Keigo Ashida

c-erbB-2 protein is expressed in hepatolithiasis and cholangiocarcinoma.

The c‐erbB‐2 proto‐oncogene encodes a transmembrane protein which is highly homologous to epidermal growth factor receptor. Overexpression of this c‐erbB‐2 protein has been reported in many human carcinomas, including breast carcinoma. However, there have been few studies of the expression of c‐erbB‐2 in cholangiocarcinoma and hepatolithiasis, a condition occasionally associated with cholangiocarcinoma.

Expression of epithelial-cadherin, alpha-catenin and beta-catenin during human intrahepatic bile duct development: a possible role in bile duct morphogenesis

BACKGROUND/AIMS Cell adhesion molecules play an important role in the morphogenesis of developing organs. However, little is known about their expression during intrahepatic bile duct development. METHODS We immunohistochemically investigated the expression of E-cadherin (E-Cad), alpha-catenin (A-Cat) and beta-catenin (B-Cat) during human intrahepatic bile duct development, using 31 fetal livers of various gestational ages. The developmental stages of bile ducts were classified into the ductal plate, migrating biliary cells (remodeling stage), and immature bile ducts (remodeled stage). RESULTS E-Cad was broadly and strongly expressed in the ductal plate with a cytoplasmic pattern, heterogeneously and weakly expressed in the migrating biliary cells with a cytoplasmic pattern, and broadly and strongly expressed in immature bile ducts with a membranous pattern. A-Cat was broadly and strongly expressed in the ductal plate with a membrane pattern, broadly and moderately expressed in the migrating biliary cells with a membranous pattern, and broadly and strongly expressed in immature bile ducts with a membranous pattern. In contrast, expression of B-Cat was weak or slight in the ductal plate, but B-Cat was expressed broadly and strongly with a membranous pattern in migrating biliary cells and in immature bile ducts. Immature hepatocytes rarely expressed E-Cad and A-Cat, but expressed B-Cat with a membranous pattern throughout development. CONCLUSIONS These results suggest that E-Cad, A-Cat and B-Cat are involved in the normal developmental morphogenesis of human intrahepatic bile ducts.

Endocrine cells in intraductal papillary-mucinous neoplasms of the pancreas : A histochemical and immunohistochemical study

Abstract The endocrine cells in intraductal papillary-mucinous neoplasms (IPN) of the pancreas have rarely been investigated. In the normal pancreatic ducts of normal pancreases (n=5) there were a few endocrine cells: argyrophil in 5 (100%), chromogranin A in (100%), pancreatic polypeptide (PP) in 3 (60%), and insulin in 7 (20%). These endocrine cells were scattered, and located in the basal portions of pancreatic ducts. In IPN of the pancreas (n=9), there were many endocrine cells: argyrophil in 7 (78%), argentaffin in 8 (89%), chromogranin A in 8 (89%), PP in 7 (78%), serotonin in 7 (78%), insulin in 4 (44%), and gastrin in 5 (56%). In invasive ductal adenocarcinoma of the pancreas (n=6), many endocrine cells were also detected: argyrophil cells in (67%), chromogranin A in 3 (50%), insulin in 3 (50%), glucagon in 4 (67%), and somatostatin in 3 (50%). In positive cases, endocrine cells were situated under or among the neoplastic cells and the proportion of endocrine cells in IPN was less than 5% of the total neoplastic cell population. These data show that normal pancreatic ducts contain endocrine cells and that IPN frequently contain argyrophil, argentaffin, chromogranin A, and hormone-containing endocrine cells. These data also suggest that endocrine differentiation occurs during neoplastic transformation and progression of IPN of the pancreas.

Topoisomerase I expression in tumors as a biological marker for CPT-11 chemosensitivity in patients with colorectal cancer.

Irinotecan (CPT-11) is used as a first- and second-line chemotherapy for advanced or recurrent colorectal cancer (CRC). However, only 20%–30% of patients show an objective response to CPT-11 and the drug has severe toxicities, such as delayed-onset diarrhea, neutropenia, nausea, and vomiting. It is important to select patients who will demonstrate sensitivity to CPT-11 treatment to avoid unnecessary drug toxicities and to introduce anticancer treatment benefits to CRC patients. DNA topoisomerase I (Topo I) is essential for vital cellular processes such as DNA replication, transcription, translation, recombination, and repair. This article reviews the possibility of assessing Topo I protein expression in tumors as a biological marker for CPT-11 treatment in CRC.

