胆管経路を利用した胎仔肝前駆細胞による脱細胞化肝臓グラフトの効率的な再細胞化

京都大学0048新制・課程博士博士(医学)甲第20280号医博第4239号新制||医||1021(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 川口 義弥, 教授 羽賀 博典, 教授 坂井 義治学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

McKeown esophagectomy with concomitant median arcuate ligament release in a case of esophageal cancer with celiac artery stenosis

[Background] The celiac artery stenosis due to compression by median arcuate ligament (MAL) has been reported in many cases of pancreaticoduodenectomy, but not in cases of esophagectomy. Recently, the celiac artery stenosis due to MAL or arteriosclerosis has been reported to be associated with the gastric tube necrosis or anastomotic leakage following Ivor–Lewis esophagectomy. Herein, we present the first reported case of esophageal cancer with celiac artery stenosis due to compression by the MAL successfully treated by McKeown esophagectomy and gastric tube reconstruction following prophylactic MAL release. [Case presentation] A 72-year-old female patient was referred to our department for esophagectomy. The patient had received two courses of neoadjuvant chemotherapy with 5-FU and cisplatin for T2N0M0 squamous cell carcinoma of the middle esophagus. Preoperative contrast-enhanced computed tomography (CECT) showed celiac artery stenosis due to compression by the MAL. The development of collateral arteries around the pancreatic head was observed without evidence of aneurysm formation. The patient reported no abdominal symptoms. After robot-assisted esophagectomy with mediastinal lymphadenectomy, gastric mobilization, supra-pancreatic lymphadenectomy, and preparation of the gastric tube were performed under laparotomy. Subsequently, the MAL was cut, and released to expose the celiac artery. Improved celiac artery blood flow was confirmed by decreased pulsatility index on intraoperative Doppler sonography. The operation was completed with the cervical esophagogastric anastomosis following cervical lymphadenectomy. Postoperative CECT on postoperative day 7 demonstrated increased celiac artery patency. The patient had an uncomplicated postoperative course thereafter. [Conclusions] Prophylactic MAL release may be considered in patients with celiac artery stenosis due to compression by the MAL on preoperative CECT for esophagectomy

The usefulness of preoperative bile cultures for hepatectomy with biliary reconstruction

[Background] Infectious complications can cause lethal liver failure after hepatectomy with biliary reconstruction. This study assessed the increased risk for postoperative infectious complications in patients who underwent hepatectomy with biliary reconstruction and explored the possibility of predicting pathogenic microorganisms causing postoperative infectious complications based on preoperative monitoring of bile cultures. [Methods] This study involved 310 patients who received major hepatectomy with or without biliary reconstruction at our institution between January 2010 and December 2019. The relationship between the microorganisms detected through perioperative monitoring of bile culture and those in the postoperative infectious foci was examined. [Results] Forty-nine patients underwent major hepatectomy with biliary reconstruction, and 261 received hepatectomy without biliary reconstruction. The multivariate analysis revealed hepatectomy with biliary reconstruction to be associated with an increased risk of postoperative infectious complications (odds ratio: 22.9, 95% confidence interval: 5.2–164.3) compared to hepatectomy without biliary reconstruction. In the patients with biliary reconstruction, the concordance rates between the microorganisms detected in the postoperative infectious foci and those in preoperative bile cultures were as follows: incisional surgical site infection (44.4%), organ/space surgical site infection (52.9%), bacteremia (47.1%), and pneumonia (16.7%); the concordance rates were high, and the risk of infection increased over time. [Conclusions] Biliary reconstruction is a significant risk factor for postoperative infectious complications, and preoperative bile cultures may aid in prophylactic and therapeutic antimicrobial agent selection

A subcentimeter duodenal neuroendocrine neoplasm with a liver metastasis upgraded to G3: a case report

