AIM: To investigate the relationship between loss of heterozygosity (LOH) for mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) and the outcomes for primary HCC patients treated with partial hepatectomy.
METHODS: The LOH for M6P/IGF2R in primary HCC patients was assessed using six different gene-specific nucleotide polymorphisms. The patients studied were enrolled to undergo partial hepatectomy.
RESULTS: M6P/IGF2R was found to be polymorphic in 73.3% (22/30) of the patients, and of these patients, 50.0% (11/22) had tumors showing LOH in M6P/IGF2R. Loss of heterozygosity in M6P/IGF2R was associated with significant reductions in the two year overall survival rate (24.9% vs 65.5%; P = 0.04) and the disease-free survival rate (17.8% vs 59.3%; P = 0.03).
CONCLUSION: These results show M6P/IGF2R LOH predicts poor clinical outcomes in surgically resected primary HCC patients.
Loss of heterozygosity; Mannose 6-phosphate/insulin-like growth factor 2 receptor; Hepatocellular carcinoma
Rho GDP dissociation inhibitor 2 (RhoGDI2) expression correlates with tumor growth, metastasis, and chemoresistance in gastric cancer. Here, we show that RhoGDI2 functions in the epithelial-mesenchymal transition (EMT), which is responsible for invasiveness during tumor progression. This tumorigenic activity is associated with repression of E-cadherin by RhoGDI2 via upregulation of Snail. Overexpression of RhoGDI2 induced phenotypic changes consistent with EMT in gastric cancer cells, including abnormal epithelial cell morphology, fibroblast-like properties, and reduced intercellular adhesion. RhoGDI2 overexpression also resulted in decreased expression of the epithelial markers E-cadherin and β-catenin and increased expression of the mesenchymal markers vimentin and fibronectin. Importantly, RhoGDI2 overexpression also stimulated the expression of Snail, a repressor of E-cadherin and inducer of EMT, but not other family members such as Slug or Twist. RNA interference-mediated knockdown of Snail expression suppressed RhoGDI2-induced EMT and invasion, confirming that the effect was Snail-specific. These results indicate that RhoGDI2 plays a critical role in tumor progression in gastric cancer through induction of EMT. Targeting RhoGDI2 may thus be a useful strategy to inhibit gastric cancer cell invasion and metastasis.
RhoGDI2; EMT; Snail; gastric cancer; invasion
The extract of Allium cepa Linn is commonly used as adjuvant food for cancer therapy. We assumed that it includes a potential source of anti-cancer properties.
We investigated anti-cancer effects of polyphenols extracted from lyophilized A. cepa Linn (PEAL) in AGS human cancer cells.
PEAL inhibited cell growth in a dose-dependent manner. It was related to caspase-dependent apoptosis. We confirmed this finding with annexin V staining. PEAL up-regulated p53 expression, and subsequent Bax induction, down regulated Bcl-2 protein, anti-apoptotic protein. In addition, PEAL suppressed Akt activity and PEAL-induced apoptosis were significantly accentuated with Akt inhibitor (LY294002).
Our data suggested that PEAL induce caspase-dependent apoptosis through mitochondrial pathway by up-regulating p53 protein, and subsequent Bax protein as well as by modulating Bcl-2 protein, and that PEAL induces caspase-dependent apoptosis at least in part through the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. This study provides evidence that PEAL might be useful for the treatment of cancer.
Allium cepa; polyphenols; Apoptosis; Bcl-2; Akt
Rho GDP dissociation inhibitor 2 (RhoGDI2) promotes tumor growth and malignant progression and enhances chemoresistance of gastric cancer. Recently, we noted an inverse correlation between RhoGDI2 and 14-3-3σ expression, which suggests that 14-3-3σ is a target of gastric cancer metastasis and the chemoresistance-promoting effect of RhoGDI2. Herein, we evaluated whether 14-3-3σ is regulated by RhoGDI2 and is functionally important for the RhoGDI2-induced cisplatin resistance of gastric cancer cells. We used highly metastatic and cisplatin-resistant RhoGDI2-overexpressing SNU-484 cells and observed decreased 14-3-3σ mRNA and protein expression. Depletion of 14-3-3σ in SNU-484 control cells enhanced cisplatin resistance, whereas restoration of 14-3-3σ in RhoGDI2-overexpressing SNU-484 cells impaired cisplatin resistance in vitro and in vivo. We also found that the phosphorylation levels of Erk and p38 kinases significantly decreased in RhoGDI2-overexpressing SNU-484 cells and recovered after 14-3-3σ expression, and that decreased activities of these kinases were critical for RhoGDI2-induced cisplatin resistance. In conclusion, 14-3-3σ is a RhoGDI2-regulated gene that appears to be important for suppressing the chemoresistance of gastric cancer cells.
