渡邉 俊介

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory disease of unknown etiology. Although various new drugs have been developed in recent years, many of them are expensive, generating a demand for inexpensive and useful therapeutic drugs. Ogikenchuto (TJ‐98), an existing Kampo medicine, has been used to treat ulcers and similar conditions for some time. The current study therefore investigated whether TJ‐98 could be a new therapeutic agent for UC, a chronic inflammatory disease. Methods This study used 6‐week‐old female C57BL/6J mice to establish a mouse model of dextran sulfate sodium (DSS)‐induced colitis. We then evaluated the therapeutic effects of tacrolimus and TJ‐98 on colitis based on body weight, intestinal length, intestinal fibrosis, and cytokines. Sirius red staining was used to evaluate intestinal fibrosis, while interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor‐alpha (TNF‐α) were used to evaluate cytokines involved in inflammation. Results Neither tacrolimus nor TJ‐98 ameliorated weight loss. Although tacrolimus did not remediate intestinal shortening, intestinal fibrosis, or cytokine levels (IL‐1β, IL‐6, and TNF‐α), TJ‐98 did ameliorate intestinal shortening and intestinal fibrosis and decrease IL‐1β levels. Conclusions This study confirmed that TJ‐98 suppressed the inflammation caused by DSS‐induced enteritis and decreased the associated intestinal fibrosis, highlighting its potential as an inexpensive novel therapeutic agent for UC.

BACKGROUND: Focal intestinal perforation (FIP) is a devastating complication of premature birth, and extremely low birth weight (ELBW) infants are at highest risk. This study aimed to evaluate the relationship of the superior mesenteric artery (SMA) and portal vein (PV) blood flow velocities to investigate the association between intestinal blood flow and FIP. In addition, the herbal formula Daikenchuto (TJ-100) is expected to improve intestinal blood flow disorders; therefore, we evaluated its effect. METHODS: We conducted a prospective cohort study of 15 ELBW infants from January 2020 to August 2021. Measured variables included birth weight, 5-minute Apgar score, time of oral feeding initiation, ductus arteriosus (PDA) closure (percent), diastolic and systolic blood pressure, SMA and PV blood flow velocity, and FIP onset data. Fifteen infants were divided into three groups: a non-surgery group (Group I; 6), a surgery group with FIP (Group II; 4), and a TJ-100 administration group (Group III; 5). The main outcome parameters included SMA and PV blood flow velocities with TJ-100. RESULTS: SMA and PV blood flow differed significantly for the SMA of Group I and the SMA and PV of Group III (P < 0.01, P = 0.01, and P = 0.04, respectively). There was a correlation between SMA and PV in Group III (P = 0.03). CONCLUSION: TJ-100 may increase SMA and PV blood flow and improve intestinal blood flow in ELBW infants at risk of FIP. Therefore, the effects of TJ-100 should undergo further study.

BACKGROUND: We previously reported that polyphyllin D, the main component of the traditional herbal medicinal Paris polyphylla, exhibited anticancer effects in vitro against human neuroblastoma cells. The aim of this investigation was to examine in vivo antitumor effects of polyphyllin D. METHODS: Subcutaneous tumors were established in immune-deficient BALB/c nude mice using human neuroblastoma cell lines IMR-32 and LA-N-2. To evaluate the polyphyllin D activity, we used a mouse model of IMR-32 or LA-N-2 cell lines and analyzed subcutaneous tumors. RESULTS: Subcutaneous tumor models were successfully established in mice using two human neuroblastoma cell lines. In the subcutaneous tumor model, porphyrin D was found to suppress tumor volume. We found that polyphyllin D suppressed the number of foci by Ki-67 staining (IMR-32 and LA-N-2; p < 0.01, 0.02, respectively). We found that polyphyllin D induces the RIPK3 expression, while polyphyllin D phosphorylates Ser358 in IMR-32 and Ser358 and Tyr376 in LA-N-2. CONCLUSION: We developed a mouse model of subcutaneous tumors of neuroblastoma and demonstrated for the first time that polyphyllin D has an antitumor effect on neuroblastoma. Polyphyllin D can cause necroptosis depending on the cell type. The new drug can be expected by investigating a method to selectively induce cell death through the analysis of necroptosis.