Expression of pancreatic digestive enzymes in normal and pathologic epithelial cells of the human gastrointestinal system

Abstract Pancreatic digestive enzymes have rarely been reported in human nonpancreatic organs. We examined their expression in the epithelial cells of the nonpancreatic gastrointestinal organs, looking for pancreatic α-amylase, trypsin, chymotrypsin and pancreatic lipase. Western blotting, enzyme assay and pancreatic α-amylase mRNA were also used in selected specimens. In normal tissues, immunoreactivity of one or more of these enzymes was frequently noted in cells of the salivary glands, stomach, duodenum, large pancreatic ducts, extrahepatic bile ducts and gall bladder. The epithelium of the normal oesophagus, small intestine and colon were consistently negative for these enzymes. In pathologic tissues, immunoreactivity for one or more enzymes was present in epithelial cells of pleomorphic adenomas of the salivary glands, oesophageal squamous cell carcinoma, gastric adenoma and adenocarcinoma, pancreatic adenocarcinoma, cholecystitis, adenocarcinoma of the gall bladder and extrahepatic bile duct, and colon adenoma and adenocarcinoma. Western blotting showed a specific band of each enzyme in some specimens of normal stomach. In situ hybridization for pancreatic α-amylase mRNA showed specific signals in the normal stomach, but not in the normal colon. Reverse transcriptase polymerase chain reaction analysis for pancreatic α-amylase mRNA revealed specific signals in the normal stomach. Enzyme assay revealed that the stomach and gall bladder showed these activities. The data suggest that pancreatic digestive enzymes are produced by several epithelial cell types of the nonpancreatic gastrointestinal organs, that the organs positive for pancreatic enzyme have a common cell lineage, and that neoplasms continue to express or neoexpress these enzymes after neoplastic transformation.

Prognostic Significance of Pre- and Postoperative Lymphocyte Counts in Patients with Gastric Cancer

Background: Although preoperative lymphopenia is reportedly a prognostic factor in cancer patients, the association between postoperative lymphopenia and patient prognosis has not been widely studied. Methods: We enrolled 352 patients who underwent surgery for gastric cancer (GC) between January 2005 and April 2013 to analyze correlations among pre- and postoperative lymphocyte counts (LCs) and prognosis in GC patients. Results: Pre- and postoperative (obtained 1 day after surgery) LCs were significantly correlated (r = 0.496, p < 0.0001). Pre- and postoperative LCs of elderly patients were significantly lower than those of non-elderly patients. Postoperative lymphocyte count was significantly lower in patients with a differentiated tumor than in those with an undifferentiated tumor. Based on the results of receiver operating characteristic analysis, patients were classified into subgroups as: preoperative LC ≥1,676 (pre-LCHigh), preoperative LC <1,676 (pre-LCLow); and as postoperative LC ≥855 (post-LCHigh), and postoperative LC <855 (post-LCLow). Five-year overall survival rates significantly differed between pre-LCHigh (82.5%) and pre-LCLow (71.6%) groups (p = 0.023); and also between the post-LCHigh (81.5%) and post-LCLow (69.5%) groups (p = 0.0072). The 5-year disease specific survival rates were 91.3 and 82.4% in patients with post-LCHigh and those with post-LCLow, respectively, and differences were statistically significant (p = 0.015). Multivariate analysis indicated that postoperative lymphocyte count was an independent prognostic indicator, along with age, gender, tumor size, lymph node metastasis, and venous invasion. Conclusions: Postoperative lymphocyte count is a useful predictive factor for prognosis in GC patients.

Combined analysis of the pre- and postoperative neutrophil–lymphocyte ratio predicts the outcomes of patients with gastric cancer

PurposeThe neutrophil–lymphocyte ratio (NLR) is a biochemical marker of the systemic inflammatory response and has been associated with prognosis for various types of cancer. This retrospective study investigates the relationship between the pre- and postoperative NLR and the prognosis of gastric cancer patients.MethodsThe subjects were 280 patients who underwent curative surgery for histopathologically diagnosed gastric adenocarcinoma.ResultsThe preoperative NLR was significantly correlated with tumor size, tumor depth, lymphatic invasion, venous invasion, and disease stage. In contrast, there was no correlation between the postoperative NLR and the various clinicopathological variables. Prognosis was significantly worse for patients with a high preoperative NLR than for those with a low preoperative NLR. Prognosis was also significantly worse for patients with a high postoperative NLR than for those with a low postoperative NLR. Furthermore, the prognosis was worse for gastric cancer patients whose pre- and postoperative NLRs were both high. Multivariate analysis indicated that a high pre- and postoperative NLR was an independent prognostic indicator.ConclusionsThe combination of pre- and postoperative NLRs appears to be useful for predicting the prognosis of gastric cancer patients.

