Junji Ieda

Re‐expression of CEACAM1 long cytoplasmic domain isoform is associated with invasion and migration of colorectal cancer

Carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) is known to be downregulated at the transcriptional level in adenoma and carcinoma. Recent reports have shown that CEACAM1 is overexpressed at protein level in colorectal cancer and correlated with clinical stage. The reason why colorectal cancer cells re‐expressed CEACAM1 remains unclear. The aim of our study was to clarify the implication of CEACAM1 re‐expression in colorectal cancer. Immunohistochemical analyses were conducted with CEACAM1 long (CEACAM1‐L) or short (CEACAM1‐S) cytoplasmic domain‐specific antibodies on clinical samples from 164 patients with colorectal cancer. The risk factors for metastasis and survival were calculated for clinical implication of CEACAM1 re‐expression. Invasion chamber and wound healing assays were performed for the effect of CEACAM1 expression on invasion and migration of colorectal cancer cells. CEACAM1‐L and CEACAM1‐S stained with greater intensity at the invasion front than at the luminal surface of tumors. Differences between the long and short cytoplasmic isoform expression levels were observed at the invasion front. Multivariate analysis showed that CEACAM1‐L dominance was an independent risk factor for lymph node metastasis, hematogenous metastasis and short survival. The Kaplan–Meier evaluation demonstrated that CEACAM1‐L dominance was associated with shorter survival time (p < 0.0001). In the invasion chamber and wound healing assays, CEACAM1‐L promoted invasion and migration. Re‐expression of CEACAM1 is observed at the invasion front of colorectal cancer. CEACAM1‐L dominance is associated with metastasis and shorter survival of the patients with colorectal cancer. CEACAM1‐L dominance is important for colorectal cancer cells invasion and migration.

Randomized clinical trial of defaecatory function after anterior resection for rectal cancer with high versus low ligation of the inferior mesenteric artery

Defaecatory function is often poor after anterior resection. Denervation of the neorectum following high ligation of the inferior mesenteric artery (IMA) is a possible cause of impaired defaecatory function. The purpose of this randomized clinical trial was to clarify whether the level of ligation of the IMA in patients with rectal cancer affects defaecatory function.

Predicting lymph node metastasis in early colorectal cancer using the CITED1 expression.

BACKGROUND The identification of molecular markers that are useful for predicting lymph node metastasis is urgently needed to determine treatment strategies for T1 colorectal cancer (CRC). We previously showed that 10 candidate genes are correlated with de-differentiation at the invasion front of CRC using a gene expression analysis. These 10 genes are potential markers that may predict lymph node metastasis by CRC. MATERIALS AND METHODS Samples were obtained from 161 patients with CRC. Quantitative real-time reverse transcription-polymerase chain reaction assays were performed using 66 T3 samples in order to extract genes correlated with lymph node metastasis. Immunohistochemical studies of the extracted genes were performed on 66 T3 and 95 T1 samples. A univariate analysis followed by a multivariate logistic regression model was used to examine independent risk factors for lymph node metastasis. RESULTS The CITED1 messenger RNA expression was found to be an independent risk factor for lymph node metastasis in T3 CRC patients (P = 0.040). A high CITED1 protein expression, as detected with immunohistochemistry, was also an independent risk factor in T3 CRC patients (P = 0.035). In T1 colorectal cancer patients, a high CITED1 protein expression was found to be an independent risk factor for lymph node metastasis (P = 0.010). The positive predictive and negative predictive values in the T1 colorectal cancer patients were 27.5% and 95.5%, respectively. CONCLUSIONS The CITED1 expression is correlated with lymph node metastasis in patients with CRC. In T1 colorectal cancer patients, CITED1 has the potential ability to predict the presence of lymph node metastasis.

CEACAM1 and hollow spheroid formation modulate the chemosensitivity of colorectal cancer to 5-fluorouracil

PurposeCarcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) re-expressed and promoted hollow spheroid (HS) formation beyond the invasion front of colorectal cancer. The aim of the present study was to clarify whether CEACAM1 cytoplasmic domain isoform balance and HS are associated with resistance to 5-fluorouracil (5FU).MethodsTwo-dimensional (D) or 3D culture systems were employed to evaluate the effects of CEACAM1 cytoplasmic isoform balance and HS formation on the chemosensitivity of colorectal cancer cells to 5FU. The risk factors for postoperative recurrence were calculated based on the presence of HS and various clinicopathological characteristics in 82 patients with Stage III colorectal cancer who had undergone curative surgery followed by 5FU-based chemotherapy.ResultsCEACAM1-4L-transfected HT29 and CEACAM1-4L and 4S expressing parental LS174T cells had significantly higher resistance to 5FU in comparison with CEACAM1-4S- or vector control-transfected cells. In 3D culture, HS formation induced by CEACAM1-4L induced chemoresistance to 5FU, whereas the solid spheres formed in response to CEACAM1-4S were destroyed by 5FU treatment. HS was identified as an independent factor for recurrence of Stage III colorectal cancer after curative resection followed by 5FU-based chemotherapy. Kaplan–Meier survival curves demonstrated that patients with HS had lower recurrence-free survival rate.ConclusionsCEACAM1 long cytoplasmic domain isoform dominance and HS formation are phenotypes associated with chemoresistance to 5FU.

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.

