Colorectal (Bowel) Cancer
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Colorectal cancer (or bowel cancer) is one of the most common types of cancer in both men and women. Approximately four fifths of these cancers are found in the colon (large intestine), and one fifth in the rectum. Prevention and early detection of colorectal cancer is important. Some of most common symptoms include a change in bowel habit (eg. constipation, and bleeding), mucus discharge, and discomfort or pain in the lower abdomen. The vast majority of colon and rectum cancers are adenocarcinomas, around 10% of these are mucinous (protein contained in mucus). The median age at diagnosis is 70, age adjusted incidence rates are slightly higher in males compared to females. A substantial proportion of cases are in those with a genetic predisposition to colorectal cancer. Diet may also have an influence on the incidence of colorectal cancer, diatry fibre, retinoids, and calcium are thought to be protective, while high intake of animal fats may increases risk. Colorectal cancer may develop from benign polyps (a polyp is a tumour on a stem most commonly found on mucous membranes). World-wide about 782,000 people are diagnosed with colorectal cancer each year.

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Prevention of Colorectal (Bowel) Cancer

Information Patients and the Public (18 links)

Information for Health Professionals / Researchers (12 links)

Herdiatry Colorectal Cancers (5 links)

Between 15-20% of all colorectal cancers are thought to be familial. Some types of colon cancers and pre-disposing conditions are known to have an inherited element, in particular, Lynch Syndrome (hereditary non-polyposis colon cancer, HNPCC) and familial adenomatous polyposis (FAP).See also: Gene and Chromosome Abnormalities (Cancer GeneWeb)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Popp C, Stăniceanu F, Micu G, et al.
Long-standing ulcerative colitis complicated with mantle-cell lymphoma transformed in diffuse large B cell lymphoma.
Rom J Intern Med. 2014; 52(3):176-82 [PubMed] Related Publications
Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease of the colon and rectum. Its etiology and pathogenesis are incompletely elucidated, although there are many studies concerning these problems. Chronic inflammation and immunosuppressive treatment are risk factors for epithelial and lymphoid malignancies. We present a case of a 39-year-old man who died after a long-standing untreated UC complicated with mantle cell colonic lymphoma and then with transformation towards a high grade diffuse large B cell lymphoma. Multiple colonic biopsies were collected in various moments of the disease. Microscopic and immunohistochemical features are comparatively presented. This case emphasizes the importance of constant surveillance for UC patients and reaffirms the role of multidisciplinary approach in UC management.

Related: Mantle Cell Lymphoma

Bergeles C, Pratt P, Merrifield R, et al.
Multi-view stereo and advanced navigation for transanal endoscopic microsurgery.
Med Image Comput Comput Assist Interv. 2014; 17(Pt 2):332-9 [PubMed] Related Publications
Transanal endoscopic microsurgery (TEM), i.e., the local excision of rectal carcinomas by way of a bimanual operating system with magnified binocular vision, is gaining acceptance in lieu of more radical total interventions. A major issue with this approach is the lack of information on submucosal anatomical structures. This paper presents an advanced navigation system, wherein the intraoperative 3D structure is stably estimated from multiple stereoscopic views. It is registered to a preoperatively acquired anatomical volume based on subject-specific priors. The endoscope motion is tracked based on the 3D scene and its field-of-view is visualised jointly with the preoperative information. Based on in vivo data, this paper demonstrates how the proposed navigation system provides intraoperative navigation for TEM1.

Hong SH, Cha JM, Lee JI, et al.
Association of hyper-LDL cholesterolemia with increased risk of colorectal adenoma.
Hepatogastroenterology. 2014; 61(134):1588-94 [PubMed] Related Publications
BACKGROUND/AIMS: Previous studies on the association between dyslipidemia and the presence of colorectal adenoma showed conflicting results, and were limited due to small sample sizes, inconsistent definitions of dyslipidemia, or a lack of data on full lipid profiles. The aim of this study was to determine the association between colorectal adenomas and dyslipidemia according to the definition by the National Cholesterol Education Program- Adult Treatment Panel III.
METHODOLOGY: We conducted a retrospective, cross-sectional study in subjects who underwent screening colonoscopy and blood tests for full lipid profiles. Serum dyslipidemia profiles were compared between the adenoma group and the control group, and multivariate analysis was performed to identify independent predictors of the presence of colorectal adenomas.
RESULTS: Patients with hyper-LDL cholesterolemia were more frequently included in the adenoma group than the control group (46.7% vs. 32.1%, respectively, p=0.023), and hyper-LDL cholesterolemia (OR = 1.954, 95% CI=0.981-3.893, p=0.057) showed a statistical trend for the positive association with the presence of colorectal adenomas by multivariate analysis. Furthermore, proximal colorectal adenomas were more prevalent in the hyper-LDL cholesterolemia group than in the normal LDL cholesterolemia group (p=0.026).
CONCLUSIONS: Hyper-LDL cholesterolemia was associated with the presence of colorectal adenomas, especially in the proximal colon.

Nakanishi M, Kuriu Y, Murayama Y, et al.
Efficacy of perioperative chemotherapy in patients with colorectal cancer undergoing hepatectomy for resectable synchronous liver metastasis.
Hepatogastroenterology. 2014; 61(134):1582-7 [PubMed] Related Publications
BACKGROUND/AIMS: Although aggressive resection is recommended for the treatment of resectable liver metastasis of colorectal cancer, recurrences often develop in the remaining liver. In our department, perioperative chemotherapy was introduced for the treatment of colorectal cancer associated with resectable synchronous liver metastasis. The results of this treatment are reported herein. The study population was 20 patients (9 men, 11 women) with colorectal cancer associated with resectable synchronous liver metastasis whose data were collected between April 2009 and September 2012.
METHODOLOGY: The patients received chemotherapy (mFOLFOX6 or XELOX + bevacizumab) for 3 months each before and after hepatectomy following resection of the primary lesion.
RESULTS: Preoperative chemotherapy yielded a response rate of 66.7%, and no serious postoperative complications were noted. Although recurrence was found in 9 patients after treatment, 4 have so far remained cancer-free after re-resection. Thus, re-resection of the recurrent lesion resulted in patients maintaining cancer-free status for a prolonged period.
CONCLUSIONS: The use of perioperative chemotherapy in patients with colorectal cancer associated with resectable synchronous liver metastasis may improve outcomes after hepatectomy.

