Sung-Heun Kim

Mutant p53 (G199V) Gains Antiapoptotic Function through Signal Transducer and Activator of Transcription 3 in Anaplastic Thyroid Cancer Cells

In the present study, we identified a missense mutation (G199V) in KAT-18 cell line established from primary cultures of anaplastic thyroid cancer (ATC). Notably, knockdown of this mutant (mt) p53 reduced cell viability and exerted antitumor activity equivalent to high doses of several chemotherapeutic agents. We showed that p53 knockdown had an antitumor effect via the induction of apoptosis. We further examined the underlying mechanism by which mt p53 (G199V) gains antiapoptotic function in KAT-18 cells. Microarray analysis revealed that p53 knockdown modified the expression of numerous apoptosis-related genes. Importantly, p53 knockdown led to downregulation of signal transducer and activator of transcription-3 (STAT3) gene expression. We further observed that p53 knockdown induced the downregulation of STAT3 protein. We also observed that a STAT3 inhibitor augmented the reduction of cell viability induced by p53 knockdown, whereas interleukin-6 treatment alleviated this effect. In addition, overexpression of STAT3 protected ATC cells against cell death induced by p53 knockdown. Taken together, these data show that mt p53 (G199V) gains antiapoptotic function mediated by STAT3 in ATC cells. Inhibition of the function of mt p53 (G199V) could be a novel and useful therapeutic strategy for decreasing the extent and severity of toxicity due to chemotherapeutic agents. (Mol Cancer Res 2009;7(10):1645–54)

Sutureless Intestinal Anastomosis With the Biofragmentable Anastomosis Ring: Experience of 632 Anastomoses in a Single Institute

PURPOSEUncertainty with the safety of the biofragmentable anastomosis ring makes surgeons hesitate in its widespread use in intestinal surgery. This study was designed to evaluate the validity of the biofragmentable anastomosis ring as a routine anastomotic device in enterocolic surgery.METHODSThe study analyzed the nine-year experience of 632 biofragmentable anastomosis ring anastomoses performed in 617 patients: 525 (83 percent) as elective procedures and 107 (17 percent) as emergency. Three classic types of anastomosis, end-to-end (n = 354), end-to-side (n = 263), and side-to-side (n = 15), were performed with a standard technique.RESULTSAnastomotic sites included ileocolic/ileorectal in 283 patients (45 percent), colorectal in 148 (23 percent), enteroenteric in 101 (16 percent), and colocolic in 100 patients (16 percent). Anastomotic leakage with clinical relevance was observed in five patients (0.8 percent): three elective cases, and two emergency (2 colorectal anastomoses and 1 ileorectal required diversions). Among 13 instances (2.1 percent) with postoperative intestinal obstruction, only 1 required relaparotomy for closed-loop obstruction. Seven patients (1.1 percent; 4 elective cases, and 3 emergency) died postoperatively; no deaths were directly related to the biofragmentable anastomosis ring technique.CONCLUSIONSOur data suggest that the anastomosis using the biofragmentable anastomosis ring is a uniform and highly reliable technique even in high-risk emergency surgery. Along with its clinical validities, clinical application of the biofragmentable anastomosis ring in different types of anastomoses in enterocolic surgery is expected to be expanded with a high level of technical safety.

Intensity of Tumor Budding as an Index for the Malignant Potential in Invasive Rectal Carcinoma

