Kinuko Nagayoshi

Tumor deposit is a poor prognostic indicator for patients who have stage II and III colorectal cancer with fewer than 4 lymph node metastases but not for those with 4 or more.

BACKGROUND: Extranodal tumor deposits are involved in TNM classification. However, it is uncertain whether a tumor deposit is a regular lymph node metastasis, and its prognostic significance in patients with stage II or III colorectal cancer remains to be established. OBJECTIVE: This study aimed to determine the prognostic significance of tumor deposits for stage II and III colorectal cancer. DESIGN: This study is a retrospective review of clinicopathological data. SETTING: This study was conducted at a tertiary care hospital/referral center in Japan. PATIENTS: We reviewed the clinical course of 171 stage II and 173 stage III consecutive patients between January 1999 and December 2006. MAIN OUTCOME MEASURES: We examined the clinicopathological features of colorectal cancers with tumor deposits and calculated overall survival and recurrence-free survival of the patients according to the status of tumor deposits. The primary outcome was the impact of tumor deposits on patient survival. RESULTS: Thirty-five (10.2%) patients with colorectal cancers had tumor deposits in the pericolic and/or mesocolic region. Survival rates among the patients with tumor deposits were significantly lower than those without (5-year overall survival: 58.4% vs 81.0%, p < 0.0001; 5-year recurrence-free survival: 47.1% vs 73.4%, p < 0.0001). Tumor deposit was an independent prognostic factor for patients with colorectal cancer in multivariate analysis (overall survival: HR, 2.30; 95% CI, 1.26–4.04; p = 0.04; recurrence-free survival: HR, 2.42; 95% CI, 1.04–4.90; p = 0.04). Tumor deposit was an independent prognostic factor in N0 and N1 colorectal cancer, whereas N2 cancer had poor survival outcome regardless of tumor deposit. LIMITATIONS: Our study was a single-institution retrospective study, and the numbers of patients were relatively small to draw firm conclusions. CONCLUSION: Tumor deposit may be an independent adverse prognostic factor for stage II and III N1 colorectal cancer.

Galanin plays an important role in cancer invasiveness and is associated with poor prognosis in stage II colorectal cancer

Reliable predictors of tumor recurrence for patients with stage II colorectal cancer (CRC) are needed to select patients who should receive adjuvant chemotherapy. Although galanin (GAL) is expressed in several malignant tumors and is associated with cell proliferation and tumor growth, the prognostic value of GAL expression in CRC is poorly understood. We compared GAL expression between 56 patients with stage II and III CRC who developed tumor recurrences and 56 patients who did not. The clinical and prognostic significance of GAL expression was examined using our data and independent public datasets. We also analyzed the influence of GAL expression on the proliferation and invasive activity of CRC cells. Higher expression of GAL was associated with tumor recurrence among the CRC patients (P<0.001). Stage II CRC patients who presented with high expression levels of GAL had significantly poorer prognosis than those with low expression levels of GAL [5-year overall survival: hazard ratio (HR), 7.31; 95% confidence interval (CI), 2.38–24.04; P<0.001; 5-year recurrence-free survival: HR, 3.99; 95% CI, 1.61–9.44; P=0.004], but there was no association between GAL expression and survival in stage III CRC patients. These findings were supported by analysis of two public datasets. Functionally, siRNA-mediated silencing of GAL resulted in a significant decrease in the proliferative and invasive activities of CRC cells. In conclusion, high expression of GAL is associated with poor prognosis of stage II CRC patients and GAL expression may be related to the aggressive behavior of CRC.

A CpG island methylator phenotype of colorectal cancer that is contiguous with conventional adenomas, but not serrated polyps.

A subset of colorectal cancers (CRCs) harbor the CpG island methylator phenotype (CIMP), with concurrent multiple promoter hypermethylation of tumor-related genes. A serrated pathway in which CIMP is developed from serrated polyps is proposed. The present study characterized CIMP and morphologically examined precursor lesions of CIMP. In total, 104 CRCs treated between January 1996 and December 2004 were examined. Aberrant promoter methylation of 15 cancer-related genes was analyzed. CIMP status was classified according to the number of methylated genes and was correlated with the clinicopathological features, including the concomitant polyps in and around the tumors. The frequency of aberrant methylation in each CRC showed a bimodal pattern, and the CRCs were classified as CIMP-high (CIMP-H), CIMP-low (CIMP-L) and CIMP-negative (CIMP-N). CIMP-H was associated with aberrant methylation of MLH1 (P=0.005) and with an improved recurrence-free survival (RFS) rate following curative resection compared with CIMP-L/N (five-year RFS rate, 93.8 vs. 67.1%; P=0.044), while CIMP-N tumors were associated with frequent distant metastases at diagnosis (P=0.023). No concomitant serrated lesions were present in the tumors, whereas conventional adenoma was contiguous with 11 (10.6%) of 104 CRCs, including four CIMP-H CRCs. CIMP-H was classified in CRCs by a novel CIMP marker panel and the presence of concomitant tumors revealed that certain CIMP-H CRCs may have arisen from conventional adenomas.

Comparative detection of aberrantly methylated DNA in preoperative and postoperative stool from patients with colorectal cancers.

