Biomedical subjects

Tzu-Chen Lin

Publications and source records attributed to Tzu-Chen Lin.

At least 19 recordsLinked to original sources

PubMed2025

Modular Photoswitchable Molecular Glues for Chemo-Optogenetic Control of Protein Function in Living Cells.

Optogenetic systems using photosensitive proteins and chemically induced dimerization/proximity (CID/CIP) approaches enabled by chemical dimerizers (also termed molecular glues), are powerful tools to elucidate the dynamics of biological systems and to dissect complex biological regulatory networks. Here, we report a versatile chemo-optogenetic system using modular, photoswitchable molecular glues (sMGs) that can undergo repeated cycles of optical control to switch protein function on and off. We use molecular dynamics (MD) simulations to rationally design the sMGs and further expand their scope by incorporating different photoswitches, resulting in sMGs with customizable properties. We demonstrate that this system can be used to reversibly control protein localization, organelle positioning, protein-fragment complementation as well as posttranslational protein levels by light with high spatiotemporal precision. This system enables sophisticated optical manipulation of cellular processes and thus opens up a new avenue for chemo-optogenetics.

Optogenetics↗

PubMed2006

p53 protein accumulation as a prognostic marker in sporadic colorectal cancer.

BACKGROUND AND AIMS: p53 protein plays a crucial role in the pathogenesis of a large number of malignancies. In this study, our goal was to elucidate the prognostic role of p53 overexpression and its relationship to clinicopathological variables in colorectal cancer. MATERIALS AND METHODS: Between 1999 and 2004, surgical specimens of 258 patients who received surgical treatment for colorectal cancer at the Veterans General Hospital, Taipei were collected. p53 expression in tumor tissue was evaluated by immunohistochemical analysis using the human p53-specific mouse monoclonal antibody, PAb 1801. RESULTS: Of the 258 patients, 97 (37.6%) had overexpression of p53 in tumor tissues. The accumulation of p53 protein in tumor tissues did not correlate with age, gender, preoperative serum carcinoembryonic antigen (CEA) level, mucin content, nodal status, and tumor stage. A statistically significant correlation was found between p53 overexpression and location of the tumor in the rectum (p=0.038). Well to moderately differentiated tumors had significantly higher frequency of p53 overexpression than poorly differentiated tumors (40.0 vs 20.0%, p=0.050). Each patient was followed up for a minimum of 2 years (median 35 months). In univariate analysis, 3-year cancer-specific survival rate was significantly higher in patients with tumor p53 overexpression (88.2%) than in patients without overexpression (log rank test, p=0.037). However, in multivariate analysis, the tumour node metastasis stage remained the most significant independent prognostic factor. CONCLUSION: The accumulation of p53 protein might have a favorable prognostic value in colorectal cancer, but it is not an independent prognostic factor.

Adolescent↗

PubMed2006

Distinctive clinicopathological features of Ki-ras mutated colorectal cancers.

BACKGROUND AND OBJECTIVES: We explored the relationship between the mutation pattern of Ki-ras and the clinicopathological features of colorectal cancers (CRCs). METHODS: Relationships between clinicopathological parameters and Ki-ras mutation status were analyzed in 255 CRC patients using the chi-square and student t-tests. Kaplan-Meier survival curves were compared using the log-rank test. RESULTS: Ki-ras mutation occurred in 43.9% of tumors, and 83% affected codon 12. The most frequent mutations were GGT->GAT (Gly->Asp) (37.5%), followed by GGT->GTT (Gly->Val) (31.3%), both in codon 12. The frequency of Ki-ras mutation was similar for different tumor stages (38.2-47.8%). The mucin component of tumors was significantly associated with Ki-ras mutation. The 4-year overall and disease-free survival was 61% and 54%, respectively, for patients with Ki-ras mutated tumors, and 73% and 60% for patients with nonmutated tumors (not statistically significant). Patients with Ki-ras mutated tumors had lower plasma folate (24 ng/dl) than those bearing nonmutated tumors (37 ng/dl). Patients with G->T Ki-ras mutations had the lowest folate level (22 ng/dl), followed by those with G->A mutations (25 ng/dl). CONCLUSIONS: Ki-ras mutated colorectal tumors have a higher mucin production and higher differentiation, and are associated with lower plasma folate levels and a relatively poorer disease outcome.

