太田 昌幸

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been used to diagnose and stage lung cancer. Acquire™ Pulmonary and Expect™ Pulmonary dedicated EBUS-TBNA needles were introduced as the Franseen and Lancet needles, respectively. It is still unclear whether the Franseen or Lancet needles yield a higher quality specimen especially focusing on next-generation sequencing-based molecular testing. METHODS: A single-center, prospective study performed at the Chiba University Hospital randomly assigned patients to two groups: Group A, wherein the first and second EBUS-TBNA were performed using Lancet and Franseen needles, respectively, and Group B, wherein the first and second EBUS-TBNA were performed using Franseen and Lancet needles, respectively. Each specimen was compared and analyzed pathologically. The primary outcome was the histological tissue area except blood clot and the cellularity of each sample. We also examined the success rate of molecular testing. RESULTS: Twelve patients who underwent EBUS-TBNA between November 2022 and February 2023 were enrolled in this study. The tissue area of the specimens obtained by the Franseen and Lancet needles was 13.3 ± 6.4 mm2 and 10.6 ± 6.3 mm2, respectively (P = .355). The tumor cellularity in the specimens obtained using the Franseen and Lancet needles was 54.0 ± 30.3 and 46.2 ± 36.3%, respectively (P = .608). The success rate of molecular testing using the single-pass sample by Franseen needle was 85.7 and 57.1% by Lancet needle. No serious complications were reported. CONCLUSIONS: The Franseen needle tended to show a greater amount of specimen with higher tumor cellularity than the Lancet needle which may contribute higher success rate of molecular testing. Further studies must be conducted to validate the results of this study. KEY FINDINGS: What is known and what is new?  What is the implication, and what should change now?

Rectal metastases of prostate cancer are rare and may be difficult to diagnose. In this report, we describe a case in which an extramural growth-type rectal tumor was resected and pathologically diagnosed as prostate cancer metastasis. A 70-year-old man on hormone therapy for prostate cancer with seminal vesicle invasion and pelvic lymph node metastasis was referred to our department after an imaging scan showed an extramural growth-type rectal tumor. Endoscopic ultrasound-guided fine needle aspiration was considered for diagnosis, but the patient preferred an early resection without the exam, so surgery was performed. Histopathological examination revealed that the lesion was in the adventitia of the rectum and metastasis of prostate cancer. Metastatic lesions of prostate cancer are not indicated for resection. A detailed preoperative study with the possibility of prostate cancer metastasis in mind is necessary because it is relevant to choosing the treatment strategy.

BACKGROUND: Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are diagnosed on their unique histological characteristics. Comprehensive cross-organ studies on SGTCs are limited. METHODS: We retrospectively analyzed the data of patients with salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), mucoepidermoid carcinoma (MEC), epithelial-myoepithelial carcinoma (EMC), acinic cell carcinoma (AcCC), and polymorphous adenocarcinoma (PAC) who visited our institution between 2009 and 2019. The primary tumor sites were classified into four categories; major salivary glands, head/neck (H/N) excluding (exc) major salivary glands (MSG) regions, broncho-pulmonary regions, and "others". H/N exc MSG was further divided into three subcategories, nasal/paranasal sinus, oral and pharynx/larynx. RESULTS: We identified 173 patients with SGTCs, with SDC, AdCC, MEC, EMC, AcCC, and PAC accounting for 20%, 42%, 27%, 3%, 8%, and 1% of the cases, respectively. The most frequent primary site was the major salivary glands (64%), followed by H/N exc MSG regions (27%), broncho-pulmonary regions, and "others", thus non-salivary gland origins accounted for 9% of all cases. Patients with SDC, MEC, AcCC, or SGTC of the major salivary glands and broncho-pulmonary regions were more frequently treated by surgery. The overall survival time of the patients with MEC was significantly better than that of patients with SDC or EMC. CONCLUSIONS: This cross-organ study highlights the clinical significance of SGTCs, underscoring the need for developing novel therapies for this rare disease entity.

