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Background Institutional variation in outcomes is a key factor to ascertain the generalizability of results and reliability of the clinical trial. This study evaluated institutional variation in survival and postoperative complications using data from JCOG0404 comparing laparoscopic colectomy (LAP) with open colectomy (OP). Methods Institutions with fewer than 10 registered patients were excluded from this analysis. Institutional variation was evaluated in terms of early postoperative complications, overall survival, and relapse‐free survival and estimated using a mixed‐effect model with institution as a random effect after adjusting for background factors. Results This analysis included 1028 patients in the safety analysis and 1040 patients in the efficacy analysis from 26 institutions. In the safety analysis, there was no variation in grades 3–4 early postoperative complications (in OP, median 6.3% [range 6.3%–6.3%]; in LAP, median 2.6% [range 2.6%–2.6%]), but some variation in grades 1–4 early postoperative complications was observed (in OP, median 20.8% [range 13.2%–31.8%]; in LAP, median 11.9% [range 7.2%–28.7%]), and that in grades 2–4 was observed only in LAP (median 8.8% [range 4.7%–24.0%]; in OP, median 12.7% [range 12.7%–12.7%]). Two specific institutions showed especially high incidences of postoperative complications in LAP. In the efficacy analysis, there was no institutional variation in OP, although a certain variation was observed in LAP. Conclusions Some institutional variations in safety and efficacy were observed, although only in LAP. We conclude that a qualification system, including training and education, is needed when new surgical techniques such as laparoscopic surgery are introduced in clinical practice., We evaluated institutional variation in survival and postoperative complications (PCs) using JCOG0404 data. Institutional variation was observed in laparoscopic surgery in grades 1–4 and 2–4 early PCs and 5‐y relapse‐free survival. A qualification system through training and education is needed when new surgeries, including laparoscopic surgery, are introduced.

Colon cancer (CC) is a leading cause of cancer mortality. Novel biomarkers are needed to identify CC patients at high risk of recurrence and those who may benefit from therapeutic intervention. The aim of this study is to investigate if miR-21 expression from RNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue sections is associated with prognosis and therapeutic outcome for patients with CC. The expression of miR-21 was measured by quantitative reverse transcriptase-polymerase chain reaction in a Japanese cohort (stage I-IV, n = 156) and a German cohort (stage II, n = 145). High miR-21 expression in tumors was associated with poor survival in both the stage II/III Japanese (p = 0.0008) and stage II German (p = 0.047) cohorts. These associations were independent of other clinical covariates in multivariable models. Receipt of adjuvant chemotherapy was not beneficial in patients with high miR-21 in either cohort. In the Japanese cohort, high miR-21 expression was significantly associated with poor therapeutic outcome (p = 0.0001) and adjuvant therapy was associated with improved survival in patients with low miR-21 (p = 0.001). These results suggest that miR-21 is a promising biomarker to identify patients with poor prognosis and can be accurately measured in FFPE tissues. The expression of miR-21 may also identify patients who will benefit from adjuvant chemotherapy.

Claudin-18 plays a key role in constructing tight junctions, and altered claudin-18 expression has been documented in various human malignancies; however, little is known about the biological significance of claudin-18 in colorectal cancer (CRC). The aim of this study is to investigate the significance of claudin-18 expression in CRC and its association with clinicopathological factors. We performed clinicopathological analysis of claudin-18 expression in a total of 569 CRCs by immunohistochemistry. Moreover, we investigated the association between claudin-18 and various markers including gastric/intestinal phenotype (MUC5AC, MUC6, MUC2 and CD10), CDX2, claudin-3, claudin-4, p53 and Ki-67. Claudin-18 expression was detected in 21 of the 569 CRCs (4%) and was seen exclusively on the cell membrane. Positive expression of claudin-18 showed a significant correlation with positive expression of MUC5AC (P < 0.0001) and negative expression of CDX2 (P= 0.0013). The prognosis of patients with positive claudin-18 expression was significantly poorer than in negative cases (P= 0.0106). Multivariate analysis revealed that T grade, M grade and claudin-18 expression were independent predictors of survival in patients with CRC. We revealed that claudin-18 expression correlates with poor survival in patients with CRC and is associated with the gastric phenotype.

Gastric cancer (GC) is one of the most common malignancies worldwide. Genes expressed only in cancer tissue, and especially on the cell membrane, will be useful molecular markers for diagnosis and may also be good therapeutic targets. To identify genes that encode transmembrane proteins present in GC, we generated Escherichia coli ampicillin secretion trap (CAST) libraries from two GC cell lines and normal stomach. By sequencing 4320 colonies from CAST libraries, we identified 30 candidate genes that encode transmembrane proteins present in GC. Quantitative reverse transcription-polymerase chain reaction analysis of these candidates revealed that ZDHHC14, BST2, DRAM2, and DSC2 were expressed much more highly in GC than in 14 kinds of normal tissues. Among these, DSC2 encodes desmocollin 2, which is one of three known desmocollins. Immunohistochemical analysis demonstrated that 22 (28%) of 80 GC cases were positive for desmocollin 2, and desmocollin 2 expression was observed frequently in GC with the intestinal mucin phenotype. Furthermore, desmocollin 2 expression was correlated with CDX2 expression. These results suggest that expression of desmocollin 2, induced by CDX2, may be a key regulator for GC with the intestinal mucin phenotype. Our results provide a list of genes that have high potential as a diagnostic and therapeutic target for GC. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

It is generally accepted that both dysfunction of the Wnt signaling pathway, including mutations in the adenomatous polyposis coli (APC) and beta-catenin genes, and genetic instability play important roles in colorectal carcinogenesis. However, alteration of the components in the Wnt signaling pathway in colorectal cancer (CRC) with microsatellite instability (MSI) has not been elucidated. In order to assess the status of the Wnt signaling components in CRC with MSI, mutational analyses of the beta-catenin, APC, Axin 1, and T cell factor 4 (TCF4) genes were performed. Three of 33 samples had mutations in exon 3 of the beta-catenin gene and two in the APC gene. Eight mutations in seven samples were detected by single-strand conformation polymorphism and subsequent direct sequence analysis of the entire coding region of the Axin 1 gene. Furthermore, TCF4, which is one of the transcriptional factors in the Wnt signaling pathway and has a mononucleotide repeat sequence (a nine- adenine repeat, (A)9) in its C-terminal region, was mutated in 13 of the 33 samples. Thus, alteration in the Wnt signaling pathway is frequently observed in CRC with MSI, including hereditary nonpolyposis colorectal cancer, as well as in familial adenomatous polyposis and sporadic CRC without MSI.

In rectal cancer, lateral lymphatic spread is considered to worsen the prognosis. Therefore, accurate determination of lymph node involvement preoperatively is helpful in assessing the malignant character of the tumor and in determining resectability. The present study was performed to evaluate the accuracy, limitations, and usefulness of endoluminal ultrasonography in preoperatively diagnosing the localization of lymph node metastasis in rectal cancer. Seventy-six patients with rectal cancer underwent preoperative endoscopic ultrasonography. Three of these patients had lateral lymphatic spread and all could be distinguished on endoscopic ultrasonography by the detection of involvement of lymph nodes in the anterior rectal space. These findings suggest that endoscopic ultrasonography plays a potentially useful role in the strategy for dealing with rectal cancer prior to surgery.