排便と関連のない心窩部痛とそれに伴う腹部膨満,腹痛は機能性ディスペプシアの症状の一つであるが治療に難渋することが多い。症例は15歳女児。14歳9ヵ月時から心窩部痛,午後に腹部膨満感と腹痛があるため近医受診したが改善されず当院小児科紹介となった。血液生化学検査や腹部超音波検査は明らかな異常は認めず血液生化学検査と腹部超音波検査で有意な異常所見は認めなかったため,過敏性腸症候群の可能性を考えトリペブチンマレイン酸塩が投与された。投与開始後も症状の改善なく原因精査のため当科紹介となった。腹部単純X線検査,上部消化管造影検査から器質的疾患は認めなかった。そのため機能性ディスペプシアと診断した。15歳3ヵ月時に半夏厚朴湯を開始した。投与開始3週間後には腹部膨満感と腹痛は改善したが,心窩部痛はないも心窩部の違和感は残存していたため,半夏厚朴湯を継続し4ヵ月後に心窩部の違和感も消失し投薬中止後6ヵ月が経過したが症状の再燃は認めていない。(著者抄録)

PURPOSE: We previously reported that polyphyllin D, a main component of the traditional Chinese medicinal herb Paris polyphylla, exhibited anticancer effects in vitro against human neuroblastoma cells. The aims of this investigation was to examine the presence or absence of in vivo anti-metastasis effects of polyphyllin D were to establish a liver metastasis model of neuroblastoma and to evaluate the anti-metastasis effects of polyphyllin D. METHODS: Subcutaneous and intraperitoneal tumors, and metastasis models were established in immune-deficient BALB/c nude and BALB/c Rag-2/Jak3 double-deficient (BRJ) mice using the human neuroblastoma cell lines IMR-32, LA-N-2, or NB-69. For evaluating polyphyllin D activity, we used a mouse model of liver metastasis with the IMR-32 cells line injected through the tail vein. We analyzed the livers number and area of liver tumors in of the phosphate buffer solution- and polyphyllin D-treated groups. RESULTS: Liver metastasis and intraperitoneal dissemination models were successfully established in immune-deficient BRJ mice using the three human neuroblastoma cell lines. In the liver metastasis, the model of IMR-32 cells, we found that polyphyllin D suppressed both the number and total area of metastatic foci the average number of metastatic foci, average focus areas, and number of cleaved caspase-3-positive cells were significantly lower in the polyphyllin D group (p = 0.016, 0.020, 0.043, respectively). CONCLUSIONS: We developed a mouse models of neuroblastoma metastasis and demonstrated for the first time that polyphyllin D has an antitumor effect on neuroblastoma liver metastases.

BACKGROUND: Biliary atresia (BA) is a rare disorder characterized by obstructive jaundice in infants, shortly after birth. Postoperatively, some patients exhibit portal hypertension and progressive liver fibrosis. Splenomegaly is a symptom of portal hypertension. We aimed to investigate splenomegaly as a marker for complications of portal hypertension and the relationship between splenomegaly and liver fibrosis in the long-term native liver (NL). METHODS: Between 1977 and 2018, 71 patients underwent hepaticojejunostomy. We included 54 patients (34 NL group, 20 liver transplant (LT) group) who fulfilled the eligibility criteria. Spleen volume (SV), total bile acids, hyaluronic acid, type IV collagen, and aspartate aminotransferase-to-platelet ratio index (APRi) were measured. Data were analyzed using Student's t-test, regression analysis, and receiver operating characteristic (ROC) curve analysis (P < 0.05). RESULTS: Total bile acids, hyaluronic acid, type IV collagen, and APRi increased in NL patients with a large SV at >25 years. SV and type IV collagen were correlated with NL for >25 years (r = 0.79 [P = 0.006], y = 1.1 - [0.03 × type IV collagen] [P = 0.008]). In the ROC curve analysis, the cutoff value for type IV collagen was 165 ng/mL (P = 0.07). CONCLUSIONS: We suggest that SV as a prognostic index for End-Stage Liver Disease may be useful in biliary atresia. Long-term follow-up is necessary because the clinical course may be favorable in childhood but worsen during adulthood.

