Toshiji Tominaga

Identification of the Molecular Mechanisms for Dedifferentiation at the Invasion Front of Colorectal Cancer by a Gene Expression Analysis

Purpose: The aim of this study is to identify gene expression signatures that accompany dedifferentiation at the cancer invasion front in colorectal cancer. Experimental Design: Two types of colorectal cancer were selected. Both types were well-differentiated adenocarcinomas at the superficial lesion. One type showed a dedifferentiated phenotype at the invasion front (type A, 13 samples); the other showed almost no dedifferentiated cancer cells at the invasion front (type B, 12 samples). Laser microdissection was combined with a cDNA microarray analysis to investigate the superficial lesions and the invasion front in colorectal cancers. Results: Eighty-three genes were differentially expressed between types A and B in the superficial lesions, and the samples of superficial lesions were divided correctly into two clusters by these genes. Interestingly, the samples of the invasion front were also divided into the two same clusters by these genes. The text mining method selected 10 genes involved in potential mechanisms causing dedifferentiation of cancer cells at the invasion front. The potential mechanisms include the networks of transforming growth factor-β, Wnt, and Hedgehog signals. The expression levels of 10 genes were calculated by quantitative reverse transcription-PCR and 8 genes were confirmed to be significantly differentially expressed between two types (P < 0.05). The gene expression profiles of 8 genes divided 12 test cases into two clusters with one misclassification. Conclusions: The molecular mechanisms constructed with 8 genes from three networks of transforming growth factor-β, Wnt, and Hedgehog signals were found to correlate with dedifferentiation at the invasion front of colorectal cancer.

Combination of p53 codon 72 polymorphism and inactive p53 mutation predicts chemosensitivity to 5-fluorouracil in colorectal cancer

There are increasing reports showing the clinical significance of the p53 polymorphism status in terms of the response to chemotherapy. We investigated whether p53 polymorphism and mutation were associated with in vitro sensitivity to 5‐fluorouracil (5‐FU) in patients with colorectal cancer. Chemosensitivity to 5‐FU was evaluated by the collagen gel droplet embedded culture drug sensitivity test. 5‐FU sensitivity of tumor cells without inactive p53 mutation in the arginine/arginine (Arg/Arg) variant was significantly higher than that of tumor cells with or without inactive p53 mutation in other variants (p = 0.022), whereas the 5‐FU sensitivity of tumor cells with inactive p53 mutation in the Arg/Arg variant was significantly lower than that of tumor cells with or without inactive p53 mutation in other variants (p = 0.002). In the Arg/Arg variant, apoptotic cells induced by 5‐FU treatment in patients without inactive p53 mutation were more markedly increased than those in patients with inactive p53 mutation (p = 0.037). Bax and Bcl‐2 protein expressions in tumor tissue treated with 5‐FU were associated with both 5‐FU sensitivity and the apoptotic cell count. Our data show that the Arg/Arg genotype without inactive p53 mutation could be predictive of a more favorable response and the Arg/Arg genotype with inactive p53 mutation a less favorable response to chemotherapy using 5‐FU in CRC. The combination of the p53 codon 72 polymorphism and p53 mutation status is a potential predictive marker of sensitivity to 5‐FU in CRC.

Literature review of the energy sources for performing laparoscopic colorectal surgery.

Laparoscopic surgery for colorectal disease has become widespread as a minimally invasive treatment. This is important because the increasing availability of new devices allows us to perform procedures with a reduced length of surgery and decreased blood loss. We herein report the results of a literature review of energy sources for laparoscopic colorectal surgery, focused especially on 6 studies comparing ultrasonic coagulating shears (UCS) and other instruments. We also describe our laparoscopic dissection techniques using UCS for colorectal cancer. The short-term outcomes of surgeries using UCS and Ligasure for laparoscopic colorectal surgery were superior to conventional electrosurgery. Some authors have reported that the length of surgery or blood loss when Ligasure was used for laparoscopic colorectal surgery is less than when UCS was used. On the other hand, a recent study demonstrated that there were no significant differences between the short-term outcomes of UCS and Ligasure for laparoscopic colorectal surgery. It is therefore suggested that the choice of technique used should be made according to the surgeons preference. We also describe our laparoscopic dissection techniques using UCS (Harmonic ACE) for colorectal cancer with regard to the retroperitoneum dissection, dissection technique, dissection technique around the feeding artery, and various other dissection techniques. We therefore review the outcomes of using various energy sources for laparoscopic colorectal surgery and describe our laparoscopic dissection techniques with UCS (Harmonic ACE) for colorectal cancer.

