Chyloperitoneum signifying late bowel obstruction following gastric clipping with proximal jejunal bypass: A case report.

Chyloperitoneum (CP) is a rare complication after bariatric surgery. We present a 37-year-old female with CP caused by a bowel volvulus following a gastric clipping with proximal jejunal bypass for morbid obesity. An abdominal CT image of a mesenteric swirl sign and abnormal triglyceride level of ascites fluid can confirm the diagnosis. In this patient, laparoscopy demonstrated dilated lymphatic ducts caused by a bowel volvulus resulting in the exudation of chylous fluid into the peritoneal cavity. After the reduction of bowel volvulus, she made an uneventful recovery with complete resolution of the chylous ascites. The presence of CP could indicate a situation of small bowel obstruction in patients with a history of bariatric surgery.

Totally Laparoscopic Colectomy with Intracorporeal Side-to-End Colorectal Anastomosis and Transrectal Specimen Extraction for Sigmoid and Rectal Cancers.

BACKGROUND: The techniques of intracorporeal anastomosis and specimen extraction after laparoscopic colectomy via a natural orifice have gained interest increasingly. We evaluated the feasibility of our unique techniques for colorectal reconstruction and report immediate postoperative outcomes in patients with rectosigmoid cancer. METHODS: Patients with sigmoid or rectal cancer were selected depending on the size of the tumor and its distance from the anal verge. Demographic data, operative parameters, and postoperative outcomes were assessed. After complete resection of the tumor, all patients underwent an intracorporeal side-to-end colorectal anastomosis following transrectal specimen extraction. RESULTS: Laparoscopic resection with our technique of intracorporeal anastomosis was successful in 32 patients. The average operative time was 192 ± 29 min, and mean blood loss was 51 ± 18 ml. All patients experienced mild postoperative pain, and bowel function returned before postoperative day 3 in most patients. They had an uneventful postoperative course with a median hospital stay of 6 days. Major perioperative complications or anastomotic leak were not encountered in this study. The mean size of the lesion was 3.3 ± 1.8 cm, and the mean number of harvested nodes was 14 ± 6. During the follow-up period, there were no functional disorders associated with the intracorporeal anastomosis or transrectal specimen extraction. CONCLUSIONS: Intracorporeal side-to-end colorectal anastomosis with transrectal specimen extraction in laparoscopic colorectal surgery is a safe and effective procedure for patients with rectosigmoid malignancy.

Paravesical gossypiboma following inguinal herniorrhaphy: Laparoscopic retrieval.

Retained surgical sponge (gossypiboma) following an inguinal herniorrhaphy is a rare condition and may cause medicolegal problems. Differential diagnosis for the lesion should be made meticulously. We report a case of a 45-year-old man who had a herniorrhaphy about 8 years previously. He presented one episode of painless gross hematuria. Laboratory and imaging studies excluded any significant lesion in the urological organs. Abdominal CT scan demonstrated a heterogeneous neoplasm of 4 cm in size in the left paravesical area that was retrieved laparoscopically. Abdominal CT and clinical suspicion are helpful for diagnosis. Laparoscopy may be used to confirm the diagnosis and to remove the retained surgical gauze, and considered as an alternative therapy for some selected patients.

Risk factors for the development of metachronous liver metastasis in colorectal cancer patients after curative resection.

