Intramucosal gastric cancer (IGC) is associated with a very low risk of lymph node metastasis; thus it is the main candidate for minimally invasive surgical procedures, such as endoscopic submucosal dissection (ESD). Herein, we document an extraordinary case of IGC, which showed a very aggressive clinical course. A 66-year-old female underwent ESD for early gastric cancer. Histologically, the tumor consisted mainly of moderately differentiated adenocarcinoma measuring 1.6 cm in diameter, and the tumor was confined to the mucosa. Despite annual esophagogastroduodenoscopic follow-up, the tumor recurred, with wide metastasis to multiple lymph nodes and bones throughout the body after three years. Fluorescence in situ hybridization study demonstrated MET gene amplification as well as low grade polysomy 7 in both original and recurrent tumors. The clinical characteristics of metastatic IGCs and the implication of MET amplification are discussed.
Early gastric cancer; MET amplification; Metastasis
The histopathological diagnosis of gastric mucosal biopsy and endoscopic mucosal resection/endoscopic submucosal dissection specimens is important, but the diagnostic criteria, terminology, and grading system are not the same in the East and West. A structurally invasive focus is necessary to diagnose carcinoma for most Western pathologists, but Japanese pathologists make a diagnosis of cancer based on severe dysplastic cytologic atypia irrespective of the presence of invasion. Although the Vienna classification was introduced to reduce diagnostic discrepancies, it has been difficult to adopt due to different concepts for gastric epithelial neoplastic lesions. Korean pathologists experience much difficulty making a diagnosis because we are influenced by Japanese pathologists as well as Western medicine. Japan is geographically close to Korea, and academic exchanges are active. Additionally, Korean doctors are familiar with Western style medical terminology. As a result, the terminology, definitions, and diagnostic criteria for gastric intraepithelial neoplasia are very heterogeneous in Korea. To solve this problem, the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has made an effort and has suggested guidelines for differential diagnosis: (1) a diagnosis of carcinoma is based on invasion; (2) the most important characteristic of low grade dysplasia is the architectural pattern such as regular distribution of crypts without severe branching, budding, or marked glandular crowding; (3) if nuclear pseudostratification occupies more than the basal half of the cryptal cells in three or more adjacent crypts, the lesion is considered high grade dysplasia; (4) if severe cytologic atypia is present, careful inspection for invasive foci is necessary, because the risk for invasion is very high; and (5) other structural or nuclear atypia should be evaluated to make a final decision such as cribriform pattern, papillae, ridges, vesicular nuclei, high nuclear/cytoplasmic ratio, loss of nuclear polarity, thick and irregular nuclear membrane, and nucleoli.
Intraepithelial neoplasia; Stomach; Dysplasia; Adenoma; Carcinoma; Japanese; Western; Consensus; Vienna
Transferrin and alpha-1 antitrypsin are reportedly associated with liver fibrosis. We evaluated the usefulness of serum transferrin and alpha-1 antitrypsin as new liver fibrosis markers in patients with chronic hepatitis B.
The study included 293 patients with chronic hepatitis B who underwent a liver biopsy between October 2005 and June 2009, and who had no history of hepatocellular carcinoma. Serum markers and liver fibrosis stages were compared.
Univariate analysis revealed that age (P<0.001), serum platelet count (P<0.001), and serum alkaline phosphatase level (P=0.003) differed significantly between the patients with and without liver cirrhosis. Serum transferrin levels were significantly lower in advanced fibrosis than in mild fibrosis in both univariate analysis (P=0.002) and multivariate analysis (P=0.009). In addition, the serum transferrin level was significantly lower in cirrhotic patients than in noncirrhotic patients (P=0.020). However, the serum level of alpha-1 antitrypsin was not significantly associated with liver cirrhosis in patients with chronic hepatitis B.
Serum transferrin could be promising serum marker for predicting advanced liver fibrosis in patients with chronic hepatitis B.
Chronic hepatitis B; Liver cirrhosis; Transferrin; Alpha-1 antitrypsin
AIM: To investigate the clinicopathological risk factors for immediate post-operative fatal recurrence of hepatocellular carcinoma (HCC), which may have practical implication and contribute to establishing high risk patients for pre- or post-operative preventive measures against HCC recurrence.
METHODS: From June 1994 to May 2004, 269 patients who received curative resection for HCC were reviewed. Of these patients, those who demonstrated diffuse intra-hepatic or multiple systemic recurrent lesions within 6 mo after surgery were investigated (fatal recurrence group). The remaining patients were designated as the control group, and the two groups were compared for clinicopathologic risk factors.