Giant cell myocarditis (GCM) is a rare but fatal disease that can lead to cardiac failure. Survival with a cardiac standstill requires mechanical circulatory support or a biventricular assist device (BiVAD) and prolonged survival is extremely rare. Drug-induced hypersensitivity syndrome (DIHS) is a severe cutaneous adverse reaction. Some cases of DIHS are reportedly associated with the onset of GCM. We present a case of a 28-year-old woman who developed GCM during steroid tapering after DIHS. She went into continuous cardiac standstill but survived for 74 days under BiVAD support. Our case is noteworthy because the histopathologic specimens obtained on three occasions contributed to the diagnosis of this particular condition over time. We also reviewed previous literature on concomitant cases of GCM and DIHS. We found that two are potentially associated and most cases of GCM occur within 3 months of DIHS during steroid tapering.

BACKGROUND Immunoglobulin A (IgA) vasculitis is a systemic vasculitis that involves the small vessels. It is mainly characterized by skin symptoms such as purpura, arthritis/arthralgia, abdominal symptoms, and nephropathy, which are caused by IgA adherence to the vessel walls. Herein, we report the case of an advanced non-small cell lung cancer (NSCLC) and a purpuric skin rash of the legs that developed during fourth-line chemotherapy with tegafur/gimeracil/oteracil (S-1). CASE REPORT A 68-year-old man diagnosed with NSCLC 2 years ago was undergoing S-1 as fourth-line chemotherapy when he developed purpura and edema on the lower extremities. Biopsy renal specimens were consistent with IgA vasculitis. Considering his medical history, both IgA vasculitis induced by S-1 and a paraneoplastic syndrome were considered, although the exact cause could not be identified. Subsequently, chemotherapy was discontinued because of his deteriorating general condition, and he received optimal supportive care. The purpura spontaneously disappeared; however, his ascites and renal function deteriorated. Systemic steroids improved renal function, but the ascites did not resolve. One month after being diagnosed with IgA vasculitis, the patient died due to deterioration of his general condition. CONCLUSIONS This case emphasizes the occurrence of IgA vasculitis during lung cancer treatment and its potential impact on the disease course of lung cancer. Moreover, the possible causes of IgA vasculitis in this case were paraneoplastic syndrome or S-1 adverse effects, but further case series are needed to gain a more comprehensive understanding. Refractory, steroid-unresponsive ascites may occur as an abdominal manifestation of IgA vasculitis.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease that often causes progressive pulmonary fibrosis (HPS-PPF) in some genetic types with high mortality rates. No effective treatment for HPS-PPF other than lung transplantation has been established. Herein, we report a case of HPS type 1 with progressive pulmonary fibrosis treated with long-term nintedanib administration followed by lung transplantation. The resected lungs revealed diffuse interstitial lung lesions, including fibroblastic foci, suggesting the potential beneficial effects of anti-fibrotic drugs in HPS-PPF. Together with previous reports, the present case suggests that nintedanib might be a safe and effective drug for HPS-PPF.

