Juvenile polyposis syndrome might be misdiagnosed as familial adenomatous polyposis: a case report and literature review.

BACKGROUND: Juvenile polyposis syndrome (JPS) is a rare disorder characterized by the presence of multiple juvenile polyps in the gastrointestinal tract, and germline mutations in SMAD4 or BMPR1A. Due to its rarity and complex clinical manifestation, misdiagnosis often occurs in clinical practice. CASE PRESENTATION: A 42-year-old man with multiple pedunculated colorectal polyps and concomitant rectal adenocarcinoma was admitted to our hospital. His mother had died of colon cancer. He was diagnosed with familial adenomatous polyposis (FAP) and underwent total proctocolectomy and ileal pouch anal anastomosis. Two polyps were selected for pathological examination. One polyp had cystically dilated glands with slight dysplasia. The other polyp displayed severe dysplasia and was diagnosed as adenoma. Three years later, his 21-year-old son underwent a colonoscopy that revealed more than 50 pedunculated colorectal juvenile polyps. Both patients harbored a germline pathogenic mutation in BMPR1A. Endoscopic resection of all polyps was attempted but failed. Finally, the son received endoscopic resection of polyps in the rectum and sigmoid colon, and laparoscopic subtotal colectomy. Ten polyps were selected for pathological examination. All were revealed to be typical juvenile polyps, with cystically dilated glands filled with mucus. Thus, the diagnosis of JPS was confirmed in the son. A review of the literatures revealed that patients with JPS can sometimes have adenomatous change. Most polyps in patients with JPS are benign hamartomatous polyps with no dysplasia. A review of 767 colorectal JPS polyps demonstrated that 8.5% of the polyps contained mild to moderate dysplasia, and only 0.3% had severe dysplasia or cancer. It is difficult to differentiate juvenile polyps with dysplasia from adenoma, which could explain why juvenile polyps have been reported to have adenomatous changes in patients with JPS. Therefore, patients with JPS, especially those with concomitant dysplasia and adenocarcinoma, might be easily diagnosed as FAP in clinical practice. CONCLUSIONS: Juvenile polyp with dysplasia is often diagnosed as adenoma, which might lead to the misdiagnosis of JPS as FAP. The differential diagnosis of JPS versus FAP, should be based on comprehensive evaluation of clinical presentation, endoscopic appearance and genetic investigations; not on the presence or absence of adenoma.

Clinical significance of multiple gene detection with a 22-gene panel in formalin-fixed paraffin-embedded specimens of 207 colorectal cancer patients.

BACKGROUND: Simultaneous detection of multiple molecular biomarkers is helpful in the prediction of treatment response and prognosis for colorectal cancer (CRC) patients. METHODS: A 22-gene panel consisting of 103 hotspot regions was utilized in the formalin-fixed paraffin-embedded (FFPE) tissue samples of 207 CRC patients, using the next-generation sequencing (NGS)-based multiplex PCR technique. Those 22 genes included AKT1, ALK, BRAF, CTNNB1, DDR2, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, FGFR2, FGFR3, KRAS, MAP2K1, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, STK11, and TP53. RESULTS: Of the 207 patients, 193 had one or more variants, with 170, 20, and 3 having one, two, and three mutated genes, respectively. Of the total 414 variants identified in this study, 384, 25, and 5 were single-nucleotide variants, deletion, and insertion. The top four frequently mutated genes were TP53, KRAS, PIK3CA, and FBXW7. There was high consistency between the results of NGS-PCR technique and routine ARMS-PCR in KRAS and BRAF mutation detection. Univariate and multivariate analyses demonstrated that advanced TNM stage, elevated serum CEA, total variants number ≥ 2, AKT1 and PTEN mutation were independent predictors of shorter DFS; poor differentiation, advanced TNM stage, total variants number ≥ 2, BRAF, CTNNB1 and NRAS mutation were independent predictors of shorter OS. CONCLUSIONS: It is feasible to detect multiple gene mutations with a 22-gene panel in FFPE CRC specimens. TNM stage and total variants number ≥ 2 were independent predictors of DFS and OS. Detection of multiple gene mutations may provide additional prognostic information to TNM stage in CRC patients.

Trends, clinicopathological features, surgical treatment patterns and prognoses of early-onset versus late-onset colorectal cancer: A retrospective cohort study on 34067 patients managed from 2000 to 2021 in a Chinese tertiary center.

