Koon Hee Han

Gastric Micropapillary Carcinoma: A Distinct Subtype With a Significantly Worse Prognosis in Tnm Stages I and Ii

Micropapillary carcinoma (MPC) is an aggressive variant of adenocarcinoma, with a high incidence of lymph node (LN) metastasis in several organs, although not yet well described in the stomach. Thus, we compared the clinicopathologic characteristics, including survival data and immunohistochemical profiles of cell adhesion molecules (E-cadherin, &bgr;-catenin, IQGAP-1, and CD44v6), of MPCs with those of adenocarcinomas lacking MPC components (non-MPC) in the stomach. We compared 72 MPC cases with 160 non-MPC cases. Most gastric MPCs arose from tubular or papillary adenocarcinomas, and the proportion of MPC components ranged from 5% to 80%. MPCs were characterized by more frequent lymphovascular invasion and LN metastasis (P<0.0001), higher tumor node metastasis (TNM) stage (P=0.019), advanced age (>65 y; P<0.0001), and more frequent CD44v6 and aberrant &bgr;-catenin expression (P<0.0001). The overall 5-year survival rates for patients with MPC were significantly worse than those with non-MPC (30% vs. 67%; P=0.002). Furthermore, when it was stratified by TNM stages, the survival rates were distinguished between MPC and non-MPC groups in TNM stages I to II (P=0.0003), but not in TNM stages III to IV. The presence of the MPC component was associated with a significantly worse patient survival by univariate (P=0.0003) and multivariate (P=0.04) analyses in patients with stages I to II gastric carcinoma. In conclusion, recognition of the MPC component in gastric carcinoma is critical, because the MPC component is associated with more frequent LN metastasis and a worse prognosis, especially in stages I to II gastric cancer.

Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells.

Colorectal micropapillary carcinoma has recently been reported as an aggressive variant of adenocarcinoma with a high incidence of lymph node metastasis, but has not been well investigated in terms of survival analysis. This study analyzed the clinicopathological characteristics, including survival data, of the patients with micropapillary carcinoma. We hypothesized that the aggressive features of micropapillary carcinoma might be related to the presence of more tumor cells with stem cell phenotype in colorectal cancer. Fifty-five (10%) micropapillary carcinoma cases were identified among 561 cases of colorectal cancer. We compared the clinicopathological characteristics, including survival data and immunohistochemical profiles of stem cell markers (SOX2, NOTCH3, CD44v6, CD166, ALDH1) of micropapillary carcinomas with those of randomly selected 112 conventional adenocarcinomas lacking micropapillary carcinoma components (non-micropapillary carcinoma) in the colorectum. To exclude the possibility of dilution of control group by patients with microsatellite instability-high carcinomas, we divided non-micropapillary carcinomas into microsatellite instability-high carcinoma and microsatellite stable tumors. Micropapillary carcinomas were characterized by more frequent lymphovascular invasion (P<0.0001) and lymph node metastasis (P<0.0001), higher pathological T and tumor node metastasis stages (P=0.047 and P=0.001), and more frequent SOX2 (P=0.038) and NOTCH3 expressions (P=0.005). Overall 5-year survival rate for patients with micropapillary carcinoma (37%) was significantly lower than for microsatellite instability-high carcinoma and microsatellite stable carcinoma patients (92 and 72%, P<0.0001). The presence of the micropapillary carcinoma component was shown to be associated with a significantly worse survival rate in univariate (P<0.0001) and multivariate (P=0.003, Cox hazard ratio 2.402) analyses. In conclusion, recognition of the micropapillary carcinoma component in colonic adenocarcinoma is very important, because the micropapillary carcinoma has been associated with a significantly worse prognosis. We also found a higher expression rate of cancer stem cell markers in micropapillary carcinomas, suggesting their potential contribution to the survival disadvantage of micropapillary carcinoma.