妊娠子宮嵌頓症は子宮が後屈したまま増大し,子宮底部が骨盤腔に陥入する状態である.経腟分娩は困難であり,子宮が嵌頓していることを認識せずに帝王切開を行うと膀胱損傷,腟壁裂傷をきたす.今回,全身性エリテマトーデス(systemic lupus erythematosus,SLE)罹患女性へ妊娠子宮嵌頓症の診断で帝王切開術を施行したところ,子宮底部ではなく子宮憩室がダグラス窩に陥入していた症例を報告する.36歳の初産婦が妊娠11週でSLE合併妊娠の管理目的に当科へ紹介された.子宮は後屈で妊娠19週の内診で子宮腟部を確認することができず,経腟超音波で頸管の延長と内子宮口の頭側への偏位を認めた.妊娠30週のMRIで妊娠子宮嵌頓症と診断した.SLEの病勢が悪化し妊娠31週5日に緊急帝王切開術を施行した.子宮底部は小骨盤腔の頭側にあり,子宮右後壁の筋層が膨隆して子宮憩室を形成しダグラス窩に陥入していた.子宮を腹腔外へ挙上し体部の回転と頸部の過伸展を解除した後,体下部を横切開し児を娩出した.憩室の筋層は菲薄化し胎盤の癒着を認めたため,憩室壁を胎盤と共に切除した.組織学的には癒着胎盤であった.SLE合併妊娠では子宮筋層が脆弱となることがある.本例では妊娠中にSLEの病勢が悪化しており,胎盤付着部の子宮筋層が菲薄化し子宮憩室を形成した可能性が考えられた.(著者抄録)

INTRODUCTION: The incidence of bladder cancer following transplantation is high; however, no previous studies have reported the development of bladder cancer following bone marrow and bilateral lung transplantations. CASE PRESENTATION: A 42-year-old man who was followed for bilateral lung transplantation due to chronic graft-versus-host disease following bone marrow transplantation complained of gross hematuria. Transurethral resection of the bladder tumor was performed for cT1N0M0 bladder cancer. On the following night, he experienced severe respiratory failure and was intubated. He was discharged on postoperative day 32 with the introduction of home oxygen therapy. The pathological diagnosis was invasive urothelial carcinoma, high-grade, pT1, with urothelial carcinoma in situ. Further treatment could not be performed because of his poor performance status and immunosuppressive state. CONCLUSION: Vigorous screening for bladder cancer coexisting with other malignancies should be performed for transplant recipients for the early diagnosis and prompt treatment of a relatively aggressive bladder cancer.

BACKGROUND AND AIMS: This randomized controlled trial (RCT) was designed to evaluate the short-term outcomes of underwater endoscopic mucosal resection (UEMR) and endoscopic submucosal dissection (ESD) of 21-30 mm colonic polyps. METHOD: We conducted a single-center RCT. Patients diagnosed with suspected colorectal intramucosal carcinoma (21-30 mm and adaptable for both UEMR and ESD) were randomly assigned to the UEMR and ESD groups at a 1:1 ratio. The primary endpoint was the R0 resection rate. We independently performed one-sample tests against the set threshold for each treatment. The significance level was set at p = 0.224. RESULT: Eleven polyps each in the UEMR and ESD groups, respectively, were analyzed. The R0 resection rate (%) was 36 (95% confidence interval 11-69) and 100 (72-100) for UEMR and ESD, respectively, with a significant difference between the two groups (p = 0.002). The p-value against the set threshold for UEMR was 0.743, whereas that for ESD was < 0.001 (one-sample binomial test). The en bloc resection rates (%) were 82 (48-97) and 100 (72-100) for UEMR and ESD, respectively; however, no significant difference was observed (p = 0.167). The mean treatment time (min) was significantly shorter in the UEMR group (8 ± 6) than in the ESD group (48 ± 29) (p = 0.001). CONCLUSION: ESD could achieve a high R0 resection rate, while the en bloc resection rate was comparable between the two treatment techniques with less burden on patients undergoing UEMR for 21-30-mm colorectal polyps. CLINICAL TRIAL REGISTRATION: The study was registered at the Japan Registry of Clinical Trial as jRCT1030210015 and jRCT1030210177.

Metaplastic breast carcinoma (MBC) is a heterogeneous group of invasive breast carcinomas (IBCs) characterized by the differentiation of the neoplastic epithelium toward squamous cells and/or mesenchymal-appearing elements. The present study describes the case of a 42-year-old woman who underwent a mastectomy and sentinel lymph node biopsy for two tumors in their left breast. One of the resected tumors was diagnosed as MBC with neuroendocrine (NE) differentiation and the other was diagnosed as IBC of no special type. The MBC tumor contained a matrix composed of basal lamina with a focal area of myxoid matrix and squamoid differentiation. To the best of our knowledge, the present study is the first report of MBC producing prominent basal lamina. The patient has remained alive and well for >10 years without recurrence, and has been treated with oral and injected anticancer drugs.

