Genetic variations affecting serum carcinoembryonic antigen levels and status of regional lymph nodes in patients with sporadic colorectal cancer from Southern China.

BACKGROUND: Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications. METHODS AND FINDINGS: Genome-wide association study (GWAS) was conducted in a cohort study with 4,346 healthy male adults using the Illumina Omni 1 M chip. Candidate SNPs associated with elevated sCEA levels were validated in 194 CRC patients on ABI Taqman platform. Eight candidate SNPs were validated in CRC patients. The rs1047781 (chr19- FUT2) (A/T) was associated with elevated sCEA levels, and rs8176746 (chr9- ABO) was associated with the regional lymph metastasis in the CRC patients. The preoperative sCEA level was a risk factor for tumor recurrence in 5 years after operation (OR = 1.427, 95% CI: 1.005∼1.843, P = 0.006). It was also one of the risk factors for regional lymph node metastasis (OR = 2.266, 95% CI: 1.196∼4.293, P = 0.012). The sCEA level in rs1047781-T carriers was higher than that in the A carriers in CRC patients without lymph node metastasis (P = 0.006). The regional lymph node metastasis in patients with homozygote AA of rs8176746 was more common than that in the heterozygote AG carriers (P = 0.022). In addition, rs1047781-AT and TT CRC patients exhibited a worse disease-free survival than AA genotype carriers (P = 0.023). CONCLUSIONS: We found candidate SNPs associated with elevated sCEA levels in both healthy males and CRC population. Rs1047781 (chr19- FUT2) may be the susceptible locus for recurrence of CRC in a population from Southern China.

[Analysis of 61 cases undergoing sphincter-preserving procedure with intersphincteric resection by telescopic anastomosis for ultra-low rectal cancer].

OBJECTIVE: To investigate the efficacy and safety of sphincter-preserving procedure with transabdominal intersphincteric resection for ultra-low rectal cancer. METHODS: Clinical data of 61 cases with ultra-low rectal cancer (distance from anal verge ranged from 4-5 cm) were analyzed retrospectively. The patients underwent sphincter-preserving procedure with intersphincteric resection and telescopic anastomosis. RESULTS: There were 34 males and 27 females. The mean age was 56.7 years. The inferior border of the tumor was 4 cm above the anal verge in 21 cases, and 5 cm in 40 cases. There 55 patients with rectal adenocarcinoma in this cohort. The tumor was well-differentiated in 24 cases, moderately-differentiated in 29 cases, and poorly-differentiated in 2 cases. There were 6 cases with malignant adenoma. The TNM staging was T1N0M0 in 36 cases, T2N0M0 in 23, and T3N1M0 in 2. The ability to control defecation significantly improved in 1-3 months postoperatively, and returned to normal in 6-12 months. Two patients developed anastomotic leak (3.3%), and 3 anastomotic stenosis (4.9%) postoperatively. Fifty-four patients(88.5%) had follow-up. The median follow-up time was 6.2 years. The local recurrence rate was 5.6%, and the 5-year-survival rate was 73.5%. CONCLUSION: Sphincter-preserving procedure with intersphincteric resection and telescopic anastomosis is a safe and effective procedure for ultra-low rectal cancer.

[Clinical experience of 371 cases of sphincter-preservation with telescopic anastomosis after radical excision for low-middle rectal cancer].

OBJECTIVE: To evaluate the clinical efficacy, feasibility and safety of sphincter-preservation with telescopic anastomosis of colon and rectal mucosa in low-middle rectal cancer. METHODS: A retrospective analysis was carried out in 371 patients with low-middle rectal cancer in whom telescopic anastomosis was used. There were 224 males and 147 females, with a mean age of 57.9 (21-99) years. The lower margins of the tumors located between 5-8 cm from the anal verge. On histopathology, there were 361 adenocarcinomas, including 138 well-differentiated, 201 moderately differentiated, 11 poorly differentiated, 11 mucinous adenocarcinoma, and 10 adenomas with neoplastic changes. According to the Duke's stage classification, 120 were TNM stage I, 222 stage II, 26 stage III, and 3 stage IV. RESULTS: Three hundred and eighteen (318/371, 85.7%) cases were followed up, and the median follow up time was 5.8 years. Postoperative complications were observed, including 16(4.3%) cases with anastomotic leak, and 8 (2.1%) with anastomotic stenosis. All the patients resumed normal bowel function during 12-24 weeks after operation, with 1-3 times per day. The local recurrence rate was 6.3% (20/318). Hepatic and lung metastasis was 14.5% (46/318) and 2.5% (8/318), respectively. The 5-year survival rate was 69.7%. CONCLUSION: The sphincter-preservation with telescopic anastomosis procedure is safe and effective for low-middle rectal cancer, and the sphincter function can be well-preserved.

