Yueh-Tsung Lee

Regulation of Androgen Receptor and Prostate Cancer Growth by Cyclin-dependent Kinase 5

Prostate cancer is the most frequently diagnosed male malignancy. The normal prostate development and prostate cancer progression are mediated by androgen receptor (AR). Recently, the roles of cyclin-dependent kinase 5 (Cdk5) and its activator, p35, in cancer biology are explored one after another. We have previously demonstrated that Cdk5 may regulate proliferation of thyroid cancer cells. In addition, we also identify that Cdk5 overactivation can be triggered by drug treatments and leads to apoptosis of prostate cancer cells. The aim of this study is to investigate how Cdk5 regulates AR activation and growth of prostate cancer cells. At first, the data show that Cdk5 enables phosphorylation of AR at Ser-81 site through direct biochemical interaction and, therefore, results in the stabilization of AR proteins. The Cdk5-dependent AR stabilization causes accumulation of AR proteins and subsequent activation. Besides, the positive regulations of Cdk5-AR on cell growth are also determined in vitro and in vivo. S81A mutant of AR diminishes its interaction with Cdk5, reduces its nuclear localization, fails to stabilize its protein level, and therefore, decreases prostate cancer cell proliferation. Prostate carcinoma specimens collected from 177 AR-positive patients indicate the significant correlations between the protein levels of AR and Cdk5 or p35. These findings demonstrate that Cdk5 is an important modulator of AR and contributes to prostate cancer growth. Therefore, Cdk5-p35 may be suggested as diagnostic and therapeutic targets for prostate cancer in the near future.

Competitive Edge of Laparoscopic Appendectomy Versus Open Appendectomy: A Subgroup Comparison Analysis

BACKGROUND With the advances in laparoscopic instruments and surgical techniques, the use of laparoscopic appendectomy (LA) has been increasing rapidly in recent years. In this retrospective analysis, we aimed to determine the competitive edge of LA versus open appendectomy (OA) in different settings of disease complexity, gender, and age difference. METHODS A retrospective analysis of the patients diagnosed with acute appendicitis at Changhua and Chang-Bing Show-Chwan Memorial Hospitals from January 1, 2004 to December 31, 2009 was conducted. Trend and indication of OA and LA were recorded, combined with a comparison of medical costs, complication rates, wound infection rates, and hospital stays in different settings of disease complexity, gender, and age group. RESULTS A total of 1366 appendicitis patients were enrolled, and the rate of LA use increased rapidly, from 8.1% in 2004 to 90.3% in 2009. The increased use of LA was seen in both the uncomplicated and complicated appendicitis patients and in both gender and age groups (pediatric, adult, and elderly). Compared with OA, LA was associated with a lower complication rate (9.5% versus 5.8%; P = .013), a lower wound infection rate (8.6% versus 4.2%; P = .001), and a shorter hospital stay (4.60 ± 3.64 versus 4.06 ± 1.84 days; P = .001), but a higher mean cost (32,670 ± 28,568 versus 37,567 ± 12,064 New Taiwan dollars). In the subgroup analysis, the patients with complicated appendicitis, female patients, and pediatric and elderly patients benefited from a reduced hospital stay. LA is about 15% more expensive than OA. CONCLUSIONS LA is as safe and effective as OA in many settings of appendicitis and may be selectively advantageous in patients with complicated appendicitis and in elderly subgroups.

Ruptured appendiceal cystadenoma presenting as right inguinal hernia in a patient with left colon cancer: A case report and review of literature

BackgroundMucoceles resulting from cystadenomas of the appendix are uncommon. Although rare, rupture of the mucoceles can occur with or without causing any abdominal complaint. There are several reports associating colonic malignancy with cystadenomas of the appendix. Herein, we report an unusual and interesting case of right inguinal hernia associated with left colon cancer.Case presentationA case of ruptured mucocele resulting from cystadenoma of the appendix was presented as right inguinal hernia in a 70-year-old male. The patient underwent colonoscopy, x-ray, ultrasound and computed tomography. Localized pseudomyxoma peritonei associated with adenocarcinoma of the descending colon was diagnosed. The patient underwent segmental resection of the colon, appendectomy, debridement of pseudomyxoma and closure of the internal ring of right inguinal canal. He is free of symptoms in one year follow-up.ConclusionSynchronous colon cancer may occur in patients with appendiceal mucoceles. In such patients, the colon should be investigated and colonoscopy can be performed meticulously in cases of ruptured mucoceles and localized pseudomyxoma peritonei. Surgical intervention is the current choice of management.

