Jen-kou Lin - Academia.edu (original) (raw)
Papers by Jen-kou Lin
The Lancet. Oncology, Jan 13, 2015
In the international randomised phase 3 CORRECT trial (NCT01103323), regorafenib significantly im... more In the international randomised phase 3 CORRECT trial (NCT01103323), regorafenib significantly improved overall survival versus placebo in patients with treatment-refractory metastatic colorectal cancer. Of the 760 patients in CORRECT, 111 were Asian (mostly Japanese). This phase 3 trial was done to assess regorafenib in a broader population of Asian patients with refractory metastatic colorectal cancer than was studied in CORRECT. In this randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done in 25 hospitals in mainland China, Hong Kong, South Korea, Taiwan, and Vietnam, we recruited Asian patients aged 18 years or older with progressive metastatic colorectal cancer who had received at least two previous treatment lines or were unable to tolerate standard treatments. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, and adequate bone marrow, liver, and renal function, without othe...
Journal of the Formosan Medical Association = Taiwan yi zhi, 1991
One hundred and thirty partially gastrectomized subjects, who had been operated on for benign pep... more One hundred and thirty partially gastrectomized subjects, who had been operated on for benign peptic ulcers, were studied to assess the histologic changes in the remaining gastric mucosa and its implications for gastric carcinogenesis. Endoscopic examination and multiple mucosal biopsies from the gastroenterostomy area and gastric body were compared histopathologically. Gastric carcinoma was found in two instances among these 130 patients, making a prevalence rate of 1.5% for carcinoma in the residual stomach. Chronic atrophic gastritis and pseudopyloric metaplasia were found to have developed more often in the gastroenterostomy mucosa than in the gastric body mucosa (p less than 0.001). The mean value of the gastritis score for gastroenterostomy mucosa (2.7 +/- 1.3) was statistically higher than that for the gastric body (2.1 +/- 1.0; p less than 0.001). The degree and types of histologic alteration in the gastric mucosa were also affected by the type of operation and by the postop...
Intestinal Research, 2014
Background/Aims: Only moderate to severe Crohn' s Disease (CD) patients without a satisfactory co... more Background/Aims: Only moderate to severe Crohn' s Disease (CD) patients without a satisfactory conventional therapy effect are eligible to get reimbursement from the National Health Insurance of Taiwan for using adalimumab. These are more stringent criteria than in many Western countries and Japan and Korea. We aim to explore the efficacy of using adalimumab in CD patients under such stringent criteria. Methods: A retrospective analysis was conducted in nine medical centers in Taiwan and we collected the results of CD patients receiving adalimumab from Sep 2009 to Mar 2014. The clinical characteristics, response measured by CDAI (Crohn' s Disease Activity Index), adverse events and survival status were recorded and analyzed. CR-70, CR-100, and CR-150 were defined as attaining a CDAI decrease of 70, 100 or 150 points compared with baseline. Results: A total of 103 CD patient records were used in this study. Sixty percent of these patients received combination therapy of adalimumab together with immunomodulators. CR-70 was 68.7%, 74.5% and 88.4% after week 4, 8 and 12 of treatment, respectively. The steroid-free rate, complications and survival were 47.6%, 9.7% and 99% of patients, respectively. In considering the mucosal healing, only 25% patients achieve mucosal healing after treatment for 6 to12 months. Surgery was still needed in 16.5% of patients. Combination treatment of adalimumab with immunomodulators further decreased the level of CDAI at week 8 when compared with the monotherapy. Conclusions: Even under the stringent criteria for using adalimumab, the response rate was comparable to those without stringent criteria. (Intest Res 2014;12:287-292)
World Journal of Surgery, 2004
Despite widespread use of laparoscopic surgery for colorectal operations, its application for cur... more Despite widespread use of laparoscopic surgery for colorectal operations, its application for curative resection of colorectal cancer is still controversial. One of the major concerns is the impact of the laparoscopic procedure on dissemination of tumor cells. The main purpose of this study was to investigate the impact of laparoscopic surgery on circulating tumor cells in colorectal cancer patients. Quantitation of circulating free tumor cells (FTCs) was performed preoperatively, during the operation, and 14 days later by means of real-time quantitative reverse transcriptasepolymerase chain reaction (RT-PCR) targeting guanylyl cyclase C (GCC) mRNA in 42 colorectal cancer patients undergoing laparoscopic resections. Despite an increasing trend of FTC detection in patients with advancing stage, there is no significant difference in the preoperative FTC level by disease stage. No elevation in FTC level was found during the laparoscopic procedure in most patients compared with their preoperative FTC value. Patients with a persistently high FTC load [per nucleated blood cells (NBCs)] (> 10 2 FTCs/10 6 NBCs) 2 weeks postoperatively portends a poor prognosis regarding disease recurrence and tumor-related mortality when compared to those with an undetectable or low FTC load (≤ 10 2 FTCs/ 10 6 NBCs). We concluded that the laparoscopic procedure itself had no significantly deleterious effect on circulating FTCs and that the detection of FTCs by real-time qRT-PCR might be of clinical importance during the postoperative follow-up for colorectal cancer patients.
