by gastric cancer responding to S-1 with a review of the literature.

Broncholithiasis managed by surgical resection.

Broncholithiasis is frequently associated with hemoptysis and infection. The most common cause of the disease is the presence of calcified material in a bronchus or in a cavity communicating with a bronchus. We present two cases of broncholithiasis treated by surgery. Case 1 involves a 57-year-old woman who presented with cough and bloody sputum. She had suffered from recurrent pneumonia in the left lower lobe caused by broncholithiasis for 2 years. We performed left S6 segmentectomy with bronchoplasty after unsuccessful bronchoscopic removal. Case 2 is a 65-year-old man who had had hilar tuberculous lymphoadenopathy at the age of 20. Recently he had suffered from recurrent bloody sputum and pulmonary suppuration for 3 years. We performed right upper lobectomy because the right B3 was occluded by inflammatory granulation with calcification. Postoperatively, these two patients have been alive and well with no complications. The indications of surgery for broncholithiasis include a difficult bronchoscopic broncholithectomy, massive hemoptysis, and irreversible complications such as chronic pulmonary suppurative disease.