BACKGROUND: In recent decades, the incidence of early-onset colorectal cancer (EOCRC) has reportedly increased in several developed countries, whereas that of late-onset colorectal cancer (LOCRC) has decreased continuously. The trends, clinicopathological features, surgical treatment patterns, and prognoses of EOCRC and LOCRC in China remain unclear. MATERIALS AND METHODS: This retrospective cohort study was performed in China using data from our pathology registry collected in 2000-2021. Pathologically confirmed cases of colorectal cancer (CRC) were analyzed. The average annual percentage change (AAPC) was estimated to quantify the secular trends. Clinicopathological features, surgical treatment patterns, and prognoses were compared between the two groups. Multivariate Cox regression analyses were performed for disease-free survival and overall survival. RESULTS: A total of 34,067 cases of CRC were included, with 6,369 cases of EOCRC and 27,698 cases of LOCRC. Overall, the numbers of EOCRC (AAPC = 8.4%), LOCRC (AAPC = 11.6%), and CRC (AAPC = 11.0%) cases increased significantly from 2000 to 2021. Compared to the LOCRC group, the EOCRC group had fewer men, comorbidities, concomitant cancers, polyps, and KRAS mutations; more symptoms, rectal cancers, multiple primary CRCs, deficient mismatch repair tumors, poorly differentiated, mucinous adenocarcinoma or signet ring cell carcinoma, advanced TNM stage, vascular invasion, perineural invasion; less laparoscopic surgery and sphincter-preserving surgery; more extended radical resection, perioperative chemoradiotherapy and targeted therapy; and similar disease-free and overall survival rates. CONCLUSION: The numbers of EOCRC and LOCRC cases have continuously increased over the last two decades. The EOCRC group has more aggressive features, advanced TNM stage, intensified surgical treatment and perioperative treatment than the LOCRC group, but similar disease-free and overall survival rates. More CRC screening programs are recommended for younger adults to combat the rapidly increasing trend of EOCRC.

Laparoscopic-assisted ileal pouch-rectal muscle sheath anastomosis for the treatment of familial adenomatous polyposis.

PURPOSE: Familial adenomatous polyposis (FAP) is a colorectal disease treated by proctocolectomy. While ileal pouch-anal anastomosis preserves the anus, defecation dysfunction and incontinence can occur. We herein report the results of an improved laparoscopic-assisted ileal pouch-rectal muscle sheath anastomosis after total proctocolectomy which preserves anal function, and compare the results with ileal pouch-anal anastomosis. METHODS: A total of 22 patients with FAP were randomized to receive either ileal pouch-anal anastomosis (n = 11) or ileal pouch-rectal muscle sheath anastomosis (n = 11) after total proctocolectomy. Operation time, intraoperative blood loss, postoperative complications, length of hospitalization and postoperative anal pressure, defecation frequency, and quality of life were recorded and compared between the two groups. RESULTS: All patients completed a minimum follow-up of 1 year. At the 1 year after the surgery, the daytime defecation frequency was 4.64 ± 0.92 times/day in the ileal pouch-rectal muscle sheath anastomosis group and 6.55 ± 1.13 times/day in the ileal pouch-anal anastomosis group (P = 0.004). Resting anal pressure, maximum squeeze pressure, and average number of daytime defecations in the ileal pouch-rectal muscle sheath group were all better than in the ileal pouch-anal anastomosis group (all, P < 0.05) CONCLUSIONS: Ileal pouch-rectal muscle sheath anastomosis is associated with better anal function than ileal pouch-anal anastomosis.

Local recurrence after intended curative excision of presacral lesions: causes and preventions.

