Say-June Kim

The Short-term Outcomes of Conventional and Single-port Laparoscopic Surgery for Colorectal Cancer

Objective:The aim of this study was to show the safety and feasibility of single-port laparoscopic surgery (SPLS) by comparing its short-term outcomes with those following conventional laparoscopic surgery. Summary Background Data:Single-port laparoscopic surgery maximizes the advantages of laparoscopic surgery, and therefore it can be an ultimate attainment of laparoscopic surgery. However, no comparative study has addressed its role in colorectal cancer. Methods:Prospectively collected data of patients who had undergone either conventional laparoscopic surgery (n = 106) or SPLS (n = 73) for colorectal cancer between March 2006 and May 2010 were analyzed retrospectively. The short-term outcomes of these 2 operative modalities were compared. Results:Of the 179 study subjects, 103 (57.5%) had colon cancer and 76 (42.5%) had rectal cancer. Various operative methods, from right hemicolectomy to abdominoperineal resection, were used according to location through either conventional laparoscopic or SPLS approach. In its comparison, mean surgical time was greater in the SPLS group (255 vs 276 minutes, P < 0.008). Acquired length of sufficient surgical margins and the number of harvested lymph nodes were comparable. Postoperative recovery was faster in the SPLS group, in terms of shorter time duration before first flatus (SPLS vs conventional laparoscopic surgery; 2.5 ± 1.2 vs 3.2 ± 1.8 days, P = 0.004), earlier initiation of free oral fluids (1.8 ± 2.2 vs 2.6 ± 1.7 days, P = 0.000) and of a solid diet (4.2 ± 2.9 vs 6.5 ± 2.7 days, P = 0.000), less frequent usage of parenteral narcotics (2.2 ± 3.2 vs 3.5 ± 4.0 times, P = 0.029), and shorter hospital stay (9.6 ± 9.6 vs 15.5 ± 9.8 days, P = 0.000). Conclusion:This study shows that SPLS is both safe and feasible in colorectal cancer, and that it has equivalent or better short-term outcomes than conventional laparoscopic surgery. Accordingly, the authors conclude that SPLS can be an alternative to conventional laparoscopic surgery for colorectal cancer.

Therapeutic potential of adipose tissue-derived stem cells for liver failure according to the transplantation routes

Purpose Even though adipose tissue-derived stem cells (ADSCs) have been spotlighted as a possible alternative for liver transplantation in an experimental setting, the mechanism by which ADSCs improve liver dysfunction remains poorly characterized. The objective of this study was to evaluate the therapeutic ability of undifferentiated ADSCs, and find a few clues on how ADSCs alleviate liver damage by comparing the transplantation routes. Methods In vitro generated human ADSCs were checked for surface markers and stage-specific genes for characterization. Afterwards, they were transplanted into C57BL/6 mice with CCl4-induced liver injury. The transplantations were made via tail vein, portal vein, and direct liver parenchymal injection. At 1 and 3 post-transplantation days, serum biochemical parameters and/or liver specimens were evaluated. Results We have shown here that ADSCs have the characteristics of mesenchymal stem cells, and belong to endodermal and/or early hepatic differentiation stage. After transplantation into the mice with acute liver failure, markers of liver injury, such as alanineaminotransferase, aspartateaminotransferase, as well as ammonia, decreased. Of these transplantation routes, transplantation via tail vein rendered the most prominent reduction in the biochemical parameters. Conclusion Undifferentiated ADSCs have the ability to improve hepatic function in mice with acute liver injury. Moreover, our transplantation route study supports the theory that ADSCs in systemic circulation can exert endocrine or paracrine effects to ameliorate the injured liver.

