Successful recovery from a subclavicular ulcer caused by lenvatinib for thyroid cancer: a case report

Background: There are currently no effective therapeutic methods for locally recurrent, metastatic, or progressive radioactive iodine (RAI)-refractory differentiated thyroid cancer. However, multitargeted tyrosine kinase inhibitors (TKIs) such as lenvatinib or sorafenib have been approved for patients with RAI-refractory differentiated thyroid cancer as a second targeted therapy, and these agents can prolong patient survival. However, several cases have been reported that TKIs have caused fatal complications such as fistula formation or bleeding. Case presentation: We report a case of a 53-year-old woman, who underwent repeated neck dissections and RAI therapy after total thyroidectomy in an outside hospital. Pathology revealed a papillary carcinoma of the tall cell variant. Locoregional recurrence was not under control; therefore, she visited our hospital. Although surgery was performed for locoregional recurrences three times in our hospital, they were not under control and distant metastases were found in the lung and bone a year later. Therefore, although sorafenib was initiated, the locoregional recurrence progressed 6months later and computed tomography (CT) showed a 7-cm mass in the right subclavicular lesion. Lenvatinib was started at a dose of 24mg daily. However, although tumor was rapidly reduced, an ulcer occurred in the right subclavicular lesion and was gradually increasing in size. The pulsation of subclavicular artery was found in the deep portion of the ulcer. Therefore, a pectoralis major myocutaneous flap was transplanted to cover the ulcer. Lenvatinib was an antiangiogetic TKI; therefore, it was preoperatively discontinued for 8days and postoperatively for 12days. The postoperative course was uneventful. Conclusions: Fistula formation or bleeding is known to be a severe side effect of antiangiogenic TKIs such as lenvatinib or sorafenib. There is a possibility that severe complications can occur when initiating TKIs in patients whose tumor has invaded into the skin, vessels, trachea, esophagus, and other areas. Therefore, it is necessary to use antiangiogenic TKIs very carefully. It is important to determine the appropriate time to start TKIs; however, there is no established protocol for this, and it is a problem that needs urgent attention

A Multicenter Phase II Trial of Docetaxel, Cisplatin, and Cetuximab (TPEx) Followed by Cetuximab and Concurrent Radiotherapy for Patients With Local Advanced Squamous Cell Carcinoma of the Head and Neck (CSPOR HN01: ECRIPS Study)

Background: Induction chemotherapy (IC) is a treatment option for locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). However, treatment with docetaxel, cisplatin, and 5-FU (TPF) followed by cisplatin and radiotherapy is controversial because of toxicity concerns. The aim of this phase II study was to assess the feasibility of docetaxel, cisplatin, and cetuximab (TPEx) followed by cetuximab and concurrent radiotherapy for LA SCCHN.Patients and Methods: We enrolled patients with histological evidence of squamous cell carcinoma of the oropharynx, hypopharynx, or larynx without distant metastases. IC comprised cisplatin (75 mg/m2) and docetaxel (75 mg/m2) on day 1, repeated every 3 weeks for up to three courses. Cetuximab was initiated at 400 mg/m2, followed by 250 mg/m2 doses weekly until the end of radiotherapy. Radiotherapy (70 Gy/35 fr/7 w) was initiated after the last docetaxel administration. The primary endpoint was the rate of treatment completion.Results: We enrolled 54 patients (median age, 58 years) between August 2013 and October 2015. Our patients were 49 males and 5 females with hypopharyngeal (n = 28), oropharyngeal (n = 19), or laryngeal (n = 7) cancers, and 48 of them had stage IV disease. The overall response rate was 72.2% with a median follow-up of 36.1 months and a 3-year overall survival of 90.7%. The treatment completion rate was 76%; 50 patients (93%) received ≥2 courses of IC, and 41 (76%) completed radiotherapy. The frequencies of grade ≥3 febrile neutropenia or allergy/infusion reactions were 39% and 11%, respectively. There was one treatment-related death.Conclusions: IC with TPEx followed by cetuximab with concurrent radiotherapy showed acceptable compliance for the treatment of LA SCCHN. However, high frequency of febrile neutropenia remains a challenge and further improvement in the management of TPEx is necessary.Trial Registration: UMIN00000992

イヌモデルにおける脱細胞性細胞外マトリックスを用いた再生医学的手法による喉頭再生

京都大学0048新制・論文博士博士(医学)乙第12844号論医博第2084号新制||医||1006(附属図書館)31427(主査)教授 妻木 範行, 教授 開 祐司, 教授 伊達 洋至学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDA

