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TNM stage still serves as the best prognostic marker in gastric cancer (GC). The next step is to find prognostic biomarkers that detect subgroups with different prognoses in the same TNM stage. In this study, the expression levels of epidermal growth factor receptor (EGFR) and cyclin D1 were assessed in 96 tissue samples, including non-tumorous tissue, adenoma, and carcinoma. Then, the prognostic impact of EGFR and cyclin D1 was retrospectively investigated in 316 patients who underwent R0 resection for GC. EGFR positivity increased as gastric tissue became malignant, and cyclin D1 positivity was increased in all the tumorous tissues. However, there was no survival difference caused by the EGFR positivity, while the cyclin D1-postive group had worse overall survival (OS) than the cyclin D1-negative group in stage I GC (10-year survival rate (10-YSR): 62.8% vs. 86.5%, p = 0.010). In subgroup analyses for the propensity score-matched (PSM) cohort, there were also significant differences in the OS according to the cyclin D1 positivity in stage I GC but not in stage II and III GC. Upon multivariate analysis, cyclin D1 positivity was an independent prognostic factor in stage I GC. In conclusion, cyclin D1 may be a useful biomarker for predicting prognosis in stage I GC.

Purpose We previously demonstrated that CD44v9 and Ki-67 played an important role in predicting poor prognosis of early gastric cancer (EGC). However, little is known about combined use of both biomarkers as prognostic biomarker. The present study was performed to investigate the significance of CD44v9 and Ki-67 expression as a combination biomarker for EGC. Materials and methods With tissue microarray for 158 EGC tissues, we performed immunohistochemical staining for CD44v9 and Ki-67. The whole patients were divided into three groups (group A, CD44v9- negative/Ki-67-low; group B, neither group A or C; and group C, CD44v9-positive/Ki-67- high). Its clinical significance was re-analyzed with adjustment via propensity score matching (PSM). For validation, we performed bootstrap resampling. Results The median follow-up duration was 90.4 months (range, 3.7 to 120.4 months). In the comparison according to CD44v9/Ki-67 expression, the combined use of the two biomarker clearly separated the three groups by 5-year survival rates (5-YSR, 96.3%, 89.8%, and 76.8% in group A, B, and C, respectively; p=0.009). After PSM, 5-YSR were 97.7% and 76.8% in group A+B and group C, respectively (p=0.002). Multivariable analysis demonstrated that group C had independently poor prognosis (hazard ratio, 9.137; 95% confidence interval, 1.187 to 70.366; p=0.034) compared with group A. Bootstrap resampling internally validated this result (p=0.016). Conclusion This study suggests that both positive CD44v9 and high Ki-67 expression are associated with poor prognosis in EGC, and the combined use of these markers provides better prognostic stratification than the single use of them.

Laparoscopic primary repair is one of the main procedures used for perforated gastric ulcers, and this technique requires reproducible and secure suturing. The aim of this study was to investigate the safety and efficacy of a novel continuous suture method with barbed sutures during laparoscopic repair for perforated peptic ulcers. Clinical data from 116 consecutive patients undergoing laparoscopic repair for perforated peptic ulcers were collected between November 2009 and October 2015. Continuous suturing with 15-cm-long unidirectional absorbable barbed sutures was used for laparoscopic repair in the study group, termed group V (n = 51). Patients who underwent laparoscopic repair with conventional interrupted sutures were defined as group C (n = 65). The complication and operative data were compared between groups. Although there was no difference between group V and group C in the overall complication rate (15.7% vs. 24.6%; p = 0.259), the complication rate related to suturing was lower (3.9% vs. 15.4%; p = 0.04) in group V. Group V showed rates of 0% for leakage, 2% for intra-abdominal fluid collection, and 2% for stricture; the corresponding rates in group C were 3.1, 7.7, and 4.6%, respectively. Regarding operative data, the total operation time (V vs. C, 87.7 min vs. 131.2 min), total suture time (7.1 min vs. 25.3 min), and suture time per stitch (1.2 min vs. 6.2 min) were significantly shorter in group V than in group C (p

An 84-year-old man was diagnosed with two synchronous adenocarcinomas, a Borrmann type IV advanced gastric adenocarcinoma in his antrum and a well-differentiated Borrmann type I carcinoma on the anterior wall of the higher body of his stomach. Pre-operatively, computed tomography of the abdomen revealed the presence of advanced gastric cancer with peri-gastric and para-aortic lymph node (LN) metastasis. He planned for palliative total gastrectomy owing to the risk of obstruction by the antral lesion. We performed a frozen biopsy of a para-aortic LN during surgery and found that the origin of the para-aortic LN metastasis was from undiagnosed prostate cancer. Thus, we performed radical total gastrectomy and D2 LN dissection. Post-operatively, his total prostate-specific antigen levels were high (227 ng/mL) and he was discharged 8 days after surgery without any complications.

