Effect of dental metal artifact conversion volume on dose distribution in head‐and‐neck volumetric‐modulated arc therapy

Purpose: During treatment planning for head‐and‐neck volumetric‐modulated arc therapy (VMAT), manual contouring of the metal artifact area of artificial teeth is done, and the area is replaced with water computed tomography (CT) values for dose calculation. This contouring of the metal artifact areas, which is performed manually, is subject to human variability. The purpose of this study is to evaluate and analyze the effect of inter‐observer variation on dose distribution. Methods: The subjects were 25 cases of cancer of the oropharynx for which VMAT was performed. Six radiation oncologists (ROs) performed metal artifact contouring for all of the cases. Gross tumor volume, clinical target volume, planning target volume (PTV), and oral cavity were evaluated. The contouring of the six ROs was divided into two groups, small and large groups. A reference RO was determined for each group and the dose distribution was compared with those of the other radiation oncologists by gamma analysis (GA). As an additional experiment, we changed the contouring of each dental metal artifact area, creating enlarged contours (L), reduced contours (S), and undrawn contours (N) based on the contouring by the six ROs and compared these structure sets. Results: The evaluation of inter‐observer variation showed no significant difference between the large and small groups, and the GA pass rate was 100%. Similar results were obtained comparing structure sets L and S, but in the comparison of structure sets L and N, there were cases with pass rates below 70%. Conclusions: The results show that the artificial variability of manual artificial tooth metal artifact contouring has little effect on the dose distribution of VMAT. However, it should be noted that the dose distribution may change depending on the contouring method in cases where the overlap between PTV and metal artifact areas is large

Sphingosine 1-Phosphate (S1P) in the Peritoneal Fluid Skews M2 Macrophage and Contributes to the Development of Endometriosis

Sphingosine 1-phosphate (S1P), an inflammatory mediator, is abundantly contained in red blood cells and platelets. We hypothesized that the S1P concentration in the peritoneal cavity would increase especially during the menstrual phase due to the reflux of menstrual blood, and investigated the S1P concentration in the human peritoneal fluid (PF) from 14 non-endometriosis and 19 endometriosis patients. Although the relatively small number of samples requires caution in interpreting the results, S1P concentration in the PF during the menstrual phase was predominantly increased compared to the non-menstrual phase, regardless of the presence or absence of endometriosis. During the non-menstrual phase, patients with endometriosis showed a significant increase in S1P concentration compared to controls. In vitro experiments using human intra-peritoneal macrophages (MΦ) showed that S1P stimulation biased them toward an M2MΦ-dominant condition and increased the expression of IL-6 and COX-2. An in vivo study showed that administration of S1P increased the size of the endometriotic-like lesion in a mouse model of endometriosis

Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden

Introduction The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples. Methods Autopsied samples were obtained from lung, liver, and renal tumors from a 51-year-old male patient with advanced ALK-positive lung cancer who had acquired resistance to alectinib in only 3 months. We established an alectinib-resistant cell line (ABC-14) from pleural effusion and an alectinib/crizotinib-resistant cell line (ABC-17) and patient-derived xenograft (PDX) model from liver tumors. Additionally, we performed next-generation sequencing, direct DNA sequencing, and quantitative real-time reverse transcription polymerase chain reaction. Results ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression. Additionally, combined treatment with crizotinib/erlotinib inhibited cell growth. ABC-17 and PDX tumors harbored ALK G1202R, and PDX tumors metastasized to multiple organs in vivo, whereas the third-generation ALK-inhibitor, lorlatinib, diminished tumor growth in vitro and in vivo. Next-generation sequencing indicated high tumor mutation burden and heterogeneous tumor evolution. The autopsied lung tumors harbored ALK G1202R (c. 3604 G>A) and the right renal metastasis harbored ALK G1202R (c. 3604 G>C); the mutation thus comprised different codon changes. Conclusions High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy

群馬県訪問看護事業所における医療処置及び人工呼吸療法の事故発生状況，安全対策への取組の実態調査

目的：群馬県訪問看護事業所における医療処置及び人工呼吸器装着者の事故発生状況，安全対策への取組を明らかにし，地域における安全対策の体制整備を検討する． 方法：群馬県の訪問看護事業所の管理者421人を対象に自記式質問紙調査を実施した．有効回答は67人（15.9％），記述統計量を算出し，自由記述は類似性に基づき整理した． 結果：医療処置の事故は訪問看護提供時間内に14件（n＝31），影響度はレベル3以下，人工呼吸療法に関する事故は介護者在宅時が11件（n＝25），影響度はレベル4が1件（4.0％），レベル5が3件（12.0％）であった．発生時の対応は，介護職のケア時間に発生した事故の検討47.4％，地域の多機関で話し合う30.6％であった． 結論：人工呼吸器装着者の安全対策は，介護者のみの時間の療養者・家族が行う対策が重要であり，支援チーム，地域の多機関での事故に関する情報共有・検討が課題である．Purpose: This study examined the development of local safety measure systems by clarifying the incidence of accidents in medical procedures and among users of ventilators, as well as initiatives for safety measures at home-visit nursing stations in Gunma Prefecture. Methods: A self-administered questionnaire was distributed to 421 administrators of home-visit nursing stations in Gunma Prefecture and valid responses were obtained from 67 respondents (15.9％). Each item was subject to descriptive statistics and open-ended answers were organized based on similarities. Results: The respondents reported 14 (45.2％) medical procedure accidents that occurred during home-visit nursing hours with an impact level on patients of 3 or lower, and 11 (44.0％) ventilation therapy accidents that occurred while the caregiver was home, one of which had an impact level of 4 (4.0％) and three of which had an impact level of 5 (12.0％). Measures taken to address accidents were investigations into accidents that occurred during care hours by care workers in 47.4％ of cases and discussions among various local agencies in 30.6％ of cases. Conclusions: Regarding safety measures for users of ventilators, measures carried out by the patient and their family while only the caregiver was home were important. In the future, it is necessary to address the sharing and review of information on accidents among support teams and various local agencies.報

Transoral surgery for superficial head and neck cancer: National Multi‐Center Survey in Japan

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1–75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2–357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1–113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment