Gastrointestinal System Cancers
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Digestive and Gastrointestinal System cancers.

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General Resources for GI Cancer
Latest Research Publications

General Resources for GI Cancer (9 links)

Latest Research Publications

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

Jin X, Zhu Z, Shi Y
Metastasis mechanism and gene/protein expression in gastric cancer with distant organs metastasis.
Bull Cancer. 2014; 101(1):E1-12 [PubMed] Related Publications
Metastasis is the most fatal characteristics of malignancy tumor, which accounted for more than 90% of tumor-related mortality. Distant organ or tissue metastasis is a sign of poor prognosis in patients with gastric cancer. Tumor cells metastasis is a very complex process including tumor cell transformation, growth, angiogenesis, invasion, dissemination and survival in the circulation, and subsequent adhesion and colonization the secondary organ or tissue. The origin of tumor cell, genetic variation, the circulatory mode and the physiological structure of the metastatic organ determines the specific sites of distant metastasis. In theory, the metastatic lesion is originated from their primary tumor, so they should have the same molecular profile with the primary tumor. But this view has been confirmed to be wrong in various tumors, including gastric cancer. The gene expression of primary gastric cancer and its metastasis have differences, which may contribute to the early diagnosis and individualized treatment of metastasis. However, the heterogeneity of tumor cells is still unclear in different metastasis lesion of gastric cancer, which will be a major focus of future research. In this review, we discuss the basic principles of cancer metastasis, the unique physiological characteristics of the various metastasis organs and the expression of different functions of gene/protein in primary and metastasis of gastric cancer. In addition, we also discuss the diagnosis, prognosis and treatment in various organ metastasis of gastric cancer.

Related: Angiogenesis and Cancer Stomach Cancer Gastric Cancer

Jurisić I, Paradzik MT, Jurić D, et al.
National program of colorectal carcinoma early detection in Brod-Posavina County (east Croatia).
Coll Antropol. 2013; 37(4):1223-7 [PubMed] Related Publications
Colorectal carcinoma (CRC) is a major public health problem as the third leading malignant tumor in men and fourth in women in Croatia. Prognosis and treatment greatly depend on tumor stage at the time of detection. Therefore, the National Program of Colorectal Carcinoma Early Detection has been performed since 2007. The aim is to present the response rate, colonoscopy findings and number of newly detected CRC cases in Brod-Posavina County. During five years of the National Program performance, 28 CRC cases were detected in Brod-Posavina County, with the 3.3% rate of carcinoma detection. The majority of CRC cases were found in the 50-64 age group. The response rate in the County was low (20.4%), corresponding to the national rate but far from the recommended one. Such a result could be attributed to the low level of awareness in the population at large, complex testing technique for general population, fear from disease detection and from colonoscopy as a diagnostic procedure. Note should be made of the underestimated role of family physicians; their involvement in the National Program should certainly result in better response rate in our County as well as at the national level.

Related: Colorectal (Bowel) Cancer Screening for Colorectal (Bowel) Cancer

Wikman A, Johar A, Lagergren P
Presence of symptom clusters in surgically treated patients with esophageal cancer: implications for survival.
Cancer. 2014; 120(2):286-93 [PubMed] Related Publications
BACKGROUND: It is not known whether symptoms cluster together after esophageal cancer surgery or whether such symptom clusters are associated with survival in patients with esophageal cancer who are treated surgically.
METHODS: Data from a prospective Swedish nationwide cohort study of surgically treated patients with esophageal cancer recruited between 2001 and 2005 were used. General and esophageal cancer-specific symptoms were assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 quality of life questionnaire and the QLQ-OES18 module at 6 months after surgery. Associations between symptom clusters and survival were analyzed using Cox proportional hazards models, providing hazards ratios with 95% confidence intervals, adjusted for other known prognostic factors.
RESULTS: Among 402 patients reporting symptoms 6 months after surgery, 3 symptom clusters were identified. The first symptom cluster (“fatigue/pain”) was characterized by symptoms of pain, fatigue, insomnia, and dyspnea and was present in 30% of patients. The second symptom cluster (“reflux/cough”) was characterized by symptoms of dry mouth, problems with taste, coughing, and reflux and was present in 27% of patients. The third symptom cluster (“eating difficulties”) was characterized by appetite loss, dysphagia, eating difficulties, and nausea/vomiting and was present in 28% of patients. The presence of the reflux/cough and eating difficulties symptom clusters was associated with a statistically significantly increased risk of mortality (adjusted hazards ratio, 1.43 [95% confidence interval, 1.08-1.89] and adjusted HR, 1.41 [95% confidence interval, 1.06-1.87], respectively).
CONCLUSIONS: Symptoms experienced by surgically treated patients with esophageal cancer appear to cluster together, and the presence of these symptom clusters appears to have strong prognostic value.

