Inter-observer Reproducibility in the Pathologic Diagnosis of Gastric Intraepithelial Neoplasia and Early Carcinoma in Endoscopic Submucosal Dissection Specimens: A Multi-center Study

PURPOSE: The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. Materials and Methods: We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions. RESULTS: The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. CONCLUSION: The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.ope

A Case of Epstein-Barr Virus-associated Primary Gastric T-cell Lymphoma with Rapidly Progressive Endoscopic Features and Clinical Course

Primary gastric T-cell lymphoma is very rare. Only a few cases have been reported in the literature. Moreover, Epstein-Barr virus-associated primary gastric T-cell lymphoma is extremely rare. We report a case of Epstein-Barr virus-associated primary gastric T-cell lymphoma, which showed rapidly progressive endoscopic features. Three esophagogastroduodenoscopic examinations in a 26-day period revealed different findings at different locations. The lymphoma cells were positive for UCHL-1, but negative for L26 and Ki-1 in immunohistochemical staining.ope

Clinical Study of Multiple Intestinal Ulcerations and Perforations Caused by Methicillin-Resistant Staphylococcus aureus in Infants

Purpose: In recent years, the authors experienced a distinctive clinical entity of multiple intestinal ulcerations and perforations in infants. The purpose of this study was to describe the clinical characteristics of this entity, examine th possible pathogenesis and the effective treatment. Methods: Seven infants underwent abdominal exploration under suspicion of surgical abdomen and were noted to have multiple intestinal ulcerations and perforations without evidence of necrotizing enterocolitis by the members of the Korean Association of Pediatric Surgeons. The clinical courses, operative findings, bacterial cultures, pathologic findings, treatment and prognosis of these seven cases were evaluated retrospectively. Results: The characteristics of this entity are as follows : The initial presenting symptoms were all different. Despite conservative treatment with a broad spectrum of antibiotics, diarrhea and abdominal distention developed and progressively grew worse. At laparotomy, all patients exhibited numerous typical transverse linear ulcerative lesions with pin-point perforations scattered mainly in the small bowel. Histologic evaluations of the resected specimens revealed mucosal ulcerations with neutrophil infiltration, submucosal microabscesses and colonies of gram-positive cocci. Methicillin-resistant Staphylococcus aureus(MRSA) was the predominant organism cultured from the body fluid. Only two cases, the completely-resected one and the one immediately treated with vancomycin after operation, survived. Conclusion: We think this distinct clinical entity exhibiting multiple intestinal ulcerations and perforations is caused by MRSA occurring in infants. It has a high mortality because it is very difficult to diagnosis in young infants before laparotomy. Vancomycin is highly effective in treating MRSA, so we think the early diagnosis of this entity can make the treatment successful.ope

Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability

Many lines of evidence suggest that the retinoblastoma protein interacting zinc finger gene RIZ is a strong candidate for the tumor suppressor locus on 1p36, a region commonly deleted in many human cancers with chromosomal instability. In addition, a role for RIZ in tumors of the microsatellite instability pathway is suggested by frequent frameshift mutations in hereditary non-polyposis colorectal carcinomas. Here we studied RIZ mutations in sporadic cancers with microsatellite instability. Frameshift mutations in the two coding polyadenosine tracks of RIZ were found in 19 (48%) of 40 gastric carcinomas, 6 (33%) of 18 endometrial carcinomas, 14 (26%) of 51 of colorectal carcinomas, and 7 (54%) of 13 cell lines. Eleven tumor tissues showed biallelic inactivation of RIZ. In contrast, no frameshift mutations were found in 70 microsatellite stable tumors. These results suggest an important role for RIZ in sporadic cancers with microsatellite instability.ope

Tumor-Associated Alterations in Caspase-14 Expression in Epithelial Malignancies

PURPOSE: Caspase-14 is unique among caspase family proteases in that its proteolytic processing has been principally associated with epithelial cell differentiation rather than apoptosis or inflammation. We investigated caspase-14 expression in several types of human epithelial malignancy by immunohistochemistry, correlating results with stage, histologic grade, and patient survival. EXPERIMENTAL DESIGN: Tumor-associated alterations in caspase-14 expression were observed for cervical, ovarian, breast, gastric, and colon cancers. RESULTS: In cervical (n = 445), ovarian (n = 91), and colon (n = 106) specimens, expression of caspase-14 was significantly reduced in cancers compared with normal epithelium. Decreases in caspase-14 immunopositivity correlated with the histologic progression of cervical cancer (P < 0.0001, ANOVA). In localized gastric cancers, caspase-14 immunostaining was significantly lower in poorly differentiated tumors compared with well-differentiated tumors (P = 0.02, Pearson's chi(2) analysis). Lower caspase-14 expression was associated with advanced clinical stage in ovarian cancer (P = 0.04, ANOVA) and with shorter overall survival among ovarian cancer patients with serous tumors (n = 62) in both univariate (P = 0.005) and multivariate (P = 0.03) analysis. Lower caspase-14 expression correlated with shorter overall survival among patients with T(3)N(0)M(0) stage gastric cancers (n = 94; P = 0.006, log-rank test). In contrast to cervical, ovarian, and colon cancers, caspase-14 expression was increased in ductal carcinoma in situ and invasive cancers compared with normal mammary epithelium (P = 0.001, t test). CONCLUSIONS: The findings reveal tumor-specific alterations in caspase-14 expression and suggest that differences in its expression may define subsets of epithelial cancers with distinct clinical behaviors.ope