Life-threatening hemobilia caused by hepatic pseudoaneurysm after T-tube choledochostomy: report of a case.

BackgroundHemobilia is a rare but lethal biliary tract complication. There are several causes of hemobilia which might be classified as traumatic or nontraumatic. Hemobilia caused by pseudoaneurysm might result from hepatobiliary surgery or percutaneous interventional hepatobiliary procedures. However, to our knowledge, there are no previous reports pertaining to hemobilia caused by hepatic pseudoaneurysm after T-tube choledochostomy.Case presentationA 65-year-old male was admitted to our hospital because of acute calculous cholecystitis and cholangitis. He underwent cholecystectomy, choledocholithotomy via a right upper quadrant laparotomy and a temporary T-tube choledochostomy was created. However, on the 19th day after operation, he suffered from sudden onset of hematemesis and massive fresh blood drainage from the T-tube choledochostomy. Imaging studies confirmed the diagnosis of pseudoaneurysm associated hemobilia. The probable association of T-tube choledochostomy with pseudoaneurysm and hemobilia is also demonstrated. He underwent emergent selective microcoils emobolization to occlude the feeding artery of the pseudoaneurysm.ConclusionsPseudoaneurysm associated hemobilia may occur after T-tube choledochostomy. This case also highlights the importance that hemobilia should be highly suspected in a patient presenting with jaundice, right upper quadrant abdominal pain and upper gastrointestinal bleeding after liver or biliary surgery.

The Relationship between the Methylated Septin‐9 DNA Blood Test and Stool Occult Blood Test for Diagnosing Colorectal Cancer in Taiwanese People

Colorectal cancer (CRC) is a common and lethal disease in the world. There is an increasing number of cases in Taiwan and a higher rate at advanced stages. The immune fecal occult blood test (iFOBT) has been used as a screening method in Taiwan for years. A new novel diagnostic tool, the Methylated Septin‐9 (MS‐9) DNA blood test, had been reported to have high sensitivity and specificity for CRC detection. There are no available data in Taiwan, so we conducted this prospective randomized trial to investigate the relationship among the MS‐9 DNA blood test, iFOBT, and a combination of the two tests for diagnosing CRC in Taiwanese people.

Conversion From Cephalic Vein to External Jugular Vein Success Rate Increased on Totally Implantable Access Ports With Cut-down Method

Background. Totally implantable access ports (Port-A) can be inserted using 2 techniques: cut-down and percutaneous. The cut-down method is safer than the percutaneous method. However, the cut-down method has a higher failure rate. We report an alternative method to decrease the failure rate of the cut-down method. Patients and Methods. In all, 758 cases of Port-A implantation with cephalic vein cut-down were tried, and 56 cases failed. Of the 56 cases, 29 cases were converted to the percutaneous subclavian method (group A), and 27 cases were converted to the external jugular vein cut-down method (group B). The patient’s characteristics, causes of failure of cephalic vein cut-down, operating time, and complications were compared. Results. The failure rate of cephalic vein cut-down was 7.4%. The causes of failure of cephalic vein cut-down are described. There were 4 complications in group A, including one pneumothorax (1/29), one fracture of the catheter (1/29), one embolization of the catheter (1/29), and one hematoma formation in the port site (1/29); 2 complications occurred in group B, including one embolization of the catheter (1/27) and one hematoma in the port site (1/27). The total complications were 17.7%. Conclusion. Conversion to external jugular vein cut-down is safely and easily applied in cases of cephalic vein cut-down failure. This method did not take more time than the percutaneous subclavian method. However, placement of the port should be made more carefully to prevent angulation of the catheter. We provide an alternative method to deal with failure of cephalic vein cut-down.

Inverted appendix in an asymptomatic patient without intussusception or previous appendectomy.

A 54-year-old woman visited our institution for physical check up because of a family history of colonic cancer. Her medical history was unremarkable. Physical examination and pelvic examination were normal and the laboratory data were within reference ranges. Tumour markers, including CA199, CA125 and CEA were normal. Colonoscopy revealed a tubular polypoid mass in the caecum (Fig. 1a). Contrast-enhanced computed tomography (CT) of the abdomen showed a long tubular filling defect in caecal area (Fig. 1b). For reasons of the undetermined nature of the polypoid mass lesion, laparoscopy was arranged, showing absence of vermiform appendix at the confluence of taeniae coli. The patient underwent laparoscopic-assisted excision of the polypoid mass, revealing a tubular mass with normal appearing mucosa 4 cm in length originating from the appendiceal orifice (Fig. 1c). No intussusception was present during the operation. Histopathological examination of the resected specimen showed typical features of appendiceal inversion (Fig. 1d). The postoperative course was uneventful and the patient was discharged 5 days later.