[Clinical study of 231 cases of radical excision with sphincter preservation by casing anastomosis in low rectal cancer].

OBJECTIVE: To investigate the clinical efficacy, feasibility and safety of sphincter-preserving procedure by casing anastomosis of colon and rectal mucosa in low rectal cancer. METHODS: A retrospective analysis was carried out in 231 cases of low rectal cancer performed casing anastomosis. RESULTS: One hundred and ninety-seven (197/231, 85.3%) cases were followed up, the median time of the follow up was 5.9 years (range, 2 months-14 years). Eight (3.4%) cases of stoma leak and 3 (1.2%) cases of stoma stenosis were found post operation. Defecating function recovered normally (1 - 3 times per day) in 12 - 24 weeks after operation in all patients. Local recurrence was found in 5.1% (10/197) of the cases. Hepatic and lung metastasis was found in 15.2% (30/197) and 2.5% (5/197) of the patients, respectively. The five-year survival rate was 71.6% totally. CONCLUSIONS: The casing anastomosis procedure with sphincter preservation is safe and efficacy for low rectal cancer. With the procedure, the anal function can be preserved well, stoma leak is decreased, and the five-year survival rate is the same as Miles operation.

[Clinical analysis of therapeutic effects of sphincter-preserving operation and Miles operation for rectal cancer].

OBJECTIVE: To investigate and compare therapeutic effects of sphincter-preserving operation and Miles operation for rectal cancer. METHODS: A retrospective analysis was carried out in 572 cases of rectal cancer operations performed from January 1980 to December 2006. RESULTS: Sphincter-preserving operation was carried out in 403 cases and Miles procedure in 169 cases. The follow-up rate was 76.2% (436/572) with a period of 0.5 - 25.0 years (median, 9.5 years). Local recurrence occurred in 6.3% (20/317) of sphincter-preserving operation and 7.6% (9/119) of Miles operation, the differences was not significant (chi2 = 1.3942, P > 0.05). Distal metastasis was found in 50 cases (15.7%) of sphincter-preserving operation and 19 cases (16.2%) of the Miles operation with no significant difference (chi2 = 0.6672, P > 0.05). There was no significant difference in five-year survival rate between the two groups, with 67.8% in sphincter-preserving operation and 67.2% in Miles operation. CONCLUSIONS: Sphincter-preserving operations can improve the quality of life in rectal cancer although with the same five-year survival rate and recurrence rate as Miles operation. The operation for rectal cancer should be performed individually according to the location, the bionomics and the clinical stage.

[Extended parietal cell vagotomy in the treatment of acute perforation of duodenal ulcer in 176 cases].

OBJECTIVE: To evaluate the long-term therapeutic efficacy of extended parietal cell vagotomy (EPCV) in the treatment of duodenal ulcer complicated with acute perforation. METHODS: Therapeutic efficacy of EPCV in 176 cases subjected to duodenal ulcer with acute perforation since 1979 was evaluated, including postoperative complication, ulcer recurrence rate, gastric empting function, endoscopic and radiographical examination, nutritional status and Visick classification. RESULTS: Among 176 patients, 153 (86.9%) cases were successfully followed-up for 5 years after operation. No operative death was found. Postprandial superior belly fullness occurred in 13 cases (8.5%) and heartburn in 12 cases (7.8%), which could be relieved by Domperidone. Adhesive ileus was noted in 4 cases (2.6%) which was cured by adhesiolysis. The total ulcer recurrence rate was 2.6% (4 cases) within 2 to 3 years after operation. Superficial gastritis occurred in 21 cases (13.7%) and duodenal bulb in 31 cases (20.3%). Sinus ventriculi vermicular motion was good and gastric emptying was normal. No anemia was found. Body weight gained in 116 cases (75.8%). One hundred and forty-six cases(95.4%) were reforming Visick grade I and II , 3 cases(2.0%) grade III , and 4 cases (2.6%) IV . CONCLUSIONS: EPCV is convenient for performance with low postoperative complication rate. Its long-term efficacies are quite good, which including normal nutritional status, high quality of life and low ulcer recurrence rate. EPCV is one of effective and safe treatments for duodenal ulcer complicated with acute perforation.