World Journal of Surgery, 1997
The incidence of tuberculosis is rising in the United States. Similarly, the incidence of pulmona... more The incidence of tuberculosis is rising in the United States. Similarly, the incidence of pulmonary tuberculosis in Taiwan is increasing, but that of large bowel tuberculosis in this region has not been reported. The purpose of this study was to investigate the changing disease pattern and to determine some possible surgical prognostic factors for large bowel tuberculosis. Seventy cases of large bowel tuberculosis treated at our institute during the period 1965-1995 were reviewed and analyzed. A steady decline in the case number of large bowel tuberculosis were noted from 1975, but there seems to be a slight increase in cases since 1990. The average age of these patients was 65.1 years, and none had human immunodeficiency virus infection. The ileocecum is the most common region of involvement. Of these 70 patients, 59 had not been definitively diagnosed until surgery. Active pulmonary tuberculosis was found in 18 patients (25.7%). The incidence of postoperative pulmonary complications was higher in patients with active pulmonary tuberculosis or disseminating large bowel tuberculosis. Postoperative abdominal complications, including intestinal obstruction, abdominal cutaneous fistula, and wound infection, were seen in 13 patients, none of whom had active pulmonary tuberculosis. Although the incidence of tuberculosis has been reduced for years, it is now rising. Physicians should bear in mind the possibility of large bowel tuberculosis in patients with intestinal obstruction without specific origin. Postoperative respiratory care is important for patients with pulmonary tuberculosis, with either active or disseminating lesions.
Journal of Surgical Oncology, 2011
Background and Objectives: The colon is a rare location for gastrointestinal non-Hodgkin's lympho... more Background and Objectives: The colon is a rare location for gastrointestinal non-Hodgkin's lymphoma. We retrospectively analyzed the demographic data of patients with colonic lymphoma and the possible prognostic factors of the disease. Methods: We studied data obtained from 6,944 patients and performed a retrospective review of patients with primary colonic lymphoma (PCL) by using a pathology registry database. We employed well-established and accepted diagnostic criteria and clinical staging method. Results: Twenty-nine patients (19 men; 10 women) were diagnosed with PCL. The cecum was the most common tumor location (14/29 patients), and 17 cases (17/29) showed diffuse large-B-cell lymphomas. Four patients died of sepsis within 30 days of an emergency surgery for perforation of intestine. Two-thirds of the patients were in the early disease stages (stages I and II). The overall 5-year survival rate was 47.3%. Disease stage was not a prognostic factor for survival. The overall 5-year survival rate in patients treated with surgery followed by chemotherapy was statistically significant as compared to that in the patients treated with chemotherapy alone. Conclusion: PCL is a rare malignancy of the gastrointestinal tract, and surgical resection should be considered a part of the standard treatment to achieve a better outcome.
International Journal of Colorectal Disease, 2010
Adjuvant systemic 5-fluorouracil (5-FU)-based chemotherapy improves survival after resection of s... more Adjuvant systemic 5-fluorouracil (5-FU)-based chemotherapy improves survival after resection of synchronous colorectal liver metastases (CLMs), but not metachronous. We retrospectively examined if adjuvant chemotherapy with new regimen containing oxaliplatin or irinotecan improved survivals after resection of metachronous CLMs. Between 2000 and 2007, 52 patients having undertaken resection of metachronous CLMs with curative intent were identified from Taipei Veterans General Hospital hospitalization registry. One patient with perioperative mortality and another being lost to follow-up within 3 months after metastasectomy were excluded. Thirty-one patients experienced six to 12 cycles of FOLFOX or FOLFIRI chemotherapy while 19 patients with 5-FU/leucovorin (LV)-based chemotherapy following CLM resection. The primary end point was disease-free survival (DFS) and secondary end point, overall survival (OS). By the univariate analysis, median DFS was 34.3 months in the FOLFOX/FOLFIRI group vs 14.2 months in the 5-FU/LV group (P = 0.022). The median OS and 5-year survival rates were longer than 57.7 months (not reached, with median follow-up of 35.5 months) and 54.0%, respectively, in the FOLFOX/FOLFIRI group compared to 49 months and 34.6% in the 5-FU/LV group (P = 0.027). FOLFOX/FOLFIRI chemotherapy was shown by multivariate analyses to be an independent factor predicting a better DFS (hazard ratio [HR] = 0.37; 95% CI: 0.15-0.94; P = 0.036) and a better OS (HR = 0.27; 95% CI: 0.083-0.86, P = 0.026) than 5-FU/LV-based. Adjuvant FOLFOX/FOLFIRI chemotherapy following resection of metachronous CLMs is demonstrated to have better DFS and OS than 5-FU/LV chemotherapy.
Diseases of the Colon & Rectum, 1999
In patients with colorectal cancer, brain metastasis is infrequent. This study aims to elucidate ... more In patients with colorectal cancer, brain metastasis is infrequent. This study aims to elucidate the risk, pattern of occurrence, and survival time after different treatment modalities. A retrospective review of all patients with colorectal cancer admitted to the Veterans General Hospital-Taipei between 1970 and 1996 from our hospital was performed. Univariate analysis for survival determination was performed. Brain metastases developed subsequent to surgery for colorectal cancer in 53 well-documented patients, at a median of 36 months after surgery. Brain metastases were more commonly seen in rectal cancer and often occurred concurrently with lung metastases. Forty of these patients received active intervention in terms of surgery, chemotherapy, or radiotherapy, with surgical intervention achieving a significantly increased mean survival time (+/- standard deviation) compared with chemotherapy or radiotherapy or both of 86.6 +/-17.35 vs. 2.9 +/- 0.59 months (P < 0.05). Increased awareness of the possibility of brain metastases, early diagnosis, and aggressive therapy can provide increased survival time for patients with colorectal cancer with brain metastases.