Aged↗

PubMed2005

Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma.

AIM: To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with histologically confirmed metastatic colorectal cancers receiving treatment at Taipei Veterans General Hospital were enrolled. All patients had measurable metastatic lesions and life expectancies of more than 3 mo. Plasma vWF levels were measured by immuno-turbidimetric assay and compared with results from 40 non-metastatic colorectal cancer patients and 22 healthy controls. Patients with metastatic colorectal cancer were divided into two groups according to serum vWF levels and the differences between these two groups were analyzed using chi2 test. Data on age, gender, performance status, location of primary tumor, extent of metastasis, site of metastases, histological differentiation, serum CEA and plasma vWF levels were analyzed to determine association with survival. Survival curves were constructed by Kaplan-Meier product limit method and the data was analyzed using log-rank test on a microcomputer. Multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the independent prognostic indicators among all of the possible variables. RESULTS: Colorectal cancer patients were identified as having significantly higher plasma vWF concentrations than healthy controls (P<0.05). Moreover, higher vWF plasma levels were associated with advanced tumor stage (P<0.05) and the presence of multiple metastases (P = 0.014). Patients with lower vWF plasma levels (< or =160%) survived significantly longer than those with a higher plasma vWF level (log-rank test, P = 0.0043). By multivariate analysis, plasma vWF levels (P<0.001), the extent of metastasis (P = 0.012), and the performance status (P = 0.014) were identified as independent prognostic factors. CONCLUSION: Our data indicates that high plasma vWF concentrations correlate with advanced diseases and significantly poor prognosis of patients with metastatic colorectal carcinoma. It may serve as a potential biological marker of disease progression in these patients.

Adult↗

PubMed2005

Pre-operative chemoradiotherapy with oral tegafur-uracil and leucovorin for rectal cancer.

BACKGROUND: To evaluate the efficacy and toxicity of pre-operative radiotherapy (RT) combined with oral tegafur-uracil (UFUR) plus leucovorin (LV) in rectal cancer. PATIENTS: Sixty-five patients with rectal adenocarcinoma (clinical staged T2-4N0-2M0) received pelvic RT of 45 Gy in 20 fractions over 28 days. Concurrent chemotherapy consisted of UFUR (200 mg/m(2)/day) and LV (45 mg/day) on day 1-28. UFUR (250 mg/m(2)/day) and LV were continued on day 36-63. Surgery was performed on day 70. RESULTS: Sixty-three patients completed the concurrent chemoradiotherapy (CCRT) and 56 received curative or palliative surgery. Among the 52 patients receiving curative resection, downstaging (DS) occurred in 39 (75%), pathological complete response in 13 (25%), and sphincter preservation was achieved in 16 of 29 (55%) with lower-seated tumors. With a median follow-up time of 33 months, local failure developed in 4 (8%) and distant metastases occurred in 7 (14%). The 3-year overall survival was 92% and disease-free survival 76%. For all 65 patients, grade 3-4 diarrhea developed in 6 (9%) and grade 3-4 leucopenia observed in 2 (3%). CONCLUSIONS: Oral UFUR + LV administered with pre-operative RT are effective in tumor DS, pathological complete response, and sphincter preservation with tolerable toxicity in rectal cancer.

Adenocarcinoma↗

PubMed2005

Loss of heterozygosity: an independent prognostic factor of colorectal cancer.

