Characterization of BRAFThr599dup mutation as a targetable driver mutation identified in lung adenocarcinoma by comprehensive genomic profiling

浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科thesi

Distribution of coronal plane alignment of the knee classification does not change as knee osteoarthritis progresses: a longitudinal study from the Toei study

浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科thesi

Two cases of malignant peritoneum mesothelioma diagnosed by diagnostic laparoscopic surgery

悪性中皮腫は主に胸膜、腹膜に発生する予後不良な疾患である。アスベスト曝露との関連性がよく知られているが、明らかではない症例もみられる。そして悪性腹膜中皮腫は稀な疾患であり、臨床的に特異的な所見もないため鑑別に苦慮する。今回我々は癌性腹膜炎を指摘され、診断的腹腔鏡手術により悪性中皮腫と診断できた2例を経験した。症例1: 37歳　発熱、食欲不振を主訴に近医を受診し癌性腹膜炎のため紹介されたが、腹水細胞診、セルブロック法による確定診断は困難であった。症例2: 65歳　咳嗽を主訴に近医を受診し、癌性腹膜炎のため当科を紹介されたが腹水貯留は限定的であり、腹腔穿刺を実施できなかった。2症例とも診断的腹腔鏡手術を行い、症例1は悪性腹膜中皮腫　肉腫型もしくは二相型、症例2は悪性腹膜中皮腫もしくは胸膜中皮腫　上皮型と診断された。癌性腹膜炎の原因疾患は多岐にわたり、その確定診断はしばしば困難なこともある。その中でも稀な悪性腹膜中皮腫の2症例の確定診断に診断的腹腔鏡手術が有用であった。Malignant mesothelioma is a disease with a poor prognosis that occurs primarily in the pleura and peritoneum. Although the association with asbestos exposure is well known, it is unclear in some cases. Malignant peritoneal mesothelioma is a rare condition characterized by the absence of specific findings, making it difficult to distinguish. In this report, we describe two cases of malignant mesothelioma diagnosed through diagnostic laparoscopic surgery in patients with peritonitis carcinomatosa. Case 1: A 37-year-old woman was referred for peritonitis carcinomatosa due to fever and anorexia. However, the diagnosis was difficult to make by cytology and cell block of ascites. Case 2: A 65-year-old woman was referred for peritonitis carcinomatosa with a chief complaint of cough. Nevertheless, the ascites was limited in some area and abdominal paracentesis could not be performed. Consequently, diagnostic laparoscopic surgery was performed in both cases. We found that the diagnosis of Case1 was malignant peritoneal mesothelioma sarcomatoid type or biphasic and that of Case2 was malignant peritoneal mesothelioma or pleural mesothelioma epithelioid type. The diagnosis of peritonitis carcinomatosa is complicated and malignant peritoneal mesothelioma should be considered as a differential diagnosis, and diagnostic laparoscopic surgery proved to be a valuable option in achieving a precise diagnosis.journal articl

A case of stage IIB adenocarcinoma of the cervix identified as cervical mass at 24 weeks' gestation