Bertani E, Chiappa A, Della Vigna P, et al.
The Impact of pelvimetry on anastomotic leakage in a consecutive series of open, laparoscopic and robotic low anterior resections with total mesorectal excision for rectal cancer. .
Hepatogastroenterology. 2014; 61(134):1574-81 [PubMed] Related Publications
BACKGROUND/AIMS: Recently, pelvic anatomy has been taken into consideration and related to surgical outcome indicators after low anterior resection (LAR). Several pelvimetric parameters have been matched with conversion rate, postoperative complications and duration of surgery in laparoscopic series, and with the quality of specimen and pathologic outcomes in further open surgical series.
METHODOLOGY: In 97 consecutive patients submitted to sphincter-saving LAR with total mesorectal excision (TME) five pelvic dimensions were measured by abdominal computed tomography scan: anteroposterior and transverse diameters in the pelvic inlet (IAP and ITRA), anteroposterior and transverse diameters in the pelvic outlet (OAP and OTRA), and the pelvic depth. The endpoint evaluated was anastomotic leakage (AL) rate.
RESULTS: There were 51 open, 12 laparoscopic and 34 robotic LARs. The sum of IAP OAP and OTRA (Pelvic Index) significantly predicted AL showing that starting from the cut-point of 290 mm down to a PI of 278 mm the odds-ratio of having an AL increased from 2.63 (95% CI: 1.10,5.47) to 5.07 (95% CI: 1.35,8.02).
CONCLUSIONS: The sum of the 3 pelvic dimensions which we termed “Pelvic Index” was associated to AL following sphinctersaving LAR. This may be considered in planning the surgical strategy for rectal cancer patients.

Wang Y, Duan B, Shen C, et al.
Treatment and multivariate analysis of colorectal cancer with liver metastasis.
Hepatogastroenterology. 2014; 61(134):1568-73 [PubMed] Related Publications
BACKGROUND/AIMS: The aim of this study was to identify the influencing factors related to outcome of patients of colorectal cancer with liver metastasis.
METHODOLOGY: From January 1999 to January 2009, 293 cases of colorectal cancer with liver metastasis undergoing surgery were analysised retrospectively. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate analysis. Results: The 1-, 3- and 5-year survival rates of patients after resection were 58.3%, 26.4%, and 11.3%, respectively. Univariate analysis showed that preoperative CEA level, degree of primary tumor differentiation, resection margin, number of liver metastases, resection of liver metastases were prognostic impacts. The difference was statistically significant (p<0.05). Cox multivariate analysis showed that preoperative CEA level, number of liver metastases, and resection of liver metastases are three separate prognostic factors.
CONCLUSIONS: Racical resection is the key to improve the long-term survival rate of colorectal cancer with liver metastasis. Important predictive factors related to poor survival are preoperative CEA level and number of liver metastases.

Kashihara H, Shimada M, Kurita N, et al.
CD133 expression is correlated with poor prognosis in colorectal cancer.
Hepatogastroenterology. 2014; 61(134):1563-7 [PubMed] Related Publications
BACKGROUND/AIMS: Cancer stem cells (CSC) was reported to play an important role in various kinds of cancer. CD133 is one of the cancer stem cell markers in solid cancers. However, the correlation between CD133 expression and the clinicopathological factors in colorectal cancer (CRC) remains unclear.
METHODOLOGY: Forty patients with CRC who underwent operations were enrolled. Expression of CD133 was investigated by immunohistochemistry (IHC). The staining was observed in the cytoplasm of cancer cells and the patients who have the staining were defined as CD133-positive cases. The patients were divided into two groups: the CD133-positive group (n = 22) and negative group (n = 18). Clinicopathological factors were compared between the two groups. The prognostic factors were investigated by multivariate analysis.
RESULTS: In the CD133-positive group, the incidence of lymph node and liver metastasis, lymphatic and venous invasion, as well as the progression of stage of cancer were higher than that in the CD133-negative group. The 5-year survival rate and the disease-free survival rate in the CD133-positive group were lower than that in the CD133-negative group. The multivariate analysis revealed that CD133 expression tended to be an independent prognostic factor.
CONCLUSIONS: CD133 expression is correlated with poor prognosis in CRC.

Kobayashi T, Kawakamil M, Hara Y, et al.
Combined evaluation of the Glasgow prognostic score and carcinoembryonic antigen concentration prior to hepatectomy predicts postoperative outcomes in patients with liver metastasis from colorectal cancer.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1359-62 [PubMed] Related Publications
BACKGROUND/AIMS: Little is known about the ability of the inflammation-based Glasgow prognostic score (GPS).
METHODOLOGY: 106 patients who underwent curative resection for colorectal liver metastasis (CRLM) were analyzed. Patients with an elevated Creactive protein concentration (>10 mg/L) and hypoalbuminemia (<35 g/L) at admission were assigned a GPS 2, those with only 1 of these biochemical abnormalities were assigned a GPS 1, and those without either abnormality were assigned a GPS 0.
RESULTS: Multivariate analysis showed that 2 variables, carcinoembryonic antigen (CEA) concentration > 30 ng/mL and a GPS 1 or 2, were independently prognostic of survival. Patients were classified into 3 groups on the basis of these 2 variables. Patients with GPS 1 or 2 and CEA concentration > 30 ng/mL were assigned a new score of 2, those with either 1 factor were assigned a new score of 1, and those with neither factors were assigned a new score of 0. The 5-year overall survival rates of new scores of 0, 1, 2 were 71.5%, 31.6%, and 0%, respectively (P < 0.0001).
CONCLUSIONS: This simple staging system may be able to identify a subgroup of patients who are eligible for curative resection but show poor prognosis.