RESULTS: Among the 269 patients reviewed, 30 patients were enrolled in the fatal recurrence group. Among the latter, 20 patients showed diffuse intra-hepatic recurrence type and 10 showed multiple systemic recurrence type. Multivariate analysis between the fatal recurrence group and control group showed that pre-operative serum alpha-fetoprotein (AFP) level was greater than 1 000 μg/L ( P= 0.02; odds ratio = 2.98), tumor size greater than 6.5 cm (P = 0.03; OR = 2.98), and presence of microvascular invasion (P = 0.01; OR = 4.89) were the risk factors in the fatal recurrence group. The 48.1% of the patients who had all the three risk factors and the 22% of those who had two risk factors experienced fatal recurrence within 6 mo after surgery.
CONCLUSION: Three distinct risk factors for immediate post-operative fatal recurrence of HCC after curative resection are pre-operative serum AFP level > 1 000 μg/L, tumor size > 6.5 cm, and microvascular invasion. The high risk patients with two or more risk factors should be the candidates for various adjuvant clinical trials.
Hepatocellular carcinoma; Hepatectomy; Early recurrence; Risk factors
Clinical usefulness of sentinel lymph node (SLN) mapping in colorectal cancer remains controversial. The aim of this study is to evaluate the accuracy of the SLN mapping technique using serial sectioning, and to compare the results between ex vivo and in vivo techniques.
From February 2011 to October 2012, 34 colon cancer patients underwent SLN mapping during surgical resection. Eleven patients were analyzed with the in vivo method, and 23 patients with the ex vivo method. Patient characteristics and results of SLN mapping were evaluated.
The SLN mapping was performed in 34 patients. Mean age was 67.3 years (range, 44-81 years). Primary tumors were located in the following sites: 13 in the right colon (38.2%) and 21 in the left colon (61.8%). SLN mapping was performed successfully in 88.2% of the patients. There was no significant difference in the identification rate between the two methods (90.9% vs. 87.0%, P = 1.000). Both the mapping methods showed a low sensitivity and high rate of skip metastasis.
This study showed that SLN evaluation using serial sectioning could not predict the nodal status with clinically acceptable accuracy despite the high detection rate.
Sentinel lymph node biopsy; Colon neoplasms
The role of peritoneal washing cytology in determining further treatment strategies after surgery for gastric cancer remains unclear. One reason for this is the fact that optimal procedures to increase the accuracy of predicting peritoneal metastasis have not been established. The aim of this study was to evaluate the efficacy of cytology using samples harvested from two different abdominal cavity sites during gastric cancer surgery.
Materials and Methods
We prospectively recruited 108 patients who were clinically diagnosed with locally advanced gastric cancer (higher than cT1 stage disease). Peritoneal washing fluids were collected from the pouch of Douglas and the subphrenic area. Patients were prospectively followed up for 2 years to determine the recurrence and survival rates.
Thirty-three patients dropped out of the study for various reasons, so 75 patients were included in the final analysis. Seven patients (9.3%) showed positive cytology findings, of whom, three showed peritoneal recurrence. Tumor size was the only factor associated with positive cytology findings (P=0.037). The accuracy and specificity of cytology for predicting peritoneal recurrence were 90.1% and 94.2%, respectively, whereas the sensitivity was 50.0%. The survival rate did not differ between patients with positive cytology findings and those with negative cytology findings (P=0.081).
Peritoneal washing cytology using samples harvested from two different sites in the abdominal cavity was not able to predict peritoneal recurrence or survival in gastric cancer patients. Further studies will be required to determine whether peritoneal washing cytology during gastric cancer surgery is a meaningful procedure.
Stomach neoplasms; Cytology; Peritoneum; Recurrence
Glycogenic hepatopathy (GH) is a rare complication of type 1 diabetes mellitus. We report the case of a 13-year-old diabetic female with poorly controlled blood sugar levels who presented with abdominal pain and distention 1 month in duration. She exhibited tender hepatomegaly, an elevated lipid profile, and elevated serum transaminase levels. Her liver histology was consistent with GH. The pathophysiology and/or underlying genetic background of GH remains unclear. The optimum treatment for GH is optimal glycemic control, and the prognosis is favorable. Clinicians should be aware of the possibility of GH and observe the clinical response to optimal glycemic control prior to invasive investigation.