AIM: Colorectal cancers result from the accumulation of several distinct genetic alterations. This study was to investigate the frequency and prognostic value of loss of heterozygosity (LOH) and microsatellite instability (MSI) at 14 genetic loci located near or within regions containing important genes implicated in colorectal tumorigenesis. METHODS: We studied colorectal cancers with corresponding normal mucosae in 207 patients (139 males and 68 females, mean age at the time of tumor resection 66.2+/-12.4 years, range 22-88 years). There were 37 right-sided colonic tumors, 85 left-sided colonic tumors and 85 rectal tumors. The distribution of tumor staging was stage I in 25, stage II in 73, stage III in 68, and stage IV in 41. We analyzed the LOH and MSI of HPC1, hMSH2, hMLH1, APC, MET, P53, NH23-H1, DCC, BAT25, BAT26, D17S250, MYCL1 and D8S254 with fluorescent polymerase chain reaction and denatured gel electrophoresis. High-frequency LOH was determined to be greater than three, or more than 50% of the informative marker with LOH. High-frequency MSI (MSI-H) was determined as more than four markers with instability (>30%). Correlations of LOH and MSI with clinical outcomes and pathological features were analyzed and compared. RESULTS: The occurrence of MSI-H was 7.25%, located predominantly in the right colons (7/15) and had a higher frequency of poor differentiation (6/15) and mucin production (7/15). LOH in at least one genetic locus occurred in 78.7% of the tumors and was significantly associated with disease progression. Of the 166 potentially cured patients, 45 developed tumor recurrence within 36 mo of follow-up. Clinicopathological factors affecting 3-year disease-free survival (DFS) were TNM staging, grade of differentiation, preoperative CEA level, and high LOH status. Patients with high LOH tumors had a significantly lower DFS (50%) compared with patients with low LOH tumors (84%). Of the patients developing subsequent tumor recurrence, the number and percentage of LOH were 2.97 and 46.8% respectively, similar to the stage IV disease patients. TNM staging had the most significant impact on DFS, followed by high LOH status. CONCLUSION: Clinical manifestations of LOH and MSI are different in colorectal cancer patients. High-frequency LOH is associated with high metastatic potential of colorectal cancers.

Adult↗

PubMed2005

Curative resection of T1 colorectal carcinoma: risk of lymph node metastasis and long-term prognosis.

PURPOSE: The features of T1 colorectal adenocarcinoma and the risk determination of lymph node metastasis were reviewed. Prognostic factors were assessed to verify whether the risk of lymph node metastasis would influence the long-term prognosis. METHODS: Patients undergoing curative resection of T1 colorectal adenocarcinoma at the Taipei Veterans General Hospital from December 1969 to August 2002 were retrospectively studied. Patients with synchronous colorectal cancer, distant metastasis, familiar adenomatous polyposis, or inflammatory bowel disease were excluded. The associations between lymph node metastasis and clinicopathologic variables were evaluated univariately using chi-squared test, Fisher's exact test, or Student's t -test, and multivariately using logistic regression. Univariate analysis by the log-rank test and multivariate analysis by Cox regression hazards model determined the factors influencing the overall survival. RESULTS: A total of 159 patients were included. Sixteen patients (10.1 percent) had lymph node metastasis. The risk of lymph node metastasis included histologic grade (P = 0.005), lymphatic vessel invasion (P = 0.023), inflammation around cancer (P = 0.049), and budding at the invasive front of tumor (P = 0.022). Age (P = 0.001) and number of total sampling lymph nodes (P < 0.0001) were found to be the factors influencing the overall survival. CONCLUSIONS: Variables that predict lymph node metastasis in surgically resected T1 colorectal carcinoma may not impact the long-term prognosis.

Adenocarcinoma↗

PubMed2005

Is it reasonable to add preoperative serum level of CEA and CA19-9 to staging for colorectal cancer?

BACKGROUND: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the most common tumor markers for colorectal cancer. The aim of this study was to evaluate the possibility of adding them into the current staging system by analyzing their prognostic significance. MATERIALS AND METHODS: The study population was patients (n = 574, 67.1 +/- 11.3 years old, 397 males) who received potentially curative resection of colorectal adenocarcinoma (stage I-III) between January 1994 and August 2002, including preoperative measurements of CEA and CA19-9. Clinicopathological characteristics and associated follow-up data were retrospectively collected by reviewing available medical charts. CEA higher or equal to 5 ng/ml was defined as abnormal (CEA+). The CA19-9 level was set at 37 U/ml (CA19-9+). Patients were further divided into four groups (1, 2, 3, 4) according to the results of these two markers (CEA/CA19-9: -/-, -/+, +/-, and +/+). Survival was analyzed for AJCC staging, CEA (+) versus (-), CA19-9 (+) versus (-), and four groups. RESULTS: CEA and CA19-9 survival curves were not significantly different. However, the combined use of the two markers revealed a significant survival benefit (P = 0.035) of group 1 ("-" for both markers) over 4 ("+" for both) in stage II. CONCLUSIONS: Patients with an elevated level of both CEA and CA19-9 in stage II of colorectal cancer have a significantly poorer prognosis than those with normal levels of these markers. We recommend adding both CEA and CA19-9 to the current staging system.