[Analysis of 618 cases of radical resection of rectal carcinoma].

OBJECTIVE: To investigate and analyse curative effects of Miles operation and anal sphincter preserving operation for rectal carcinoma in 20 years. METHODS: From 1984 to 2004, 618 cases of rectal carcinoma that underwent radical resection including Miles operation and anal sphincter preserving procedures were analysed retrospectively each 10 years, earlier 10 years from 1984 to 1994, and later 10 years from 1994 to 2004. RESULTS: Among the 618 cases, 492 (79.6%) were followed up. The median of the follow-up time was 5.4 years. In the earlier 10 years, local recurrence rate of post operation was 6.9% (14/201), for Miles operation and anal sphincter preserving procedures the local recurrence rate was 6.7% and 7.1% respectively. In the later 10 years, the local recurrence rate was 5.1% (15/291), 4.8% for Miles operation, 5.2% for anal sphincter preserving procedures. With the procedure of canular anastomosis of colon and rectal mucosa, the local recurrence rate was 4.9%. Overall five-year survival rate was 64.7% (130/201) in the earlier 10 years, 66.3% (59/89) for Miles operation, 63.4% (71/112) for anal sphincter preserving procedures. In the later 10 years, the five-year survival rate was 68.0% (198/291) in all, for Miles operation 66.3% (55/83), for anal sphincter preserving procedures 68.7% (143/208). With the procedure of canular anastomosis of colon and rectal mucosa, the five-year survival rate was 71.3% (62/87). CONCLUSIONS: The operation for rectal cancer should be chosen individually according to locus, biological character, and clinical stages. Anal sphincter preserving procedures are performed increasingly, and they provide the same five-year survival rate as Miles operation does, and the patient's quality of life can be improved obviously.

Comparative study of proteome between primary cancer and hepatic metastatic tumor in colorectal cancer.

AIM: To identify the differential proteins associated with colorectal cancer genesis and hepatic metastasis. METHODS: Hydrophobic protein samples were extracted from normal colorectal mucosa, primary cancer lesion and hepatic metastatic foci of colorectal cancer. With two-dimensional electrophoresis and image analysis, differentially expressed protein spots were detected, and the proteins were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry and peptide mass fingerprint analysis. RESULTS: Significant alterations of the proteins in number and expression levels were discovered in primary cancer and hepatic metastatic foci, the expression of a number of proteins was lost in 25-40 ku, but protein spots was increased in 14-21 ku, compared with normal mucosa. Nine differentially expressed protein spots were identified. Three proteins expressed in normal mucosa, but lost in primary cancer and hepatic metastasis, were recognized as calmodulin, ribonuclease 6 precursor and mannosidase-alpha. Proapolipoprotein was expressed progressively from normal mucosa to primary cancer and hepatic metastasis. The differentially expressed protein of beta-globin was found in normal mucosa and hepatic metastatic tumor, but lost in primary cancer lesion. Cdc 42, a GTP-binding protein, was identified in hepatic metastasis. The protein spots of C4 from primary cancer, M7 and M9 from hepatic metastasis had less homology with the proteins in database. CONCLUSION: Variations of hydrophobic protein expression in colorectal cancer initiation and hepatic metastasis are significant and can be observed with two-dimensional electrophoresis. The expression of calmodulin, ribonuclease 6 precursor and mannosidase-alpha is lost but the expression of proapolipoprotein is enhanced which is associated with colorectal cancer genesis and hepatic metastasis. Cdc 42 and beta-globin are expressed abnormally in hepatic metastasis. Protein C4, M7 and M9 may be associated with colorectal cancer genesis and hepatic metastasis.