Primary Umbilical Endometriosis: Unusual and Rare Clinical Presentation.

Primary umbilical endometriosis is a rare disorder and is defined as the presence of ectopic endometrial tissue within the umbilicus. A patient with painful mass in the umbilicus during menstrual period is studied in this paper. The possibility of subcutaneous endometriosis should be considered when an umbilical mass is detected despite the absence of previous surgery. In this case, urachal cancer, urachal remnant, umbilical endometriosis, and its malignant transformation were among the diseases considered in the differential diagnosis. Complete excision and histology are necessary to obtain a definitive diagnosis and optimal treatment for umbilical subcutaneous endometriosis.

Postoperative ratio of the maximum C-reactive protein level to the minimum peripheral lymphocyte count as a prognostic indicator for gastric cancer patients

PurposeInflammation, together with immune and nutritional status, are associated with the progression of various cancer types. We evaluated the prognostic significance of the postoperative ratio (post-CLR) of the maximum C-reactive protein value (post-CRPMax) to the minimum peripheral lymphocyte count (post-LCMin) in patients with gastric cancer (GC).MethodsThe subjects of this retrospective study were 227 patients who underwent curative surgery for histopathologically diagnosed gastric adenocarcinoma.ResultsThe 5-year overall survival (OS) rates differed significantly between the post-CLRHigh (≥ 152.6) group and the post-CLRLow (< 152.6) group for all patients (45.0% vs. 68.4%, respectively; P < 0.001). The 5-year disease-specific survival (DSS) rates were also significantly related to post-CLR for all patients, (80.6% vs. 64.3% for the post-CLRLow and the post-CLRHigh groups, respectively; P = 0.002). Among patients without infectious complications, the CLR affected both the 5-year OS rate (48.4% vs. 69.2% for the post-CLRHigh and the post-CLRLow groups, respectively; P = 0.006) and the 5-year DSS rate (80.2% vs. 67.0% for the post-CLRLow and the post-CLRHigh groups, respectively; P = 0.027). Multivariate analysis revealed that post-CLR was an independent prognostic indicator for both the OS and DSS of all patients.ConclusionsOur finding show that the post-CLR can help predict the prognosis of GC patients.

Combined Pre- and Postoperative Lymphocyte Count Accurately Predicts Outcomes of Patients with Colorectal Cancer

Background: Although preoperative lymphopenia is reportedly a prognostic factor in cancer patients, the association between postoperative lymphopenia and patient prognosis has not been widely studied. Methods: We enrolled 379 patients who underwent surgery for colorectal cancer (CRC) to analyze correlations among pre- and postoperative lymphocyte counts (LCs) and prognosis in patients with CRC. Results: Pre- and postoperative LCs were significantly correlated (r = 0.615, p < 0.0001). Based on results of receiver operating characteristic analysis, patients were subgrouped as preoperative LC ≥1,280 (pre-LCHigh, n = 234), preoperative LC < 1,280 (pre-LCLow, n = 145); and as postoperative LC ≥680 (post-LCHigh, n = 246), and postoperative LC < 680 (post-LCLow, n = 133). Five-year disease-specific survival rates significantly differed between pre-LCHigh (88.6%) and pre-LCLow (72.5%) groups (p < 0.0001); and also between the post-LCHigh (88.5%) and post-LCLow (71.1%) groups (p < 0.0001). Five-year disease-specific survival rates of patients who were both pre-LCLow and post-LCLow was significantly lower than those for patients who were either pre-LCHigh or post-LCHigh or pre-LCHigh/post-LCHigh (p = 0.0003). Multivariate analysis indicated that the combination of pre- and postoperative LC was an independent prognostic indicator. Conclusions: The combination of pre- and postoperative LC is a predictive factor for prognosis in CRC patients.