Gastrointestinal System Cancers
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Digestive and Gastrointestinal System cancers.

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Latest Research Publications

General Resources for GI Cancer (9 links)

Latest Research Publications

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

Deshpande G, Samarasam I, Chandran BS, et al.
Extended multiorgan resection in locally advanced gastric cancer: a single centre experience from south India.
Trop Gastroenterol. 2013 Oct-Dec; 34(4):259-63 [PubMed] Related Publications
BACKGROUND: The prognostic and survival benefit of extended multiorgan resection for locally advanced gastric adenocarcinoma remains controversial. The morbidity associated with additional organ resection has been found to be higher when compared to patients undergoing gastrectomy alone. The aim of our study was to evaluate the morbidity, mortality and survival benefit associated with extended multiorgan resection for locally advanced gastric adenocarcinoma.
METHODS: From January 2004 to December 2011, 721 patients underwent resectional surgery for gastric adenocarcinoma at the Christian Medical College, Vellore, India. Out of this group, 36 patients underwent primary resection and had one or more organs resected in addition to the stomach. A retrospective analysis of the case records of all these patients was performed. The Kaplan-Meier survival probability was estimated. Cox regression analysis was used to evaluate the clinico-pathological variables affecting the survival of these patients.
RESULTS: The perioperative morbidity and mortality rates were 25% and 5.5% respectively. The most common organs resected were colon and spleen. The incidence of pathologically confirmed T4b cancers was only 50%. The median survival of these patients was 28 months. The survival was influenced by a R0 or curative resection. However, it was not statistically significant.
CONCLUSION: Extended multiorganresection in locally advanced gastric cancer can be performed with acceptable morbidity and mortality. In our study, overstaging was found in 50% of the patients and hence, when the real nature of invasion is unclear, the surgeon may proceed with en bloc resection of the stomach with the involved adjacent organs. As long as an R0 resection can be achieved, extended multiorgan resection can be performed for carcinoma stomach.

Related: Stomach Cancer Gastric Cancer


Namuslu M, Kocaoglu H, Celik HT, et al.
Effects of aqueous soybean, mistletoe and red clover extracts on activities of adenosine deaminase and xanthine oxidase enzyme.
Bratisl Lek Listy. 2014; 115(6):367-71 [PubMed] Related Publications
Soybean (Glycine max), mistletoe (Viscum album) and red clover (Trifolium pratence) have been argued to have anti-cancer effects. In the present study it was aimed to investigate possible effects of these plant extracts on the activities of DNA turn-over enzymes, namely adenosine deaminase (ADA) and xanthine oxidase (XO) in cancerous and non-cancerous gastric and colon tissues. For this aim, 6 cancerous and 6 non-cancerous adjacent human gastric tissues, and 7 cancerous and 7 non-cancerous adjacent colon tissues were obtained by surgical operations. Our results suggest that aqueous soybean, mistletoe and red clover extracts may exhibit anti-tumoral activity by depleting hypoxanthine concentration in the cancer cells through XO activation, which may lead to lowered salvage pathway activity necessary for the cancer cells to proliferate in the cancerous colon tissue. Some foods like soybean, mistletoe and red clover may provide nutritional support to medical cancer therapy through inhibiting and/or activating key enzymes in cancer metabolism (Tab. 4, Ref. 33).


Maya S, Sarmento B, Lakshmanan VK, et al.
Actively targeted cetuximab conjugated gamma-poly(glutamic acid)-docetaxel nanomedicines for epidermal growth factor receptor over expressing colon cancer cells.
J Biomed Nanotechnol. 2014; 10(8):1416-28 [PubMed] Related Publications
Receptor targeted therapy is advantageous in overcoming the toxicity burden of conventional cancer chemotherapeutics. Over expression of epidermal growth factor receptor (EGFR) on cancer cells and its role in metastasis, malignancy and drug resistance in many human cancers lead to its selection as a promising target for cancer treatment. The present work investigated the preparation and characterization of docetaxel (DTXL) loaded gamma-poly (glutamic acid) (gamma-PGA) nanoparticles (Nps) conjugated with EGFR antibody (Cetuximab, CET) targeted to colon cancer cells (HT-29), highly over expressing EGFR. The flow cytometric analysis revealed two fold increased cellular uptake of CET-DTXL-gamma-PGA Nps by HT-29 (EGFR +ve) cells compared to that of IEC-6 (EGFR-ve) cells confirming the active targeting. Cytotoxicity assays (MTT and LDH) showed superior anti-proliferative activity of CET-DTXL-gamma-PGA NPs over DTXL-gamma-PGA Nps against HT-29 cells. The cell cycle analysis indicated that CET-DTXL-gamma-PGA NPs induced cell death in enhanced percentage of HT-29 cells by undergoing cell cycle arrest in G2/M phase compared to that of DTXL-gamma-PGA Nps. The mechanism of cancer cell death was analyzed via apoptotic and mitochondrial membrane potential assays and showed that targeted Nps treatment reduced the mitochondrial membrane potential thereby inducing enhanced HT-29 cell death (apoptosis and necrosis). The biodistribution of targeted and non-targeted Nps were analyzed in vivo in Swiss albino mice using NIR imaging. ICG-CET-DTXL-gamma-PGA Nps (targeted) and ICG-DTXL-gamma-PGA Nps (non-targeted) followed the similar biodistribution pattern in vivo, but with different elimination time. In short, CET-DTXL-gamma-PGA nanoparticles enhance the tumor selective therapeutic efficacy for colon cancer.