RhoGDI2; 14-3-3σ; gastric cancer; chemoresistance; metastasis
Tight junctions (TJs) are a mode of cell-to-cell adhesion in epithelial or endothelial cells, and serve as a physical barrier to maintenance of homeostasis in body by controlling paracellular transport. Claudins are the most important molecules of the TJs, but paradoxically these proteins are frequently over-expressed in cancers and their overexpression is implicated in the invasive potential of cancer. Hence, we investigated the effects of flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) on TJs and the expression of claudins as well as cancer invasion along with in LnCaP human prostate cancer. FEOJ suppressed cancer cell motility and invasiveness at the concentrations where FEOJ did not show anti-proliferative activity. FEOJ increased transepithelial electrical resistance (TER) associated with tightening TJs, and suppressed expression of claudin proteins. Furthermore, FEOJ suppressed the activities of MMP-2 and -9 in a dose-dependent manner, which came from the activation of tissue inhibitor of metalloproteinases (TIMPs) by FEOJ. FEOJ suppressed migration and invasion by suppressing PI3K/Akt signaling pathway. Taken together, this study suggest that FEOJ suppresses cancer migration and invasion by tightening TJs through the suppression of claudin expression, and by suppressing MMPs in LnCaP human prostate cancer cells, which at least in part results from the suppression of PI3K/Akt signaling pathway.
Orostachys japonicus; flavonoids; LnCaP cells; tight junctions; Akt
Acute gastric volvulus requires emergency surgery, and a laparoscopic approach for both acute and chronic gastric volvulus was reported recently to give good results. The case of a 50-year-old patient with acute primary gastric volvulus who was treated by laparoscopic reduction and percutaneous endoscopic gastrostomy is described here. This approach seems to be feasible and safe for not only chronic gastric volvulus, but also acute gastric volvulus.
Stomach volvulus; Intestinal volvulus; Laparoscopy; Endoscopy; Gastrostomy
F-actin capping protein α1 subunit (CAPZA1) was previously identified in a proteomic analysis of human gastric cancer clinical specimens and selected for further study. The association between CAPZA1 overexpression, detected by immunohistochemistry, and clinicopathological features including survival were evaluated. In vitro gain-of-function and loss-of-function approaches were utilized to assess the function of CPAZA1 in malignancy. Univariate analysis revealed that poorly differentiated disease, according to the World Health Organization (WHO) classification, advanced T stage, positive lymph nodes, high TNM stage, D2 lymph node dissection, adjuvant chemotherapy and CAPZA1 underexpression were significantly associated with cancer-related death (p<0.05); however, only high TNM stage remained significantly associated by multivariate analysis (p<0.01). CAPZA1 overexpression was associated with well differentiated histology, smaller tumor size, lower T stage, absence of lymph node metastasis, lower TNM stage, lower recurrence rate and longer survival time, compared to CAPZA1 underexpression. In vitro, forced expression of CAPZA1 caused a significant decrease in gastric cancer cell migration and invasion, whereas CAPZA1 depletion had the opposite effect. The present study suggests that CAPZA1 could be a marker of good prognosis in gastric cancer and shows that CAPZA1 is associated with decreased cancer cell migration and invasion.
stomach neoplasm; CAPZA1; F-actin capping protein; immunohistochemistry; biomarker
The aim of this study was to investigate the current status of the use of antiadhesive agents (AAdAs) via a questionnaire and to discuss the availability of AAdAs.
The survey was sent to a list of members that was approved by the Korean Gastric Association. The survey included questions on AAdA use by surgeons, the type of AAdAs used, and the reasons for not using AAdAs. Surgeons were also asked to describe complications related to AAdAs, and the reliability of its use.