Background Early detection of colorectal cancer (CRC) is crucial to reducing tumor-related mortality. Evaluating aberrantly methylated DNA in stool is promising for CRC screening. However, DNA methylation in the colonic epithelium of background mucosa may compromise stool DNA (sDNA) test results. Thus, we compared aberrant methylation of cancer-related genes in preoperative and postoperative sDNA, with the aim of demonstrating that a cancer-specific methylated allele in sDNA originates from CRCs. Methods Patients who were to undergo CRC resection in Kyushu University Hospital during 2003-2010 were prospectively enrolled. Preoperative (pre) stool samples from 54 patients, postoperative (post) samples from 52 of the patients and tumor samples were collected. Aberrant promoter methylation of CDH4 and GATA5 was assessed in the primary tumors by methylation-specific polymerase chain reaction (MSP) and in stool samples by real-time MSP. Results Aberrant methylation of CDH4 and/or GATA5 was detected in 45 of CRC tissue samples (83.3%) and identified in 23 pre sDNA samples (42.3%) from CRC patients. Aberrant methylation was not found in pre sDNA obtained from CRC patients without aberrant methylation of these genes or in post sDNA in any patient. The detection rate of methylated alleles did not correlate with depth of invasion or tumor stage. Conclusion Our findings demonstrate that aberrantly methylated alleles identified in sDNA originate from CRCs. Although tumor-specific aberrant methylation is found in sDNA from patients harboring early and advanced CRC throughout the colon and rectum, the sensitivity of this test needs to be improved for early detection of CRC.

Reduced-port laparoscopic restorative proctocolectomy without diverting ileostomy

We introduced a reduced‐port procedure for laparoscopic restorative proctocolectomy without diverting ileostomy for patients with familial adenomatous polyposis and ulcerative colitis.

Feasibility of laparoscopic surgery for complex Crohn's disease of the small intestine

The laparoscopic approach for complex Crohns disease (CD), which involves abscess formation, fistula formation, and recurrent CD, is controversial. The aim of this study was to investigate the feasibility and safety of the laparoscopic approach for complex CD.

Laparoscopic en bloc excision of gastrointestinal stromal tumors of the rectum after neoadjuvant imatinib therapy: anteriorly extended intersphincteric resection combined with partial resection of the prostate

We herein present a novel technique for laparoscopic en bloc excision involving anteriorly extended intersphincteric resection with partial resection of the posterior lobe of the prostate for large rectal gastrointestinal stromal tumors (GISTs). The sequence of neoadjuvant imatinib therapy and this less invasive surgery for marginally resectable rectal GISTs has the potential to obviate the need for urinary reconstruction and permanent stomas without jeopardizing the tumor margin status.

Application of ultrasonography to high-tie and low-tie vascular ligation of the inferior mesenteric artery in laparoscopic colorectal cancer surgery: technical notes

BackgroundTwo ligation techniques can be applied in laparoscopy for left-sided colorectal cancer: (1) high-tie (HT), transection at the level of the inferior mesenteric artery (IMA); and (2) low-tie (LT), transection below the IMA, at the level of superior rectal artery (SRA), preserving the left colic artery (LCA). However, even with preoperative images, it can still be a challenge to identify these structures due to intraoperative individual conditions. In this study, we assess the use intraoperative ultrasonography (IOUS) to aid us in identifying the IMA and its branches to the SRA, LCA, and sigmoid artery.MethodsWe performed IOUS in 18 patients diagnosed with left-sided colorectal cancer. Preoperatively, a three-dimensional computed tomography (3D-CT) angiography was obtained in majority of the patients, to visualize the IMA and its branches. Two patients were contraindicated to receive a contrast study, hence, was unable to undergo 3D-CT angiography. The resected specimen was grossly examined for the study. The bifurcation types were identified and compared using different modalities: preoperative 3D-CT, IOUS, and gross examination of the resected specimen.ResultsThe branching of the IMA revealed by IOUS was consistent to the findings preoperatively by the 3D-CT and postoperatively by the resected specimen. The IOUS result of the two patients without preoperative 3D-CT evaluation was also consistent with the post-operative bifurcation type.ConclusionsIOUS is an easy and feasible modality which aids in detecting the branching of the IMA during LT and HT ligation in laparoscopic left-sided colorectal surgery. It can serve as an adjunct modality for 3D-CT angiography and can also be considered a safe alternative option for cases wherein 3D-CT angiography is unavailable.

Laparoscopic excision of neurogenic retrorectal tumors

Retrorectal tumors (RT) are uncommon and usually managed by open surgical excision. Laparoscopic excision for RT has been reported in only a small number of papers. We aimed to assess the laparoscopic approach for RT and to discuss the factors that made this procedure difficult. We performed laparoscopic excision using a five‐trocar technique for neurogenic RT in three patients. Tumors were successfully excised laparoscopically in two patients. However, the third patient required open conversion because the tumor was strongly adhered to the sacrum and could not be mobilized by dissection, resulting in poor visualization of the dissected site. Laparoscopic excision for RT provides excellent intraoperative visualization and good cosmesis in selected patients, but firm adherence to the sacrum may cause difficulty with this procedure.