[Analysis on clinical factors affecting transrectal natural orifice specimen extraction in rectal cancer surgery].

Objective: To identify the factors associated with successful transrectal specimen extraction after laparoscopic rectal cancer resection. Methods: A retrospective case-control study was conducted. Clinical data of rectal cancer patients who did or did not successfully undergo transrectal specimen extraction in Shanghai East Hospital between January 2017 and December 2017 were retrieved through the rectal cancer database of Shanghai East Hospital. Case inclusion criteria: (1) tumor size ≤7 cm by pelvic MRI; (2) body mass index (BMI)≤ 30 kg/m(2); (3) no history of neoadjuvant chemoradiotherapy; (4) no anal stenosis. Clinical data including age, gender, BMI, tumor obstruction, distance from tumor to anal verge, history of abdominal operation, maximal diameter of tumor and width of mesorectum in the anteroposterior dimension measured by pelvic MRI, etc. were collected. The χ(2) test was used to perform univariate analysis. Multivariate logistic regression was used to identify factors affecting transrectal specimen extraction. Results: A total of 208 patients were included in the analysis. Of 208 patients, 132 were men and 76 were women; mean age was (63±11) years old and median tumor size was 3.8 (IQR, 3.0 to 5.0) cm. Sixty-six (31.7%) patients completed transrectal specimen extraction successfully. Univariate analysis showed that patients who completed transrectal specimen extraction were more likely to have a lower BMI (χ(2)=7.420, P=0.006), be free from malignant obstruction (χ(2)=8.972, P=0.003), have a shorter distance from tumor to the anal verge (<5.0 cm) (χ(2)=14.960, P<0.001), a smaller tumor size (≤5.0 cm) (χ(2)=18.495, P<0.001) and a thinner mesorectum in the anteroposterior dimension (≤6.0 cm) (χ(2)=34.612, P<0.001) than those who failed to perform transrectal specimen extraction. Gender, age or history of abdominal operation were not associated with the successful extraction (all P>0.05). Multivariate analysis revealed that BMI ≤25.0 kg/m(2) (OR=2.32, 95% CI: 1.06 to 5.06, P=0.034), free from malignant obstruction (OR=3.01, 95% CI: 1.82 to 6.69, P<0.001), the distance from tumor to the anal verge <5.0 cm (OR=3.73, 95% CI: 1.22 to 11.43, P=0.021), tumor size ≤ 5.0 cm (OR=4.43, 95% CI: 1.39 to 14.09, P=0.012), and the anteroposterior width of mesorectum ≤ 6.0 cm (OR=4.30, 95% CI: 2.02 to 9.18, P<0.001) were independent protective factors for successful transrectal specimen extraction. Conclusion: Preoperative assessment of BMI, malignant obstruction, distance from tumor to the anal verge, tumor size and anteroposterior width of mesorectum is beneficial to choose appropriate patients with rectal cancer to undergo transrectal specimen extraction.

Secreted protein acidic and rich in cysteine expression in human colorectal cancer predicts postoperative prognosis.

OBJECTIVE: Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix glycoprotein involved in cell proliferation, migration and angiogenesis. The aim of this study was to assess its expression in colorectal cancer, see whether and how it correlates with clinicopathological features, and evaluate its potential prognostic significance. PATIENTS AND METHODS: SPARC expression was detected by microarrays containing 847 immunohistochemically stained specimens, and further correlated with the clinicopathological and prognostic data. The prognostic significance of its expression was assessed using Kaplan-Meier survival with log-rank tests. Multivariate regression utilizing Cox's proportional hazard model was used to evaluate prognostic factors. RESULTS: SPARC expression in the normal colorectal mucosa and colorectal cancer tissue was significantly different (p < 0.001). Low SPARC expression was found to be associated with poor prognosis, and it was unfavorably correlated with overall survival and disease-free survival in colorectal cancer patients. In addition, SPARC expression in surrounding mesenchymal and stromal cells, bowel wall invasion, lymph node metastasis, and distant metastasis were independent prognostic factors for overall survival and disease-free survival. CONCLUSIONS: Reduced expression of SPARC in colorectal cancer tissue is associated with poor prognosis and aggressive clinicopathological features. Therefore, SPARC expression could potentially be used as a prognostic predictor for colorectal cancer patients.

