Chih-Jen Chen

Costunolide causes mitotic arrest and enhances radiosensitivity in human hepatocellular carcinoma cells

PurposeThis work aimed to investigate the effect of costunolide, a sesquiterpene lactone isolated from Michelia compressa, on cell cycle distribution and radiosensitivity of human hepatocellular carcinoma (HCC) cells.MethodsThe assessment used in this study included: cell viability assay, cell cycle analysis by DNA histogram, expression of phosphorylated histone H3 (Ser 10) by flow cytometer, mitotic index by Lius stain and morphological observation, mitotic spindle alignment by immunofluorescence of alpha-tubulin, expression of cell cycle-related proteins by Western blotting, and radiation survival by clonogenic assay.ResultsOur results show that costunolide reduced the viability of HA22T/VGH cells. It caused a rapid G2/M arrest at 4 hours shown by DNA histogram. The increase in phosphorylated histone H3 (Ser 10)-positive cells and mitotic index indicates costunolide-treated cells are arrested at mitosis, not G2, phase. Immunofluorescence of alpha-tubulin for spindle formation further demonstrated these cells are halted at metaphase. Costunolide up-regulated the expression of phosphorylated Chk2 (Thr 68), phosphorylated Cdc25c (Ser 216), phosphorylated Cdk1 (Tyr 15) and cyclin B1 in HA22T/VGH cells. At optimal condition causing mitotic arrest, costunolide sensitized HA22T/VGH HCC cells to ionizing radiation with sensitizer enhancement ratio up to 1.9.ConclusionsCostunolide could reduce the viability and arrest cell cycling at mitosis in hepatoma cells. Logical exploration of this mitosis-arresting activity for cancer therapeutics shows costunolide enhanced the killing effect of radiotherapy against human HCC cells.

Comparison of coplanar and noncoplanar intensity-modulated radiation therapy and helical tomotherapy for hepatocellular carcinoma

BackgroundTo compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT).MethodsNine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46 - 54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30 < 30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram.ResultsHT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively.ConclusionNoncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.

Spontaneous Clearance of Helicobacter pylori Colonization in Patients with Partial Gastrectomy: Correlates with Operative Procedures and Duration After Operation

BACKGROUND/PURPOSE For patients undergoing gastric surgery because of complications of peptic ulcers, such as bleeding or perforation in the pre-Helicobacter pylori eradication era, their infection status was not surveyed or it was neglected altogether. Previous reports have shown spontaneous clearance of H. pylori in these patients but the determining factors remain ill-defined. METHODS Seventy-six patients with previous partial gastrectomy for complicated peptic ulcers were enrolled prospectively. Patients with peptic ulcers but without gastrectomy were selected as a control group. Gastric biopsy specimens were obtained from each patient for histological H. pylori staining and rapid urease test on endoscopic evaluation. Spontaneous clearance of H. pylori colonization was defined when patients who were positive for H. pylori prior to operation became negative, without eradication treatment. RESULTS The prevalence of H. pylori colonization was significantly lower in patients with partial gastrectomy (22.4%, 17/76 vs. 67.1%, 51/76, p < 0.001). There was a trend towards decreasing prevalence of H. pylori colonization as time after operation increased: 1-15 years, 29.5% (13/44); 16-30 years, 13.6% (3/22); and > 31 years, 10% (1/10). The spontaneous clearance rate of H. pylori after partial gastrectomy was 43% (13/30). The time after operation in the spontaneous clearance group was longer than that in those without (20.8 +/- 11.7 vs. 12.1 +/- 11.0 years, p = 0.048). Billroth-II procedure had a higher bile reflux rate and a lower H. pylori infection prevalence than the Billroth-I procedure. CONCLUSION Spontaneous clearance of H. pylori develops in a certain number of patients who undergo distal gastrectomy. The clearance rate is related to operative procedures and time after operation.

