Very Early Colorectal Anastomotic Leakage within 5 Post-operative Days: a More Severe Subtype Needs Relaparatomy.

Early anastomotic leakage (AL), usually defined as leakage within 30 post-operative days, represents a severe entity. However, mounting evidence has indicated that majorities of leakage occur within one week after surgery, making late AL rarity. Here we analyzed 101 consecutive colorectal AL, all of which occurred within 30 post-operative days, during Jan 2013 and Dec 2015 in cancer hospital of Fudan University. AL occurring within 5 post-operative days was defined as very early AL (vE-AL). We evaluated risk factors of vE-AL compared with non-vEAL and correlated with post-leakage peritonitis and need of relaparatomy. We found that AL occurred at median time of 7 days after surgery. 23 cases were vE-AL. Reconstruction of post-peritoneum for mid-low rectal carcinoma significantly reduced incidence of vE-AL compared with non-vE-AL (p = 0.042). Patients with vE-AL was associated with presence of peritonitis (p = 0.031), the latter significantly correlated with increased re-operation rate (p = 6.8E-13). Besides, patients with vE-AL trended to correlate with increased re-operation rate after leakage (p = 0.088). In concludsion, vE-AL occurring within 5 post-operative days represents a severe subtype associated with general peritonitis and need of relaparatomy.

High expression of lncRNA MALAT1 suggests a biomarker of poor prognosis in colorectal cancer.

OBJECTIVE: This study sought to investigate the role of the long noncoding RNA MALAT1 in the prognosis of stage II/III colorectal cancer (CRC) patients. METHODS: The expression of MALAT1 was evaluated in cancer tissues from 146 stage II/III CRC patients undergoing radical resection and 23 paired normal colonic mucosa samples using quantitative real-time reverse transcriptase PCR. Differences in the expression of MALAT1 between 23 CRC and paired normal colonic mucosa samples were analysed with the Wilcoxon test. Relationships between the expression level of MALAT1, patient clinicopathological parameters and disease-free survival (DFS) and overall survival (OS) were analysed using the univariate Kaplan-Meier method and the multivariate COX regression model. RESULTS: The MALAT1 levels in cancerous tissues were 2.26 times higher than those measured in noncancerous tissues, and this difference was statistically significant (P = 0.0004). Based on their expression level of MALAT1, the patients were divided into a high MALAT1 expression group (n = 73) and a low expression group (n = 73). Patients with tumours harbouring higher expression of MALAT1 showed a significantly worse prognosis with a hazard ratio (HR) of 2.863 (95% CI, 1.659 to 4.943; P < 0.001) for DFS and 3.968 (95% CI, 1.665 to 9.456; P = 0.002) for OS. Furthermore, patients with perineural invasion demonstrated significantly worse DFS (HR = 3.459, 95% CI 2.008 to 5.957; P < 0.001) and OS (HR = 3.750, 95% CI 1.743 to 8.069; P = 0.001) than those without perineural invasion. Multivariate analyses indicated that MALAT1 expression and perineural invasion were two independent prognostic risk factors for patients with CRC. CONCLUSION: The expression of MALAT1 is upregulated in CRC tissues, and a higher expression level of MALAT1 might serve as a negative prognostic marker in stage II/III CRC patients.

Icariin-mediated inhibition of NF-κB activity enhances the in vitro and in vivo antitumour effect of 5-fluorouracil in colorectal cancer.

Colorectal cancer (CRC) is an aggressive malignancy that has a poor prognosis. 5-Fluorouracil (5-FU) is a first line chemotherapeutic medication used in the treatment of gallbladder cancer; however, the efficacy is below satisfactory. Icariin is a natural compound that is conventionally reported to have activity against a variety of cancers. This study was carried out to investigate the anti-cancer effect of icariin in CRC cells and to determine whether the compound can enhance the antitumour activity of 5-FU. Cell proliferation and apoptosis were measured using an MTT assay and flow cytometry, respectively. The activity of transcription factor NF-κB was determined by EMSA method. The expression of apoptosis- and proliferation-related proteins was determined by western blotting. The in vivo antitumour effect of combination treatment with icariin and 5-FU on CRC was also assessed using a murine model of CRC. Icariin sensitized the CRC cells to 5-FU both in vitro and in vivo. The antitumour activity of icariin and its potentiating effect on the antitumour activity of 5-FU implicated the suppression of NF-κB activity and consequent down-regulation of the gene products regulated by NF-κB. Our results showed that icariin, suppressed tumour growth and enhanced the antitumour activity of 5-FU in CRC by inhibiting NF-κB activity. Therefore, we suggest that combination of icariin with 5-FU might offer a therapeutic benefit to the patients with CRC; however, further studies are required to ascertain this proposition.

Diffusion-weighted magnetic resonance imaging for predicting the response of rectal cancer to neoadjuvant concurrent chemoradiation.