Treatment for early ultralow rectal cancer: pull-through intersphincteric stapled transection and anastomosis (PISTA) versus low anterior resection.

BACKGROUND: The aim of this study was to compare the functional and oncologic results of pull-through intersphincteric stapled transection and anastomosis (PISTA) with low anterior resection (LAR) in the treatment for early ultralow rectal cancer. METHODS: A total of 278 patients with early ultralow rectal cancer were retrospectively included and analyzed, with 136 in the PISTA group and 142 in the LAR group. RESULTS: Gender, age, tumor diameter, distance from the dentate line to the inferior margin of the tumor, tumor stage, length of operation and postoperative complications were comparable in the two groups. Compared with the LAR group, the PISTA group had a more accurate distal transection site, a lower daily fecal frequency (6 (5-7) vs. 8 (7-9), p < 0.001) and a lower Wexner incontinence score (13 (10-14) vs. 14 (13-16), p < 0.001) 3 months after ileostomy reversal, and a higher rate of satisfactory fecal continence (97.1 % vs. 90.8 %, p = 0.043). The follow-up period of the PISTA group was similar to that of the LAR group (56 (30-81) months vs. 54 (30-80) months, p = 0.982). The PISTA group was associated with a lower local recurrence rate (2.2 % vs. 11.3 %, p = 0.003). Kaplan-Meier analysis also showed that the PISTA group was associated with longer overall survival (p = 0.018) and longer local recurrence-free survival (p = 0.004) than the LAR group, while distant metastasis-free survival (p = 0.896) was comparable in the two groups. Multivariate analysis identified lymph node metastasis (p < 0.001) and operation (PISTA vs. LAR, p = 0.031) as independent predictive factors for local recurrence-free survival. CONCLUSIONS: PISTA is a technically simple, oncologically safe and functionally favorable procedure for the treatment for early ultralow rectal cancer.

More advanced or aggressive colorectal cancer is associated with a higher incidence of "high-grade intraepithelial neoplasia" on biopsy-based pathological examination.

BACKGROUND: Invasion of submucosa (ISM) is required for the pathological diagnosis of colorectal cancer according to the WHO criteria. A large proportion of colorectal cancers may be underdiagnosed as high-grade intraepithelial neoplasia (HGIN) because ISM is not identified in the preoperative biopsy. The aim of this study was to investigate the clinicopathologic features that are associated with missing the diagnosis of ISM in biopsy specimens of invasive colorectal cancer. METHODS: Three hundred and sixteen patients diagnosed with colorectal cancer between January 2007 and December 2008 with well-preserved preoperative biopsy specimens were enrolled in the study. Three hundred and eleven patients had an isolated lesion, and five had two lesions. Biopsy specimens were reevaluated by two senior pathologists. Clinicopathologic features, biopsy pathology and surgical pathology results of all patients were analyzed by univariate and multivariate analyses. RESULTS: ISM was identified in 216 cases (67.3 %) by biopsy-based pathological examination, and missed in 105 (32.7 %) cases, 72 of which were diagnosed as HGIN. Univariate analysis indicated that in colorectal cancer patients with smaller biopsy specimens (P = 0.042), mucinous or signet-ring cell carcinoma (P = 0.003), higher WHO tumor grade (P = 0.001) and positive lymph nodes (P = 0.011), ISM was more likely to be missed. There was a trend toward an increased diagnosis of ISM with the increase in the number of biopsy specimens (P = 0.105). On multivariate logistic regression analysis, smaller biopsy specimens (OR, 1.810; 95 % CI, 1.081-3.032; P = 0.024) and higher WHO tumor grade (OR, 2.073; 95 % CI, 1.046-4.107; P = 0.037) were the only factors associated with failure to identify ISM. CONCLUSIONS: A large number of invasive colorectal cancers are at risk of being underdiagnosed as HGIN by biopsy-based pathology. The smaller the biopsy size, the less likely it is that the muscularis mucosae is included in the specimen. Also, in the more advanced or aggressive colorectal cancers, ISM is more likely to be missed on biopsy, which may be due to the destruction of the muscularis mucosae by more aggressive cancers.