症例は40歳代男性で、乾性咳嗽と就寝時呼吸困難感を自覚して近医を受診し、胸部単純X線およびCTで縦隔から右肺門部に巨大な腫瘤を指摘され、縦隔腫瘍疑いで精査加療目的に紹介受診となった。18F-FDG PET/CTでは病変全体に強い集積がみられ、明らかな遠隔臓器転移はなかった。疾患頻度から原発性肺癌の臨床診断となり、病理組織型確認のため気管支鏡でのリンパ節転移からの生検(EBUS-TBNA)が行われた。HE染色では背景に広範に壊死組織が存在した。腫瘍は明瞭な核小体を伴う核/細胞質比の高い細胞で、腺腔形成や角化などの特定の分化傾向はみられなかった。免疫染色の結果から、胸部SMARCA4欠損腫瘍の診断に至り、1st-lineの化学療法としてCBDCA+PTXが行われた。一時縮小(寛解)が得られたがすぐに再増大し、2nd-lineの化学療法として免疫チェックポイント阻害薬投与を予定するも、急速な全身状態悪化のため実施できなかった。主訴自覚から7ヵ月、加療4ヵ月で死亡した。

膵癌が原発巣の転移性卵巣癌は稀であり,その特徴はあまり知られていない.今回,膵癌の卵巣転移を3症例経験した.症例1は68歳,膵体尾部癌IIB期のため標準治療を施行し寛解していた.膵癌発症から1年4ヵ月後,右卵巣多房性嚢胞性腫瘤を認めた.化学療法を開始したが,腹部膨満感と腹痛の緩和目的に両側付属器切除術(bilateral salpingo-oophorectomy:BSO)を施行した.症例2は69歳,膵体部癌IV期で切除不能のため化学療法を施行した.膵癌発症1年3ヵ月目,骨盤内に多房性嚢胞性腫瘤を認め,腹痛の緩和目的でBSOを施行した.症例3は81歳,子宮筋腫で単純子宮全摘術と右付属器切除術後である.膵体部癌IV期のため膵体部切除術と右肺部分切除術後,化学療法を施行し寛解していた.膵癌発症から3年10ヵ月後,左卵巣多房性嚢胞性腫瘤を認めた.左卵巣腫瘍は増大傾向のため,左付属器切除術を施行した.膵癌の卵巣転移は多房性嚢胞性であることが比較的多いが,原発性粘液性卵巣癌も多房性嚢胞性であり,それだけで両者の鑑別は困難である.今回の3症例に共通して,超音波検査で認めた多房性腫瘤を呈し血流を伴う薄い隔壁は,膵癌卵巣転移の特徴的な所見の1つと考えられた.膵癌の治療歴を有する卵巣腫瘍は,この超音波所見と合わせることで,膵癌の卵巣転移と術前に診断できる可能性が示唆された.(著者抄録)

症例は日齢11女児。胆汁性嘔吐を主訴に近医入院となった。ミルクアレルギーが疑われアレルギー用ミルクに変更されたが、その後も胆汁性嘔吐が持続したため精査目的に当院に紹介転院となった。小腸造影検査にてトライツ靱帯より約50cmの空腸に狭窄像を認め、先天性空腸狭窄症の術前診断にて開腹手術を施行した。トライツ靱帯より45cmの空腸に狭窄を認め、同部位を切除した。切除腸管の内腔には4/5周にわたり腫瘤が存在し、狭窄の原因となっていた。術後4日から経口摂取を開始し、経過良好にて術後25日に退院となった。病理組織学的所見では、楕円形〜卵円形の核を持つ紡錘形の細胞が束状に増殖しており、乳幼児筋線維腫症(infantile myofibromatosis、solitary type)の診断に至った。全身検索においては他臓器に腫瘤性病変はなく、小腸孤発型の乳幼児筋線維腫症として後治療は行わなかった。術後6年経過し再発はない。(著者抄録)