BACKGROUND: Metachronous liver metastasis (MLM) occurs in 20-40% of colorectal cancer (CRC) patients following surgical treatment. The aim of the present study was to determine the risk factors affecting the development of MLM in CRC patients following curative resection. METHODS: A total of 1,356 patients who underwent curative intent resection for CRC were retrospectively studied. Of these patients, those who with 30 days postoperative mortality (n=23), incomplete medical record (n=32), synchronous liver metastasis (n=148) and UICC stage IV (n=54) were excluded, and finally 1,099 patients were analyzed, including 977 patients without liver metastasis and 122 patients with MLM-only. Clinical and pathological records for each patient were reviewed from medical charts. The clinicopathologic characteristics of 1,099 patients were investigated. RESULTS: The median timing of developing MLM was 13 months with a range of 4 to 79 months. Univariate analysis identified that preoperative serum carcinoembryonic antigen (CEA) level, depth of invasion, lymph nodes metastasis, vascular invasion, and perineural invasion were significantly correlated with the development of MLM (all P<0.05). Meanwhile, a multivariate analysis showed that preoperative serum carcinoembryonic antigen (CEA) level>5 ng/ml (Odds Ratio [OR]=1.591; 95% Confidence Interval [CI], 1.065-2.377; P=0.024), tumor depth (OR=2.294; 95% CI, 1.103-4.768; P=0.026), positive lymph node metastasis (OR=2.004; 95% CI, 1.324-3.031; P=0.001) and positive vascular invasion (OR=1.872; 95% CI, 1.225-2.861; P=0.004) were independent prognostic factors contributing to the occurrence of MLM. CONCLUSIONS: The present study demonstrates that preoperative serum CEA level, tumor depth, lymph node metastasis, and positive vascular invasion could affect the occurrence of MLM in CRC patients following curative resection, and thus could help to define these high-risk patients who would benefit from enhanced surveillance and therapeutic program(s).

Preoperative serum carcinoembryonic antigen, albumin and age are supplementary to UICC staging systems in predicting survival for colorectal cancer patients undergoing surgical treatment.

BACKGROUND: The aim of this study was to determine influence of prognostic factors in addition to UICC staging systems, on cancer-specific and overall survival rates for patients with colorectal cancer (CRC) undergoing surgical treatment. METHODS: Between January 1996 and December 2006, a total of 1367 CRC patients who underwent surgical treatment in Kaohsiung Medical University Hospital were analyzed. We retrospectively investigated clinicopathologic features of these patients. All patients were followed up intensively, and their outcomes were investigated completely. RESULTS: Of 1367 CRC patients, there were seven hundred and fifty-seven males (55.4%) and 610 (44.6%) females. The median follow-up period was 60 months (range, 3-132 months). A multivariate analysis identified that low serum albumin level (P = 0.011), advanced UICC stage (P < 0.001), and high carcinoembryonic antigen (CEA) level (P < 0.001) were independent prognostic factors of cancer-specific survival. Meanwhile, a multivariate analysis showed age over 65 years (P < 0.001), advanced UICC stage (P < 0.001), and high CEA level (P < 0.001) were independent prognostic factors of overall survival. Furthermore, combination of UICC stage, serum CEA and albumin levels as predictors of cancer-specific survival showed that the poorer the prognostic factors involved, the poorer the cancer-specific survival rate. Likewise, combination of UICC stage, age and serum CEA level as predictors of overall survival showed that the poorer the prognostic factors involved, the poorer the overall survival rate. Of these prognostic factors, preoperative serum CEA level was the only significant prognostic factor for patients with stage II and III CRCs in both cancer-specific and overall survival categories. CONCLUSION: Preoperative serum albumin level, CEA level and age could prominently affect postoperative outcome of CRC patients undergoing surgical treatment. In addition to conventional UICC staging system, it might be imperative to take these additional characteristics of factors into account in CRC patients prior to surgical treatment.

Adult intussusception secondary to lymphangioma of the cecum: a case report.

We report the case of a patient with ileocolic intussusception caused by cecal lymphangioma. A 45-year-old man visited our hospital with a 2-month history of frequent episodes of watery diarrhea (>/= 5 times/day) and intermittent abdominal pain. A cecal submucosal tumor with mucosal ulceration and partial obstruction of the colonic lumen was identified by colonoscopy. He was admitted to our hospital 2 days later due to aggravation of his abdominal pain. Physical examination revealed tenderness over the right abdomen with no peritoneal signs. A double-contrast lower gastrointestinal series showed a right-side colonic lesion with indentation and a peripheral, beak-like sign. Abdominal computed tomography scanning revealed an intra-abdominal mass with the characteristic sausage sign, highly suggestive of intussusception. The patient subsequently underwent right hemicolectomy. The final diagnosis was ileocolic intussusception with cecal lymphangioma, which was confirmed by histopathology. He had an uneventful recovery with follow-up in our hospital. This case highlights the possibility of colonic lymphangioma as the leading point of adult intussusception, and this should be taken into consideration as a possible diagnosis in this uncommon clinical condition.

