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

AIM:To identify the differential proteins associated withcolorectal cancer genesis and hepatic metastasis.METHODS:Hydrophobic protein samples were extractedfrom normal colorectal mucosa,primary cancer lesion andhepatic metastatic foci of colorectal cancer.With two-dimensional electrophoresis and image analysis,differentially expressed protein spots were detected,andthe proteins were identified by matrix assisted laserdesorption/ionization-time of flight-mass spectrometry andpeptide mass fingerprint analysis.RESULTS:Significant alterations of the proteins in numberand expression levels were discovered in primary cancerand hepatic metastatic foci,the expression of a number ofproteins was lost in 25-40 ku,but protein spots wasincreased in 14-21ku,compared with normal mucosa.Ninedifferentially expressed protein spots were identified.Threeproteins expressed in normal mucosa,but lost in primarycancer and hepatic metastasis,were recognized ascalmodulin,ribonuclease 6 precursor and mannosidase-αProapolipoprotein was expressed progressively from normalmucosa to primary cancer and hepatic metastasis.Thedifferentially expressed protein of beta-globin was found innormal mucosa and hepatic metastatic tumor,but lost inprimary cancer lesion.Cdc 42,a GTP-binding protein,wasidentified in hepatic metastasis.The protein spots of C4from primary cancer,M7 and M9 from hepatic metastasishad less homology with the proteins in database.CONCLUSION:Variations of hydrophobic protein expressionin colorectal cancer initiation and hepatic metastasis aresignificant and can be observed with two-dimensionalelectrophoresis.The expression of calmodulin,ribonuclease6 precursor and mannosidase-α is lost but the expressionof proapolipoprotein is enhanced which is associated withcolorectal cancer genesis and hepatic metastasis.Cdc 42and beta-globin are expressed abnormally in hepaticmetastasis.Protein C4,M7 and M9 may be associated withcolorectal cancer genesis and hepatic metastasis.     

Which kind of surgery in elderly people for colorectal cancer?

Colo-rectal cancers are of high incidence in elderly patients. Different clinical features and the peculiar behavior of the tumor may influence surgical results and should be considered in the decision making, when the surgeon has to decide whether to perform radical gut resection or less straining palliative procedures. In a retrospective study, 102 large bowel cancer patients are analyzed submitted to surgery in the period 1989-1994. Patients were divided in two age classes: Group A: above 70 years of age, 45 cases (44.2%); Group B: under 70 years of age, 57 cases (55.8%). Emergency surgery procedures were necessary in 35 patients (34.4%), 20 cases (57%) in Group A and 15 cases (43%) in Group B. Radical resections could be performed in 25 (37%) old patients, 67% of the cases underwent a curative resection. Perioperative mortality and surgical complication rates were significantly higher in Group A than in Group B. The technical and biological difficulties in performing radical curative resections, the high complication rates and the occurrence of negative results of treatments provide a reason for careful evaluation of the risk/benefit ratio in older patients, where less straining palliative therapies may sometimes offer similar results.     

Radical surgery for early colorectal cancer—anachronism or oncologic necessity?

Background and aims Because of their low morbidity and mortality, limited resection or local excision are accepted therapeutical approaches in early colorectal cancer treatment. Even though, recent publications report recurrence rates after local excision of rectal cancer in up to 30%. This prompted us to evaluate our data for T1N0 colorectal cancer treated by radical surgery regarding recurrence, morbidity, mortality, and survival rates. Materials and methods Clinical, histopathological, and surveillance data from our prospective “colorectal cancer database” from 1979 to 2005 were analyzed to evaluate outcome and prognosis of T1N0 colorectal cancer treated by radical surgery. Only curative resections were included in this study. All patients were followed in an internal surveillance program, which enabled us to prospectively assess morbidity, mortality, and survival. Results A total of 105 T1N0 colon and 69 rectal carcinomas were included in the study. Overall morbidity was 25% (colon) and 34% (rectum). Thirty-day mortality was 1.9% (colon) and 4.3% (rectum). After a median follow-up of 92 and 87 month, no isolated local recurrence occurred. One patient developed both local recurrence and liver metastases. Distant metastases were seen in 4.9% (colon) and 7.5% (rectum). The 5- and 10-year overall survival was 86 and 71% (colon) and 82 and 68% (rectum), respectively. Conclusion Even if radical surgical approaches are associated with a higher rate of morbidity and mortality, our data show that radical surgery for T1N0 colorectal cancer results in excellent tumor control which is of paramount importance for the patients’ prognosis and survival. Combining the data presented with those of the current literature suggests that local approaches to rectal cancer can be recommended for highly selected T1N0 tumors, in palliative situations, or if the patient is unfit for general surgery.     

How often should we perform surveillance colonoscopy after surgery for colorectal cancer?

Purpose

Surveillance colonoscopy is undertaken after resection of colorectal cancer to detect and treat local recurrence and metachronous lesions, with the aim of improving survival. This study aimed to clarify the current timing of surveillance colonoscopies and evaluate the rates of local recurrence and metachronous tumors.