Related: Cancer of the Esophagus Esophageal Cancer

Gala MK, Mizukami Y, Le LP, et al.
Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas.
Gastroenterology. 2014; 146(2):520-9 [PubMed] Related Publications
BACKGROUND & AIMS: Little is known about the genetic factors that contribute to the development of sessile serrated adenomas (SSAs). SSAs contain somatic mutations in BRAF or KRAS early in development. However, evidence from humans and mouse models indicates that these mutations result in oncogene-induced senescence (OIS) of intestinal crypt cells. Progression to serrated neoplasia requires cells to escape OIS via inactivation of tumor suppressor pathways. We investigated whether subjects with multiple SSAs carry germline loss-of function mutations (nonsense and splice site) in genes that regulate OIS: the p16-Rb and ATM-ATR DNA damage response pathways.
METHODS: Through a bioinformatic analysis of the literature, we identified a set of genes that function at the main nodes of the p16-Rb and ATM-ATR DNA damage response pathways. We performed whole-exome sequencing of 20 unrelated subjects with multiple SSAs; most had features of serrated polyposis. We compared sequences with those from 4300 subjects matched for ethnicity (controls). We also used an integrative genomics approach to identify additional genes involved in senescence mechanisms.
RESULTS: We identified mutations in genes that regulate senescence (ATM, PIF1, TELO2,XAF1, and RBL1) in 5 of 20 subjects with multiple SSAs (odds ratio, 3.0; 95% confidence interval, 0.9–8.9; P =.04). In 2 subjects,we found nonsense mutations in RNF43, indicating that it is also associated with multiple serrated polyps (odds ratio, 460; 95% confidence interval, 23.1–16,384; P = 6.8 x 10(-5)). In knockdown experiments with pancreatic duct cells exposed to UV light, RNF43 appeared to function as a regulator of ATMATRDNA damage response.
CONCLUSIONS: We associated germline loss-of-function variants in genes that regulate senescence pathways with the development of multiple SSAs.We identified RNF43 as a regulator of the DNA damage response and associated nonsense variants in this gene with a high risk of developing SSAs.

Related: BRAF gene RBL1 retinoblastoma-like 1 (p107) KRAS gene

Collura A, Lagrange A, Svrcek M, et al.
Patients with colorectal tumors with microsatellite instability and large deletions in HSP110 T17 have improved response to 5-fluorouracil–based chemotherapy.
Gastroenterology. 2014; 146(2):401-11.e1 [PubMed] Related Publications
BACKGROUND & AIMS: Patients with colorectal tumors with microsatellite instability (MSI) have better prognoses than patients with tumors without MSI, but have a poor response to 5-fluorouracil–based chemotherapy. A dominant-negative form of heat shock protein (HSP)110 (HSP110DE9) expressed by cancer cells with MSI, via exon skipping caused by somatic deletions in the T(17) intron repeat, sensitizes the cells to 5-fluorouracil and oxaliplatin.We investigated whether HSP110 T(17) could be used to identify patients with colorectal cancer who would benefit from adjuvant chemotherapy with 5-fluorouracil and oxaliplatin.
METHODS: We characterized the interaction between HSP110 and HSP110DE9 using surface plasmon resonance. By using polymerase chain reaction and fragment analysis, we examined how the size of somatic allelic deletions in HSP110 T(17) affected the HSP110 protein expressed by tumor cells. We screened 329 consecutive patients with stage II–III colorectal tumors with MSI who underwent surgical resection at tertiary medical centers for HSP110 T(17).
RESULTS: HSP110 and HSP110DE9 interacted in a1:1 ratio. Tumor cells with large deletions in T(17) had increased ratios of HSP110DE9:HSP110, owing to the loss of expression of full-length HSP110. Deletions in HSP110 T(17) were mostly biallelic in primary tumor samples with MSI. Patients with stage II–III cancer who received chemotherapy and had large HSP110 T(17) deletions (≥5 bp; 18 of 77 patients, 23.4%) had longer times of relapse-free survival than patients with small or no deletions (≤4 bp; 59 of 77 patients, 76.6%) in multivariate analysis (hazard ratio, 0.16; 95% confidence interval, 0.012–0.8; P = .03). We found a significant interaction between chemotherapy and T17 deletion (P =.009).
CONCLUSIONS: About 25% of patients with stages II–III colorectal tumors with MSI have an excellent response to chemotherapy, due to large, biallelic deletions in the T(17) intron repeat of HSP110 in tumor DNA.

Related: Colorectal (Bowel) Cancer Fluorouracil Leucovorin Oxaliplatin

Abrams TA, Meyer G, Schrag D, et al.
Chemotherapy usage patterns in a US-wide cohort of patients with metastatic colorectal cancer.
J Natl Cancer Inst. 2014; 106(2):djt371 [PubMed] Related Publications
BACKGROUND: Since the introduction of biologic therapies for the treatment of metastatic colorectal cancer (mCRC), few studies have examined patterns of care or predictors of specific treatment approaches.
METHODS: We assessed 4877 mCRC patients who received chemotherapy between January 2004 and March 2011 at academic, private, and community-based oncology practices subscribing to a US-wide chemotherapy order entry (system capturing disease, patient, provider, and treatment data. Multivariable analyses of these prospectively recorded characteristics were used to identify independent predictors of specific therapeutic choices. All statistical tests were two-sided.
RESULTS: Throughout the study period, fluoropyrimidine/oxaliplatin combination was the most commonly used first-line chemotherapy regimen, representing 71% of first-line therapy by 2007. First-line bevacizumab use averaged 51%, peaking at 55% in 2006. Of those who received first-line bevacizumab, 34% continued to receive bevacizumab in the second-line. Only 26% of patients in our cohort ever received an anti-EGFR monoclonal antibody (cetuximab = 22%; panitumumab = 6%) at some point in their treatment course. Patients treated at academic centers, with longer duration of first-line therapy, and at sites in the western United States were statistically more likely to receive an anti-EGFR antibody. Anti-EGFR antibody use fell by 18% after the US Food and Drug Administration limited its use to patients with KRAS wild-type tumors in June 2009.
CONCLUSIONS: Analysis of this US-wide mCRC cohort demonstrates that bevacizumab has been more consistently integrated into treatment regimens than anti-EGFR antibody therapies, particularly in first-line therapy. However, treatment choices vary substantially according to specific patient, practice, and provider characteristics.