Cervical lymph node metastasis is common in patients with papillary thyroid carcinoma (PTC).Salmonellaspecies are rarely reported as causative agents in focal infections of the head and neck. The cooccurrence of lymph node metastasis from PTC and a bacterial infection is rare. This report describes a 76-year-old woman with a cervical lymph node metastasis from PTC andSalmonellainfection of the same lymph node. The patient presented with painful swelling in her left lateral neck region for 15 days, and neck ultrasonography and computed tomography showed a cystic mass along left levels II–IV. The cystic mass was suspected of being a metastatic lymph node; modified radical neck dissection was performed. Histopathological examination confirmed the presence of PTC in the resected node and laboratory examination of the combined abscess cavity confirmed the presence ofSalmonella Typhi. Following antibiotic sensitivity testing of the culturedSalmonella Typhi, she was treated with proper antibiotics. Cystic lesions in lymph nodes with metastatic cancer may indicate the presence of cooccurring bacterial infection. Thus, culturing of specimen can be option to make accurate diagnosis and to provide proper postoperative management.

Biomarker is defined as biological variables that correlate with biologic outcome. This review will discuss investigations into gastric cancer (GC) biomarkers by proteomic analysis. Proteomic analysis consists of 3 steps. The first step is the digestion and separation process using 2-dimensional electrophoresis gel or liquid chromatography. The second step is mass analysis using mass spectrometry. The third step is protein identification using databases. Clinical validation of proteins identified can help estimate expressions of cancer tissue and cancer cell line using Western blot and immunohistochemistry. Researchers can validate the association between protein expression and clinical data (tumor stage, cell type, survival, and recurrence), which helps identify the possibility of biomarkers for GC. After clinical validation, the next step is functional analysis in vitro and in vivo. This step is commonly performed by knock-in and knock-out studies on the proliferation, migration, and invasion using the cancer cell line. Animal studies also provide indirect evidence for the role of the proteins in tumor growth and metastasis in vivo. In conclusion, the proteomic analysis is one of the useful methods for detecting biomarkers for GC. Multidisciplinary approaches to protein, DNA, RNA, and epigenetics are crucial to the investigation for molecular biomarkers for GC.

PURPOSE The present study is to investigate the significance of CD44 variant 9 (CD44v9) expression as a biomarker in primary gastric cancer. MATERIALS AND METHODS With various gastric tissues, we performed immunohistochemical staining for CD44v9. RESULTS The positive expression rates for CD44v9 in tumor, including adenoma, early gastric cancer (EGC), and advanced gastric cancer (AGC), were higher than those in non-tumor tissues (p=0.003). In addition, the higher expression for CD44v9 was observed as the tissue becomes malignant. In the analysis of 333 gastric cancer tissues, we found that positive expression rates for CD44v9 were higher in the intestinal type or well differentiated gastric cancer than in the diffuse type or poorly differentiated gastric cancer. Interestingly, the positive expression indicated poor prognosis in EGC (5-year survival rate [5-YSR] in stage I, 81.7% vs. 95.2%; p=0.013), but not in AGC (5-YSR in stage II, 66.9% vs. 62.2%; p=0.821; 5-YSR in stage III, 34.5% vs. 32.0%; p=0.929). Moreover, strong positive expression (3+) showed a trend suggesting worse prognosis only in EGC, and it appeared to be associated with lymph node metastasis. CONCLUSION This study suggests that CD44v9 may be a good biomarker for prognosis prediction and for chemoprevention or biomarker-driven therapies only for EGC.

Inflammation is associated with several tumor development and progression. However, these associations are not clear in well-differentiated thyroid carcinomas. We assessed whether NLR is a useful prognostic marker in patients with papillary thyroid carcinomas (PTC). The medical records of all patients who underwent thyroid surgery at a single institution between March 2005 and September 2012 were retrospectively evaluated; as a control group, patients who underwent routine health examinations in 2012 were also evaluated. Differences in mean NLR among patient groups were assessed, and clinical characteristics according to NLR quartile were evaluated in patients with PTC. The association between NLR and disease-free survival (DFS) in PTC patients was determined. NLR was significantly higher in the groups with than without thyroid nodules, but did not differ significantly in patients with benign and malignant thyroid nodules. Mean NLR was significantly higher in patients with solid or mixed thyroid than in patients with cystic nodules (1.75 ± 0.92 vs. 1.65 ± 0.74, p = 0.004). Patient follow-up ranged from 6 to 99 months. At 5-year follow-up, 11 patients had disease-specific events. We found that 5-year DFS rate was significantly worse in stages III and IV patients with NLR ≥1.5 than NLR

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

Infection with cagA-positive Helicobacter pylori is a risk factor for the development of severe gastritis and gastric cancer (GC). CagA protein is injected into gastric epithelial cells and deregulates a variety of cellular signaling molecules. Phospholipase D (PLD) is elevated in many different types of human cancers and has been implicated as a critical factor in inflammation and carcinogenesis. In this study, we show that infection with cagA-positive H. pylori in GC cells significantly induces PLD1 expression via CagA-dependent activation of nuclear factor κB (NFκB). Interestingly, the level of PLD1 protein and IκBα phosphorylation is aberrantly upregulated in H. pylori-infected human GC tissues. Infection with cagA-positive H. pylori and expression of CagA enhanced the binding of NFκB to the PLD1 promoter, and two functional NFκB-binding sites were identified within the PLD1 promoter. Rebamipide, a mucosal-protective antiulcer agent, abolished H. pylori cagA-induced PLD1 expression via inhibition of binding of NFκB to the PLD1 promoter, and also inhibited PLD activity. Moreover, rebamipide suppressed H. pylori-induced matrix metalloproteinase-9, interleukin-8 and activation-induced cytidine deaminase expression as well as invasion of GC cells through downregulation of PLD1. Our data suggest that H. pylori cagA targets PLD1 for invasion of GC cells, and rebamipide might contribute to the antitumorigenic effect of GC cells via inhibition of the H. pylori cagA-NFκB-PLD1 signaling pathway.