Primary racemose hemangioma of the bronchial artery (RHBA) is one of the causes of massive hemoptysis. A 72-year-old woman was admitted to our hospital with recurrent hemoptysis. Bronchoscopy showed an endobronchial lesion, and the angiography of the right bronchial arteries indicated RHBA. Bronchial arterial embolization (BAE) was performed to prevent hemoptysis. Although the endobronchial lesion shrank after the first BAE, the lesion re-increased and caused massive hemoptysis. A thoracoscopic right upper lobectomy was performed, and hemoptysis did not recur. Therefore, in cases of RHBA where there is recurrent hemoptysis and the endobronchial lesions that remain after BAE, additional treatments should be considered.

Intracranial myxoid mesenchymal tumors (IMMTs) with EWSR1-CREB1 family gene fusion are rare brain neoplasms characterized by gene fusion between the EWSR1 gene and one of the cyclic AMP response element-binding (CREB) family transcription factor (CREB1, ATF1, or CREM) genes. Although half of reported cases are pediatric, the clinical, histologic, and genomic features of IMMTs with EWSR1 rearrangement in pediatric populations are not yet well clarified. Here we describe the case of a 7-year-old girl who presented with seizures due to an extra-axial tumor in the left parietal convexity. Gross total resection was achieved, and the tumor displayed a multilobular structure with solid hypercellular and myxoid hypocellular areas, separated by a variable amount of stroma. The hypercellular areas consisted of round to polygonal cells, whereas the myxoid areas were ovoid to spindled cells. Immunophenotypically, the tumor cells were positive for vimentin, desmin, and EMA. Next-generation sequencing of tumoral DNA revealed EWSR1-CREM gene fusion and a pathogenic mutation of MAP3K13. No recurrence was detected 9 months after resection, without chemotherapy or radiotherapy. In comparison to other pediatric and adult patients with EWSR1 rearrangement, many clinical, radiological, and immunohistochemical features were shared. However, signs of elevated intracranial pressure were more frequently observed, and postoperative radiation was less frequently administered for pediatric patients. Gross total resection (GTR) was the key prognostic factor for better disease control especially among pediatric patients. Further reports of cases with EWSR1 rearrangement with detailed genetic profiles are essential for clarifying the oncogenic pathway and establishing a standard treatment strategy.

<title>Abstract</title>The genetic characteristics of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) in the Japanese population is unclear. This study aims to investigate the genetic characteristics from nondysplastic BE (NDBE) to early EAC in Japan. Clinical information was collected. Moreover, the genetic profile of NDBE without concurrent dysplasia, early EAC, and surrounding BE were also investigated using endoscopic biopsy samples and formalin-fixed, paraffin-embedded specimens from Japanese patients by targeted next-generation sequencing. Immunohistochemical staining for p53 was also performed for EAC lesions. Targeted NGS was performed for 33 cases with 77 specimens. No significant difference exists in the NDBE group between the number of putative drivers per lesion in the short-segment Barrett’s esophagus (SSBE) and long-segment Barrett’s esophagus (LSBE) [0 (range, 0–1) vs. 0 (range, 0–1). <italic>p</italic> = 1.00]. <italic>TP53</italic> putative drivers were found in two patients (16.7%) with nondysplastic SSBE. <italic>TP53</italic> was the majority of putative drivers in both BE adjacent to EAC and EAC, accounting for 66.7% and 66.7%, respectively. More putative drivers per lesion were found in the EAC than in the NDBE group [1 (range, 0–3) vs. 0 (range, 0–1). <italic>p</italic> &lt; 0.01]. The genetic variants of <italic>TP53</italic> in the Japanese early EAC were similar to those in western countries. However, <italic>TP53</italic> putative drivers were detected even in Japanese patients with nondysplastic SSBE. This is significant because such nondysplastic SSBE might have higher risk of progressing to high-grade dysplasia or EAC. The risks of progression may not be underestimated and appropriate follow-ups may be necessary even in patients with SSBE. <bold>Trial registration:</bold> This study was registered at the University Hospital Medical Information Network (UMIN000034247).

