Ching-Chung Lin

Caffeic acid phenethyl ester induces apoptosis of human pancreatic cancer cells involving caspase and mitochondrial dysfunction.

Aims: This study aimed to investigate the effect of caffeic acid phenethyl ester (CAPE), an active component isolated from honeybee propolis, in inducing apoptosis in human pancreatic cancer cells. Methods: Inhibition of viability of BxPC-3 and PANC-1 cell lines induced by CAPE was estimated by a trypan blue dye exclusion test. The type of cell death in BxPC-3 after CAPE treatment was characterized by observation of morphology, sub-G1 DNA content, annexin-V/PI staining, caspase-3 and caspase-7 assay, and DNA agarose gel electrophoresis. Results: CAPE (10 µg/ml) resulted in marked inhibition of viability of BxPC-3 (80.4 ± 4.1%) and PANC-1 (74.3 ± 2.9%) cells. CAPE induced a time-dependent increase in hypodiploid percentage and a significant decrease in mitochondrial transmembrane potential in BxPC-3 cells. It induced morphological changes of typical apoptosis, but no DNA fragmentation was noted by DNA electrophoresis. The inhibition of growth and increased in the proportion of sub-G1 cells was partially blocked by pretreatment with the pan-caspase inhibitor Z-VAD-fmk (50 µM) in BxPC-3 cells indicating a caspase-related mechanism in CAPE-induced apoptosis. Caspase-3/caspase-7 activity was approximately 2 times greater in CAPE-treated BxPC-3 cells compared with control cells. Conclusions: These results suggest that CAPE is a potent apoptosis-inducing agent. Its action is accompanied by mitochondrial dysfunction and activation of caspase-3/caspase-7.

Combination of Sorafenib and Intensity Modulated Radiotherapy for Unresectable Hepatocellular Carcinoma

Unresectable hepatocellular carcinoma (HCC) has a poor therapeutic outcome. We report here on a 40-year-old male HCC patient who had undergone partial hepatectomy and was refractory to therapeutic embolization. In addition, the tumour expressed phosphorylated extracellular signal-regulated kinase and CD34. Sorafenib was administered as salvage treatment and resulted in a rapid decline in α-fetoprotein (AFP) levels. However, this was accompanied by a grade 3 skin reaction, which improved as sorafenib dosage was gradually reduced. Unfortunately, reducing the dose of sorafenib also resulted in a rebound in AFP levels and portal vein thrombosis was noted thereafter. Sorafenib 800 mg/day was resumed, but the tumour failed to respond. Intensity-modulated radiation therapy (IMRT) combined with sorafenib was administered, resulting in marked tumour shrinkage and causing recurrence of the systemic skin reaction and development of photosensitivity. The patient survived for 20 months after the start of sorafenib treatment. This case suggests that the combination of sorafenib and IMRT might provide clinical benefits in patients with HCC who express potential targets but fail to respond to sorafenib; however, skin reactions should be monitored.

Benign esophageal lesions: Endoscopic and pathologic features

Benign esophageal lesions have a wide spectrum of clinical and pathologic features. Understanding the endoscopic and pathologic features of esophageal lesions is essential for their detection, differential diagnosis, and management. The purpose of this review is to provide updated features that may help physicians to appropriately manage these esophageal lesions. The endoscopic features of 2997 patients are reviewed. In epithelial lesions, the frequency of occurrence was in the following order: glycogenic acanthosis, heterotopic gastric mucosa, squamous papilloma, hyperplastic polyp, ectopic sebaceous gland and xanthoma. In subepithelial lesions, the order was as follows: hemangioma, leiomyoma, dysphagia aortica and granular cell tumor. Most benign esophageal lesions can be diagnosed according to their endoscopic appearance and findings on routine biopsy, and submucosal lesions, by endoscopic resection. Management is generally based upon the confidence of diagnosis and whether the lesion causes symptoms. We suggest endoscopic resection of all granular cell tumors and squamous papillomas because, while rare, these lesions have malignant potential. Dysphagia aortica should be considered in the differential diagnosis of dysphagia in the elderly.

