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Background & Aims: There is a sparsity of data on the impact of cachexia on human muscle function. This study examined the relationship between cachexia, quality of life and the mass/function/mechanical quality of lower limb skeletal muscle in gastrointestinal cancer patients., Methods: Quadriceps strength and lower limb power were measured in 54 patients with gastrointestinal cancer (n = 24 ≥ 10% weight-loss) and 18 healthy controls. Quadriceps cross-sectional area was measured in 33/54 patients and in all controls using MRI. Muscle mechanical quality was defined as quadriceps strength/unit quadriceps cross-sectional area. Quality of life was assessed using the EORTC QLQ-C30. Patients with weight-loss ≥ 10% were classified as cachectic., Results: In male cachectic patients, quadriceps strength (p = 0.003), lower limb power (p = 0.026), quadriceps cross-sectional area (p = 0.019) and muscle quality (p = 0.008) were reduced compared with controls. In female cachectic patients, quadriceps strength (p = 0.001) and muscle quality (p = 0.001) were reduced compared with controls. Physical function (p = 0.013) and fatigue (p = 0.004) quality of life scores were reduced in male cachectic compared with non-cachectic patients, but not in females., Conclusions: Muscle quality is reduced in cancer patients. The degree of impairment of lower limb muscle mass, quality and function and the impact on quality of life varies with weight-loss and sex., (Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Enteropathy-associated T-cell lymphoma (EATL) is a rare primary gastrointestinal T-cell lymphoma. A multicenter study from the Asia Lymphoma Study Group identified 38 EATL patients within a 19-year period. All cases were type II EATL. Men were affected twice as common as women, at a median age of 59 (23-89) years. None had a history of celiac disease. The sites of involvement were small bowel and stomach (5%), small bowel (63%), small and large bowel (16%), and large bowel (18%). Common presenting features were bowel perforation (34%), pain (32%), and obstruction (21%). Lymphomas showed monomorphic neoplastic lymphoid infiltrates that were CD3⁺ (100%), CD56⁺ (91%), TIA-1⁺ (96%), CD4⁻CD8⁺ (63%), CD4⁺CD8⁺ (19%), CD4⁻CD8⁻ (16%), and CD4⁺CD8⁻ (3%). Epstein Barr virus was demonstrable in three cases. Despite chemotherapy and/or surgical resection, the overall response and complete response rates were poor at 46% and 38%. The median overall survival (OS) was 7 months and progression-free-survival (PFS) 1 month. Five patients underwent hematopoietic stem cell transplantation all were alive. Age and the prognostic index for peripheral T-cell lymphoma were not prognostically significant. Good performance status was associated with better OS (P = 0.03), and response to initial treatment led to better OS and PFS (P < 0.001)., (Copyright © 2012 Wiley Periodicals, Inc.)