Yao HH, Shao F, Huang Q, et al.
Nomogram to predict anastomotic leakage after laparoscopic anterior resection with intracorporeal rectal transection and double-stapling technique anastomosis for rectal cancer.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1257-61 [PubMed] Related Publications
BACKGROUND/AIMS: Laparoscopic rectal cancer surgery involving rectal division with intracorporeal stapling devices is technically difficult. This study aimed to identify risk factors for anastomotic leakage associated with laparoscopic anterior resection for rectal cancer.
METHODOLOGY: 476 patients who underwent laparoscopic anterior resection with intracorporeal rectal transection and double-stapling technique (DST) anastomosis for rectal cancer between July 2007 and February 2013 were retrospectively studied. All clinical variables were examined by univariate and multivariate analyses. A nomogram was developed to predict postoperative anastomotic leakage, given associated risk factors, and bootstrap validation was performed. The outcome of interest was clinical anastomotic leakage.
RESULTS: In multivariate analysis, tumor location (p=0.001), operation time (p=0.001) and preservation of the left colic artery (p=0.037) were independently and significantly associated with anastomotic leakage. The resulting nomogram demonstrated good accuracy in predicting long-term complication, with a bootstrapcorrected concordance index 0.835.
CONCLUSIONS: Our results suggest that we found that tumor localization, preservation of the left colic artery and operation time are predictive factors for clinical anastomotic leakage in laparoscopic anterior resection with intracorporeal rectal transection and double-stapling technique (DST) anastomosis for rectal cancer.

Sakata N, Sakata Y, Shimoda R, et al.
Repeated screening with fecal immunochemical tests reduced the incidence of colorectal cancers in Saga, Japan.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1224-8 [PubMed] Related Publications
BACKGROUND/AIMS: Screening with fecal occult blood test has reduced mortality from colorectal cancer (CRC), with fecal immunochemical tests (FIT) widely utilized for CRC screening in Japan. To evaluate the importance of repeated FIT screening, the incidence of CRC was compared in patients undergoing initial and repeated screening.
METHODOLOGY: Participants aged ≥40 years in Saga, Japan, were invited to undergo a 2-day FIT. FIT positive subjects were verified by colonoscopy to evaluate the CRC incidence rates.
RESULTS: From 2005 to 2007, 55,595 individuals were invited to undergo CRC screening, including 47,168 undergoing repeated and 8,427 undergoing initial screening. Of the 5,832 FIT-positive subjects, 4,615 were assessed by colonoscopy, with 114 diagnosed as having CRC. Of these 114 patients, 67 had early and 47 had advanced CRC. The risk of CRC was 63% lower in the repeated than in the initial screening group (p<0.0001). Of the 67 patients with early CRC, 42 underwent endoscopic resection, with the rate significantly higher in the repeated than in the initial screening group (p = 0.01). Overall survival was longer in screened subjects than in those who visited hospitals with clinical symptoms.
CONCLUSIONS: Repeated CRC screening with FIT reduced the incidence of CRC in Saga, Japan.

Related: Cancer Screening and Early Detection

Nakayama M, Yoshimatsu K, Yokomizo H, et al.
Incidence and risk factors for incisional hernia after open surgery for colorectal cancer.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1220-3 [PubMed] Related Publications
BACKGROUND/AIMS: To confirm the incidence and risk factors of incisional hernia after colorectal cancer surgery, we analyzed the clinical data including the surveillance computed tomography (CT) examination.
METHODOLOGY: One hundred sixty seven patients with open abdominal surgery for colorectal cancer were analyzed retrospectively.
RESULTS: Incisional hernia was recognized in 27 cases (16.2%), and occurred at median 7 (1-21) months after surgery. Multivariate analysis showed the risk factors for incisional hernia were female (p=0.0014), distal colon and rectal cancer (p=0.0038), high body mass index (p=0.0055) and lower serum albumin (p=0.0081).
CONCLUSIONS: Obesity, lower median incision and malnutrition might seem to relate to the incisional hernia after colorectal cancer surgery.

Tan YN, Li XF, Li JJ, et al.
The accuracy of computed tomography in the pretreatment staging of colorectal cancer.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1207-12 [PubMed] Related Publications
Colorectal cancer (CRC) is one of the most frequent cancers around the world. Multimodality therapies are used for CRC including surgery, chemotherapy, radiotherapy and targeted therapy. Correct treatment plan depends greatly on the accurate pretreatment staging. Computed tomography (CT) is a widely used detection and staging modality for CRC patients in clinical practice. The role of CT in assessing the patients with CRC has been well established, but the accuracy of pretreatment staging by CT varies in different reports. With the development of CT techniques, some reformations such as multi-detector CT (MDCT), CT with water enema or air insufflations, multiple planner reconstruction (MPR) help to give us higher resolution images in shorter time. The accuracy of CT for N staging was still not so ideal, but CT played an important role in chest and liver staging. Magnetic resonance imaging (MRI) and endorectal ultrasound (ERUS) may provide more precise images and evaluation of local T and N staging for rectal cancer. And positron emission tomography (PET) or PET/CT is recommended as a complement of CT, only for cases suspected of residual or recurrent colorectal carcinoma or before metastasectomy, not for routine use.

