Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Background

Recently, two molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) have been proposed: the “Classical” and “Basal-like” subtypes, with the former showing better clinical outcomes than the latter. However, the “molecular” classification has not been applied in real-world clinical practice. This study aimed to establish patient-derived organoids (PDOs) for PDAC and evaluate their application in subtype classification and clinical outcome prediction.

Methods

We utilized tumor samples acquired through endoscopic ultrasound-guided fine-needle biopsy and established a PDO library for subsequent use in morphological assessments, RNA-seq analyses, and in vitro drug response assays. We also conducted a prospective clinical study to evaluate whether analysis using PDOs can predict treatment response and prognosis.

Results

PDOs of PDAC were established at a high efficiency (> 70%) with at least 100,000 live cells. Morphologically, PDOs were classified as gland-like structures (GL type) and densely proliferating inside (DP type) less than 2 weeks after tissue sampling. RNA-seq analysis revealed that the “morphological” subtype (GL vs. DP) corresponded to the “molecular” subtype (“Classical” vs. “Basal-like”). The “morphological” classification predicted the clinical treatment response and prognosis; the median overall survival of patients with GL type was significantly longer than that with DP type (P < 0.005). The GL type showed a better response to gemcitabine than the DP type in vitro, whereas the drug response of the DP type was improved by the combination of ERK inhibitor and chloroquine.

Conclusions

PDAC PDOs help in subtype determination and clinical outcome prediction, thereby facilitating the bench-to-bedside precision medicine for PDAC.

DOI： 10.1007/s00535-024-02103-0

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Other Link： https://link.springer.com/article/10.1007/s00535-024-02103-0/fulltext.html

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Digestive Endoscopy  

DOI： 10.1111/den.14798

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Language：English   Publisher：Oxford University Press  

Language：English   Publisher：シュプリンガー・ジャパン(株)  

膵神経内分泌腫瘍(PanNET)は膵臓の稀な腫瘍である。特異的ホルモンの高発現症状の有無により、機能性と非機能性腫瘍に分類される。副腎皮質刺激ホルモン(ACTH)-産生PanNETは稀な機能性腫瘍で、その臨床的特徴と治療成績は十分に明らかにされていない。疾患の経過中に異所性ACTH症候群(EAS)を認めたPanNETの2例を報告した。症例1は手術時には非機能性PanNETであった。再発肝転移の治療中、肝転移巣からのACTHおよび副甲状腺ホルモン関連ペプチド(PTHrP)産生によると考えられるEASおよび腫瘍関連高カルシウム血症が認められた。症例2はガストリノーマで、症例1と同様、再発肝転移の治療中にEASが認められた。原発巣と転移巣で腫瘍表現型が異なっているにも関わらず、PanNET症例が複数のホルモンを有し、疾患の経過中に続発性のホルモン分泌をきたすことは稀ではない。以上より、機能性PanNET症例では、特に迅速な診断と治療が必要な内分泌緊急事態であるEASが認められる場合、抗ホルモン治療による症状の制御が、抗腫瘍治療と共に重要であることが明らかとなった。

Language：Japanese   Publisher：Japan Pancreas Society  

<p>The incidence of pancreatic neuroendocrine neoplasms (PanNENs) has been increasing worldwide due to improved disease recognition and advances in diagnostic modalities such as computed tomography and endoscopic ultrasound. The number of older adult patients with PanNENs is expected to increase in Japan's rapidly aging society. Therefore, it is important to establish treatment strategies for older adult patients. The only curative treatment for PanNENs is surgical resection, which can be safely performed in older adult patients when selected appropriately. Depending on age, comorbidities, and tumor size, nonsurgical management, such as observation and systemic therapy, should also be considered. Systemic therapies, including somatostatin analogs, targeted therapies, cytotoxic chemotherapy, and peptide receptor radionuclide therapy, are available for patients with unresectable or metastatic pancreatic neuroendocrine tumors (PanNETs). When administering these therapies to older adult patients with PanNETs, it is important to balance the treatment, and the adverse events which can be linked to it, with the patient's comorbidities and cognitive function. Further studies on older adult patients with PanNETs are warranted to establish an optimal treatment strategy.</p>

DOI： 10.2958/suizo.39.33

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Journal of Clinical Oncology  

BACKGROUND: Streptozocin has been used to treat neuroendocrine tumors in Europe and the USA; however, its actual status in Japan has not been fully clarified owing to the rarity of this disease and the relatively recent approval of streptozocin in Japan. METHODS: We retrospectively analyzed 53 patients with gastroenteropancreatic neuroendocrine tumors who were treated with streptozocin-based chemotherapy at two Japanese hospitals between January 2004 and June 2023. RESULTS: The overall response and disease control rates were 27.7 and 74.5%, respectively, and the median progression-free survival and overall survival were 7.1 and 20.3 months, respectively. Performance status ≥1 showed a significant negative correlation with progression-free survival, and performance status ≥1 and liver tumor burden ≥25% showed a significant negative correlation with overall survival. No significant differences were observed in the treatment response between pancreatic and gastrointestinal neuroendocrine tumors. No treatment-related serious adverse events were observed; however, 87.7% of patients expressed a decrease in the estimated glomerular filtration rate, which negatively correlated with the duration of streptozocin treatment (r = 0.43, P = 0.0020). In the streptozocin re-administration group (n = 5), no differences were found in efficacy between the initial and second streptozocin treatments. CONCLUSIONS: Although streptozocin is a safe, streptozocin-induced renal dysfunction is a dilemma in streptozocin responders. Streptozocin may benefit patients with gastroenteropancreatic neuroendocrine tumors, especially those with a good performance status; however, in some cases, planned streptozocin withdrawal or switching to other drugs should be considered.

DOI： 10.1093/jjco/hyae026

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Language：Japanese   Publisher：(一社)日本腹部救急医学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Clinical Journal of Gastroenterology  

Pancreatic neuroendocrine tumors (PanNETs) are rare malignant tumors that occur in the pancreas. They are divided into functioning and non-functioning tumors based on the presence or absence of their specific hormonal hyper-expression symptoms. Adrenocorticotropic hormone (ACTH)-producing PanNETs are rare, functional tumors, and their clinical characteristics and outcomes have not been well reported.Here, we report the cases of two patients with PanNETs who presented with ectopic ACTH syndrome (EAS) during the course of their disease. Case 1 involved a non-functioning PanNET at the time of surgery. During treatment for recurrent liver metastases, the patient presented with EAS and tumor-associated hypercalcemia, probably due to ACTH and parathyroid hormone-related peptide (PTHrP) production from the liver tumor. Case 2 was a gastrinoma, and similar to Case 1, this patient presented with EAS during the treatment of recurrent liver metastases.It is not uncommon for patients with PanNETs to have multiple hormones and develop secondary hormone secretion during their disease course, although tumor phenotypes differ between primary and metastatic sites. In patients with functioning PanNETs, symptom control with anti-hormonal therapy is essential, in addition to anti-tumor therapy, especially for EAS, which is an endocrine emergency disease that requires prompt diagnosis and treatment.