Large Epidermoid Cyst of the Breast: Report of a Case

Epidermoid cysts are located mainly in the subcutaneous layer of the trunk and are often small and asymptomatic. When they develop in the breast parenchyma they are a rare benign condition, yet have the potential for malignancy. We report on a 39 year-old female who presented with a large protruding lump from her left breast. The mass grew up to more than 10 cm in diameter during the period of five years. Enlarged left axillary lymph nodes were noted also. A malignant tumor was suspected based on the imaging and clinical features. She underwent tumor excision and an epidermoid cyst was confirmed by histopathologic assessment. We collected the breast images, the surgical specimen photographs and reviewed the literature. To the best of our knowledge, the cyst reported here is the largest of the epidermoid cysts arising within the breast that have been reported. Although at times, the epidermoid cyst is difficult to distinguish from a malignant tumor, surgical excision is justified because of its potential for malignancy.

Suppression of Breast Cancer Cell Growth by Her2-Reduced AR Serine 81 Phosphorylation

Breast cancer is a hormone-related carcinoma and the most commonly diagnosed malignancy in women. Although Her-2, estrogen receptor (ER), and progesterone receptor (PR) are the major diagnostic markers and therapeutic targets to breast cancer, searching for additional molecular targets remains an important issue and one of the candidates is androgen receptor (AR). AR has been shown expressed in 70% breast cancer patients and connects to low recurrence and high survival rate. Our previous study demonstrates that Ser81 phosphorylation of AR in prostate cancer cells is critical for its protein stability modulated by human epidermal growth factor receptor-2 (Her2). The aim of this study is to investigate the influence of Her2 and AR in proliferation of breast cancer cell line, MDA-MB-453. The data show that AR which was activated by synthetic androgen R1881 suppressed the proliferation of MDA-MB-453 cells. Notably, AR activation decreased the protein levels of cell growth-related proteins, including cyclin A, cyclin B, and early growth response protein 1 (Egr1), while cell-cycle inhibitor protein p27 was increased. Besides, Heregulin (HRG)-induced Her2 activation decreased the AR protein levels and its Ser81 phosphorylation. Her2 small molecular inhibitor, Lapatinib, dose-dependently suppressed cell proliferation while the levels of phospho-Ser81 AR and p27 protein were increased. Phospho-Ser81 AR was also increased after Her2 knockdown. Specifically, the influence of phospho-Ser81 AR by Lapatinib was primarily found in the nucleus of MDA-MD-453 cells, where the cell proliferation might directly be interfered. In conclusion, our findings indicate that Her2 might negatively regulate AR phosphorylation/activation and contribute to regulate the proliferation of MDA-MB 453 cells.

Effect of Minimally Invasive Surgical Training Center on Laparoscopic Surgery: Observation from Preliminary Results for Primary Stomach GastroIntestinal Stromal Tumor in a Health Care System

Gastrointestinal stromal tumors (GISTs), are different from other mesenchymal tumors by immunohistochemistric biomarkers and are often encountered in the alimentary tract and less commonly originating from omentum, mesentery and peritoneum. They usually present as subepithelial tumors in the gastrointestinal tract or intraabdominal masses with malignant potential. The tumors might cause symptoms such as pain, intraluminal or extraluminal GI tract bleeding and obstruction but might also present as incidental findings. Gastroscopy, Ultrasonography and CT scan are employed for preoperative evaluation. The surgical principles are to excise the tumor with safe margin microscopically. Minimally invasive procedures are revolutionary innovation in surgery. Asian Institute of TeleSurgery training center is established in mid Taiwan in 2008 with the cooperation between Show Chwan Health Care System and European Institute of TeleSurgery in Strasbourg, France. We retrospectively reviewed 24 primary stomach GISTs operated at our institution in the past four years. The patients were divided into laparoscopy group (18 patients) and laparotomy group (6 patients) depending on the main surgical methods. The patients’ age, gender, hospital stay, operative time, blood loss, tumor size and complication rate were used for stastical analysis. There were significant differencesin tumor size and blood loss between the two groups with a p value of less than 0.05. In the past 4 years, 75% of primary gastric GISTs in our hospital were managed by laparoscopic surgery. Our experience showed that laparoscopic surgery is feasible for primary stomach GISTs in selective cases.