Related: Docetaxel Cetuximab (Erbitux)


Caplin ME, Pavel M, Ćwikła JB, et al.
Lanreotide in metastatic enteropancreatic neuroendocrine tumors.
N Engl J Med. 2014; 371(3):224-33 [PubMed] Related Publications
BACKGROUND: Somatostatin analogues are commonly used to treat symptoms associated with hormone hypersecretion in neuroendocrine tumors; however, data on their antitumor effects are limited.
METHODS: We conducted a randomized, double-blind, placebo-controlled, multinational study of the somatostatin analogue lanreotide in patients with advanced, well-differentiated or moderately differentiated, nonfunctioning, somatostatin receptor-positive neuroendocrine tumors of grade 1 or 2 (a tumor proliferation index [on staining for the Ki-67 antigen] of <10%) and documented disease-progression status. The tumors originated in the pancreas, midgut, or hindgut or were of unknown origin. Patients were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide (Autogel [known in the United States as Depot], Ipsen) at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks. The primary end point was progression-free survival, defined as the time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.0) or death. Secondary end points included overall survival, quality of life (assessed with the European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-GI.NET21), and safety.
RESULTS: Most patients (96%) had no tumor progression in the 3 to 6 months before randomization, and 33% had hepatic tumor volumes greater than 25%. Lanreotide, as compared with placebo, was associated with significantly prolonged progression-free survival (median not reached vs. median of 18.0 months, P<0.001 by the stratified log-rank test; hazard ratio for progression or death, 0.47; 95% confidence interval [CI], 0.30 to 0.73). The estimated rates of progression-free survival at 24 months were 65.1% (95% CI, 54.0 to 74.1) in the lanreotide group and 33.0% (95% CI, 23.0 to 43.3) in the placebo group. The therapeutic effect in predefined subgroups was generally consistent with that in the overall population, with the exception of small subgroups in which confidence intervals were wide. There were no significant between-group differences in quality of life or overall survival. The most common treatment-related adverse event was diarrhea (in 26% of the patients in the lanreotide group and 9% of those in the placebo group).
CONCLUSIONS: Lanreotide was associated with significantly prolonged progression-free survival among patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 (Ki-67 <10%). (Funded by Ipsen; CLARINET ClinicalTrials.gov number, NCT00353496; EudraCT 2005-004904-35.).

Related: Cancer of the Pancreas Pancreatic Cancer


Baber J, Anusionwu C, Nanavaty N, Agrawal S
Anatomical distribution of colorectal cancer in a Veterans Affairs Medical Center.
South Med J. 2014; 107(7):443-7 [PubMed] Related Publications
OBJECTIVES: The incidence of sporadic colorectal cancer (CRC) among individuals younger than 50 years of age and the incidence of proximal cancers has varied based on demographic factors in previous studies, and multisociety screening guidelines advise various modalities for average-risk individuals beginning at age 50. We studied the incidence and anatomic distribution of CRC in a population of military veterans to determine whether screening at a younger age is warranted.
METHODS: In a retrospective review of the electronic medical records of patients diagnosed as having CRC at the Dayton Veterans Affairs Medical Center between 2000 and 2010, a descriptive analysis of age at diagnosis, race, indication for colonoscopy, and anatomical distribution of the tumor was performed.
RESULTS: A total of 280 patients with CRC were identified, 272 of whom were histologically confirmed as having adenocarcinoma. The majority (98.6%) were men, with 25.6% of them African American. The mean age at diagnosis was 68.9 years (range 41-89 years), with 35% diagnosed in the eighth decade of life. Only 8 patients (2.9%) were younger than age 50. Most tumors (55%) were located distal to the splenic flexure, with synchronous lesions identified in seven patients. Screening colonoscopy identified only 18 (3.6%) cases.
CONCLUSIONS: Sporadic colorectal adenocarcinoma in patients younger than age 50 was identified in only 2.9% of all cases, whereas 42.5% of all cases were located proximal to the splenic flexure. This reinforces the American College of Gastroenterology guideline recommendation to initiate CRC screening in average-risk individuals at age 50. This study supports optical colonoscopy as the preferred screening modality.

Related: Colorectal (Bowel) Cancer Cancer Screening and Early Detection


Gidron Y, De Couck M, De Greve J
If you have an active vagus nerve, cancer stage may no longer be important.
J Biol Regul Homeost Agents. 2014 Apr-Jun; 28(2):195-201 [PubMed] Related Publications
The parasympathetic system, and primarily the vagus nerve, informs the brain about multiple signals and returns the body to homeostasis. Recent studies have shown that vagal nerve activity independently predicts prognosis in cancer. Here, we take this one step further and show that when vagal nerve activity is high, cancer stage no longer predicts tumor burden. We examined whether vagal nerve activity, indexed by Heart Rate Variability (HRV), moderated the effects of initial tumor stage on tumor burden at followup. Patients' HRVs were derived from ECGs near diagnosis in colorectal cancer (CRC) and in prostate cancer (PC) patients. Outcomes included the tumor markers carcinoembryonic antigen (CEA) at 12 months for CRC and prostate-specific antigen (PSA) at 6 months for PC. As would be expected, initially advanced tumor stages of CRC or PC predicted higher tumor marker levels at follow-up than did early stages. However, this occurred only in patients with low, not high, vagal activity (HRV). Furthermore, in patients with advanced tumor stage at diagnosis, high HRV predicted lower tumor marker levels than did low HRV, in both cancers. Estimating a cancer patient's prognosis by determining his tumor stage needs to also consider the vagal nerve activity. This activity is easily measurable, and it determines in which subjects the tumor stage is prognostic. Importantly, higher vagal activity may even protect against the adverse effects of advanced cancer stage. These findings, observed in two distinct cancers, support the hypothesized neuroimmunomodulatory effects of vagal nerve activity on tumors.

Related: Colorectal (Bowel) Cancer Prostate Cancer


Oh E, Ro JY, Gardner JM, et al.
Inflammatory myofibroblastic tumor of the appendix arising after treatment of gastric cancer: a case report and review of the literature.
APMIS. 2014; 122(7):657-9 [PubMed] Related Publications
Inflammatory myofibroblastic tumor (IMT) is a rare soft tissue neoplasm of uncertain malignant potential and unclear etiology. IMT involving the appendix is very rare. Herein, we report a case of IMT of the appendix in a gastric cancer patient who was treated with radical gastrectomy and adjuvant systemic chemotherapy. Rare cases of IMT associated with preceding events have been described in other organs/sites, but not in the appendix. A previous intra-abdominal operation for gastric cancer may contribute to the development of IMT in the appendix as seen in the present patient. To our knowledge, this is the first case of appendiceal IMT arising after a previous operation.