Diseases of the Colon & Rectum, 1992
Digestive and Liver Disease, 2008
Intrahepatic cholangiocarcinoma and colorectal cancer liver metastasis are the most primary and s... more Intrahepatic cholangiocarcinoma and colorectal cancer liver metastasis are the most primary and secondary adenocarcinoma of the liver, respectively. A large-scale long-term comparative study of these two cohort patient is lacking. A total of 166 colorectal cancer liver metastasis patients and 206 intrahepatic cholangiocarcinoma patients who had undergone curative liver resection were retrospectively analysed. Among 206 intrahepatic cholangiocarcinoma, there were 47 intraductal growth type-intrahepatic cholangiocarcinoma and 159 non-intraductal growth type-intrahepatic cholangiocarcinoma. The demographics, clinicopathological data, immunohistochemical study and survival were analysed. The intrahepatic cholangiocarcinoma patients were more female-predominated, associated with hepatolithiasis, symptomatic, jaundiced, and with larger tumour size compared with those of colorectal cancer liver metastasis. Prognostic factors of intrahepatic cholangiocarcinoma were pathologic staging, histologic pattern and section margin; whereas prognostic factors of colorectal cancer liver metastasis were rectal origin, differentiation, section margin and bilobar distribution. CK7 and CK20 differentiated majority of intrahepatic cholangiocarcinoma from colorectal cancer liver metastasis, while CDX2 and MUC5AC helped to differentiate inconclusive cases. The 1-, 3-, 5- and 10-year survival rates of colorectal cancer liver metastasis were 77%, 31%, 20% and 14%, compared to 53%, 21%, 13% and 7% of intrahepatic cholangiocarcinoma (p=.0001). Furthermore, the survival of colorectal cancer liver metastasis was comparable to staged II intrahepatic cholangiocarcinoma (p=.8866) and intraductal growth type-intrahepatic cholangiocarcinoma (p=.1915). Demographics, precipitating factor, clinical manifestations, and prognostic factors of colorectal cancer liver metastasis and intrahepatic cholangiocarcinoma differed remarkably. High incidence of CDX2 and MUC2 expression in colorectal cancer liver metastasis and intraductal growth type-intrahepatic cholangiocarcinoma might explain their similar cytoarchitecture and survival.
Anti-Cancer Drugs, 2004
Selective cyclooxygenase-2 (COX-2) inhibitors have been found to induce anti-proliferative and ap... more Selective cyclooxygenase-2 (COX-2) inhibitors have been found to induce anti-proliferative and apoptotic activity in many cancer cells. However, interaction between COX-2 inhibitors and other chemotherapeutic agents remains to be determined. We investigated the interactive effects of a selective COX-2 inhibitor, etodolac, in combination with 5-fluorouracil (5-FU) or SN-38 (active metabolite of irinotecan) on colon cancer cell lines, HT29 and SW620, in simultaneous and sequential administration schedules. Isobologram analysis demonstrated that etodolac in combination with 5-FU or SN-38 according to a simultaneous schedule resulted in only an additive effect; however, synergism was achieved in a sequential schedule. Apoptosis induction in both cell lines was also significantly increased after sequential treatment with etodolac followed by either 5-FU or SN-38 compared to that after simultaneous treatment with etodolac and either 5-FU or SN-38. Our study suggests apoptosis-inducing synergism resulted from administration of etodolac and either 5-FU or SN-38 sequentially, but not simultaneously.
Annals of surgical oncology, Jan 15, 2015
Colorectal cancer (CRC) is a heterogeneous disease caused by genetic and epigenetic alterations. ... more Colorectal cancer (CRC) is a heterogeneous disease caused by genetic and epigenetic alterations. This study aimed to describe the mutation frequency of 12 genes in different CRC phenotypes. Patients who underwent surgery at the Taipei Veterans General Hospital during 2000-2010 for CRC (n = 1249) were enrolled. The endpoint was overall survival. The prognostic value was determined with the log-rank test and Cox regression analysis. We found 1836 mutations of 12 genes in 997 (79.8 %) tumors. Mutations were most frequently in KRAS (485, 38.8 %), TP53 (373, 29.9 %), APC (363, 29.0 %), and PIK3CA (179, 14.3 %); 137 (11.0 %) cancers had high microsatellite instability (MSI). Women had significantly higher high MSI (14.3 %) and BRAF mutation (6.3 %) frequencies. The abnormal MSI (21.7 %) and KRAS (44.6 %), BRAF (8.6 %), PIK3CA (19.4 %), AKT1 (2.2 %), and TGF - βR (9.6 %) mutation frequencies were significantly higher in proximal colon cancer. The high MSI (35.6 %) and BRAF (20.3 %), TGF - ...