Abstract Case Advanced glycation end products (AGEs) associated with diabetes, renal failure, and non‐alcoholic fatty liver disease have recently been receiving attention. The present study aimed to investigate therapeutic effects of Astragali Radix (AR) using skin autofluorescence (SAF) to evaluate AGEs. Treatment group (May 2019 to May 2020) was 18 patients. AR administration period was six months. SAF, body mass index, mean blood pressure, hemoglobin A1c, serum creatinine, estimated glomerular filtration rate (eGFR), aspartate transaminase, and alanine transaminase (ALT) were used. Outcome Significant differences in SAF (P &lt;0.01) and serum creatinine (P = 0.03) were observed in the treatment group. Regression analysis showed that SAF was correlated with serum creatinine and ALT. Conclusion We suggest that AR may improve SAF, serum creatinine, and ALT. Improving AGEs through AR may ameliorate liver function, and eGFR with improvement of serum creatinine. Future studies are necessary to confirm our findings.

BACKGROUND: Disseminated intravascular coagulation (DIC) with Kasabach-Merrit syndrome from a large hepatic hemangioma is life-threatening. We report a case of giant hepatic hemangioma of the newborn with KMS. RESULTS: The patient was born at 37 gestational weeks and 2 days via cesarean section; weight at birth was 2952 g. Congenital duodenal atresia was noted during the fetal period. DIC developed after delivery and a giant liver hemangioma was diagnosed via abdominal CT. The cause of DIC was Kasabach–Merritt syndrome owing to a giant hepatic hemangioma. First, combination therapy of 2 mg/kg/day of prednisolone and 0.2 mg/kg/day of propranolol was initiated form enterostomy. However, the size of the hepatic hemangioma did not alter, as observed via image evaluation. Therefore, 0.3 mg/kg/day of everolimus was administered frorm enterostomy. Subsequently, the size of the hepatic hemangioma was assessed via image evaluation. Although it did not alter, blood flow to the hepatic hemangioma decreased and thrombocytopenia was also suppressed. We performed hepatic lateral segmentectomy, radical operation for duodenal atresia. The pathological diagnosis of the removed tumor was infantile hemangioma. CONCLUSION: We report everolimus may be useful when PSL and propranolol are ineffective.

Pectus excavatum has been performed using techniques such as sternum elevation and sternum reversal however, the Nuss method is now widely used. The Nuss method is considered less invasive, but it requires a plate. We have performed open-repair surgery that can be completed at once without using a plate as a standard procedure. Conversely, the usefulness of the internal thoracic artery (ITA) in coronary artery bypass surgery and breast reconstruction has increased in recent years. Therefore, since 2017, we changed the surgical procedure to preserve the ITA here, we mainly report on the surgical procedure. Five patients, four boys and one girl, were examined for in Haller index, operation time, blood loss, postoperative complications, and postoperative hospital stay. Among the five cases, before the change of surgical procedure, the operation time, blood loss, and hospitalization period postoperatively were not significantly different from those before the change. Bilateral ITA could be preserved except in one patient in whom one side was damaged and ligated during the operation. No postoperative complications were observed in all cases. It is possible to preserve the ITA, and we intend to perform additional studies to evaluate its long-term effectiveness.