The Relevance of Serum Ghrelin Concentration to Severity of Acute Pancreatitis

BACKGROUND/AIMS Ghrelin has recently been reported as exerting a protective effect in the damaged pancreas in rats. We investigated the correlation between severity of acute pancreatitis and serum ghrelin concentrations. METHODS Blood samples were collected three times (at admission, after 48 hours, and at discharge) from patients admitted with acute pancreatitis. We divided the patients into nonrisk and risk groups. The risk group was defined as the presence of at least one of following risk factors for severe acute pancreatitis: Ransons score >/=3, acute physiology and chronic health evaluation (APACHE) II score >/=8, C-reactive protein (CRP) >/=150 mg/L, and CT severity index (CTSI) >/=4. Serum ghrelin concentrations were measured with RIA kit and analyzed based on clinical and biochemical parameters. RESULTS A total of 53 patients was enrolled in this study: 28 in the nonrisk group and 25 in the risk group. At admission, the ghrelin concentration was significantly higher in the risk group (286.39+/-272.19 vs 175.96+/-138.87 pg/mL [mean+/-SD], p=0.049). However, the ghrelin concentration did not differ significantly between the two groups after 48 hours (p=0.450) and at discharge (p=0.678). The overall ghrelin concentration was significantly lower at admission than at discharge (240.65+/-247.96 vs 369.41+/-254.27 pg/mL, p=0.001). CONCLUSIONS Patients with risk factors for severe acute pancreatitis have higher serum ghrelin concentrations.

A Case of Gastric Inverted Hyperplastic Polyp Found with Gastritis Cystica Profunda and Early Gastric Cancer

A gastric inverted hyperplastic polyp is a rare type of gastric polyp and is characterized by downward growth of a variety of mucosal components into the submucosa. The polyp consists of columnar cells resembling foveolar epithelium and pyloric gland epithelium and can coexist with gastritis cystica profunda. Frequently, adenocarcinoma can coexist, but the relation is not clear. A 77-year-old male underwent endoscopic submucosal dissection due to early gastric cancer. A gastric inverted hyperplastic polyp was found in the removed specimen and gastric cystica profunda was also found. We report a case of gastric inverted hyperplastic polyp coexisting with gastric cystica profunda and gastric adenocarcinoma.

Colon Cancer After Acute Diverticulitis Treatment

Diverticulitis is the most common clinical complication of diverticular disease, affecting 10-25% of the patients with diverticula. The prevalences of diverticulitis and colon cancer tend to increase with age and are higher in industrialized countries. Consequently, diverticulitis and colon cancer have been reported to have similar epidemiological characteristics. However, the relationship between these diseases remains controversial, as is the performance of routine colonoscopy after an episode of diverticulitis to exclude colon cancer. Recently, we experienced three cases of colon cancer after treating acute diverticulitis, based on which we suggest the importance of follow-up colonoscopy after acute diverticulitis.

A Case of a Mucinous Adenocarcinoma Arising from a Rectal Diverticulum

The occurrence of an adenocarcinoma arising from a rectal diverticulum that causes mechanical ileus is very rare. Recently, we diagnosed a case of a mucinous adenocarcinoma in a rectal diverticulum after an emergent abdominal perineal resection and permanent colostomy by laparotomy. Here, we present a case report and a review of the literature.

Proteomic Analysis of Colonic Mucosal Tissue from Tuberculous and Ulcerative Colitis Patients

Changes in the expression profiles of specific proteins leads to serious human diseases, including colitis. The proteomic changes related to colitis and the differential expression between tuberculous (TC) and ulcerative colitis (UC) in colon tissue from colitis patients has not been defined. We therefore performed a proteomic analysis of human TC and UC mucosal tissue. Total protein was obtained from the colon mucosal tissue of normal, TC, and UC patients, and resolved by 2-dimensional electrophoresis (2-DE). The results were analyzed with PDQuest using silver staining. We used matrix-assisted laser desorption ionization time-of-flight/time-of-flight spectrometry (MALDI TOF/TOF) to identify proteins differentially expressed in TC and UC. Of the over 1,000 proteins isolated, three in TC tissue and two in UC tissue displayed altered expression when compared to normal tissue. Moreover, two proteins were differentially expressed in a comparative analysis between TC and UC. These were identified as mutant β-actin, α-enolase and Charcot-Leyden crystal protein. In particular, the expression of α-enolase was significantly greater in TC compared with normal tissue, but decreased in comparison to UC, implying that α-enolase may represent a biomarker for differential diagnosis of TC and UC. This study therefore provides a valuable resource for the molecular and diagnostic analysis of human colitis.