BACKGROUND AND AIM: Immune checkpoint inhibitors and their combination with other agents have recently been available in advanced hepatocellular carcinoma (HCC). Hence, a thorough understanding of the tumor microenvironment based on tumor samples is yet to be achieved. This study aimed to explore the tumor microenvironment in advanced HCC in terms of microsatellite instability-high (MSI-H) by using tumor samples from advanced HCC patients eligible for systemic therapy. METHODS: MSI-H was assessed by polymerase chain reaction, and the expression of mismatch repair proteins, PD-L1, CD8, VEGF, and HLA-class1 was evaluated by immunohistochemistry. Whole-exome sequencing was performed for MSI-H tumor samples. RESULTS: Of 50 patients, one (2.0%) was confirmed with MSI-H. In the MSI-H advanced HCC tumor, a high tumor mutation burden, infiltration of CD8+ lymphocytes, and low expression of VEGF were identified. Although PD-L1 expression was negative, there was shrinkage of tumor following pembrolizumab. However, another tumor nonresponsive to pembrolizumab was present simultaneously. Checking the Cancer Genome Atlas (TCGA) database, we found a similar case to this patient. The TCGA case had unique gene features of miR-21 and miR-155 overexpression and hypermethylation of the MSH2 gene. CONCLUSION: We identified a very small number of MSI-H cases in HCC using one tumor biopsy sample for each patient with advanced HCC. In addition, epigenetic aberrations possibly lead to MSI-H in HCC patients. Since different HCC clones might coexist in the liver, sampling from multiple tumors should be considered to clarify the true proportion of MSI-H in HCC and to analyze tumor microenvironments.

To our knowledge, the in situ phase of small cell lung carcinoma (SCLC) has not been reported previously although in situ/pre-invasive lesions are commonly observed in murine models. We report a patient diagnosed with SCLC presenting mostly as carcinoma in situ after photodynamic therapy (PDT) under the diagnosis of bronchial squamous cell carcinoma (SqCC) in situ.

<title>Abstract</title> <sec> <title>Objectives</title> Complete hydatidiform moles (CHMs) are androgenetic and have a high rate of progression to gestational trophoblastic neoplasia (GTN). CHMs are negative when immunostained for p57KIP2 protein, the product of the maternally expressed gene on chromosome 11p15.5, whereas biparental partial hydatidiform moles and hydropic abortion are positive for p57KIP2. This study presents two cases of p57KIP2-positive androgenetic CHMs and explores the cause of this inconsistency. </sec> <sec> <title>Methods</title> Androgenetic CHMs were diagnosed using multiplex short tandem repeat polymorphism analysis. Single-nucleotide polymorphism arrays were performed for molecular karyotyping. </sec> <sec> <title>Results</title> Among the consecutive 188 androgenetic CHMs, two cases were positive for p57KIP2. The first case remitted spontaneously, whereas the second case developed into low-risk GTN. The first case was positive for p57KIP2 in all villi. The karyotype was 48,XX,+7,+11, with the additional chromosome 11 confirmed to be of maternal origin. The second case presented a mosaic of both positively and negatively stained villi. The karyotype was 46,XX. </sec> <sec> <title>Conclusions</title> The cause of one of the CHMs was trisomy with an additional maternal chromosome 11. Although rare, the confirmation of p57KIP2-positive androgenetic CHM status is necessary to manage GTN risk. </sec>