Nao Yoshida

Activation of WNT/β-Catenin Signaling Enhances Pancreatic Cancer Development and the Malignant Potential Via Up-regulation of Cyr61

Pancreatic ductal adenocarcinoma (PDAC), a poor prognostic cancer, commonly develops following activating mutations in the KRAS oncogene. Activation of WNT signaling is also commonly observed in PDAC. To ascertain the impact of postnatal activation of WNT-stimulated signaling pathways in PDAC development, we combined the Elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-KrasG12D, Ptf1a-cre model. Delivery of RCAS viruses encoding β-cateninS37A and WNT1 stimulated the progression of premalignant pancreatic intraepithelial neoplasias (PanIN) and PDAC development. Moreover, mice injected with RCAS-β-cateninS37A or RCAS-Wnt1 had reduced survival relative to RCAS-GFP-injected controls (P < .05). Ectopic expression of active β-catenin, or its DNA-binding partner TCF4, enhanced transformation associated phenotypes in PDAC cells. In contrast, these phenotypes were significantly impaired by the introduction of ICAT, an inhibitor of the β-catenin/TCF4 interaction. By gene expression profiling, we identified Cyr61 as a target molecule of the WNT/β-catenin signaling pathway in pancreatic cancer cells. Nuclear β-catenin and CYR61 expression were predominantly detected in moderately to poorly differentiated murine and human PDAC. Indeed, nuclear β-catenin- and CYR61-positive PDAC patients demonstrated poor prognosis (P < .01). Knockdown of CYR61 in a β-catenin-activated pancreatic cancer cell line reduced soft agar, migration and invasion activity. Together, these data suggest that the WNT/β-catenin signaling pathway enhances pancreatic cancer development and malignancy in part via up-regulation of CYR61.

Hepatocellular Carcinoma with Sarcomatoid Change without Anticancer Therapies

Hepatocellular carcinoma (HCC) with sarcomatoid change is a rare neoplasm of the liver, and recurrent therapies for HCC such as transcatheter arterial chemoembolization and percutaneous ablation therapy are presumed to promote sarcomatoid change. A 73-year-old man was admitted to our hospital diagnosed as having liver cancer originating from hepatitis C-related cirrhosis without any previous treatment for HCC. Ultrasonography showed that the tumor was hypoechoic, 3 cm in diameter, with unclear margins. Computed tomography demonstrated a low-density lesion with ring enhancement on delayed phase. Under a diagnosis of poorly differentiated HCC the patient underwent liver resection. Histologically, the tumor consisted of proliferation of spindle-shaped sarcomatoid carcinoma cells with unclear trabecular and pseudoglandular structures including a nodule of typical moderately differentiated HCC, which was observed to shift mutually in one region. Here, we report a case of sarcomatoid HCC with a review of the literature.

Duodenal Stenosis Caused by Cystic Dystrophy in Heterotopic Pancreas : Report of a Case

We herein describe the first reported case of duodenal stenosis caused by cystic dystrophy in heterotopic pancreas (CDHP) in Asia. A 63-year-old man was admitted to the hospital presenting with nausea and vomiting of 2 days’ duration. Laboratory examinations showed an elevation in both the serum amylase level (275 IU/l) and white blood cell count (13 600/µl). A 3-cm-diameter tumor close against the duodenum was pointed out from the results of computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP); the tumor contained a cystic and solid component. Endoscopic examinations and an upper gastrointestinal series showed stenosis of the second portion of the duodenum without any mucosal change. The tumor was considered to be located at the submucosal layer of the second duodenum. The biopsy specimen of the duodenum revealed no malignancy. We strongly doubted the presence of a malignant submucosal tumor in the duodenum based on the findings of diagnostic imaging, and a pancreaticoduodenectomy was thus performed. Histopathologically, the lesion was diagnosed to be CDHP. The postoperative course was uneventful. The patient was symptomatic but was free of any symptoms after surgery. He continues to be regularly followed up on an outpatient basis and has had no recurrence of symptoms. This case demonstrates the need to consider CDHP in the differential diagnosis as a rare cause of duodenal stenosis.