Multiple molecular markers as predictors of colorectal cancer in patients with normal perioperative serum carcinoembryonic antigen levels.

PURPOSE: In this study, a high-sensitivity colorimetric membrane array method was used to detect circulating tumor cells (CTC) in the peripheral blood of colorectal cancer (CRC) patients with normal perioperative serum carcinoembryonic antigen (CEA) levels. This membrane array method was evaluated as a potential diagnostic and postoperative surveillance tool. STUDY DESIGN: Membrane arrays consisting of a panel of mRNA markers that include human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and CEA mRNA were used to detect CTCs in the peripheral blood of 157 postoperative CRC patients with normal perioperative serum CEA levels and in 80 healthy individuals. Digoxigenin-labeled cDNA were amplified by reverse transcription-PCR from the peripheral blood samples, which were then hybridized to the membrane array. The sensitivity, specificity, and accuracy of membrane arrays for the detection of CTCs were then calculated. RESULTS: Using the four markers in combination, expression of any three markers or all the four markers in this panel was significantly correlated with the clinicopathologic characteristics, including depth of tumor invasion, lymph node metastasis, tumor-node-metastasis stage, and postoperative relapse (all P < 0.05). The interval between the detection of all four positive molecular markers and subsequent elevated CEA ranged from 3 to 8 months (median 6 months). The expression of all four mRNA markers was an independent predictor for postoperative relapse. CRC patients with all four mRNA markers expression showed a significantly poorer survival rate than those with less than four positive markers. CONCLUSIONS: The constructed membrane array method was helpful in the early prediction of postoperative relapse in CRC patients with normal perioperative serum CEA levels.

Randomized, controlled study of branched chain amino acid-enriched total parenteral nutrition in malnourished patients with gastrointestinal cancer undergoing surgery.

The objective of this study was to investigate the potential benefit of branched chain amino acid (BCAA)-enriched total parenteral nutrition (TPN) for malnourished surgical patients with gastrointestinal cancer. Sixty-four malnourished patients with gastrointestinal cancer with elective surgical intervention were equally allocated into two groups to receive isonitrogenous and isocaloric TPN. All of them must have received TPN soon after surgery and were subsequently randomized and divided into either BCAA-enriched TPN (30% BCAA; intervention group) or standard TPN (24% BCAA; control group). Patient biochemical data, nutritional parameters, and clinical outcome were collected to analyze the significance of BCAA-enriched TPN. After a period of TPN, laboratory data, including white blood cell (WBC), C-reactive protein (CRP), alkaline phosphatase (ALK-P), and gamma-glutamyltransferase (gamma-GT) levels, were significantly different between these two groups (all P < 0.05). Decreasing white blood cell and C-reactive protein levels were observed in the intervention group that might partially explain the reduced numbers of infectious complications. Furthermore, elevating alkaline phosphatase and gamma-glutamyltransferase levels being also less prominent might indicate a lesser hepatic burden by using BCAA-enriched TPN. The BCAA-enriched TPN can maintain a patient's serum visceral protein (albumin and prealbumin) and positive nitrogen balance better than standard TPN (all P < 0.05). Furthermore, a prominently decreased frequency of postoperative morbidity was also found in the BCAA-enriched TPN group (P = 0.021) despite no difference regarding surgical mortality. Our observations show that BCAA-enriched TPN may be beneficial in improving the nutritional status and reducing postoperative complications for malnourished patients with gastrointestinal cancer undergoing major surgery.

Serum albumin level in the management of postoperative enteric fistula for gastrointestinal cancer patients.

