Targeted Therapy of Hepatocellular Carcinoma Using Gemcitabine-Incorporated GPC3 Aptamer.

Hepatocellular carcinoma (HCC) is the most common malignancy of the liver, which can progress rapidly and has a poor prognosis. Glypican-3 (GPC3) has been proposed to be an important diagnostic biomarker and therapeutic target for HCC. Aptamers have emerged as promising drug delivery vehicles because of their high binding affinity for target molecules. Herein, we developed G12msi, a gemcitabine-incorporated DNA aptamer, targeting GPC3, and evaluated its binding specificity and anti-tumor efficacy in GPC3-overexpressing HCC cell lines and murine xenograft models. GPC3-targeted aptamers were selected by using the SELEX process and the chemotherapy drug gemcitabine was internally incorporated into the aptamer. To determine the binding affinity and internalization of the G12msi, flow cytometry and confocal microscopy were performed on GPC3-positive HepG2, Hep3B, and Huh7 cells, as well as a GPC3-negative A431 cell. The anti-tumor activities of G12msi were evaluated with in vitro and in vivo models. We found that G12msi binds to GPC3-overexpressing HCC tumor cells with high specificity and is effectively internalized. Moreover, G12msi treatment inhibited the cell proliferation of GPC3-positive HCC cell lines with minimal cytotoxicity in control A431 cells. In vivo systemic administration of G12msi significantly inhibited tumor growth of HCC HepG2 cells in xenograft models without causing toxicity. These results suggest that gemcitabine-incorporated GPC3 aptamer-based drug delivery may be a promising strategy for the treatment of HCC.

Primary Gastric Choriocarcinoma Coexisting with Adenocarcinoma.

Choriocarcinoma is an aggressively growing and widely metastasizing tumor that originates from trophoblastic cells. A primary gastric choriocarcinoma (PGC), however, is very rare. A 76-year-old female patient visited the emergency department of Wonkwang University Hospital with abdominal discomfort and melena. Esophagogastroduodenoscopy revealed a huge ulceroinfiltrative mass lesion with blood clots on the boundary between the greater curvature side and the posterior wall side of the stomach lower body. CT showed a 3-cm exophytic mass lesion with heterogeneous enhancement, an ulcer lesion at the posterior wall side of the stomach lower body, and multiple enlarged lymph nodes at the splenic artery and left gastric artery nodal stations. She underwent a radical subtotal gastrectomy with a D2 lymph node dissection. The final diagnosis was PGC coexisting with adenocarcinoma based on the pathology results. This paper reports a rare case of primary gastric choriocarcinoma coexisting with adenocarcinoma and discusses the characteristics of this neoplasm with reference to the literature.

Association between genetic polymorphisms in cortactin and susceptibility to gastric cancer.

PURPOSE: Overexpression of cortactin (CTTN) in human tumors has been proposed to result in increased cell migration and metastatic potential. Here, we determined the frequencies of CTTN g.-9101C>T, g.-8748C>T, and g.72C>T polymorphisms in apparently healthy subjects and gastric cancer patients, respectively, and the influence of the CTTN polymorphisms on gastric cancer susceptibility. METHODS: Blood samples were collected from 267 patients and 533 controls. CTTN g.-8748C>T and g.-9101C>T polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism; the g.72C>T polymorphism was determined using the TaqMan method. RESULTS: Genotype frequencies of the CTTN g.-9101C>T polymorphism were 97.5% (TT), 2.5% (TC), and 0% (CC) in the patient group, and 98.6% (TT), 1.4% (TC), and 0% (CC) in the control group. Genotype frequencies of the CTTN g.-8748C>T polymorphism were 93.3% (TT), 6.8% (TC), and 0% (CC) in the patient group, and 94.2% (TT), 5.8% (TC), and 0% (CC) in the control group. Genotype frequencies of the CTTN g.72C>T polymorphism were 82.4% (CC), 17.2% (CT), and 0.4% (TT) in the patient group, and 78.0% (CC), 20.1% (CT), and 1.9% (TT) in the control group. Genotype and allele frequencies of the CTTN g.-9101C>T polymorphism differed significantly between the advanced gastric cancer and control groups. Patients with advanced gastric cancer, possessing the TC genotype, had a significantly poorer prognosis than the group with the TT genotype. CONCLUSION: The CTTN g.-9101C>T polymorphism might influence advanced gastric cancer susceptibility. However, the role of the CTTN g.-9101C>T, g.-8748C>T, and g.72C>T polymorphisms requires careful interpretation and confirmation through larger studies.

Chronic gastric anisakiasis provoking a bleeding gastric ulcer.

