鈴木 達也

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.

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.

<title>Abstract</title><sec> <title>Background</title> Acute obstruction of the hepatic vein (HV) or the portal vein (PV), particularly when it occurs during liver surgery, is potentially fatal unless repaired swiftly. As surgical interventions for this problem are technically demanding and potentially unsuccessful, other treatment options are needed. </sec><sec> <title>Case presentation</title> We report two cases of acute, surgically uncorrectable HV or PV obstruction during liver resection or living donor liver transplantation (LDLT), which was successfully treated with urgent intraoperative placement of endovascular stents using interventional radiology (IVR). In Case 1, a patient with colonic liver metastases underwent a non-anatomic partial hepatectomy of the segments 4 and 8 with middle hepatic vein (MHV) resection. Additionally, the patient underwent an extended right posterior sectionectomy with right hepatic vein (RHV) resection for tumors involving RHV. Reconstruction of the MHV was needed to avoid HV congestion of the anterior section of the liver. The MHV was firstly reconstructed by an end-to-end anastomosis between the MHV and RHV resected stumps. However, the reconstruction failed to retain the HV outflow and the anterior section became congested. Serial trials of surgical revisions including re-anastomosis, vein graft interposition and vein graft patch-plasty on the anastomotic wall failed to recover the HV outflow. In Case 2, a pediatric patient with biliary atresia underwent an LDLT and developed an intractable PV obstruction during surgery. Re-anastomosis with vein graft interposition failed to restore the PV flow and elongated warm ischemic time became critical. In both cases, the misalignment in HV or PV reconstruction was likely to have caused flow obstruction, and various types of surgical interventions failed to recover the venous flow. In both cases, an urgent IVR-directed placement of self-expandable metallic stents (SEMS) restored the HV or PV perfusion quickly and effectively, and saved the patients from developing critical conditions. Furthermore, in Cases 1 and 2, the SEMS placed were patent for a sufficient period of time (32 and 44 months, respectively). </sec><sec> <title>Conclusions</title> The IVR-directed, urgent, intraoperative endovascular stenting is a safe and efficient treatment tool that serves to resolve the potentially fatal acute HV or PV obstruction that occurs in the middle of liver surgery. </sec>

Objectives: Proximal stoma creation in neonates results in growth failure and distal intestinal atrophy. "Recycling stool" consists of stool injection from the proximal limb to the distal limb of a stoma. Because this method may prevent distal bowel atrophy and increase body weight, we investigated the effects of recycling stool upon distal intestinal mucosa by generating an ileostomy model in rats. Methods: An ileostomy was created 5 cm proximal to the cecum in male Wistar/ST rats. Discharged stool or saline was injected into the distal limb, twice per day for 7 days. The intestinal adaptation was assessed by measuring the villus height and counting goblet cell number. Proliferation and apoptosis were analyzed by Ki67 and TUNEL immunostaining. Results: The ratios of the height of the distal villi (D) to the that of proximal villi (P) were 0.97 (median [range] of D and P length: 421 [240-729] μm and 436 [294-638] μm, P<0.05) in the stool-injected group and 0.81 in the saline-injected group (442 [315-641] μm and 548 [236-776] μm, P<0.05). Compared with the saline-injected group, the stool-injected group showed elevated numbers of goblet cells (3.6 [2.0-7.6] vs. 4.9 [2.4-7.5] cells/100-μm villus length) and Ki67-positive cells (26.8% [13.8%-35.4%] vs. 40.1% [31.2%-45.7%]), along with a reduced number of apoptotic cells (5.0 [2.0-14.0] vs. 4.0 [1.0-9.0] cells/100-μm villus length). Conclusions: Recycling stool prevented distal intestinal atrophy; this experimental design may facilitate further studies concerning alternative methods to prevent intestinal atrophy and growth failure.

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)