我々は稀な肝未分化肉腫を2例経験したので報告する.症例1は11歳女児.発熱,腹痛で発症し,CTで肝右葉に巨大腫瘍,PET-CTでは腫瘍辺縁に強く集積を認めた.血液検査所見ではLDHとCA125が高値を示し,生検にて肝未分化肉腫と診断した.VAC療法(ビンクリスチン,アクチノマイシンD,シクロフォスファミド)(5クール)後に腫瘍核出術を施行した.術後VAC療法(8クール)を行い治療終了後5年2ヶ月経過し再発なく生存中である.症例2は12歳男児.右上腹部膨隆と腹痛で発症し,CTで肝右葉に腫瘍,PET-CTで腫瘍辺縁に集積を認めた.血液検査所見ではLDHとCA125が高値を示し,肝未分化肉腫と術前診断し右3区域切除術を行った.摘出腫瘍は肝未分化肉腫の病理診断であった.術後VAC療法(5クール)行い治療終了後1年4ヶ月経過し無病生存中である.年長児で特異的腫瘍マーカーの上昇が伴わない肝腫瘍においては,本疾患を想起することが肝要である.(著者抄録)

【目的】胆道閉鎖症(以下、BA)スクリーニングのために便色カラーカードが2012年に母子健康手帳へ導入され5年が経過した。しかしながら未だに3ヵ月を越えて紹介されてくる患児も多く、便カラーカードの意義や本症に対して医療従事者らがBAおよびカードをどのように認識しているかを評価し、知識を深めることを目的にアンケート調査と啓蒙活動を行った。【方法】当院に勤務する小児科医、産婦人科医、小児もしくは産科病棟の看護師および准看護師、助産師ら172名を対象に便色カードに関するアンケートテストと本症に関するプレゼンテーションを行い、結果と効果を確認する。【結果】109名(63.3%)の回答を得られた。カラーカードを知らないと回答したのは13名(11.9%)であった。カラーカードを用いずに便色を判定していただき39名(35.7%)がわからないと回答した。一方でBAを知っていると回答したのは105名(96.3%)で、59名(54.1%)が生後1ヵ月以内で発見されると回答した。BAが完治すると回答したのは45名(41.2%)であった。BAに関するプレゼンテーションについて「ものすごく勉強になった」と回答したのは92名(84.4%)であった。【結論】今回のアンケートから、小児外科医以外の医師や看護師のBAに対する認識は低いものと考えられた。カラーカードは導入されたが、その意義やBAに対する認識を患者両親に正しく伝えるためにも、今後さらなる啓蒙活動の推進が必要である。(著者抄録)

【目的】胆道閉鎖症(以下、BA)スクリーニングのために便色カラーカードが2012年に母子健康手帳へ導入され5年が経過した。しかしながら未だに3ヵ月を越えて紹介されてくる患児も多く、便カラーカードの意義や本症に対して医療従事者らがBAおよびカードをどのように認識しているかを評価し、知識を深めることを目的にアンケート調査と啓蒙活動を行った。【方法】当院に勤務する小児科医、産婦人科医、小児もしくは産科病棟の看護師および准看護師、助産師ら172名を対象に便色カードに関するアンケートテストと本症に関するプレゼンテーションを行い、結果と効果を確認する。【結果】109名(63.3%)の回答を得られた。カラーカードを知らないと回答したのは13名(11.9%)であった。カラーカードを用いずに便色を判定していただき39名(35.7%)がわからないと回答した。一方でBAを知っていると回答したのは105名(96.3%)で、59名(54.1%)が生後1ヵ月以内で発見されると回答した。BAが完治すると回答したのは45名(41.2%)であった。BAに関するプレゼンテーションについて「ものすごく勉強になった」と回答したのは92名(84.4%)であった。【結論】今回のアンケートから、小児外科医以外の医師や看護師のBAに対する認識は低いものと考えられた。カラーカードは導入されたが、その意義やBAに対する認識を患者両親に正しく伝えるためにも、今後さらなる啓蒙活動の推進が必要である。(著者抄録)