Hollow spheroids beyond the invasive margin indicate the malignant potential of colorectal cancer

Objective Tumour budding formed by histologically undifferentiated cancer cells beyond the border of the tumour margin is associated with lymph node metastasis. However, hollow tumour nests, a possible histologically advanced phenotype of tumour budding, have not been discussed. We examined whether hollow spheroids exist beyond the border of the invasive margin and are associated with metastasis and prognosis. Moreover, we suggest that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) isoform balance is associated with hollow spheroid formation. Methods Immunohistochemical analyses with CEACAM1 and M30 as an apoptosis marker were performed to examine the importance of hollow spheroid CEACAM1 expression and central cell apoptosis in hollow spheroid formation. The correlations between the presence of hollow spheroids beyond the invasive margin and the clinicopathological characteristics of 314 patients with colorectal cancer were retrospectively evaluated. A 3D culture with colorectal cancer cells transfected with CEACAM1 cDNA or shRNA was used to determine whether CEACAM1 isoform balance controls colorectal hollow spheroid formation. Results Hollow spheroid formation accompanying central cell apoptosis was confirmed by M30 staining and serial section with CEACAM1 staining. Of the 314 patients, 96 (30.4%) were classified as having hollow spheroids. The presence of hollow spheroids is an independent risk factor for metastases and shorter survival. In 3D culture, CEACAM1 isoform balance modulated hollow spheroid formation of colorectal cancer cells. Conclusions Hollow spheroid formation beyond the border of the tumour margin in colorectal cancer is more important than tumour budding for the prediction of malignant potential.

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.

Horizontal rectal transection using an endolinear stapler for laparoscopic low anterior resection

Multiple firings with multiple cartridges for rectal transection have been reported as potential causes of anastomotic leakage in laparoscopic low anterior resection with the double-stapling technique [1]. Here we demonstrate an effective new method for horizontal transection of the rectum that we have used for laparoscopic low anterior resection, using a large endovascular clip for rectal alignment. The patient is placed in the head-down lithotomy position with the right side tilted down and the surgeon on the patient’s right. Five-port trocars including two 12-mm ports, two 5-mm ports, and a blunt port were introduced (Fig. 1). Pneumoperitoneum is created using carbon dioxide, and laparoscopic exploration is performed. After complete mobilization of the rectum to the levators, the surgeon inserts the linear stapler through the right lower quadrant port (Fig. 2a, b). The assistant through the left upper quadrant port pulls the rectum forward and cranially rolling it in a counterclockwise direction. The surgeon through the right upper quadrant port also rolls the rectum in a counterclockwise direction to align the horizontal line of the rectum with the linear staple insertion line (Fig. 2c, d). A 70-mm endovascular clip (B. Braun Aesculap Co., Tokyo, Japan) is introduced through the right lower quadrant port aligning, and the rectal wall is clamped below the tumor (Figs. 2e, 3a). Figure 3b shows the 70-mm endovascular clip. A distal rectal washout is performed using 1000 ml of 5% povidone-iodine solution. An endolinear stapler (Echelon FLEX 60 ; Ethicon EndoSurgery, Cincinnati, OH, USA) is inserted through the right lower quadrant port and then applied at the rectal wall parallel and caudal to the 70-mm endovascular clip (Fig. 3c). The assistant forceps in the left lower quadrant port pushes the distal rectum to the right, and the endolinear stapler with opened jaws is simultaneously pushed deeper into the left side space. The jaws are then closed at a position that enabled transection of the rectum with one firing using a single cartridge (Fig. 3d). Figure 3e shows Fig. 1 Port sites

Perineural Invasion Is Associated with Poor Survival after Preoperative Chemoradiation Therapy for Advanced Lower Rectal Cancer

Background: Preoperative chemoradiation therapy (pCRT) is a standard procedure for patients with advanced lower rectal cancer. It has been reported that pCRT cannot prolong the survival of patients with advanced lower rectal cancer. The aim of this study is to address the controllable and uncontrollable pathological factors of pCRT in predicting local and distant recurrences. Methods: One hundred two patients with stages 2 and 3 cancer were consecutively enrolled to the study. The first 51 patients (October 2008-August 2010) underwent curative resection without pCRT. The latter 51 patients (September 2010-May 2015) underwent curative resection after pCRT. Pathological factors of patients were evaluated to assess the association between local and distant recurrences. Results: Multivariate analyses for local and distant recurrences of patients without pCRT revealed that the independent risk factors were tumor deposit and perineural invasion respectively. pCRT was able to diminish circumferential resection margin, tumor deposit, venous invasion, and lymphatic permeation but not neural invasion and lymph node involvement. Kaplan-Meier curve of local and distant recurrence-free survival of patients with pCRT illustrated that tumor deposit is controllable, whereas perineural invasion is uncontrollable by pCRT. Conclusion: pCRT-uncontrollable perineural invasion may be a factor for distant recurrence of advanced rectal cancer patients, leading to poor survival.

Expression of P4H9-detecting molecule on spindle-shaped fibroblasts to indicate malignant phenotype of colorectal cancer.

539 Background: Cancer cells and fibroblasts are coordinated for cancer progression. Our previous study has shown that P4H9, produced by epitope for b2 integrin, detected a molecule on fibroblasts in mammary fat pad mouse model in response to Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expressing cancer cells. P4H9 detecting molecule (PDM) expression appeared to be associated with myofibroblast differentiation. The aim of the present study is to investigate whether PDM express on fibroblast and cancer cells in clinical tissue samples, and whether PDM expressing cells in colorectal cancer tissue are correlated with clinicopathological features of patients with colorectal cancer. Methods: Immunohistochemistry were conducted with P4H9 on clinical tissue samples from 156 patients with colorectal cancer. The risk factors for metastases and survival were calculated for clinical implication of PDM expressing spindle shaped fibroblasts. Immunofluorescence with P4H9 were performed on CCD-18...