OBJECTIVE: This study was designed to explore causes for local recurrence of presacral lesions after intended curative surgery and discuss prevention strategies. METHODS: Medical data of presacral lesions in our hospital from January 2001 to September 2009 were retrospectively studied, including preoperative examinations, intraoperative findings, and postoperative histopathologies. RESULTS: Of 39 patients (29 women and 10 men) with presacral lesions, who ranged in age from 14 to 71 (mean, 39.56) years, 7 patients were diagnosed with recurrent presacral lesions on admission. Preoperative pelvic MRI, pelvic CT, and endorectal ultrasonography (ERUS) were performed in 23, 22, and 8 cases, respectively. MRI/CT showed that five cases had two coexisting lesions and three cases had lobulated or dumbbell shaped lesions, all of which were confirmed by intraoperative findings. ERUS suspected involvement of the rectal wall in three cases: adhesion to the rectal wall in two cases, and tumor invasion in the remaining case. During the operation, 26, 8, and 2 cases were resected by the transsacral, transabdominal, and combined abdominosacral approach, respectively. Four patients underwent simultaneous coccygectomy, and three patients received simultaneous resection of the sacrum and coccyx. Simultaneous partial resection of the invaded sigmoid colon or rectum was performed in two patients, respectively. By postoperative pathological examination, three cases were found to have ruptured cystic lesions, three had previous cyst rupture history, and five had infected lesions. CONCLUSIONS: Presacral lesions are likely to be multiple, lobulated, infected, ruptured, and adhesive to the sacrococcyx and rectum, which contribute to the high local recurrence rate. Preoperative CT/MRI/ERUS and careful intraoperative exploration are required to direct surgical treatment and to reduce local recurrence. Optimal selection of surgical approach also is very important to reduce local recurrence. Presacral lesions attached to the sacrococcyx or rectum require simultaneous partial resection of the sacrococcyx or rectum to reduce local recurrence.

Dielectric-barrier discharge (DBD) plasma treatment reduces IgG binding capacity of ß-lactoglobulin by inducing structural changes.

The present study investigated the effects of dielectric-barrier-discharge (DBD) plasma treatment (12 kHz, 40 kV) at 1, 2, 3, and 4 min on the reduction of the immunoglobulin G (IgG) binding capacity of ß-lactoglobulin (ß-LG). The IgG binding capacity of ß-LG was reduced by 58.21% following a plasma treatment time of 4 min, as confirmed by western-blot and ELISA analyses. The reduction in IgG binding capacity of ß-LG was directly related to a stepwise change in its structure. The initial drop in the IgG binding capacity of ß-LG was found to be caused by conformational alteration, free sulfhydryl exposure and cross-linkage of molecules induced by oxidation of NH-/NH2- functional groups of peptide bonds and of sensitive amino acid residues (Tyr, Trp) as confirmed by SDS-PAGE, surface hydrophobicity and multi-spectroscopic analyses. Plasma treatment of more than 3 min resulted in cleavage of disulfidebonds and fragmentation of ß-LG that was confirmed by LC-MS/MS analysis, which resulted a further decline in the IgG binding capacity of ß-LG. Plasma treatment therefore has great potential as a substitute treatment for enzymatic hydrolysis for the production of hypoallergenic milk protein-based products.

Diagnosis and treatment of diffuse cavernous hemangioma of the rectum: report of 17 cases.

BACKGROUND: Diffuse cavernous hemangioma of the rectum (DCHR) is a rare benign vascular disease, which is often misdiagnosed and difficult to treat. METHODS: Seventeen cases of DCHR in our hospitals from 1995 to 2009 were identified. The detailed data of diagnosis, treatment, and prognosis were carefully studied. RESULTS: Seven, three, two, and one patient were mistaken as having hemorrhoids, colitis, portal hypertension, and rectal polypus, respectively. The mean delay time between initial symptoms and final diagnosis was 17.63 years (range = 0-48 years). Colonoscopy and MRI were important in the diagnosis of DCHR because of their high positive rates and specific features. All of the lesions originated from the dentate line, extending to the proximal colorectal wall. Most of the lesions were found to be restricted to the rectosigmoid wall and the rectal mesentery. Involvement of right gluteus maximus and right leg was revealed by MRI in two patients. After admission, six patients underwent coloanal sleeve anastomosis and seven patients underwent pull-through transection and coloanal anastomosis. The latter procedure was superior to the former with respect to length of operation, intraoperative blood loss, intraoperative blood transfusion, and perioperative complications. CONCLUSION: DCHR is often misdiagnosed. Preoperative colonoscopy and MRI are essential in making the correct diagnosis and to depict the extent of the lesion accurately. Due to its origination from the dentate line and the involvement of the whole layer of the rectal wall and the rectal mesentery, the treatment of choice for DCHR is complete resection by the pull-through transection and coloanal anastomosis.

[Lymph node metastasis and its risk factors in T1-2 staging invasive rectal carcinoma].