Adenocarcinoma↗

PubMed2005

Genetic alteration of p53, but not overexpression of intratumoral p53 protein, or serum p53 antibody is a prognostic factor in sporadic colorectal adenocarcinoma.

Mutation of p53 is a common event in colorectal cancer and can result in cellular accumulation of p53 protein and induction of p53 antibodies. We investigated the association of colorectal cancer with alterations in p53 DNA, protein and serum antibody levels to determine their prognostic value in colorectal cancer. Colorectal cancer patients (n=167) who underwent surgery in Taipei Veterans General Hospital from January 1999 to December 2000 were enrolled [age 62.91+/-12.61 years (range: 22-85); 111 (66.5%) males]. Of these, 20 were stage I (12%), 54 stage II (32.3%), 58 stage III (34.7%), and 35 stage IV (21%). Median follow-up was 36.3 months (range: 4-58). p53 alteration was detected by DNA sequencing from exon 5 to 9 and loss of heterozygosity (LOH) at two microsatellite markers near p53; and demonstrating intratumoral accumulation of p53 protein and detection of serum p53 antibodies using ELISA. p53 mutation frequency was 41.9% (70/167). Of 127 informative cases for LOH analysis, 73 (57.5%) tumors that had LOH had at least one microsatellite marker. Genetic p53 alterations were found for 56.3% of cases when LOH and DNA sequencing methods were combined. Genetic p53 alterations were associated with advanced tumor stage and tumor differentiation. Overexpression of intratumoral p53 and anti-p53 antibody positivity were 44.9% and 28.1%. The presence of p53-Ab was associated with p53 mutations (chi2 test, 42.9% vs. 17.5%, p=0.001), but not with overexpression of intratumoral p53 protein. The mutations at exon 6 (57.1%) and 7 (53.3%) were associated with presence of serum p53-Ab. Of 132 potentially cured patients, 3-year disease-free survival (DFS) was affected by: advanced TNM stage (I, II, III: 90%, 84%, and 41%), genetic p53 alteration (89% vs. 43%), intratumoral p53 accumulation (71% vs. 56%), and preoperative CEA level >5 ng/ml (74% vs. 58%). In multivariate analysis, genetic alteration of p53 was the most significant independent prognostic factor [hazard ratio (HR) = 6.09; 95% confidence interval (CI): 2.45-15.11], followed by advanced tumor stage (HR = 3.93; 95% CI: 2.14-7.23), and preoperative CEA >5 ng/ml (HR = 1.98; 95% CI: 1.12-3.17). Genetic alterations in p53 but not intratumoral p53 protein accumulation or p53-Ab appear to play a significant role in the progression of colorectal cancer.

Adenocarcinoma↗

PubMed2004

Metachronous colorectal cancer: necessity of post-operative colonoscopic surveillance.

BACKGROUND AND AIMS: The aim of this study was to identify the occurrence and analyze the characteristics of metachronous colorectal cancers, and to compare the characteristics of these cases (index tumor) with the control group to find any predicting factor that may influence the occurrence of metachronous cancer. PATIENTS AND METHODS: The database of colorectal cancer in the Veterans General Hospital-Taipei, from January 1981 to September 2001 was reviewed. In total, 3,846 cases of adenocarcinoma of the colon and rectum, which received curative resection during this period, were found. The criteria of metachronous cancer were: occurrence more than 12 months after curative surgery; with pre-operative complete colonoscopy or one negative post-operative colonoscopic follow-up to rule out synchronous tumor; tumor arising from mucosa at a site other than anastomosis. The age, gender of the patients, the location, pathological characteristics of the metachronous tumors, occurrence of associated adenomas, the number of lesions, and the tumor stage were analyzed and compared with the control group. RESULTS: In total, 43 cases of metachronous cancer were identified, giving an annual incidence of 0.18%. The distribution of the location of the index tumor of metachronous cases was predominantly left-sided, which was not different from that of the control group. The mean duration of occurrence of metachronous cancer after the primary operation was 71+/-46.6 months. The association of adenomas had no relationship with the occurrence of the metachronous cancer. No significant predicting factors for the development of metachronous tumors were found. CONCLUSION: Lifelong regular post-operative colonoscopic surveillance is essential for colorectal cancer patients.