Glycogenic hepaptopathy; Type 1 diabetes mellitus; Hepatomegaly
Tantalum-oxide-based bi-layered resistance-change memories (RRAMs) have recently improved greatly with regard to their memory performances. The formation and rupture of conductive filaments is generally known to be the mechanism that underlies resistive switching. The nature of the filament has been studied intensively and several phenomenological models have consistently predicted the resistance-change behavior. However, a physics-based model that describes a complete bi-layered RRAM structure has not yet been demonstrated. Here, a complete electro-thermal resistive switching model based on the finite element method is proposed. The migration of oxygen vacancies is simulated by the local temperature and electric field derived from carrier continuity and heat equations fully coupled in a 3-D geometry, which considers a complete bi-layered structure that includes the top and bottom electrodes. The proposed model accurately accounts for the set/reset characteristics, which provides an in-depth understanding of the nature of resistive switching.
Duodenal immune alterations have been reported in a subset of patients with functional dyspepsia (FD). The aim of this study was to investigate the effect of acute stress on immune cell counts and the expression of tight junction proteins in the duodenal mucosa.
Twenty-one male rats were divided into the following three experimental groups: 1) the nonstressed, control group, 2) the 2-hour-stressed group, and 3) the 4-hour-stressed group. Eosinophils, mast cells and CD4+ and CD8+ T lymphocytes in the duodenal mucosa were counted. The protein and mRNA expressions of occludin and zonula occludens-1 (ZO-1) were examined.
Eosinophils, mast cells and CD8+ T lymphocyte counts did not differ between the stressed and control groups. The number of CD4+ T lymphocytes and the protein and mRNA expressions of occludin and ZO-1 were significantly lower in the 4-hour-stressed group compared with the control group. The plasma adrenocorticotrophic hormone and cortisol levels of the 4-hour-stressed group were significantly higher than those of the control group.
Acute stress reduces the number of CD4+ T lymphocytes and the expression of tight junction proteins in the duodenal mucosa, which might be associated with the duodenal immune alterations found in a subset of FD patients.
Duodenum; Lymphocytes; Stress; Tight junction protein
In contrast to mitochondria in healthy cells, which utilize oxidative phosphorylation, malignant cells undergo elevated glycolysis for energy production using glucose. The objectives of this study were to evaluate whether the expression of various molecules, including pyruvate dehydrogenase kinase-1 (PDK-1), is involved in the altered glucose metabolism associated with gastric cancer prognosis and to assess the role of a therapeutic agent in targeting glucose metabolism in gastric cancer. Immunohistochemistry was performed on gastric cancer tissues obtained from 152 patients who underwent curative resection to assess the expression of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), hexokinase-2 (HK-2) and PDK-1. In an in vitro analysis, the lactate production and glucose uptake levels, cellular viability and 5-fluorouracil (5-FU) responses were evaluated before and after treatment with dichloroacetate (DCA), a PDK-1 inhibitor, in the MKN45 and AGS gastric cancer cell lines and in the non-cancerous HEK293 cell line. GLUT-1 and PDK-1 expression was significantly associated with tumor progression, although only PDK-1 expression was an independent prognostic factor for patients who received 5-FU adjuvant treatment. There was no significant difference in cell viability between the HEK293 and gastric cancer cell lines following DCA treatment. However, DCA treatment reduced lactate production and increased responsiveness to 5-FU in MKN45 cells, which expressed high levels of PDK-1 in comparison to the other cell lines. Thus, PDK-1 may serve as a biomarker of poor prognosis in patients with gastric cancer. In addition, PDK-1 inhibitors such as DCA may be considered an additional treatment option for patients with PDK-1-expressing gastric cancers.
gastric neoplasm; chemotherapy; pyruvate dehydrogenase; prognosis
The goal of this study was to assess the correlation between the Helicobacter pylori status of patients who underwent curative resection for gastric adenocarcinoma and their prognosis in Eastern societies where H. pylori infection is prevalent.
Between 2006 and 2007, 192 patients who had a curative resection for the treatment of gastric adenocarcinoma were enrolled in the study. Of these patients, 18 were excluded due to an inexact evaluation of the H. pylori status, thereby leaving 174 patients in the final analysis. Serologic testing for H. pylori was assessed using an enzyme-linked immunosorbent assay kit for immunoglobulin G, and the histological presence of H. pylori was identified using the Giemsa stain.
Of the 174 patients, 111 patients (63.8%) were confirmed for H. pylori infection. H. pylori status did not correlate with the overall or disease-free survival. For patients with stage III or IV gastric cancer, a positive H. pylori status was a significant predictive factor for recurrence over that of a negative H. pylori status (P = 0.019). Negative H. pylori status was a predictive factor for recurrence in multivariable analysis (relative risk, 2.724; 95 confidence interval, 1.192 to 6.228).