OBJECTIVE: To investigate the lymph node metastasis and its risk factors in T1-2 staging invasive rectal carcinoma. METHODS: The data of 1116 patients with rectal cancer treated with total mesorectal excision (TME) technique from January 2000 to April 2009 was analyzed retrospectively. The clinicopathological factors analyzed included gender, age, primary symptom type, number of symptoms, duration of symptom, synchronous polyps, preoperative serum carcino-embryonic antigen level, preoperative serum CA19-9 level, the distance of tumor from the anal verge, tumor size, tumor morphological type, tumor circumferential extent, tumor differentiation and tumor T staging. Statistical analysis was performed by using Logistic regression analysis and Chi-square test. RESULTS: A total of 1116 patients were enrolled, and 358 cases (32.1%) were classified as with T1-2 staging tumor. Two cases (5.6%, 2/36) in patients with a T1 staging tumor were found with lymph node metastasis, and 75 cases (23.3%, 75/322) in patients with a T2 staging tumor, respectively. Compared with patients with T3-4 staging tumor, lymph node metastasis rate of the patients with T1-2 staging tumor was significantly lower [21.5% (77/358) vs. 51.6% (391/758), P < 0.05]. Only the tumor T staging was found as the independent risk factor for the lymph node metastasis in patients with T1-2 staging tumor on multivariate Logistic regression analysis (odds ratio: 5.162; 95%CI: 1.212 to 21.991; P = 0.026). CONCLUSIONS: A substantial proportion of T1-2 staging rectal cancers harbor metastatic lymph nodes and the clinicopathological features except for T staging fail to predict the lymph node metastasis. Further research is warranted to identify the risk factors and guide the clinical practice in patient with T1-2 staging tumor.

Which Definition of Upper Rectal Cancer Is Optimal in Selecting Stage II or III Rectal Cancer Patients to Avoid Postoperative Adjuvant Radiation?

BACKGROUND: In most guidelines, upper rectal cancers (URC) are not recommended to take neoadjuvant or adjuvant radiation. However, the definitions of URC vary greatly. Five definitions had been commonly used to define URC: 1) >10 cm from the anal verge by MRI; 2) >12 cm from the anal verge by MRI; 3) >10 cm from the anal verge by colonoscopy; 4) >12 cm from the anal verge by colonoscopy; 5) above the anterior peritoneal reflection (APR). We hypothesized that the fifth definition is optimal to identify patients with rectal cancer to avoid adjuvant radiation. METHODS: The data of stage II/III rectal cancer patients who underwent radical surgery without preoperative chemoradiotherapy were retrospectively reviewed. The height of the APR was measured, and compared with the tumor height measured by digital rectal examination (DRE), MRI and colonoscopy. The five definitions were compared in terms of prediction of local recurrence, survival, and percentages of patients requiring radiation. RESULTS: A total of 576 patients were included, with the intraoperative location of 222 and 354 tumors being above and straddle/below the APR, respectively. The median distance of the APR from anal verge (height of APR) as measured by MRI was 8.7 (range: 4.5-14.3) cm. The height of APR positively correlated with body height (r=0.862, P<0.001). The accuracy of the MRI in determining the tumor location with respect to the APR was 92.1%. Rectal cancer above the APR had a significantly lower incidence of local recurrence than those straddle/below the APR (P=0.042). For those above the APR, there was no significant difference in local recurrence between the radiation and no-radiation group. Multivariate analyses showed that tumor location regarding APR was an independent risk factor for LRFS. Tumor height as measured by DRE, MRI and colonoscopy were not related with survival outcomes. Fewer rectal cancer patients required adjuvant radiation using the definition by the APR, compared with other four definitions based on a numerical tumor height measured by MRI and colonoscopy. CONCLUSIONS: The definition of URC as rectal tumor above the APR, might be the optimal definition to select patients with stage II/III rectal cancer to avoid postoperative adjuvant radiation.

Comparison of Fresh Frozen Tissue With Formalin-Fixed Paraffin-Embedded Tissue for Mutation Analysis Using a Multi-Gene Panel in Patients With Colorectal Cancer.