The response rate was 21%. The rates of frequent use stratified by procedure were 26.9% (14/52) for open gastrectomy, 5.9% (3/51) for laparoscopic gastrectomy, and 31.5% (17/54) for surgery for postoperative bowel obstruction (P < 0.01). After including data from the occasional use group, the corresponding values were 51.9% (27/52), 19.6% (10/51), and 70.4% (38/54), respectively (P < 0.01). Sefrafilm and Guardix were most commonly used for open procedures. Guardix and Interceed were most commonly used for laparoscopic surgery. The primary reasons for nonuse of AAdAs were ineffectiveness and high cost. Ten percent (4/40) of surgeons observed complications associated with AAdAs. A minority (17.3%, 9/52) had positive attitudes toward AAdAs. The majority of respondents expressed neutral (73.1%, 38/52) or negative (9.6%, 5/52) attitudes toward AAdAs.
The low use rates of AAdAs in gastric cancer surgery may be attributable to perceptions that AAdAs are ineffective, unreliable, and costly. We anticipate the emergence of promising antiadhesive strategies that reach far beyond the limitations of current products.
Peritoneal adhesions; Questionnaires; Adhesion barriers; Postoperative complication; Stomach neoplasms
The aims are to: (i) display the multidimensional learning curve of totally laparoscopic distal gastrectomy, and (ii) verify the feasibility of totally laparoscopic distal gastrectomy after learning curve completion by comparing it with laparoscopy-assisted distal gastrectomy.
Materials and Methods
From January 2005 to June 2012, 247 patients who underwent laparoscopy-assisted distal gastrectomy (n=136) and totally laparoscopic distal gastrectomy (n=111) for early gastric cancer were enrolled. Their clinicopathological characteristics and early surgical outcomes were analyzed. Analysis of the totally laparoscopic distal gastrectomy learning curve was conducted using the moving average method and the cumulative sum method on 180 patients who underwent totally laparoscopic distal gastrectomy.
Our study indicated that experience with 40 and 20 totally laparoscopic distal gastrectomy cases, is required in order to achieve optimum proficiency by two surgeons. There were no remarkable differences in the clinicopathological characteristics between laparoscopy-assisted distal gastrectomy and totally laparoscopic distal gastrectomy groups. The two groups were comparable in terms of open conversion, combined resection, morbidities, reoperation rate, hospital stay and time to first flatus (P>0.05). However, totally laparoscopic distal gastrectomy had a significantly shorter mean operation time than laparoscopy-assisted distal gastrectomy (P<0.01). We also found that intra-abdominal abscess and overall complication rates were significantly higher before the learning curve than after the learning curve (P<0.05).
Experience with 20~40 cases of totally laparoscopic distal gastrectomy is required to complete the learning curve. The use of totally laparoscopic distal gastrectomy after learning curve completion is a feasible and timesaving method compared to laparoscopy-assisted distal gastrectomy.
Laparoscopy; Stomach neoplasms; Anastomosis; Learning curve; Morbidity
Before laparoscopic gastrectomy for gastric cancer can be planned, it is very important to know the precise location of the tumor. The aim of this study was to evaluate 3 methods of predicting the exact location of the tumor: preoperative gastrofibroscopy (GFS), preoperative computed tomography gastroscopy (CT), and intraoperative gastroscopy-guided laparoscopy (Lap).
In this study, 15 patients were prospectively identified, and endoscopic clips were preoperatively placed on the proximal 1 cm of the tumor, at the angle on the greater curvature and opposite the angle on the greater curvature. The distances between the pylorus and the proximal tumor clip (PT), the angle clip (PA), the greater curvature clip (PG), and the gastroesophageal junction were measured by preoperative GFS, preoperative CT, intraoperative Lap, and visual inspection (Vis).
PT, PA, and PG values measured by preoperative GFS differed significantly from the Vis values (P < 0.01). However, preoperative CT measurements of PT, PA, and PG did not differ from the Vis values (P = 0.78, P = 0.48, and P = 0.53, respectively). Intraoperative Lap and Vis PT values differed by only 1.1 cm on an average (P = 0.10), but PA and PG values varied by 1.9 and 3.4 cm, respectively (P = 0.01 for both).