Related: Stomach Cancer Gastric Cancer


Sheets N, Powers J, Richmond B
Cutaneous metastasis of colon cancer: case report and literature review.
W V Med J. 2014 May-Jun; 110(3):22-4 [PubMed] Related Publications
Cutaneous metastases arising from an internal malignancy are a rare phenomenon, occurring in 0.001% of all skin biopsies performed. Of these, 6.5% originate from the a primary colon cancer. Colon cancer, when metastatic to the skin, typically appears as a painless flesh-colored nodule or as a mass with occasional ulceration. We report a case of a large cutaneous metastasis to the suprascapular region as the initial presenting symptom of an underlying colon cancer.


Kim J, Jang SG, Kwon SY, et al.
MicroRNA signature for HER2-positive breast and gastric cancer.
Anticancer Res. 2014; 34(7):3807-10 [PubMed] Related Publications
BACKGROUND/AIM: The molecular mechanism for aggressive clinical behaviour related to v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) amplification is not fully-understood. In particular, little is known about microRNAs in the human epidermal growth factor receptor 2 (HER2) signaling network.
PATIENTS AND METHODS: Using microRNA microarray, the microRNA profiles of 16 HER2-positive breast carcinomas were compared with those of five luminal-type breast carcinomas. Additionally, two frozen, ERBB2-amplified gastric carcinomas were compared with their adjacent normal tissue samples. MicroRNAs that were differentially expressed according to the HER2 status in breast and gastric carcinomas were identified as the HER2 microRNA signature.
RESULTS: MiR-337 and miR-302f were commonly overexpressed in HER2-postive breast and gastric cancer. MiR-139 and miR-129 were commonly underexpressed in HER2-positive breast and gastric cancer. A concordant pattern of microRNA expression was noted between discovery sets and the majority of candidate microRNAs (two out of three) in three validation sets.
CONCLUSION: Our study identified novel microRNAs that were differentially expressed according to the HER2 status across different tumor types.

Related: Breast Cancer Signal Transduction Stomach Cancer Gastric Cancer


Matsumoto H, Kubota H, Higashida M, et al.
Docetaxel/ TS-1 with radiation for unresectable squamous cell carcinoma of the esophagus--a phase II trial.
Anticancer Res. 2014; 34(7):3759-63 [PubMed] Related Publications
BACKGROUND: We tried a new regimen of docetaxel / TS-1 (tegafur-gimestat-otastat potassium) combined with radiation for squamous cell carcinoma of the esophagus in a phase II trial.
PATIENTS AND METHODS: The patients, whose tumor invaded other organs without other organ metastasis, were given TS-1 (60 mg/m2/day) from days 1 to 14, and docetaxel (20-30 mg/m2) on days 1 and 8. They received radiation in 2.0 Gy from days 1 to 21. Patients were given a seven-day rest after the first course, and then were treated with the same regimen from days 28 to 49.
RESULTS: Seventeen cases were enrolled in the study. The response rate was 76.4% (13/17). The overall 5-year survival rate was 29.6% (5/17) and median survival time was 15.2 months. Adverse events more than grade 3 occurred in 10 cases.
CONCLUSION: This combination therapy may be one of the most effective treatments because of its lower rate of non-hematological adverse events and higher response rate. Three cases also underwent salvage surgery when the tumor recurred, and in one case, chemoradiation to a metastatic nodule on the thoracic wall was added.

Related: Cancer of the Esophagus Esophageal Cancer Tegafur-uracil Docetaxel


Shibutani M, Maeda K, Nagahara H, et al.
Significance of CEA and CA19-9 combination as a prognostic indicator and for recurrence monitoring in patients with stage II colorectal cancer.
Anticancer Res. 2014; 34(7):3753-8 [PubMed] Related Publications
BACKGROUND: The purpose of this study was to evaluate the significance of the combination of the carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels as a prognostic indicator and for monitoring for recurrence and metastasis after potentially curative surgery for patients with stage II colorectal cancer.
PATIENTS AND METHODS: A total of 238 patients with stage II colorectal cancer who underwent potentially curative surgery were enrolled in the study. A high CEA level was defined as a level exceeding 5 ng/ml and a high CA19-9 level was defined as a level exceeding 37 U/ml.
RESULTS: Out of these 238 patients, 92 (38.7%) patients had high CEA levels, 23 (9.7%) patients had high CA19-9 levels and 15 (6.3%) patients had both high CEA and CA19-9 levels. The disease-free and overall survival rates were significantly worse in patients with both a high CEA level and high CA19-9 level. Tumor marker(s) elevated before the operation tended to be elevated again at the time of relapse.
CONCLUSION: The combination of preoperative CEA and CA19-9 levels was useful for predicting the prognosis and for monitoring recurrence and metastasis after potentially curative surgery in patents with stage II colorectal cancer.

Related: Colorectal (Bowel) Cancer


Kuo HY, Yeh KH
Molecular-targeted therapy for chemotherapy-refractory gastric cancer: a case report and literature review.
Anticancer Res. 2014; 34(7):3695-9 [PubMed] Related Publications
The prognosis of advanced gastric cancer (AGC) remains poor despite therapeutic advances in recent decades. Several recent positive phase III trials established the efficacy of second-line chemotherapy for metastatic gastric cancer in prolonging overall survival. However, malnutrition and poor performance of AGC in late stages usually preclude such patients from intensive treatment. Many targeted-therapies failed to show a significant survival benefit in AGC, but have regained attention after the positive result of ramucirumab was announced last year. Among all targeted agents, only trastuzumab, a monoclonal antibody against Human epidermal growth factor receptor-2 (HER2) protein, has been proven as having survival benefit by addition to first-line chemotherapy. Herein we reported a patient who benefited from adding trastuzumab to the same second-line combination chemotherapy (paclitaxel, 5-fluorouracil, and leucovorin) upon progression of bulky liver metastases. At least five months of progression-free survival were achieved without any additional toxicity. We also reviewed literature of molecularly-targeted therapy for chemotherapy-refractory gastric cancer, including several large phase III trials (REGARD, GRANITE-1, EXPAND, and REAL-3) published in 2013-2014.

