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

BACKGROUND: 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. METHODS: From July 1, 2012 to December 31, 2013, we prospectively selected 60 plasma samples from patients who were diagnosed with CRC and otherwise, the healthy group by colonoscopy in our hospital. Patients were divided into the CRC group and healthy group. CRC stages 0, I, II and stages III and IV were separately analyzed. We calculated the sensitivity and specificity of each group to determine the relationship among the MS-9 DNA blood test, iFOBT, and a combination of the two tests for diagnosing CRC in Taiwanese people. RESULTS: The results of the MS-9 DNA blood test for the 60 samples were divided into three groups, and the sensitivity as well as the specificity of the MS-9 DNA blood test to detect CRC were 47% and 89%, respectively. The results of iFOBT were also divided into three groups, and had higher sensitivity (84%) but lower specificity (55%) using iFOBT to detect CRC. Higher rates could be predicted to detect CRC if both the tests were positive. CONCLUSIONS: A combined MS-9 DNA blood test and iFOBT may help in a higher detection rate of CRC. It could be offered to individuals who are unwilling or unable to undergo colonoscopy. Further large prospective, randomized studies are needed in the future.

Cdk5 Directly Targets Nuclear p21CIP1 and Promotes Cancer Cell Growth.

The significance of Cdk5 in cell-cycle control and cancer biology has gained increased attention. Here we report the inverse correlation between the protein levels of Cdk5 and p21CIP1 from cell-based and clinical analysis. Mechanistically, we identify that Cdk5 overexpression triggers the proteasome-dependent degradation of p21CIP1 through a S130 phosphorylation in a Cdk2-independent manner. Besides, the evidence from cell-based and clinical analysis shows that Cdk5 primarily regulates nuclear p21CIP1 protein degradation. S130A-p21CIP1 mutant enables to block either its protein degradation or the increase of cancer cell growth caused by Cdk5. Notably, Cdk5-triggered p21CIP1 targeting primarily appears in S-phase, while Cdk5 overexpression increases the activation of Cdk2 and its interaction with DNA polymerase δ. The in vivo results show that Cdk2 might play an important role in the downstream signaling to Cdk5. In summary, these findings suggest that Cdk5 in a high expression status promotes cancer growth by directly and rapidly releasing p21CIP1-dependent cell-cycle inhibition and subsequent Cdk2 activation, which illustrates an oncogenic role of Cdk5 potentially applied for future diagnosis and therapy. Cancer Res; 76(23); 6888-900. ©2016 AACR.

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.

Emodin and Aloe-Emodin Suppress Breast Cancer Cell Proliferation through ER α Inhibition.

The anthraquinones emodin and aloe-emodin are abundant in rhubarb. Several lines of evidence indicate that emodin and aloe-emodin have estrogenic activity as phytoestrogens. However, their effects on estrogen receptor α (ER α ) activation and breast cancer cell growth remain controversial. The goal of this study is to investigate the effects and molecular mechanisms of emodin and aloe-emodin on breast cancer cell proliferation. Our results indicate that both emodin and aloe-emodin are capable of inhibiting breast cancer cell proliferation by downregulating ER α protein levels, thereby suppressing ER α transcriptional activation. Furthermore, aloe-emodin treatment led to the dissociation of heat shock protein 90 (HSP90) and ER α and increased ER α ubiquitination. Although emodin had similar effects to aloe-emodin, it was not capable of promoting HSP90/ER α dissociation and ER α ubiquitination. Protein fractionation results suggest that aloe-emodin tended to induce cytosolic ER α degradation. Although emodin might induce cytosolic ER α degradation, it primarily affected nuclear ER α distribution similar to the action of estrogen when protein degradation was blocked. In conclusion, our data demonstrate that emodin and aloe-emodin specifically suppress breast cancer cell proliferation by targeting ER α protein stability through distinct mechanisms. These findings suggest a possible application of anthraquinones in preventing or treating breast cancer in the future.

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.

Laparoscopy-assisted billroth I gastrectomy for ectopic pancreas in the prepyloric region.

Ectopic pancreatic tissue is an uncommon developmental anomaly. The condition mostly occurs in the gastrointestinal tract and is usually asymptomatic. It rarely causes symptoms of inflammation, bleeding and perforation, and has potential for malignant change. Though it is an uncommon condition, cases of ectopic pancreas have been reported worldwide. Preoperative diagnosis of ectopic pancreas is challenging because of its nonspecific symptoms and signs. Owing to the revolution of minimally invasive surgery, submucosal tumors of the stomach can be resected by laparoscopic techniques. We have earlier reported on a case of ectopic pancreas in the stomach treated by robotics-assisted laparoscopic wedge resection. Herein, we report a case of ectopic pancreas in the prepyloric region of the stomach. A 44-year-old female presented with a two-week history of epigastralgia with radiation to the back. She received endoscopy check-up which disclosed a mass in the stomach. By endoscopic findings, a submucosal lesion in the prepyloric region with umbilical folding on the mucosa was identified. The umbilical folding on the mucosa hint the orifice of the duct of ectopic pancreas into the gastric mucosa suggestive of ectopic pancreas. Contrast-enhanced abdominal computed tomography showed a 5 cm cystic mass with heterogeneous content. To sum it up, the patient was diagnosed as ectopic pancreas in the stomach. She underwent laparoscopy-assisted antrectomy with Billroth I anastomosis (excision of the antrum and prepyloric region with reconstruction of gastrointestinal continuity by gastroduodenostomy) and had an uneventful hospitalization course. The histopathology of the resected tumor demonstrated ectopic pancreatic tissue in the gastric wall. To the best of our knowledge, excision of gastric ectopic pancreas using laparoscopy-assisted antrectomy with Billroth I anastomosis has never been reported in the literature.