Herrigel DJ, Moss RA
Diabetes mellitus as a novel risk factor for gastrointestinal malignancies.
Postgrad Med. 2014; 126(6):106-18 [PubMed] Related Publications
Evidence of an emerging etiologic link between diabetes mellitus and several gastrointestinal malignancies is presented. Although a correlation between pancreatic cancer and diabetes mellitus has long been suspected, the potential role diabetes mellitus plays in the pathogenicity of both hepatocellular carcinoma and colon cancer is becoming increasingly well defined. Further supporting the prospect of etiologic linkage, the association of diabetes mellitus with colon cancer is consistently demonstrated to be independent of obesity. An increasing incidence of diabetes and obesity in the United States has led to a recent surge in incidence of hepatocellular cancer on the background of nonalcoholic fatty liver disease, and this disease is expected to commensurately grow in incidence. Widespread recognition of this emerging risk factor may lead to a change in screening practices. Although the mechanisms underlying the correlation are still under investigation, the role of insulin, the insulin-like growth factor-I, and related binding and signaling pathways as regulators of cell growth and cell proliferation are implicated in carcinogenesis and tumor growth. The potential role of metformin and other medications for diabetes mellitus in the chemoprevention, carcinogenesis, and treatment of gastrointestinal malignancies is also presented.

Related: Liver Cancer Cancer of the Pancreas Pancreatic Cancer

Cakmakkaya OS, Kolodzie K, Apfel CC, Pace NL
Anaesthetic techniques for risk of malignant tumour recurrence.
Cochrane Database Syst Rev. 2014; 11:CD008877 [PubMed] Related Publications
BACKGROUND: Surgery remains a mainstay of treatment for malignant tumours; however, surgical manipulation leads to a significant systemic release of tumour cells. Whether these cells lead to metastases is largely dependent on the balance between aggressiveness of the tumour cells and resilience of the body. Surgical stress per se, anaesthetic agents and administration of opioid analgesics perioperatively can compromise immune function and might shift the balance towards progression of minimal residual disease. Regional anaesthesia techniques provide perioperative pain relief; they therefore reduce the quantity of systemic opioids and of anaesthetic agents used. Additionally, regional anaesthesia techniques are known to prevent or attenuate the surgical stress response. In recent years, the potential benefit of regional anaesthesia techniques for tumour recurrence has received major attention and has been discussed many times in the literature. In preparing this review, we aimed to summarize the current evidence systematically and comprehensively.
OBJECTIVES: To establish whether anaesthetic technique (general anaesthesia versus regional anaesthesia or a combination of the two techniques) influences the long-term prognosis for individuals with malignant tumours.
SEARCH METHODS: We searched The Cochrane Library (2013, Issue 12), PubMed (1950 to 15 December 2013), EMBASE (1974 to 15 December 2013), BIOSIS (1926 to 15 December 2013) and Web of Science (1965 to 15 December 2013). We handsearched relevant websites and conference proceedings and reference lists of cited articles. We applied no language restrictions.
SELECTION CRITERIA: We included all randomized controlled trials or controlled clinical trials that investigated the effects of general versus regional anaesthesia on the risk of malignant tumour recurrence in patients undergoing resection of primary malignant tumours. Comparisons of interventions consisted of (1) general anaesthesia alone versus general anaesthesia combined with one or more regional anaesthetic techniques; (2) general anaesthesia combined with one or more regional anaesthetic techniques versus one or more regional anaesthetic techniques; and (3) general anaesthesia alone versus one or more regional anaesthetic techniques. Primary outcomes included (1) overall survival, (2) progression-free survival and (3) time to tumour progression.
DATA COLLECTION AND ANALYSIS: Two review authors independently scanned the titles and abstracts of identified reports and extracted study data.All primary outcome variables are time-to-event data. If the individual trial report provided summary statistics with odds ratios, relative risks or Kaplan-Meier curves, extracted data enabled us to calculate the hazard ratio using the hazard ratio calculating spreadsheet. To assess risk of bias, we used the standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS: We included four studies with a total of 746 participants. All studies included adult patients undergoing surgery for primary tumour resection. Two studies enrolled male and female participants undergoing major abdominal surgery for cancer. One study enrolled male participants undergoing surgery for prostate cancer, and one study male participants undergoing surgery for colon cancer. Follow-up time ranged from nine to 17 years. All four studies compared general anaesthesia alone versus general anaesthesia combined with epidural anaesthesia and analgesia. All four studies are secondary data analyses of previously conducted prospective randomized controlled trials.Of the four included studies, only three contributed to the outcome of overall survival, and two each to the outcomes of progression-free survival and time to tumour progression. In our meta-analysis, we could not find an advantage for either study group for the outcomes of overall survival (hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.86 to 1.24) and progression-free survival (HR 0.88, 95% CI 0.56 to 1.38). For progression-free survival, the level of inconsistency was high. Pooled data for time to tumour progression showed a slightly favourable outcome for the control group (general anaesthesia alone) compared with the intervention group (epidural and general anaesthesia) (HR 1.50, 95% CI 1.00 to 2.25).Quality of evidence was graded low for overall survival and very low for progression-free survival and time to tumour progression. The outcome of overall survival was downgraded for serious imprecision and serious indirectness. The outcomes of progression-free survival and time to tumour progression were also downgraded for serious inconsistency and serious risk of bias, respectively.Reporting of adverse events was sparse, and data could not be analysed.
AUTHORS' CONCLUSIONS: Currently, evidence for the benefit of regional anaesthesia techniques on tumour recurrence is inadequate. An encouraging number of prospective randomized controlled trials are ongoing, and it is hoped that their results, when reported, will add evidence for this topic in the near future.