IWR-1 inhibits epithelial-mesenchymal transition of colorectal cancer cells through suppressing Wnt/β-catenin signaling as well as survivin expression

Aberrant activation of Wnt/β-catenin signaling is frequently observed in patients with colorectal cancer (CRC) and is considered a major determinant of CRC pathogenesis. CRC pathogenesis is particularly accompanied by epithelial-mesenchymal transition (EMT) and survivin expression. Here, we investigated the potential and mechanism of a novel Wnt/β-catenin inhibitor IWR-1 to suppress tumor metastasis in relation with EMT and survivin expression. We first determined the EMT reversal effects of IWR-1 in in vitro (HCT116 and HT29 cells) and ex vivo (specimens of CRC patients) CRC models. It was shown that IWR-1 inhibited cell proliferation and EMT even in the presence of TNF-α-induced cancer cell stimulation. IWR-1 also significantly suppressed cell migration, invasion, and matrix metalloproteinase activities of CRC cell lines. Furthermore, we showed the evidence that IWR-1 provides EMT reversal effects by directly suppressing survivin expression by the followings: 1) IWR-1 could not completely inhibit EMT in survivin-overexpressing HCT116 cells, 2) EMT reversal effects of IWR-1 were more pronounced in survivin-suppressed cells, and 3) Survivin promoter assay directly identified the survivin promoter region responsible for inhibition of survivin transcription by IWR-1. Taken altogether, our results demonstrate that IWR-1 has the potential to suppress tumor metastasis by inhibiting Wnt/β-catenin pathway as well as survivin expression. Therefore, IWR-1 could be considered for future clinical use as a therapeutic agent to treat CRC.

Overview of single-port laparoscopic surgery for colorectal cancers: past, present, and the future.

Single-port laparoscopic surgery (SPLS) is implemented through a tailored minimal single incision through which a number of laparoscopic instruments access. Introduction of operation-customized port system, utilization of a camera without a separate external light, and instruments with different lengths has brought the favorable environment for SPLS. However, performing SPLS still creates several hardships compared to multiport laparoscopic surgery; a single-port system inevitably leads to clashing of surgical instruments due to crowding. To overcome such difficulties, investigators has developed novel concepts and maneuvers, including the concept of inverse triangulation and the maneuvers of pivoting, spreading out dissection, hanging suture, and transluminal traction. The final destination of SPLS is expected to be a completely seamless operation, maximizing the minimal invasiveness. Specimen extraction through the umbilicus can undermine cosmesis by inducing a larger incision. Therefore, hybrid laparoscopic technique, which combined laparoscopic surgical technique with natural orifice specimen extraction (NOSE)--i.e., transvaginal or transanal route-, has been developed. SPLS and NOSE seemed to be the best combination in pursuit of minimal invasiveness. In the near future, robotic SPLS with natural orifice transluminal endoscopic surgerys way of specimen extraction seems to be pursued. It is expected to provide a completely or nearly complete seamless operation regardless of location of the lesion in the abdomen.

Clinical analysis of living donor liver transplantation in patients with portal vein thrombosis

Kim S‐J, Kim D‐G, Park J‐H, Moon I‐S, Lee M‐D, Kim J‐I, Yoon Y‐C, Yoo Y‐K. Clinical analysis of living donor liver transplantation in patients with portal vein thrombosis.
Clin Transplant 2011: 25: 111–118.

Hepatic artery reconstruction and successful management of its complications in living donor liver transplantation using a right lobe.

Kim S‐J, Yoon Y‐C, Park J‐H, Oh D‐Y, Yoo Y‐K, Kim D‐G. Hepatic artery reconstruction and successful management of its complications in living donor liver transplantation using a right lobe. 
Clin Transplant 2011: 25: 929–938.

The feasibility of single-port laparoscopic appendectomy using a solo approach: a comparative study.

Purpose To investigate the feasibility and safety of solo surgery with single-port laparoscopic appendectomy, which is termed herein solo-SPLA (solo-single-port laparoscopic appendectomy). Methods This study prospectively collected and retrospectively analyzed data from patients who had undergone either non-solo-SPLA (n = 150) or solo-SPLA (n = 150). Several devices were utilized for complete, skin-to-skin solo-SPSA, including a Lone Star Retractor System and an adjustable mechanical camera holder. Results Operating times were not significantly different between solo- and non-solo-SPLA (45.0 ± 21.0 minutes vs. 46.7 ± 26.1 minutes, P = 0.646). Most postoperative variables were also comparable between groups, including the necessity for intravenous analgesics (0.7 ± 1.2 ampules [solo-SPLA] vs. 0.9 ± 1.5 ampules [non-solo-SPLA], P = 0.092), time interval to gas passing (1.3 ± 1.0 days vs. 1.4 ± 1.0 days, P = 0.182), and the incidence of postoperative complications (4.0% vs. 8.7%, P = 0.153). Moreover, solo-SPLA effectively lowered the operating cost by reducing surgical personnel expenses. Conclusion Solo-SPLA economized staff numbers and thus lowered hospital costs without lengthening of operating time. Therefore, solo-SPLA could be considered a safe and feasible alternative to non-solo-SPLA.