Background: Next generation sequencing (NGS)-based multi-gene panel tests have been performed to predict the treatment response and prognosis in patients with colorectal cancer (CRC). Whether the multi-gene mutation results of formalin-fixed paraffin-embedded (FFPE) tissues are identical to those of fresh frozen tissues remains unknown. Methods: A 22-gene panel with 103 hotspots was used to detect mutations in paired fresh frozen tissue and FFPE tissue from 118 patients with CRC. Results: In our study, 117 patients (99.2%) had one or more variants, with 226 variants in FFPE tissue and 221 in fresh frozen tissue. Of the 129 variants identified in this study, 96 variants were present in both FFPE and fresh frozen tissues; 27 variants were found in FFPE tissues only; 6 variants were found only in fresh frozen tissues. The mutation results demonstrated >94.0% concordance in all variants, with Kappa coefficient >0.500 in 64.3% (83/129) of variants. At the gene level, concordance ranged from 73.8 to 100.0%, with Kappa coefficient >0.500 in 81.3% (13/16) of genes. Conclusions: The results of mutation analysis performed with a multi-gene panel and FFPE and fresh frozen tissue were highly concordant in patients with CRC, at both the variant and gene levels. There were, however, some important differences in mutation results between the two tissue types. Therefore, fresh frozen tissue should not routinely be replaced with FFPE tissue for mutation analysis with a multi-gene panel. Rather, FFPE tissue is a reasonable alternative for fresh frozen tissue when the latter is unavailable.

Rectal cancer patients with downstaging after neoadjuvant chemoradiotherapy and radical resection do not benefit from adjuvant chemotherapy.

BACKGROUND: Whether adjuvant chemotherapy is beneficial for rectal cancer patients who respond well to neoadjuvant chemoradiotherapy (NCRT) and undergo radical resection is controversial. This study aimed to assess the effect of adjuvant chemotherapy on the oncological outcomes of ypT0-2N0 rectal cancer patients after NCRT and radical resection, and identify the prognostic factors. METHODS: The clinical and pathological data of rectal cancer patients with ypT0-2N0 who underwent NCRT and radical resection between January, 2010 and June, 2018 were collected and retrospectively analyzed. The oncological outcomes of the chemotherapy (chemo) group and the non-chemotherapy (non-chemo) group were compared. Multivariate analysis, using a Cox proportional hazard model, was performed to identify independent predictors of oncological outcome. RESULTS: Of the 121 rectal cancer patients enrolled, 90 patients received postoperative adjuvant chemotherapy with no fewer than 3 cycles (the chemo group), and the other 31 patients with fewer than 3 cycles (the non-chemo group). There was no significant difference in the 5-year disease-free survival (DFS) or overall survival (OS) rates between the two groups (DFS: 79.1% vs. 82.9%, P=0.442; OS: 87.5% vs. 78.2%, P=0.667). cT4 is an independent risk factor for OS (HR =4.227, 95% CI: 1.128-15.838, P=0.02) and DFS (HR =4.878, 95% CI: 1.752-13.578). Preoperative consolidation chemotherapy with Capeox or FOLFOX after NCRT significantly improved the DFS rate (HR =0.212, 95% CI: 0.058-0.776, P=0.019). CONCLUSIONS: Rectal cancer patients with ypT0-2N0 who underwent NCRT and radical resection did not benefit significantly from postoperative adjuvant chemotherapy. For these patients, cT4 was an independent risk factor for OS and DFS. Preoperative consolidation chemotherapy with Capeox or FOLFOX after NCRT can significantly improve DFS.

Influencing factors of symptomatic anastomotic leakage after anterior resection of the rectum for cancer.