Helicobacter pylori status did not correlate with the clinicopathologic factors of gastric adenocarcinoma. However, a negative Helicobacter pylori status may be a predictive factor for recurrence in patients diagnosed with advanced gastric adenocarcinoma.
Helicobacter pylori; Stomach neoplasm; Prognosis; Survival
Higher cyclooxygenase 2 (COX-2) expression is often observed in aggressive colorectal cancers (CRCs). Here, we attempt to examine the association between COX-2 expression in therapy-refractory CRC, how it affects chemosensitivity, and whether, in primary tumors, it is predictive of clinical outcomes. Our results revealed higher COX-2 expression in chemoresistant CRC cells and tumor xenografts. In vitro, the combination of either aspirin or celecoxib with 5-fluorouracil (5-FU) was capable of improving chemosensitivity in chemorefractory CRC cells, but a synergistic effect with 5-FU could only be demonstrated with celecoxib. To examine the potential clinical significance of these observations, in vivo studies were undertaken, which also showed that the greatest tumor regression was achieved in chemoresistant xenografts after chemotherapy in combination with celecoxib, but not aspirin. We also noted that these chemoresistant tumors with higher COX-2 expression had a more aggressive growth rate. Given the dramatic response to a combination of celecoxib + 5-FU, the possibility that celecoxib may modulate chemosensitivity as a result of its ability to inhibit MDR-1 was examined. In addition, assessment of a tissue microarray consisting of 130 cases of CRCs revealed that, in humans, higher COX-2 expression was associated with poorer survival with a 68% increased risk of mortality, indicating that COX-2 expression is a marker of poor clinical outcome. The findings of this study point to a potential benefit of combining COX-2 inhibitors with current regimens to achieve better response in the treatment of therapy-refractory CRC and in using COX-2 expression as a prognostic marker to help identify individuals who would benefit the greatest from closer follow-up and more aggressive therapy.
Liver cirrhosis; Clinical practice guideline
A 48 year old woman was diagnosed with a huge cystic mass in her abdominal cavity. She complained of significant abdominal discomfort due to the mass. The abdominal computed tomography revealed a giant multi-lobulated mass, measuring 26×12 cm in size, adjacent to the lesser curvature of the stomach. In the operation field, the mass was found to originate from the lesser omentum, including the right and left gastric vessels and the vagus nerves, and to invade the lesser curvature of the stomach. For curative resection, distal subtotal gastrectomy with mass excision followed by gastroduodenostomy were performed. This mass was pathologically diagnosed to be a mesenteric cystic lymphangioma; in fact, the largest ever reported. The patient had no complications during the postoperative period and was discharged from the hospital on the seventh day after surgery.
Lymphangioma; Gastrectomy; Omentum
Epidural block is useful for chronic pain and thoracic surgery. However, there are several complications, which include vessels or dural puncture, pleural puncture, misplacement of epidural catheter and trauma to the spinal cord. We report a case of intercostal misplacement of an epidural catheter in a 66-year-old patient who scheduled for left thoracotomy.
Complication; Epidural catheter; Intercostal; Misplacement
Iliac screw fixation has been used to prevent premature loosening of sacral fixation and to provide more rigid fixation of the sacropelvic unit. We describe our technique for iliac screw placement and review our experience with this technique.
Thirteen consecutive patients who underwent spinopelvic fixation using iliac screws were enrolled. The indications for spinopelvic fixation included long segment fusions for spinal deformity and post-operative flat-back syndrome, symptomatic pseudoarthrosis of previous lumbosacral fusions, high-grade lumbosacral spondylolisthesis, lumbosacral tumors, and sacral fractures. Radiographic outcomes were assessed using plain radiographs, and computed tomographic scans. Clinical outcomes were assessed using the Oswestry Disability Index (ODI) and questionnaire about buttock pain.
The median follow-up period was 33 months (range, 13-54 months). Radiographic fusion across the lumbosacral junction was obtained in all 13 patients. The average pre- and post-operative ODI scores were 40.0 and 17.5, respectively. The questionnaire for buttock pain revealed the following: 9 patients (69%) perceived improvement; 3 patients (23%) reported no change; and 1 patient (7.6%) had aggravation of pain. Two patients complained of prominence of the iliac hardware. The complications included one violation of the greater sciatic notch and one deep wound infection.
Iliac screw fixation is a safe and valuable technique that provides added structural support to S1 screws in long-segment spinal fusions. Iliac screw fixation is an extensive surgical procedure with potential complications, but high success rates can be achieved when it is performed systematically and in appropriately selected patients.