Adenocarcinoma↗

PubMed2004

Long-term prognosis of patients with obstructing carcinoma of the right colon.

BACKGROUND: The long-term prognosis of patients with colon cancer is dependent on many factors. The aim of this retrospective study was to assess the long-term prognosis of patients with obstructing carcinoma of the right colon. METHODS: From 1981 to 1988, 256 patients at the Veterans General Hospital-Taipei who were status postcurative resection of right colon adenocarcinoma were classified as obstruction group (n = 35) or nonobstruction group (n = 221) as appropriate. RESULTS: Analysis revealed no differences in age, sex, tumor location, or stage (P >0.05) between the two groups. However, the overall and distant recurrence rates were significant higher in obstructed patients than in nonobstructed patients. Further, long-term crude and cancer-specific survival rates were significantly lower in obstructed patients when examining either overall patient outcome or stage-matched outcomes. Multivariate analysis demonstrated that obstruction and tumor stage were both independent prognostic factors. CONCLUSIONS: Obstruction status was an independent prognostic factor for patients with right colon carcinoma. The long-term prognosis of patients with obstructing carcinoma of the right colon was poor.

Adenocarcinoma↗

PubMed2003

Retained rectal foreign bodies.

BACKGROUND: Retained rectal foreign bodies have been encountered more frequently and present a dilemma for management. Most of the reports on these cases were documented in the form of case report and from Western countries. The present study was a review on the authors' experiences in such cases. METHODS: Data from January 1979 to January 2000 were extracted from a computerized database of Taipei Veterans General Hospital. The clinical features, treatment strategies and outcomes were analyzed. RESULTS: Ten male patients (mean age: 57.0 years) with 12 presentations of retained rectal foreign bodies were collected. Glass bottles and vibrators were the most common objects encountered, while anal eroticism was reported as the reason for insertion in 50% of the cases. The majority of the objects were extracted by non-surgical methods through either anoscope (n = 4), rigid sigmoidoscope (n = 2) or colonoscope (n = 1). Obstetric forceps was utilized to remove an incarcerated bowling bottle. Emergent laparotomies were performed in cases with overt peritonitis (n = 2), pelvic sepsis (n = 1) and an impacted high-lying glass bottle. Minor complications, such as mucosal abrasion or superficial tear, were found in 62.5% of the non-surgically treated cases. Delayed bleeding was found in 2 of them. There was no mortality in our series. CONCLUSIONS: Despite its rarity, the retained rectal foreign body had varying clinical features. Most of the uncomplicated rectal foreign bodies could be simply extracted transanally under adequate anesthesia. Fiberoptic colonoscopic extraction provided an alternative choice. Open surgery should be reserved only for those patients with overt peritonitis or pelvic sepsis.

Adult↗

PubMed2002

Comparison between straight and J-pouch coloanal anastomoses in surgery for rectal cancer.

PURPOSE: This study was designed to compare the long-term results of straight and J-pouch coloanal anastomoses after resection of rectal cancers located in the critical position of 5-6cm from the anal verge. METHODS: The subjects of this study were 81 patients who underwent radical resection of rectal cancers located 5-6 cm from the anal verge, followed by straight or J-pouch coloanal anastomosis, performed in 41 and 40 patients, respectively. Careful clinical and manometric follow-up was conducted and the results were compared. RESULTS: There were no differences in the incidence of local recurrence, the disease-free survival rate, postoperative stool frequency, continence, sphincter pressures, or functional length between the two groups. Both groups had a high incidence of clustering or fragmented defecation; however, the J-pouch patients had better urgency control, a greater capacity before feeling the urge to defecation, superior rectal tolerance, and better compliance. CONCLUSIONS: Both straight and J-pouch coloanal anastomoses are oncologically and functionally acceptable for the treatment of rectal cancer located 5-6cm from the anal verge, but the J pouch has slight superiority in urgency control, as a result of larger urge threshold and tolerable volume, and better compliance. The reason for the high incidence of clustering defecation in both groups needs to be investigated.

Aged↗

PubMed2002

Pulmonary resection for metastases from colorectal adenocarcinomas.