Endoscopic clipping combined with preoperative CT gastroscopy is more useful than preoperative GFS for preoperatively predicting the location of early gastric cancers and will be helpful for planning laparoscopic gastrectomy.
Stomach neoplasms; Laparoscopy; Gastrectomy; X-ray computed tomography; Gastroscopy
The feasibility of laparoscopic left hemihepatectomy for the management of intrahepatic duct (IHD) stones was evaluated.
The clinical data of 26 consecutive patients who underwent total laparoscopic left hemihepatectomy for IHD stones at Gyeongsang National University Hospital between January 2009 and June 2011 were reviewed retrospectively.
The mean operation time was 312.1 ± 63.4 minutes and the mean postoperative hospital stay was 11.8 ± 5.0 days. There were 2 cases of postoperative bile leakage and 3 cases of intra-abdominal fluid collection, which were successfully managed conservatively. Remnant stones were detected in 2 patients. The initial success rate of stone clearance was 92.3% (24 of 26). The remnant stones were located in the common bile duct in both cases and were removed by endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy. Therefore, the final success rate of stone clearance was 100% (26 of 26). During a mean follow-up of 22 months (range, 7 to 36 months), there was no patient with recurrent stone.
Laparoscopic surgery could be an effective treatment modality for the management of IHD stones in select patients.
Since laparoscopic liver resection was first introduced in 2001, Korean surgeons have chosen a laparoscopic procedure as one of the treatment options for benign or malignant liver disease. We distributed and analyzed a nationwide questionnaire to members of the Korean Laparoscopic Liver Surgery Study Group (KLLSG) in order to evaluate the current status of laparoscopic liver resection in Korea. Questionnaires were sent to 24 centers of KLLSG. The questionnaire consisted of operative procedure, histological diagnosis of liver lesions, indications for resection, causes of conversion to open surgery, and postoperative outcomes. A laparoscopic liver resection was performed in 416 patients from 2001 to 2008. Of 416 patients, 59.6% had malignant tumors, and 40.4% had benign diseases. A total laparoscopic approach was performed in 88.7%. Anatomical laparoscopic liver resection was more commonly performed than non-anatomical resection (59.9% vs 40.1%). The anatomical laparoscopic liver resection procedures consisted of a left lateral sectionectomy (29.3%), left hemihepatectomy (19.2%), right hemihepatectomy (6%), right posterior sectionectomy (4.3%), central bisectionectomy (0.5%), and caudate lobectomy (0.5%). Laparoscopy-related serious complications occurred in 12 (2.8%) patients. The present study findings provide data in terms of indication, type and method of liver resection, and current status of laparoscopic liver resection in Korea.
Laparoscopic Liver Resection; Laparoscopy; Anatomical Liver Resection; Liver Diseases; HCC
Clinical outcomes of papillary thyroid microcarcinoma (PTMC) vary. In general, age at diagnosis is an independent prognostic factor in conventional papillary thyroid carcinoma. However, it is unclear in patients of PTMC. The purpose of this study was to identify clinicopathologic features and prognostic factors of PTMC according to patients' age.
Five hundred twenty-seven patients who received thyroid surgery and diagnosed as having PTC between January 2001 and December 2009 were included. The clinical data were retrospectively analyzed.
We divided the patients into two groups; group I who were younger than 45 years, and group II who were 45 years old or older. The mean tumor size and incidences of neck lymph nodes involvement of group I was larger than group II. In group II, however, there were more patients who had multiple cancer foci and were body mass index ≥ 25 kg/m2. The overall incidence of recurrent disease was 3.2%. The incidence of recurrence was higher in group II (2.0% vs. 4.0%), without a statistical difference. In multivariate analysis, the significant risk factors of recurrence were male gender and multifocality in group I, and lymph node metastasis and multifocality in group II. In particular, the male gender and multifocality showed the highest odds ratio (OR) on each group (OR, 4.721 and 6.177).
The patients with PTMCs had different clinical features and prognostic factors according to age. Hence, clinicians should consider a different strategy for therapy and plan for follow-up according to age.