Related: Monoclonal Antibodies Colorectal (Bowel) Cancer Fluorouracil USA KRAS gene Panitumumab (Vectibix) Bevacizumab (Avastin) Oxaliplatin Irinotecan EGFR Cetuximab (Erbitux)

Terazawa T, Nishitani H, Kato K, et al.
The feasibility of a short bevacizumab infusion in patients with metastatic colorectal cancer.
Anticancer Res. 2014; 34(2):1053-6 [PubMed] Related Publications
BACKGROUND: Typically, bevacizumab is initially infused for 90 min, then for 60 min, and subsequently for 30 min. The objective of the present study was to evaluate the safety profile of a short infusion of bevacizumab in Japanese colorectal cancer patients.
PATIENTS AND METHODS: The records of 58 patients who received bevacizumab (5 mg/kg) from June 2010 to September 2010 were reviewed. Bevacizumab was administered for 30 min at the first time. If patients had no infusion reaction, the infusion time was shortened to 10 min.
RESULTS: None of the 58 patients who received bevacizumab experienced an infusion reaction (95% confidence interval 0-6.2). The only serious adverse event related to bevacizumab infusion was grade 3 proteinuria in 2 patients.
CONCLUSION: Short infusion of bevacizumab for 30 min the first time and 10 min is safe and feasible.

Related: Angiogenesis Inhibitors Colorectal (Bowel) Cancer Fluorouracil Leucovorin Bevacizumab (Avastin)

Batsaikhan BE, Kurita N, Iwata T, et al.
The role of activation-induced cytidine deaminase expression in gastric adenocarcinoma.
Anticancer Res. 2014; 34(2):995-1000 [PubMed] Related Publications
BACKGROUND: Gastric adenocarcinoma is one of the most common malignant tumors and the leading cause of malignancy-related death worldwide. Studies have reported overexpression of activation-induced cytidine deaminase (AID) and protein kinase c iota (PKCi) proteins showing involvement in the regulation of carcinogenesis. In the present study, we investigated the expression of AID and PKCi in patients with gastric adenocarcinoma and determined the correlation between these proteins.
MATERIALS AND METHODS: This study was conducted between September 2009 and September 2010 on a total of 59 patients with gastric adenocarcinoma at the Tokushima University Hospital. AID, PKCi and mutated p53 protein expressions were evaluated by immunohistochemistry in gastric adenocarcinoma.
RESULTS: High AID and PKCi expression was significantly (p<0.05) associated with poorly-differentiated gastric adenocarcinoma. In addition, PKCi expression was significantly correlated with clinicopathological findings such as a lymph node metastasis, and venous and lymphatic invasion (p<0.05). Furthermore, AID expression was significantly correlated with PKCi and mutated p53 protein expression in gastric adenocarcinoma (p<0.05).
CONCLUSION: High AID and PKCi expressions were significantly correlated with poorly-differentiated gastric adenocarcinoma.

Related: Stomach Cancer Gastric Cancer TP53

Matsumoto A, Ishibashi Y, Urashima M, et al.
High UBCH10 protein expression as a marker of poor prognosis in esophageal squamous cell carcinoma.
Anticancer Res. 2014; 34(2):955-61 [PubMed] Related Publications
BACKGROUND/AIM: Ubiquitin-conjugating enzyme H10 (UBCH10) is required in the cell-cycle transition from metaphase to anaphase. Therefore, we investigated whether its expression level in cancerous esophageal lesions affected prognosis of patients with esophageal squamous-cell carcinoma.
MATERIALS AND METHODS: Paraffin-embedded tissue samples from 121 patients with esophageal squamous cell carcinoma were stained with antibody to UBCH10 for immunohistochemical analysis.
RESULTS: UBCH10 was expressed in cancerous and dysplastic lesions, but not in normal tissue. Patients were grouped according to expression: High (N=33) or low (N=88), depending on the staining pattern. There were significant differences between the groups in terms of invasion into lymphatic vessels, number of metastatic lymph nodes, TNM classification, and stages, as well as in survival: the 50% survival rate in the high expression group was 2.3 years, whereas it was 9.9 years for the low-expression group (p<0.0001). Even with multivariate adjusting for stage 0 to stage IV using the Cox proportional hazard model, patients belonging to the high-expression group had a poor prognosis (Hazard ratio=2.5; 95% Confidence Interval=1.3-4.5; p=0.004).
CONCLUSION: High protein expression of UBCH10 is a marker of poor prognosis in esophageal squamous cell carcinoma.

Related: Cancer of the Esophagus Esophageal Cancer

Kiss I, Bortlicek Z, Melichar B, et al.
Efficacy and toxicity of bevacizumab on combination with chemotherapy in different lines of treatment for metastatic colorectal carcinoma.
Anticancer Res. 2014; 34(2):949-54 [PubMed] Related Publications
UNLABELLED: The aim of the present study was to describe treatment outcomes for bevacizumab in combination with chemotherapy based on data from the Czech registry of targeted therapies for metastatic colorectal cancer (mCRC).
PATIENTS AND METHODS: In total, 4,487 patients with mCRC who received bevacizumab combined with chemotherapy in first line (n=3,990, 88.9%), second line (n=386, 8.6%), or third/higher line (n=111, 2.5%) had evaluable data and were included in the present retrospective analysis.
RESULTS: The median progression-free survival (PFS) was 11.3 months (95% conficence interval [CI]=11.0-11.7 months), 9.5 months (95% CI=8.2-10.9 months), and 7.3 months (95% CI=5.9-8.7 months; p<0.001), and the median overall survival from the start of bevacizumab-containing therapy was 28.4 months (95% CI=27.1-29.8 months), 25.9 months (95% CI=19.4-32.4 months), and 15.0 months (95% CI=10.7-19.3 months; p<0.001), respectively.
CONCLUSION: The data describe efficacy of bevacizumab with chemotherapy for different treatment lines in a large patient cohort.

