Chang In Choi

Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer

BackgroundEpithelial–mesenchymal transition (EMT) plays a significant role in tumor progression and invasion. Snail is a known regulator of EMT in various malignant tumors. This study investigated the role of Snail in gastric cancer.MethodsWe examined the effects of silenced or overexpressed Snail using lenti-viral constructs in gastric cancer cells. Immunohistochemical analysis of tissue microarrays from 314 patients with gastric adenocarcinoma (GC) was used to determine Snail’s clinicopathological and prognostic significance. Differential gene expression in 45 GC specimens with Snail overexpression was investigated using cDNA microarray analysis.ResultsSilencing of Snail by shRNA decreased invasion and migration in GC cell lines. Conversely, Snail overexpression increased invasion and migration of gastric cancer cells, in line with increased VEGF and MMP11. Snail overexpression (≥75% positive nuclear staining) was also significantly associated with tumor progression (P < 0.001), lymph node metastases (P = 0.002), lymphovascular invasion (P = 0.002), and perineural invasion (P = 0.002) in the 314 GC patients, and with shorter survival (P = 0.023). cDNA microarray analysis revealed 213 differentially expressed genes in GC tissues with Snail overexpression, including genes related to metastasis and invasion.ConclusionSnail significantly affects invasiveness/migratory ability of GCs, and may also be used as a predictive biomarker for prognosis or aggressiveness of GCs.

PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis.

Gastric adenocarcinoma is a common form of cancer associated with a poor prognosis. We analyzed microarray profiling data from 48 patients with gastric adenocarcinoma to characterize gastric cancer subtypes and identify biomarkers associated with prognosis. We identified two major subtypes of gastric adenocarcinoma differentially associated with overall survival (P = 0.025). Genes that were differentially expressed were identified using specific criteria (P < 0.001 and >1.5-fold); expression of 294 and 116 genes was enriched in good and poor prognosis subtypes, respectively. Genes related to translational elongation and cell cycle were upregulated in the poor prognosis group. Of these genes, upregulation of proteasome subunit beta type 8 PSMB8 and PDZ binding kinase PBK was confirmed by real-time reverse transcription-PCR analysis. PSMB8 or PBK knockdown had no effect on gastric cancer cell proliferation but suppressed cell migration and invasion, respectively. Furthermore, immunohistochemistry analysis of 385 gastric cancer patients revealed that increased nuclear expression of PSMB8 and PBK was correlated with depth of invasion, lymph node metastasis, and lower survival rates. Taken together, two gastric adenocarcinoma subtypes were predictive of prognosis. PSMB8 and PBK were predictive of gastric cancer prognosis and could be potential gastric cancer subtype-specific biomarkers.

Risk of lymph node metastasis in mixed-type early gastric cancer determined by the extent of the poorly differentiated component

AIM To predict the rate of lymph node (LN) metastasis in diffuse- and mixed-type early gastric cancers (EGC) for guidelines of the treatment. METHODS We reviewed 550 cases of EGC with diffuse- and mixed-type histology. We investigated the clinicopathological factors and histopathological components that influence the probability of LN metastasis, including sex, age, site, gross type, presence of ulceration, tumour size, depth of invasion, perineural invasion, lymphovascular invasion, and LN metastasis status. We reviewed all slides and estimated the proportions of each tumour component; pure diffuse type, mixed-predominantly diffuse type (diffuse > intestinal type), mixed-predominantly intestinal type (intestinal > diffuse type), and mixed diffuse = intestinal type. We calculated the extents of the respective components. RESULTS LN metastasis was observed in 12.9% (71/550) of early gastric cancers cases [15/288 mucosal EGCs (5.2%) and 56/262 submucosal EGCs (21.4%)]. Of 550 cases, 302 were diffuse-type and 248 were mixed-type EGCs. Of 248 mixed-type EGCs, 163 were mixed-predominantly diffuse type, 82 were mixed-predominantly intestinal type, and 3 were mixed diffuse = intestinal type. Mixed-type cases with predominantly diffuse type histology showed a higher frequency of LN metastasis (20.2%) than cases of pure diffuse type (9.3%) and predominantly intestinal type (12.2%) histology. We measured the dimensions of each component (intestinal and diffuse type) to determine the association of the extent of each component with LN metastasis in mixed-type gastric carcinoma. The total tumour size and the extent of poorly differentiated components was associated with LN metastasis, while that of signet ring cell components was not. CONCLUSION We recommend careful identification and quantitative evaluation of mixed-type early gastric cancer components after endoscopic resection to determine the intensity of the treatment.

