Yosuke Shimizu

Frequent alterations in the Wnt signaling pathway in colorectal cancer with microsatellite instability

It is generally accepted that both dysfunction of the Wnt signaling pathway, including mutations in the adenomatous polyposis coli (APC) and β‐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 β‐catenin, APC, Axin 1, and T cell factor 4 (TCF4) genes were performed. Three of 33 samples had mutations in exon 3 of the β‐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.

Combined immunohistochemistry of β-catenin, cytokeratin 7, and cytokeratin 20 is useful in discriminating primary lung adenocarcinomas from metastatic colorectal cancer

BackgroundIt is important to discriminate between primary and secondary lung cancer. However, often, the discriminating diagnosis of primary lung acinar adenocarcinoma and lung metastasis of colorectal cancer based on morphological and pathological findings is difficult. The purpose of this study was to evaluate the clinical usefulness of immunohistochemistry of β-catenin, cytokeratin (CK) 7, and CK20 for the discriminating diagnosis of lung cancer.MethodsWe performed immunohistochemistry of β-catenin, CK7, and CK20 in 19 lung metastasis of colorectal cancer samples, 10 corresponding primary colorectal cancer samples and 11 primary lung acinar adenocarcinoma samples and compared the levels of accuracy of the discriminating diagnosis by using antibodies against these antigens.ResultsPositive staining of β-catenin was observed in all the lung metastasis of colorectal cancer samples as well as in the primary colorectal cancer samples but in none of the primary lung acinar adenocarcinoma samples. Positive staining of CK7 was observed in 90.9% of the primary lung acinar adenocarcinoma samples and in 5.3% of the lung metastasis of colorectal cancer samples, but in none of the primary colorectal cancer samples. Positive staining of CK20 was observed in all the primary colorectal cancer samples and in 84.2% of the lung metastasis of colorectal cancer samples, but in none of the primary lung acinar adenocarcinoma samples.ConclusionCombined immunohistochemistry of β-catenin, CK7, and CK20 is useful for making a discriminating diagnosis between lung metastasis of colorectal cancer and primary lung acinar adenocarcinoma. This method will enable accurate diagnosis of a lung tumor and will be useful for selecting appropriate therapeutic strategies, including chemotherapeutic agents and operation methods.

Impact of endoscopic stent insertion on detection of viable circulating tumor cells from obstructive colorectal cancer

The placement of a self-expanding metallic stent (SEMS) in obstructive colorectal cancer (OCRC) is acknowledged to be a safe and effective procedure for the relief of obstruction. However, there is concern that shear forces acting on the tumor during stent expansion may release cancer cells into the circulation, resulting in a poor prognosis. The aim of the present study was to determine whether colonic stent insertion increases viable circulating tumor cells (v-CTCs). A telomerase-specific replication-selective adenovirus-expressing GFP (TelomeScanF35) detection system was used to detect v-CTCs in 8 OCRC patients with a SEMS before and after stent insertion and after surgical resection. In 7 patients, a SEMS was inserted as a bridge to surgery (BTS), and in one patient, a SEMS was inserted for palliation. Surgical resection (R0) was performed in 7 patients. Four patients had no v-CTCs before SEMS placement, two of four measurable patients had an increased number of v-CTCs after SEMS placement (1-3 v-CTCs), and one of two patients with increased v-CTCs developed distant lymphatic metastasis despite curative resection. Four patients had v-CTCs (1-19 cells) before SEMS placement, and two of these four patients had an increase in the number of v-CTCs (20-21 cells) after SEMS placement, while one of the four patients died early with distant metastasis. The present study demonstrated that endoscopic stent insertion for OCRC may result in tumor cell dissemination into the peripheral circulation and may induce distant metastases.

A new method for laparoscopic percutaneous tube gastrostomy with a single 1-Cm-long incision for patients with esophageal obstruction

Since the introduction of percutaneous endoscopic gastrostomy (PEG) by Gauderer and Ponsky in 1981, this method of gastrostomy has been widely used because of its small degree of invasiveness. In the original technique, the gastrostomy tube was delivered from the mouth into the stomach by withdrawing the guidewire connected to the tube. Russel and colleagues modified this method and inserted the gastrostomy tube into the stomach directly from the skin over the guidewire. Both methods require the use of a gastrofiberscope, which cannot be used in patients with esophageal obstruction. Esophageal obstruction is a common symptom of a malignant tumor in the neck, and even a metallic stent cannot maintain patency of the esophagus throughout the patient’s life. For this reason, patients with advanced esophageal cancer require prophylactic PEG before complete esophageal obstruction or else they must undergo open gastrostomy, which usually requires an incision of 5 to 8 cm in length. Laparoscopic tube gastrostomy was first reported in 1990 as a method that can be used in patients with esophageal obstruction, but this method has not become popular because it is complicated and requires multiple wounds. We describe here a new method for laparoscopic percutaneous tube gastrostomy (LPTG) with a single 1-cmlong incision for patients with esophageal obstruction. METHODS Patients LPTG was performed in seven patients with esophageal obstruction caused by malignant neck tumors, such as laryngeal, thyroid, and esophageal tumors.