DOI： 10.1007/s12328-023-01908-5

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Language：Japanese   Publisher：医学図書出版(株)  

近年,腫瘍領域においてliquid biopsyが注目を集めているが,神経内分泌腫瘍(NEN)においても同様である。Liquid biopsyは従来の組織学的検査とは異なり,末梢血などの体液から非侵襲的にサンプルを抽出するため,腫瘍間・腫瘍内不均一性が問題となることはなく,容易にリアルタイムの病状を把握することができる。中でもmessenger RNAを用いたNETestはエビデンスが蓄積され,NETestから派生したpeptide receptor radionuclide therapy(PRRT)prediction quotientはPRRTの層別化マーカーとしての有用性が報告されている。このようにliquid biopsyは診断・モニタリング・治療効果の予測・予後と,NEN診療の全般にわたって有用でNEN診療体系の再構築が期待されるが,実臨床への導入にはさらなるエビデンスの蓄積に加えて,ハード・ソフト面の整備が必要であり,課題が多い。(著者抄録)

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Language：Japanese   Publisher：Japan Pancreas Society  

<p>In 2015, the Japanese Society for Neuroendocrine Tumors (JNETS) published the first clinical practice guidelines for pancreatic and gastrointestinal neuroendocrine neoplasms (NEN) to standardize diagnosis and treatment. NEN is a rare tumor that develops in all organs and presents with various clinical symptoms. Pathological classification is ultimately important for the diagnosis of NEN, and it is necessary to select drug treatment strategies based on the pathological diagnosis. The second edition of revised guidelines was published in 2019 to reflect new trends, including WHO classification revision, the advent of somatostatin receptor scintigraphy, the addition of target diseases for molecularly targeted drugs and the somatostatin analogue lanreotide, and reexamination of surgical indications for non-functional pancreatic NEN. Peptide receptor radionuclide therapy (PRRT) has also emerged. In this article, we review the current status and future prospects of pancreatic NEN management.</p>

DOI： 10.2958/suizo.38.361

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Endoscopy  

DOI： 10.1055/a-2072-5740

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Publisher：日本メディカルセンター  

DOI： 10.19020/cg.0000002867

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Language：Japanese   Publisher：医学図書出版(株)  

術後膵液瘻(postoperative pancreatic fistula:POPF)は発生頻度の高い膵切除術後合併症であり,適切なタイミングでドレナージを行う必要がある。従来は経皮的ドレナージが主流であったが,近年では内視鏡治療,とくにEUSガイド下経消化管ドレナージ(EUS-guided transluminal drainage:EUS-TD)の報告が増えている。EUS-TDで用いるステントとして,主に経鼻胆道ドレナージチューブ,ダブルピッグテイル型プラスチックステント,lumen-apposing metal stent,などがあり,POPFの部位,大きさ,性状に応じて,適切なステント選択を心がける必要がある。事前に外科医と情報共有のうえで,内視鏡治療にあたることが重要である。(著者抄録)

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(NPO)日本消化吸収学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Asia-Pacific Journal of Clinical Oncology  

AIM: Drug-induced interstitial lung disease (DI-ILD) is a serious adverse event during chemotherapy. This study aimed to obtain real-world data of the incidence, clinical characteristics, predictive factors, and prognosis of patients with pancreatic cancer who developed DI-ILD. METHODS: In patients with locally advanced or metastatic pancreatic cancer who underwent standard chemotherapy at our hospital and its participating facilities between April 2014 and March 2019, the clinical features, occurrence rate and clinical course of DI-ILD, and prognosis were retrospectively evaluated. RESULTS: Altogether, 390 patients were finally enrolled. DI-ILD occurred in 24 cases (6.2%). The median period from diagnosis of pancreatic cancer to the onset of DI-ILD was 2.2 months (.6-13.3 months). The rate of DI-ILD onset according to each regimen was 5.8% of gemcitabine (GEM) plus albumin-bound paclitaxel therapy (18/308), 3.8% of GEM (4/106), and 2.3% of FOLFIRINOX (2/88). The incidence of DI-ILD in GEM-based regimens was significantly higher than that in non-GEM-based regimens (p < .01). The median overall survival (OS) of the patients with and without DI-ILD after propensity score matching was 11.5 months and 11.4 months (p = .99), respectively. After the resolution of DI-ILD, no statistical significance in the median OS of the patients with and without subsequent treatment (11.0 vs. 6.8 months, p = .18) was observed. CONCLUSION: DI-ILD is not a rare adverse event in the current standard chemotherapy for pancreatic cancer in Japan. With appropriate management of DI-ILD, the prognosis of patients with DI-ILD can be equivalent to that of patients without DI-ILD.

DOI： 10.1111/ajco.13903

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Gastroenterology  

BACKGROUND: Pancreatic neuroendocrine neoplasms (PanNENs) are a heterogeneous group of tumors. Although the prognosis of resected PanNENs is generally considered to be good, a relatively high recurrence rate has been reported. Given the scarcity of large-scale reports about PanNEN recurrence due to their rarity, we aimed to identify the predictors for recurrence in patients with resected PanNENs to improve prognosis. METHODS: We established a multicenter database of 573 patients with PanNENs, who underwent resection between January 1987 and July 2020 at 22 Japanese centers, mainly in the Kyushu region. We evaluated the clinical characteristics of 371 patients with localized non-functioning pancreatic neuroendocrine tumors (G1/G2). We also constructed a machine learning-based prediction model to analyze the important features to determine recurrence. RESULTS: Fifty-two patients experienced recurrence (14.0%) during the follow-up period, with the median time of recurrence being 33.7 months. The random survival forest (RSF) model showed better predictive performance than the Cox proportional hazards regression model in terms of the Harrell's C-index (0.841 vs. 0.820). The Ki-67 index, residual tumor, WHO grade, tumor size, and lymph node metastasis were the top five predictors in the RSF model; tumor size above 20 mm was the watershed with increased recurrence probability, whereas the 5-year disease-free survival rate decreased linearly as the Ki-67 index increased. CONCLUSIONS: Our study revealed the characteristics of resected PanNENs in real-world clinical practice. Machine learning techniques can be powerful analytical tools that provide new insights into the relationship between the Ki-67 index or tumor size and recurrence.