Hepato-gastroenterology
Survival of patients with colorectal cancer confined to the muscularis propria (stage I) is excel... more Survival of patients with colorectal cancer confined to the muscularis propria (stage I) is excellent after curative resection. However, some patients are likely to develop lymph node and distant metastasis that can ultimately cause death. The purpose of this study was to identify the possible predictors of lymph node and distant metastasis in T1 and T2 colorectal cancers. In total 208 patients with T1 and T2 colorectal cancers who underwent surgical resection in Taipei Veterans General Hospital from July 1996 to December 2001 were enrolled. The clinicopathological variables including age, gender, tumor location (rectum/colon), preoperative carcinoembryonic antibody level, depth of tumor invasion, lymphovascular invasion, and unfavored histology corresponding to the metastasis assessed pathologically were analyzed. Categorical variables were analyzed using Chi-square with Yates&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; correction. The independent predictor of lymph node and distant metastasis was determined with multivariate binary logistic regression. Of the 208 T1 and T2 colorectal cancer patients, 36 (17.3%) had lymph node metastasis and 5 (2.4%) had distant metastasis at surgery. The risk of lymph node metastasis was 14.3% (8/56) in T1 and 18.4% (28/52) in T2 colorectal cancer. The tumors with evidence of lymphovascular invasion had a significantly higher incidence of lymph node metastasis than those without lymphovascular invasion (43.6% vs. 9.4%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The independent risk factor for lymph node metastasis was lymphovascular invasion only (95% confidence interval, 3.37-19.97; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), whereas that for distant metastasis was preoperative carcinoembryonic antibody level &amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;5ng/mL only (95% confidence interval, 0.03-0.21; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The negative predictive value of possible adverse risk factors including preoperative carcinoembryonic antibody level &amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;5ng/mL, lymphovascular invasion, and unfavored differentiation for metastasis was 93.5%. Considering the negative predictive value of combined possible adverse risk factors, the risk of metastasis still was 6.5%. Therefore radical surgery was recommended for all T1 and T2 stage colorectal cancer patients except if the patient had a very high surgical risk.
Background. The aim of this study was to compare surgical outcomes of primary resection and delay... more Background. The aim of this study was to compare surgical outcomes of primary resection and delayed resection as emergent curative surgery for obstructive left-sided colorectal cancer (CRC). Methods. Between January 1980 and December 2002, a total of 143 ...
Hepato-gastroenterology
The significance of tumor volume and its change after concurrent chemoradiotherapy (CCRT) was eva... more The significance of tumor volume and its change after concurrent chemoradiotherapy (CCRT) was evaluated. Standard-dose external radiation and oral UFUR plus leucovorin were used to treat 30 middle and lower rectal adenocarcinoma patients. Volume of tumor calculated from images obtained by dynamic MRI of the rectum before and after CCRT was compared to pathological results after definite resection and other clinical data. The T-stage in 15 patients (50%), the N-stage in 13 (72.2%), and overall, the TNM stage in 18 (60%), were downstaged, including 7 (23.3%) with complete responses (CR). Volume of tumor before CCRT (Vpre) and after CCRT (VPost) was 10.3+/-6.1cm3 and 4.2+/-2.2cm3, respectively, and VPre correlated with initial T stage, N stage, age, and location. The net decrease ratio (NDR) of tumor volume was related to Vpre and initial T stage. As to the downstaging effect, VPre was related to incidence of CR; NDR was related to the downstaging of the N stage. All tumors showed volume reduction after CCRT, but the downstaging benefits were not in proportion to the size change. Initially larger tumors had higher ratios of volume reduction, and smaller tumors had higher chance of CR.
Hepato-gastroenterology
We evaluated the prognostic significance of clinicopathologic features recommended by the majorit... more We evaluated the prognostic significance of clinicopathologic features recommended by the majority of guidelines for identifying high-risk stage it colon cancer patients. We enrolled 665 stage II colorectal cancer patients at Taipei Veterans General Hospital in 2002-2006. Patients who received preoperative or postoperative chemotherapy were excluded (124). The measured endpoint was disease-free survival. Of 541 patients, 59 showed stage T4 tumors; 35, lymphovascular invasion; 19, poor differentiation, and 251, carcinoembryonic antigen levels of > 5 ng/mL; 53 underwent emergent operations. Colorectal cancer recurred in 84 patients. The 5-year disease-free survival rate was 84.5%. Univariate and multivariate analyses revealed 3 independent factors affecting the prognosis significantly tumor stage T4, high carcinoembryonic antigen level, and presence of lymphovascular invasion. Considering the cumulative effect of risk factors, the 5-year disease-free survival rate of patients with ...
Hepato-gastroenterology
The significance of prognostic value of DNA ploidy patterns of colorectal cancer has not yet been... more The significance of prognostic value of DNA ploidy patterns of colorectal cancer has not yet been fully understood. The present study was designed to determine the prognostic value of DNA ploidy patterns for colorectal adenocarcinomas after resection. We have prospectively collected tumor specimens from 420 patients with colorectal cancer since 1996. The DNA ploidy patterns were determined with the use of DNA flow cytometry. The correlation of DNA ploidy pattern and various characteristics of tumors and the prognostic significance of DNA ploidy patterns were evaluated by univariate as well as Cox's proportional hazard model. The disease-free survival curves were calculated with Kaplan-Meier's analysis, and the survival difference was determined by log-rank test. DNA ploidy patterns were diploid in 115 (27.4%) and aneuploid in 305 patients (72.6%). The pattern of DNA ploidy did not correlate with age, gender, location, differentiation, and stage of the tumors. In 146 patients...
Purpose. Stool occult blood tests and serum CEA level examinations are widely used at health chec... more Purpose. Stool occult blood tests and serum CEA level examinations are widely used at health check-up of detecting colorectal lesions. The aim of this study is to evaluate the effectiveness of using single stool occult blood tests or serum CEA levels in routine health check up. Methods. We examined 1404 patients who came for health check up at Veterans General Hospital, Taipei, Taiwan from April 2004 to May 2005. They were all underwent single stool occult blood test, serum CEA level and complete colonoscopy during the check up. Results. There were patients with colorectal cancers in 9 (0.6%), polyps in 268 (19.1%) (Significant polyps in 95), diverticulum in 86 (6.1%) and other lesions in 9 (0.6%). Positive stool occult blood tests were noted in 97 patients (6.9%). The sensitivity, specificity, false positive rate and false negative rate of stool occult blood test to detect significant colorectal neo- plasm were 14.4%, 93.1%, 6.9% and 85.6% respectively. There were 39 (2.8%) patient...