Related: Colorectal (Bowel) Cancer Bevacizumab (Avastin)

Fukuchi M, Mochiki E, Suzuki O, et al.
Is gastric tube reconstruction the optimal surgical procedure for Siewert type II esophagogastric junction carcinoma?
Anticancer Res. 2014; 34(2):915-9 [PubMed] Related Publications
BACKGROUND/AIM: To evaluate the potential risk of gastric tube reconstruction for Siewert type II esophagogastric junction carcinoma.
PATIENTS AND METHODS: We retrospectively analyzed clinicopathological and survival data of 41 patients who had undergone total gastrectomy for Siewert type II carcinoma, focusing on lymph node metastasis around the middle to lower greater curvature or parapyloric area.
RESULTS: Histological examination showed involvement of at least one lymph node in six patients (14%). Multivariate Cox proportional hazard regression analysis of seven clinicopathological variables showed that lymph node metastasis around the middle to lower greater curvature, or parapyloric area was the only significant independent unfavorable factor (odds ratio=6.62; 95% confidence interval=1.27-41.1; p=0.03) for survival. We identified no significant predictors of lymph node metastasis in analyzed patients.
CONCLUSION: From an oncological point of view, we do not recommend routine gastric tube reconstruction for Siewert type II carcinoma.

Related: Stomach Cancer Gastric Cancer

Sohda M, Honjyo H, Hara K, et al.
L-[3-18F]-α-methyltyrosine accumulation as a definitive chemoradiotherapy response predictor in patients with esophageal cancer.
Anticancer Res. 2014; 34(2):909-13 [PubMed] Related Publications
AIMS: L-[3-(18)F]-α-Methyltyrosine ((18)F-FAMT) has high specificity for malignant tumors on positron emission tomography (PET), and its role and potential usefulness has been previously investigated in operable esophageal carcinoma. We aimed to assess the ability of (18)F-FAMT PET to predict the response of esophageal cancer to definitive chemoradiotherapy.
PATIENTS AND METHODS: We retrospectively reviewed 40 patients with esophageal cancer imaged with (18)F-FAMT PET. The relationship between (18)F-FAMT PET uptake before chemoradiotherapy and clinical outcomes was assessed.
RESULTS: The primary tumor was visualized in 95% patients. (18)F-FAMT uptake was significantly positively correlated with lymph node metastasis. The low-(18)F-FAMT accumulation group had significantly higher complete response (CR) rates than did the high-accumulation group. The addition of a lymph node metastasis category with low (18)F-FAMT uptake provides a more precise predictor of CR.
CONCLUSION: (18)F-FAMT uptake prior to treatment is a good predictor of CR rate after CRT for esophageal cancer.

Related: Cancer of the Esophagus Esophageal Cancer

Rediti M, Pellegrini E, Molinara E, et al.
Complete pathological response in advanced extra-gastrointestinal stromal tumor after imatinib mesylate therapy: a case report.
Anticancer Res. 2014; 34(2):905-7 [PubMed] Related Publications
BACKGROUND: Gastrointestinal stromal tumors are uncommon intra-abdominal tumors. In fewer than 5% of cases, they originate primarily from the mesentery, omentum or peritoneum and these extra-gastrointestinal stromal tumors tend to have characteristics similar to gastrointestinal stromal. Case Report: We report a case of extra-gastrointestinal stromal tumor in a 76-year-old male, Eastern Cooperative Oncology Group (ECOG) performance status of 2. Abdominal Computed Tomography (CT) showed multiple non-homogeneous confluent nodules at the level of the greater omentum and mesentery, involving the bladder and rectum, with additional peritoneal nodules in the upper abdomen. In March 2008, the patient started imatinib mesylate at 400 mg/day. Instrumental examinations showed progressive response until thoracic-abdominal CT in February 2012 which documented a complete response. Follow-up ended in October 2013. Treatment with imatinib, in addition to pathological response, provided clinical benefit, a progressive regression of symptoms and improved the patient's ECOG performance status from 2 to 0.

Related: Gastrointestinal Stromal Tumors Bladder Cancer Bladder Cancer - Molecular Biology Imatinib (Glivec)

Kasashima H, Kubo N, Ohira M, et al.
Successful resection of esophageal carcinoma with aberrant right subclavian artery using video-assisted thoracoscopic surgery: report of two cases.
Anticancer Res. 2014; 34(2):899-904 [PubMed] Related Publications
The right non-recurrent inferior laryngeal nerve (NRILN) is a rare nerve anomaly that communicates the laryngeal nerve to the right vagal nerve trunk directly in the neck, which is usually accompanied by aberrant right subclavian artery (ARSA). We report on two cases of thoracic esophageal carcinoma undertaken in patients with these abnormalities: a 73-year-old woman with progressive dysphagia and a 63-year-old asymptomatic man. Although there have been 10 cases of thoracic esophageal carcinomas associated with ARSA and NRILN in literature, as far as we are aware of, this is the first report to describe successful resection using video-assisted thoracoscopic surgery (VATS). We found that the combination of preoperative recognition of the ARSA using three-dimensional computed tomography (3D-CT) and VATS in the prone position allowed for visual magnification with an excellent thoracoscopic view and facilitated successful tumor resection and preservation of NRILN.