Related: Stomach Cancer Gastric Cancer Trastuzumab (Herceptin)


Farkouh A, Scheithauer W, Buchner P, et al.
Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab.
Anticancer Res. 2014; 34(7):3669-73 [PubMed] Related Publications
AIM: Capecitabine, designed as a pro-drug to the cytotoxic agent 5-fluorouracil, is widely used in the management of colorectal cancer. This study was designed to investigate whether co-administration of the monoclonal antibody bevacizumab (BVZ) shows potential to modulate the plasma disposition of capecitabine (CCB) and its metabolites.
PATIENTS AND METHODS: Nine patients treated with CCB and BVZ for advanced colorectal cancer entered this pharmacokinetic study. In the first cycle CCB was given alone at doses of 1,250 mg/m2 bi-daily for two weeks with one week rest. In the second cycle BVZ co-administration started simultaneously with oral intake of CCB by short infusion of 7.5 mg/kg.
RESULTS: Mean plasma concentration time curves of CCB and its metabolites were insignificantly lower in the BVZ combination regimen compared to CCB monotherapy. After repeated cycles of BVZ no significant pharmacokinetic interaction was observed.
CONCLUSION: From the pharmacokinetic point of view and in agreement with numerous clinical study data, co-administration of BVZ with CCB appears to be safe and efficient.

Related: Colorectal (Bowel) Cancer Fluorouracil Bevacizumab (Avastin) Capecitabine


Walker EJ, Simko JP, Ko AH
Hepatitis B viral reactivation secondary to imatinib treatment in a patient with gastrointestinal stromal tumor.
Anticancer Res. 2014; 34(7):3629-34 [PubMed] Related Publications
Hepatitis B virus (HBV) reactivation is a known risk in cancer patients receiving cytotoxic or immunosuppressive therapy; however, the risk associated with newer molecularly-targeted agents has not been well-quantified. Imatinib, a small molecule inhibitor directed against BCR-ABL, CKIT, and other tyrosine kinases, has been associated with HBV reactivation primarily in patients treated for chronic myelogenous leukemia. Herein we present the first reported case of a patient who developed HBV reactivation while receiving imatinib therapy for a gastrointestinal stromal tumor (GIST) in the adjuvant setting. This eventually resulted in fulminant liver failure and was effectively treated with living-related donor liver transplant and anti-viral medication. Currently, no guidelines exist for HBV screening prior to imatinib therapy. This report emphasizes the need for such guidelines and supports the idea that viral reactivation is a risk in all imatinib-treated patients, regardless of the underlying disease.

Related: Gastrointestinal Stromal Tumors Imatinib (Glivec)


Sohda M, Sakai M, Honjyo H, et al.
Use of pre-treatment 18F-FAMT PET to predict patient survival in squamous cell carcinoma of the esophagus treated by curative surgery.
Anticancer Res. 2014; 34(7):3623-8 [PubMed] Related Publications
BACKGROUND: [18F]-3-fluoro-alpha-methyl tyrosine (18F-FAMT) as an amino acid tracer in positron emission tomography (PET) has been widely investigated in several tumor types. Herein we investigated the clinical significance of 18F-FAMT PET uptake as a prognostic marker together in our updated data of patients with esophageal cancer.
PATIENTS AND METHODS: We retrospectively assessed the treatment outcomes of 42 patients with histologically-confirmed esophageal cancer. The survival rate was analyzed using the median peak standardized uptake value (SUV) with 2.2 as the cut-off value.
RESULTS: FAMT uptakes were significantly correlated with factors reflecting tumor progression. Moreover, a significant correlation was observed between FAMT uptake and disease-free survival (p=0.023). Moreover, on evaluation of individual lymph node groups, the specificity and positive predictive value were significantly higher for 18F-FAMT-PET than for 18F-FDG-PET and computed tomography (CT).
CONCLUSION: 18F-FAMT is an important pre-treatment diagnostic modality and its accumulation is a good predictor of disease-free survival (DFS) in patients with operable esophageal cancer.

Related: Cancer of the Esophagus Esophageal Cancer


Gonzalez-Hormazabal P, Musleh M, Bustamante M, et al.
Role of cytokine gene polymorphisms in gastric cancer risk in Chile.
Anticancer Res. 2014; 34(7):3523-30 [PubMed] Related Publications
AIM: To assess the role of pro- and anti-inflammatory polymorphisms in gastric cancer susceptibility.
PATIENTS AND METHODS: We genotyped 12 polymorphisms in eight cytokine genes (Interleukin-1β -IL1B-, IL8, IL17A, IL17F, IL32, tumor necrosis factor-α -TNF-, IL1RN, IL10) in a case-control study of 147 patients with gastric cancer and 172 controls.
RESULTS: Single polymorphism analysis revealed an association between the IL10 -592C>A single nucleotide polymorphism and cases with moderately- or well-differentiated tumors [AA vs. GG, odds ratio (OR)=3.01; 95% confidence interval (CI)=1.08-8.50]. We further analyzed gene-gene interactions using a combined attribute network implemented in multifactor dimensionality reduction software. The analysis revealed an interaction between IL8 -251A>T and IL32 rs28372698 SNPs among cases with moderately- or well-differentiated tumors. Homozygosity for both IL8 -251T and IL32 T alleles increases the odds for developing gastric cancer up to 2.63-fold (OR=2.63; 95% CI=1.15-6.03). This association was higher compared to the homozygosity for the IL8-251 T allele alone (OR=1.11; 95% CI=0.51-2.43) or the IL32 T allele alone (OR=1.21; 95% CI=0.54-2.72).
CONCLUSION: These findings suggest that IL10 -592C>A increases the odds for developing gastric cancer. An interaction between IL8 -251A>T and IL32 rs28372698 SNPs is also proposed.