BACKGROUND: Although duodenal neuroendocrine neoplasms (DuNENs) usually have indolent phenotypes, some DuNENs exhibit aggressive clinical manifestations. Tumor size > 1 cm, lymph node metastasis, and high grade have been associated with poor prognosis. However, preoperative risk evaluation is often difficult, because Ki-67 index on biopsy is frequently underestimated due to the intratumor heterogeneity. Here, we present a case of a subcentimeter DuNEN with a low Ki-67 index on endoscopic biopsy, who developed lymph node metastasis and high-grade liver metastasis. CASE PRESENTATION: The patient was a 52-year-old female who presented an epigastric pain. Esophagogastroduodenoscopy revealed a duodenal submucosal lesion with a size of 8 mm. The endoscopic biopsy showed DuNEN with a Ki-67 index of 3.3% (G2 categorized by the World Health Organization 2019 classification). We performed an open partial duodenectomy with adjacent lymph node dissection. Pathological examination of the resected specimens revealed a Ki-67 index of 13.5% (G2) in the "hot spot" and lymph node metastasis. A hepatic low-density area detected on preoperative contrast-enhanced computed tomography appeared to be a liver metastasis on postoperative gadoxetic acid-enhanced magnetic resonance imaging. Subsequently, we performed a laparoscopic partial hepatectomy. Pathological examination of the liver specimen showed a metastatic neuroendocrine tumor with a Ki-67 index of 27.5% (NET-G3). The patient has been alive for 14 months since the hepatectomy. CONCLUSIONS: This case shows the possibility of high malignant potential of DuNEN even if the primary lesion is < 1 cm and has a low Ki-67 index on biopsy

En bloc excision of giant polycystic liver with hepatic cava and its auto-transplant caval reconstruction as a safe surgical procedure for liver transplantation

Safely excising a giant liver while leaving the hepatic inferior vena cava intact is difficult. Hata et al. present images and videos describing their novel technique consisting of total hepatectomy including the hepatic cava; extracorporeal retrieval; and auto‐transplant inferior vena cava reconstruction, for an extremely enlarged polycystic liver weighing 24 kg.[Image: see text

SOX9 is a novel cancer stem cell marker surrogated by osteopontin in human hepatocellular carcinoma

The current lack of cancer stem cell (CSC) markers that are easily evaluated by blood samples prevents the establishment of new therapeutic strategies in hepatocellular carcinoma (HCC). Herein, we examined whether sex determining region Y-box 9 (SOX9) represents a new CSC marker, and whether osteopontin (OPN) can be used as a surrogate marker of SOX9 in HCC. In HCC cell lines transfected with a SOX9 promoter-driven enhanced green fluorescence protein gene, FACS-isolated SOX9+ cells were capable of self-renewal and differentiation into SOX9-cells, and displayed high proliferation capacity in vitro. Xenotransplantation experiments revealed that SOX9+ cells reproduced, differentiated into SOX9-cells, and generated tumors at a high frequency in vivo. Moreover, SOX9+ cells were found to be involved in epithelial-mesenchymal transition (EMT) and activation of TGFb/Smad signaling. Gain/loss of function experiments showed that SOX9 regulates Wnt/beta-catenin signaling, including cyclin D1 and OPN. Immunohistochemistry of 166 HCC surgical specimens and serum OPN measurements showed that compared to SOX9-patients, SOX9+ patients had significantly poorer recurrence-free survival, stronger venous invasion, and higher serum OPN levels. In conclusion, SOX9 is a novel HCCCSC marker regulating the Wnt/beta-catenin pathway and its downstream target, OPN. OPN is a useful surrogate marker of SOX9 in HCC

Cholangiocarcinoma after flow diversion surgery for congenital biliary dilatation: A case report and review of literature

BACKGROUND: Pancreaticobiliary maljunction (PBM) can be classified into two categories, PBM with congenital biliary dilatation (CBD) or PBM without biliary dilatation, and the management of PBM is often controversial. The treatment for PBM with CBD is prophylactic flow diversion surgery, and some authors have reported that the incidence of cancer after extrahepatic bile duct excision is less than 1%. A very rare case of intrahepatic cholangiocarcinoma 6 years after flow diversion surgery for PBM with CBD is reported. CASE SUMMARY: A 30-year-old man was diagnosed as having PBM with CBD, Todani classification type IVA, because of abnormal liver enzyme profiles. He underwent flow diversion surgery and cholecystectomy, and the specimen showed adenocarcinoma foci, pT1, pStage IA. Five and a half years passed without any recurrence of bile duct cancer. However, 6 years after his operation, computed tomography showed a gradually growing nodule in the bile duct. Fluorodeoxyglucose positron emission tomography showed high uptake, and magnetic resonance imaging showed restricted diffusion signals. On double balloon enteroscopy, the nodule at the posterior bile duct-jejunum anastomosis was directly visualized, and its biopsy specimen showed adenocarcinoma. The patient underwent right lobectomy and biliary reconstruction. The pathological diagnosis was intraductal papillary neoplasm with high-grade intraepithelial neoplasia, pTis, pN0, pStage 0. The patient’s postoperative course was uneventful, and he has had no recurrence up to the present time. CONCLUSION: This case suggests the necessity of careful observation after flow diversion surgery, especially when PBM with CBD is detected in adulthood