Gastric anisakiasis is a parasitic disease caused by the gastric mucosal penetration of the Anisakis larvae ingested with raw fish. Acute gastric anisakiasis is diagnosed by the endoscopic visualization of Anisakis larvae along with mucosal edema, erythema, hemorrhage, and/or an ulcer, whereas chronic anisakiasis is often observed as a localized tumor commonly occurring in the submucosal layer, and is characterized by eosinophilic granuloma with edema and embedded Anisakis larvae on pathological examination of surgical specimens. We report here a case of chronic gastric anisakiasis provoking a bleeding gastric ulcer, which is a rare clinical manifestation of this condition.

Postoperative pain relief using wound infiltration with 0.5% bupivacaine in single-incision laparoscopic surgery for an appendectomy.

PURPOSE: Recently, single-incision laparoscopic surgery (SILS) has been popular for minimally invasive surgery and cosmetic improvement. However, some papers have reported that SILS for an appendectomy (SILS-A) has had the more postoperative complaints of pain. We investigated postoperative pain relief using wound infiltration with 0.5% bupivacaine in SILS-A and compared the result with that for conventional SILS-A. METHODS: Between July 2010 and September 2012, 75 patients who underwent SILS-A were enrolled in this study. The patients were randomly assigned to two groups: conventional SILS-A group (C-SILS-A) or wound infiltrated with 0.5% bupivacaine in SILS-A group (W-SILS-A). Forty-five patients were in the C-SILS-A, and 30 patients were in the W-SILS-A. Patients with perforated appendicitis were excluded. The clinical outcomes were compared between the groups by using the verbal numerical rating scale (VNRS). RESULTS: Clinical outcomes were similar in both study groups except for the pain score. The W-SILS-A group showed significantly lower numbers of additional pain killers and lower VNRS scores 1, 6, and 12 hours after surgery than the C-SILS-A group. CONCLUSION: W-SILS-A is a technically simple and effective method of reducing early postoperative pain. It may be applicable in SILS-A for pain control system.

Association of CTTN polymorphisms with the risk of colorectal cancer.

PURPOSE: Various studies searching for biomarkers to predict tumor metastasis or prognosis in both esophageal squamous cell carcinoma (ESCC) and head and neck squamous cell carcinoma (HNSCC) are currently underway. However, few data have been reported on its association with colorectal cancer (CRC). Single nucleotide polymorphisms (SNPs) are the most common known form of human genetic variation and may contribute to an increased susceptibility to cancer including CRC. The present study aimed to investigate whether the polymorphisms in the CTTN gene are associated with susceptibility to CRC in the Korean population. METHODS: A case-control study was performed to examine the relationship between the CTTN g.-9101C>T, g.-8748C>T, and g.72C>T polymorphisms and the risk of CRC. Polymerase chain reaction-restriction fragment length polymorphism analysis of g.-8748C>T, g.-9101C>T and Taqman analysis of g.72C>T were performed on blood samples from 218 patients with CRC and 533 control individuals. The g.-9101C>T, g.-8748C>T, and g.72C>T SNPs in CTTN and their haplotypes were analyzed. RESULTS: The genotype and allele frequencies of g.-9101C>T, g.-8748C>T, and g.72C>T did not differ between the patient group and the control group. Further, the haplotype of CTTN g.-9101C>T, g.-8748C>T, and g.72C>T did not differ between patient group and the control group. However, the genotype and allele frequencies of CTTN g.-9101C>T were significantly increased in the lymph node positive CRC group compared to the control group. CONCLUSION: The CTTN g.-9101C>T polymorphism may influence lymph node positive CRC.

Application of single incision laparoscopic surgery for appendectomy in children.

PURPOSE: Recently, single incision laparoscopic surgery (SILS) has been popular in use with its progress studied for more minimally invasive surgery and cosmetic improvement. We investigated the feasibility and efficacy of SILS for appendectomy (SILS-A) in children and compare it with conventional laparoscopic appendectomy (C-LA). METHODS: We studied, retrospectively, adolescent patients who underwent C-LA or SILS-A. There were 25 patients in the C-LA group and 30 patients in the SILS-A group. The clinical outcomes were compared between the groups. RESULTS: The SILS-A procedures were performed successfully in adolescent patients . There were no significant difference between the C-LA and SILS-A group with respect to demographic data and post-operative outcomes. There was one complication (4%) in the C-LA group and two complications (6.6%) in the SILS-A group, but there was no significant difference. CONCLUSION: SILS-A was technically feasible and safe in children. Considering little postoperative scar and no difference in post-operative outcomes compared to C-LA, SILA could be applicable in adolescent patients. Larger studies and further technical implements will be necessary to assess the true benefit of this approach.

The haplotypes of TNFRSF17 polymorphisms are associated with colon cancer in a Korean population.