Related: Cytokines Stomach Cancer Gastric Cancer TNF


Kim YW, Kim SK, Kim CS, et al.
Association of serum and intratumoral cytokine profiles with tumor stage and neutrophil lymphocyte ratio in colorectal cancer.
Anticancer Res. 2014; 34(7):3481-7 [PubMed] Related Publications
BACKGROUND: We examined cytokine profiles and evaluated the association between cytokine levels, pathological stages, and neutrophil/lymphocyte ratio (NLR).
MATERIALS AND METHODS: Patients with colorectal cancer (n=20, TNM stage I, II, and III) were enrolled. Levels of nine cytokines [interleukin (IL)-4,-6, -8, -10, -12, tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-γ), and vascular endothelial growth factor (VEGF)] were measured in serum, normal mucosa, and tumor using the Bio-Plex® cytokine assay.
RESULTS: The mean IL8, GM-CSF and VEGF levels were higher in tumors, whereas the mean IL6 level was higher in serum. Cytokine levels correlated with TNM stage (IL6 and IL8 in serum, and IL8 and VEGF in tumor) and with NLR (IL6 and IL8 in serum, and IL8 in tumor).
CONCLUSION: Different cytokine profiles were observed in serum, normal mucosa, and tumor tissue. The elevation of specific cytokines in sera or tumors reflects features of advanced disease.

Related: Colorectal (Bowel) Cancer Cytokines


Taban O, Cimpean AM, Raica M, Olariu S
PROX1 expression in gastric cancer: from hypothesis to evidence.
Anticancer Res. 2014; 34(7):3439-46 [PubMed] Related Publications
BACKGROUND: PROX1 is involved in cancer development and progression as both a tumor suppressor and oncogene. Immunohistochemical (IHC) PROX1 nuclear expression is a widely accepted pattern. Scattered data reported PROX1 IHC cytoplasmic expression in different tumors, including gastric cancer but it is not clear if this holds true.
MATERIALS AND METHODS: Evaluation of the cytoplasmic expression of PROX1 in normal gastric mucosa and gastric cancer was performed by IHC followed by RNAscope, an in situ hybridization-based method for detecting PROX1 mRNA amplification on paraffin-embedded samples and to evaluate its clinical impact.
RESULTS: Twenty five out of 48 cases of gastric cancer showed PROX1 nuclear and cytoplasmic immunohistochemical expression. Twelve out of these 20 cases positive for PROX1 on IHC (54.5%) had PROX1 mRNA gene amplification. The overlapping of PROX1 cytoplasmic expression assessed by immunohistochemistry and cytoplasmic RNAscope amplification was statistically significant (p=0.031). PROX1 mRNA gene amplification correlated with tumor grade (p=0.05) and regional lymph node metastasis as well (p=0.033). No significant correlation was obtained between PROX1 and histopathology, tumor size or distal metastasis.
CONCLUSION: A significant correlation was found between IHC and RNAscope PROX1 expression in the cytoplasm of normal and gastric cancer cells. This strongly supports its validation as a true expression on immunohistochemistry. A strong correlation between PROX1 mRNA amplification and regional lymph node metastasis supports its implications in cancer spreading and metastasis and sustains its utility, not only as a lymphatic marker, but also as a potential tumor marker in various tumor types, including gastric cancer.

Related: Stomach Cancer Gastric Cancer


Sakurai T, Okumura H, Matsumoto M, et al.
Endoglin (CD105) is a useful marker for evaluating microvessel density and predicting prognosis in esophageal squamous cell carcinoma.
Anticancer Res. 2014; 34(7):3431-8 [PubMed] Related Publications
BACKGROUND: Angiogenic molecular markers such as vascular endothelial growth factor and tumor microvessel density reflect prognosis of human cancers. The present study clarified the usefulness of endothelial marker endoglin (CD 105) by assessing microvessel density in esophageal squamous cell carcinoma (ESCC).
MATERIALS AND METHODS: We immunohistochemically investigated CD105, CD31, and vascular endothelial growth factor-A VEGF-A expression in primary esophageal squamous cell carcinoma specimens from 142 patients.
RESULTS: Microvessel density was 35.9±21.2 for CD105 and 46.3±25.4 for CD31. CD105 microvessel density was significantly associated with tumor length, tumor invasion depth, lymph node metastasis, stage, lymphatic invasion, venous invasion, and VEGF-A expression; its correlation with almost all clinicopathological parameters was stronger than CD31 microvessel density. And significantly better prognosis was achieved in patients with low, compared to high CD105, microvessel density.
CONCLUSION: CD105 microvessel density reflected the degree of angiogenesis and prognosis in patients with esophageal squamous cell carcinoma.

Related: Cancer of the Esophagus Esophageal Cancer Angiogenesis and Cancer VEGFA


Kawamura M, Tanaka K, Toiyama Y, et al.
Clinical significance of tartrate-resistant acid phosphatase type-5 expression in human gastric cancer.
Anticancer Res. 2014; 34(7):3425-9 [PubMed] Related Publications
AIM: The present study investigated the clinical significance of tartrate-resistant acid phosphatase type-5 (ACP5) expression in gastric cancer.
MATERIALS AND METHODS: In 150 specimens of gastric cancer and adjacent normal mucosa, expression of ACP5 protein and mRNA and was determined by immunohistochemical staining and quantitative real-time polymerase chain reaction, respectively.
RESULTS: Expression of ACP5 mRNA was significantly higher in cancer tissues than in adjacent normal mucosa. Elevated ACP5 mRNA was associated with lymph node metastasis and peritoneal dissemination. Logistic regression analysis revealed that elevated ACP5 expression was an independent risk factor for peritoneal dissemination and was associated with shorter survival. Immunohistochemical staining of primary carcinomas showed ACP5 to be expressed mainly in the cytoplasm.
CONCLUSION: ACP5 is predictive of peritoneal dissemination in patients with gastric cancer, and might play a crucial role in the establishment of peritoneal dissemination.