Related: Prostate Cancer

Liang PS, Dominitz JA
Editorial: Bowel preparation: is fair good enough?
Am J Gastroenterol. 2014; 109(11):1725-7 [PubMed] Related Publications
The effectiveness of colonoscopy in reducing colorectal cancer incidence and mortality has been shown to be associated with an endoscopist's adenoma detection rate, although the ability to detect adenomas depends, in part, on the quality of bowel preparation. Many endoscopists routinely recommend shorter examination intervals for colonoscopies with a fair or intermediate-quality bowel preparation, assuming that the preparation is insufficient for the purpose of colorectal cancer screening. In this issue, Clark et al. performed a systematic review and meta-analysis to assess the adequacy of a fair-quality bowel preparation, finding no difference in the adenoma detection rate of colonoscopies with an intermediate-quality bowel preparation relative to those with a high-quality preparation. Although this finding has potentially significant implications for patient care and healthcare costs, the limitations of the adenoma detection rate as a performance measure and variability in the application of bowel preparation ratings are important issues that must be considered.

Agarwal A, Daly KP, Butler-Bowen H, Saif MW
Safety and efficacy of radiofrequency ablation with aflibercept and FOLFIRI in a patient with metastatic colorectal cancer.
Anticancer Res. 2014; 34(11):6775-8 [PubMed] Related Publications
BACKGROUND: A vast majority of patients with metastatic colorectal cancer (mCRC) are not candidates for surgical resection. Radiofrequency ablation (RFA) is a safe and effective technique for treatment of isolated liver metastasis. After radiofrequency ablation, residual tumor can have aggressive growth, part of which is driven by the up-regulation of vascular endothelial growth factor (VEGF). Angiogenesis inhibitor bevacuzimab has been used in the management of mCRC with RFA. We present a patient with recurrent colorectal cancer and four hepatic metastases who was treated with RFA combined with aflibercept, another VEGF inhibitor and systemic chemotherapy. We believe that this is the first report of using aflibercept with RFA.
CASE REPORT: A 35-year-old female with stage IV rectal cancer with metastasis to a lymph node and multiple hepatic metastases was treated with chemo-radiation, surgical resection of the tumor and surgical resection of two segments of the liver. She underwent RFA of the hepatic lesions that could not be resected. She received adjuvant chemotherapy consisting of 5-fluorouracil (5-FU) and oxaliplatin for a total of 6 months. However, a positron emission tomography (PET) scan showed progression of disease with new and growing lymph nodes. She was treated with 6 cycles of capecitabine monotherapy. A follow-up PET scan showed four new liver lesions. She has RFA of her four liver lesions and was started on a combination of aflibercept and FOLFIRI. She received 10 cycles and a repeat magnetic resonance imaging (MRI) and PET scan showed stable disease.
DISCUSSION: This is the first reported case of a patient managed with RFA with aflibercept, an anti-VEGF agent, and FOLFIRI. This case showed both efficacy, as well as safety for the combined modalities in the management of mCRC.

Related: Fluorouracil Leucovorin Oxaliplatin

Eisterer W, De Vries A, Öfner D, et al.
Preoperative treatment with capecitabine, cetuximab and radiotherapy for primary locally advanced rectal cancer--a phase II clinical trial.
Anticancer Res. 2014; 34(11):6767-73 [PubMed] Related Publications
BACKGROUND/AIM: To investigate the feasibility and safety of preoperative capecitabine, cetuximab and radiation in patients with MRI-defined locally advanced rectal cancer (LARC, cT3/T4).
PATIENTS AND METHODS: 31 patients with LARC were treated with cetuximab and capecitabine concomitantly with 45 Gy radiotherapy and resected by total mesorectal excision. Histopathological response and association with KRAS status was evaluated.
RESULTS: R0-resection was possible in 27 of 31 (86%) patients. No complete pathological remission was observed. Radiochemotherapy with capecitabine and cetuximab was safe to administer and diarrhea was the main toxicity. KRAS-status did not correlate to down-staging or pathological response concerning T- or N-stage.
CONCLUSION: Neoadjuvant therapy with capecitabine and cetuximab in combination with radiotherapy did not lead to complete pathological remission. Treatment tolerability was excellent and toxicity remained low. KRAS status did not influence treatment outcomes. Capecitabine in combination with radiotherapy remains a standard therapy for locally advanced rectal cancer.

Related: Fluorouracil Capecitabine Cetuximab (Erbitux)

Beppu T, Emi Y, Tokunaga S, et al.
Liver resectability of advanced liver-limited colorectal liver metastases following mFOLFOX6 with bevacizumab (KSCC0802 Study).
Anticancer Res. 2014; 34(11):6655-62 [PubMed] Related Publications
BACKGROUND/AIM: The Kyushu Study group of Clinical Cancer (KSCC) conducted phase II trials (KSCC0802-UMIN000001308) concerning liver resectability after first-line treatment of advanced liver-limited colorectal metastases (CRLM) by a prospective, multi-center study.
PATIENTS AND METHODS: Patients received 6 cycles of mFOLFOX6 with bevacizumab followed by evaluating liver resectability. The primary end-point was liver resection rate.
RESULTS: The 40 patients enrolled from September 2008 to August 2010. The median number of administration cycles was 6 (range=1-7). The liver resectability cases were 16/40 (40.0 %) and the number of R0 cases was 10 patients (25.0%). An overall response rate was 30.0% (95% CI=15.2%-44.8%). Median progression-free and overall survival of all patients was 9.7 months and 33.0 months), respectively.
CONCLUSION: mFOLFOX6 with bevacizumab regimen is safe and effective for advanced liver-limited CRLM and might lead to high liver resectability.