Mucosal Incision and Forceps Biopsy for Reliable Tissue Sampling of Gastric Subepithelial Tumors

Background/Aims The diagnostic efficacy of current tissue sampling techniques for gastric subepithelial tumors (SETs) is limited. Better tissue sampling techniques are needed to improve pathological diagnosis. The aim of this study was to evaluate the safety and efficacy of a new technique, mucosal incision and forceps biopsy, for reliable tissue sampling of gastric SETs. Methods This study enrolled 12 consecutive patients who underwent mucosal incision and forceps biopsy of gastric SETs between November 2011 and September 2014 at Gangneung Asan Hospital. The medical records of patients were reviewed retrospectively. The safety and diagnostic yield of this method were evaluated. Results By performing mucosal incision and forceps biopsy, we were able to provide a definitive histological diagnosis for 11 out of 12 cases. The pathological diagnoses were leiomyoma (3/11), gastrointestinal stromal tumor (GIST; 2/11), lipoma (2/11), schwannoma (1/11), and ectopic pancreas (3/11). In cases of leiomyoma (n=3) and GIST (n=2), tissue samples were of sufficient size to allow immunohistochemical staining. In addition, the mitotic index was evaluated in two cases of GIST. There were no procedure-related complications. Conclusions Mucosal incision and forceps biopsy can be used as one of several methods to obtain adequate tissue samples from gastric SETs.

Liver Metastasis of Early Gastric Cancer with Mixed Histology after Endoscopic Submucosal Dissection

The Japanese Classification of Gastric Carcinoma histologically classifies endoscopically resected gastric cancer into differentiated and undifferentiated types according to the presence or absence of tubular structures on histology. The former includes papillary adenocarcinoma and tubular types, and the latter includes poorly differentiated adenocarcinoma, signet ring cell carcinoma and mucinous adenocarcinoma. However, gastric cancer sometimes contains a mixture of differentiated and undifferentiated components, and the clinical outcomes of the histological mixture are unknown, especially following endoscopic resection of early gastric cancer (EGC). This case was within the guideline indications for endoscopic submucosal resection (ESD), although it contained a partly signet ring cell carcinoma component; it recurred after 19 months with multiple lymph node and liver metastases. This case shows that additional surgical resection after ESD should be performed for patients with any mixed signet ring cell component, even in mild or moderately differentiated EGC.

A role for focal adhesion kinase in facilitating the contractile responses of murine gastric fundus smooth muscles

Activation of focal adhesion kinase (FAK) by integrin signalling facilitates smooth muscle contraction by transmitting the force generated by myofilament activation to the extracellular matrix and throughout the smooth muscle tissue. Here we report that electrical field stimulation (EFS) of cholinergic motor neurons activates FAK in gastric fundus smooth muscles, and that FAK activation by EFS is atropine‐sensitive but nicardipine‐insensitive. PDBu and calyculin A contracted gastric fundus muscles Ca2+‐independently and also activated FAK. Inhibition of FAK activation inhibits the contractile responses evoked by EFS, and inhibits CPI‐17 phosphorylation at T38. This study indicates that mechanical force or tension is sufficient to activate FAK, and that FAK appears to be involved in the activation of the protein kinase C–CPI‐17 Ca2+ sensitization pathway in gastric fundus smooth muscles. These results reveal a novel role for FAK in gastric fundus smooth muscle contraction by facilitating CPI‐17 phosphorylation.