Postoperative enteric fistula is a serious complication and cause of death following gastrointestinal (GI)-tract surgery. Many reports have demonstrated the effectiveness of parenteral nutrition in the spontaneous closure of enteric fistula. Our study was aimed at analyzing the prognostic factors of parenteral nutritional support in the treatment of enteric fistula for patients with GI-tract cancer following surgery. GI-tract cancer patients receiving surgical interventions, which then unfortunately developed enteric fistula, were included in our study. All of them had to have received parenteral nutrition soon after leakages were recognized, and they were subsequently divided into successful and unsuccessful (classified as "failure") groups according to spontaneous closure of fistula or not, respectively. The studied patients' laboratory data were collected to identify the clinically relevant prognostic factors. Fifty-three primary GI-tract cancer patients with postoperative enteric fistulas were enrolled into our study. Of these, 33 patients were considered as successful parenteral nutritional therapy (successful group) and the other 20 patients (failure group) were not. After a period of parenteral nutritional therapy, serum total bilirubin, creatinine, C-reactive protein (CRP), hemoglobin, and albumin were significantly different between these two groups (all p < .05). Using a multivariate logistic regression analysis, it was determined that increased serum albumin level was an independent predictive factor of successful management for enteric fistula (p = .029), in addition to the well-known lower drainage amount (< 500 mL/day) from the enteric fistula (p = .013). Our observations show that both serum albumin levels and drainage amounts from the enteric fistula can be potentially used as important prognostic predictors of healing enteric fistula under total parenteral nutrition in patients following surgery for GI-tract malignancies.

Experience with adjuvant chemotherapy for pseudomyxoma peritonei secondary to mucinous adenocarcinoma of the appendix with oxaliplatin/fluorouracil/leucovorin (FOLFOX4).

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare condition characterized by mucinous tumors, disseminated intra-peritoneal implants, and mucinous ascites. So far its diagnosis remains challenging to most clinicians. CASE PRESENTATION: A 55-year-old male patient had suffered from acute onset of abdominal pain and abdominal distension for one day prior to his admission. Physical examination revealed tenderness over the right lower quadrant of the abdomen without diffuse muscle guarding. A large amount of ascites was identified by abdominal computed tomography (CT) scan. Paracentesis showed the appearance of sticky mucinous ascites. He underwent laparotomy under the impression of pseudomyxoma peritonei. There was a lot of mucinous ascites, one appendiceal tumor and multiple peritoneal implants disseminated from the subphrenic space to the recto-vesicle pouch. Pseudomyxoma Peritonei caused by mucinous adenocarcinoma of appendiceal origin, was confirmed by histopathology. We performed an excision of the appendiceal tumor combined with copious irrigation and debridement. After the operation, he received 10 cycles of systemic chemotherapy with FOLFOX4 regimen, without specific morbidity. Follow-up of abdominal CT and colonoscopy at post-operative 17 months showed excellent response without evidence of local recurrence or distal metastasis. He made an uneventful recovery (up to the present) for 21 months after the operation. CONCLUSION: This case report emphasizes the possible new role of systemic chemotherapy in the treatment of patients with this rare clinical syndrome.

Oxaliplatin/5-fluorouracil/leucovorin (FOLFOX4) regimen as an adjuvant chemotherapy in the treatment of advanced jejunal adenocarcinoma: a report of 2 cases.

OBJECTIVE: To present our clinical experience of 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen administered as an adjuvant chemotherapy to 2 patients with advanced jejunal adenocarcinoma. CASE PRESENTATION AND INTERVENTION: A 55-year-old woman presented with recurrent upper abdominal pain, nausea and vomiting. A small bowel series as well as the abdominal computed tomography scan revealed an irregular narrowing lesion at the proximal jejunum. The patient then underwent an exploratory laparotomy and the jejunal adenocarcinoma with localized peritoneal metastasis was found (R0 resection, T3N1M1, stage IV). Chemotherapy with FOLFOX4 regimen of 12 cycles was initiated after the curative resection. No adverse event was observed during the period of chemotherapy. She has been well without evidence of recurrence for over 20 months postoperatively. The second case was a 77-year-old female presenting with mechanical ileus. Surgical exploration revealed a proximal jejunal adenocarcinoma with regional lymph node involvement (R0 resection, T3N1M0, stage III). She also received the FOLFOX4 chemotherapy of 12 cycles with an uneventful course. No obvious toxicity developed except for temporary grade I peripheral neuropathy and skin eruption. This patient has survived well and has been free of this disease for over 12 months since the operation. CONCLUSION: This report showed that adjuvant chemotherapy with FOLFOX4 regimen seems effective and well tolerated in these 2 patients with advanced jejunal adenocarcinoma. Further investigation of a large number of patients with long-term follow-up is needed to confirm these findings.

