New diagnostic strategy using narrow-band imaging (NBI) during laparoscopic surgery for patients with colorectal cancer.

BACKGROUND: Accurate tumor stage diagnosis during laparoscopic surgery remains difficult. We clarify the impact of new diagnostic strategy using narrow-band imaging (NBI) during laparoscopic surgery for colorectal cancer compared with other strategies. METHODS: We defined angiogenesis (Ag) and fibrosis (Fib) grades using NBI laparoscopy (lap-NBI), and assessed the clinicopathological features associated with these grades for 67 patients with colorectal cancer who underwent surgery. We assessed vessel density and gray scale with computer software. RESULTS: NBI-Ag-grade and NBI-Fib-grade of the serosal surface of cancer lesions and peritoneal nodules correlated with vessel density and gray scale of those assessed by Image J computer software. NBI-Fib-grades of liver nodules also correlated with gray scale. NBI-Ag- grade and Fib-grade of the serosal surface of cancer lesions correlated with pathological depth of invasion. These NBI grades of pathological metastatic peritoneal nodules were higher than those of pathologically benign peritoneal nodules. NBI- Fib grades of pathological metastatic liver nodules were higher than those of pathologically benign liver nodules. In multivariate analysis, lap-NBI was associated with different diagnosis for T3, T4 and non-T3, and non-T4. Moreover, lap-NBI was associated with different diagnosis for T4 and non-T4. Predictive value for T4 by lap-NBI showed high sensitivity (85%) specificity (87%), positive predictive value (74%), negative predictive value (93%), and overall accuracy (87%). Sensitivity and overall accuracy of lap-NBI was superior to that of other diagnostic modalities. CONCLUSION: We clarified the usefulness of the new diagnostic strategy using lap-NBI during laparoscopic surgery for colorectal cancer in comparison with other strategies.

Laparoscopic ventral rectopexy using the transanal vacuum test for complete rectal prolapse.

Laparoscopic ventral rectopexy was performed in 84 patients with complete rectal prolapse from January 2016 to December 2019. In the initial 27 cases, three cases had recurrence, especially in cases of a long rectal prolapse measuring over 10 cm. In order to avoid recurrence, the transanal vacuum test was performed following the dissection of the rectovaginal septum towards the pelvic floor. The disappearance of rectal prolapse is confirmed by the intraoperative transanal vacuum test. When the posterior wall of the rectum showed the presence of prolapse according to the transanal vacuum test, then laparoscopic ventral rectopexy was converted to laparoscopic posterior rectopexy. In 94 cases in which laparoscopic ventral rectopexy was attempted, laparoscopic ventral rectopexy was completed in 57 cases, while the procedure was converted to laparoscopic posterior rectopexy in 37 cases. The recurrence rate following laparoscopic ventral rectopexy decreased from 11.1% (3/27) to 1.7% (1/57) after beginning to use the transanal vacuum test. Laparoscopic ventral rectopexy using the transanal vacuum test is therefore considered to be a useful technique to reduce postoperative recurrence.

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.

Laparoscopic abdominoperineal resection with lateral lymph node dissection for anorectal melanoma: A case report.

Because anorectal melanoma, a rare cancer with a poor outcome, does not respond well to local radiation therapy or systemic chemotherapy, surgery is the primary treatment. Herein, we present a case of anorectal melanoma with lateral and inguinal lymph node metastases. A 61-year-old woman presented with rectal bleeding. Colonoscopy revealed a black tumor with ulceration in the anorectum. A CT scan revealed an anorectal tumor with left lateral lymph node swelling and right inguinal lymph node swelling. We performed a laparoscopic abdominoperineal resection with lateral lymph node dissection and right inguinal lymph node dissection. One year after the initial operation, pulmonary metastases were observed, and pulmonary resection was performed. After the pulmonary resection, brain metastases developed, and surgical resection was performed. Despite the recurrence of disease, the patient has survived for 52 months since the initial surgery and continues to receive systemic chemotherapy.