Related: Fluorouracil Leucovorin Oxaliplatin Bevacizumab (Avastin)

Lim SH, Chua W, Cheng C, et al.
Effect of neoadjuvant chemoradiation on tumor-infiltrating/associated lymphocytes in locally advanced rectal cancers.
Anticancer Res. 2014; 34(11):6505-13 [PubMed] Related Publications
BACKGROUND: Lymphocytes and natural killer cells (NK) appear to be important in colorectal cancer. Their role in chemoradiotherapy for rectal cancers is unclear. We evaluated T-lymphocytes (CD3), sub-groups CD4 and CD8, and NK cells (CD56+CD57) in normal and rectal tumor tissues pre- and post-chemoradiotherapy, and investigated their relationship to tumor regression grade, disease-free survival and pathological stage.
MATERIALS AND METHODS: Tissue microarrays from colonoscopic biopsies, resection specimens and normal tissues, from 52 patients, were immunostained.
RESULTS: NK cell counts were significantly lower in tumor samples compared to normal tissues (p=0.007). T-lymphocyte counts were higher in post-treatment compared to pre-treatment samples (p=0.025), specifically in the CD8 subgroup after long-course treatment. The results suggested an association between post-treatment CD8 and NK cell counts with higher tumor regression. No associations were found with regard to stage or disease-free survival.
CONCLUSION: NK cell counts were significantly reduced in rectal cancers compared to normal tissues, while total T-lymphocyte counts increased post-chemoradiotherapy. Both appeared important in tumor regression.

Related: Fluorouracil

Kim NK, Park JK, Shin E, Kim YW
The combination of nuclear factor kappa B, cyclo-oxygenase-2 and vascular endothelial growth factor expression predicts poor prognosis in stage II and III colorectal cancer.
Anticancer Res. 2014; 34(11):6451-7 [PubMed] Related Publications
BACKGROUND/AIM: To evaluate immunohistochemical expression of nuclear factor-kappa B (NFκB), cyclo-oxygenase (COX)-2, and vascular endothelial growth factor (VEGF) and the impacts thereof on clinicopathological tumor features and survival in patients with colorectal cancer.
MATERIALS AND METHODS: Sixty-six patients with colorectal cancer (stage II or III) were enrolled.
RESULTS: The positive expression rates of NF-κB, COX2, and VEGF were 62.1%, 51.5%, and 63.6%, respectively. Sixteen tumor samples (24.2%) coexpressed all three markers. Coexpression of all three markers correlated with pTNM III, poor histological grade, larger tumor diameter, and elevated carcinoembryonic antigen level. pTNM III and coexpression of all three markers were independent prognostic factors for cancer-specific and disease-free survival.
CONCLUSION: The combination of NFκB, COX2, and VEGF expression correlated with advanced pathological features and had a prognostic impact on cancer-specific and disease-free survival. These findings suggest that coexpression of three markers may have a synergistic effect on aggressive tumor biology.

Related: COX2 (PTGS2) VEGFA

Batsaikhan BE, Yoshikawa K, Kurita N, et al.
Cyclopamine decreased the expression of Sonic Hedgehog and its downstream genes in colon cancer stem cells.
Anticancer Res. 2014; 34(11):6339-44 [PubMed] Related Publications
UNLABELLED: Backround: Most solid cancers including colon cancer are believed to be initiated from and maintained by cancer stem cells (CSCs), that are responsible for treatment resistance, resulting in tumor relapse. The aim of this study was to clarify the possible role of the Sonic Hedgehog (Shh) signaling pathway in the regulation of cancer stem cells.
MATERIALS AND METHODS: The HCT-116 cell line was cultured with fetal bovine serum in RPMI-1640 medium and its sphere was grown in serum-free non-adherent culture. Gene expressions were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) from cells treated with and without cyclopamine.
RESULTS: HCT-116 sphere-derived cells grown in serum-free, non-adherent culture, showed significantly increased expression of stem cell markers, Shh downstream genes and epithelial-mesenchymal transition (EMT) markers compared to parental cells grown in conventional culture. The expression of stemness markers, Shh downstream genes and EMT markers were higher in cancer spheres than the parental cell line and down-regulated by cyclopamine treatment in a dose-dependent manner.
CONCLUSION: Overall, these findings show that cyclopamine treatment could down-regulate the expression of stemness markers, shh downstream genes and EMT markers on HCT-116 spheres.

Ranger GS
Current concepts in colorectal cancer prevention with cyclooxygenase inhibitors.
Anticancer Res. 2014; 34(11):6277-82 [PubMed] Related Publications
Colorectal cancer is one of the commonest malignancies worldwide. Recently, there has been much speculation regarding the role of cyclooxygenase-2 (COX-2) suppression in chemoprevention. Drugs with the ability to inhibit COX-2 expression include aspirin, nonsteroidal anti-inflammatory drugs (NSAID) and selective COX-2 inhibitors. Any strategy for chemoprevention must be able to quantify how effective the potential treatment is likely to be and which drugs will be most useful. We would also need to know for how long the agent could be taken safely and if any side-effects could preclude long-term use. Evidence from observational studies and recent updates of randomised controlled trials have been very encouraging - at least indicating benefit from the long term use of aspirin, even at low dose, with greatest impact on prevention of proximal colon cancers and adenomas. Most studies do, however, also warn that risks of gastrointestinal bleeding increase with long-term use of aspirin and related drugs. The risk-to-benefit ratio of a chemoprevention regimen using these medications needs to be carefully examined.

Crocetti D, Sapienza P, Sterpetti AV, et al.
Surgery for symptomatic colon lipoma: a systematic review of the literature.
Anticancer Res. 2014; 34(11):6271-6 [PubMed] Related Publications
AIM: Isolated colon lipomas are rare benign tumors. We herein conducted a systematic review of the literature to identify clinical characteristic, diagnostic and treatment options.
MATERIALS AND METHODS: A search for relevant studies was conducted in Scopus, Embase and Medline databases until the end of May 2014. The search terms were "colonic lipoma and colon lipoma". Articles were included if they had information on symptoms, lipoma characteristics and type of procedure performed.
RESULTS: 88 articles describing 184 patients affected with colonic lipomas were found. One hundred and twenty-seven patients were selected for further analysis. The most common signs included abdominal pain, rectal bleeding and alteration in bowel habits. Colonic lipomas were frequently localized in the right colon (50%). The majority of patients had open surgery, whereas current treatment is laparoscopic resection.
CONCLUSIONS: Laparoscopic surgery is the current standard-of-treatment of symptomatic colonic lipomas greater than 2 cm in diameter or when malignancy can not be preoperatively excluded.