DOI： 10.1007/s00535-023-01987-8

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

切除した膵神経内分泌腫瘍(PanNEN)は再発率が高いので、その予測因子を検索した。22医療機関で1987年1月～2020年7月に切除したPanNEN573例のデータベースを作成した。局在性の非機能性膵神経内分泌腫瘍(G1/G2)の371名の患者の臨床的特徴を分析した。再発を決定付ける特徴を分析するため、機械学習予測モデルを構築した。経過観察中に患者52名に再発がみられ、再発までの中央値は33.7ヵ月であった。ランダムサバイバルフォレスト(RSF)モデルはCox比例ハザード回帰モデルよりもHarrell C指数が優れていた。Ki-67指数、残存腫瘍、WHOグレード、腫瘍サイズ、リンパ節転移がRSFモデルの上位5予測因子で、腫瘍サイズ20mm以上が再発の可能性の上昇する分岐点で、Ki-67指数の上昇とともに5年無増悪生存率が直線的に低下した。

Language：Japanese   Publisher：医学図書出版(株)  

慢性膵炎の臨床像は,病期や合併症の有無により患者ごとに大きく異なる。長期間の経過のなかで,膵石や膵管・胆管狭窄,仮性嚢胞,膵性胸腹水などさまざまな合併症を有することがあり,これらの病態には内視鏡治療が第一選択になる。慢性膵炎診療ガイドライン2021を念頭に,ERCPによる経乳頭的治療とEUSによる経消化管的治療,必要に応じて外科的治療を組み合わせて,慢性膵炎合併症の治療にあたる必要がある。本稿では慢性膵炎の合併症に対する内視鏡治療を中心に概説する。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publisher：日本消化器病学会-九州支部  

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Language：Japanese   Publisher：医学図書出版(株)  

長らく進行性膵神経内分泌腫瘍(PanNETs)の予後の改善は得られていなかったが,薬物療法の進歩によって,進行性PanNETsの治療成績は飛躍的に向上してきている。多くのPanNETsは細胞膜上にソマトスタチン受容体を高発現するため,診断や治療のターゲットとされてきた。ソマトスタチンアナログ(SSA)であるoctreotideは,従来ホルモン過剰症状の緩和目的に使用されてきたが,その後消化管NETsに対して抗腫瘍効果が示され,2011年に保険承認された。一方で,PanNETsに対しても近年の臨床試験結果に基づいて,持続性SSA徐放性製剤であるlanreotideが2017年に保険承認された。SSAは有害事象も少なく,実臨床でも汎用されているが,一方で各薬剤との使い分けなど,解決すべき課題も多い。本稿ではlanreotideを中心に,SSAの腫瘍増殖抑制効果について述べる。(著者抄録)

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Publisher：東京医学社  

DOI： 10.24479/endo.0000000565

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Clinical Journal of Gastroenterology  

A 66-year-old Japanese woman had been diagnosed with a neuroendocrine tumor of the pancreatic head (G2) 3 years previously and undergone pancreaticoduodenectomy. Nine months postoperatively, recurrence with multiple liver metastases developed and she was referred to our department. A regimen of 10 mg of everolimus for 2 weeks plus 1-week washout was instituted, and no adverse events were observed. Fourteen months after treatment initiation, she developed severe generalized erythema multiforme (EM). Skin biopsy revealed spongiosis in the epidermis and interface change and edema in the superficial dermis. Mast cells were observed from the dermis to the subcutaneous tissue, as well as perivascular eosinophilic infiltration, leading to EM being diagnosed. Oral everolimus was discontinued, and the EM was relieved by treatment including steroid therapy. Everolimus is an inhibitor of the mammalian target of rapamycin, and its indications include neuroendocrine tumors. Skin disorders are commonly seen in the early stages of everolimus treatment, but their severity is almost always mild and never severe. This is the first report on a patient who presented with severe generalized EM more than 1 year after everolimus treatment initiation. Patients on everolimus therapy should be monitored for skin disorders on a long-term basis.

DOI： 10.1007/s12328-022-01709-2

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Language：Japanese   Publisher：日本消化器病学会-九州支部  

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

症例は66歳女性で、3年前に膵頭部の神経内分泌腫瘍(G2)と診断され、膵頭十二指腸切除術を受けた。術後9ヵ月目に多発性肝転移が認められ、紹介受診した。10mgのエベロリムスを2週間投与し、1週間休薬するレジメンを導入し、特に有害事象は認められなかった。治療開始から14ヵ月後に、重篤な全身の多形性紅斑(EM)が出現した。皮膚生検の結果、表層皮膚の海綿状変化、界面の変化、および浅層皮膚の浮腫が認められた。肥満細胞は真皮から表皮まで認められ、血管周囲の好酸球浸潤も同様に認められたため、EMと診断された。経口的エベロリムス投与を中止し、EMはステロイドを含む治療で軽快した。本症例は、エベロリムス投与開始から1年以上経過した後に発症した重篤なEMの初回報告例である。

Language：Japanese   Publisher：日本消化器病学会-九州支部  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japan Endocrine Society  

<p>VIPomas are generally rare functioning pancreatic neuroendocrine tumors (PanNETs) that cause watery diarrhea, hypokalemia, and achlorhydria. Due to their extreme rarity, the clinicopathological features and outcomes of VIPomas have not been well reported. This study aimed to determine the diagnostic and therapeutic characteristics and prognosis of VIPomas and to compare them with other PanNETs at a Japanese reference hospital. Medical records of 293 patients with PanNETs were collected. Patient and tumor characteristics and outcomes were retrospectively reviewed. This cohort had only 1.4% (four patients) of patients with VIPomas, and three of these patients changed from non-functioning (NF-) PanNETs during their disease course. Recurrences of hormonal symptoms were observed in all patients despite the initial controls, and all of them died from their disease, more specifically mainly from hormonal symptoms. Compared to the other PanNETs, VIPomas were all located at the pancreatic tail, were larger, and had a higher Ki-67 index and more metastasis. The median survival time was significantly shorter for patients with VIPoma than for those with NF-PanNET (5.9 <i>vs.</i> 26.7 years, <i>p</i> < 0.0001), insulinoma (21.8 years, <i>p</i> < 0.0001), and gastrinoma (12.3 years, <i>p</i> = 0.0325). This study presents the possibility of shifting from non-symptomatic to symptomatic VIPomas as they grow or of transforming from NF-PanNETs to VIPomas. VIPomas should be considered in patients with relatively large NF-PanNETs, especially those located in the pancreatic tail, when diarrhea is continuously observed. As hormonal symptoms are an important cause of death in VIPomas, long-term symptomatic control, which is relatively difficult, is of great significance.</p>