Related: Cancer of the Esophagus Esophageal Cancer

Ikari N, Nakajima G, Taniguchi K, et al.
HER2-positive gastric cancer with paraaortic nodal metastasis successfully resected after chemotherapy with trastuzumab: a case report.
Anticancer Res. 2014; 34(2):867-72 [PubMed] Related Publications
We report on a case of human epidermal growth factor receptor-2 (HER2)-positive gastric cancer with paraaortic lymph node metastasis. The patient (a 49-year-old female) received chemotherapy (capecitabine and cisplatin) plus molecular-targeted therapy (trastuzumab), followed by curative resection. Interestingly, the resected residual cancer was HER2-negative. Intra-tumor heterogeneity hinders molecular-targeted therapy for gastric cancer. In our case, continued trastuzumab administration presented few benefits since the residual cancer cells were HER2-negative. No consensus exists regarding the appropriate therapy for unresectable gastric cancers whose non-curative factors disappear following trastuzumab chemotherapy. The principal options are treatment with surgery or continued chemotherapy with trastuzumab. In our case, resection treated the HER2-negative residual cancer effectively, resulting in curative therapy. This is the first case of positive-to-negative change in the HER2 expression of residual tumor cells following trastuzumab therapy. It suggests that, due to intra-tumor heterogeneity, the risks presented by remnant HER2-negative cancer cells persist despite trastuzumab therapy.

Related: Stomach Cancer Gastric Cancer Trastuzumab (Herceptin)

Sugimoto N, Fujitani K, Imamura H, et al.
Randomized phase II trial of S-1 plus irinotecan versus S-1 plus paclitaxel as first-line treatment for advanced gastric cancer (OGSG0402).
Anticancer Res. 2014; 34(2):851-7 [PubMed] Related Publications
BACKGROUND: S-1-based regimens are commonly used for advanced gastric cancer (AGC) in Japan. We performed this trial to evaluate the efficacy and safety of S-1 plus irinotecan (SIri) and S-1 plus paclitaxel (SPac) as first-line treatments for AGC in order to select the optimal regimen for a subsequent phase III trial.
PATIENTS AND METHODS: Patients with previously untreated, locally advanced or metastatic measurable gastric adenocarcinoma were randomly assigned to receive SIri (irinotecan 80 mg/m(2) was administered intravenously (i.v.) on day 1 and 15, while 40 mg/m(2) S-1 was orally administered twice daily for three weeks from days 1-21 followed by a two-week pause) or SPac (paclitaxel 50 mg/m(2) was administered i.v. on day 1 and 8, while 40 mg/m(2) S-1 was orally administered twice daily for two weeks from day 1-14 followed by a one-week pause) regimen. The primary end-point was the overall response rate (ORR), and the secondary end-points were progression-free survival (PFS), overall survival (OS), and toxicity.
RESULTS: A total of 102 patients were enrolled. The ORR was 33.3% for SIri and 31.4% for SPac, which did not achieved the predicted ORR in either group. PFS and OS were 5.7 and 12.4 months for SIri, 4.6 and 11.9 months for SPac respectively. No treatment-related deaths occurred during the study. Although grade 3/4 neutropenia and anemia were more frequent in the Siri group, both regimens were well-tolerated.
CONCLUSION: Both regimens were well-tolerated in patients with AGC, but we conclude that neither regimen was optimal for a phase III trial.

Related: Paclitaxel Stomach Cancer Gastric Cancer Tegafur-uracil Irinotecan

Spindler KL, Pallisgaard N, Andersen RF, et al.
Gemcitabine and capecitabine for heavily pre-treated metastatic colorectal cancer patients - a phase II and translational research study.
Anticancer Res. 2014; 34(2):845-50 [PubMed] Related Publications
UNLABELLED: Aim: We investigated the efficacy and safety of capecitabine and gemcitabin (GemCap) in heavily pre-treated, therapy-resistant metastatic colorectal cancer (mCRC) patients and the clinical importance of cell-free DNA (cfDNA) measurement.
PATIENTS AND METHODS: Patients' inclusion criteria included histopathologically-verified mCRC refractory to standard chemotherapy, adequate organ function and performance status. Treatment included capecitabine (2,000 mg/m(2) day on days 1-7 q2w) and gemcitabine (1,000 mg/m(2) on day 1). The number of DNA alleles was measured in pre-treatment plasma samples using an in-house developed qPCR.
RESULTS: Forty-nine patients were included in the study. GemCap was well-tolerated in the majority of patients. Disease control rate was 30%, median progression-free survival (PFS) and overall survival (OS) by intention-to-treat were 2.7 (95%CI=2.6-2.8) and 6.8 (95%CI=5.0-7.7) months. Median OS in patients with cfDNA concentrations above the median (13,200 alleles/ml) was 4.7 (3.7-9.6) months compared to 7.8 months in the remaining patients (HR=2.22; 1.07-3.9; p=0.0186). The prognostic value of the cell-free DNA (cfDNA) was confirmed by multivariate analysis.
CONCLUSION: GemCap was well-tolerated with encouraging efficacy, and cfDNA was shown to hold a strong prognostic value.