Effects of cell membrane phospholipid level and protein kinase C isoenzyme expression on hepatic metastasis of colorectal carcinoma.

BACKGROUND: The molecular mechanism of hepatic metastasis of colorectal cancer is not well understood. The aim of this study was to assess the relations between phospholipid contents of cellular membrane and isoenzyme expression of protein kinase C (PKC) and their effects on hepatic metastasis of colorectal cancer. METHODS: High performance liquid chromatography was used to detect contents of cell membrane phospholipids: phosphatidylinosital (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in primary foci, paratumor mucosa and hepatic metastatic foci in patients with colorectal carcinoma. The mRNA expression levels of PKC-alpha, -betaII, -delta, -epsilon, -lambda, -zeta isoenzymes were detected with the QRT-PCR technique. RESULTS: The levels of PI, PC and PE in primary foci and hepatic metastatic foci were higher than those in paratumor mucosa. The level of PE in hepatic metastatic foci was much higher than that in primary foci (t=98.88, P<0.01); but the levels of PI and PC were not significantly different between primary foci and hepatic metastatic foci (t=1.73, 1.36, P>0.05). The expression levels of PKC-betaII, -delta, -epsilon, -lambda, -zeta were enhanced in primary foci and hepatic metastatic foci, but the level of PKC-alpha in primary foci was decreased as compared with that in paratumor mucosa. The levels of PKC-delta, -epsilon, -lambda, -zeta in hepatic metastatic foci were higher than those in primary foci. A positive correlation was observed between the expression levels of PI, PC and PKC-betaII and also between those of PE and PKC-delta, -epsilon, -lambda, -zeta. However, there was a close negative correlation between PE and PKC-alpha. CONCLUSION: Increased levels of PI and PC and decreased ratio of PKC-alpha to PKC-betaII are related to colorectal cancer genesis. Increased levels of PE, increased expression of PKC-delta, -epsilon, -lambda, -zeta isoenzymes and decreased level of PKC-alpha are related to hepatic metastasis in colorectal carcinoma.

[Clinical significance of transrectal ultrasound in detecting of rectal cancer margin and deciding of distal surgical incisal edge].

OBJECTIVE: To study the role of transrectal ultrasound in detecting and deciding rectal cancer margin and surgical incisal edge. METHODS: 33 surgical specimens of rectal carcinoma were examined with transrectal ultrasound. Cancerous margin and surgical incisal edge were determined. The results were compared with pathological examination. p53 and K-ras gene mutation as tumor molecular markers of residue cancer cells were detected in incisal edge tissue with PCR-SSCP method. RESULTS: General accuracy for cancer infiltration depth with transrectal ultrasound was 86.6%. For mucosa and submucosa infiltration lesions, the accuracy was 72.7%. For lamina muscularis, the accuracy was 90.9%. And for adventitia and peripheral tissue infiltration of rectum, the accuracy was 88.5% and 100% respectively. No remains of cancer cells and tumor molecular markers were detected at distal incisal edges of 1.0 cm, 2.0 cm and 3.0 cm determined with transrectal ultrasound. CONCLUSIONS: Rectal cancer margine and surgical incisal edge determined with transrectal ultrasound are close to examined by pathology. Transrectal ultrasound is helpful and reliable to define incisal edge in rectal cancer surgery.

[A clinical study of 214 cases of modified radical mastectomy with preservation of major and minor pectoral muscles].

OBJECTIVE: To study clinical effects of modified radical mastectomy with preservation of major and minor pectoral muscles. METHODS: A retrospective analysis was carried out in 214 cases of breast cancer patients (including stage I 66 cases, stage II 141 cases and stage III 7 cases). Modified radical mastectomy with preservation of major and minor pectoral muscles was performed on all the patients. RESULTS: Out of 214 cases, 12 (5.6%) had subcutaneous fluid, 16 (7.4%) had skin flap margin necrosis. Upper limb lymphatic edema was found in 8 (3.7%) patients, and pectoral muscle contracture with dyspraxia of upper arm occurred in 11 (5.1%) cases. Three year survival rate was 82.3% and five year survival rate was 63.4%. For stage I patients, the five year survival rate attained to 79.6%, and stage II 56.3%. CONCLUSIONS: Preservation of lateral branch of pectoral nerve can avoid complication of pectoral muscle contracture with dyspraxia of upper arm. Early chemotherapy of postoperation prevents breast cancer occurrence and metastasis. Comprehensive treat approaches for operative wound avert subcutaneous fluid, and complex therapy improves long-term effect of breast cancer patients.