A Longitudinal Computed Tomography Imaging in the Diagnosis of Gallbladder Cancer

Background/Aim. To assess whether the diagnostic power of longitudinal multiplanar reformat (MPR) images is superior to that of conventional horizontal images for gallbladder cancer (GBC). Methods. Between 2006 and 2010, a total of 54 consecutive patients with preoperatively diagnosed gallbladder neoplasms located in gallbladder bed were analyzed. These patients underwent cholecystectomy with resection of the adjacent liver parenchyma. The patients were divided into the GBC group (n = 30) and the benign group (n = 24). MPR images obtained by preoperative multidetector row CT (MDCT) were assessed. Results. Mucosal line was more significantly disrupted in GBC group than that in benign group (93% [28/30 patients] versus 13% [3/24], p < 0.001). Maximum (9.3 [4.2–24.8] versus 7.0 mm [2.4–22.6], p = 0.29) and minimum (1.2 [1.0–2.4] versus 1.3 mm [1.0–2.6], p = 0.23) wall thicknesses on a single MPR plane did not differ significantly; however, the wall thickness ratio (max/min) differed significantly (6.8 [1.92–14.0] versus 5.83 [2.3–8.69], p = 0.04). Partial liver enhancement adjacent to tumor on longitudinal images was more common in GBC (40.0% [12/30 patients] versus 12.5% [3/24], p = 0.03). Mucosal line disruption was the most reliable independent predictor of diagnosis (odds ratio, 8.5; 95% CI, 5.99–28.1, p < 0.001). Conclusion. Longitudinal MPR images are more useful than horizontal images for the diagnosis of GBC.

Neither ischemic parenchymal volume nor severe grade complication correlate transient high transaminase elevation after liver resection

To clarify whether high transient elevation of serum transaminase predicts severe complications and is related to the ischemic area on CT. Postoperative laboratory data and ischemia area on CT were analyzed on the basis of the presence of high transaminase elevation (aspartate aminotransferase (AST) > 1,000 IU/L within postoperative day (POD) 2 after liver resection. In the high elevation group, volume of ischemic areas was assessed by CT on POD2. The 538 patients were divided into a high transaminase group (n = 51) and a control group (n = 487). Median operation time (527 min vs. 360 min, p < 0.01) and liver ischemia time (121 min vs. 70 min, p < 0.01) were significantly longer, and intraoperative blood loss (478 mL [85-1572 mL] vs. 269 mL [5-4491 mL], p < 0.01) was significantly greater in the high transaminase group. No significant differences observed in frequency of severe complications (Clavien-Dindo classification Grade III or more) or postoperative hospitalization. Operation time (> 500 min; odds ratio (OR), 4.86; 95% confidence interval (CI), 2.40-9.89; p < 0.01) and liver ischemia time (> 120 min; OR, 3.47; 95%CI, 1.67-7.17; p < 0.01) were independent predictors of high transaminase elevation. No relationship was observed between degree of transaminase elevation and ischemic area (correlation coefficients: AST, R2 < 0.001; alanine aminotransferase, R2 = 0.005) CT volumetry on POD2. In conclusions, high transaminase elevations do not predict severe complications or reflect remnant ischemic area.

Safety and feasibility of a novel non-thermal device for tissue dissection: A preliminary study of the DD1 differential dissector

Energy devices can cause significant thermal damage to surrounding tissues causing unanticipated organ trauma. To evaluate the safety and feasibility of a novel electric device (DD1) for soft tissue dissection. Three series of measurements were performed in a pig model. First, macro- and microscopic tissue damage was compared between the DD1 and an electric scalpel (ES). Second, the time course of tissue temperature was measured for the DD1 and three other energy devices (ES, Harmonic and LigaSure). Third, the time required for mobilization of a peripheral artery of the intestine was compared between the DD1 and manual, non-energized forceps. First, the tissue damage area caused by ES was significantly larger compared to that in the DD1 at all time points (p < 0.0001). The number of damaged cells due to thermal damage was significantly larger for ES than for DD1, even when the DD1 was applied to a single point at maximum power for 60 sec (p < 0.0001). Second, the maximum temperature of Harmonic was 160°C 3 sec after use and dropped to 68°C after 10 sec. At the same time points after use, we observed: ES (84°C, 45°C), LigaSure (61°C, 49°C), and DD1 (30.5°C, 29°C). Third, the median dissection time for the artery using DD1 was significantly shorter than that for dissecting forceps (DD1: 100 sec, range 70-205 sec vs. forceps: 130 sec, range 90-210 sec, p = 0.0325). DD1 was a safe non-thermal device which causes less tissue damage while also providing shorter dissection times than manual dissection.