Papillary thyroid cancer; Microcarcinoma; Prognosis; Age
Emergency operations for perforated peptic ulcer are associated with a high incidence of postoperative complications. While several studies have investigated the impact of perioperative risk factors and underlying diseases on the postoperative morbidity after abdominal surgery, only a few have analyzed their role in perforated peptic ulcer disease. The purpose of this study was to determine any possible associations between postoperative morbidity and comorbid disease or perioperative risk factors in perforated peptic ulcer.
Materials and Methods
In total, 142 consecutive patients, who underwent surgery for perforated peptic ulcer, at a single institution, between January 2005 and October 2010 were included in this study. The clinical data concerning the patient characteristics, operative methods, and complications were collected retrospectively.
The postoperative morbidity rate associated with perforated peptic ulcer operations was 36.6% (52/142). Univariate analysis revealed that a long operating time, the open surgical method, age (≥60), sex (female), high American Society of Anesthesiologists (ASA) score and presence of preoperative shock were significant perioperative risk factors for postoperative morbidity. Significant comorbid risk factors included hypertension, diabetes mellitus and pulmonary disease. Multivariate analysis revealed a long operating time, the open surgical method, high ASA score and the presence of preoperative shock were all independent risk factors for the postoperative morbidity in perforated peptic ulcer.
A high ASA score, preoperative shock, open surgery and long operating time of more than 150 minutes are high risk factors for morbidity. However, there is no association between postoperative morbidity and comorbid disease in patients with a perforated peptic ulcer.
Peptic ulcer; Peptic ulcer perforation; Septic shock; Health status index
A trocar site hernia is a rare complication. We report a patient who had an abdominal wall mass at a previous trocar site after laparoscopic distal gastrectomy. It was diagnosed as omental herniation and fat necrosis. We conclude that patients with trocar site masses exhibiting fat density on a computed tomography scan could be followed up without surgery, and that fascial defects located at 10-mm or larger trocar sites should be closed whenever possible to prevent hernia formation.
Omentum; Hernia; Trocar; Gastric neoplasms; Laparoscopy
Excess weight and obesity have been associated with numerous diseases including thyroid cancer, but the relationship has been weak. The objective of this study was to evaluate the relationship of body sizes on thyroid nodules in healthy Korean population.
A total of 7,763 persons who underwent a health examination in our health examination center were included in this study. The epidemiologic factors, body size and thyroid ultrasound results were reviewed. We investigated the effects of body size on the presence of thyroid nodules and malignancy.
The incidence of thyroid nodules was 20.6%. In the group who were found to have thyroid nodules, mean height, weight and body surface area (BSA) were significantly smaller compared to the others. Especially, in the women, smaller height (less than 160 cm) and overweight (≥ 60 kg) were identified as independent risk factors for the presence of thyroid nodules. The patients with body mass index (BMI) subgroups of normal or overweight had a tendency to have thyroid nodules more frequently. The detection rate of thyroid cancer was 0.47%. The patients with thyroid cancer tended to be smaller in height and BSA than the others.
A higher frequency of thyroid nodules was associated with women and, older age. In women, there were significant correlations in height, weight and BMI subgroups to the presence of thyroid nodules.
Thyroid nodule; Body mass index; Body surface area
Laparoscopic resection of appendiceal mucoceles has recently been described, but the safety and efficacy are controversial. We present two cases of laparoscopic mucocelectomies involving 14 and 15 cm cystic masses originating from the appendix. The laparoscopic mucocelectomies were performed using four ports. From the beginning of the procedure, a laparoscopic bag was used to safely contain the mucocele, prevent rupture of the mucocele, and retract the mucocele. An endoscopic stapling device was used to transect the base of the cecum. Minimal handling was achieved by gravity and with the use of laparoscopic instruments. Laparoscopic appendectomies are widely performed for acute appendicitis, but laparoscopic resection is not routinely performed for an appendiceal mucocele because of the risk of perforation and subsequent pseudomyxoma peritonei. We report two cases of laparoscopic appendiceal mucocelectomies, which were performed safely with laparoscopic instruments and minimal manipulation.
Mucocele; Laparoscopy; Appendiceal neoplasm
The incidence of papillary thyroid carcinoma (PTC) is increasing worldwide. Positive associations between indices of body size and thyroid cancer have been reported. However, the relationships to cancer severities and/or behaviors are uncertain.