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.

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

BACKGROUND: Hemobilia 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 PRESENTATION: A 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. CONCLUSIONS: Pseudoaneurysm 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.

Impact of AITS laparoscopic training center on surgeons' preference for appendectomy.

BACKGROUND: Acute appendicitis is the most common acute abdomen in general surgery. Show-Chwan Memorial Hospital began an AITS/IRCAD laparoscopic training program in late May 2008. In this retrospective analysis, we surveyed the impact of the AITS training program on surgeons' preference for open appendectomy (OA) versus laparoscopic appendectomy (LA). METHODS: From January 1, 2004 to July 31, 2009, patients diagnosed with acute appendicitis in Changhua Show-Chwan Memorial Hospital and Chang-Bing Show-Chwan Memorial Hospital were retrospectively analyzed. Demographic data, laboratory examinations, surgical methods, hospital stay, and complication rate data were collected and analyzed. The LA rate and effect of surgeons' preference before and after AITS were compared. RESULTS: In all, 1,267 patients (58.2% male and 41.8% female; mean age, 36.6 years) were diagnosed with acute appendicitis during this period. Among them, 78.9% of patients had uncomplicated and 21.1% complicated appendicitis; 784 patients (61.9%) underwent OA, and 465 (36.7%) received LA. In 2004, only 8.1% of patients underwent LA, but the number increased rapidly to 90.4% in 2009 (P < 0.001). The average LA rate before AITS was 21%; however, after AITS, the LA rate increased to 84.6% (P < 0.001). The LA rate increased for all surgeons completing the training course, ranging from 16 to 83%. The overall appendectomy complication rate was 8.4%, with no significant difference between OA (9.7%) and LA (6.5%; P = 0.174). Hospital stay was shorter in the LA group (4.05 ± 1.9 days) compared with the OA group (4.55 ± 3.6; P = 0.006). CONCLUSIONS: Attending the laparoscopic training course significantly increased surgeons' preference for LA.

Primary retroperitoneal mucinous cystadenoma: Report of a case and review of the literature.

Primary retroperitoneal mucinous cystadenomas (RMCs) are very rare and their biological behavior and histogenesis remain speculative. An accurate preoperative diagnosis of these tumors is difficult because no effective diagnostic measures have been established. We describe a 29-year-old woman with abdominal pain and a palpable mass. Computed tomography (CT) of the abdomen revealed a retroperitoneal cystic mass which was resected successfully at laparotomy. Histopathological examination of the resected mass confirmed the diagnosis of RMC. There was no evidence of disease 2 years after surgery.

Intraperitoneal metastasis of hepatocellular carcinoma after spontaneous rupture: a case report.

Rupture of hepatocellular carcinoma (HCC) is a life-threatening complication. Peritoneal metastasis of HCC after spontaneous rupture was seldom noted. We report a case of intraperitoneal metastasis of HCC after spontaneous rupture. A previously asymptomatic 72-year-old man was admitted due to dull abdominal pain with abdominal fullness. He had a history of HCC rupture 10 mo ago and transarterial embolization was performed at that time. Abdominal computer tomography (CT) scan showed a huge peritoneal mass over the right upper quadrant area. Surgical resection was arranged and subsequent microscopic examination confirmed a diagnosis of moderately-differentiated HCC.

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

BACKGROUND: Mucoceles 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 PRESENTATION: A 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. CONCLUSION: Synchronous 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.

Squamous cell carcinoma arising from longstanding colocutaneous fistula: a case report.

A 60-year-old female patient suffered unhealed wounds over left flank for around 30 years after surgical removal of left renal stones. Fecal material spilled from the two small openings of the scar, bothered her all day long. During the course of the 30 years, she suffered from intermittent fever, diarrhea and wound pain and presented with malnourished condition. After serial examinations, tumor associated with iatrogenic colo-cutaneous fistula was impressed and she received en bloc resection. Pathology revealed squamous cell carcinoma arising from the fistula with colon and spleen invasion. To the best of our knowledge, no such case has been reported, as yet.

Robotic-assisted laparoscopic resection of ectopic pancreas in the posterior wall of gastric high body: case report and review of the literature.

Minimally invasive surgery has revolutionized the treatment of gastrointestinal tumors. Submucosal tumors of the stomach can be resected using laparoscopic techniques. We report here a case of ectopic pancreas tissue in the gastric wall that was removed using robotic-assisted laparoscopic resection. The patient was a 15-year-old female who presented with abdominal discomfort and tarry stools. Laboratory analysis showed iron deficiency anemia. Preoperative endoscopy revealed a submucosal lesion in the posterior wall of the gastric high body. Intraoperative upper endoscopy clearly located the lesion. A robotic-assisted laparoscopic wedge resection of the putative gastric submucosal tumor was performed. The pathology results showed an ectopic pancreas. The patient had an uneventful recovery and we believe that this is a valid treatment option for this benign condition.