Abstract

In Taiwan, the prevalence of colorectal cancer has been increasing in recent decades. As a result, the fecal occult blood test (FOBT) has been advocated and widely used for colorectal cancer screening in areas with limited colonoscopy capacity. The goal of this study was to analyze the sensitivity of a single immunochemical FOBT (I-FOBT) and correlate it with the results of colonoscopy for detecting colorectal neoplasia in the asymptomatic Taiwanese population. Data were collected from the results of health examinations conducted on asymptomatic adults older than 40 years and who simultaneously underwent one-time I-FOBT and colonoscopy examinations between January 01, 2008 and June 30, 2009. The sensitivity and specificity of the I-FOBT were calculated in correlation to age, size, and pathologic result. A total of 6096 patients were analyzed, including 3418 men and 2678 women, aged 40–87 years. I-FOBT result was positive in 229 patients (3.8%), the sensitivity of detection of total colorectal neoplasia and advanced neoplasia were 6.98% and 22.1%, respectively. A total of 13 participants were found to have invasive cancer in this study, and the sensitivity and specificity of the I-FOBT in this group were 69.2% and 96.4%, respectively. Besides, the positive rate of I-FOBT increased with age, with 40–49 years (2.89%), 50–75 years (4.21%), and >75 years (5.68%). In addition, the sensitivity for detecting total neoplasia and advanced neoplasia was similar in patients ≥50 years and ≥40 years of age. The I-FOBT has better sensitivity for detecting invasive cancer and advanced neoplasia than for detecting nonadvanced neoplasia. Repeated I-FOBT examinations with good adherence to the screening program may improve the detection rate and sensitivity of the I-FOBT.

Abstract

Statins are a class of drugs used to lower cholesterol levels, accompanying increased high-density lipoprotein (HDL) levels. Previous studies have suggested that statins can inhibit inflammation, and also reduce tumor proliferation. We therefore hypothesized that pravastatin, a member of the statins, mediating the inhibitory functions in tumor growth may be associated with the upregulated HDL constituent, apolipoprotein A1 (ApoA1). Pravastatin-induced inhibition in tumor proliferation in vitro and in xenografts was investigated. Reduced ApoA1 expressions were detected in the tumor regions in specimens from tumor patients as well in xenografts using Western Blotting. Moreover, ApoA1 was administered to inhibit tumor proliferation, and pravastatin was given to enhance the chemotherapeutic efficacy of doxorubicin (DOX). We found a significant statistical reduction of ApoA1 in the tumor regions of specimens from gastric cancer and colorectal cancer patients. MKN45 cells proliferation was inhibited by 18% under the growing medium containing pravastatin. ApoA1 levels were elevated in liver Clone 9 cells administered pravastatin, but not in MKN45 cells. In vitro studies revealed that ApoA1 can reduce MKN45 tumor proliferation. Moreover, the tumor volume was significantly reduced in in vivo xenografts after the administration of pravastatin. Combined treatments of pravastatin with DOX significantly minimized the size of tumors, leading to a better therapeutic efficacy. This study demonstrated that pravastatin elevated ApoA1, an HDL major constituent with anti-inflammatory characteristics, which displayed strong adversary associations with tumor developments and growth. Increasing the amounts of ApoA1 by pravastatin coupled with DOX may improve the therapeutic efficacy for cancer treatment.

Abstract

Compared with intravenous chemotherapy, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival in patients with recurrent colorectal disease confined to the peritoneum. We report our experience with CRS and HIPEC for colorectal cancer patients with peritoneal carcinomatosis, evaluating prognostic factors for disease-free survival (DFS), overall survival (OS), and perioperative morbidity and mortality. All patients who underwent CRS and HIPEC were included in our study. Clinical characteristics, operative data, and 30-day morbidity and mortality were collected and evaluated. Between January 2001 and December 2012, there were 35 consecutive patients who underwent CRS and HIPEC at our institution. Thirty-three patients (94%) had optimal cytoreduction. No 30-day mortality was reported, but 14 patients had postoperative complications. The median DFS was 9.4 months (95% confidence interval 5.5–18.7 months), and DFS at 1 year, 3 years, and 5 years were 43.8%, 22.3%, and 22.3%, respectively. The median OS was calculated to be 27.1 months (95% confidence interval 15.3–39.1), and the OS at 1 year, 3 years, and 5 years were 83.7%, 38.2%, and 19.1%, respectively. CRS and HIPEC can provide survival benefit, with reasonable morbidity and mortality for Asian patients with peritoneal carcinomatosis from colorectal cancer. Patient selection and perioperative management of the patients are key to the success of the procedure.