Inorganic pyrophosphatase (PPase) catalyzes the hydrolysis of pyrophosphate to form orthophosphate. Pyrophosphate can substitute for ATP under certain circumstances. We previously conducted a proteomic analysis to investigate tumor-specific protein expression in gastric cancer, and PPase was identified as a potential gastric tumor-specific marker; it was therefore selected for further study. Clinicopathological analysis, using proteomic analysis and immunohistochemistry, was used to validate PPase as a prognostic marker in gastric cancers. Proteomic analysis showed that PPase was overexpressed in patients with lymph node (LN) metastases and high tumor node metastasis (TNM) stages (p < 0.05). Based on immunohistochemistry, patients whose tumors overexpressed PPase had higher T stages, LN metastasis, a higher TNM stage, a higher cancer recurrence rate, and shorter survival times than patients whose tumors exhibited PPase underexpression (p < 0.05). Gain-of-function and loss-of-function approaches were employed to examine the malignant phenotypes of PPase-overexpressing or PPase-depleted cells. A decrease in PPase expression caused a significant decrease in gastric cancer cell migration and invasion in vitro, whereas forced overexpression of PPase enhanced migration but not invasion. Our findings indicate that PPase is involved in gastric tumor progression and that PPase may be a useful marker for poor prognosis of human gastric cancers.

Purpose: 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. Results: 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. Conclusions: 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.

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.

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.

The risk of recurrence after laparoscopy-assisted radical gastrectomy (LAG) was investigated. Clinical data of 398 consecutive patients who underwent radical gastrectomy with R0 resection for gastric cancer at Gyeongsang National University Hospital between January 2005 and December 2007 were reviewed retrospectively. Of the patients, 65.4% (n = 261) and 34.6% (n = 138) underwent LAG and open radical gastrectomy (OG), respectively. Of the LAG cases, 73.2% (n = 192), 10.7% (n = 28), 12.6% (n = 33), and 3.1% (n = 8) had stage I, II, III, and IV gastric cancer, respectively. All patients were followed up for a mean of 36.8 ± 13.7 months, and 14.6% (n = 58) had recurrence during the follow-up period. Univariate analysis revealed that tumor size, tumor–node–metastasis (TNM) stage, method of approach (LAG versus OG), and operation type were associated significantly with recurrence. Multivariate analysis revealed that only high TNM stage was significantly associated with recurrence (P = 0.00). While patients who underwent OG had higher incidence of recurrence than patients who underwent LAG, OG was not significantly associated with recurrence on multivariate analysis (P = 0.06). LAG and OG did not differ significantly in terms of recurrence, even when used in advanced gastric cancer cases. Multivariate analysis revealed that high TNM stage was significantly associated with recurrence. Thus, LAG appears to be a safe and feasible procedure that has the potential to be an alternative to open surgery, even for advanced gastric cancer.

Purpose: The aim of this study is to identify the potential tumor markers that function in carcinogenesis and tumor progression, thus providing important diagnostic and prognostic information. Experimental design: We performed 2-D gel electrophoresis and MALDI-TOF MS to investigate the differentially expressed proteins in 25 papillary thyroid carcinoma tissues. For validation of candidate proteins and investigation of clinical significance, we performed Western, Northern blot analysis and immunohistochemical staining. Results: Our proteomic analyses revealed significantly decreased annexin A3 expression in papillary thyroid carcinoma at both the protein and mRNA levels, compared with normal thyroid tissue. ANXA3 immunoreactivity was not significantly correlated with lymph node metastasis, multifocality, capsular invasion or perithyroidal extension in thyroid cancer. However, the tumor subgroup with a lymph node metastasis score of >3 displayed significantly lower ANXA3 expression than did subgroups with negative and ≤3 scores (p=0.001). Moreover, ANXA3 expression was markedly lower in large tumors (>1 cm in diameter) than in microcarcinomas (p=0.001). Conclusion and clinical relevance: Decreased expression of ANXA3 in papillary thyroid cancer supports the idea that ANXA3 may be an effective marker of microcarcinoma, and a negative predictor of papillary thyroid cancer progression.

This study investigated the factors affecting the length of the minilaparotomy incision (LOMI) in laparoscopy-assisted distal gastrectomy with Billroth I reconstruction. By using abdominal computed tomography scans, we measured the thickness of the rectus muscle (TRM), the thickness of the abdominal wall (TAW), and the distance from the gastroduodenal artery to the skin (GDAS) in 80 patients with early gastric cancer who had undergone surgery. There were positive correlations between the LOMI and body mass index (BMI), TRM, and TAW, and the LOMI increased significantly in patients with BMI > or =25 kg/m2, TAW > or =2.1 cm, and TRM > or =1.0 cm. These observations suggest that patients with two or more of the following clinical factors, BMI > or =25 kg/m2, TAW > or =2.1 cm, and TRM > or =1.0 cm, may require surgical procedures other than laparoscopy-assisted Billroth I, such as total laparoscopic intracorporeal Billroth I, Billroth II, or uncut Roux-en-Y reconstruction.