Successful management of perforated duodenal diverticulitis with intra-abdominal drainage and feeding jejunostomy: a case report and literature review.

We report the clinical experience of one patient with perforated duodenal diverticulitis who was successfully treated by intra-abdominal drainage and feeding jejunostomy. A 53-year-old male patient visited our hospital due to acute onset of abdominal pain and distension. Physical examination revealed tenderness over the epigastric area and right-lower quadrant of the abdomen without obvious rebound tenderness or muscle guarding. Duodenal diverticulitis with a retroperitoneal abscess was identified by abdominal computed tomography scan. Surgical intervention was performed after the failure of conservative treatment. The operative findings were compatible with perforated duodenal diverticulitis, and intra-abdominal drainage of retroperitoneal abscess with simultaneous feeding jejunostomy was undertaken. The patient was doing well at the 4-month postoperative follow-up visit. We suggest the use of a conservative operative method, as opposed to conventional diverticulectomy and duodenorrhaphy, as an alternative approach for the management of this disorder, especially when conservative treatment has failed.

The prognostic significance of total lymph node harvest in patients with T2-4N0M0 colorectal cancer.

In patients with radically resected colorectal carcinoma, lymph node involvement is particularly important for a good prognosis and adjuvant therapy. The number of such lymph node recoveries is still controversial, with recommendations ranging from 6 to 17 nodes. The aim of this study is to determine if a specified minimum number of lymph nodes examined per surgical specimen can have any effect on the prognosis of patients who have undergone curative resection for T(2-4)N(0)M(0) colorectal carcinoma. Between September 1999 and January 2005, a total of 366 patients who underwent radical resection for T(2-4)N(0)M(0) colorectal carcinoma were retrospectively analyzed in a single institution. All specimen segments were fixed, with node identification performed by sight and palpation. We excluded 186 patients who received postoperative adjuvant chemotherapy via oral or intravenous transmission to prevent possible chemotherapeutic effects on patients' prognosis; therefore, a total of 180 patients with T(2-4)N(0)M(0) colorectal carcinoma were enrolled into this study. After the pathological examination, a mean of 12 lymph nodes (range 0-66) was harvested per tumor specimen. No postoperative relapse was found in this group, where the number of examined lymph nodes was 18 or more. Univariate analysis identified the size of the tumor, depth of invasion, grade of tumor, and number of examined lymph nodes, which were significantly correlated with postoperative relapse (all P < 0.05). Meanwhile, both the depth of tumor invasion and the number of harvested lymph nodes were independent predictors for postoperative relapse (P < 0.05). The 5-year overall survival rate of T(2-4)N(0)M(0) colorectal carcinoma patients who had 18 or more lymph nodes examined was significantly higher than those who had less than 18 nodes examined (P = 0.015). Nodal harvest in patients undergoing radical resection for colorectal carcinoma was highly significant in the current investigation. Our results suggest that harvesting and examining a minimum of 18 lymph nodes per surgical specimen might be taken into consideration for more reliable staging of lymph node-negative colorectal carcinoma.

The differentially mutational spectra of the APC, K-ras, and p53 genes in sporadic colorectal cancers from Taiwanese patients.