Related: Stomach Cancer Gastric Cancer


Schreiber V, Kitzmueller M, Poxhofer M, et al.
Impact of co-administered drugs on drug monitoring of capecitabine in patients with advanced colorectal cancer.
Anticancer Res. 2014; 34(7):3371-6 [PubMed] Related Publications
BACKGROUND: Drug monitoring is a useful tool for obtaining detailed information about the disposition of a drug in an individual patient during chemotherapy. According to the international guidelines, the analytical assay for quantification of a compound in biological samples must be validated. Among a number of parameters, peak purity is an important requirement.
MATERIALS AND METHODS: We analyzed pharmacokinetics in patients who received chemotherapy with capecitabine and up to 10 various co-medications.
RESULTS: Out of seven investigated co-administered drugs, we found evidence that the proton pump inhibitor pantoprazole causes peak interferences with capecitabine during high-performance liquid chromatography analysis. Therefore quantification of capecitabine in plasma samples can be inaccurate.
CONCLUSION: We recommend an altered time schedule for co-administered drugs or changing the mobile phase used in the assay.

Related: Colorectal (Bowel) Cancer Fluorouracil Capecitabine


Lee WY, Hong HK, Ham SK, et al.
Comparison of colorectal cancer in differentially established liver metastasis models.
Anticancer Res. 2014; 34(7):3321-8 [PubMed] Related Publications
BACKGROUND: Metastasis is one of the main reasons for colorectal cancer (CRC)-related deaths due to the lack of effective therapeutics mainly for liver metastasis. In the present study, we established an orthotopic colorectal cancer mouse model using different transplantation protocols to determine the optimal conditions for CRC liver metastasis.
MATERIALS AND METHODS: Luciferin-expressing HCT116 cells were used to induce liver metastasis models of colorectal cancer following both intra-splenic and cecal injections. Magnetic resonance imaging (MRI) and the In Vivo Imaging system were used to monitor internal growth of the primary tumor and metastasis.
RESULTS: The intra-splenic injection with high cell number (5×10(6) cells/50 μL)-group achieved rapid tumor formation, and the highest metastatic rate. However, survival rates were shorter than those of the other groups. The time to develop primary tumors and liver metastases was slightly different between the two transplantation protocols followed and should be considered depending on the specific aim of each experiment. MRI and optical images correlated well with the pathological findings at necropsy with respect to both tumor growth and location.
CONCLUSION: The model described herein will be effective in studying new therapeutic strategies against metastatic disease when used in conjunction with small animal MRI and optical imaging.

Related: Colorectal (Bowel) Cancer


Berlth F, Mönig SP, Schlösser HA, et al.
Validation of 2-mm tissue microarray technology in gastric cancer. Agreement of 2-mm TMAs and full sections for Glut-1 and Hif-1 alpha.
Anticancer Res. 2014; 34(7):3313-20 [PubMed] Related Publications
BACKGROUND/AIM: Tissue Microarray (TMA) is a widely used method to perform high-throughput immunohistochemical analyses on different tissues by arraying small sample cores from paraffin-fixed tissues into a single paraffin block. TMA-technology has been validated on numerous cancer tissues and also for gastric cancer studies, although it has not been validated for this tumor tissue so far. The objective of this study was to assess, whether the 2-mm TMA-technology is able to provide representative samples of gastric cancer tissue.
MATERIALS AND METHODS: TMA paraffin blocks were constructed by means of 220 formalin-fixed and paraffin-embedded gastric cancer samples with a sample diameter of 2 mm. The agreement of immunohistochemical stainings of Glut-1 and Hif-1 alpha in TMA sections and the original full sections was calculated using kappa statistics and direct adjustment.
RESULTS: The congruence was substantial for Glut-1 (kappa 0.64) and Hif-1 alpha (kappa 0.70), but with an agreement of only 71% and 52% within the marker-positive cases of the full-section slides.
CONCLUSION: Due to tumor heterogeneity primarily, the TMA technology with a 2-mm sample core shows relevant limitations in gastric cancer tissue. Although being helpful for tissue screening purposes, the 2-mm TMA technology cannot be recommended as a method equal to full-section investigations in gastric cancer.

Related: SLC2A1 HIF1A Stomach Cancer Gastric Cancer


Weeks JC, Uno H, Taback N, et al.
Interinstitutional variation in management decisions for treatment of 4 common types of cancer: A multi-institutional cohort study.
Ann Intern Med. 2014; 161(1):20-30 [PubMed] Related Publications
BACKGROUND: When clinical practice is governed by evidence-based guidelines and there is consensus about their validity, practice variation should be minimal. For areas in which evidence gaps exist, greater variation is expected.
OBJECTIVE: To systematically assess interinstitutional variation in management decisions for 4 common types of cancer.
DESIGN: Multi-institutional, observational cohort study of patients with cancer diagnosed between July 2006 through May 2011 and observed through 31 December 2011.
SETTING: 18 cancer centers participating in the formulation of treatment guidelines and systematic outcomes assessment through the National Comprehensive Cancer Network.
PATIENTS: 25 589 patients with incident breast cancer, colorectal cancer, lung cancer, or non-Hodgkin lymphoma.
MEASUREMENTS: Interinstitutional variation for 171 binary management decisions with varying levels of supporting evidence. For each decision, variation was characterized by the median absolute deviation of the center-specific proportions.
RESULTS: Interinstitutional variation was high (median absolute deviation >10%) for 35 of 171 (20%) oncology management decisions, including 9 of 22 (41%) decisions for non-Hodgkin lymphoma, 16 of 76 (21%) for breast cancer, 7 of 47 (15%) for lung cancer, and 3 of 26 (12%) for colorectal cancer. Forty-six percent of high-variance decisions involved imaging or diagnostic procedures and 37% involved choice of chemotherapy regimen. The evidence grade underpinning the 35 high-variance decisions was category 1 for 0%, 2A for 49%, and 2B/other for 51%.
LIMITATION: Physician identifiers were unavailable, and results may not generalize outside of major cancer centers.
CONCLUSION: The substantial variation in institutional practice manifest among cancer centers reveals a lack of consensus about optimal management for common clinical scenarios. For clinicians, awareness of management decisions with high variation should prompt attention to patient preferences. For health systems, high variation can be used to prioritize comparative effectiveness research, patient-provider education, or pathway development.
PRIMARY FUNDING SOURCE: National Cancer Institute and National Comprehensive Cancer Network.