Methods

We retrospectively analyzed data from 459 patients who underwent surveillance colonoscopy at our institution after curative resection of colorectal cancer. The number and timing of surveillance colonoscopies, incidence of local recurrence and metachronous lesions, pathological findings of lesions, treatment of lesions, and outcomes were recorded.

Results

The first surveillance colonoscopy was undertaken at 6–18 months after surgery in 73 % of patients. Local recurrence was detected in three cases (0.7 %), all during the first surveillance colonoscopy, which was performed >1 year after surgery. These three patients all underwent additional surgery and were alive 5 years later. Invasive metachronous cancers were detected in six patients (1.3 %) at 18–57 months after surgery, and advanced adenomas were detected in 30 patients.

Conclusion

Considering the low incidence of postoperative lesions and the timing of lesion detection, reducing the number of surveillance colonoscopies after surgery for colorectal cancer may be appropriate.     

Can Hemoccult-IIℳ replace colonoscopy in surveillance after radical surgery for colorectal cancer and after polypectomy?

Surveillance after colorectal carcinoma and adenoma includes colonoscopy, which is a demanding procedure for the patient, doctor, and society. Therefore, it was investigated whether a simple fecal occult blood test could replace colonoscopy. Hemoccult-II (H-II) was performed before 1,244 colonoscopies in patients with previous cancer and before 328 colonoscopies in an adenoma surveillance program. The H-II test was positive in 3 of 9 patients with local recurrence, in 2 of 13 with metachronous cancer, and in 31 of 186 with adenomas. The test was positive more often in patients with large and multiple adenomas, sigmoid adenomas, and adenomas with villous elements and moderate-to-severe dysplasia, but the sensitivity did not reach more than 25 to 40 percent. It was concluded that markers more sensitive than H-II are needed to detect metachronous cancers and new adenomas. In the meantime, colonoscopy has to be used with intervals of several years, but not for detection of local recurrent cancer, which in most cases may be found by simpler means.Supported by grants from the Danish Cancer Society.     

Who gets chemotherapy for metastatic lung cancer?

STUDY OBJECTIVES: To determine the prevalence and factors associated with chemotherapy use in elderly patients presenting with advanced lung cancer. DESIGN: A retrospective cohort study using administrative data. SETTING AND PATIENTS: We analyzed the medical bills for the 6,308 Medicare patients > 65 years old with diagnosed stage IV non-small cell lung cancer (NSCLC) in the 11 SEER (survival, epidemiology, and end results) regions between 1991 and 1993. The main outcome measure, chemotherapy administration, was identified by the relevant medical billing codes. Patient sociodemographic and disease characteristics were obtained from the SEER database and census data. RESULTS: Almost 22% of patients received chemotherapy at some time for their metastatic NSCLC. As expected, younger patients and those with fewer comorbid conditions were more likely to receive chemotherapy. However, several nonmedical factors, such as nonblack race, higher socioeconomic status, treatment in a teaching hospital, and living in the Seattle/Puget Sound or Los Angeles SEER regions, also significantly increased a patient's likelihood of receiving chemotherapy. CONCLUSION: Compared to previous reports, the prevalence of chemotherapy use for advanced NSCLC appears to be increasing. However, despite uniform health insurance coverage, there is wide variation in the utilization of palliative chemotherapy among Medicare patients, and nonmedical factors are strong predictors of whether a patient receives chemotherapy. While it is impossible to know the appropriate rate of usage, nonmedical factors should only influence a patient's likelihood of receiving treatment if they reflect patient treatment preference. Research to further clarify the costs, benefits, and patient preferences for chemotherapy in this patient population is warranted in order to minimize the effect of nonmedical biases on management decisions.     

Phytochemicals and colorectal cancer prevention--myth or reality?

Chemoprevention of colorectal cancer has been the focus of intensive research for more than two decades. Epidemiological evidence has shown a small, but significant association between fruit and vegetable intake and a reduction in colorectal cancer risk. In vitro and animal data have also demonstrated that many dietary phytochemicals have potent chemopreventive activities. However, in humans, single-agent compounds have yielded conflicting results. A key concept is that dietary phytochemicals exert beneficial effects at low concentrations when working in synergy with each other. As the gut microflora evolved in an environment rich in dietary fiber and phytochemicals, the rapid shift towards a Western diet creates an environment in which the gut is more vulnerable to carcinogens, genetic alterations and inflammation. As enforcing dietary interventions on large populations is not realistic, we believe future chemopreventive work should focus on delivering phytochemical mixtures that target the multiple molecular events involved in colorectal carcinogenesis.     

Dukes C colorectal cancer: is the metastatic lymph node ratio important?

Purpose  

Although the regional lymph node status is essential for staging of colorectal cancer, the importance of the total number of collected nodes remains controversial. Our aim was to examine the impact of the metastatic lymph node ratio (LNR) on the survival of patients with Dukes C colorectal cancer.     

Adjuvant therapy for stage II colorectal cancer: Who and with what?

Opinion statement The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-riskrd stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and metaanalyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-riskrd stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.