Spinopelvic fixation; Iliac screws; Lumbosacral fusion; Outcome; Complication
This study was performed in order to assess whether acute stress can increase mast cell and enterochromaffin (EC) cell numbers, and proteinase-activated receptor-2 (PAR2) expression in the rat colon. In addition, we aimed to investigate the involvement of corticotrophin-releasing factor in these stress-related alterations. Eighteen adult rats were divided into 3 experimental groups: 1) a saline-pretreated non-stressed group, 2) a saline-pretreated stressed group, and 3) an astressin-pretreated stressed group. The numbers of mast cells, EC cells, and PAR2-positive cells were counted in 6 high power fields. In proximal colonic segments, mast cell numbers of stressed rats tended to be higher than those of non-stressed rats, and their PAR2-positive cell numbers were significantly higher than those of non-stressed rats. In distal colonic segments, mast cell numbers and PAR2-positive cell numbers of stressed rats were significantly higher than those of non-stressed rats. Mast cell and PAR2-positive cell numbers of astressin-pretreated stressed rats were significantly lower than those of saline-pretreated stressed rats. EC cell numbers did not differ among the three experimental groups. Acute stress in rats increases mast cell numbers and mucosal PAR2 expression in the colon. These stress-related alterations seem to be mediated by release of corticotrophin-releasing factor.
Corticotropin-releasing Factor; Enterochromaffin Cells; Irritable Bowel Syndrome; Mast cells; Receptor, PAR-2; Stress
The percutaneous placement of a totally implantable vascular access port via the subclavian vein is commonly used in patients with a need for multiple intravenous infusions such as administration of chemotherapy. Unfortunately, the use of central venous ports have been associated with adverse events that are hazardous to patients. Here we report the case of a 5-year-old child who died of catastrophic hemothorax after several attempts at insertion of an implantable subclavian venous access device and removal of an infected port. Massive hemothorax occurred on the side contralateral to unsuccessful attempts at insertion of a new port and ipsilateral to the removal of an infected port. We could not confirm the cause of death and hemothorax without autopsy, but we discuss several possible causes of massive hemothorax.
Cause of death; Hemothorax; Subclavian vein; Vascular access port
Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies.
Gastrointestinal Stromal Tumors; Epidemiology; Pathology; Prognosis
Behçet's disease (BD) is a multisystemic chronic inflammatory disease. It is characterized by recurrent oral and genital ulcers, uveitis, skin lesions and other manifestations, including neurologic, vascular, joint, and gastrointestinal ulcers of variable severity. Recurrent aphthous ulcer (RAU) represents a very common, but poorly understood, mucosal disorder. If a patient of RAU without any other typical symptoms of BD has gastrointestinal symptoms, it is difficult to distinguish this RAU from true BD with gastrointestinal involvement. Because pathognomonic clinical features and tools are absent, the differential diagnosis of these two diseases relies on the characteristic clinical features and the judgement of an experienced physician. Sixty-five out of a total 960 RAU patients and forty-four of 556 BD patients with gastrointestinal symptoms between January 1996 and December 2003 participated in this study. All were evaluated with esophagogastroduodenoscopy and colonoscopy. Clinical, endoscopic and histopathologic findings were analyzed and ELISA tests were conducted to detect serum levels of ASCA and pANCA. No significant difference was found between the two groups. Differential diagnosis between RAU with gastrointestinal symptoms and BD with gastrointestinal involvement requires further prospective, large-scale study.
Behçet's Syndrome; Stomatitis, Aphthous; Saccharomyces cerevisiae; Antibodies, Antineutrophil Cytoplasmic; Gastrointestinal Tract
Extraskeletal chondroma can occur in the hands, feet, head and neck. This tumor usually presents as a small solitary nodule. The histogenesis of the tumor is controversial, but some have suggested a metaplastic origin. Chondroma of the fallopian tube is very rare. There is only one report in English literature. The origin of this tumor can be subcoelomic mesenchyme of the tubal serosa or mesenchyme of the myosalpinx. We describe a case of chondroma arising from the serosal surface of the fallopian tube with a review of literature. A 30-yr-old woman visited hospital due to left adnexal mass. On operating finding, 2 x 3 cm sized nodular mass was noted on the left tubal serosal area. The excised mass showed multilobulated appearance covered with thin fibrous membrane. The cut surface was solid, grayish yellow, and myxoid with a focal gelatinous area. The microscopic finding showed islands and elongated lobules of mature benign cartilage without cytologic atypia.