Single-port laparoscopic surgery for sigmoid volvulus

AIM To report our experience with single-port laparoscopic surgery (SPLS) for sigmoid volvulus (SV). METHODS Between October 2009 and April 2013, 10 patients underwent SPLS for SV. SPLS was performed transumbilically or through a predetermined stoma site. Conventional straight and rigid-type laparoscopic instruments were used. After intracorporeal, segmental resection of the affected sigmoid colon, the specimen was extracted through the single-incision site. Patient demographics and perioperative data were analyzed. RESULTS SPLS for SV was successful in all 10 patients (4, resection and primary anastomosis; 6, Hartmanns procedure). The median operative time and postoperative hospitalization period were 168 (range, 85-315) min and 6.5 (range, 4-29) d, respectively. No intraoperative complications were noted; there were 2 postoperative complications, including 1 anastomotic leak. CONCLUSION SPLS was a safe and feasible therapeutic approach for SV, when performed by a surgeon experienced in conventional laparoscopic surgery.

Determination of surgical priorities in appendicitis based on the probability of undetected appendiceal perforation.

AIM To identify risk factors of actual appendiceal perforation when computed tomography (CT) scans suggest nonperforated appendicitis and accordingly determine surgical priority. METHODS We collected database of 1362 patients who underwent an appendectomy for acute appendicitis between 2006 and 2013. A single radiologist selected 1236 patients whose CT scans were suggestive of nonperforated appendicitis. Patients were divided into 2 groups: actual nonperforation group and actual perforation group according to intraoperative and pathologic features. Comparison of the 2 groups were made using binary logistic regression. RESULTS Of 1236 patients, 90 (7.3%) were found to have actual appendiceal perforation. Four risk factors related with actual appendiceal perforation were identified: body temperature≥37.6  °C (HR=1.912, 95%CI: 1.161-3.149; P=0.011), out-of-hospital symptom duration≥72 h (HR=2.454, 95%CI: 1.292-4.662; P=0.006), age≥35 years (HR=3.358, 95%CI: 1.968-5.728; P<0.001), and appendiceal diameter on CT scan≥8 mm (HR=4.294, 95%CI: 1.034-17.832; P=0.045). Actual appendiceal perforation group showed longer operation time, later initiation of diet, longer use of parenteral narcotics, longer hospital stay, and higher incidence of postoperative complications (P<0.05). CONCLUSION We proposed here new criteria to select patients with adverse clinical outcomes after appendectomy among the patients with radiologically nonperforated appendicitis. Surgical appendectomy outcomes could be improved by determining the surgical priority according to our criteria.

Potentiation of the anticancer effects of everolimus using a dual mTORC1/2 inhibitor in hepatocellular carcinoma cells

There is lots of evidence to support the critical involvement of mTOR signaling in the carcinogenesis of hepatocellular carcinoma (HCC). However, it has not been determined how the roles of individual mTORC1 and mTORC2 inhibitors played in the HCC therapeutics. We thus compared the effects of everolimus, Ku0063794, and a combination of the two therapies on HCC cells, using various in vitro studies (HepG2, Hep3B, and Huh7 cells), ex vivo culturing of HCC tissues obtained from patients, and the in vivo mouse xenograft model of HCC cells. Our in vitro, ex vivo, and in vivo experiments consistently demonstrated that everolimus and Ku0063794 combination therapy was superior to individual monotherapies, as manifested by higher reduction of proliferation, migration, and invasion of HCC cells, and the higher inhibition of EMT process as well. Although individual monotherapies could not inhibit SIRT1 (positive regulator of EMT) expression, the combination therapy significantly inhibited SIRT1 expression. However, overexpression of SIRT1 mitigated the EMT-inhibiting effect of the combination therapy, suggesting that the combination therapy inhibits the EMT by way of suppressing SIRT1 expression. Therefore, when considering everolimus as an anti-HCC agent, the improved anticancer effects provided by combining it with an inhibitor of both mTORC1 and mTORC2 should be recognized.