P4H9-detected molecule expression on spindle-shaped fibroblasts indicates malignant phenotype of colorectal cancer.

BACKGROUND: Our previous study using a mammary fat pad mouse model showed that P4H9, produced by the ß2 integrin epitope, detected a molecule on fibroblasts in response to carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)-expressing cancer cells. P4H9-detected molecule (PDM) expression appeared to be associated with myofibroblast differentiation. In this study, we investigated whether PDM is expressed on fibroblasts and cancer cells in clinical tissue samples, and whether the presence of PDM-expressing colorectal cancer cells is correlated with clinicopathological features of patients. METHODS: Immunohistochemistry was conducted to detect P4H9 on clinical tissue samples from 156 patients with colorectal cancer. Risk factors for metastases and survival were calculated for clinical implication of PDM-expressing spindle-shaped fibroblasts. RESULTS: Multivariate analysis showed that PDM-expressing spindle-shaped fibroblasts were an independent risk factor for lymph node metastasis, hematogenous metastasis, and poor survival. A Kaplan-Meier survival curve indicated that PDM-expressing spindle-shaped fibroblasts were associated with shorter survival time (P<0.0001). Immunofluorescence showed PDM expression on CCD-18Co fibroblasts and two colorectal cancer cell lines (HCT116 and HCT-15). CONCLUSIONS: PDM-expressing spindle-shaped fibroblasts are associated with metastasis and shorter survival in colorectal cancer patients. PDM-expressing spindle-shaped fibroblasts may have a role in eliciting the malignant phenotype of colorectal cancer.

Clinical characteristics of anastomotic leakage after an anterior resection for rectal cancer by assessing of the international classification on anastomotic leakage.

PURPOSE: The International Study Group of Rectal Cancer (ISREC) has proposed a new definition of anastomotic leakage (AL) which was simply classified into three grades; however, these criteria have not been assessed well. The aims of this study are to assess the new definition and to show the clinical features of AL after an anterior resection for rectal cancer. METHODS: Fifty consecutive patients developed AL after an anterior resection for rectal cancer was retrospectively assessed. AL was defined by the ISREC criteria. RESULTS: Twenty-seven (54 %) patients with AL were diagnosed by drain contents. The postoperative day of diagnosis for AL was later in grade A versus grades B and C (p = 0.038 vs p = 0.006, respectively). Permanent stoma (PS) was significantly more frequent in patients with grade C but not grade B compared to the patients with no AL (p < 0.001 and p = 0.171, respectively). In patients without diverting stoma, there was more serious grade of AL (p < 0.001). CONCLUSIONS: Differences were observed in the postoperative day of diagnosis, the creation rate of PS, and impact on diverting stoma after AL between each grade of leakage. The new classification was easy and reasonable to evaluate AL. As a result, it should be widely used in future studies.

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

PURPOSE: Carcinoembryonic 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). METHODS: Two-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. RESULTS: CEACAM1-4L-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. CONCLUSIONS: CEACAM1 long cytoplasmic domain isoform dominance and HS formation are phenotypes associated with chemoresistance to 5FU.

The impact of a pelvic pillow on learning how to perform laparoscopic low anterior resection for rectal cancer.

PURPOSE: This study evaluated the impact of the pelvic pillow on a single surgeon's learning how to perform laparoscopic low anterior resection (LAR) for rectal cancer. METHODS: We compared the outcomes for 23 patients with rectal cancer including the first 11 patients who underwent laparoscopic LAR without the pelvic pillow, and the latter 12 patients with the pelvic pillow by a single surgeon. RESULTS: The stage of the pelvic pillow (+) was more advanced than that of the pelvic pillow (-). The length of the operation and postoperative start of oral intake for the pelvic pillow (+) were shorter and earlier than those of the pelvic pillow (-). The pelvic surgical field in the pelvic pillow (+) was better and allowed better evaluation than the pelvic pillow (-). CONCLUSIONS: Maintaining an excellent view of the pelvic surgical field with the pelvic pillow might have an impact on learning laparoscopic LAR.