Related: Colorectal (Bowel) Cancer Fluorouracil Capecitabine Gemcitabine

Hong IK, Kim SY, Chung JH, et al.
3'-Deoxy-3'-[18F]fluorothymidine positron emission tomography imaging of thymidine kinase 1 activity after 5-fluorouracil treatment in a mouse tumor model.
Anticancer Res. 2014; 34(2):759-66 [PubMed] Related Publications
AIM: We aimed to investigate whether 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) positron emission tomography (PET) can estimate thymidine kinase 1 (TK1) activity after thymidylate synthase (TS) inhibition by 5-fluorouracil (5-FU) in a mouse tumor model.
MATERIALS AND METHODS: Nude mice with HT29 tumors were injected with phosphate-buffered saline or 5-FU (16.7 or 50 mg/kg). Twenty-four hours later, 2-hour dynamic images were acquired after injection of [(18)F]FLT. In another group of mice with HT29 cells, static PET images were obtained 110 min after [(18)F]FLT injection.
RESULTS: Kinetic parameters related to [(18)F]FLT retention increased significantly, whereas the de-phosphorylation of [(18)F]FLT monophosphate decreased significantly. The standardized uptake value (SUVmean) of HT29 tumors correlated significantly with the net influx constant and the distribution volume for phosphorylated [(18)F]FLT. There was a significant correlation between the tumor SUVmean and TK1 activity.
CONCLUSION: SUVmean at 110-120 min after [(18)F]FLT, can quantitatively evaluate kinetic parameters and TK1 activity after TS inhibition.

Related: Fluorouracil

Kim ME, Ha TK, Yoon JH, Lee JS
Myricetin induces cell death of human colon cancer cells via BAX/BCL2-dependent pathway.
Anticancer Res. 2014; 34(2):701-6 [PubMed] Related Publications
Myricetin is a flavonol found in various berries, herbs, and walnuts. Previous studies have demonstrated that myricetin has anticancer effects against several types of cancer, including hepatocarcinoma, skin carcinoma, and pancreatic cancer. However, the anticancer activity of myricetin on human colon cancer has not been yet established. In the present study, we investigated the anticancer effects of myricetin on HCT-15 human colon cancer cells. We found that myricetin induces cytotoxicity and DNA condensation in human colon cancer cells in a dose-dependent manner. We also determined that myricetin increases the BCL2-associated X protein/B-cell lymphoma 2 ratio, but not cleavage of caspase-3 and -9. In addition, myricetin induced the release of apoptosis-inducing factor from mitochondria. These results suggest that myricetin induces apoptosis of HCT-15 human colon cancer cells and may prove useful in the development of therapeutic agents for human colon cancer.

Related: Signal Transduction BAK1

Patru CL, Surlin V, Georgescu I, Patru E
Current issues in gastric cancer epidemiology.
Rev Med Chir Soc Med Nat Iasi. 2013 Jan-Mar; 117(1):199-204 [PubMed] Related Publications
Gastric cancer, one of the most common malignant tumors of digestive tract continues to be a major health problem by frequency, aggressiveness and low rate of cure in symptomatic stage. Although its incidence is decreasing (especially in the West), globally the gastric cancer is ranked fourth in incidence among cancers at various sites. Despite these developments, the gastric cancer mortality, overall declining globally, is high. especially in the West where even if diagnosed fewer cases of gastric cancer, TNM stages are advanced and have a poor prognosis. In contrast, in Japan, where the incidence is still high, the percentage of cases diagnosed at the stage of "early gastric cancer" has greatly increased, thus improving prognosis. Gastric neoplasia affects more men, age range 50-70 years, disadvantaged social classes and black race. In Romania the gastric cancer incidence is increasing over recent years, presenting variations across the country being more common in men compared with women, reaching a peak of incidence around age 60. Gastric cancer mortality in the world places Romania among the countries with average mortality. Gastric cancer prognosis remains extremely reserved, in close correlation with tumor stage at diagnosis, surgical treatment being the only possibility to provide improved survival, especially in the early stages. Improvement of survival rate in recent years is due to increased gastric resectability result of an earlier diagnosis, a more complex treatment and a closer monitoring of the population at risk.

Related: Stomach Cancer Gastric Cancer

Vemuri AS, Nicolau SA, Ayache N, et al.
Inter-operative trajectory registration for endoluminal video synchronization: application to biopsy site re-localization.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 1):372-9 [PubMed] Related Publications
The screening of oesophageal adenocarcinoma involves obtaining biopsies at different regions along the oesophagus. The localization and tracking of these biopsy sites inter-operatively poses a significant challenge for providing targeted treatments. This paper presents a novel framework for providing a guided navigation to the gastro-intestinal specialist for accurate re-positioning of the endoscope at previously targeted sites. Firstly, we explain our approach for the application of electromagnetic tracking in acheiving this objective. Then, we show on three in-vivo porcine interventions that our system can provide accurate guidance information, which was qualitatively evaluated by five experts.

Related: Cancer of the Esophagus Esophageal Cancer

Bhushan M, Schnabel JA, Chappell M, et al.
The impact of heterogeneity and uncertainty on prediction of response to therapy using dynamic MRI data.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 1):316-23 [PubMed] Related Publications
A comprehensive framework for predicting response to therapy on the basis of heterogeneity in dceMRI parameter maps is presented. A motion-correction method for dceMRI sequences is extended to incorporate uncertainties in the pharmacokinetic parameter maps using a variational Bayes framework. Simple measures of heterogeneity (with and without uncertainty) in parameter maps for colorectal cancer tumours imaged before therapy are computed, and tested for their ability to distinguish between responders and non-responders to therapy. The statistical analysis demonstrates the importance of using the spatial distribution of parameters, and their uncertainties, when computing heterogeneity measures and using them to predict response on the basis of the pre-therapy scan. The results also demonstrate the benefits of using the ratio of Ktrans with the bolus arrival time as a biomarker.