Diffuse cavernous hemangioma of the rectosigmoid colon.

Diffuse cavernous hemangioma of the rectosigmoid colon is an uncommon benign vascular lesion. We report 5 cases of diffuse cavernous hemangioma, focusing on the clinical features, diagnosis procedure and treatment. Five patients have undergone sphincter-saving procedures, 3 cases had coloanal sleeve anastomoses and 1 patient each had pull-through anastomosis and lower anterior resection. During the follow-up, which ranged from 3 to 10 years, 3 patients had no further anal bleeding and 2 patients had minor intermittent anal bleeding. Continence for normal stool was satisfactory in all patients. In conclusion, sphincter-saving procedure is most appropriate and curative approach for the treatment of diffuse cavernous hemangioma. Imaging study plays an important role in the diagnosis, preoperative staging and follow-up.

Study on the retention behaviour of metal-tetraphenyl porphine chelates in reversed-phase high performance liquid chromatography.

The retention behaviour of metal chelates of alpha,beta,gamma,delta-tetraphenylporphine (TPP) was studied in reversed-phase high performance liquid chromatography (RP-HPLC). On C18 column, with various organic solvents as mobile phases, the retention of the chelates tends to increase in the following order: ZnTPP < TPP < NiTPP < CuTPP. This retention behaviour can get a good explanation from Horvath's "solvophobic theory". With the assumption that the electrostatic field strength of metal chelates can be measured by the ratio of electronegativity vs. ionic radius (EN/ri) of central metal ion, EN/ri was established to be an index for the retention behaviour of metal-TPP chelates. It was found that lnk' is in good linear relationship with the EN/ri value.

5-Fluorouracil induces apoptosis in human colon cancer cell lines with modulation of Bcl-2 family proteins.

Recently, apoptosis has been implicated as one of the end points of cells exposed to chemotherapeutic agents. The p53 and Bcl-2 family of proteins are involved in chemotherapy-induced apoptosis, but in a cell type-dependent manner. We sought to determine the roles played by the p53 and Bcl-2 family of proteins in 5-fluorouracil (5-FU)-induced apoptosis of human colon cancer cell lines. We first studied the p53 genetic and functional status, and then 5-FU, at inhibitory concentration of 50% (IC50) doses, was used to induce apoptosis, which was confirmed by morphological analysis and enzyme-linked immunosorbent assay (ELISA). Bcl-2, Bcl-X(L), Bax, Bad, Bak and p53 protein expression was analysed by Western blotting. Using five human colon cancer cell lines, we found that equitoxic (IC50) doses of 5-FU induced apoptosis in both wild-type p53 and mutant p53 cells. Analysis of the steady-state levels of Bcl-2 family proteins showed high expression of Bcl-X(L) in all of the cell lines except Colo320. Bcl-2 was expressed in two of them. Bax presented with the lowest basal expression and Bad showed homogeneous expression. On the other hand, Bak expression varied more than fivefold among these cells. In cells containing wild-type p53 (e.g. LoVo), 5-FU-induced apoptosis was accompanied by increased expression of Bax and Bak without consistent modulation of other bcl-2 family proteins. In contrast in cells containing mutant p53 (e.g. DLD1), Bak expression was remarkably increased. There was a significant correlation between chemosensitivity and Bcl-X(L) to Bax ratio, rather than Bcl-2 to Bax. In conclusion, these results suggest that some members of the Bcl-2 family of proteins, in human colon cancer cell lines, are modulated by 5-FU and that the ratio of Bcl-X(L) to Bax may be related to chemosensitivity to 5-FU.

Role of p53 and p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients.