DOI： 10.1507/endocrj.EJ22-0111

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Language：English   Publisher：(一社)日本内分泌学会  

1987～2021年9月に当大学病院で治療された機能性膵神経内分泌腫瘍患者293例の診療記録を後向きに検討し、VIPomasの診断および治療上の特徴および予後を他の膵神経内分泌腫瘍と比較検討した。患者を、非機能性膵神経内分泌腫瘍213例(男性107例、中央値57歳)、機能性膵神経内分泌腫瘍80例(VIPomas 4例[男性3例、中央値63.5歳]、インスリノーマ45例[男性16例、中央値59歳]、ガストリノーマ27例[男性11例、中央値51歳]、その他4例[男性3例、中央値57歳])に分けた。その結果、VIPomas患者4例中3例は当初、非機能性膵神経内分泌腫瘍と診断されたが、経過中にVIPomasと診断されていた。ホルモン症状の再発は初期コントロールにもかかわらず、VIPomas全例で認められ、全例がホルモン症状により死亡した。他の膵神経内分泌腫瘍と比較して、VIPomasはすべて膵尾部に位置しており、サイズが大きく、Ki-67 indexが高く、転移も多かった。VIPomasの生存期間中央値は非機能性膵神経内分泌腫瘍、インスリノーマ、ガストリノーマと比較して有意に短かった(p<0.0001、p<0.0001、p<0.0325)。以上のように、VIPomasが成長するにつれて無症候から症候性へと移行する可能性や非機能性膵神経内分泌腫瘍からVIPomasへと変化する可能性が示された。

Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Clinical Medicine  

Although the combination of nanoliposomal irinotecan plus fluorouracil/folinic acid (nal-IRI/FF) exhibited survival benefits in gemcitabine-refractory patients with advanced pancreatic cancer (APC) in the phase III NAPOLI-1 trial, there is limited data on the efficacy and safety of this regimen in real-world settings in Japan. This multicenter, prospective observational study enrolled patients with APC who received nal-IRI/FF after a gemcitabine-based regimen from July 2020 to June 2021. We collected and analyzed clinical data and conducted survival and multivariate analyses. Thirty-one (78%) of the 40 patients had metastases. Nal-IRI/FF was the second-line therapy in 36 patients (90%). The median duration was 3.2 months. The disease control rate was 57%. The median progression-free survival and overall survival (OS) were 4.5 months (95% confidence interval [CI]: 2.8−5.5) and 7.4 months (95% CI: 5.1−10.6), respectively. Common ≥grade 3 toxicities included neutropenia (28%) and fatigue (23%). Fatigue led to treatment discontinuation in 6 out of 10 patients. Multivariate analysis showed that a neutrophil-to-lymphocyte ratio > 4 was a significant risk factor for a short OS (hazard ratio (HR) = 3.08, 95% CI: 1.21−7.85, p = 0.02). In conclusion, nal-IRI/FF is an appropriate treatment option for APC following gemcitabine-containing regimens.

DOI： 10.3390/jcm11175084

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Language：Japanese   Publisher：(株)アークメディア  

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Language：English   Publishing type：Research paper (scientific journal)  

This study aimed to evaluate the safety and efficacy of endoscopic transpapillary pancreatic duct stent placement (ETPS) for symptomatic peripancreatic fluid collection caused by postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). ETPS was also compared with percutaneous drainage (PTD). Retrospectively 38 patients were studied who developed clinically relevant POPF. Of 38 patients, 4 underwent PTD and 11 underwent ETPS. Technical and clinical success rates of ETPS (100&#37; and 91&#37;, respectively) were comparable with PTD (100&#37; and 75&#37;, respectively). The tip of a pancreatic stent was placed over the pancreatic stump in 4 patients and draining of pus through the pancreatic stent was observed. The hospital stay after DP and the interval from intervention to discharge were significantly shorter in the ETPS group than in the PTD group. ETPS is safe and successful for managing peripancreatic fluid collection caused by POPF after DP and should be considered as a therapeutic option.

DOI： 10.1097/SLE.0000000000000694

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: This study was performed to evaluate the surgical indication for intraductal papillary mucinous neoplasm (IPMN) advocated by the 2017 revised International Association of Pancreatology consensus guidelines (IAPCG2017). METHODS: The medical records of 63 patients who underwent pancreatectomy for IPMN were retrospectively reviewed. RESULTS: Thirteen patients had main-duct IPMN, 25 had mixed IPMN, and 25 had branch-duct IPMN with frequencies of high-grade dysplasia or invasive carcinoma of 62, 24, and 28&#37;, respectively. The sensitivity and specificity of high-risk stigmata for high-grade dysplasia or invasive carcinoma advocated by the IAPCG2017 were 90 and 67&#37;, respectively. Of 17 patients with invasive carcinoma, all patients had high-risk stigmata, and 16 had an enhanced mural nodule (MN) of ≥ 5 mm. The sensitivity and specificity of a ≥ 5-mm enhanced MN for predicting invasive carcinoma were 94&#37; and 87&#37;, respectively. CONCLUSIONS: Introducing a size threshold for enhanced MNs into the assessment of high-risk stigmata increases the specificity without jeopardizing the sensitivity. The surgical indication for any type of IPMN may be determined using only a ≥ 5-mm enhanced MN. When the type of IPMN is classified strictly, about half of IPMNs are mixed type, and most are benign. The surgical indication for mixed IPMN should be reconsidered.

DOI： 10.1007/s00595-018-1691-2

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. METHODS: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. RESULTS: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8&#37;; weekly regimen 46.4&#37;) was 21.8&#37;, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0&#37; (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0&#37; (P = 0.766). A Ki67 proliferation index (Ki67) of > 5&#37; was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). CONCLUSIONS: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5&#37; was the sole predictive marker of an objective response.