The Lancet. Oncology, Jan 13, 2015
In the international randomised phase 3 CORRECT trial (NCT01103323), regorafenib significantly im... more In the international randomised phase 3 CORRECT trial (NCT01103323), regorafenib significantly improved overall survival versus placebo in patients with treatment-refractory metastatic colorectal cancer. Of the 760 patients in CORRECT, 111 were Asian (mostly Japanese). This phase 3 trial was done to assess regorafenib in a broader population of Asian patients with refractory metastatic colorectal cancer than was studied in CORRECT. In this randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done in 25 hospitals in mainland China, Hong Kong, South Korea, Taiwan, and Vietnam, we recruited Asian patients aged 18 years or older with progressive metastatic colorectal cancer who had received at least two previous treatment lines or were unable to tolerate standard treatments. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, and adequate bone marrow, liver, and renal function, without othe...
Journal of the Formosan Medical Association = Taiwan yi zhi, 1991
One hundred and thirty partially gastrectomized subjects, who had been operated on for benign pep... more One hundred and thirty partially gastrectomized subjects, who had been operated on for benign peptic ulcers, were studied to assess the histologic changes in the remaining gastric mucosa and its implications for gastric carcinogenesis. Endoscopic examination and multiple mucosal biopsies from the gastroenterostomy area and gastric body were compared histopathologically. Gastric carcinoma was found in two instances among these 130 patients, making a prevalence rate of 1.5% for carcinoma in the residual stomach. Chronic atrophic gastritis and pseudopyloric metaplasia were found to have developed more often in the gastroenterostomy mucosa than in the gastric body mucosa (p less than 0.001). The mean value of the gastritis score for gastroenterostomy mucosa (2.7 +/- 1.3) was statistically higher than that for the gastric body (2.1 +/- 1.0; p less than 0.001). The degree and types of histologic alteration in the gastric mucosa were also affected by the type of operation and by the postop...
Intestinal Research, 2014
Background/Aims: Only moderate to severe Crohn' s Disease (CD) patients without a satisfactory co... more Background/Aims: Only moderate to severe Crohn' s Disease (CD) patients without a satisfactory conventional therapy effect are eligible to get reimbursement from the National Health Insurance of Taiwan for using adalimumab. These are more stringent criteria than in many Western countries and Japan and Korea. We aim to explore the efficacy of using adalimumab in CD patients under such stringent criteria. Methods: A retrospective analysis was conducted in nine medical centers in Taiwan and we collected the results of CD patients receiving adalimumab from Sep 2009 to Mar 2014. The clinical characteristics, response measured by CDAI (Crohn' s Disease Activity Index), adverse events and survival status were recorded and analyzed. CR-70, CR-100, and CR-150 were defined as attaining a CDAI decrease of 70, 100 or 150 points compared with baseline. Results: A total of 103 CD patient records were used in this study. Sixty percent of these patients received combination therapy of adalimumab together with immunomodulators. CR-70 was 68.7%, 74.5% and 88.4% after week 4, 8 and 12 of treatment, respectively. The steroid-free rate, complications and survival were 47.6%, 9.7% and 99% of patients, respectively. In considering the mucosal healing, only 25% patients achieve mucosal healing after treatment for 6 to12 months. Surgery was still needed in 16.5% of patients. Combination treatment of adalimumab with immunomodulators further decreased the level of CDAI at week 8 when compared with the monotherapy. Conclusions: Even under the stringent criteria for using adalimumab, the response rate was comparable to those without stringent criteria. (Intest Res 2014;12:287-292)
World Journal of Surgery, 2004
Despite widespread use of laparoscopic surgery for colorectal operations, its application for cur... more Despite widespread use of laparoscopic surgery for colorectal operations, its application for curative resection of colorectal cancer is still controversial. One of the major concerns is the impact of the laparoscopic procedure on dissemination of tumor cells. The main purpose of this study was to investigate the impact of laparoscopic surgery on circulating tumor cells in colorectal cancer patients. Quantitation of circulating free tumor cells (FTCs) was performed preoperatively, during the operation, and 14 days later by means of real-time quantitative reverse transcriptasepolymerase chain reaction (RT-PCR) targeting guanylyl cyclase C (GCC) mRNA in 42 colorectal cancer patients undergoing laparoscopic resections. Despite an increasing trend of FTC detection in patients with advancing stage, there is no significant difference in the preoperative FTC level by disease stage. No elevation in FTC level was found during the laparoscopic procedure in most patients compared with their preoperative FTC value. Patients with a persistently high FTC load [per nucleated blood cells (NBCs)] (> 10 2 FTCs/10 6 NBCs) 2 weeks postoperatively portends a poor prognosis regarding disease recurrence and tumor-related mortality when compared to those with an undetectable or low FTC load (≤ 10 2 FTCs/ 10 6 NBCs). We concluded that the laparoscopic procedure itself had no significantly deleterious effect on circulating FTCs and that the detection of FTCs by real-time qRT-PCR might be of clinical importance during the postoperative follow-up for colorectal cancer patients.