Prenatal diagnosis of choledochal cyst using ultrasound and magnetic resonance imaging

A 25-year-old primigravid woman was referred at 30 weeks’ gestation to evaluate a fetal intra-abdominal cystic mass. Sonographic examinations revealed a singleton fetus with biometry consistent with 30 weeks of gestation. An intra-abdominal cystic mass measuring 22 × 12 mm was noted. The amniotic fluid volume was normal. Color Doppler ultrasound revealed no flow within the mass. The cyst connected via the cystic duct to the gallbladder, raising the suspicion of a choledochal cyst (Figure 1). Ultrafast magnetic resonance imaging (MRI) scans further depicted a detailed anatomical relationship of the choledochal cyst to the liver, gallbladder and biliary tract (Figure 2). The choledochal cyst consisted of a cystic dilation of the common bile duct without dilation of the gallbladder and intrahepatic bile ducts. A diagnosis of Type IA choledochal cyst was thus made. The size of the cyst remained unchanged during follow-up ultrasound examinations. At 39 weeks’ gestation a female infant was born by vaginal delivery with Apgar scores of 10 and 10 at 1

Prenatal diagnosis of otocephaly with microphthalmia/anophthalmia using ultrasound and magnetic resonance imaging

A 30-year-old primigravid woman was referred to hospital at 29 weeks’ gestation because of polyhydramnios and regular uterine contractions. She and her husband were non-consanguineous and healthy. There was no family history of congenital malformations, nor any history of teratogenic medication, recent infection, diabetes mellitus, or hypertension during this pregnancy. A level II, twodimensional (2D) ultrasound examination revealed a single live fetus with a biparietal diameter of 7.99 cm (appropriate for 29 weeks’ gestation), a femur length of 5.4 cm (29 weeks), an abdominal circumference of 24 cm (29 weeks), polyhydramnios with an amniotic fluid index of 45 cm, absence of the mandible, hypotelorism, lowset ventromedially displaced ears, left microphthalmia with an ocular diameter of 1.29 cm (< 5th centile), and right anophthalmia with absence of the right lens (Figure 1). A tentative diagnosis of otocephaly was made. Magnetic resonance imaging (MRI) demonstrated agnathia and right anophthalmia (Figure 2). The other internal organs were unremarkable. A 1404-g female baby (Figure 3) was delivered 1 day later because of premature rupture of the membranes and preterm labor. The proband died shortly after birth. Autopsy confirmed the diagnosis of otocephaly, which was characterized by the isolated agnathia, aglossia, microstomia, and synotia without central nervous system and other organ defects except for the ocular abnormalities of left microphthalmia and absence of the right lens. The karyotype of the proband was 46,XX. Computed tomography (CT) scans following three-dimensional (3D) reconstruction showed a characteristic otocephalic skull (Figure 4). Prenatal diagnosis of otocephaly using 2D and 3D ultrasound has been well described in the literature1–5. To the best of our knowledge, this

Simulating a target lesion for endoscopic submucosal dissection training in an ex vivo pig model

BACKGROUND Currently, there is no training model that simulates the target lesion encountered during endoscopic submucosal dissection. OBJECTIVE To develop a novel method simulating a target lesion for endoscopic submucosal dissection. DESIGN Training program with the use of an ex vivo porcine stomach model. SETTING Clinical skills training center. INTERVENTION A pseudopolyp was created by using an esophageal variceal ligation device to simulate a protruding (0-Ip) lesion, and the pseudopolyp was transected with a snare cautery to simulate a depressed (0-IIc) lesion. MAIN OUTCOME MEASUREMENTS Evaluate the histological depth of the target lesions and resected specimens. RESULTS Histological findings of the simulated targets showed artificial ulcerative or polypoid lesions involving the muscularis mucosa or superficial submucosa. The resected specimen was limited to the submucosal layer, and no perforation was noted. LIMITATIONS Pilot study in an ex vivo porcine stomach model. CONCLUSION The most important advantage of the model is to simulate realistic target lesions like those encountered in clinical practice in endoscopic submucosal dissection training. It allows trainees to practice how to make proper markings, delineate adequate safety margins, and properly manage different subtypes of early gastric cancer.

The add-on N-acetylcysteine is more effective than dimethicone alone to eliminate mucus during narrow-band imaging endoscopy: a double-blind, randomized controlled trial.

Abstract Objective. Recent studies have shown that pronase can improve mucosal visibility, but this agent is not uniformly available for human use worldwide. This study aimed to assess the efficacy of N-acetylcysteine (NAC), a mucolytic agent, in improving mucus elimination as measured by decreased endoscopic water flushes during narrow-band imaging (NBI) endoscopy. Material and methods. A consecutive series of patients scheduled for upper gastrointestinal endoscopy at outpatient clinics were enrolled in this double-blind, randomized controlled trial. The control group drank a preparation of 100 mg dimethicone (5 ml at 20 mg/ml) plus water up to 100 ml, and the NAC group drank 300 mg NAC plus 100 mg dimethicone and water up to 100 ml. During the endoscopy, the endoscopist used as many flushes of water as deemed necessary to produce a satisfactory NBI view of the entire gastric mucosa. Results. In all, 177 patients with a mean age of 51 years were evaluated in this study. Significantly lesser water was used for flushing during NBI endoscopy for the NAC group than the control group; 40 ml (30–70, 0–120) versus 50 ml (30–100, 0–150) (median (interquartile range, range), p = 0.0095). Conclusions. Considering the safety profile of NAC, decreasing the number of water flushes for optimal vision and unavailability of pronase in some areas, the authors suggest the use of add-on NAC to eliminate mucus during NBI endoscopy.