Related: Breast Cancer Colorectal (Bowel) Cancer Lung Cancer Non Hodgkin's Lymphoma


Sparks D, Bhalla A, Dodge J, Saldinger P
Isolated gastric amyloidoma in the setting of marginal zone MALT lymphoma: case report and review of the literature.
Conn Med. 2014; 78(5):277-80 [PubMed] Related Publications
A 52-year-old female presented with hematochezia. A computed topography (CT) scan revealed diffuse proximal gastric thickening with enlarged perigastric lymph nodes. The esophagogastroduodenoscopy (EGD) revealed a diffusely thickened gastric wall with hemorrhagic, friable mucosa, and multiple areas of ulceration. The biopsies showed diffuse amyloid deposition along with transmural proliferation of small- to medium-sized lymphocytes and plasma cells. The gastric mucosa showed lymphoepithelial lesions and chronic inactive gastritis. Immunohistochemical staining of the neoplastic lymphocytes revealed expression of CD20, bcl-2, bcl-10, Ki-67 proliferative index of 5%, and lambda light chain restriction. There was no expression of CD5, CD43, CD10, CD3, cyclin D1, and bcl-6. Immunophenotyping by flow cytometry revealed an abnormal B lymphocyte population with expression of CD45, CD19, CD20, and FMC7. The histomorphological, immunohistochemical and flow cytometric features were consistent with primary gastric amyloidosis associated with extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma).

Related: MALT Lymphoma Stomach Cancer Gastric Cancer


Noreen F, Röösli M, Gaj P, et al.
Modulation of age- and cancer-associated DNA methylation change in the healthy colon by aspirin and lifestyle.
J Natl Cancer Inst. 2014; 106(7) [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Aberrant DNA methylation in gene promoters is associated with aging and cancer, but the circumstances determining methylation change are unknown. We investigated the impact of lifestyle modulators of colorectal cancer (CRC) risk on the stability of gene promoter methylation in the colonic mucosa.
METHODS: We measured genome-wide promoter CpG methylation in normal colon biopsies (n = 1092) from a female screening cohort, investigated the interaction of lifestyle factors with age-dependent increase in methylation with log-linear multivariable regression, and related their modifying effect to hypermethylation in CRC. All statistical tests were two-sided.
RESULTS: Of 20025 promoter-associated CpGs analyzed, 1713 showed statistically significant age-dependent methylation gains. Fewer CpGs acquired methylation in users of aspirin (≥ 2 years) and hormonal replacement therapy (HRT age ≥ 50 years) compared with nonusers (43 vs 1355; 1 vs1377, respectively), whereas more CpGs were affected in smokers (≥ 20 years) and individuals with a body mass index (BMI) of 25 kg/m(2) and greater compared with control groups (180 vs 39; 554 vs 144, respectively). Fifty percent of the CpGs showing age-dependent methylation were found hypermethylated in CRC (odds ratio [OR] = 20; 95% confidence interval [CI] = 18 to 23; P < 2 × 10(-16)). These loci gained methylation with a higher median rate compared with age-only methylated sites (P = 2 × 10(-76)) and were enriched for polycomb regions (OR = 3.67). Importantly, aspirin (P < .001) and HRT use (P < .001) reduced the methylation rate at these cancer-related genes, whereas smoking (P < .001) and high BMI (P = .004) increased it.
CONCLUSIONS: Lifestyle, including aspirin use, modulates age-associated DNA methylation change in the colonic epithelium and thereby impacts the evolution of cancer methylomes.

Related: Colorectal (Bowel) Cancer Screening for Colorectal (Bowel) Cancer Cancer Screening and Early Detection


Apisarnthanarak P, Pansri C, Maungsomboon K, Thamtorawat S
The CT appearances for differentiating of peripheral, mass-forming cholangiocarcinoma and liver meatastases from colorectal adenocarcinoma.
J Med Assoc Thai. 2014; 97(4):415-22 [PubMed] Related Publications
OBJECTIVE: To evaluate the computed tomographic (CT) appearances for differentiating of primary hepatic adenocarcinoma (peripheral, mass-forming cholangiocarcinoma) and secondary hepatic adenocarcinoma (liver metastases from colorectal carcinoma).
MATERIAL AND METHOD: Between January 2004 and December 2010, 45 patients with peripheral, mass-forming cholangiocarcinoma (Group 1) and 45 patients with liver metastases from colorectal adenocarcinoma (Group 2) who underwent abdominal CT scan at the authors' institution were included in the present retrospective study. Two experienced, abdominal radiologists blinded to the participants 'clinical histories and pathological results, separately reviewed the CT findings of each participant (number of liver mass(es), size, margin, internal calcification, hepatic capsule retraction, vascular invasion, peripheral bile duct dilatation, proximal bile duct enhancement, extrahepatic spreading, nearby lymphadenopathy and nearby organ invasion) and gave the presumed diagnosis of each individual case. Any discrepancies were solved by a consensus review. Finally, the authors conducted a stratified analysis of the patients in both groups based on their CT appearances.
RESULTS: Ninety participants were 35 (38.9%) female, 55 (61.1%) male, age range from 43 to 88 years (mean 63.4 years, SD = 10.7). There were 28.9% vs. 48.9% female with the mean age (SD) of 61.5 (9.4) vs. 65.4 (11.6) years in Group 1 and 2, respectively. The mean size (SD) were 7.4 (3.7) cm vs. 4.0 (2.1) cm, in Group 1 and 2, respectively (p < 0.001). The presence of hepatic capsule retraction, vascular invasion, peripheral bile duct dilatation, proximal bile duct enhancement, extrahepatic spreading, nearby lymphadenopathy, and nearby organ invasion were significantly higher in Group 1 than Group 2 (p < 0.001). In contrary, the presence of multiple lesions with separated locations, and smooth margin were significantly suggested of Group 2 (p < 0.001 and p = 0.007, respectively). By logistic regression analysis, peripheral bile duct dilatation, extrahepatic spreading, and proximal bile duct enhancement were the sole predictors of peripheral, mass-forming cholangiocarcinoma. The interobserver agreement for the presumed diagnosis of liver mass was good (kappa = 0.76).
CONCLUSION: The presence of peripheral bile duct dilatation, extrahepatic spreading, and proximal bile duct enhancement were highly suggestive of peripheral, mass-forming cholangiocarcinoma.