Hemispheric Outflow Reconstruction with Autologous Umbilical Vein in Living Donor Liver Transplantation

A 44-year-old man with hepatitis C virus-related cirrhosis underwent LDLT. The donor was his identical twin elder brother. On computed tomography, the markedly dilated umbilical vein was observed a...

Verification of inferior right hepatic vein-conserving segments 7 to 8 resection of the liver.

This study aims to investigate the safety of inferior right hepatic vein (IRHV)-conserving surgery by comparing the surgical data and postoperative complications between IRHV-conserving segments 7 to 8 (S7 to S8) resection and conventional right hemihepatectomy (RH). Five patients who underwent IRHV-conserving S7 to S8 segmentectomy between 2007 and 2011 (IRHV group) and 25 liver cancer patients who underwent RH without biliary tract reconstruction during the same period (RH group) were investigated. The surgical data, postoperative complications, and duration of hospital stay were compared. The IRHV and RH groups included 2 (40%) and 13 (52%) hepatocellular carcinoma patients, respectively. There were no significant differences in liver function before surgery between the groups. The presence of the IRHV did not adversely affect the processing of the short hepatic vein or frontal dissection of the inferior vena cava. The operative time was shorter (median, 366 minutes versus 501 minutes; P = 0.0001), the postoperative bilirubin level was lower (12 mg/dL versus 1.8 mg/dL; P = 0.037), and the duration of hospital stay was shorter (10 days versus 14 days; P = 0.002) in the IRHV group. No significant differences were noted in the intraoperative blood loss, postoperative transaminase levels, or the incidence of severe complications (Clavien grade IIIb or higher) between the groups. IRHV-conserving resection of the liver is a safe surgical procedure that is useful in preventing postoperative elevation of bilirubin level and in shortening the duration of hospital stay.

A CASE OF PROTEIN-LOOSING GASTROENTEROPATHY CAUSED BY DOUBLE GASTRIC CANCER

消化管粘膜から血漿蛋白,特にアルブミンが再吸収 される量を超えて異常に漏出し,低蛋白血症を呈する 病態は蛋白漏出性胃腸症と総称される.その原因疾患 は多岐にわたるが,悪性腫瘍も2次性に本症をきたす ことが知られている.山田ら は1973年~2005年まで に本邦で報告された62例を集計しているが,多発胃癌 によるものは報告されていない.今回われわれは低蛋 白血症を呈した多発胃癌の1例を経験したため報告す る. 症 例 患者:80歳,男性. 主訴:上腹部痛. 既往歴・家族歴:特記すべきことなし. 現病歴:2007年3月に上腹部痛を主訴に紹介医を受 診した.4月に上部消化管内視鏡検査を施行,噴門部 と前庭部の2カ所に腫瘍を認めたため当科に紹介とな った. 現症:腹部は平坦・軟.体表のリンパ節は触知せず. 下肢に中等度の浮腫を認めた. 血液検査所見:HGBは11.4g/dlで軽度貧血を認 めた.TP4.9g/dl,Alb1.8g/dlと著明な低蛋白血症を 認めた.肝・腎機能は正常で,糞便中のα1-アンチト リプシン1日排泄量は470mg/dayと著明に上昇(正常 は60mg/day以下),α1-アンチトリプシンクリアラン スは22.5ml/day(正常は20ml/day以下)であった. 腫瘍マーカーはCEA,CA19-9ともに正常範囲内であ った. 上部消化管造影検査(図 1):体上部後壁に直径9 cmの隆起性病変,前庭部後壁に直径8cmの潰瘍性病 変を認めた.十二指腸への通過障害は認めなかった. 上部消化管内視鏡検査(図 2):体上部後壁にBorrmann1型,胃角から前庭部後壁にBorrmann2型の 腫瘍を認めた.両腫瘍とも生検で groupV,adenocar-