Steffen A, Weber MF, Roder DM, Banks E
Colorectal cancer screening and subsequent incidence of colorectal cancer: results from the 45 and Up Study.
Med J Aust. 2014; 201(9):523-7 [PubMed] Related Publications
OBJECTIVE: To investigate the association of colorectal cancer (CRC) screening history and subsequent incidence of CRC in New South Wales, Australia.
DESIGN, SETTING AND PARTICIPANTS: A total of 196,464 people from NSW recruited to the 45 and Up Study, a large Australian population-based prospective study, by completing a baseline questionnaire distributed from January 2006 to December 2008. Individuals without pre-existing cancer were followed for a mean of 3.78 years (SD, 0.92 years) through linkage to population health datasets.
MAIN OUTCOME MEASURES: Incidence of CRC; hazard ratio (HR) according to screening history, adjusted for age, sex, body mass index, income, education, remoteness, family history, aspirin use, smoking, diabetes, alcohol use, physical activity and dietary factors.
RESULTS: Overall, 1096 cases of incident CRC accrued (454 proximal colon, 240 distal colon, 349 rectal and 53 unspecified cancers). Ever having undergone CRC screening before baseline was associated with a 44% reduced risk of developing CRC during follow-up (HR, 0.56; 95% CI, 0.49-0.63) compared with never having undergone screening. This effect was more pronounced for those reporting endoscopy (HR, 0.50; 95% CI, 0.43-0.58) than those reporting faecal occult blood testing (FOBT) (HR, 0.61; 95% CI, 0.52-0.72). Associations for all screening exposures were strongest for rectal cancer (HR, 0.35; 95% CI, 0.27-0.45) followed by distal colon cancer (HR, 0.60; 95% CI, 0.46-0.78), while relationships were weaker for cancers of the proximal colon (HR, 0.76; 95% CI, 0.62-0.92).
CONCLUSION: CRC incidence is lower among individuals with a history of CRC screening, through either FOBT or endoscopy, compared with individuals who have never had CRC screening, lasting for at least 4 years after screening.

Related: Australia

De Meis E, Brandão BC, Capella FC, et al.
Catastrophic antiphospholipid syndrome in cancer patients: an Interaction of clotting, autoimmunity and tumor growth?
Isr Med Assoc J. 2014; 16(9):544-7 [PubMed] Related Publications
Thrombosis is a common phenomenon in patients with malignancies. It is believed that thrombosis is multifactorial and that in addition to mechanisms directly associated with cancer and its treatment, it may also be related to the interaction between the immune system and clotting. The present work describes four cancer patients (three adults and one child) whose clinical course was characteristic of catastrophic antiphospholipid syndrome (CAPS) in intensive care units of the National Cancer Institute of Rio de Janeiro. The presence of findings similar to those in CAPS can be attributed to an unbalanced interaction between the immune system and coagulation.

Related: Extra-Hepatic Bile duct cancer (cholangiocarcinoma) Bone Cancers Lung Cancer Ewing's Sarcoma

Moszkowicz D, Peschaud F, El Hajjam M, et al.
Can we predict complete or major response after chemoradiotherapy for rectal cancer by noninvasive methods? Results of a prospective study on 61 patients.
Am Surg. 2014; 80(11):1136-45 [PubMed] Related Publications
Rectal preservation has been proposed as an alternative to radical resection in patients with presumed complete or major response to chemoradiotherapy (CRT). The aim of this prospective study was to evaluate the accuracy of digital rectal examination (DRE) and magnetic resonance imaging (MRI) to predict major or complete rectal cancer response to CRT. Over 2 years, 61 patients underwent radical resection after CRT for rectal cancer. DRE and MRI were carried out before and 6 to 8 weeks after the end of CRT. Data from DRE and MRI post-CRT were compared with pathological examinations. At pathological examination, major/complete responses were recorded for tumors classified ypT1N0 and ypT0N0, respectively. DRE post-CRT showed major/complete response in 26 cases, of which 14 (54%) were confirmed by pathology. The positive (PPV) and negative (NPV) predictive values of DRE to predict major/complete response were 54 and 88 per cent, respectively. MRI post-CRT showed major/complete response in 12 cases, of which nine (75%) were confirmed by pathology. The PPV and NPV of MRI to predict major/complete response were 75 and 82 per cent, respectively. Data from DRE and RMI post-CRT were concordant in 45 patients. The PPV and NPV of concordant DRE and MRI to predict major/complete response were 82 and 91 per cent, respectively. DRE and MRI do not appear to be sufficiently accurate for safe selection of patients appropriate for a rectum-sparing strategy because the risk of leaving an invasive tumor untreated is 18 per cent.

Shao Y, Zou LL, Zhou QH, et al.
Fast-track surgery for gastroenteric neoplasms: a meta-analysis.
Tumori. 2014 Sep-Oct; 100(5):e197-203 [PubMed] Related Publications
AIMS AND BACKGROUND: Fast-track surgery has been shown to enhance postoperative recovery. The objective of the study was to determine the differences of fast-track surgery and conventional care for patients with gastroenteric neoplasms.
METHODS AND STUDY DESIGN: We searched PubMed, EMBASE, and the Cochrane Library for related trials to compare hospital stay and rates of complications and readmission.
RESULTS: Thirteen randomized controlled trials, with 1,962 patients, were included. Results showed the length of hospital stay was significantly reduced in the fast-track group. The complications rate was lowered in colorectal surgery. There were no significant differences in rate of readmissions.
CONCLUSIONS: Current trials show that fast-track surgery may reduce the length of hospital stay and lower the rate of complications of gastroenteric surgery.