World Journal of Surgery, 1997
The incidence of tuberculosis is rising in the United States. Similarly, the incidence of pulmona... more The incidence of tuberculosis is rising in the United States. Similarly, the incidence of pulmonary tuberculosis in Taiwan is increasing, but that of large bowel tuberculosis in this region has not been reported. The purpose of this study was to investigate the changing disease pattern and to determine some possible surgical prognostic factors for large bowel tuberculosis. Seventy cases of large bowel tuberculosis treated at our institute during the period 1965-1995 were reviewed and analyzed. A steady decline in the case number of large bowel tuberculosis were noted from 1975, but there seems to be a slight increase in cases since 1990. The average age of these patients was 65.1 years, and none had human immunodeficiency virus infection. The ileocecum is the most common region of involvement. Of these 70 patients, 59 had not been definitively diagnosed until surgery. Active pulmonary tuberculosis was found in 18 patients (25.7%). The incidence of postoperative pulmonary complications was higher in patients with active pulmonary tuberculosis or disseminating large bowel tuberculosis. Postoperative abdominal complications, including intestinal obstruction, abdominal cutaneous fistula, and wound infection, were seen in 13 patients, none of whom had active pulmonary tuberculosis. Although the incidence of tuberculosis has been reduced for years, it is now rising. Physicians should bear in mind the possibility of large bowel tuberculosis in patients with intestinal obstruction without specific origin. Postoperative respiratory care is important for patients with pulmonary tuberculosis, with either active or disseminating lesions.
Journal of Surgical Oncology, 2011
Background and Objectives: The colon is a rare location for gastrointestinal non-Hodgkin's lympho... more Background and Objectives: The colon is a rare location for gastrointestinal non-Hodgkin's lymphoma. We retrospectively analyzed the demographic data of patients with colonic lymphoma and the possible prognostic factors of the disease. Methods: We studied data obtained from 6,944 patients and performed a retrospective review of patients with primary colonic lymphoma (PCL) by using a pathology registry database. We employed well-established and accepted diagnostic criteria and clinical staging method. Results: Twenty-nine patients (19 men; 10 women) were diagnosed with PCL. The cecum was the most common tumor location (14/29 patients), and 17 cases (17/29) showed diffuse large-B-cell lymphomas. Four patients died of sepsis within 30 days of an emergency surgery for perforation of intestine. Two-thirds of the patients were in the early disease stages (stages I and II). The overall 5-year survival rate was 47.3%. Disease stage was not a prognostic factor for survival. The overall 5-year survival rate in patients treated with surgery followed by chemotherapy was statistically significant as compared to that in the patients treated with chemotherapy alone. Conclusion: PCL is a rare malignancy of the gastrointestinal tract, and surgical resection should be considered a part of the standard treatment to achieve a better outcome.
International Journal of Colorectal Disease, 2010
Adjuvant systemic 5-fluorouracil (5-FU)-based chemotherapy improves survival after resection of s... more Adjuvant systemic 5-fluorouracil (5-FU)-based chemotherapy improves survival after resection of synchronous colorectal liver metastases (CLMs), but not metachronous. We retrospectively examined if adjuvant chemotherapy with new regimen containing oxaliplatin or irinotecan improved survivals after resection of metachronous CLMs. Between 2000 and 2007, 52 patients having undertaken resection of metachronous CLMs with curative intent were identified from Taipei Veterans General Hospital hospitalization registry. One patient with perioperative mortality and another being lost to follow-up within 3 months after metastasectomy were excluded. Thirty-one patients experienced six to 12 cycles of FOLFOX or FOLFIRI chemotherapy while 19 patients with 5-FU/leucovorin (LV)-based chemotherapy following CLM resection. The primary end point was disease-free survival (DFS) and secondary end point, overall survival (OS). By the univariate analysis, median DFS was 34.3 months in the FOLFOX/FOLFIRI group vs 14.2 months in the 5-FU/LV group (P = 0.022). The median OS and 5-year survival rates were longer than 57.7 months (not reached, with median follow-up of 35.5 months) and 54.0%, respectively, in the FOLFOX/FOLFIRI group compared to 49 months and 34.6% in the 5-FU/LV group (P = 0.027). FOLFOX/FOLFIRI chemotherapy was shown by multivariate analyses to be an independent factor predicting a better DFS (hazard ratio [HR] = 0.37; 95% CI: 0.15-0.94; P = 0.036) and a better OS (HR = 0.27; 95% CI: 0.083-0.86, P = 0.026) than 5-FU/LV-based. Adjuvant FOLFOX/FOLFIRI chemotherapy following resection of metachronous CLMs is demonstrated to have better DFS and OS than 5-FU/LV chemotherapy.
Diseases of the Colon & Rectum, 1999
In patients with colorectal cancer, brain metastasis is infrequent. This study aims to elucidate ... more In patients with colorectal cancer, brain metastasis is infrequent. This study aims to elucidate the risk, pattern of occurrence, and survival time after different treatment modalities. A retrospective review of all patients with colorectal cancer admitted to the Veterans General Hospital-Taipei between 1970 and 1996 from our hospital was performed. Univariate analysis for survival determination was performed. Brain metastases developed subsequent to surgery for colorectal cancer in 53 well-documented patients, at a median of 36 months after surgery. Brain metastases were more commonly seen in rectal cancer and often occurred concurrently with lung metastases. Forty of these patients received active intervention in terms of surgery, chemotherapy, or radiotherapy, with surgical intervention achieving a significantly increased mean survival time (+/- standard deviation) compared with chemotherapy or radiotherapy or both of 86.6 +/-17.35 vs. 2.9 +/- 0.59 months (P < 0.05). Increased awareness of the possibility of brain metastases, early diagnosis, and aggressive therapy can provide increased survival time for patients with colorectal cancer with brain metastases.