As more patients undergo diagnostic thyroid surgery, the development of posthemithyroidectomy hypothyroidism is becoming a major concern. We hypothesized that the preoperative thyrotropin (thyroid-stimulating hormone, TSH) level and ultrasonographically measured thyroid volume, both commonly available in thyroid nodule patients, may predict the development of posthemithyroidectomy hypothyroidism. Among the 132 patients who underwent hemithyroidectomy from January 2004 to January 2006, a total of 101 patients who were followed for more than a year were included in the analysis. Biochemical hypothyroidism developed in 37 patients (36.6%). Patients who developed postoperative hypothyroidism showed higher TSH levels (P

Sentinel-node navigation surgery (SNNS) for breast cancer and melanoma has been accepted as a reasonable oncologic surgery worldwide. On the other hand, in gastric cancers that do metastasize well to the lymph node, the use of SNNS has been approached with care and performed in only limited cases. Some obstacles still have to be overcome, such as the shortcomings of SN tracers and the technical limitations of laparoscopic SN detection. The aims of this study were to determine whether laparoscopic SNNS is possible, and which biopsy method is more suitable for SN tracers, in gastric cancer, preoperatively diagnosed asor =T2 and withor =4-cm-sized lesions.Between January 2005 and October 2006, 92 consecutive patients that underwent LSNNS, using a combined indocyanine green and (99m)Tc-labeled tin colloid technique, were prospectively studied. SNs were laparoscopically removed by using two biopsy methods: a basin dissection and pick-up method, with the results of these two SN biopsy methods then compared with the final diagnosis obtained from a permanent section.With the pick-up method, SNs were identified in 23 of 42 patients (54.8%); however, with basin dissection, the detection rate was 96% (48 of 50 patients). The average number of SNs detected by the two methods were 2.1 (range, 0-4) and 3.5 (range, 1-7), respectively. The sensitivities of the two methods were 66% (4/6) and 85.7% (12/14), with specificities of 100% (17/17) and 100% (34/34), respectively.In gastric cancer, it was possible to perform LSNNS. At this moment, we believe the laparoscopic basin dissection technique with a dual-tracer injection, followed by SN detection on the back table, will be a reasonable procedure for gastric cancer, owing to the shortcomings related to the dye and radioisotope, the so-called "stained lymphatic duct only" and "shine-through phenomenon."

Obesity is closely related to the development of colorectal cancer as well as other metabolic complications. We investigated the prognostic significance of visceral obesity and body mass index (BMI) in 161 resectable colorectal cancer patients. Ratios of visceral fat area (VFA) to subcutaneous fat area (SFA) were measured from the digital images of patients’ computed tomography taken before the surgery, and patients were divided into those with high and those with low VFA/SFA ratio according to the degree of proportional visceral adiposity, and into an overweight and a normal-weight group according to their preoperative BMI. The overweight group showed a borderline decrease in cumulative disease-free survival compared to the normal-weight group (P = 0.064). Patients with high VFA/SFA ratio (more than 50 percentiles) had significantly lower cumulative disease-free survival rate compared to patients with low VFA/SFA ratio (P = 0.008). BMI and visceral adiposity showed no influence on overall survival of patients. Increased visceral adiposity was a significant predictor of disease-free survival in patients with resectable colorectal cancer. The prognostic significance of visceral adiposity should further be determined in a larger set of patients.

The use of ultrasonography (USG) has become an essential part of endocrine surgical practice. We evaluated the value of USG in predicting malignancy of thyroid nodules. The accuracy of USG in 857 patients who underwent fine-needle aspiration (FNA) with or without surgery was analyzed in a prospective setting. The diagnostic accuracy of USG was compared to that of FNA and of combined models in 153 operated patients. The malignancy-predicting value of USG in follicular neoplasms and its relation to nodule size were also investigated. Sensitivity, specificity, and overall accuracy (OA) of USG were 84.9%, 95.5%, and 93.7%, respectively. In operated patients, USG had accuracy comparable to that of FNA and combined models (sensitivity 93.3%, specificity 90.6%, OA 92.0%) regardless of nodule size but showed a significant rate of indeterminate results (29.4%). For follicular neoplasms, the sensitivity, specificity, and OA of USG were 100%, 95.4%, and 96.1%, respectively, with indeterminate results for three malignant nodules (42.8%). This acceptable malignancy-predicting value of USG in thyroid nodules supports the potential role of USG for predicting malignancy in selected patients with thyroid nodules. However, the high rate of indeterminate results precludes it from being a standard independent diagnostic method for the present time.

Purpose This study aimed to evaluate the association between low body mass index (BMI) and morbidity after gastric cancer surgery. Methods A total of 1,805 patients were included in the study. These subjects had undergone gastric cancer surgery at a single institution between January 1997 and December 2013. Clinicopathologic and morbidity data were analyzed by dividing the patients into 2 groups: underweight patients (BMI < 18.5 kg/m2) and nonunderweight patients (BMI ≥ 18.5 kg/m2). Results The overall complication rate as determined by our study was 24.4%. Pulmonary complications occurred more frequently in the underweight group (UWG) than in the non-UWG (10.5% vs. 3.8%, respectively; P = 0.012). Multivariate analysis revealed two independent factors responsible for postoperative pulmonary complications—weight of the patients (UWG vs. non-UWG, 10.8% vs. 3.8%; P < 0.007) and stage of gastric cancer (early stage vs. advanced stage, 3.1% vs. 6.8%; P < 0.023). Multivariate analysis revealed that underweight (UWG vs. non-UWG, 10.8% vs. 3.8%, respectively, P < 0.007) and advanced cancer stage (early stage vs. advanced stage, 3.1% vs. 6.8%, respectively, P = 0.023) were significant risk factors for postoperative pulmonary complications. Conclusion We concluded that underweight patients had a higher pulmonary complication rate. Additionally, underweight and advanced cancer stage were determined to be independent risk factors for the development of postoperative pulmonary complications.