DOI： 10.1007/s00280-018-3656-y

Language：English   Publishing type：Research paper (scientific journal)  

Pancreatic cancer is a malignant neoplasm that originates from acinar cells. Acinar cells get reprogrammed to become duct cells, resulting in pancreatic cancer. Pancreatitis is an acinar cell inflammation, leading to "impaired autophagy flux". Pancreatitis promotes acinar-to-ductal transdifferentiation. Expression of amylase gets eliminated during the progression of pancreatic cancer. Amylase is considered as an acinar cell marker; however, its function in cells is not known. Thus, we investigated whether amylase affects the acinar cell autophagy and whether it plays any role in development of pancreatitis. Here, we knocked out ATG12 in a pancreatic cancer cells and acinar cells using CRISPR/Cas9. Autophagy inhibition led to an increase in the expression of duct cell markers and a simultaneous decrease in that of acinar cell markers. It also caused an increase in cell viability and changes in mitochondrial morphology. Next, we knocked out amylase in acinar cells. Amylase deficiency decreased autophagy induced by pancreatitis. Our results suggest that amylase controls pancreatitis-induced autophagy. We found that eliminating amylase expression contributes to pancreatic cancer etiology by decreasing autophagy. Furthermore, our results indicate that amylase plays a role in selective pancreatitis-induced autophagy of pancreatic enzyme vesicles.

DOI： 10.1155/2018/8719397

Language：English   Publishing type：Research paper (scientific journal)  

Objective The selective arterial secretagogue injection (SASI) test is considered indispensable for the accurate localization of insulinoma. However, the optimum timing of the post-injection evaluation is controversial, as some studies recommend 60 seconds [SASI (60 seconds)] while others support 120 seconds [SASI (120 seconds)]. The aim of this study was to determine the optimum timing for the SASI test evaluation for insulinoma localization. Methods Thirteen patients with surgically proven insulinoma were studied retrospectively. For the SASI test, immunoreactive insulin (IRI) was determined at baseline and at 30, 60, 90, and 120 seconds after calcium gluconate injection. A two-fold or greater increase in IRI over the baseline value was considered positive. The localization abilities of SASI (60 seconds) and SASI (120 seconds) were then compared. Results In 13 patients, a secretagogue was injected into 40 arteries supplying the pancreas. In the SASI (60 seconds) and SASI (120 seconds), the respective findings were as follows: positive predictive value, 72.2&#37; and 68.2&#37;; false positive rate, 25.0&#37; and 35.0&#37;; and rate of positivity in the head and body/tail, 38.5&#37; and 46.2&#37;. When the artery with the largest change was taken as the dominant artery, the localization detection sensitivity was 76.9&#37; for SASI (60 seconds) and 92.3&#37; for SASI (120 seconds). The sensitivity of morphological imaging techniques for localization ranged from 61.5-91.7&#37;. Conclusion Compared with SASI (60 seconds) or morphological imaging, the insulinoma localization ability of SASI (120 seconds) was superior. Given these findings, we believe that the IRI level should be measured at 120 seconds in the SASI test.

DOI： 10.2169/internalmedicine.9107-17

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Currently, serum chromogranin A is a well-established biomarker for pancreatic neuroendocrine tumors; however, other pancreatic diseases, oral use of a proton pump inhibitor and renal impairment can affect chromogranin A. Meanwhile, chromogranin B, belonging to the same granin family as chromogranin A, is not fully examined in these conditions. The present study aimed to evaluate the utility of chromogranin B as a pancreatic neuroendocrine tumor biomarker. METHODS: Serum chromogranin B levels were determined by radioimmunoassay and serum chromogranin A levels by enzyme-linked immunosorbent assay in pancreatic neuroendocrine tumor (n = 91) and other pancreatic conditions, and in healthy people (n = 104), to assess the relationships with clinical features. RESULTS: The diagnostic ability of chromogranin B was as good as chromogranin A. The area under the curve was 0.79 for chromogranin B (sensitivity/specificity: 72&#37;/77&#37;), and 0.78 for chromogranin A (sensitivity/specificity: 79&#37;/64&#37;). Chromogranin B was not affected by proton pump inhibitor use and age, which affected chromogranin A. The number of cases without liver metastases was larger in pancreatic neuroendocrine tumor patients with positive chromogranin B and negative chromogranin A. Though chromogranin A significantly elevated cases with proton pump inhibitor treatment and had positive correlation with age, chromogranin B did not have the tendencies. However, both chromogranin B and chromogranin A elevated in the case with renal impairment. In addition, the logistic regression analysis showed that chromogranin B was superior to chromogranin A in differentiation of pancreatic neuroendocrine tumor from other pancreatic diseases. CONCLUSIONS: Compared with chromogranin A, chromogranin B may be more useful during proton pump inhibitor treatment and can detect tumors without liver metastases. In addition, chromogranin B may be an excellent biomarker when differentiation of pancreatic neuroendocrine tumor from other pancreatic diseases is required.

DOI： 10.1093/jjco/hyx032

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: To evaluate the utility of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA + -M2BP) level as a marker for chronic pancreatitis (CP). METHODS: We measured the serum WFA+ -M2BP level of 74 patients with CP who had undergone endoscopic retrograde cholangiopancreatography and 30 normal controls (NC) using a glycan sugar chain-based immunoassay and investigated the relationship between serum WFA+ -M2BP levels and the Cambridge classification of CP. RESULTS: Serum WFA+ -M2BP level was significantly higher in patients with CP than in NC (0.64 ± 0.28 vs 0.34 ± 0.25, P < 0.001). The levels (expressed as cut-off index) of WFA+ -M2BP for the classification of mild, moderate and marked CP were 0.44, 0.63 and 0.87, respectively. Thus, serum WFA+ -M2BP levels increased with increasing CP severity. With a cut-off value of 0.34, 0.59 and 0.61, the area under the receiver operating characteristic curve, sensitivity and specificity were 0.829, 91.9&#37; and 63.3&#37; for mild CP; 0.891, 81.8&#37; and 85.0&#37; for moderate CP; and 0.888, 92.0&#37; and 74.7&#37; for marked CP, respectively. Multivariate analysis revealed that elevated serum WFA+ -M2BP was independently associated with moderate and marked CP, respectively. CONCLUSION: Serum WFA+ -M2BP level is a useful marker for grading CP severity.