Related: Colorectal (Bowel) Cancer

Fanetti G, Ferrari LA, Pietrantonio F, Buzzoni R
Reversible bilateral blepharoptosis following oxaliplatin infusion: a case report and literature review.
Tumori. 2013 Sep-Oct; 99(5):e216-9 [PubMed] Related Publications
Oxaliplatin, a platinum analogue employed in the treatment of colorectal cancer and various other neoplasms, is characterized by a broad range of adverse events. Peripheral neuropathy is probably the most peculiar and clinically relevant toxicity associated with its use and can be distinguished into two types: acute and chronic neurotoxicity.We report a case of acute reversible bilateral palpebral ptosis and dyspnea without bronchospasm or laryngospasm which occurred at the end of the third administration of adjuvant oxaliplatin by infusion for stage III colon cancer in a 54-year-old woman. Chlorphenamine and hydrocortisone were administered with fast resolution of dyspnea and slight improvement of ptosis. Complete resolution with no sequelae occurred in one hour. No further recurrence of blepharoptosis was described during the following days. The subsequent cycles were prescribed at reduced dosage without acute complications.

Related: Oxaliplatin

Vasiliadisl K, Papavasiliou C, Pervana S, et al.
Acute pancreatitis as the initial manifestation of an adenocarcinoma of the major duodenal papilla in a patient with familial adenomatous polyposis syndrome: a case report and literature review.
Acta Chir Belg. 2013 Nov-Dec; 113(6):463-7 [PubMed] Related Publications
We report a case of an ampullary carcinoma presenting as acute pancreatitis in a patient with familial adenomatous polyposis (FAP) syndrome and severe duodenal adenomatosis. A 48-year-old woman was hospitalised because of an episode of acute pancreatitis. She had a history of prophylactic total colectomy for FAP 2 years earlier. On admission, abdominal ultrasonography and computed tomography revealed dilatation of the main pancreatic and common bile duct. Spigelman's stage IV duodenal adenomatosis involving the major duodenal papilla was diagnosed on endoscopy and a classical Whipple procedure was proposed. Pathologic examination of the duodenopancreatectomy specimen revealed a tubular adenocarcinoma of the papilla that occluded the major pancreatic ducts. The patient had no evidence of disease and experienced no recurrent attacks of acute pancreatitis during a 36-month period of follow-up.

Kornmann VN, Hagendoorn J, van Koeverden S, et al.
Totally laparoscopic right hemicolectomy with intracorporeal anastomosis is a technically and oncologically safe procedure.
Acta Chir Belg. 2013 Nov-Dec; 113(6):439-43 [PubMed] Related Publications
BACKGROUND: During laparoscopic right hemicolectomy, most surgeons perform an extracorporeal anastomosis. A totally laparoscopic procedure with intracorporeal anastomosis may improve cosmesis because midline- or paraumbilical incisions can be avoided. Here, we investigate the safety of an intracorporeal anastomosis from a technical and oncological perspective.
METHODS: All patients who underwent right hemicolectomy with intracorporeal anastomosis between 2003-2011 were retrospectively analyzed. Parameters were duration of surgery, intraoperative blood loss, mortality and morbidity. Adequacy of oncologic resections was scored by resectional margins and number of harvested lymph nodes.
RESULTS: A total of 162 patients were included with a median age of 69 years (IQR60-76). The duration of surgery was 100 minutes (80-120) and intraoperative blood loss was 30 mL (10-100). Hundred-twenty patients (74%) underwent an oncologic resection. Number of harvested lymph nodes was 12 (9-18). RO-resection was achieved in 100%. Four patients died (2.5%). Postoperative complications were: anastomotic leakage (3.1%; n = 5), ileus (4.9%; n = 8), abscesses (2.5% ; n = 4), wound infection (3.1% ; n = 5) and cardiopulmonary complications (10.5% ; n = 17). Duration of oncological follow-up was 2.5 years (1.3-4.6). Local recurrence and overall survival rates at two years were 0.8% and 85.4%, respectively.
CONCLUSION: Right hemicolectomy with intracorporeal anastomosis is a technically and oncologically safe procedure with acceptable operating time and low mortality.

Keskin S, Tas F, Karabulut S, et al.
The role of surgical methods in the treatment of anorectal malignant melanoma (AMM).
Acta Chir Belg. 2013 Nov-Dec; 113(6):429-33 [PubMed] Related Publications
PURPOSE: Anorectal malignant melanoma (AMM) is a rare tumor with a poor prognosis. The aim of this study was to investigate the clinicopathological characteristics and treatment outcomes in patients with AMM.
METHODS: The study included 21 patients diagnosed with AMM between 2000 and 2010 that were evaluated with regard to age, sex, disease stage, treatment modality, and survival. Stage I, II, and III were defined as localized primary malignant melanoma, regional lymph node metastasis, and distant metastasis, respectively.
RESULTS: In all, 12 (57%) patients were female and 9 (43%) were male ; median age was 61 years (range : 30-84 years). Among the 21 patients, 7 (47%) underwent abdominoperineal resection and 8 (53%) were treated using wide local excision. Four (19%) patients were classified as stage I, 10 (48%) as stage II, and 7 (33%) patients as stage III. In total, 10 patients received adjuvant therapy. Median overall and progression-free survival was 12 and 9 months, respectively. The 1-year and 5-year overall survival estimates were 59% and 42%, and progression free survival were 49% and 7%, respectively. Patients aged > 60 years (P = 0.145), female patients (P = 0.076), patients with localized disease (P = 0.045), patients that underwent wide local excision (P = 0.619), and patients that received adjuvant therapy (P = 0.962) had longer survival.
CONCLUSIONS: The prognosis of AMM remains very poor and disease stage is the only predictor of survival. Abdominoperineal resection does not confer an advantage, in terms of survival, in patients with AMM.