Tetraarsenic hexoxide (As4O6) has been used in Korean traditional medicine for the treatment of cancer since the late 1980's, and arsenic trioxide (As2O3) is currently used as a chemotherapeutic agent. Previous studies suggest that the As4O6-induced cell death pathway is different from that of As2O3 and its mechanism of anticancer activity remains unclear. Nuclear factor (NF)-κB is a well-known transcription factor involved in cell proliferation, invasion and metastasis. Hence, in the present study, we investigated the effects of As4O6 on NF-κB activity and NF-κB-regulated gene expression in vitro and in vivo. The cytotoxicity assay revealed that As4O6 inhibited the growth of SW620 cells in a dose-dependent manner, and the half maximal inhibitory concentration (IC50) was ~1 µM after a 48 h treatment. As4O6 suppressed NF-κB activation and suppressed inhibitory κBα (IκBα) phosphorylation stimulated by tumor necrosis factor (TNF). As4O6 also suppressed downstream NF-κB-regulated proteins involved in cancer anti-apoptosis, proliferation, invasion and metastasis. In addition, As4O6 marginally suppressed tumor growth and the anti-NF-κB activity was confirmed using an in vivo xenograft mouse model in which animals were injected with SW620 cells. The present study provides evidence that As4O6 has anticancer properties through suppression of NF-κB activity and NF-κB-mediated cellular responses.

We herein report a rare case of myositis ossificans originating from the abdominal rectus muscle, found in a 38-year-old woman who presented with a left upper abdominal mass. The mass was initially suspected to be a malignant neoplasm because no history of either operation or trauma existed for this patient. Moreover, the location of the mass was unusual and the enhancement patterns of the dynamic magnetic resonance images were similar to that of a malignant tumor. Based on the radiologic findings, a surgical exploration was performed. A well-circumscribed mass, which measured 3.2 x 2 cm, was found in the rectus muscle. Microscopic findings showed a typical zonal pattern with a fibroblastic central zone and a zone of ossification at the periphery. Although abdominal myositis ossificans is extremely rare, it is one of the causes of abdominal mass lesions and can be mistaken for a malignant tumor. Therefore, a thorough knowledge of the evolution of myositis ossificans is necessary and in cases with malignant suggestion on magnetic resonance imaging, like that seen in our case, we suggest that a surgical excision may be necessary for both the diagnosis and treatment.

The intraoperative assessment of lymph node status is important when performing limited surgery in gastric cancer patients. Currently available techniques for this assessment are frozen section, imprint cytology, and other molecular methods; most current studies use the frozen-section method. In the present study, we focused on the accuracy and feasibility of imprint cytology as a tool to assess lymph node status intraoperatively in gastric cancer surgery.Between April 2001 and March 2003, we performed imprint cytology of the sentinel nodes in 260 consecutive patients. After review by an experienced cytopathologist, the sensitivity, specificity, and overall accuracy of the method were determined.The time required for the intraoperative imprint cytology was 8 min, and the sensitivity, specificity, and overall accuracy were 52.2%, 88.8%, and 73.8%, respectively.Imprint cytology could be a useful technique for the assessment of lymph node status intraoperatively if the sensitivity and specificity can be improved to an acceptable level.

Purpose The relationship between serum cholesterol levels and mortality is complex. Serum cholesterol levels correlate positively with coronary artery disease, but some studies have suggested a negative relationship in cancer patients. Because the serum cholesterol levels are one of the most frequently assayed laboratory values, trends in the levels of cholesterol were investigated, in patients with gastric cancer and assumed a possible role in cancer screening. Materials and methods The serum cholesterol levels were retrospectively analyzed in a group of 220 patients, diagnosed with gastric cancer, and in 177 healthy subjects. Anthropometric (body mass index: BMI) and biochemical indices of their nutritional status were also determined in the study subjects. Statistical analyses were performed by analyses of variance and covariance, and a discriminant analysis. Results The levels of serum cholesterol, albumin, Hb and the BMI were significantly lower in the gastric cancer-patients group than in the healthy-subjects group. The serum cholesterol and Hb levels were shown to be independent of each other, when adjusted for the effects of the BMI. In the patients with gastric cancer the levels of cholesterol and Hb showed decreasing tendencies as did the tumor extension, as defined by the TNM system. Conclusion The serum cholesterol and Hb levels were significantly lower in patients with gastric cancer than in the healthy subjects, which seemed to be linked to the progression of gastric cancer. Therefore, further study is required for the serum cholesterol and Hb levels to be used as markers in cancer screening and its progression, in patients with gastric cancer.