PURPOSE: We previously found that the haplotypes of TNFRSF17 single nucleotide polymorphisms (SNPs) were associated with the susceptibility to inflammatory bowel disease on Korean population. The present study aimed to investigate whether the polymorphisms in the TNFRSF17 gene are associated with susceptibility to colorectal cancer (CRC). METHODS: Genotype analysis in the TNFRSF17 SNPs was performed by high-resolution melting and TaqMan probe analysis, and the genotype and allele frequencies of TNFRSF17 SNPs were compared between the CRC patients and the healthy controls. The haplotype frequencies of TNFRSF17 for multiple loci were estimated using the expectation maximization algorithm. RESULTS: Although, the genotype and allelic frequencies of these SNPs, in the colon cancer and rectal cancer patients, were not significantly different from those in the healthy controls, the genotype and allele frequency of g.2493G>A was significantly different between the healthy controls and the right colon cancer patients (P = 0.014 and 0.004, respectively). Moreover, the haplotypes frequencies in the healthy controls were significantly different from those in the colon cancer patients. CONCLUSION: Our results suggest that TNFRSF17 may be a candidate gene associated with the pathogenesis of colon cancer, and the haplotypes of the TNFRSF17 polymorphisms might be one of the markers for colon cancer susceptibility.

Laparoscopic treatment of adult sigmoidorectal intussusception caused by a mucinous adenocarcinoma of the sigmoid colon: a case report.

Intussusception is a rare cause of intestinal obstruction in adult patients, but is common in children. In fact, it accounts for an estimated 1% of all cases of bowel obstruction in adults, although adult intussusception of the large intestine is rare. Sigmoidorectal intussusception, however, is a rare variety with few cases reported in the literature. A mucinous adenocarcinoma, a subtype of adenocarcinoma, is characterized by extracellular mucin production and accounts for between 5% and 15% of the neoplasms of the colon and rectum. Despite the general consensus supporting surgical resections for adult intussuceptions, controversy remains over whether intussuceptions should be reduced before resection. Most cases of colon intussusception should not be reduced before resection because they most likely represent a primary adenocarcinoma. However, prior reduction followed by a resection can be considered for the sigmoidorectal intussusception to avoid inadvertent low rectal cancer sugery. We experienced one case of sigmoidorectal intussusception caused by a mucinous adenocarcinoma of the sigmoid colon in a 79-year-old woman. Abdominal computed tomography demonstrated a sigmoidorectal intussusception. After the end-to-end anastomosis-dilator-assisted reduction, the patient underwent a laparoscopic oncological anterior resection under the impression that a sigmoidorectal intussusception existed. We report a successful laparoscopic anterior resection in a patient with an intussusception caused by a sigmoid malignant tumor.

[Small bowel obstruction caused by acute invasive enteric anisakiasis].

Anisakiasis usually occurs in the stomach and can easily be diagnosed by digestive tract endoscopy as opposed to enteric anisakiasis which is very rare and difficult to be diagnosed definitively. The most important and useful tool in diagnosing enteric anisakiasis is obtaining an accurate patient history of having eaten raw fish before the onset of symptoms. We report a case of small bowel obstruction caused by acute invasive enteric anisakiasis. A 60-year-old woman visited the emergency room suffering from sudden abdominal pain. She had eaten raw fish 1 day before the onset of symptom. Radiologic studies showed small bowel obstruction. However, no definitive cause could be found. An emergency laparotomy revealed edematous and dilated proximal jejunum and a focal stenosis of the distal jejunum. Segmental resection of the jejunum was performed, and histopathological examination revealed enteric anisakiasis. The patient was discharged on the 7th day after surgery following an uneventful course of recovery.

Application of single incision laparoscopic surgery for appendectomies in patients with complicated appendicitis.

PURPOSE: Recently, single incision laparoscopic surgery (SILS) has been studied for its being less invasive surgery and having cosmetic improvement. We investigated the application of SILS for an appendectomy (SILS-A) in cases of complicated appendicitis and compare it with a conventional laparoscopic appendectomy (C-LA). METHODS: This study involved a total of 40 patients who underwent C-LA or SILS-A in patients with complicated appendicitis; 25 patients received a C-LA, and the other 15 patients received a SILS-A. The clinical outcomes and cosmetic results were compared between the groups. RESULTS: The SILS-A procedures were performed successfully in patients with complicated appendicitis, but 6 patients who underwent SILS-A needed an additional port for dissection and drainage. Clinical outcomes and postoperative complications were similar in both study groups. The SILS-A group showed significantly higher numbers of pain control than the C-LA group, and the one port SLLS-A group showed significantly better cosmetic result than the C-LA group. CONCLUSION: SILS-A is technically feasible and safe in patients with complicated appendicitis. However, SILS-A has more postoperative pain than C-LA, and more active pain control should be considered for patients undergoing SILS-A.