BACKGROUND: Colorectal cancer is one of the most common cancers in Taiwan, as in the other part of the world. Surgical intervention is the best treatment of choice, yet some patients still developed distant metastasis after primary lesions were controlled. Metastasectomy is reported to improve the survival. This retrospective study was carried out to evaluate the relationship between the prognostic factors of lung metastasectomy and patient survival. METHODS: From 1981 to 2000, 68 patients undergoing complete lung metastasectomy in our section were studied. The prognostic factors influencing survival were analyzed, and the survival analysis was made with Kaplan-Meier method and compared by log-rank test. RESULTS: There was no surgical mortality in our series. The 5-year survival was 36.1%. None of parameters such as age, sex, stage of primary colorectal cancer, surgical method, size, number of metastatic deposits and disease free interval showed to relate with the survival. CONCLUSIONS: We concluded that lung metastasectomy for colorectal cancer is safe and effective to improve the survival. Since there were no significant factors influencing the survival, there should be no absolute contraindication against resectable pulmonary metastasis after primary lesions were adequately controlled.

Adenocarcinoma↗

PubMedDate not supplied

CA19-9 as the most significant prognostic indicator of metastatic colorectal cancer.

BACKGROUND/AIMS: Colorectal cancer is the third leading cause of cancer-related mortality in Taiwan. We became interested in searching for the factors predictive of survival. Serum CA19-9 (carbohydrate antigen 19-9) level has been reported as a factor predictive of survival in patients with colorectal cancer. A few articles have reported that patients with metastatic colorectal cancer who have normal (< or = 37 U/mL) serum CA19-9 levels survived significantly longer than those with higher serum CA19-9 levels. However, these reports are contradictory and lack definite conclusions. This study was carried out in an effort to evaluate the prognostic significance of serum CA19-9 levels in patients with metastatic colorectal cancer in Taiwan. METHODOLOGY: Between 1991 and 1994, a total of 128 patients with histologically confirmed metastatic colorectal cancers were evaluated retrospectively at Veterans General Hospital-Taipei. All patients had measurable metastatic lesions and life expectancies of more than 3 months. 5-Fluorouracil-based chemotherapy, either in a weekly bolus regimen or a monthly 5-day bolus schedule, were administered to all of them. Data on age, sex, performance status, location of primary tumor, extent of metastases, site of metastases, histological differentiation, serum CEA (carcinoembryonic antigen) and CA19-9 levels were analyzed before chemotherapy to determine their association with survival. Blood samples for CEA and CA19-9 measurement were analyzed using the radioimmunoassay method. Multivariate analysis by the Cox's proportional hazards regression model was performed to determine independent prognostic factors among all of the possible variables. RESULTS: By univariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.022) were identified as prognostic factors, while age, sex, location of primary tumor, site of metastasis, histological differentiation, and pre-treatment serum CEA levels were not considered significant. By multivariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.014) were still found as independent prognostic factors of these patients. CONCLUSIONS: The data from our study indicate that serum CA19-9 level is the most significant prognostic indicator of patients with metastatic colorectal cancer. It is recommended that stratification for further clinical trials for patients with metastatic colorectal cancer should be carried out according to serum CA19-9 levels.

Adenocarcinoma↗

PubMedDate not supplied

Tumor marker CEA in monitoring of response to tegafur-uracil and folinic acid in patients with metastatic colorectal cancer.