DOI： 10.1111/1751-2980.12475

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: This study aimed to evaluate the usefulness of the 48-hour fasting test and insulin surrogates followed by a glucagon stimulatory test (GST) for the diagnosis of insulinoma. METHODS: Thirty-five patients with suspected insulinoma who underwent 48-hour fasting test and GST were retrospectively included in our study: 15 patients with surgically proven insulinomas and 20 patients in whom insulinoma was clinically ruled out. We determined the duration of the fasting test, plasma glucose levels, serum levels of immunoreactive insulin and C-peptide, and insulin surrogates (serum levels of β-hydroxybutyrate, free fatty acid, and response of plasma glucose to intravenous glucagon [ΔPG]) at the end of the fast. RESULTS: The sensitivity and specificity of the 48-hour fasting test were 100.0&#37; and 80.0&#37;, respectively, for the diagnosis of insulinoma. When the 48-hour fasting test and immunoreactive insulin, C-peptide, or insulin surrogates were combined, the combination with GST showed the best results. The sensitivity, specificity, and accuracy rate were 93.3&#37;, 95.0&#37;, and 94.3&#37;, respectively, with 1 false-negative case and 1 false-positive case occurring. CONCLUSIONS: A more accurate and less invasive diagnosis of insulinoma was possible by combining the 48-hour fasting test with the GST, compared with the existing method.

DOI： 10.1097/MPA.0000000000000772

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Although everolimus has become a key therapeutic agent in patients with advanced pancreatic neuroendocrine neoplasms (PNEN), its efficacy and safety in clinical practice remains unclear. METHODS: Forty-seven patients with advanced PNEN treated with everolimus were reviewed retrospectively. To evaluate the safety of everolimus as a long-term treatment, the patients were divided into two groups according to treatment duration: group A, ≤1 year (n = 21); group B, >1 year (n = 26). RESULTS: Among 42 patients with pancreatic neuroendocrine tumors (PNET), the median progression-free survival, overall survival, and objective response rate were 27.5 months, 60.8 months, and 19.0&#37;, respectively. Two patients with pancreatic neuroendocrine carcinomas (PNEC) with lower Ki-67 index and well-differentiated tumors showed favorable responses. More patients in group A discontinued everolimus owing to adverse drug reactions (ADRs) than in group B. The median relative dose intensity was significantly lower in group B than group A (P = 0.045), whereas the drug interruption rate was significantly higher in group B than group A (P < 0.001). CONCLUSIONS: Everolimus showed significant clinical benefit in Japanese patients with advanced PNEN. Prevention of severe ADRs by appropriate dose reduction and interruption is necessary for a long-term continuation of everolimus.

DOI： 10.1002/jhbp.418

Language：English   Publishing type：Research paper (scientific journal)  

Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.

DOI： 10.1007/s00535-015-1149-x

Language：English   Publishing type：Research paper (scientific journal)  

Pancreatic neuroendocrine tumors (PNETs) were considered an extremely rare disease. However, in recent years, the number of patients with PNET has increased rapidly. According to an epidemiological survey conducted in Japan, the number of treated patients with PNETs in 2010 was approximately 1.2-times that in 2005, and the number of new incidences of non-functional PNETs in 2010 was approximately 1.7-times that in 2005. Among functional PNETs, insulinoma was most prevalent, followed by gastrinoma. To diagnose PNETs, correct histological diagnosis is most important. According to the World Health Organization 2010 classification criteria, neuroendocrine tumors (NETs) are categorized into well-differentiated NETs and poorly differentiated neuroendocrine carcinomas (NECs). NECs accounted for 7.6&#37; of all NETs, and functional and non-functional PNETs accounted for 2.1&#37; and 10.1&#37;, respectively. Patients with distant metastasis accounted for 19.9&#37;, and those with multiple endocrine neoplasia type 1 accounted for 4.3&#37;. When treating PNETs, it is necessary to correctly evaluate the functionality and progression of tumors, the presence or absence of metastasis, and the degrees of differentiation and malignant potential of tumors. A new registration system from the Japan Neuroendocrine Tumor Society will start to be used in 2015, which will help further dissemination of Japanese epidemiological information to the world.

DOI： 10.1002/jhbp.225

Language：English   Publishing type：Research paper (scientific journal)  

We recently encountered the case of a patient with a synchronous duodenal gastrointestinal stromal tumor (GIST) and pancreatic neuroendocrine tumor (PNET). This is the first report of this specific combination of multiple primary tumors, although three cases involving both PNET and gastric GIST have previously been reported. Since the duodenal GIST developed close to the pancreatic uncus in this case, we considered the possibility of multiple PNETs in the differential diagnosis. However, a histopathological examination using endoscopic ultrasonography-guided fine-needle aspiration confirmed the diagnosis of multiple primary lesions, involving PNET and duodenal GIST.

Language：Japanese   Publishing type：Research paper (scientific journal)  

The case was a 58-year-old woman who visited our hospital for a thorough examination after multiple liver tumors were found in her at a nearby hospital. By liver tumor biopsy, we diagnosed them as carcinoid. Bone scintigraphy showed an abnormal accumulation in the external left scapula and in both of her hip joints, but the primary lesion was unclear. She died 8 years and 5 months after disease onset from deterioration of liver lesions, inspite of our treatments, such as gemcitabine administration of systemic chemotherapy, transcatheter arterial chemoembolization for liver lesions, and radiation therapy for bone lesions. Pathological anatomy suggested a pancreatic, well-differentiated neuroendocrine carcinoma.

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Language：Japanese   Publisher：医学図書出版(株)  

膵神経内分泌腫瘍(pancreatic neuroendocrine tumor:PanNEN)の術後再発率は比較的高く,再発高リスク群を同定することが予後改善に重要である。最近,われわれはPan-NEN切除例に関する多施設後方視的研究を行い,切除例の疫学データを明らかにした。その中で,NET G1/G2 371例を対象としてAIを用いた再発予測モデルを構築した。PanNET G1/G2の術後再発率は14.0%(52/371)であり,random survival forestモデルは従来のCox比例ハザード回帰モデルよりも優れた再発予測性能を示した。5年無再発生存率はKi-67指数と反比例して直線的に低下することから,実臨床ではKi-67指数の実数値が重要である。また,病変サイズが20mmを超えると無再発生存率が急速に低下し,40mmでプラトーに達した。本稿ではPanNEN診療の現状と課題について概説するとともに,われわれの研究結果の一部を紹介する。(著者抄録)

Language：Japanese   Publisher：医学図書出版(株)  