A case of primary retroperitoneal mucinous cystadenoma with successful Laparoscopic resection

Primary retroperitoneal mucinous cystadenoma is a extremely rare tumor, reported exclusively in women. There have been about 30 cases of reports in worldwide literature, and only 3 reported cases in Korea to date. Because this tumor is histologically heterogenous and may have metastatic potential, a careful surgical excision with a thorough histopathological examination is needed, and close follow-up is mandatory. While transabdominal laparotomy and complete surgical excision is a standard of treatment, there had been a case-report of laparoscopic resection in 1998. Herein we report a case of primary retroperitoneal mucinous cystadenoma, which was successfully resected by laparoscopy, in 28-year-old woman.ope

A Case of Isolated Adenomatous Polyp of Rectum in a Child -Tubulovillous adenoma

Isolated rectal adenomatous polyp without genetic background is rarely found in children. A 4-year and 5 month-old girl was admitted for intermittent bloody stools lasting 4 months. A 1.5×1.2cm 1.5×1.2cm sized rectal polyp was found by air contrast barium enema. Endoscopic polypectomy was performed without complications. In histopathologic examination, it was found to be a tubulovillous adenoma. Typical radiologic, colonoscopic, and pathological pictures are presented.ope

Analysis of Apoptosis Protein Expression in Early-Stage Colorectal Cancer Suggests Opportunities for New Prognostic Biomarkers

PURPOSE: Although most stage II colon cancers are potentially curable by surgery alone, approximately 20% of patients relapse, suggesting a need for establishing prognostic markers that can identify patients who may benefit from adjuvant chemotherapy. We tested the hypothesis that differences in expression of apoptosis-regulating proteins account for differences in clinical outcome among patients with early-stage colorectal cancer. EXPERIMENTAL DESIGN: Tissue microarray technology was employed to assay the expression of apoptosis-regulating proteins by immunohistochemistry in 106 archival stage II colorectal cancers, making correlations with disease-specific survival. The influence of microsatellite instability (MSI), tumor location (left versus right side), patient age, and gender was also examined. RESULTS: Elevated expression of several apoptosis regulators significantly correlated with either shorter (cIAP2; TUCAN) or longer (Apaf1; Bcl-2) overall survival in univariate and multivariate analyses. These biomarkers retained prognostic significance when adjusting for MSI, tumor location, patient age, and gender. Moreover, certain combinations of apoptosis biomarkers were highly predictive of death risk from cancer. For example, 97% of patients with favorable tumor phenotype of cIAP2(low) plus TUCAN(low) were alive at 5 years compared with 60% of other patients (P = 0.00003). In contrast, only 37% of patients with adverse biomarkers (Apaf1(low) plus TUCAN(high)) survived compared with 83% of others at 5 years after diagnosis (P< 0.0001). CONCLUSIONS: Immunohistochemical assays directed at detection of certain combinations of apoptosis proteins may provide prognostic information for patients with early-stage colorectal cancer, and therefore could help to identify patients who might benefit from adjuvant chemotherapy or who should be spared it.ope

Noninvasive molecular biomarkers for the detection of colorectal cancer.

Colorectal cancer (CRC) is the third most common malignancy in the world. Because CRC develops slowly from removable precancerous lesions, detection of the disease at an early stage during regular health examinations can reduce both the incidence and mortality of the disease. Although sigmoidoscopy offers significant improvements in the detection rate of CRC, its diagnostic value is limited by its high costs and inconvenience. Therefore, there is a compelling need for the identification of noninvasive biomarkers that can enable earlier detection of CRC. Accordingly, many validation studies have been conducted to evaluate genetic, epigenetic or protein markers that can be detected in the stool or in serum. Currently, the fecal-occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics combined with developments in other relevant fields will lead to the discovery of novel non invasive biomarkers whose usefulness will be tested in larger validation studies. Here, noninvasive molecular biomarkers that are currently used in clinical settings and have the potential for use as CRC biomarkers are discussedope

Putative chromosomal deletions on 9P, 9Q and 22Q occur preferentially in malignant gastrointestinal stromal tumors.

To characterize the type of genetic alterations in gastrointestinal stromal tumors (GISTs), we performed a comprehensive allelotype study of 14 GISTs (2 benign, 7 borderline and 5 malignant) by polymerase-chain-reaction and loss-of-heterozygosity (PCR-LOH) analysis using 102 microsatellite markers, and compared the results with comparative-genomic-hybridization (CGH) analysis. Among the 38 evaluated chromosomal arms, 16 (42.1%) showed LOH in at least one patient. Most frequent LOH was observed at chromosome 14p and 14q (9/14, 64%) and this was demonstrated in all types of GISTs (50% in benign, 71% in borderline and 80% in malignant). Additional chromosomal deletions were found in several chromosomal arms. Among them, deletions on chromosomal arms of 22q (3/14, 21.4%), 9p (2/14, 14.3%) and 9q (2/14, 14.3%) were the most frequent, and were detected only in malignant GISTs both by PCR-LOH and by CGH analysis. Additionally, 2 malignant GISTs with LOH on 9p showed homozygous deletions in the restricted area of 9p by multiplex PCR-LOH analysis. Thus, several putative chromosomal changes were preferentially present in malignant GISTs but rare in benign and borderline GISTs. These findings suggest that accumulated chromosomal changes may contribute to the progression and/or malignant transformation of GISTs.ope