PURPOSE The aim of this study was to quantitatively assess the intensity of tumor budding in rectal carcinoma and to determine how it correlates with the malignant potential. MATERIALS AND METHODS Intensities of the tumor budding at the invasive front of the surgical specimens from 90 patients (male, 51) with well- or moderately-differentiated rectal carcinoma were investigated. Differences in the budding intensity among pathologic variables were compared, and recurrences and survivals were analyzed in accordance with degree of the budding intensity. The patients ranged in age from 33 to 75 years (mean, 55.4) with the median follow-up being 43 months (range, 12 approximately 108). RESULTS Tumor budding was identified in 89 patients (98.9%) with a mean intensity of 7.5+/-5.3. The budding intensity was significantly higher in tumors with lymphatic invasion (p=0.0081), blood vessel invasion (p<0.0001), and perineural invasion (p=0.0013) than in those tumor without these findings. It became significantly higher with the increase in nodal stage (p<0.0001). The intensity of tumor budding in patients with relapse (29 patients) was significantly higher than that in patients without relapse (6.2+/-5.0 vs. 10.2+/-4.9; p=0.0005), but this difference in the intensity was observed only for the node-positive patients (8.0+/-3.4 vs. 11.9+/-5.1; p=0.0064). When the patients were stratified into two groups on either side of the mean of the intensity, the higher intensity group showed a significantly less favorable disease-free (DFS) and overall survival (OS) (p=0.0026 and 0.0205, respectively). Based on the multivariate analysis, the nodal stage and the intensity of budding proved to be the independent variables associated with DFS (p=0.023 and 0.03, respectively). CONCLUSION Tumor budding at the invasive margin is a reliable pathologic index that indicates a higher malignant potential and a less favorable prognosis for patients with advanced rectal carcinoma.

How Much Progress Has Been Made in Minimally Invasive Surgery for Gastric Cancer in Korea?: A Viewpoint From Korean Prospective Clinical Trials

AbstractGastric cancer is the most common cancer in Korea. Because the incidence of gastric cancer is still high even with early detection and because of developments in surgical instruments and technological advances, minimally invasive surgery has rapidly become an accepted treatment for gastric cancer in Korea. Many Korean gastric surgeons have contributed to the rapid adaptation of minimally invasive surgery for gastric cancer: not only the Korean Laparoscopic Gastrointestinal Surgery Study (KLASS) group, but also other expert surgeons after the 2000s. Thanks to their vigorous efforts involving active learning, education, workshops, academic communications, and international communications with active laparoscopic gastric surgeons in Korea, numerous results and well-designed large-scale clinical studies have been published or are actively ongoing, thus increasing its wide acceptance as an option for gastric cancer. Now, Korea has become one of the leading countries using minimally invasive surgery for the treatment of gastric cancer. This review article will summarize the current status and issues, as well as the clinical trials that have finished or are ongoing, regarding minimally invasive surgery for gastric cancer in Korea.

Role of Percutaneous Transhepatic Biliary Drainage in Patients With Complications After Gastrectomy

OBJECTIVE The aim of this study was to elucidate the role of PTBD in patients with DSL and ALS post-gastrectomy for malignancy or benign ulcer perforation. SUMMARY OF BACKGROUND DATA Percutaneous transhepatic biliary drainage (PTBD) is an interventional radiologic procedure used to promote bile drainage. Duodenal stump leakage (DSL) and afferent loop syndrome (ALS) can be serious complications after gastrectomy. METHODS From January 2002 through December 2014, we retrospectively reviewed 19 patients who underwent PTBD secondary to DSL and ALS post-gastrectomy. In this study, a PTBD tube was placed in the proximal duodenum near the stump or distal duodenum in order to decompress and drain bile and pancreatic fluids. RESULTS Nine patients with DSL and 10 patients with ALS underwent PTBD. The mean hospital stay was 34.3 days (range, 12-71) in DSL group and 16.4 days (range, 6-48) in ALS group after PTBD. A liquid or soft diet was started within 2.6 days (range, 1-7) in the ALS group and within 3.4 days (range, 0-15) in the DSL group after PTBD. One patient with DSL had PTBD changed, and 2 patients with ALS underwent additional surgical interventions after PTBD. CONCLUSIONS The PTBD procedure, during which the tube was inserted into the duodenum, was well-suited for decompression of the duodenum as well as for drainage of bile and pancreatic fluids. This procedure can be an alternative treatment for cases of DSL and ALS post-gastrectomy.

Afferent Loop Syndrome After Subtotal Gastrectomy With Billroth-II Reconstruction: Etiology and Treatment

The aim of this study was to evaluate the clinical characteristics, treatment, and prognosis of afferent loop syndrome (ALS) following radical subtotal gastrectomy with B-II reconstruction in gastr...