Diseases of the Colon & Rectum, 1992
Digestive and Liver Disease, 2008
Intrahepatic cholangiocarcinoma and colorectal cancer liver metastasis are the most primary and s... more Intrahepatic cholangiocarcinoma and colorectal cancer liver metastasis are the most primary and secondary adenocarcinoma of the liver, respectively. A large-scale long-term comparative study of these two cohort patient is lacking. A total of 166 colorectal cancer liver metastasis patients and 206 intrahepatic cholangiocarcinoma patients who had undergone curative liver resection were retrospectively analysed. Among 206 intrahepatic cholangiocarcinoma, there were 47 intraductal growth type-intrahepatic cholangiocarcinoma and 159 non-intraductal growth type-intrahepatic cholangiocarcinoma. The demographics, clinicopathological data, immunohistochemical study and survival were analysed. The intrahepatic cholangiocarcinoma patients were more female-predominated, associated with hepatolithiasis, symptomatic, jaundiced, and with larger tumour size compared with those of colorectal cancer liver metastasis. Prognostic factors of intrahepatic cholangiocarcinoma were pathologic staging, histologic pattern and section margin; whereas prognostic factors of colorectal cancer liver metastasis were rectal origin, differentiation, section margin and bilobar distribution. CK7 and CK20 differentiated majority of intrahepatic cholangiocarcinoma from colorectal cancer liver metastasis, while CDX2 and MUC5AC helped to differentiate inconclusive cases. The 1-, 3-, 5- and 10-year survival rates of colorectal cancer liver metastasis were 77%, 31%, 20% and 14%, compared to 53%, 21%, 13% and 7% of intrahepatic cholangiocarcinoma (p=.0001). Furthermore, the survival of colorectal cancer liver metastasis was comparable to staged II intrahepatic cholangiocarcinoma (p=.8866) and intraductal growth type-intrahepatic cholangiocarcinoma (p=.1915). Demographics, precipitating factor, clinical manifestations, and prognostic factors of colorectal cancer liver metastasis and intrahepatic cholangiocarcinoma differed remarkably. High incidence of CDX2 and MUC2 expression in colorectal cancer liver metastasis and intraductal growth type-intrahepatic cholangiocarcinoma might explain their similar cytoarchitecture and survival.
Anti-Cancer Drugs, 2004
Selective cyclooxygenase-2 (COX-2) inhibitors have been found to induce anti-proliferative and ap... more Selective cyclooxygenase-2 (COX-2) inhibitors have been found to induce anti-proliferative and apoptotic activity in many cancer cells. However, interaction between COX-2 inhibitors and other chemotherapeutic agents remains to be determined. We investigated the interactive effects of a selective COX-2 inhibitor, etodolac, in combination with 5-fluorouracil (5-FU) or SN-38 (active metabolite of irinotecan) on colon cancer cell lines, HT29 and SW620, in simultaneous and sequential administration schedules. Isobologram analysis demonstrated that etodolac in combination with 5-FU or SN-38 according to a simultaneous schedule resulted in only an additive effect; however, synergism was achieved in a sequential schedule. Apoptosis induction in both cell lines was also significantly increased after sequential treatment with etodolac followed by either 5-FU or SN-38 compared to that after simultaneous treatment with etodolac and either 5-FU or SN-38. Our study suggests apoptosis-inducing synergism resulted from administration of etodolac and either 5-FU or SN-38 sequentially, but not simultaneously.
Annals of surgical oncology, Jan 15, 2015
Colorectal cancer (CRC) is a heterogeneous disease caused by genetic and epigenetic alterations. ... more Colorectal cancer (CRC) is a heterogeneous disease caused by genetic and epigenetic alterations. This study aimed to describe the mutation frequency of 12 genes in different CRC phenotypes. Patients who underwent surgery at the Taipei Veterans General Hospital during 2000-2010 for CRC (n = 1249) were enrolled. The endpoint was overall survival. The prognostic value was determined with the log-rank test and Cox regression analysis. We found 1836 mutations of 12 genes in 997 (79.8 %) tumors. Mutations were most frequently in KRAS (485, 38.8 %), TP53 (373, 29.9 %), APC (363, 29.0 %), and PIK3CA (179, 14.3 %); 137 (11.0 %) cancers had high microsatellite instability (MSI). Women had significantly higher high MSI (14.3 %) and BRAF mutation (6.3 %) frequencies. The abnormal MSI (21.7 %) and KRAS (44.6 %), BRAF (8.6 %), PIK3CA (19.4 %), AKT1 (2.2 %), and TGF - βR (9.6 %) mutation frequencies were significantly higher in proximal colon cancer. The high MSI (35.6 %) and BRAF (20.3 %), TGF - ...
Hepato-gastroenterology
Survival of patients with colorectal cancer confined to the muscularis propria (stage I) is excel... more Survival of patients with colorectal cancer confined to the muscularis propria (stage I) is excellent after curative resection. However, some patients are likely to develop lymph node and distant metastasis that can ultimately cause death. The purpose of this study was to identify the possible predictors of lymph node and distant metastasis in T1 and T2 colorectal cancers. In total 208 patients with T1 and T2 colorectal cancers who underwent surgical resection in Taipei Veterans General Hospital from July 1996 to December 2001 were enrolled. The clinicopathological variables including age, gender, tumor location (rectum/colon), preoperative carcinoembryonic antibody level, depth of tumor invasion, lymphovascular invasion, and unfavored histology corresponding to the metastasis assessed pathologically were analyzed. Categorical variables were analyzed using Chi-square with Yates&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; correction. The independent predictor of lymph node and distant metastasis was determined with multivariate binary logistic regression. Of the 208 T1 and T2 colorectal cancer patients, 36 (17.3%) had lymph node metastasis and 5 (2.4%) had distant metastasis at surgery. The risk of lymph node metastasis was 14.3% (8/56) in T1 and 18.4% (28/52) in T2 colorectal cancer. The tumors with evidence of lymphovascular invasion had a significantly higher incidence of lymph node metastasis than those without lymphovascular invasion (43.6% vs. 9.4%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The independent risk factor for lymph node metastasis was lymphovascular invasion only (95% confidence interval, 3.37-19.97; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), whereas that for distant metastasis was preoperative carcinoembryonic antibody level &amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;5ng/mL only (95% confidence interval, 0.03-0.21; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The negative predictive value of possible adverse risk factors including preoperative carcinoembryonic antibody level &amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;5ng/mL, lymphovascular invasion, and unfavored differentiation for metastasis was 93.5%. Considering the negative predictive value of combined possible adverse risk factors, the risk of metastasis still was 6.5%. Therefore radical surgery was recommended for all T1 and T2 stage colorectal cancer patients except if the patient had a very high surgical risk.