[Cell membrane phospholipid variation and protein kinase C expression effects on hepatic metastasis of large intestinal carcinoma].

OBJECTIVE: To study cell membrane phospholipid variation and protein kinase C (PKC) isoenzyme expression and their effects on hepatic metastasis of large intestinal carcinoma. METHODS: High function liquid chromatography was used to separate and detect cell membrane phospholipids of phosphatidylinosital (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in primary foci, paratumor intestine mucosa and hepatic metastasis of large intestinal carcinomas. And mRNA expression levels of PKC-alpha, -beta II, -delta, -epsilon, -lambda, -zeta isoenzymes were detected using QRT-PCR technique. RESULTS: Fifty-eight cases of colorectal cancer were examined. CONTENTS: of PI, PC and PE in primary foci and hepatic metastasis were higher than those in paratumor mucosa. PE content in hepatic metastasis was much higher than that in primary foci (t = 98.88, P < 0.01). But PI and PC contents had no significant differences between primary and hepatic metastasis (t = 1.73, 1.36, P > 0.05). PKC-beta II, -delta, -epsilon, -lambda, -zeta expression were enhanced in primary foci and hepatic metastasis, but PKC-alpha level decreased in comparison with paratumor mucosa. And PKC-delta, -epsilon, -lambda, -zeta levels in hepatic metastasis were higher than those in primary foci (t = 4.31, P < 0.05). PI and PC had positive correlations with PKC-beta II expression. PE had positive correlations with PKC-delta, -epsilon, -lambda, -zeta, but a negative correlation with PKC-alpha. CONCLUSIONS: The increases of PI and PC and PKC-alpha/PKC-beta II ratio change are related with colorectal cancer genesis. High content of PE and enhanced expression of PKC-delta, -epsilon, -lambda, -zeta isoenzymes and decreased PKC-alpha level improved hepatic metastasis of large intestinal carcinoma.

Pericardial devascularization combined with preservation of Latarjet's nerves trunk in treatment of patients with portal hypertension.

OBJECTIVE: To investigate the effect of pericardial devascularization combined with preservation of Latarjet's innervation on portal hypertension. METHODS: Sixty-two patients (57 men and 5 women) have been undergone pericardial devascularization combined with Latarjet's innervation since 1984. Clinical results and postoperative complications were evaluated. RESULTS: The incidence of upper-digestive tract bleeding was 3.2% (2 patients) within 1 month after operation. Four patients (6.5%) died within 1 month after operation (3 patients received emergency operation and 1 selective operation). Among them, 3 patients died from hepatic failure, and one patient from sepsis due to subphrentic infection. Among these deaths, 3 were evaluated Child's C. After operation, the number of patients with abdominal distension, sudden diarrhea and gastric retension was 7 (11.3%), 3 (4.8%) and 0, respectively. CONCLUSION: Pericardial devascularization combined with Latarjet's innervation can preserve the normal function of gastric emptying, prevent acute lesion of the gastric mucosa, and reduce the incidence of esophageal varices rebleeding after operation.

[Clinical study of 102 cases of abdominal-anus resection with telescopic anastomosis of colon rectal mucosa for lower segment of rectal cancer].