Histologic Characterization of Human Scarred Vocal Folds

Vocal fold scarring remains a significant problem. Although several animal models have been developed to improve our understanding of the histopathology, the histologic features of scarred human vocal folds have rarely been reported. The present case studies aimed to define the histologic changes of scarred human vocal folds caused by cordectomy or cordotomy. Ten patients with the scarred vocal folds were involved in this study. Nine patients with early glottic cancer underwent endoscopic cordectomy, and one patient underwent superficial cordotomy for idiopathic scar. The postcordectomy or cordotomy scar was biopsied or resected 3-13 months after the original procedure. After confirming absence of any tumor in cancer patients, the remaining specimens were used in the present study. Histologic examination investigated deposition of extracellular matrix (ECM) including collagen, elastin, hyaluronic acid (HA), fibronectin, and decorin in the lamina propria of the scarred vocal folds. There was a wide range of variation in the deposition of ECM in scarred vocal folds. Excessive and disorganized collagen deposition was observed in most cases that had undergone deep resection of the lamina propria, whereas deposition of collagen was mild and well organized after superficial resection. Decorin was retained in all cases after superficial cordectomy or cordotomy, but varied after deep resection. Deposition of elastin, HA, and fibronectin varied regardless of depth of injury. Histology of scarred vocal folds may vary with degree of injury and individual healing mechanism

Increased concentrations of protein gene product 9.5 in the synovial fluid from horses with osteoarthritis

Our previous study established protein gene product 9.5 (PGP 9.5), a ubiquitin C-terminal hydrolase, as a specific cytochemical marker of synovial lining cells (type B synoviocytes) in the horse joint. The present study aimed to detect PGP 9.5 in the synovial fluid and shows that PGP 9.5 is a valuable marker of osteoarthritis in the horse. Immunohistochemical staining confirmed rich and consistent localization of PGP 9.5 immunoreactivity in the cytoplasm of synovial lining cells in the normal horse joint. Western blot analysis of synovial fluid from normal joints could detect a significant band corresponding to that contained in the brain and synovial membrane extracts. When 60 synovial fluid samples from normal and abnormal joints were assayed with an enzyme-linked immunosorbent assay (ELISA) system, the concentration of PGP 9.5 tended to be elevated in osteochondrosis dissecance, inflammatory arthropathy and intra-articular fracture, among which a statistically significant elevation was recognizable between the intra-articular fracture and the control. Thus, this study demonstrated the possibility that PGP 9.5, derived from synovial lining cells, may be a new biochemical marker for arthritic disorders of the horse

Increased expression of phosphatidylcholine (16:0/18:1) and (16:0/18:2) in thyroid papillary cancer.

A good prognosis can be expected for most, but not all, cases of thyroid papillary cancer. Numerous molecular studies have demonstrated beneficial treatment and prognostic factors in various molecular markers. Whereas most previous reports have focused on genomics and proteomics, few have focused on lipidomics. With the advent of mass spectrometry (MS), it has become possible to identify many types of molecules, and this analytical tool has become critical in the field of omics. Recently, imaging mass spectrometry (IMS) was developed. After a simple pretreatment process, IMS can be used to examine tissue sections on glass slides with location information.Here, we conducted an IMS analysis of seven cases of thyroid papillary cancer by comparison of cancerous with normal tissues, focusing on the distribution of phospholipids. We identified that phosphatidylcholine (16:0/18:1) and (16:0/18:2) and sphingomyelin (d18:0/16:1) are significantly higher in thyroid papillary cancer than in normal thyroid tissue as determined by tandem mass (MS/MS) analysis. These distributional differences may be associated with the biological behavior of thyroid papillary cancer

Magnifying endoscopy with narrow band imaging to determine the extent of resection in transoral robotic surgery of oropharyngeal cancer.

Transoral robotic surgery (TORS) is a less invasive treatment that is becoming popular all over the world. One of the most important factors for achieving success in TORS is the ability to determine the extent of resection during the procedure as the extent of resection in the laryngopharynx not only affects oncological outcomes but also directly affects swallowing and voice functions. Magnifying endoscopy with narrow band imaging (ME-NBI) is an innovative optical technology that provides high-resolution images and is useful in detecting early superficial pharyngeal cancers, which are difficult to detect by standard endoscopy. A 55-year-old male with superficial oropharyngeal cancer has been successfully treated by combining MB-NBI with TORS and MB-NBI was useful in determining the extent of resection. ME-NBI with TORS will make it possible to achieve a higher ratio of minimally invasive treatment in pharyngeal cancer

PRDX4 Potentially Predicts the Postoperative Outcome in Advanced Papillary Thyroid Carcinoma

Background: Peroxiredoxin 4 (PRDX4), a secreted antioxidant enzyme, can protect against hepatocellular carcinoma and lung adenocarcinoma, but its role in papillary thyroid carcinoma (PTC) is still unclear. In this study, we investigated the association of the PRDX4 expression with the prognosis of patients with advanced PTC. Methods: We conducted a retrospective case-control study at Kanazawa Medical University Hospital. We selected PTC patients over 55 years of age who received surgery from 2006 to 2014. The PRDX4 expression was immunohistochemically analyzed in paraffin-embedded tumor specimens of 70 patients with stages Ⅱ–Ⅳ advanced PTC. We also investigated the key roles of PRDX4 in a human PTC cell line (K-1) in vitro. Result: The weak expression of PRDX4 was found to be significantly associated with recurrence. In a multivariate analysis, the weak expression of PRDX4—rather than other pathological features of high invasiveness—predicted a poor prognosis. In vitro, the viability of human PTC cells was significantly suppressed after PRXD4 plasmid transfection. Conclusion: The weak expression of PRDX4 can predict recurrence with a potential poor prognosis in advanced PTC