BACKGROUND: The aim of the present study was to analyze the factors associated with anastomotic leakage after anterior resection for rectal cancer. METHODS: Retrospectively collected consecutive data of 738 rectal cancer patients who underwent anterior resection in our hospital between 2005 and 2008 were reviewed. The associations between 15 patient-related and surgery-related variables and anastomotic leakage were studied with both the univariate chi-square test and multivariate logistic regression analysis. RESULTS: Univariate analysis showed that risk factors associated with anastomotic leakage were low rectal cancer (located 5 cm or less above the dentate line) (5.9% vs. 0.9%; P = 0.003), non-specialized surgeon (3.9% vs. 11.3%; P = 0.031), and defunctioning transanal catheter placement (14.5% vs. 3.6%; P < 0.001). It should be noted that the mean surgeon case volumes of anterior resection of colorectal surgeons and non-specialized general surgeons were 43 per year and 2 per year, respectively (P < 0.001). In addition, there was a tendency for colorectal surgeons to operate on a greater proportion of low rectal cancers (72.1% vs. 52.8%; P = 0.003). In the multivariate analysis, besides low rectal cancer, non-specialized surgeon, and transanal catheter placement, three other factors were associated with anastomotic leakage: diabetes mellitus (P = 0.027), free distal margins less than 1 cm (P = 0.009), and a defunctioning stoma (P = 0.031). In a further analysis of 522 patients with low rectal cancer, the leakage rate in patients with a defunctioning stoma was significantly lower (2.9% vs. 8.5%; P = 0.007). By contrast, the leakage rate in the transanal catheter placement group was higher (15.1% vs. 4.9%; P = 0.008), because of its poor protective effect as well as the selection bias. CONCLUSIONS: From the findings of this study, we believe that low rectal cancer, non-specialized surgeons, and diabetes mellitus are risk factors for anastomotic leakage after rectal surgery, and that a defunctioning stoma could significantly reduce the incidence of leakage in low rectal cancer patients.

[Factors associated with anastomotic leakage after anterior resection in rectal cancer].

OBJECTIVE: To analyze the factors associated with anastomotic leakage after anterior resection in rectal cancer with the technique of total mesorectal excision (TME). METHODS: From January 2005 and December 2007, 738 consecutive patients with rectal cancer underwent anterior resection. The data of those patients was collected and reviewed retrospectively. The associations between anastomotic leakage and 9 patient-related variables as well as 7 surgical-related variables were examined. RESULTS: Low rectal cancer (located 7 cm or less above the anal edge), non-specialized surgeon and transanal tube use were the risk factors associated with anastomotic leakage on univariate analysis. The anastomotic leakage rate of low-rectal cancer was significantly higher than that of high-rectal cancer (5.9% vs. 0.9%, P = 0.003). The anastomotic leakage rate of the cases operated by colorectal surgeon was significantly lower than that of the cases operated by non-specialized surgeon (3.9% vs. 11.3%, P = 0.031). There was a tendency for colorectal surgeons to operate on a greater proportion of low rectal cancer than non-specialized surgeons (72.1% vs. 52.8%, P = 0.003). The leakage rate of transanal tube group was unexpectedly higher than that in patients without transanal tube (14.5% vs. 3.6%, P < 0.001). On multivariate logistic regression analysis, diabetes mellitus (P = 0.027), distance less than 1 cm from tumor to distal resection margin (P = 0.009) and defunctioning stoma (P = 0.031) were also associated with anastomotic leakage rate besides low rectal cancer, non-specialized surgeon and transanal tube use. In a further analysis of 522 patients with low rectal cancer, the leakage rate of defunctioning stoma group was significantly lower than that of non-stoma group (2.9% vs. 8.5%, P = 0.007). By contract, the leakage rate of transanal tube group was still higher than that in patients without transanal tube (15.1% vs. 4.9%, P = 0.008) because of its poor protective effect as well as the selection bias. CONCLUSIONS: Low-rectal cancer, non-specialized surgeons and diabetes mellitus are risk factors of anastomotic leakage after rectal surgery. A defunctioning stoma was effective in preventing leakage after low-rectal cancer surgery.

ZNF148 modulates TOP2A expression and cell proliferation via ceRNA regulatory mechanism in colorectal cancer.