AIM: To evaluate the clinical value of diffusion-weighted magnetic resonance imaging (DW-MRI) in predicting the response of rectal cancer to neoadjuvant chemoradiation. METHODS: This prospective study was approved by our institutional review board, and informed consent was obtained from each patient. Fifteen patients (median age 56 years) with locally advanced rectal cancer were treated in our hospital from June 2006 to December 2007. All patients were stage IIIB-C according to the results of MRI and endorectal ultrasound examinations. All patients underwent pelvic irradiation with 45 Gy/25 fx per 35 days. The concurrent chemotherapy regimen consisted of capecitabine 625 mg/m², bid (Monday-Friday), and oxaliplatin 50 mg/m², weekly. The patients underwent surgery 5-8 wk after the completion of neoadjuvant therapy. T downstaging was defined as the downstaging of the tumor from cT3 to ypT0-2 or from cT4 to ypT0-3. Good regression was defined as TRG 3-4, and poor regression was defined as TRG 0-2. Diffusion-weighted magnetic resonance images were obtained prior to and weekly during the course of neoadjuvant chemoradiation, and the apparent diffusion coefficient (ADC) values were calculated from the acquired tumor images. RESULTS: Comparison with the mean pretreatment tumor ADC revealed an increase in the mean tumor ADC during the course of neoadjuvant chemoradiation, especially at the 2(nd) week (P = 0.004). We found a strong negative correlation between the mean pretreatment tumor ADC and tumor regression after neoadjuvant chemoradiation (P = 0.021). In the T downstage and tumor regression groups, we found a significant increase in the mean ADC at the 2(nd) week of neoadjuvant therapy (P = 0.011; 0.004). CONCLUSION: DW-MRI might be a valuable clinical tool to help predict or assess the response of rectal cancer to neoadjuvant chemoradiation at an early timepoint.

[Study on clinical value of three localization methods in laparoscopic colorectal tumor surgery].

OBJECTIVE: To evaluate the clinical effectiveness of three localization methods, including methylene blue, metal clips and intraoperative colonoscopy in laparoscopic colorectal surgery. METHODS: A retrospective analysis was performed to review the clinical data of 64 patients who underwent the laparoscopic colorectal operations in Cancer Hospital of Fudan University from December 2009 to June 2012. Three methods of tumor localization were used perioperatively, including 23 cases of methylene blue, 20 of metal clips and 21 of colonoscopy. RESULTS: Operations were successfully performed in this cohort and there were no deaths or complications. In methylene blue group, intraoperative colonoscopy was performed in two cases because of the inability to visualize blue dye on the serosal surface of the intestinal wall, another 2 cases were converted to open operation because of methylene blue diffusion and inability to identify resection margin. Intraoperative colonoscopic localization was required for 3 cases of sigmoid colon or upper rectal tumor because of inaccurate tumor localization by metal clips. Poor operative exposure due to obvious bowel distension prompted the conversion to open surgery in 2 cases of colonoscopy localization group, and the accurate position of the lesion was not found in another 2 cases due to long pedunculated adenoma. CONCLUSIONS: Colorectal tumor can be localized effectively by endoscopic methylene blue tattooing at a maximum of 2 tumors before operation and the method of 4-point positioning can significantly improve the accuracy of colorectal tumor localization. Tumor localization preoperatively on the day of surgery by metal clip is accurate for the right or left colon cancer. Intraoperative colonoscopy can localize tumor accurately and rapidly for rectosigmoid or descending tumor, and the incidence of bowel distension can be significantly reduced. Localization method should be considered according to the tumor location and surgical procedure.

Are biomarkers correlated with recurrence patterns in patients with resectable gastric adenocarcinoma.

The aims of this study are to analyze the failure patterns in radical resected gastric adenocarcinoma, and to evaluate the correlation between recurrence patterns and potentially prognostic factors, including clinical pathological characteristic and biomarkers. Between Jan 2004 and Jun 2006, 84 patients were enrolled into the database analysis, including 8 with clinical stage I, 20 with clinical stage II, 21 with clinical stage IIIA, 22 with clinical stage IIIB and 13 with clinical stage IV, male 61 and female 23. The collected biomarkers including: preoperative tumor markers: CEA, AFP, CA199, CA50, CA72-4 and CA24-2; postoperative immunohistochemical (IHC) markers: Bax, Bcl-2, P27, CyclinD1, TOPO2, MDR, GST-π, Ki67, epidermal growth factor receptor (EGFR), P21, P53, proliferating cell nuclear antigen (PCNA), C-myc and Neu. Three-year local control rate (LCR), disease-free survival (DFS) and over-all survival (OS) were 66, 61 and 64% respectively. Logistic regression analysis showed cyclinD1 and CEA were correlated with prognosis; cyclinD1, CEA were correlated with loco-regional recurrence; PCNA was correlated with remote metastasis; bcl-2, ki67, c-myc2 and Neu were correlated with lymph node metastasis. The present study indicate that patterns of recurrence are variable and may be associated with specific biomarkers, in addition, high level of CEA and low-expressed of cyclinD1 resulted in poor prognosis.

Retrospective analysis of perianal Paget's disease with underlying anorectal carcinoma.

AIM: To analyze clinical and pathological characteristics of an aggressive subtype of perianal Paget's disease (PPD) and explore its rational treatment modalities. METHODS: PPD patients were retrospectively collected in the institutional colorectal database of the Fudan University Shanghai Cancer Center. Detailed patient histories of past medical condition, diagnosis, treatment, and pathological findings were reviewed. Surgical specimen from diagnosis and surgery were reviewed by two independent pathologists for confirmation of diagnoses. Follow up was accomplished by clinical interview by cellphone. RESULTS: In total, eight cases of PPD were analyzed. All patients had underlying anorectal adenocarcinoma, including seven with synchronous lesions and one with metachronous lesions. Moreover, all anorectal lesions had a mucin-producing component. The median age at diagnosis was 65 (range 29-81 years), and the male/female ratio was 7:1. The Median follow-up time of all patients was 61.5 mo (range 10-204 mo). One patient treated with abdominoperineal resection (APR) died from lung metastases 10 mo after the APR operation. The other patients are still free of disease at the time of this analysis. CONCLUSION: PPD is a rare malignancy and is easily misdiagnosed. Underlying anorectal cancer was not unusual and was a significant prognostic factor. Rational treatment of both anorectal cancer and PPD lesion is essential for long-term survival.