OBJECTIVE: To investigate the reliability and feasibility of abdominal-anus resection with preservation of anal sphincter by telescopic anastomisis of colon rectal mucosa for middle-lower segment of rectal cancer. METHODS: A retrospective analysis was made for abdominal-anus resection with telescopic anastomosis of colon rectal mucosa in 102 cases of middle-lower segment of rectal cancer. RESULTS: No anastomotic fistula and anastomotic stenosis occurred in the 102 cases. The increased defecation was found during early stage of postoperation, about 6-12 times per day. But this was easily controlled by antidiarrheal drugs. Twelve to 18 weeks later, defecation returned to normal. Follow-up was performed in 91 patients, and the follow-up rate was 89.2%. Mean follow-up period was 4.7 years. Local recurrence rate of the carcinoma was 5.4% (5/91), and hepatic metastasis rate was 13.1% (12/91). Three-year survival rate of postoperation was 86.9% (60/80), and five-year survival rate was 70.7% (29/41). CONCLUSIONS: With telescopic anastomosis of colon rectal mucosa, colon stoma can be avoided, and anastomotic fistula can be prevented. The operation is safety and effective in preservation of anal sphincter for rectal cancer therapy.

[Variations of cellular membrane phospholipids with genesis and hepatic metastasis of large intestine cancer].

OBJECTIVE: To separate and detect membrane phospholipids and study the relationship of metabolism and signal transduction pathways of membrane phospholipids with genesis and hepatic metastasis of large intestinal carcinoma. METHODS: Forty-eight cases of colorectal cancer were detected with high performance liquid chromatography. Membrane phospholipids of phosphatidylinosital (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in primary foci, paratumor intestinal mucosa and hepatic metastasis of large intestine cancer were separated and analyzed. RESULTS: In primary foci, paratumor intestinal mucosa, and hepatic metastasis of the 48 cases, the contents (mg/g) of PI were: 0.92 +/- 0.12, 1.57 +/- 0.14, 1.54 +/- 0.15 respectively, and PC 56.47 +/- 5.33, 108.57 +/- 6.37, 116.35 +/- 6.85. The contents of PI and PC were higher in primary foci and hepatic metastasis than in paratumor mucosa (F = 363.10, 870.10, P < 0.01). The contents of PE in the three tissues were 18.23 +/- 3.56, 42.02 +/- 4.33, 79.51 +/- 5.52, and in hepatic metastasis was the highest (F = 1 149.63, P < 0.01). PI and PC in primary foci of hepatic metastatic group and nonmetastasis group were not significantly different (t = 3.55, P > 0.05). But the PE content was higher in hepatic metastasis than in primary foci (t = 115.87, P < 0.01). CONCLUSIONS: Membrane phospholipids have obvious variations in genesis and hepatic metastasis of large intestine cancer. Rises of PI and PC were associated with genesis of large intestine carcinoma. The increase of PE content is closely related to invasion and hepatic metastasis of large intestine cancer.

[Long-term results of extended parietal cell vagotomy in treatment of duodenal ulcers and their complications: report of 321 cases].

OBJECTIVE: To study the long-term results of extended parietal cell vagotomy (EPCV) in the treatment of patients with duodenal ulcer and their complications. METHODS: Form 1979 to 2001, EPCV was performed in 321 patients with duodenal ulcer and their complications. Of these patients 56 had chronic duodenal ulcer, 204 perforation, 16 hemorrhage and 40 stenosis. The following items were evaluated: complications of operation, gastric secretion, gastric emptying, endoscopical and radiographical findings, nutritional status, absorption function, and Visick scale. RESULTS: Postoperative follow-up ranged from 0.5 to 22.0 years (mean 11.3 years) in 289 of the 321 patients with a follow-up rate of 90.0%. Neither operative mortality nor dumping syndrome was noted. Episodic postprandial fullness occurred in 19 patients (6.5%), acid regurgitation in 17 (5.8%) and adhesive ileus in 4 (1.4%). Ulceration recurred in 16 patients (5.5%). Duodenal ulcer was seen in 8 patients (19.5%), hemorrhage in 0 (0%), stenosis in 2 (5.3%), and perforation in 6 (3.1%). Ulcers healed rapidly after medical therapy in 10 patients. Six patients received antrectomy and gastrectomy. In 289 (91.7%) patients of Grade I and II of Visick scale, 191 (95.3%) had perforation. CONCLUSIONS: EPCV is easy to perform with a low rate of post operative complication and ulcer recurrence. It should be a treatment of choice for acute perforation, hemorrhage or stenosis due to duodenal ulcer.