近年,腫瘍領域においてliquid biopsyが注目を集めているが,神経内分泌腫瘍(NEN)においても同様である。Liquid biopsyは従来の組織学的検査とは異なり,末梢血などの体液から非侵襲的にサンプルを抽出するため,腫瘍間・腫瘍内不均一性が問題となることはなく,容易にリアルタイムの病状を把握することができる。中でもmessenger RNAを用いたNETestはエビデンスが蓄積され,NETestから派生したpeptide receptor radionuclide therapy(PRRT)prediction quotientはPRRTの層別化マーカーとしての有用性が報告されている。このようにliquid biopsyは診断・モニタリング・治療効果の予測・予後と,NEN診療の全般にわたって有用でNEN診療体系の再構築が期待されるが,実臨床への導入にはさらなるエビデンスの蓄積に加えて,ハード・ソフト面の整備が必要であり,課題が多い。(著者抄録)

Language：Japanese   Publisher：(一社)日本膵臓学会  

神経内分泌腫瘍(neuroendocrine neoplasm:NEN)の診断および治療の標準化を目指して,日本神経内分泌腫瘍研究会(JNETS)より2015年に初めて膵・消化管NEN診療ガイドラインが発刊された.その後,WHO分類の改訂,ソマトスタチン受容体シンチグラフィーの登場,分子標的薬やストレプトゾシンおよびソマトスタチンアナログのランレオチドが対象疾患の追加,非機能性膵NENに対する手術適応の再検討など,多くのNENに関する新たな動向があり,2019年に第2版が改訂され発刊された.その後,ペプチド受容体放射性核種療法(PRRT)も登場してきた.NENは希少腫瘍であるとともに,全身臓器に発生して多彩な臨床症状を呈する.NENの診断には最終的に病理分類が重要であり,病理診断に基づいた薬物治療戦略の選択が必要となる.本稿では,膵NEN診療の現状および今後の展望について総説する.(著者抄録)

Language：Japanese   Publisher：(株)日本メディカルセンター  

＜文献概要＞慢性膵炎は,病期により臨床症状だけでなく画像所見も異なってくる.さらに,早期慢性膵炎という概念が提唱されて以降,慢性膵炎の病期と画像所見の関係はより複雑になっている.慢性膵炎診療において,画像所見の評価は必要不可欠であり,「慢性膵炎臨床診断基準2019」や「慢性膵炎診療ガイドライン2021」を参考に,どの時期にどの検査をすべきかを認識しておく必要がある.本稿では,早期慢性膵炎を含む慢性膵炎の各病期における画像診断とそのポイントについて概説する.

Language：Japanese   Publisher：医学図書出版(株)  

術後膵液瘻(postoperative pancreatic fistula:POPF)は発生頻度の高い膵切除術後合併症であり,適切なタイミングでドレナージを行う必要がある。従来は経皮的ドレナージが主流であったが,近年では内視鏡治療,とくにEUSガイド下経消化管ドレナージ(EUS-guided transluminal drainage:EUS-TD)の報告が増えている。EUS-TDで用いるステントとして,主に経鼻胆道ドレナージチューブ,ダブルピッグテイル型プラスチックステント,lumen-apposing metal stent,などがあり,POPFの部位,大きさ,性状に応じて,適切なステント選択を心がける必要がある。事前に外科医と情報共有のうえで,内視鏡治療にあたることが重要である。(著者抄録)

Language：Japanese   Publisher：医学図書出版(株)  

がんのリスクファクターにはさまざまなものがあり,代表的なものの一つに飲酒がある。アルコール摂取量と強い関連性を認めるがん種として口腔および喉頭・咽頭癌,食道扁平上皮癌,肝臓癌,結腸直腸癌,乳腺がんがあり,喉頭・咽頭癌,食道扁平上皮癌については禁酒による2次予防効果も報告されている。アルコールは本邦の膵癌ガイドラインにおいてリスク因子としてあげられているが,胆道癌については十分なエビデンスがない。アルコールの発癌の機序として主にアルコール代謝過程において生成されるアセトアルデヒドへの曝露が考えられているが,肝線維化,葉酸欠乏・阻害,エストロゲン濃度上昇なども報告されている。アセトアルデヒドについては日本人特有のアルコール代謝酵素遺伝子多型も大きく影響している。本稿では飲酒による発がんのメカニズム,日本人におけるアルコール代謝の特徴について述べ,各がん種について概説する。(著者抄録)

Language：Japanese  

膵癌と糖尿病には密接な関連がある。糖尿病は膵癌のリスク因子として古くから知られているが、膵癌発症の結果として糖尿病が出現することがあり、その関連性は双方向である。長期罹患糖尿病ではインスリン抵抗性とそれに伴う高インスリン血症が膵癌発症の機序であると考えられている。一方で膵癌患者ではインスリン抵抗性に加え、膵癌による膵島細胞機能不全によって糖尿病が新規発症するとされている。糖尿病が膵癌発見の契機となることや膵癌治療の予後に影響を与えること、糖尿病治療薬が膵癌発症や予後に影響を与えることも報告されており、膵癌の診断・治療において糖尿病の存在を常に意識することが重要である。(著者抄録)

Language：Japanese   Publisher：医学図書出版(株)  

慢性膵炎の臨床像は,病期や合併症の有無により患者ごとに大きく異なる。長期間の経過のなかで,膵石や膵管・胆管狭窄,仮性嚢胞,膵性胸腹水などさまざまな合併症を有することがあり,これらの病態には内視鏡治療が第一選択になる。慢性膵炎診療ガイドライン2021を念頭に,ERCPによる経乳頭的治療とEUSによる経消化管的治療,必要に応じて外科的治療を組み合わせて,慢性膵炎合併症の治療にあたる必要がある。本稿では慢性膵炎の合併症に対する内視鏡治療を中心に概説する。(著者抄録)

Language：Japanese   Publisher：日本胆膵病態・生理研究会  

膵癌と糖尿病には密接な関連がある。糖尿病は膵癌のリスク因子として古くから知られているが、膵癌発症の結果として糖尿病が出現することがあり、その関連性は双方向である。長期罹患糖尿病ではインスリン抵抗性とそれに伴う高インスリン血症が膵癌発症の機序であると考えられている。一方で膵癌患者ではインスリン抵抗性に加え、膵癌による膵島細胞機能不全によって糖尿病が新規発症するとされている。糖尿病が膵癌発見の契機となることや膵癌治療の予後に影響を与えること、糖尿病治療薬が膵癌発症や予後に影響を与えることも報告されており、膵癌の診断・治療において糖尿病の存在を常に意識することが重要である。(著者抄録)