妊娠に合併した子宮頸部扁平上皮癌は妊娠初期の頸部細胞診で診断できることが多いが、腺癌は細胞診の正診率が低いことが知られている。妊娠初期の頸部細胞診で指摘されず、妊娠中期に粗大な頸部腫瘤として発見され、診断に苦慮したが根治治療を行った子宮頸部腺癌ⅢC1期の1例を経験した。患者は29歳、4妊2産。前医で行った妊娠初期の頸部細胞診はNILMであった。妊娠24週に6cm大の頸部腫瘤が出現した。擦過細胞診はAGCで腺癌が疑われたが、組織診で確定診断できず、妊娠27週に当院へ紹介となった。頸部後唇に9cmの腫瘤を認め、直腸診では右基靭帯に硬結を触知した。針生検を施行したがやはり確定診断出来なかった。臨床的に頸部腺癌ⅡB期を強く疑い、周産期科および新生児科と検討の上、妊娠28週で帝王切開、その4週間後に広汎子宮全摘術を施行した。病理診断は子宮頸部腺癌（通常型内頸部腺癌と粘液性癌の混在、pT2bN1M0）で、腫瘤内に異なる組織型が混在していた。術後同時化学放射線療法を行い、治療終了後、再発所見なく経過観察中である。妊娠中の頸部腫瘤は悪性腫瘍を念頭におき、進行期や妊娠週数を十分に検討した管理・治療が重要である。In pregnant women, cervical squamous cell carcinoma can often be diagnosed in early pregnancy by cervical cytology, but adenocarcinoma is difficult to diagnose by cytology. The patient was 29 years old (gravida 4, para 2). Cervical cytology in early pregnancy found that she was negative for intraepithelial lesions or malignancy. A 6-cm cervical mass appeared at 24 weeks’ gestation. Uterine cervical adenocarcinoma was suspected, but histology could not confirm the diagnosis, and the patient was referred to our hospital at 27 weeks' gestation. A 9-cm cervical mass was found. A needle biopsy was performed, but the diagnosis could not be confirmed. Clinically, we strongly suspected stage IIB cervical adenocarcinoma, and, after consulting the perinatology and neonatology departments, we performed a cesarean section at 28 weeks' gestation, followed by abdominal radical hysterectomy four weeks later. The pathological diagnosis was adenocarcinoma of the cervix (mixed with endocervical adenocarcinoma, usual type and mucinous carcinoma, pT2bN1M0). The patient was treated with concurrent chemoradiotherapy and is under observation with no evidence of recurrence at 20 months after treatment. It is important to manage and treat cervical masses during pregnancy with malignancy in mind after carefully considering the disease stage and stage of pregnancy.journal articl

静岡産科婦人科学会雑誌 13巻1号 表紙

othe

A pediatric case of immediate hypersensitivity to tosufloxacin involving no cross-reactivity to other topical quinolones

キノロン系抗菌薬アレルギーの交差反応性は少しずつ知見が蓄積されているが，トスフロキサシントシル酸塩水和物（以下トスフロキサシン）への即時型アレルギー反応は報告が少なく，検査法や交差反応性が明確となっていない． 症例は6歳女児で，トスフロキサシンを内服10分後に顔面の膨疹，20分後に全身の膨疹が出現し，夜間救急室を受診した．喘鳴も出現し，SpO2が84%（室内気）のため，アナフィラキシーの診断でアドレナリンが筋注された．当院でのSkin prick test（トスフロキサシン100μg/mL）は平均膨疹径2mmと陰性で好塩基球活性化試験も陰性であった．薬物誘発試験では，内服10分後に顔全体の掻痒，口唇の血管性浮腫と眼瞼周囲の膨疹が出現したため，陽性と判定された． 他のキノロン系抗菌薬は，ナジフロキサシン軟膏，オフロキサシン眼軟膏の塗布試験，レボフロキサシン点眼液，モキシフロキサシン点眼液の塗布試験・点眼負荷試験は陰性で交差反応性が無いことが確認された．Although evidence for cross-reactivity in quinolone allergy is gradually accumulating, immediate hypersensitivity to tosufloxacin tosilate hydrate (tosufloxacin) have not been reported, and testing methods and cross-reactivity have not been clarified. A 6-year-old girl received tosufloxacin. She developed facial wheals 10 minutes after ingesting the drug, and generalized urticaria after 20 minutes, and she was taken to the emergency department. She was diagnosed with anaphylaxis based on stridor and 84% SpO2 and was treated with adrenaline intramuscularly. A skin prick test with 100 μg/mL of tosufloxacin was negative with an average wheal diameter of 2 mm. She performed a drug provocation test for tosfloxacin. She developed swelling and strong itching of her lips, mouth and eyelids 10 minutes after the initial dose. This case was diagnosed as immediate hypersensitivity to tosufloxacin using oral drug provocation test. We administered nadifloxacin and ofloxacin as ointment, levofloxacin and moxifloxacin as eye drops, which were also negative, indicating no cross-reactivity.journal articl

浜松医科大学小児科学雑誌 5巻1号 目次

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A Case of Nephrotic Syndrome with Primary Peritonitis Caused by Streptococcus pneumoniae Serotype 15B/C