Supplemental Digital Content is available in the text, Ki-67 protein is a cellular marker for proliferation. The role of Ki-67 as a prognostic biomarker has not been established in gastric cancer. The present study was performed to investigate the significance of Ki-67 expression as a biomarker in early gastric cancer (EGC). With tissue microarray for 320 patients with gastric cancer, we performed immunohistochemical staining for Ki-67. Its clinical significance was analyzed with adjustment via the propensity score-matching. For validation, we performed bootstrap resampling. The median follow-up duration was 72 months (range: 3–120 months). Ki-67-high group showed worse prognosis than Ki-67-low group in EGC (5-YSR, 78.9% vs 92.0%, P = .018), but not in advanced gastric cancer (AGC) (5-YSR, 58.5% vs 59.2%, P = .951). Interestingly, in the patients with well-differentiated histology, prognosis for Ki-67-high group was considerably worse than that for Ki-67-low group (5-YSR, 67.0% vs 94.4%, P = .012), but not in those with moderately differentiated (P = .504) and poorly differentiated histology (P = .905). In this cohort, there was a strong correlation between the proportion of EGC and well-differentiated histology (r = 0.215, P = .002). Multivariate analysis also revealed that the high-Ki-67 expression serves as a poor prognostic factor in EGC (HR 4.346, 95% CI 1.397–13.515, P = .011), especially in the well-differentiated histology, but not in all the patients (P = .171). Bootstrap resampling internally validated this result (P = .011). This study suggests that Ki-67 expression may be a good biomarker for prognosis prediction for EGC with well-differentiated histologic type.

Purpose Enolase is a cytoplasmic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in the glycolytic pathway. The aim of this study was to investigate whether the overexpression of neuron-specific enolase (NSE) can serve as a prognostic factor in patients with gastric cancer (GC). Materials and Methods To assess its prognostic value in GC, NSE expression was measured by immunohistochemistry in a clinically annotated tissue microarray comprising of 327 human GC specimens. Cytoplasmic NSE expression was scored from 0 to 4, reflecting the percentage of NSE-positive cells. Results In terms of histology as per the World Health Organization criteria (P=0.340), there were no differences between the NSE overexpression (NSE-OE) and NSE underexpression (NSE-UE) groups. The NSE-OE group showed a significantly lower rate of advanced GC (P

OBJECTIVE We investigated the prognostic importance of pre-operative Breast Imaging Reporting and Data System classification in ultrasound imaging. METHODS Histopathological differences and disease-free survival were analyzed in Breast Imaging Reporting and Data System classification subgroups. Univariate and multivariate analyses were used to identify the prognostic factors. RESULTS We identified 531 invasive breast cancer patients eligible for this study. Most patients classified as Breast Imaging Reporting and Data System 5 had large tumors and a higher rate of lymph node metastasis. However, hormonal receptor or HER-2 status did not differ according to Breast Imaging Reporting and Data System classification. During a median post-operative follow-up of 42.0 months, 43 patients were diagnosed with a disease-specific event. Disease-free survival was significantly lower in patients with Breast Imaging Reporting and Data System 5 than in patients with Breast Imaging Reporting and Data System 3-4. Subgroup analysis of patients with invasive breast cancer of Stage I showed that Breast Imaging Reporting and Data System 5 was an independent negative prognostic indicator of disease-free survival (hazard ratio 9.195; 95% confidence interval, 1.175-71.955; P = 0.035). CONCLUSIONS Breast Imaging Reporting and Data System classification might be considered as prognostic factors especially in Stage I breast cancer. Further confirmatory studies are needed.

The main requirements when performing laparoscopic local resection for early mucosal tumors of the stomach are a clearly defined cancer-free margin and precise tumor localization. In this study, a novel method for precise intraoperative tumor localization and appropriate resection in a porcine model is introduced: endoscopic submucosal cutting and light transmission (ESCLT).A total of 15 cases of laparoscopic local resection were performed in 6 pigs. The size of the target lesions was approximately 20 mm. The imaginary lesions were located in the high body anterior wall, posterior wall, lower body posterior wall, angle, and antrum anterior wall of the stomach. Mucosal marking around the lesions, mucosal precutting surrounding the marking, and submucosal cutting along the precutting line using white light endoscopy were sequentially performed. Next, an endoscopic light source was placed directly in front of the lesion. Exact oval-shaped submucosal cutting margins were identified via laparoscopy. Laparoscopic local resection was performed after the minimal distance from the stapler line to the submucosal cutting line was confirmed. The sizes of the mucosal marking, submucosal cutting line, and the entire resected mucosa and serosa were measured.The procedure was completed successfully in all pigs. Local resection was completed on all of the lesions. The mean endoscopic and laparoscopic procedure times were 26.1 and 12.7 min, respectively. The mean size of the resected specimens was: (i) marking lesion, 22 × 19.5 mm; (ii) submucosal cutting line, 26.7 × 23.2 mm; (iii) entire resected mucosa, 37 × 31 mm; and (iv) entire resected serosa, 41.7 × 33.1 mm. There was no intraoperative morbidity.ESCLT provides a precise and useful method of intraoperative tumor localization during laparoscopic local resection of the stomach in terms of minimizing the resection of normal stomach tissue and guaranteeing adequate mucosal safety margins.