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.

Scurvy in a Patient with Depression

Scurvy is a nearly-forgotten disease in developed countries where adequate nutrition is easily available. It still may occur, however, when, for a variety of reasons, people fail to eat a diet containing adequate vitamin C. We report the case of a 52-year-old patient with depression who developed scurvy.

Nodular Gastritis: An Endoscopic Indicator of Helicobacter Pylori Infection

We prospectively assessed the relationship between nodular gastritis and Helicobacter pylori infection. Of 1409 adults who underwent endoscopy for persistent dyspepsia between June 2004 and August 2005, 41 (2.9%) patients were diagnosed with nodular gastritis (11 [27%] men and 30 [73%] women). The mean age was 45.9 years. A control group of 65 patients without nodular gastritis was also evaluated. The prevalence of H. pylori infection was higher in patients with nodular gastritis than in controls (38/41 [93%] vs. 33/65 [51%]). Of 21 patients treated to eradicate H. pylori, the nodular gastritis pattern resolved or improved in 16 patients on subsequent endoscopy. This study suggests that a nodular pattern of the gastric mucosa on endocscopy is a good indicator for H. pylori infection in adults, with the high positive predictive value of 92.7%.

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.

Caffeic Acid Phenethyl Ester Inhibits Epithelial-Mesenchymal Transition of Human Pancreatic Cancer Cells

Background. This study aimed to investigate the effect of propolis component caffeic acid phenethyl ester (CAPE) on epithelial-mesenchymal transition (EMT) of human pancreatic cancer cells and the molecular mechanisms underlying these effects. Methods. The transforming growth factor β (TGF-β-) induced EMT in human pancreatic PANC-1 cancer cells was characterized by observation of morphology and the expression of E-cadherin and vimentin by western blotting. The migration potential was estimated with wound closure assay. The expression of transcriptional factors was measured by quantitative RT-PCR and immunocytochemistry staining. The orthotopic pancreatic cancer xenograft model was used for in vivo assessment. Results. The overexpression of vimentin was attenuated by CAPE, and the alteration in morphology from polygonal to spindle shape was partially reversed by CAPE. Furthermore, CAPE delayed the TGF-β-stimulated migration potential. CAPE treatment did not reduce the expression levels of Smad 2/3, Snail 1, and Zeb 1 but inhibited the expression of transcriptional factor Twist 2. By using an orthotopic pancreatic cancer model, CAPE suppressed the expression of Twist 2 and growth of PANC-1 xenografts without significant toxicity. Conclusion. CAPE could inhibit the orthotopic growth and EMT of pancreatic cancer PANC-1 cells accompanied by downregulation of vimentin and Twist 2 expression.

A novel artificial tissue simulator for endoscopic submucosal resection training – a pilot study

BackgroundWe developed a novel artificial simulator for endoscopic submucosal dissection (ESD) as a bridge between instructional videos and animal tissue training and aimed to evaluate the feasibility of using an artificial tissue model in ESD training.MethodsEight gastroenterology fellows from one medical center were enrolled in this ESD training program. Before and after the simulator training, attendees indicated on a 5-point scale the degree of difficulty in performing the following procedures: lesion marking, mucosal pre-cutting, circumferential incision, submucosal dissection, and hemostasis. After the simulator training, the participants completed a questionnaire regarding their opinions on the degree of realism and the feasibility of using this model for training.ResultsAfter watching an instructional video, attendees felt that the most difficult techniques were submucosal dissection and hemostasis. After using the artificial tissue simulator model, the attendees felt more confident in performing performing lesion marking (p = 0.026) and submucosal dissection (p = 0.037). However, they still felt that hemostasis was the most difficult techniques to master. Overall, the attendees thought the simulator was realistic in simulated lesion marking and its use was feasible for simulated lesion marking and submucosal dissection.ConclusionOur pilot study shows the feasibility of using a novel artificial tissue in performing ESD and we believe that the artificial tissue simulator acts well as a bridge between instructional videos and animal model training. The model is reusable and inexpensive, and could disseminate the techniques of the ESD more easily and quickly.