We performed a retrospective analysis of the data of patients who underwent total thyroidectomy due to PTC. The epidemiologic factor and pathologic report after operation were determined based on chart review. The relationships between indices of body size and these parameters were assessed.
Positive association between body mass index and T stage was found, but it was not statically significant. In neck lymph node metastasis, the group with metastasis had a tendency for larger mean height and weight, but significant difference was found only in height. However, in the multivariate analysis, the age and size of nodules were only identified as independent risk factors of neck lymph node metastasis (P = 0.000 and 0.019).
There was no independent association between indices of body size and stages of PTC in patients who underwent total thyroidectomy.
Body size; Height; Weight; Body mass index; Papillary thyroid carcinoma
The simultaneous occurrence of a gastrointestinal stromal tumor (GIST) and a gastric adenocarcinoma is uncommon, and has rarely been reported in the literature. The present report describes the case of a 74-year-old male patient who initially presented with an adenocarcinoma that had invaded the antral mucosa. Computed tomography then revealed the presence of a suspected GIST, in the form of a 2×2 cm mass at the hilum of the spleen. In view of the advanced age of the patient, a surgical approach that would minimize risk and maximize quality of life was preferred. The patient therefore underwent simultaneous laparoscopy-assisted distal gastrectomy for the adenocarcinoma and wedge resection for the GIST. This approach was only chosen after confirming that it would be possible to preserve three or more of the short gastric arteries that supply the area below the wedge resection site. This may be considered a feasible approach to the management of the simultaneous occurrence of a mid-to-low gastric body adenocarcinoma and a high gastric body GIST.
Gastrointestinal stromal tumors; Stomach neoplasms; Laparoscopy
Recent research has identified many genes and proteins that play specific roles in the process of systemic metastasis in various types of cancer. Rho GDP dissociation inhibitor 2 (RhoGDI2) has been shown to inhibit metastasis in human bladder cancer, but its role in breast cancer is controversial.
Materials and Methods
We examined the regulation and clinical significance of RhoGDI2 in Korean breast cancer patients by using proteomic approaches.
By using a proteomic approach, we observed an increased expression of RhoGDI2 in human breast cancer tissues when compared to that of the normal breast tissues, and we validated its up-regulation in an independent cohort of 8 breast cancer patients. The clinical implication of a RhoGDI2 expression was investigated in 57 breast cancer patients by performing immunohistochemistry. RhoGDI2 did not show a significant association with the tumor size, lymph node metastasis, the histologic grade or the hormone receptor status. However, the patients with RhoGDI2-expressing tumors had significantly shorter disease-free survival (p=0.043; hazard ratio, 3.87) and distant metastasis-free survival (p=0.039; hazard ratio, 5.15).
Our results demonstrated a potential role of RhoGDI2 as a poor prognostic marker as well as a potential therapeutic target. The pro-metastatic nature of RhoGDI2 shown in our study may indicate its organ-specific role in cancer metastasis.
Breast neoplasms; RhoGDI2 protein; Prognosis; Neoplasm metastasis; Proteomics
Angiosarcoma occurs very rarely in the gastrointestinal tract and can present great diagnostic difficulty, especially when it is associated with intraabdominal abscess or granulation tissue.
We report a case where the angiosarcoma was diagnosed after the occurrence of disseminated angiosarcoma and concurrent hemoperitoneum. The tumor developed in the fibrous capsule of a foreign body, which was possibly related to the previous appendectomy twenty years ago, and became a widely disseminated malignant neoplasm in the abdomen. After the operation, the patient's course was dominated by a fatal consumptive coagulapathy. Pathologic examination of the multiple intra-abdominal lesions showed the histological and immunohistological characteristics of the angiosarcoma.
Even though angiosarcoma in the gastrointestinal tract is extremely rare, when dealing with intraabdominal abscess or the gastrointestinal bleeding in patients who have undergone surgery or radiation therapy in the past, the possibility of angiosarcoma should be considered. To make the definite diagnosis of angiosarcoma and to avoid the misdiagnosis of foreign body granuloma, thorough histological examination and immunohistochemical staining may be prerequisite.