Arsenic hexoxide (As4O6) has been used in Korean folk remedy for the treatment of cancer since the late 1980s. Evidence suggests that the anticancer effects of As4O6 are different from those of As2O3. Tumor necrosis factor-α (TNF-α) is generally increased in advanced cancer and is closely related to cancer progression, although it has cancer-killing effects. The reason is that TNF-α activates nuclear factor-κB (NF-κB) that is involved in cell proliferation, invasion, drug resistance and metastasis. In the present study, we investigated the effects of As4O6 on NF-κB activity, NF-κB-mediated cellular responses, and NF-κB-regulated gene expressions involved in metastasis at the concentrations of As4O6 where no cytotoxicity was observed. As4O6 suppressed NF-κB activation in both TNF-α-treated and control cells, and also suppressed IκB phosphorylation in a time-dependent manner, suggesting the suppression of NF-κB results, in part, from the inhibition of IκB degradation. We also confirmed the anti-NF-κB activity of As4O6 with synergism with TNF-α by augmenting caspase-8 activation. As4O6 also suppressed NF-κB activation induced by TNF-α, and some of the downstream NF-κB-regulated proteins involved in cancer proliferation, anti-apoptosis and metastasis. In conclusion, the present study demonstrated that As4O6 has anticancer properties by inhibiting NF-κB activation and NF-κB-regulated proteins at least in part through the inhibition of IκB phosphorylation, especially in the conditions of advanced cancer where TNF-α is highly secreted.

In advanced gastric cancer, laparoscopic management has been associated with trocar-site recurrence, even though laparoscopy-assisted gastrectomies have reported positive results to treat early-stage gastric cancer in the world. There are no reports of port-site recurrence after laparoscopic gastrectomy in the literature. In this paper, we present a case report of advanced gastric cancer with port-site recurrence 12 month after the initial operation. A wide excision of this recurrence was performed. Otherwise, the evaluation of metastasis in other sites remained negative at 18 months after the original operation. The laparoscopic surgeon should be aware of trocar-site recurrence when dealing with advanced gastric cancer.

Octamer transcription factor-1 (OCT-1) is a well-known transcription factor that is reportedly overexpressed in intestinal metaplasia and gastric carcinoma in the intestine. In this study, we investigated OCT-1 overexpression as a prognostic factor for gastric cancer. The association between OCT-1 overexpression (detected using immunohistochemistry) and clinicopathological features including survival was evaluated. In vitro gain-of-function approaches were utilized to assess the function of OCT-1 in malignancy. Analysis of OCT-1 expression in patients with gastric cancer with well-differentiated carcinoma as per the World Health Organization classification showed that OCT-1 overexpression was correlated with advanced tumor invasion (58.8 % of patients with advanced tumor invasion vs. 21.2 % of patients with early tumor invasion; p0.01), lymph node metastasis (63.9 % of patients with metastasis vs. 24.1 % of those without; p=0.015), and cancer recurrence (83.3 % of patients with recurrence vs. 25.4 % of those without; p0.01), as well as a lower survival rate (62.8 vs. 87.9 Mo; p0.01). However, there were no significant differences in the levels of OCT-1 expression in gastric cancer patients with other carcinoma types (p0.05). Furthermore, we found that the proliferation rate of OCT-1-overexpressing MKN-45 cells was higher than that of the control cells. OCT-1 overexpression may be a marker for poor prognosis in patients with well-differentiated gastric adenocarcinoma.

Total gastrectomy is performed for early gastric cancer in the upper body of the stomach because of the high complication rate of endoscopic submucosal dissection (ESD). The aims of the present animal study in pigs were to verify: (1) the feasibility of the trans-umbilical route compared with the trans-oral route in gastric upper body ESD; (2) the non-inferiority of single port laparoscopic lymph node dissection (LLND) compared with multiport LLND; and (3) the safety of 2-basin LLND (upper greater and lesser curvature). We separated the pigs (~40 kg each) into two groups: conventional and experimental (n = 5 per group). We performed ESD in the fundus and upper body anterior wall (UBAW) via the trans-oral route and multiport LLND in the conventional group, and via the trans-umbilical route and single port LLND in the experimental group. The completion rates, tissue weights, and specimen diameters of both routes showed no statistical differences in either the fundus or the UBAW. The operative time was shorter with the trans-umbilical route than with the trans-oral route in both areas (p

Ki-67 protein is a cellular marker for proliferation. The role of Ki-67 as a prognostic factor has not been established in gastric cancer. We previously demonstrated that CD44v plays an important role in EThe present study was performed toinvestigate the significance of Ki-67 expression as a biomarker in early gastric cancer (EGC), but not advanced gastric cancer (AGC). With the study, we foundthat there is correlation between CD44v and Ki67. Here, evaluated the clinical significance with tissue microarray of gastric cancer by performing immunohistochemical staining for Ki-67. Its clinical significance was analyzed with adjustment via the propensity score-matching. The median follow-up duration was 72 months (range: 3 - 120 months). Ki-67 positive group showed worse prognosis than Ki-67-negative group in EGC (5-YSR, 78.9% vs. 92.0%, p = 0.018), but not in advanced gastric cancer (AGC) (5-YSR, 58.5% vs. 59.2%, p = 0.951). Interestingly, in the patients with well-differentiated histology, prognosis for Ki-67-positive group was considerably worse than that for Ki-67-negative group (5-YSR, 67.0% vs. 94.4%, p = 0.012), but not in those with moderately differentiated (p = 0.504) and poorly-differentiated histology (p = 0.905). In this cohort, there was a strong correlation between the proportion of EGC and well-differentiated histology (r = 0.215, p = 0.002). Multivariate analysis also revealed that the positive-Ki- 67 expression serve as a poor prognostic factor in EGC (HR 4.346, 95% CI 1.397 - 13.515, p = 0.011), but not in all the patients (p = 0.171). With bootstrap resampling, we internally validated these results (p = 0.011). In conclusion, this study suggests that Ki-67 expression may be a good biomarker for prognosis prediction for EGC, but not for AGC. [This study was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare & Family Affairs, Republic of Korea.(0820050).] Citation Format: Won Sup Lee, Gyung Hyuck Ko, Se-Il Go, Jeong-Hee Lee, Sang-Ho Jeong, Young-Joon Lee, Soon Chan Hong, Woo Song Ha. Ki-67 serves as a prognostic marker in early gastric cancer, but not in advanced gastric cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4930.