Related: Stomach Cancer Gastric Cancer

Kekez D, Badzek S, Prejac J, et al.
Fluorouracil, leucovorin and irinotecan combined with intra-arterial hepatic infusion of drug-eluting beads preloaded with irinotecan in unresectable colorectal liver metastases: side effects and results of a concomitant treatment schedule. Clinical investigation.
Tumori. 2014 Sep-Oct; 100(5):499-503 [PubMed] Related Publications
AIM: Safety evaluation of concomitant systemic chemotherapy and liver chemoembolization in patients with colorectal cancer.
PATIENTS AND METHODS: Seven patients with metastases confined to the liver were included and stratified into two groups, depending of dosage of systemic chemotherapy. The first group received systemic chemotherapy (FOLFIRI) with 20% dose reduction, and the second group received the full dose of the same chemotherapy. In both groups, chemoembolization of liver metastases with drug-eluting bead irinotecan (DEBIRI) was performed following the application of systemic chemotherapy. The toxicity profiles of the two groups were compared.
RESULTS: Of the 7 patients included, 4 received the reduced systemic chemotherapy dose and 3 received the full chemotherapy dose. DEBIRI was performed in all 7 patients. The main toxicities observed in the reduced chemotherapy dose group were leukopenia (25%), anorexia (75%), diarrhea (25%), vomiting (25%), right upper abdominal quadrant pain (100%) and elevated serum amylase level (25%). Main toxicities observed in the full chemotherapy dose group were anorexia (66.6%), vomiting (33.3%), right upper abdominal quadrant pain (100%), and elevated serum amylase level (66.6%). There were no significant differences between the two groups ( P = 0.78541).
CONCLUSIONS: Patients with isolated liver metastases from a colorectal primary can safely be treated with DEBIRI chemoembolization and a full dose of systemic chemotherapy (FOLFIRI).

Related: Fluorouracil Leucovorin Irinotecan

Liu BX, Zhou JY, Li Y, et al.
Hederagenin from the leaves of ivy (Hedera helix L.) induces apoptosis in human LoVo colon cells through the mitochondrial pathway.
BMC Complement Altern Med. 2014; 14:412 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Colorectal cancer has become one of the leading cause of cancer morbidity and mortality throughout world. Hederagenin, a derivative of oleanolic acid isolated from the leaves of ivy (Hedera helix L.), has been shown to have potential anti-tumor activity. The study was conducted to evaluate whether hederagenin could induce apoptosis of human colon cancer LoVo cells and explore the possible mechanism.
METHODS: MTT assay was used for evaluating cell viability while Annexin V-FITC/PI assay and Hoechst 33342 nuclear stainining were used for the determination of apoptosis and mitochondrial membrane potential. DCFH-DA fluorescence staining and flow cytometry were used to measure ROS generation. Real-time PCR and western blot analysis were performed for apoptosis-related protein expressions.
RESULTS: MTT assay showed that hederagenin could significantly inhibit the viability of LoVo cells in a concentration-dependent and time-dependent manner by IC50 of 1.39 μM at 24 h and 1.17 μM at 48 h. The apoptosis ratio was significantly increased to 32.46% and 81.78% by the induction of hederagenin (1 and 2 μM) in Annexin V-FITC/PI assay. Hederagenin could also induce the nuclear changes characteristic of apoptosis by Hoechst 33342 nuclear stainining under fluorescence microscopy. DCFH-DA fluorescence staining and flow cytometry showed that hederagenin could increase significantly ROS generation in LoVo cells. Real-time PCR showed that hederagenin induced the up-regulation of Bax and down-regulation of Bcl-2, Bcl-xL and Survivin. Western blotting analysis showed that hederagenin decreased the expressions of apoptosis-associated proteins Bcl-2, procaspase-9, procaspase-3, and polyADP- ribosepolymerase (PARP) were increased, while the expressions of Bax, caspase-3, caspase-9 were increased. However, there was no significant change on caspase-8.
CONCLUSIONS: These results indicated that the disruption of mitochondrial membrane potential might contribute to the apoptosis of hederagenin in LoVo cells. Our findings suggested that hederagenin might be a promising therapeutic candidate for human colon cancer.

Related: Apoptosis CASP3 Mitochondrial Mutations in Cancer

Deliu IC, Georgescu EF, Bezna MC
Analysis of prognostic factors in colorectal carcinoma.
Rev Med Chir Soc Med Nat Iasi. 2014 Jul-Sep; 118(3):808-16 [PubMed] Related Publications
UNLABELLED: Colorectal cancer is one of the most common malignancies in development countries. The purpose of this study was to analyze the epidemiologic profiles of the disease, to examine the results of survival at five years after diagnosis and how it was influenced by pathological aspects.
MATERIAL AND METHODS: In collaboration with Oncologic Clinic all colorectal cancer diagnosed from January 2002 to December 2006 were included in the study. Medical records of patients were retrieved and we note: age, residence, diagnosis date, grade, and stage and histology variables. Then were analyzed prognosis and survival at 5 years of patients related to these parameters.
RESULTS: A total of 238 patients with colorectal cancer were identified. The average age at diagnosis was 63.3 years and more than half of cases were men (59%). By the end of the follow-up period 103 patients had died, 66.1% of them representing colon cancer. When analyzing the survival length according to tumor location at the end of the study, we found that are no significant differences between survivals in colic tumors compared to the rectum--53.9 months for right colon, 51.4 months for left colon and 49.5 months for rectum. The majority of tumors were grade II moderately-differentiated tumors 48.7% (116 of cases), and patients with grade I had the best survival, on average of 84.52 months. Tubular forms of colorectal cancer had the best percentage of five years survival (55.81%) being also the highest rate of survival (45.24% months).
CONCLUSION: Factors that contribute to a favorable prognosis in colorectal cancer are tubular microscopic form, disease diagnosed in TNM stage I and II, GI and GII grading.

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