BACKGROUND: Competing endogenous RNA (ceRNA) regulation is a novel hypothesized mechanism that states RNA molecules share common target microRNAs (miRNAs) and may competitively combine into the same miRNA pool. METHODS: Zinc finger protein 148 (ZNF148) and TOP2A expression were analyzed in 742 colorectal cancer (CRC) tissues using immunohistochemistry (IHC). ZNF148 mRNA, TOP2A mRNA, miR101, miR144, miR335, and miR365 expression were estimated in 53 fresh frozen CRC tissues by reverse transcription polymerase chain reaction. Mechanisms underpinning ceRNA were examined using bioinformatics, correlation analysis, RNA interference, gene over-expression, and luciferase assays. RESULTS: Protein levels of ZNF148 and TOP2A detected by IHC positively correlated (Spearman correlation coefficient [rs] = 0.431, P < 0.001); mRNA levels of ZNF148 and TOP2A also positively correlated (r = 0.591, P < 0.001). Bioinformatics analysis demonstrated that ZNF148 and TOP2A mRNA had 13 common target miRNAs, including miR101, miR144, miR335, and miR365. Correlation analysis demonstrated that levels of ZNF148 mRNA were negatively associated with levels of miR144, miR335, and miR365. Knockdown and overexpression tests showed that ZNF148 mRNA and TOP2A mRNA regulated each other in HCT116 cells, respectively, but not in Dicer-deficient HCT116 cells. Luciferase assays demonstrated that ZNF148 and TOP2A regulated each other through 3'UTR. Overexpression of ZNF148 mRNA and TOP2A mRNA caused significant downregulation of miR101, miR144, miR335, and miR365 in the HCT116 cells. We also found that knockdown of ZNF148 and TOP2A significantly promoted cell growth, and overexpression of ZNF148 and TOP2A inhibited cell proliferation, which was abrogated in Dicer-deficient HCT116 cells. CONCLUSION: ZNF148 and TOP2A regulate each other through ceRNA regulatory mechanism in CRC, which has biological effects on cell proliferation.

Differences of protein expression profiles, KRAS and BRAF mutation, and prognosis in right-sided colon, left-sided colon and rectal cancer.

To compare protein expression levels, gene mutation and survival among Right-Sided Colon Cancer (RSCC), Left-Sided Colon Cancer (LSCC) and rectal cancer patients, 57 cases of RSCC, 87 LSCC and 145 rectal cancer patients were included retrospectively. Our results demonstrated significant differences existed among RSCC, LSCC and rectal cancer regarding tumor diameter, differentiation, invasion depth and TNM stage. No significant difference was identified in expression levels of MLH1, MSH2, MSH6, PMS2, ß-Tubulin III, P53, Ki67 and TOPIIα, and gene mutation of KRAS and BRAF among three groups. Progression Free Survival (PFS) of RSCC was significantly lower than that of LRCC and rectal cancer. In univariate analyses, RSCC, preoperative chemoradiotherapy, poor differentiation, advanced TNM stage, elevated serum CEA and CA19-9 level, tumor deposit, perineural and vascular invasion were found to be predictive factors of shorter PFS. In multivariate analyses, only differentiation and TNM stages were found to be independent predictors of PFS. In conclusion, compared with LSCC and rectal cancer, RSCC has larger tumor size, poor differentiation, advanced TNM stage and shorter survival. The shorter survival in RSCC might be attributed to the advanced tumor stage caused by its inherent position feature of proximal colon rather than genetic difference.

[Emergence application of colonoscopic placement of self-expandable metal stent without fluoroscopic monitoring].

OBJECTIVE: To evaluate the efficacy and safety of colonoscopy-guided placement of self-expandable metallic stent without fluoroscopic monitoring in the emergence management for acute malignant colorectal obstruction. METHODS: Clinical data of 42 patients (24 males and 18 females with a mean age of 64.3 years) undergoing colonoscopy-guided placement of self-expandable metallic stents without fluoroscopic monitoring for acute malignant colorectal obstruction between January 2010 and June 2012 were reviewed retrospectively. RESULTS: The obstruction was located in the rectum (n=19), sigmoid (n=9), descending colon (n=8), splenic flexure (n=1), hepatic flexure (n=3), and ascending colon (n=2). Technical success was achieved in all the 42 patients (100%). The mean time of operation was (11.8±10.4) min (range 1.1-51.0 min). No serious procedure-related complication occurred. Minor bleeding occurred in 3 cases (7.1%). One patient died on the second day after surgery because of heart failure. CONCLUSIONS: Colonoscopy-guided placement of self-expandable metallic stents without fluoroscopic monitoring in emergence management for acute malignant colorectal obstruction is effective and safe with shorter operative time.

[Colonoscopic restoration for sigmoid vovulus in the elderly].

OBJECTIVE: To investigate the emergency therapeutic strategy for sigmoid vovulus in the elderly. METHODS: Clinical data of 14 elderly patients with sigmoid vovulus were analyzed retrospectively. RESULTS: The mean age was(79.1±7.2) years(range, 70-93), and 11 patients (78.6%) were male. Emergency decompression and restoration with colonoscopy was performed in all the patients with a success rate of 100%. No patient required emergent surgery. Four patients(28.6%) recurred and they were managed well by repeat colonoscopic restoration. CONCLUSION: Emergency colonoscopic restoration is the first treatment of choice for sigmoid vovulus in the elderly because it is safe and effective, and can be performed repeatedly.