Impact of the post/preoperative serum CEA ratio on the survival of patients with rectal cancer.

PURPOSE: This study demonstrated the usefulness of the post/preoperative serum carcinoembryonic antigen (CEA) ratio as a predictor of survival after surgery for stage III rectal cancer patients. METHODS: One hundred and four patients with stage III rectal cancer who underwent surgery between 1991 and 2000 were enrolled. The ratio of the postoperative serum CEA value divided by the preoperative serum CEA value was defined as post/preoperative serum CEA ratio, and the patients were separated into two groups: post/preoperative serum CEA ratio ≤ 1 (n = 86) and >1 (n = 18). RESULTS: The multivariate analyses demonstrated that the intraoperative blood loss, lack of a sphincter-saving procedure and a post/preoperative serum CEA ratio >1 were independent factors predicting a poor prognosis for the overall and disease-free survival. The overall and disease-free survival rates among patients with a high preoperative serum CEA level (>5 ng/ml) or patients with a high postoperative serum CEA (>5 ng/ml) were longer in patients with a post/preoperative serum CEA ratio ≤ 1, in comparison to those with a post/preoperative serum CEA ratio >1. Liver metastasis was observed more frequently in patients with a post/preoperative serum CEA ratio >1. CONCLUSIONS: The post/preoperative serum CEA ratio may be a predictor of the prognosis after surgery for stage III rectal cancer patients.

CEACAM1 long cytoplasmic domain isoform is associated with invasion and recurrence of hepatocellular carcinoma.

BACKGROUND: The two isoforms of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), 1 with a long cytoplasmic domain (CEACAM1-L) and 1 with a short (CEACAM1-S), are involved in different signaling pathways. ß2-spectrin (ß2SP) is an adaptor protein that plays critical roles in the proper control of Smad access to activate receptors involved in regulation of TGF-ß signaling. In this study, we examined the association between CEACAM1 isoform balance and hepatocellular carcinoma (HCC) malignant potential and investigated the possibility of a molecular interaction between CEACAM1 and ß2SP. METHODS: Immunohistochemical analysis was carried out with CEACAM1-L or CEACAM1-S antibodies on 154 HCC tissues to correlate with the factors of malignancy. Invasion assay was performed for the effect of CEACAM1 expression on HCC cell lines. Moreover, immunohistochemical analysis and immunoprecipitation analysis were performed to investigate the association between CEACAM1 isoform balance and ß2SP. RESULTS: In immunohistochemical analysis, CEACAM1-L expression dominance was a risk factor for HCC recurrence (p = 0.04) and was significantly associated with a shorter survival compared with CEACAM1-S expression dominance. Invasion assay indicated that CEACAM1-4L-transfected HLF and PLC/PRF/5 cells showed significantly increased invasion (p < 0.0001) and CEACAM1-4S-transfected HLF cells showed significantly decreased invasion. Immunohistochemical analysis of ß2SP suggested that the HCCs with CEACAM1-L-dominant expression were more strongly stained with ß2SP than the HCCs with CEACAM1-S-dominant expression (p = 0.013), and coprecipitation assays indicated that CEACAM1-L could bind to ß2SP. CONCLUSIONS: CEACAM1-L may enhance the HCC invasiveness through an interaction with ß2SP and subsequent effects on TGF-ß signaling.

Survival benefit of lateral lymph node dissection according to the region of involvement and the number of lateral lymph nodes involved.

PURPOSE: The effectiveness of lateral lymph node dissection for extending the survival of patients with advanced lower rectal cancer remains unclear. The purpose of this study was to clarify the survival benefit of lateral lymph node dissection according to the region of involvement and the number of lateral lymph nodes involved. METHODS: We reviewed 131 consecutive patients with advanced lower rectal cancer, who had undergone curative resection with total mesorectal excision plus extended lateral lymph node dissection at Wakayama Medical University Hospital. Twenty-six (19.1 %) of these patients had lateral lymph involvement. We performed univariate and multivariate analyses for the 3-year disease-free and overall survival of these patients. RESULTS: Multivariate analysis revealed that the number (>1) and the region (common iliac artery region or external iliac artery region) of lateral lymph node metastasis are independent predictive factors for recurrence and survival. The Kaplan-Meier analysis demonstrated that patients with one lymph node metastasis in the internal iliac artery or obturator region had better survival. CONCLUSIONS: Lateral lymph node dissection resulted in survival benefit for patients with single lateral lymph node involvement in the internal iliac artery region or the obturator region.