Related: Colorectal (Bowel) Cancer


Cotto M, Rosado-Orozco KE, Rizek R, et al.
Clinical and pathological features of colorectal cancer in patients at a community hospital in Puerto Rico.
P R Health Sci J. 2014; 33(2):65-70 [PubMed] Related Publications
OBJECTIVE: Colorectal cancer (CRC) is among the most common cancers in Puerto Rico. Few studies have correlated clinical and pathological variables with the overall survival of CRC patients in Puerto Rico. We report the clinical and pathological characteristics of patients who underwent surgical resection at a community hospital in Puerto Rico.
METHODS: Demographic and pathological variables of patients who underwent CRC surgery at Hospital del Maestro from 2006 through 2011 were reviewed. Descriptive statistics (mean, range, and frequency) and the Cox proportional hazards model were used to determine the influence of demographic and pathological variables on survival, after adjusting for age.
RESULTS: Two hundred and five CRC pathology reports were reviewed. Adenocarcinoma represented the most common pathology (202/205; 98.5%). Females represented 52% of the population (106/202) while males represented 48% (96/202). The median age was 71 years (30-96). The right colon was the most common site of presentation (49.7%; 100/201). Stage III was the most common stage at presentation. The presence of mucin, perineural or lymphatic invasion and tumor size were not related to decreased survival. Being male, having a higher stage at diagnosis, and having a moderately or poorly differentiated tumor were characteristics related to decreased survival.
CONCLUSION: This study provides information on clinical and pathological variables and their influence on the overall survival of CRC patients at a community hospital in Puerto Rico. Further research must be performed to identify potential disparities and their influence on the prognosis of this patients.

Related: Colorectal (Bowel) Cancer


Sclafani F, Gonzalez D, Cunningham D, et al.
TP53 mutational status and cetuximab benefit in rectal cancer: 5-year results of the EXPERT-C trial.
J Natl Cancer Inst. 2014; 106(7) [PubMed] Related Publications
In this updated analysis of the EXPERT-C trial we show that, in magnetic resonance imaging-defined, high-risk, locally advanced rectal cancer, adding cetuximab to a treatment strategy with neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX is not associated with a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) in both KRAS/BRAF wild-type and unselected patients. In a retrospective biomarker analysis, TP53 was not prognostic but emerged as an independent predictive biomarker for cetuximab benefit. After a median follow-up of 65.0 months, TP53 wild-type patients (n = 69) who received cetuximab had a statistically significant better PFS (89.3% vs 65.0% at 5 years; hazard ratio [HR] = 0.23; 95% confidence interval [CI] = 0.07 to 0.78; two-sided P = .02 by Cox regression) and OS (92.7% vs 67.5% at 5 years; HR = 0.16; 95% CI = 0.04 to 0.70; two-sided P = .02 by Cox regression) than TP53 wild-type patients who were treated in the control arm. An interaction between TP53 status and cetuximab effect was found (P < .05) and remained statistically significant after adjusting for statistically significant prognostic factors and KRAS.

Related: TP53 Cetuximab (Erbitux)


Rotimi O, Abdulkareem FB
Fifty-three years of reporting colorectal cancer in Nigerians--a systematic review of the published literature.
Niger Postgrad Med J. 2014; 21(1):68-73 [PubMed] Related Publications
AIMS AND OBJECTIVES: This study aimed to perform a systematic review of all the available published data on CRC in Nigerians over a period of 53 years as a proximate indication of the burden of the disease.
MATERIALS & METHODS: The data were sourced from PubMed, MEDLINE, EMBASE and Google Scholar search engines as well as direct contact with some authors. All published studies on histologically confirmed CRC in Nigerians constitute the materials. Selected papers were independently reviewed by the authors.
RESULTS: Of 35 papers found, 19 met the criteria and a total of 2497 cases reported in these 19 publications constituted the materials utilised for the review. There is increasing incidence as evident by increase in annual frequency increased from 18.2/annum in the early years (1954-1969) to 86.8/annum in the latter years (1991-2007). The average age incidence was 46 years (peak=41-50 age group); 674 (32%) of all the cases were aged below 40 years. The male to female ratio was 1.3:1. Of the 2238 cases in which site was reported, rectum 1349 (60%) was the commonest site followed by caecum 260 (17%). All the cases were adenocarcinomas and 1043 (56%) were well differentiated. Mucinous carcinoma and signet ring type accounted for 309 (17%) and 32 (2%) respectively. Of 1061 cases in which Duke's staging was reported, 622 (59%) presented in stage B disease followed by stage C 266 (25%).
CONCLUSIONS: The incidence is of CRC is increasing in Nigeria. The mean age is low and incidence appears to be increasing in younger patients.


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