BACKGROUND/AIMS: The assessment of response to chemotherapy of solid tumors is generally made by measurement of tumors visualized by imaging, commonly computed tomography scanning. However, response assessment based on imaging is not always feasible because patients often have disease not measurable by imaging study, such as diffuse peritoneal dissemination. Furthermore, response assessment by imaging is expensive and time consuming. This study was carried out in an effort to evaluate the correlation between serial change on imaging and on CEA (carcinoembryonic antigen) levels for assessing chemotherapeutic response of patients with metastatic colorectal cancer. METHODOLOGY: Between May 1998 and August 1999, a total of 40 patients with metastatic colorectal carcinoma were enrolled in this study. All the patients had to have measurable lesions. Oral tegafur-uracil 300 mg/m2/day and folinic acid 60 mg/day were administered concurrently for four weeks, repeated every five weeks, as the first-line treatment. Tumor marker CEA was examined before and during the whole course of treatment. Response based on CEA assessment was defined as a more-than 50% drop in serum CEA level for more than four weeks. The correlation between serial change on CEA and on imaging for assessing chemotherapeutic response was evaluated. RESULTS: Forty patients received a total of 318 courses of treatment and a response rate of 32.5% (95% confidence interval, 18.0% to 47.0%), including five complete responses and eight partial responses, was achieved by imaging studies. The pretreatment CEA levels were elevated beyond the normal cut-off value in 34 (85%) patients. The response rate evaluated by CEA assessment was 42.5% (17/40). Nine responders (22.5%) based on CEA had no remission on imaging. Agreement in assessment by imaging study and by CEA was observed in 20 patients (50%), including eight responders, five stable diseases, and seven progressive diseases. The sensitivity of falling CEA levels in the prediction of true responders on imaging was 62%. The sensitivity of elevated CEA levels for the prediction of progressive disease was 70%. Concerning the diagnostic accuracy, change in CEA levels in the prediction of true responders and progressive disease on imaging were 65% and 85%, respectively. On a follow-up of 24 months, patients with remarkable falling CEA levels survived significantly longer than non-responders (P = 0.0184, log-rank test). CONCLUSIONS: The measurement of CEA levels might be useful in monitoring chemotherapeutic response and in predicting the prognosis of patients with metastatic colorectal cancer. Serum CEA level may be used as a means of monitoring chemotherapeutic response when imaging study is unsuitable for assessing the response in clinical practice.

Adult↗

PubMedDate not supplied

Prospective study of the functional results of transanal endoscopic microsurgery.

BACKGROUND/AIMS: Most clinical research addresses the technological advances and oncological outcomes of transanal endoscopic microsurgery. Our aim was to examine the functional results. METHODOLOGY: From August 1999 to November 2000, 22 Taiwanese patients (14 men, 8 women; median age, 68 years) undergoing transanal endoscopic microsurgery were prospectively examined. Functional questionnaires and anorectal manometry were assessed before surgery and at 2 weeks, 6 weeks, 3 months, and 1 year. RESULTS: The median distance from the anal verge to the tumor was 10 cm. The median tumor diameter was 2.0 cm. The median duration of surgery was 120 minutes. No surgical mortality or morbidity and no local recurrence occurred during a median follow-up of 23 months. The mean stool frequency and consistency were significantly better at 3 months after surgery than before surgery. The maximal resting pressure significantly decreased after surgery. The maximal contraction pressure and maximal tolerated volume were significantly lower at 2 and 6 weeks than before surgery; these values recovered at 1 year. CONCLUSIONS: Transanal endoscopic microsurgery is safe for the cure of benign tumors and the palliative excision of malignant tumors in middle and upper rectum. Anorectal function was preserved and improved, though some anorectal manometric parameters changed over time.

Adenocarcinoma↗

PubMedDate not supplied

Long-term outcome of anastomosis leakage after curative resection for mid and low rectal cancer.

BACKGROUND/AIMS: The aim of this study was to evaluate the relationship of the disease recurrence and prognosis of rectal cancer with anastomosis leakage after curative low anterior resection. METHODOLOGY: The records of 566 patients with primary rectal adenocarcinoma in the Veterans General Hospital-Taipei, Taiwan between 1991 and 1997 were reviewed. Patients who did not have anastomosis (abdominoperineal resection 72, Hartmann's operation 15), did not have curative resection (62) or expired within 30 days after operation (11) were excluded from the study. Another 34 patients were excluded because they did not visit our clinic or could not be reached by telephone or questionnaire after operation. 372 patients who received restorative curative resection with a colorectal anastomosis were analyzed. The product-limit method (Kaplan-Meier) and Cox proportional hazard model were used to analyze survival rate and tumor recurrence. RESULTS: Twenty-five out of the 406 patients had anastomosis leakage after the operation. The 5-year disease-free, local recurrence-free survival of the leakage group (32.5%, 58.7%) was significantly lower than that of the non-leakage group (71%, 88.3%). The multivariate analysis showed TNM staging (p = 0.0001) and histological differentiation (p = 0.0002) were associated with overall tumor recurrence. The factors affected local tumor recurrence were TNM staging (p = 0.006) and anastomosis leakage (p = 0.014). CONCLUSIONS: These results suggested that anastomotic leakage after curative rectal surgery is associated with the local tumor recurrence-free survival rate even after adjusting for stage.

Actuarial Analysis↗