[Association of tumor budding with clinicopathological characteristics and prognosis in T2 rectal cancer].

OBJECTIVE: To demonstrate the association of tumor budding with clinicopathological features and prognosis in T2 rectal cancer. METHODS: Clinicopathological data of 123 patients who underwent potentially curative resection for T2 rectal carcinoma between 2001 and 2005 at the Changhai Hospital were collected. All pathology slides were stained with hematoxylin and eosin for microscopic examinations. The maximum value of tumor buds(MV) and average value of tumor buds(AV) were calculated, which were classified as low value (≤5), median value (5 < bud value < 10), and high value (≥10). RESULTS: Univariate analysis and multivariate analysis revealed that MV(P=0.000), AV(P=0.001), and lymphatic invasion (P=0.006) were independent predictors for lymph node metastasis in T2 rectal cancer. Neural invasion and poorly differentiation were significantly associated with MV(P<0.05). Neural invasion, vascular invasion and poorly differentiation were were significantly associated to AV (P<0.01). Disease-free survival (DFS) of patients with low AV, median AV and high AV was 110.5 months, 95.8 months, and 60.0 months respectively. There were significance differences in DFS of low AV with median and high AV(P<0.05). DFS of patients with low MV, median MV and high MV was 115.1 months, 98.5 months, and 86.0 months respectively. There were significance differences in DFS between low and high AV, and median and high MV(P<0.01 and P<0.05), while no significant difference existed between low and median MV. CONCLUSION: Tumor budding is a useful marker to indicate high invasiveness of rectal cancer and a valuable prognostic predictor.

[Analysis of risk factors associated with lymph node metastasis and prognosis of T1-2 colorectal cancer].

OBJECTIVE: To investigate factors associated with lymph node metastasis and prognosis in patients with T1-2 colorectal cancer. METHODS: Patients with pT1-2 colorectal cancer between January 1999 to January 2005 were included. Chi-square test and multivariable logistic analysis were performed to evaluate risk factors associated with lymph node metastasis. Survival outcomes were analyzed using Kaplan-Meier and Cox regression model. RESULTS: Tumor location and depth of invasion were independent risk factors for lymph node metastasis(P<0.01 and P<0.05). Gender, age, tumor gross pattern, tumor differentiation, carcinoembryonic antigen level, and tumor diameter were not associated with lymph node metastasis. Lymph node metastasis and distant metastasis on postoperative follow-up were independent risk factors for survival(P<0.05 and P<0.01). CONCLUSION: Factors associated with lymph node metastasis in pT1-2 colorectal cancer do not affect the survival. However, lymph node metastasis and distant metastasis are predictive for survival.

[Preliminary study on relationship between multi-drug resistance-associated protein 4 and radiosensitivity of rectal cancer].

OBJECTIVE: To explore the correlation between multi-drug resistance-associated protein 4(MRP4) and the sensitivity of rectal cancer to radiation. METHODS: A total of 95 patients with advanced rectal cancer and received radiation therapy between January 2000 and January 2009. MRP4 and P53 protein expression in the paraffin-embedded specimen were detected by immunohistochemistry. Logistic regression analysis was used to evaluate factors associated with the sensitivity of rectal cancer to radiation. RESULTS: Forty patients(42%) were sensitive to radiation therapy, of whom 10(11%) achieved pathological complete remission. Fifty-five patients were (58%) not responsive to radiation. Patients with low expression of MRP4 had a 66.7%(24/36) response rate, significantly higher than that of patients with high MRP4 expression (29.1%,16/59)(P<0.05). Patients with low expression of P53 had a 63.9%(23/36) response rate, significantly higher than that of patients with high P53 expression(28.8%,17/59)(P<0.01). The response rate after long course radiation therapy was 83.3%(20/24), significantly higher than that of patients who underwent short and medium course radiation[(31.3%, 5/16) and(27.3%,15/55)](P<0.01). Multivariate Logistic regression analysis showed radiation regimen, the expression of P53 and MRP4 protein were independently associated with the sensitivity of rectal cancer to radiation(P<0.05). CONCLUSION: MRP4 may serve as a predictive marker for the sensitivity of rectal cancer to preoperative radiation.