BACKGROUND: Recent studies showed that p53 and p21 may play major roles in determining tumor radiosensitivity through the apoptosis pathway. The aim of this study was to investigate the predicting value of radiosensitivity in human rectal carcinoma. METHODS: p53 and p21/WAF1 expressions in formalin fixed, paraffin-embedded, preradiation biopsy samples from 49 patients with primary rectal carcinoma were analyzed immunohistochemically. p53 and p21 expressions and their relationships with histopathologic changes after radiation and other clinical features were evaluated. RESULTS: Expressions of p53 and p21/WAF1 were 49 and 28.6 percent, respectively. In 36.7 percent of total tumors, significant histopathologic effect can be observed. There was a significant inverse expression of p53 and p21. Most of the p53(+) or p21(-) tumors were radioresistant, and the majority of p53(-) or p21(+) tumors were radiosensitive. Tumors size in the radiosensitive, p53(-), or p21(+) group decreased more significantly than in radioresistant, p53(+), or p21(-) group (P < 0.01), and patients with radioresistant, p53(+), or p21(-) tumors had more local recurrence, more distant metastasis, and a shorter five-year survival rate than those with radiosensitive, p53(-), or p21(+) tumors, but without statistic significance. No statistically significant correlation can be observed between other tumor clinical features and radiosensitivity, p53, or p21 expressions. CONCLUSION: Immunohistochemistry detection of p53 and p21 expressions may be useful parameters for more radiosensitive patients selected for preoperative radiotherapy.

Results of the double stapling procedure in colorectal surgery.

In this report we review our results with the double stapling technique (DST) in 162 patients with colorectal diseases in an attempt to identify some of the potential pitfalls of this new technique. Among these 162 patients, there were 125 patients with colorectal cancer, 25 with chronic ulcerative colitis (UC), 9 with familial adenomatous polyposis (FAP), 2 with adult Hirschsprung's disease, and 1 with sigmoid colon fistula. A total of 46 anastomoses (28 for rectal cancer, 13 for UC, 3 for FAP, and 2 for adult Hirschsprung's disease) were performed at or near the dentate line. Of these, 10 had protective diverting colostomy or ileostomy. The results showed that 6 patients with rectal cancer had anastomotic leakage (3.7%); however, 4 of the 6 patients had also received preoperative irradiation. All the leaks healed after the patients had undergone diverting colostomy, but 7 patients with rectal cancer suffered from neurogenic bladder postoperatively (4.3%). Wound infection occurred in 4 patients (2.5%), anastomotic bleeding in 3 (1.9%), and anal pain in 1 (0.6%), respectively. One patient with rectal cancer and multiple liver metastases died of disseminated intravascular coagulation (DIC). These results thus suggest that the double stapling technique provides a safe anastomosis at or near the dentate line not only for rectal cancer but also for UC, FAP, and adult Hirschsprung's disease.

Zonal adult Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease is a congenital disorder which is rare in adulthood. In typical cases the aganglionosis involves mainly the rectum or rectosigmoid colon and the lesion starts from the anal valve. Zonal segmental aganglionosis is a very rare type even in children. PATIENT: A 54 year old women with zonal segmental aganglionosis had an aganglionic segment 18 cm in length located in the rectosigmoid colon with an 8 cm long normal appearing rectum and dilated proximal colon. Resection of the stenotic segment with end to end anastomosis was performed. CONCLUSION: The functional result was excellent five years after the operation.

[The effect of trilostane and dexamethasone on serum amino acids and TNF in endotoxemic rats].

By the use of specific endogenous GC biosynthesis inhibitor Trilostane and exogenous GC Dexamethasone (Dex), we established three rat models with similar severity of endotoxemia, but different plasma GC level. With these models we studied the effect of elevated plasma GC on serum TNF, pathological changes of vital organs and the changes in serum amino acids and glucose concentration in comparable endotoxemic condition. It was observed that plasma GC level was negatively correlated with the maximum TNF concentration, but positively correlated with the liver tyrosine transaminase activity, serum amino acids and glucose concentrations and as the serum GC level was elevated, the pathological changes of intestine, stomach, liver and lungs became less pronounced. From these results, it was supposed that in severe endotoxemia hypersecration of endogenous GC and maintenance of high level plasma GC are essential for animals to alleviate tissue injuries by reducing the overproduction of the host-derived mediators such as TNF and promoting the metabolism of amino acids and glucose.