Abstract

The aim of this study was to analyze our experience with rectal cancer patients who underwent surgical excision at our institution. Data on 112 rectal cancer patients who underwent surgical resection with total mesorectal excision, from January 2005 to December 2008, were evaluated retrospectively. We achieved an initial complete remission rate of 74.1%. Overall, 92.8% of patients had a complete total mesorectal excision. The overall survival analysis for all patients showed a 1-year survival rate of 98%, a 3-year survival rate of 82%, and a 5-year survival rate of 70%. We report a 41.9% rate of postoperative complications. The 1-, 3-, and 5-year survival rates for females were 100%, 90%, and 72%, respectively and for males, they were 90%, 80%, and 68%, respectively. Differences in overall survival by sex were not statistically significant (p > 0.05). Those patients who were treated with only surgery had the best outcomes with survival being worse in those treated with surgery and adjuvant therapy. Neoadjuvant treatment followed by surgery led to better results. We conclude that we have been successful in achieving high rates of curative resection, complete remission, and overall survival. Neoadjuvant and adjuvant chemotherapy significantly impact rates of remission.

Abstract

Laparoscopic colorectal surgery has been extensively used, although mostly performed in medical centers or university hospitals. We analyzed the learning curve of laparoscopic colectomy in a new regional hospital and determined the experience necessary to achieve proficiency. From July 2008 to December 2013, the retrospective clinical study enrolled 240 patients who underwent laparoscopic colectomy. They were sequentially divided into Group A (Patients 1–80), Group B (Patients 81–160), and Group C (Patients 161–240). Patient demographics and perioperative parameters were analyzed. Operation time, as a measure of learning time, was analyzed using the moving-average method. All patients were comparable for age, gender, body mass index, tumor location, cancer stage, length of hospital stay, intraoperative complication, morbidity, and mortality. Group A experienced more blood loss (p < 0.01) and longer operation time (p < 0.001). All laparoscopic operation time stabilized after 85 cases. Subgroup analysis showed that operation time stabilized after 15 cases for right hemicolectomy, 15 cases for sigmoidectomy, and 22 cases for low anterior resection with total mesorectal excision. Laparoscopic colectomy for colorectal cancer in a new regional hospital is feasible and safe. It does not need additional time for learning. Laparoscopic sigmoidectomy can be considered as the initial surgery for a trainee.

Abstract

Full-length (FL) docking protein-1 (DOK1) is an adapter protein which inhibits growth factor and immune response pathways in normal tissues, but is frequently lost in human cancers. Small DOK1 variants remain in cells of solid tumors and leukemias, albeit, their functions are elusive. To assess the so far unknown role of DOK1 in colorectal cancer (CRC), we generated DOK1 mutants which mimic the domain structure and subcellular distribution of DOK1 protein variants in leukemia patients. We found that cytoplasmic DOK1 activated peroxisome-proliferator-activated-receptor-gamma (PPARγ) resulting in inhibition of the c-FOS promoter and cell proliferation, whereas nuclear DOK1 was inactive. PPARγ-agonist increased expression of endogenous DOK1 and interaction with PPARγ. Forward translation of this cell-based signaling model predicted compartmentalization of DOK1 in patients. In a large series of CRC patients, loss of DOK1 protein was associated with poor prognosis at early tumor stages (*p = 0.001, n = 1492). In tumors with cytoplasmic expression of DOK1, survival was improved, whereas nuclear localization of DOK1 correlated with poor outcome, indicating that compartmentalization of DOK1 is critical for CRC progression. Thus, DOK1 was identified as a prognostic factor for non-metastatic CRC, and, via its drugability by PPARγ-agonist, may constitute a potential target for future cancer treatments.