Language：Japanese   Publisher：日本胆膵病態・生理研究会  

膵癌と糖尿病には密接な関連がある。糖尿病は膵癌のリスク因子として古くから知られているが、膵癌発症の結果として糖尿病が出現することがあり、その関連性は双方向である。長期罹患糖尿病ではインスリン抵抗性とそれに伴う高インスリン血症が膵癌発症の機序であると考えられている。一方で膵癌患者ではインスリン抵抗性に加え、膵癌による膵島細胞機能不全によって糖尿病が新規発症するとされている。糖尿病が膵癌発見の契機となることや膵癌治療の予後に影響を与えること、糖尿病治療薬が膵癌発症や予後に影響を与えることも報告されており、膵癌の診断・治療において糖尿病の存在を常に意識することが重要である。(著者抄録)

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Language：Japanese   Publisher：医学図書出版(株)  

神経内分泌腫瘍のなかで,機能性腫瘍ではさまざまなホルモンの過剰分泌による多彩な症状および代謝異常を引き起こす。インスリノーマでは,空腹時の低血糖発作が主要な症状であり,自律神経症状および中枢神経症状がみられる。ガストリノーマでは胃酸過剰分泌による消化性潰瘍や逆流性食道炎による症状と膵酵素不活性化による下痢が特徴である。グルカゴノーマでは耐糖能異常や糖尿病,体重減少,遊走性壊死性紅斑,精神神経症状などがみられる。その他,VIP(vasoactive intestinal peptide)オーマやソマトスタチノーマなども多彩な症状や代謝異常が認められる。本稿では機能性膵神経内分泌腫瘍の診断および代謝異常に対する薬物療法について総説する。(著者抄録)

Language：Japanese   Publisher：(株)日本臨床社  

Language：Japanese   Publisher：(株)日本臨床社  

Language：Japanese   Publisher：医学図書出版(株)  

長らく進行性膵神経内分泌腫瘍(PanNETs)の予後の改善は得られていなかったが,薬物療法の進歩によって,進行性PanNETsの治療成績は飛躍的に向上してきている。多くのPanNETsは細胞膜上にソマトスタチン受容体を高発現するため,診断や治療のターゲットとされてきた。ソマトスタチンアナログ(SSA)であるoctreotideは,従来ホルモン過剰症状の緩和目的に使用されてきたが,その後消化管NETsに対して抗腫瘍効果が示され,2011年に保険承認された。一方で,PanNETsに対しても近年の臨床試験結果に基づいて,持続性SSA徐放性製剤であるlanreotideが2017年に保険承認された。SSAは有害事象も少なく,実臨床でも汎用されているが,一方で各薬剤との使い分けなど,解決すべき課題も多い。本稿ではlanreotideを中心に,SSAの腫瘍増殖抑制効果について述べる。(著者抄録)

Language：Japanese   Publisher：(株)東京医学社  

Language：Japanese   Publisher：(株)医学出版  

わが国において神経内分泌腫瘍(neuroendocrine neoplasm:NEN)の診断および治療の標準化を目指して,日本神経内分泌腫瘍研究会(JNETS)より2015年に初めて膵・消化管NEN瘍診療ガイドラインが発刊された.その後,WHO分類の改訂,ソマトスタチン受容体シンチグラフィの登場,分子標的薬エベロリムスおよびソマトスタチンアナログのランレオチドが対象疾患の追加,非機能性膵NENに対する手術適応の再検討など,多くのNENに関する新たな動向があり,2019年に第2版が改訂され発刊された.NENは希少腫瘍であるとともに,全身臓器に発生して多彩な臨床症状を呈する.NENの診断および治療に関しては,複数の診療科が連携した診療体制が必要である.また,NENの診断には最終的に病理分類が重要であり,病理診断に基づいた薬物治療戦略の選択が必要となる.本稿では,改訂第2版のポイントを総説する.(著者抄録)

Language：Japanese   Publisher：(株)総合医学社  

＜最近の動向とガイドライン＞●神経内分泌腫瘍は、内分泌細胞や神経細胞から発症する腫瘍である。日本において、膵・消化管神経内分泌腫瘍の診断および治療の標準化を目指し、日本神経内分泌腫瘍研究会(JNETS)より、「膵・消化管神経内分泌腫瘍診療ガイドライン」が、2015年に日本で初めて発刊された。その後、神経内分泌腫瘍に関して多くの新たな動向があった。●診断部門においては、神経内分泌腫瘍全般にソマトスタチン受容体シンチグラフィが保険承認になった。さらに、膵神経内分泌腫瘍において、2017年および2019年にWHO分類が改訂となり、高分化型でK1-67指数をこすNET G3の概念が加わった。●治療においては、外科的切除による治癒を目指すのが標準であるが、切除不能例では腫瘍増殖を抑制し生命予後を改善させること、臨床症状の改善の両方を目的とした薬物治療が必要である。ソマトスタチンアナログのランレオチドが、高分化型の膵神経内分泌腫瘍に保険承認となり、治療の選択肢が増えた。これらを受けて、2019年9月に「膵・消化管神経内分泌腫瘍診療ガイドライン2019(第2版)」の出版となった。一方、ペプチド受容体放射性核種療法(PRRT)が使用可能となり、治療の選択肢は増えてきている。●膵神経内分泌腫瘍の治療においては、組織診が重要で、さらに腫瘍の機能性、進達度、転移の有無を正確に評価し、腫瘍の分化度および悪性度に合わせた治療が必要である。(著者抄録)

Language：Japanese   Publisher：(株)アークメディア  

Language：Japanese   Publisher：(有)科学評論社  

Language：Japanese   Publisher：医学図書出版(株)  

膵臓は内分泌機能と外分泌機能を併せ持つユニークな臓器である。膵機能障害により糖尿病や消化吸収障害を生じるが、その程度は膵疾患の種類や重症度、手術術式によってさまざまである。膵疾患の診断時のみならず、その経過中にも適宜、膵内外分泌機能を正確に評価し、重症度に合わせた治療介入が不可欠である。膵内分泌機能検査では空腹時血糖、HbA1c、75gOGTT、アルギニン試験などがあり、膵外分泌機能検査ではセクレチン試験、便中キモトリプシン・エラスターゼ1活性検査、BT-PABA試験、13C呼気試験などがある。本稿では現在、保険適用や試薬製造の問題で使用できない試験も併せて、膵内外分泌機能検査について概説する。(著者抄録)

Language：Japanese   Publisher：(株)アークメディア