Duodenal stump fistula after gastrectomy for gastric cancer: risk factors, prevention, and management

Purpose A duodenal stump fistula is one of the most severe complications after gastrectomy for gastric cancer. We aimed to analyze the risk factors for this problem, and to identify the methods used for its prevention and management. Methods We retrospectively reviewed the clinical data of 716 consecutive patients who underwent curative gastrectomy with a duodenal stump for gastric cancer between 2008 and 2013. Results A duodenal stump fistula occurred in 16 patients (2.2%) and there were 2 deaths in this group. Univariate analysis revealed age >60 years (odds ratio [OR], 3.09; 95% confidence interval [CI], 0.99–9.66), multiple comorbidities (OR, 4.23; 95% CI, 1.50–11.92), clinical T stage (OR, 2.91; 95% CI, 1.045-8.10), and gastric outlet obstruction (OR, 8.64; 95% CI, 2.61–28.61) to be significant factors for developing a duodenal stump fistula. Multivariate analysis identified multiple comorbidities (OR, 3.92; 95% CI, 1.30–11.80) and gastric outlet obstruction (OR, 5.62; 95% CI, 1.45–21.71) as predictors of this complication. Conclusion Multiple comorbidities and gastric outlet obstruction were the main risk factors for a duodenal stump fistula. Therefore, preventive methods and aggressive management should be applied for patients at high risk.

Single-incision intragastric resection for upper and mid gastric submucosal tumors: a case-series study

Purpose Laparoscopic gastric wedge resection is a standard treatment for removing gastric submucosal tumors (SMTs). So far, however, there have been few reports of single-incision laparoscopic intragastric wedge resection. Our aim was to describe this procedure and our experience with it. Methods From January 2010 to December 2013, a total of 21 consecutive patients with gastric SMTs underwent single-incision intragastric resection at our institution. Their clinicopathologic data were analyzed retrospectively. Results The patients consisted of nine men and 12 women with a mean age of 51.9 ± 12.9 years (22-69 years). Their mean body mass index was 22.6 ± 2.0 kg/m2. Mean tumor size was 2.4 ± 0.7 cm, with the following anatomic distribution: esophagogastric junction in three patients, fundus in twelve, upper body in three, and lower body in two. Mean operating time was 68.6 ± 12.0 minutes. There were no conversions to open surgery and no major intraoperative complications. Time to resumption of water intake was 1.4 ± 0.5 days. Mean hospital stay was 4.9 ± 1.7 days. There were no recurrences or deaths during the mean 19-month follow-up. Conclusion Single-incision intragastric wedge resection is a feasible and safe procedure. It is especially efficient for treating small endophytic gastric SMTs located on the upper and mid portion of the stomach.

Necrotizing soft tissue infection: analysis of the factors related to mortality in 30 cases of a single institution for 5 years

Purpose Necrotizing soft tissue infection is the infection of the soft tissue with necrotic changes. It is rare, but results in high mortality. We analyzed the characteristics of patients, prognosis, and mortality factors after reviewing 30 cases of a single hospital for 5 years. Methods From January 2009 to December 2013, 30 patients diagnosed with necrotizing fasciitis or Fourniers gangrene in Pusan National University Hospital were enrolled for this study. The following parameters were analyzed retrospectively: demographics, infection site, initial laboratory finding, initial antibiotics, isolated microorganisms, number of surgeries, time to first operation, length of intensive care unit, and total hospital stays. Results The overall mortality rate was 23.3%. Mean body mass index (BMI) of the survival group (24.7 ± 5.0 kg/m2) was significantly higher than the nonsurvival group (22.0 ± 1.4 kg/m2, P = 0.029). When BMI was less than 23 kg/m2, the mortality rate was significantly higher (P = 0.025). Two patients (6.7%) with chronic kidney disease requiring hemodialysis died (P = 0.048). Initial WBC count (>13×103/µL), CRP (>26.5 mg/dL), and platelet (PLT) count (<148×103/µL) were found to have negative impact on the prognosis of necrotizing soft tissue infection. Factors such as potassium level, blood urea nitrogen (>27.6 mg/dL), serum creatinine (>1.2 mg/dL) that reflected kidney function were significant mortality factors. Conclusion Patients with low BMI or abnormal values of WBC count, CRP, and PLT count reflecting the degree of infection or abnormal renal function will need more intensive care.

Atraumatic Liver Retraction Using Nelaton Catheters During Totally Laparoscopic Gastrectomy

This study introduces a novel technique for liver retraction during laparoscopic gastrectomy and assesses its impact on postoperative recovery. This study included 139 patients in whom Nelaton catheters (n=57) or Nathanson retractors (n=82) were used for liver retraction. Serum liver enzyme levels were measured preoperatively and on the first, second, third, fifth, and seventh postoperative days. Clinicopathologic features and postoperative recovery variables between the 2 groups were compared. The aspartate aminotransferase, alanine aminotransferase, and C-reactive protein levels were significantly lower (P<0.001, P<0.001, and P=0.007, respectively), and the day of first flatus, the day of initiating a soft diet, and the length of hospital stay were shorter in the Nelaton catheter U-shaped retractor group than those seen in the Nathanson retractor group (P=0.035, P=0.002, and P=0.024, respectively). Atraumatic liver retraction with Nelaton catheters is recommended in laparoscopic gastrectomy.