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.

Angiosarcoma involving colon and bone successfully responded to paclitaxel and zoledronate: case report.

Angiosarcoma involving the gastrointestinal tract is extremely rare. We present a case of multifocal angiosarcoma involving the colon and bone. A 73-year-old male presented with anemia and pain in the left supra-iliac lesion. Colonoscopy revealed multiple hemorrhagic-appearance tumors. Computed tomography scan showed masses in the sigmoid colon and bone. A left-sided colectomy was performed to prevent bleeding from the tumor. The histopathological diagnosis was angiosarcoma of multiple sites of the colon. We chose a combination of paclitaxel and zoledronate as the chemotherapy regimen. After surgery, bone lesions were diminished by chemotherapy and showed no uptake on (18)F-fluorodeoxyglucose-positron emission tomography. The patient survived for 38 months after surgery.

The impact of obesity on learning laparoscopic surgery for colon cancer.

OBJECTIVE: This study evaluated the impact of obesity on learning to perform laparoscopic surgery for colon cancer. SUBJECTS AND METHODS: We compared the outcomes for 72 patients with colon cancer treated by a single surgeon between June 2005 and July 2008. The first 36 patients who underwent surgery were considered to be during the "early period," and the other 36 patients who underwent surgery as the "late period," and the patients with a body mass index (BMI) ≥25 kg/m(2) were defined as being obese. RESULTS: During the early period, the tumor stages of obese patients were less advanced than those of nonobese patients, whereas the length of the operation, surgical blood loss, and wound diameter of obese patients were worse than those of nonobese patients. Furthermore, the tumor stages in the obese patients during the late period were more advanced than those in obese patients during the early period, whereas the length of the operation and number of dissected lymph nodes in the obese patients during the late period were better than those in obese patients during the early period. CONCLUSIONS: We demonstrated that the differences of the surgical outcomes between obese and nonobese patients undergoing laparoscopic colon resection decreased as the surgeon's experience increased.

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 surgeon's 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.

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.

Hemangiopericytoma in the sacrococcygeal space: a case report.

INTRODUCTION: A 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 PRESENTATION: We 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. CONCLUSION: A 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.

Moderately differentiated colorectal adenocarcinoma as a lymph node metastatic phenotype: comparison with well differentiated counterparts.

BACKGROUND: The differences between the metastatic property of moderately (Mod) and well (Wel) differentiated colorectal adenocarcinoma remain unclear. Since Mod is unable to form complete acini, therefore an epithelial-mesenchymal transition (EMT) can occur in that structure. Herein, we hypothesized that Mod metastasizes more easily than the Wel counterparts. METHODS: The medical records of 283 consecutive patients with Mod (n = 71) or Wel (n = 212) who underwent surgery were reviewed between January 1, 2001, and December 31, 2003, for actual 5-year overall survival. We examined the differences between the clinicopathological characteristics of the Mod and the Wel groups. RESULTS: The lymph node involvement (p < 0.0001), lymphatic permeation, venous permeation, depth of invasion, liver metastasis, and carcinomatous peritonitis were significantly higher in the Mod group in comparison to the Wel group. The independent risk factors by a logistic regression analysis for lymph node involvement were as follows: lymphatic permeation, liver metastasis, and Mod (p = 0.0291, Relative Risk of 1.991: 95% Confidence Interval: 1.073-3.697). A Kaplan-Meier survival curve showed that Mod had a trend towards a poor survival (p = 0.0517). CONCLUSION: Mod metastasizes to the lymph nodes more easily in comparison to Wel. Therefore, patients with Mod may be considered the existence of lymph node involvement.