Hemangiopericytoma in the sacrococcygeal space: a case report

IntroductionA hemangiopericytoma is a rare, soft-tissue tumor of vascular origin derived from a pericyte of Zimmerman, which is a modified smooth muscle cell that surrounds the small blood vessels. Hemangiopericytomas can occur wherever there are vascular capillaries. However, there are no previous reports of a hemangiopericytoma in the sacrococcygeal space.Case presentationWe describe the first reported case of a hemangiopericytoma found in the sacrococcygeal space. A 47-year-old Japanese woman presented with a palpable tumor on the left side of her anus. Preoperative imaging indicated that the tumor was in the sacrococcygeal space without invasion of other organs. A complete resection was performed via a parasacral incision. The histological and immunohistochemical staining patterns supported the diagnosis of a hemangiopericytoma.ConclusionA complete resection without piecemeal excision is the best way to treat a hemangiopericytoma. Recognizing the presence of a hemangiopericytoma in the sacrococcygeal space requires appropriate surgery.

Clinical Impact of Matrix Metalloproteinase-7 mRNA Expression in the Invasive Front and Inner Surface of Tumor Tissues in Patients with Colorectal Cancer

PurposeMatrix metalloproteinase-7, reversion-inducing cysteine-rich protein with Kazal motifs, chemokine receptor 7, and vascular endothelial growth factor-C have been correlated with tumor invasion and lymph node metastasis in patients with gastrointestinal cancer. Our study of patients with colorectal cancer quantified the messenger ribonucleic acid (RNA) expressions at the deepest site of tumor invasion (the invasive front) and the tumor’s inner surface. We investigated whether messenger RNA expressions can predict lymph node metastasis in colorectal cancer tumors and then evaluated the clinical implications of these results on the endoscopic treatment of early colorectal cancer.MethodsSixty patients with colorectal cancer participated in the study. Levels of matrix metalloproteinase-7, reversion-inducing cysteine-rich protein with Kazal motifs, chemokine receptor 7, and vascular endothelial growth factor-C messenger RNA in both the invasive front and inner surface of colorectal cancer tumors were measured by using real-time quantitative reverse transcriptase-polymerase chain reaction.ResultsThe matrix metalloproteinase-7 values in the invasive front and inner surface were significantly higher in tumors with lymph node metastasis than in tumors without lymph node metastasis. The matrix metalloproteinase-7 expression levels in the invasive front correlated with inner surface expression levels. Both a univariate and multiple logistic regression analysis showed the matrix metalloproteinase-7 expression levels in both the invasive front and inner surface of tumors to be significantly associated with lymph node metastasis.ConclusionsMatrix metalloproteinase-7 messenger RNA in both the invasive front and inner surface of the tumor is a predictive factor associated with lymph node metastasis for patients with colorectal cancer. The results of this study might indicate further clinical applications of an endoscopic excision for cancer with submucosal invasion.

Survival of Patients with T3 Stage III Rectal Cancer Is Significantly Worse than T2 Stage III Rectal Cancer

Background: The prognosis of T1 plus T2 stage III rectal cancer patients is better than that of T3 stage III rectal cancer patients. However, it is thought that T1 rectal cancer patients have a better prognosis than T2 rectal cancer patients. Aim: This study attempted to clarify the difference of the short- and long-term outcomes in T2 and T3 stage III rectal cancer patients deleting T1 cancer. Methods: The study demonstrated the potential predictors of the survival after surgery, the factors associated with T3 and T2, and the recurrence sites in 134 patients with stage III rectal cancer who underwent surgery, including 111 patients with T3 and 23 patients with T2. Results: The disease-free survival (DFS) of the T3 stage III patients was worse than the T2 stage III patients (5-year DFS rates, 52 vs. 78%; 10-year DFS rates, 43 vs. 78%; p =0.044). The maximum tumor size and operative blood loss were significant tumor characteristics associated with the depth of invasion (p =0.007,p =0.011,respectively). There was no significant difference in the recurrence sites after surgery between the two groups. Conclusion: As a result, a more detailed subdivision for stage III rectal cancer is considered necessary.