Risk factors for lymph node metastasis in mucosal gastric cancer and re-evaluation of endoscopic submucosal dissection

Purpose The selection of the appropriate treatment strategy for patients with mucosal gastric cancer (MGC) remains controversial. In the present study, we aimed to determine the risk factors for lymph node (LN) metastasis in MGC and reassess the role of endoscopic submucosal dissection (ESD). Methods We examined 1,191 MGC patients who underwent curative gastrectomy between January 2005 and December 2014. We determined the clinicopathologic risk factors for LN metastasis among the MGC patients. Results Among 1,191 patients with MGC, 42 patients (3.5%) had LN metastasis. Univariate analysis indicated that age ≤ 50 years (P = 0.045), tumor invasion to the muscularis mucosa (P < 0.001), tumor size > 2 cm (P = 0.014), presence of ulceration (P = 0.01), diffuse type as per Lauren classification (P = 0.005), and undifferentiated-type histology (P = 0.001) were associated with LN metastasis. Moreover, multivariate analysis indicated that tumor invasion to the muscularis mucosa (P = 0.001; odds ratio [OR], 4.909), presence of ulceration (P = 0.036; OR, 1.982), and undifferentiated-type histology (P = 0.025; OR, 4.233) were independent risk factors for LN metastasis. In particular, LN metastasis was observed in some MGC cases with indications for ESD, including absolute indications (1 of 179, 0.6%) and expanded indications (9 of 493, 1.8%). Conclusion Although MGC patients can be treated via ESD, we recommend that they undergo a more aggressive treatment strategy if they have tumor invasion to the muscularis mucosa, ulceration, or undifferentiated-type histology in the final pathology report.

Multimodal treatments of right gastroepiploic arterial leiomyosarcoma with hepatic metastasis: A case report and review of the literature

Leiomyosarcoma of an artery is very rare, and cases with hepatic metastasis are even rarer. We describe a case of a 70-year-old man who after follow up due to rectal cancer, presented with an intra-abdominal hypervascular mass and a hepatic mass. After surgical resection, it was diagnosed as a leiomyosarcoma of the right gastroepiploic artery with hepatic metastasis. Multiple metastases had recurred at the liver. He has survived more than 53 mo through multimodal treatments (three surgical resections, radiofrequency ablation, transarterial chemoembolization, chemotherapies, and targeted therapy). Multimodal treatments, including active surgical resection, may be helpful in the treatment of aggressive diseases such as arterial leiomyosarcoma with metastasis.

Importance of Timed and Detailed Evaluation of Kidney Transplantation Candidates

Kidney transplant recipients are at increased risk of cardiovascular morbidity and malignant neoplasm, and meticulous evaluation of potential recipients is needed to minimize risks of complications after transplantation. The purpose of this study was to analyze the results of preoperative assessments and document the importance of timed and detailed examinations. METHODS Medical records of patients evaluated as kidney transplant candidates from January 2015 to September 2017 were retrospectively collected and analyzed. RESULTS Of the 216 patients evaluated during the study period, 135 (62.5%) were male, 112 (51.9%) had diabetes mellitus, 163 (75.5%) had hypertension, 31 (14.4%) had a cardiovascular event history, and 7 (3.2%) had previous history of malignant neoplasms. Mean (SD) patient age was 50.7 (10.8) years. All 216 recipient candidates underwent echocardiography. Mean (SD) ejection fraction was 57.8% (5.9%), and 48 candidates (22.2%) showed regional wall motional abnormality. Coronary angiography was performed on 81 candidates, and in 57 (70.4%) of these, coronary artery disease was detected. Malignant neoplasms were detected in 10 (4.6%) candidates. Kidney transplantation was performed on 55 candidates. One recipient died of Pneumocystis jirovecii pneumonia at 15 months after kidney transplant, but there was no death-censored graft failure, newly detected malignant neoplasm, or cardiovascular event over a mean (SD) follow-up duration of 15.5 (8.6) months. CONCLUSION Evaluation of kidney transplant candidates resulted in diagnoses of malignant neoplasms in 4.6% of patients and coronary artery disease in 26.4% of patients. The results of this study demonstrate candidates for kidney transplant should undergo detailed preoperative evaluation.