Related: Anal Cancer Melanoma

Debunne H, Ceelen W
Mucinous differentiation in colorectal cancer: molecular, histological and clinical aspects.
Acta Chir Belg. 2013 Nov-Dec; 113(6):385-90 [PubMed] Related Publications
UNLABELLED: BACKGROUND : Mucinous colorectal carcinoma represents a subtype of colorectal carcinoma (CRC), which is characterized by abundant amount of extracellular mucin. We reviewed the molecular, histological and clinical aspects of mucinous CRC as compared to the non-mucinous type.
METHODS: A systematic web-based research was performed using Web of Knowledge. The combination of the Boolean search terms "COLO" AND "MUC" was used. The literature was searched until July 2013.
RESULTS: Patients with mucinous CRC have distinct clinical and pathological features. Mucinous CRC tends to occur in younger patients, are often seen in the proximal colon, are more diagnosed at an advanced stage and are more frequently associated with hereditary non-polyposis colorectal cancer (HNPCC) and young-age sporadic colorectal cancer. The prognostic significance of mucinous differentiation remains uncertain; some studies have shown a poor response to oxaliplatin and/or irinotecan based chemotherapy. Mucinous CRC is associated with a higher expression of MUC2 and MUC5AC, but a lower expression of MUC1. The differential expression of mucins has been related to altered risk of metastasis and death. Recently, mucins have been used as targets for molecular therapy and as a source of immune therapy. Mucinous differentiation is associated with other specific genetic and molecular features such as increased BRAF mutation rate and microsatellite instability.
CONCLUSION: Mucinous CRC is a distinct clinical, pathological, and molecular entity. The implications of mucinous differentiation for treatment response and outcome are not fully elucidated, but the available data suggest an adverse effect. The use of mucins as immunotargets may show therapeutic promise for mucinous CRC.

Related: Colorectal (Bowel) Cancer MUC1 gene MUC2

Moon BS, Jeong WJ, Park J, et al.
Role of oncogenic K-Ras in cancer stem cell activation by aberrant Wnt/β-catenin signaling.
J Natl Cancer Inst. 2014; 106(2):djt373 [PubMed] Related Publications
BACKGROUND: Adenomatous polyposis coli (APC) loss-of-function mutations and K-Ras gain-of-function mutations are common abnormalities that occur during the initiation and intermediate adenoma stages of colorectal tumorigenesis, respectively. However, little is known about the role these mutations play in cancer stem cells (CSCs) associated with colorectal cancer (CRC) tumorigenesis.
METHODS: We analyzed tissue from CRC patients (n = 49) to determine whether K-Ras mutations contributed to CSC activation during colorectal tumorigenesis. DLD-1-K-Ras-WT and DLD-1-K-Ras-MT cells were cultured and evaluated for their ability to differentiate, form spheroids in vitro, and form tumors in vivo. Interaction between APC and K-Ras mutations in colorectal tumorigenesis was evaluated using APC (Min/+)/K-Ras (LA2) mice and DLD-1-K-Ras-WT and DLD-1-K-Ras-MT cell xenografts. (n = 4) Group differences were determined by Student t test. All statistical tests were two-sided.
RESULTS: The sphere-forming capability of DLD-1-K-Ras-MT cells was statistically significantly higher than that of DLD-1-K-Ras-WT cells (DLD-1-K-Ras-MT mean = 86.661 pixel, 95% confidence interval [CI] = 81.701 to 91.621 pixel; DLD-1-K-Ras-WT mean = 42.367 pixel, 95% CI = 36.467 to 48.267 pixel; P = .003). Moreover, both the size and weight of tumors from DLD-1-K-Ras-MT xenografts were markedly increased compared with tumors from DLD-1-K-Ras-WT cells. Expression of the CSC markers CD44, CD133, and CD166 was induced in intestinal tumors from APC (Min/+)/K-Ras (LA2)mice, but not K-Ras (LA2) mice, indicating that APC mutation is required for CSC activation by oncogenic K-Ras mutation.
CONCLUSIONS: K-Ras mutation activates CSCs, contributing to colorectal tumorigenesis and metastasis in CRC cells harboring APC mutations. Initial activation of β-catenin by APC loss and further enhancement through K-Ras mutation induces CD44, CD133, and CD166 expression.

Related: Colorectal (Bowel) Cancer Signal Transduction KRAS gene

Hande KA
Measuring endoscopic performance for colorectal cancer prevention quality improvement in a gastroenterology practice.
Nurs Clin North Am. 2014; 49(1):15-27 [PubMed] Related Publications
A gastroenterology practice lacked quality measures to evaluate the practice's colorectal cancer prevention efforts. Colonoscopy performance data were gathered from a retrospective review of 90 charts using a modified Colorectal Cancer Prevention Data Collection Form. Practice stakeholders and project leader reviewed the data, identified practice deficiencies, conducted root cause analysis, and developed practice changes. Implementing the prioritized recommendations and routinely benchmarking care were warranted to ensure effective practice to improve outcomes for colorectal cancer prevention. Achieving higher-value care has led to increased efforts to improve systems for measuring care, using these measures for quality improvement and directly linking quality outcomes to reimbursement.

Related: Colorectal (Bowel) Cancer

Wang H, Liu J, Jiang C, et al.
Transthoracic esophagectomy using endobronchial blocker after previous pneumonectomy.
Ann Thorac Surg. 2014; 97(2):723-5 [PubMed] Related Publications
Esophagectomy after pneumonectomy is very rare. We present a case of esophagectomy for esophageal cancer after left pneumonectomy. By application of an endobronchial blocker, satisfactory results were achieved and the disadvantages of extracorporeal membrane oxygenation, cardiopulmonary bypass, and other ventilation methods were avoided.

Related: Cancer of the Esophagus Esophageal Cancer

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