Published papers

Background: Prior to the approval of sorafenib, hepatic arterial infusion chemotherapy (HAIC) was offered to patients with advanced hepatocellular carcinoma (HCC) in East Asia, particularly Japan. According to the Japanese guidelines, HAIC is recommended as one of the treatment options in patients without extrahepatic metastasis (EHM). Methods: The present cohort study compared the use of HAIC and sorafenib on outcomes of patients with advanced HCC. Consecutive patients with advanced HCC who received HAIC or sorafenib as a first-line systemic therapy were enrolled from 10 Japanese institutions. The primary outcomes were overall survival (OS) in patients with macrovascular invasion (MVI), but without EHM, and OS in patients without both MVI and EHM. Results: Between 2009 and 2016, 2,006 patients were enrolled (541 HAIC patients, 1,465 sorafenib patients). After propensity score matching, the OS of patients with MVI but without EHM was significantly longer in the HAIC group compared with the sorafenib group (10.1 vs. 9.1 months for the HAIC and sorafenib groups, respectively; n = 170 for each group; hazard ratio [HR] 0.668; 95% confidence interval [95% CI] 0.475–0.935; p = 0.018). There was no significant difference in OS between patients without both MVI and EHM (12.2 vs. 15.4 months for the HAIC and sorafenib groups, respectively; n = 76 in each cohort after propensity score matching; HR 1.227; 95% CI 0.699–2.155; p = 0.475). Conclusion: HAIC is a potential front-line treatment choice in a subpopulation of patients with advanced HCC with MVI but without EHM.

One of the standard treatments of resectable esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemotherapy followed by surgery. Nivolumab showed efficacy for metastatic ESCC. However, the safety and efficacy of neoadjuvant nivolumab with chemotherapy for ESCC is unknown. Therefore, we will conduct FRONTiER to evaluate the safety and efficacy of nivolumab adding to neoadjuvant chemotherapy. FRONTiER comprises four experimental cohorts: (A) including nivolumab plus 5-FU+CDDP (cisplatin and 5-fluorouracil [CF]); (B) including one prior administration of nivolumab and the cohort A regimen; (C) including nivolumab plus docetaxel+ CF; (D) including one prior administration of nivolumab and the cohort C regimen; an expanded cohort. The primary end point is the incidence of dose-limiting toxicities from the initial dose to the 30th postoperative day. Clinical Trial Identifier: NCT03914443

Purpose: Impaired thumb opposition associated with advanced carpal tunnel syndrome may be treated by opponensplasty at the time of open carpal tunnel release. However, it is unclear which opponensplasty technique achieves the greatest functional improvement. This study aimed to compare the biomechanics of thumb opposition after Camitz, modified Camitz, and Burkhalter opponensplasties. Methods: We used 6 fresh-frozen cadaveric arms. Each procedure was reproduced on each arm: Camitz opponensplasty, modified Camitz opponensplasty involving palmaris longus transfer routed around the flexor carpi ulnaris pulley, and Burkhalter opponensplasty. Arms were fixed with the wrist in 0° flexion and the forearm in neutral pronosupination, and sensors were placed on the thumbnail, radial styloid, and dorsal aspect of the second metacarpal head. The donor tendon was pulled using a mechanical testing machine with a maximum force of 25 N, and the locations of the sensors in thumb opposition were recorded. The first web space and thumb pronation angles were measured for each procedure and compared. Results: The mean first web space and pronation angles produced using 25 N were 55° and 20°, 57° and 26°, and 53° and 29° for the Camitz, modified Camitz, and Burkhalter opponensplasties, respectively. The first web space angle was significantly larger after modified Camitz opponensplasty compared with Burkhalter opponensplasty with 25 N loading. Camitz opponensplasty resulted in a significantly smaller pronation angle compared with modified Camitz and Burkhalter opponensplasties with 25 N loading. Conclusions: The modified Camitz opponensplasty produces a relatively balanced biomechanical outcome in terms of the first web space and pronation angles. Conversely, Burkhalter opponensplasty has been shown to be a favorable technique for improving pronation. Clinical relevance: Modified Camitz opponensplasty with a pulley offers effective restoration of thumb opposition, including pronation. On the other hand, Burkhalter opponensplasty represents a suitable option not only for patients with high median palsy and injury to the palmar aponeurosis but also for those who require improved pronation.

Aims/Introduction: Recent randomized clinical trials have suggested that sodium–glucose cotransporter 2 inhibitors might reduce cardiovascular events and heart failure, and have renal protective effects. Despite these remarkable benefits, the effects of sodium–glucose cotransporter 2 inhibitors on bone and muscle are unclear. Materials and Methods: A subanalysis of a randomized controlled study was carried out to evaluate the effects of the sodium–glucose cotransporter 2 inhibitor, ipragliflozin, versus metformin on bone and muscle in Japanese patients with type 2 diabetes mellitus (baseline body mass index ≥22 kg/m and hemoglobin A1c 7–10%) who were already receiving sitagliptin. These patients were randomly administered ipragliflozin 50 mg or metformin 1,000–1,500 mg daily. The effects of these medications on the bone formation marker, bone alkali phosphatase; the bone resorption marker, tartrate-resistant acid phosphatase 5b (TRACP-5b); handgrip strength; abdominal cross-sectional muscle area; and bone density of the fourth lumbar vertebra were evaluated. Results: After 24 weeks of treatment, the changes in bone density of the fourth lumbar vertebra, handgrip strength and abdominal cross-sectional muscle area were not significantly different between the two groups. However, TRACP-5b levels increased in patients treated with ipragliflozin compared with patients treated with metformin (median 11.94 vs −10.30%, P < 0.0001), showing that ipragliflozin can promote bone resorption. Conclusions: There were no adverse effects on bone or muscle when sitagliptin was used in combination with either ipragliflozin or metformin. However, ipragliflozin combination increased the levels of TRACP-5b. A long-term study is required to further understand the effects of this TRACP-5b increase caused by ipragliflozin. 2