Acquired Hyperplastic Gastric Polyps After Treatment of Ulcer

BACKGROUND/PURPOSE Healing of gastric ulcers requires repair by epithelial migration and proliferation. We have found a small proportion of patients with acquired hyperplastic polyps at the healed ulcer site. The aim of this study was to identify clinical characteristics that might be associated with the development of hyper-plastic polyps at the site of healed gastric ulcers. METHODS This was a retrospective review of 86 patients with gastric ulcers from April 2006 to September 2008. After initial endoscopy, the patients were all treated with proton pomp inhibitors, after which a second endoscopy was performed. Demographic data, polyp characteristics (endoscopic and histological), Helicobacter pylori status, and duration of treatment were analyzed. RESULTS A total of 24 hyperplastic gastric polyps were found in 18 patients; all at the site of the healed ulcer (20 in the antrum and 4 in the corpus). The mean size of the ulcers prior to treatment was 14.5 +/- 9.1 mm. Hyperplastic gastric polyps were more likely to occur at the site of ulcers larger than 10 mm (odds ratio = 9.57, 95% confidence interval =2.50-36.65). Age, sex, H. pylori status, ulcer location and duration of treatment did not differ significantly between patients with and without polyps. CONCLUSION Hyperplastic polyps that develop after healing of gastric ulcers are likely to be extensive mucosal injury. A gastric ulcer larger than 10 mm is associated with a significantly increased risk of hyperplastic polyps.

Early second-trimester diagnosis of fetal otocephaly.

In a recent issue of this journal, Cannie et al.1 reported the role of magnetic resonance imaging (MRI) in the field of fetal medicine and suggested that the true advantage of fetal MRI is the functional evaluation of the fetus. Here, we present the earliest application of MRI in the assessment of fetal otocephaly. A 41-year-old gravida 4, para 2 woman was referred to our hospital because of abnormal findings on an earlier scan. Ultrasound examination at 12 weeks’ gestation and MRI at 15 weeks revealed an abnormal fetal face, synotia and agnathia (Figures 1 and 2). The fetal brain, heart and internal organs were normal. At 16 weeks’ gestation, termination of pregnancy was performed and a

An aberrant renal artery arising from the iliac artery imaged by three‐dimensional power Doppler ultrasonography: a sign of fetal horseshoe kidney

We report the case of a 29-year-old primigravida, referred on the basis of suspected fetal abnormalities following routine ultrasound examination. Detailed ultrasound examination at 32 weeks’ gestation showed a fetus with multiple anomalies, and fetal karyotyping subsequently revealed trisomy 18. An enlarged right kidney was noted, but the contralateral one could not be detected owing to the fetal position. Three-dimensional (3D) power Doppler ultrasound examination with simultaneous grayscale imaging was then performed to make the differential diagnosis of renal malformation. A Toshiba highresolution imaging system (Aplio SSA-770A, Toshiba Co., Japan) with integrated function of acquisition and processing of 3D power Doppler was used. All ultrasound examinations were initiated as two-dimensional (2D) scans using a 3.5-MHz convex linear array transducer. The previously undetectable left kidney was visualized by rotating the volume data and was confirmed by detecting the presence of renal vasculature. The vasculature of the enlarged kidney could be seen (Figure 1); blood was supplied by two renal arteries, along with an aberrant artery arising from the iliac artery, which supplied its lower pole on the same side. The pregnancy was terminated at 33 weeks’ gestation. Autopsy of the neonate confirmed the diagnosis of these fetal anomalies and a horseshoe kidney (Figure 2). Embryological vascular development of the urinary tract is driven by the functional requirements of the organs concerned. Visceral arteries develop adjacent to the organs they supply and follow their relative migration to degenerate afterwards1. Knowledge of the potential variants in renal and renal vascular anatomy is thus indispensable for sonographers who perform and interpret such examinations and enhances their ability to make prenatal diagnoses.