Background. The aim of this study was to compare surgical outcomes of primary resection and delay... more Background. The aim of this study was to compare surgical outcomes of primary resection and delayed resection as emergent curative surgery for obstructive left-sided colorectal cancer (CRC). Methods. Between January 1980 and December 2002, a total of 143 ...
Hepato-gastroenterology
The significance of tumor volume and its change after concurrent chemoradiotherapy (CCRT) was eva... more The significance of tumor volume and its change after concurrent chemoradiotherapy (CCRT) was evaluated. Standard-dose external radiation and oral UFUR plus leucovorin were used to treat 30 middle and lower rectal adenocarcinoma patients. Volume of tumor calculated from images obtained by dynamic MRI of the rectum before and after CCRT was compared to pathological results after definite resection and other clinical data. The T-stage in 15 patients (50%), the N-stage in 13 (72.2%), and overall, the TNM stage in 18 (60%), were downstaged, including 7 (23.3%) with complete responses (CR). Volume of tumor before CCRT (Vpre) and after CCRT (VPost) was 10.3+/-6.1cm3 and 4.2+/-2.2cm3, respectively, and VPre correlated with initial T stage, N stage, age, and location. The net decrease ratio (NDR) of tumor volume was related to Vpre and initial T stage. As to the downstaging effect, VPre was related to incidence of CR; NDR was related to the downstaging of the N stage. All tumors showed volume reduction after CCRT, but the downstaging benefits were not in proportion to the size change. Initially larger tumors had higher ratios of volume reduction, and smaller tumors had higher chance of CR.
Hepato-gastroenterology
We evaluated the prognostic significance of clinicopathologic features recommended by the majorit... more We evaluated the prognostic significance of clinicopathologic features recommended by the majority of guidelines for identifying high-risk stage it colon cancer patients. We enrolled 665 stage II colorectal cancer patients at Taipei Veterans General Hospital in 2002-2006. Patients who received preoperative or postoperative chemotherapy were excluded (124). The measured endpoint was disease-free survival. Of 541 patients, 59 showed stage T4 tumors; 35, lymphovascular invasion; 19, poor differentiation, and 251, carcinoembryonic antigen levels of > 5 ng/mL; 53 underwent emergent operations. Colorectal cancer recurred in 84 patients. The 5-year disease-free survival rate was 84.5%. Univariate and multivariate analyses revealed 3 independent factors affecting the prognosis significantly tumor stage T4, high carcinoembryonic antigen level, and presence of lymphovascular invasion. Considering the cumulative effect of risk factors, the 5-year disease-free survival rate of patients with ...
Hepato-gastroenterology
The significance of prognostic value of DNA ploidy patterns of colorectal cancer has not yet been... more The significance of prognostic value of DNA ploidy patterns of colorectal cancer has not yet been fully understood. The present study was designed to determine the prognostic value of DNA ploidy patterns for colorectal adenocarcinomas after resection. We have prospectively collected tumor specimens from 420 patients with colorectal cancer since 1996. The DNA ploidy patterns were determined with the use of DNA flow cytometry. The correlation of DNA ploidy pattern and various characteristics of tumors and the prognostic significance of DNA ploidy patterns were evaluated by univariate as well as Cox's proportional hazard model. The disease-free survival curves were calculated with Kaplan-Meier's analysis, and the survival difference was determined by log-rank test. DNA ploidy patterns were diploid in 115 (27.4%) and aneuploid in 305 patients (72.6%). The pattern of DNA ploidy did not correlate with age, gender, location, differentiation, and stage of the tumors. In 146 patients...
Purpose. Stool occult blood tests and serum CEA level examinations are widely used at health chec... more Purpose. Stool occult blood tests and serum CEA level examinations are widely used at health check-up of detecting colorectal lesions. The aim of this study is to evaluate the effectiveness of using single stool occult blood tests or serum CEA levels in routine health check up. Methods. We examined 1404 patients who came for health check up at Veterans General Hospital, Taipei, Taiwan from April 2004 to May 2005. They were all underwent single stool occult blood test, serum CEA level and complete colonoscopy during the check up. Results. There were patients with colorectal cancers in 9 (0.6%), polyps in 268 (19.1%) (Significant polyps in 95), diverticulum in 86 (6.1%) and other lesions in 9 (0.6%). Positive stool occult blood tests were noted in 97 patients (6.9%). The sensitivity, specificity, false positive rate and false negative rate of stool occult blood test to detect significant colorectal neo- plasm were 14.4%, 93.1%, 6.9% and 85.6% respectively. There were 39 (2.8%) patient...