Objective: Sonic hedgehog is produced in gastric epithelial cells and plays a crucial role in parietal cell function and the regulation of gastric epithelial cell differentiation. Emerging evidence suggests that the sonic hedgehog pathway is not only involved in the development of cancers but also in their progression and aggressiveness. Methods: To assess its prognostic value in gastric cancer, sonic hedgehog protein expression was measured by immunohistochemistry in a clinically annotated tissue microarray comprising 319 human gastric cancer specimens. Cytoplasmic sonic hedgehog expression was scored from 0 to 4, reflecting the percentage of sonic hedgehog-positive cells. Results: Specimens were classified into two groups according to their sonic hedgehog score: those with a score ranging from 0 to 3 were considered low expressers and those with a score of 4 were considered overexpressers. The sonic hedgehog overexpression group included more patients with early gastric cancer than the low sonic hedgehog expression group (25.9 vs. 74.1%, P ¼ 0.000). Sonic hedgehog expression was lower in patients with lymph node metastasis than in patients without lymph node metastasis (31.4 vs. 68.4%, P ¼ 0.02). Similarly, patients with a lower TNM stage showed significantly higher sonic hedgehog expression. In addition, the survival time of patients with sonic hedgehog overexpression was significantly prolonged (69.27+1.39 months) compared with that of patients with low sonic hedgehog expression (61.23+2.04 months, log-rank test, P ¼ 0.03). Conclusions: These results indicate that sonic hedgehog overexpression may be a marker of good prognosis in gastric cancer.

Purpose: 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). Methods: 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). Results: 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). Conclusion: 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.

Intrahepatic cholangiocarcinoma (ICC) is a rare primary malignant liver tumor with an extremely poor prognosis. Recently its incidence has increased, however, little attention has been directed to factors related to its molecular carcinogenesis, including oncogenes, tumor suppressor genes and cell cycle-related proteins. ICC is generally characterized by strong proliferation, invasion and early metastasis. These biological behaviors of ICC, with respect to the genetic and molecular aspects, remain to be clarified. In this study, we performed a proteomic analysis to identify the proteomic alterations associated with carcinogenesis of ICC. Protein expression profiles of sixteen cases of ICC were compared with those of adjacent non-involved bile duct tissue. Among the 151 protein spots that showed a statistically significant expression difference (P

The aim of the present study was to use a porcine model to compare one- and two-port transvaginal natural orifice transluminal endoscopic surgery (NOTES) with single-port laparoscopic surgery (SPLS) for sentinel node basin dissection.Three groups (n=3 per group) of healthy female pigs were subjected to lymph node dissection. For hybrid NOTES, an endoscope was inserted via the transvaginal route. For SPLS, a 5-mm 30° telescope with two-port laparoscopic instrument was inserted via the transumbilical port. The three methods were used to dissect the regions of the pig stomach that corresponded to four lymph node areas on the lesser curvature of the anterior wall and greater curvatures in humans.For two-port NOTES, SPLS, and one-port NOTES, the overall rates of complete dissection of the lymph node stations were 91.6 %, 83%, and 50%, respectively (P.05). The mean resected tissue weights were 49.3, 37.9, and 22.5 g, respectively (P=.03). The mean operation times for two-port NOTES (69.9 minutes) and SPLS (68 minutes) were shorter than that for one-port NOTES (99 min) (P.05).Two-port NOTES and SPLS are more feasible than one-port NOTES for sentinel node basin dissection in a porcine model. One-port NOTES is difficult to perform and requires long operation times; however, we foresee this operation as becoming more common in the future.

Purpose: 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. Results: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 diseasefree survival (p=0.043; hazard ratio, 3.87) and distant metastasis-free survival (p=0.039; hazard ratio, 5.15). Conclusion: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.

Although natural orifice extraction is now widely performed, there have been no reports of this procedure following subtotal gastrectomy for gastric cancer. This report describes trans-vaginal specimen extraction in four patients with early gastric cancer. The clinical data of four patients with early gastric cancer were reviewed. Totally laparoscopic subtotal gastrectomy and D1 + β lymph node dissection was performed using five trocars and a conventional procedure. Posterior colpotomy was performed by an experienced gynecologist, who retrieved the specimens in a retrieval bag via the trans-vaginal route. The colpotomy site was repaired immediately following specimen removal. Reconstruction was performed using the intracorporeal Billroth II method and an endo-GIA 60. Totally laparoscopic subtotal gastrectomy and trans-vaginal specimen extraction was successfully accomplished in all patients without intraoperative complications. The present technique may be a safe and feasible operative procedure for some limited groups of elderly female patients with early gastric cancer.