BACKGROUND/AIMS: Adenomatous polyposis coli (APC), K-ras and p53 gene mutations are the most common genetic alterations present in colorectal cancer (CRC). The aim of this study was to analyze tumor mutation frequencies and spectra in a large cohort of Taiwanese patients with CRC. METHODOLOGY: APC, K-ras, and p53 gene mutations in primary tumor tissues and their paired normal tissues of 123 CRC patients were detected by polymerase chain reaction-single strand conformation polymorphism analysis, followed by direct sequencing. RESULTS: Of these 123 CRC patients, 43.1%, 44.7%, 35% of tumor tissue specimens presented mutations in APC, K-ras, and p53 genes, respectively. Overall, gene mutations in APC, K-ras and/or p53 were present in 78% (96/123) of tumor tissues. Among 96 CRC patients harboring gene mutations, 49 (51%) contained mutations of at least two different genes and 47 (49%) contained mutations of one gene only. The most common combination of gene mutations was APC and K-ras mutations (21.9%), followed by K-ras and p53 mutations (12.5%) and then APC and p53 mutations (10.4%). In addition, there were only 6.3% (6/96) of tumor tissues from CRC patients simultaneously containing mutations of APC, K-ras and p53 genes. The most common mutation spectrum of these genes was missense mutations, at a frequency of 38.8%, 92.7% and 70.5% for APC, K-ras and p53 genes, respectively. CONCLUSIONS: These data support that the frequencies and patterns of somatic mutation of the APC, Kras and p53 genes in CRCs are considerably variable and distinct among populations, for which the interaction between exogenous environmental factors and endogenous gene alterations may be important determinants.

Discordant findings of skeletal metastasis between tc 99M MDP bone scans and F18 FDG PET/CT imaging for advanced breast and lung cancers--two case reports and literature review.

Traditionally, Tc 99m methyl diphosphate (MDP) bone scintigraphy provides high-sensitivity detection of skeletal metastasis from breast and lung cancers in regular follow-up. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), based on the glucose metabolism of malignant cells, plays a role in describing tumor growth, proliferation of neoplasm and the extent of metastasis. In general, concordant findings of skeletal metastasis are seen on both types of image, especially in cases of breast and lung cancer. However, there were extremely discordant findings of skeletal metastasis between bone scans and F 18 FDG PET/CT imaging in two cases among 300 consecutive F 18 FDG PET/CT follow-up exams of patients with malignancies, during the past year, in our center. Both cases, one of breast cancer and one of lung cancer, had negative bone scintigraphic findings, but a diffusely high grade of F 18 FDG avid marrow infiltration in the axial spine, leading to the diagnosis of stage IV disease in both cases. Owing to variant genetic aberrance of malignance, F 18 FDG PET/CT reveals direct evidence of diffuse, rapid neoplasm metabolism in the bone marrow of the spine, but not of secondary osteoblastic reactions in vivo . F 18 FDG PET/CT should always be employed in the follow-up of patients with malignancies.

Sarco/endoplasmic reticulum calcium-ATPase 2 expression as a tumor marker in colorectal cancer.

Maintaining a high calcium concentration in the endoplasmic reticulum through the action of sarco/endoplasmic reticulum calcium-ATPases (SERCAs) is crucial in many cell functions involved in intracellular signal transduction, control of proliferation, programmed cell death, or the synthesis of mature proteins. Recent studies have found that many SERCAs have altered expression patterns in various malignancies. The purpose of the current study was to quantify the expression of SERCA2 in colorectal cancer (CRC) tissues and the corresponding noncancerous tissues, and to statistically analyze whether the SERCA2 expression levels correlate with the clinico-pathologic features and prognosis of CRC patients. Paired colorectal tissue samples from cancerous and the corresponding noncancerous tissues were obtained from 50 patients who underwent surgical resection. Semiquantitative measurements of SERCA2 messenger RNA (mRNA) expression were done using the multiplex reverse transcriptase-polymerase chain reaction. CRC tissues were analyzed through immunohistochemistry for the SERCA2 protein. SERCA2 mRNA overexpression in cancerous tissues compared with normal counterparts was observed in 45 of 50 (90%) patients. The mean expression level of SERCA2 mRNA in cancerous tissues was significantly higher than that in noncancerous tissues (P = 0.01). Increased SERCA2 protein expression was significantly correlated with serosal invasion (P = 0.012), lymph node metastasis (P = 0.009), and advanced tumor stage (P = 0.004). Furthermore, patients with high SERCA2 expression had a significantly poorer overall survival rate than patients with low SERCA2 (P = 0.032). Multivariate analyses indicated that tumor stage (P = 0.015) and SERCA2 expression were independently correlated with overall survival (P = 0.018). The result of this study indicated that SERCA2 may be a molecular determinant in the development and progression of CRC. The molecular mechanisms underlying the SERCA-dependent calcium accumulation and CRC tumorigenesis are worthy of further investigations.