基礎疾患のある小児に対して23価莢膜多糖体肺炎球菌ワクチン（PPSV23）の追加接種が推奨されてきたが， 2024年8月から沈降20価肺炎球菌結合型ワクチン（PCV20）の追加接種が本邦で可能となった．ワクチンの選択についてはガイドラインでの推奨がなく，現場の裁量に委ねられているのが現状である．症例はネフローゼ症候群初発の2歳男児．ステロイド治療開始から4日目に発熱，腹痛，嘔吐を呈し，血液培養からStreptococcus pneumoniaeが検出された．同菌による原発性腹膜炎と診断し，計2週間の抗菌薬治療を行った．本児は沈降13価肺炎球菌結合型ワクチン（PCV13）を4回接種済であったが，今回検出されたS.pneumoniaeの莢膜血清型は「15B/C」であり，PCV13非含有血清型，PCV20及びPPSV23含有血清型であった．小児に対するPPSV23接種の免疫原性が限定的であるため，本児にはPCV20を接種する方針とした．今後は症例を集積し，接種推奨について検討する必要がある．An additional dose of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for children with underlying medical conditions. However, since August 2024, vaccination with the 20-valent pneumococcal conjugate vaccine (PCV20) has also become available for the same indication in Japan. Currently, there are no guideline recommendations regarding vaccine selection, and the choice of vaccine is left to the discretion of the physician. A 2-year-old boy was referred to our hospital with chief complaints of edema and lack of vitality. He was diagnosed with nephrotic syndrome and started on steroid therapy. On the fourth day of admission, he developed fever, abdominal pain, and vomiting. Blood culture revealed Streptococcus pneumoniae, leading to a diagnosis of primary peritonitis. The patient was treated with antimicrobial agents for a total of two weeks. The capsular serotype of S. pneumoniae identified in this case was “15B/C”, which is not included in PCV13 but is covered by both PCV20 and PPSV23. Due to the limited immunogenicity of PPSV23 in children, we decided to vaccinate him with PCV20. Accumulating further cases and fostering discussions on immunization recommendations will be critical moving forward.journal articl

A preterm infant with congenital syphilis born to a mother who was untreated during pregnancy: acute-phase complications and long-term neurodevelopmental outcomes

梅毒合併妊婦に対して，妊娠中に無治療であると子宮内胎児死亡，死産，新生児死亡，早産のリスクが高まる．無治療妊婦から出生した児の約15%に先天梅毒の症状・所見を呈することが報告されているが，その多彩な合併症や神経発達予後に関する報告は少ない．症例は在胎33週4日，出生体重1,584g の女児．出生後に敗血症所見を呈するとともに新生児遷延性肺高血圧症を合併して，抗菌薬投与と一酸化窒素吸入療法を含めた集中管理を要した．妊娠中無治療母体からの出生，身体所見，骨X線所見，梅毒血清反応所見から先天梅毒と診断し，ベンジルペニシリンカリウム 5万単位/kg/日を計10日間投与した．頭部MRIや自動聴性脳幹反応検査では異常所見を認めず，修正3歳までの発達検査では明らかな発達遅延はなかったが，暦5歳の知能検査ではIQ78であり軽度知的障害が示唆された．本論文では，本症例における急性期合併症と神経発達予後について，先天梅毒との関連を文献的考察を加えて報告する．Untreated maternal syphilis during pregnancy increases the risk of intrauterine fetal death, stillbirth, neonatal death, and preterm birth. Approximately 15% of infants born to untreated pregnant women develop symptoms or findings of congenital syphilis; however, there are few reports on its diverse complications and long-term neurodevelopmental outcomes. The patient was a female infant born at 33 weeks and 4 days of gestation, with a birth weight of 1,584 g. The infant developed signs of sepsis and persistent pulmonary hypertension of the newborn, requiring intensive care, including antibiotic therapy and inhaled nitric oxide treatment. Born to an untreated mother, the infant was diagnosed with congenital syphilis based on physical and radiological findings and serological tests and was treated with benzylpenicillin potassium at 50,000 units/kg/day for 10 days. Brain MRI and automated auditory brainstem response testing showed no abnormalities. While developmental assessments up to the corrected age of three years revealed no significant delays, an intelligence test at five years of chronological age indicated a mild intellectual disability with an IQ of 78. This report discusses the acute-phase complications and neurodevelopmental outcomes of this case in relation to congenital syphilis, with a review of the relevant literature.journal articl

Intraoperative rapid diagnosis of pleural lavage cytology in non-small cell lung cancer

浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科thesi