Clinical significance of MUC1 and c-Met RT-PCR detection of circulating tumor cells in patients with gastric carcinoma.

BACKGROUND: Recently, several reverse transcription-polymerase chain reaction (RT-PCR) techniques have been proven to be useful in the detection of circulating tumor cells (CTCs) in cancer patients. We attempted to detect CTCs in patients with gastric cancer (GC) using a RT-PCR assay for c-Met and MUC1 and to evaluate their clinical value. METHODS: Using a RT-PCR assay, c-Met and MUC1 mRNAs were amplified in 52 GC patients and 36 healthy individuals. Analyses were carried out for their correlation with the patients' clinicopathologic features, the occurrence of new post-operative metastasis, as well as the overall survival rates. RESULTS: In the RT-PCR analysis of peripheral blood, 61.5% (32/52) and 71.2% (37/52) of GC patients were positive for c-Met and MUC1 mRNA, respectively. The sensitivity and specificity of either mRNA detected in peripheral blood is 82.7% and 86.1%, respectively, with an accuracy of 84.1%. The detection of c-Met or MUC1 mRNA was significantly correlated with the depth of tumor invasion, lymph node metastases, TNM stage, vessel invasion, perineural involvement, and post-operative metastasis (all P<0.05). Kaplan-Meier analysis demonstrated that the overall survival rate of patients with positive c-Met or MUC1 mRNA expression in the peripheral blood was significantly shorter than in patients negative for c-Met or MUC1 mRNA expression (both P<0.05). CONCLUSIONS: Our findings suggest that using RT-PCR for the detection of c-Met or MUC1 mRNA may be a promising tool for the early detection of micro-metastatic CTCs in GC patients. Combination of these 2 tumor-specific mRNA markers would increase the detection rate and may be clinically helpful in predicting the outcome in GC patients.

Molecular mechanisms underlying the tumorigenesis of colorectal adenomas: correlation to activated K-ras oncogene.

Mutations of K-ras gene have been demonstrated in 40-50% of colorectal cancer and large adenoma (>1 cm). This study was intended to clarify the correlation between the existence of K-ras oncogene and the pathological features of colorectal adenomas using our recently developed membrane arrays. Moreover, the downstream genes regulated by K-ras oncogene were explored to serve as potential biomarkers in the early diagnosis and risk assessment of patients with colorectal adenoma. Specimens were collected from 70 patients with colorectal adenoma. The alterations of K-ras oncogene were analyzed by direct sequencing and our constructed membrane arrays, respectively. The results of direct sequencing showed that 21 of 70 samples (30%) had K-ras gene mutations. The most frequently mutated sites included codons 12, 13, 15 and 18. Furthermore, activated K-ras oncogene was identified in 18 of 70 (25.7%) adenoma by membrane arrays. Statistical analyses showed that the membrane array had the accuracy of 90.0%, sensitivity of 88.9%, and specificity of 90.4%. The frequency of the mutational sites of K-ras gene was located as follows: codon 12, 100% (4/4); codon 13, 100% (4/4); codon 15, 75% (6/8); and codon 18, 100% (2/2). The analysis of the correlation between the experimental data and pathological characteristics of adenoma showed that activated K-ras oncogenes were significantly associated with the size, number and histology of adenomas (all P<0.001). Finally, we found the downstream genes activated by K-ras oncogene, including B-cell CLL/lymphoma 2 (BCL2), Homo sapiens H2A histone family, member Z (H2AFZ), Homo sapiens RAP1B, member of RAS oncogene family (RAP1B), Homo sapiens T-box 19 (TBX19), Homo sapiens E2F transcription factor 4, p107/p130-binding (E2F4) and matrix metallopeptidase 1 (MMP1), of which were overexpressed in most of all examined adenomas. These genes were then suggested to have functions involved in cell growth. The preliminary results indicated that the accuracy of membrane arrays was comparable to conventional DNA sequencing in the detection of activated K-ras oncogenes. Therefore, we propose that activated K-ras oncogene in colorectal adenomas may play an important role in the subsequent colorectal carcinogenesis through a group of K-ras-related molecular targets.