Oxygen free radicals in excessively high amounts are all very reactive chemically and can impose a detrimental influence on living organisms by provoking "oxidative stress" that can damage major cellular constituents. The latter includes the cell membrane, cytoplasmic proteins, and nuclear DNA. Conversely, nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS) when present in low amounts play an important role as regulatory mediators in signaling processes, through which, paradoxically, many ROS-mediated responses can protect the cells against oxidative stress by induction of "redox homeostasis." Therefore, diseases associated with free radical overproduction are provoked by "blazed ROS productions" far beyond the host's capacity to quench. Free radicals have been implicated in the pathogenesis of diverse gastrointestinal (GI) diseases including gastroesophageal reflux disease (GERD), gastritis, enteritis, colitis and associated cancers as well as pancreatitis and liver cirrhosis. This article provides an overview of the role of oxidative stress in inflammation-based GI tract diseases, including reflux esophagitis, Helicobacter pylori-associated gastritis, non-steroidal anti-inflammatory drug-induced enteritis, ulcerative colitis, and associated colorectal cancer. The challenging issue that ROS can contribute to diverse gastrointestinal dysfunction, or manifest dual roles in cancer promotion or cancer suppression will also be discussed for the opportunity to enhance understanding of inflammation-based GI diseases., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background: Highly active intermediates are formed in aerobic metabolism which in turn leads to cellular damage. It is increasingly proposed that free radicals play a key role in human cancer development. The aim of this study was to investigate changes in 8-hydroxy-deoxyguanosine, nitrite+nitrate, total glutathione, total antioxidant capacity levels and superoxide dismutase, catalase, glutathione peroxidase activities in operative patients with gastrointestinal cancer before and after surgery and compare with inoperative patients., Methods: Oxidative stress parameters were measured in 59 gastrointestinal cancer patients and 20 controls. 8-hydroxy-deoxyguanosine was quantitated by Elisa method. Superoxide dismutase, catalase, glutathione peroxidase were assayed with colorimetric methods; Nitrite+nitrate, total glutathione and total antioxidant capacity were assayed with spectrophotometric methods., Results: 8-hydroxy-deoxyguanosine levels in cancer patients were higher than those of control group (p<0.01). Similarly, glutathione levels were increased compared with controls (p<0.01). However, nitrite+nitrate, total antioxidant capacity levels and superoxide dismutase and catalase activities were decreased in cancer patients compared with controls (p<0.01, p<0.01, p<0.05, p<0.01, respectively). The patients were divided into two groups; operative (n = 30) and inoperative (n = 29). A significant difference was found in inoperative group compared with postoperative group according to glutathione peroxidase activity (p<0.05)., Discussion: Our results demonstrate that the oxidant/antioxidant balance was altered in favor of free radicals and DNA damage in gastrointestinal cancer patients. Significant increases in 8-hydroxy-deoxyguanosine, glutathione and decreases in nitrite+nitrate, SOD, CAT activities and antioxidant molecules suggest the possible involvement of oxidative stress in gastrointestinal cancer. Glutathione peroxidase activities in postoperative patients were higher compared to inoperative patients., (Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Introduction: Systemic inflammatory response in individuals with cancer is related to a progressive reduction in total body mass, especially lean mass., Objective: The aim of the present study was to determine the association between nutritional status and systemic inflammatory response in patients with gastrointestinal cancer., Methodology: A case series study was carried out involving 30 male and female adults and elderly patients with no prior treatment sent consecutively for surgery. Nutritional status was assessed using subjective and objective methods. Inflammatory response and prognosis were assessed through the determination of C-reactive protein (CRP), the Glasgow Prognostic Score and CRP/albumin ratio., Results: High prevalence values were found for systemic inflammation (73%), a greater risk of infectious and/or inflammatory complication (43%) and worse prognosis (50%). The percentage of weight loss was correlated with serum CRP (r = 0.38; p < 0.05) and the CRP/albumin ratio (r = 0.44; p < 0.05). Inflammation markers and prognosis were negatively correlated with serum albumin (r = -0.50; p < 0.05), body mass index (r = -0.39; p < 0.05) and total lymphocyte count (r = -0.37; p < 0.05). Patients with weight loss and malnourishment had significantly higher serum CRP and CRP/albumin ratio values as well as lower serum albumin levels in comparison to those without weight loss and in well-nourished., Conclusion: Nutritional status is related to inflammation markers and prognosis in patients with gastrointestinal cancer. The diagnosis and attenuation of systemic inflammation should be part of the nutritional care of these patients.

Accumulating evidence has indicated that inflammatory responses are important for cancer development. Epidemiological studies have shown that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of colon cancer development. Subsequently, mouse genetic studies have shown that cyclooxygenase (COX)-2, one of the target molecules of NSAIDs, and its downstream product, prostaglandin E(2) (PGE(2)), play an important role in gastrointestinal tumorigenesis. Bacterial infection stimulates the Toll-like receptor (TLR)/MyD88 pathway in tumor tissues, which leads to the induction of COX-2 in stromal cells, including macrophages. Induction of the COX-2/PGE(2) pathway in tumor stroma is important for the development and maintenance of an inflammatory microenvironment in gastrointestinal tumors. In such a microenvironment, tumor-associated macrophages express proinflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6, and these cytokines, respectively, activate the nuclear factor (NF)-κB and Stat3 transcription factors in epithelial cells, as well as in stromal cells. Recent mouse studies have uncovered the role of such an inflammatory network in the promotion of gastrointestinal tumor development. Genetically engineered and chemically induced mouse tumor models which mimic sporadic or inflammation-associated tumorigenesis were used in these studies. In this review article, we focus on mouse genetic studies using these tumor models, which have contributed to the elucidation of the molecular mechanisms associated with the inflammatory network in gastrointestinal tumors, and we also discuss the role of each pathway in cancer development. The involvement of immune cells such as macrophages, mast cells, and regulatory T cells in tumor promotion is also discussed.

The well-being of the intestine and its host requires that this organ execute its complex function amid colonization by a large and diverse microbial community referred to as the gut microbiota. A myriad of interacting mechanisms of mucosal immunity permit the gut to corral the microbiota in such a way as to maximize the benefits and to minimize the danger of living in close proximity to this large microbial biomass. Toll-like receptors and Nod-like receptors, collectively referred to as pattern recognition receptors (PRRs), recognize a variety of microbial components and, hence, play a central role in governing the interface between host and microbiota. This review examines mechanisms by which PRR-microbiota interactions are regulated so as to allow activation of host defense when necessary while preventing excessive inflammation, which can have a myriad of negative consequences for the host. Analysis of published studies performed in human subjects and a variety of murine disease models reveals the central theme that PRRs play a key role in maintaining a healthful stable relationship between the intestine and its microbiota. In contrast, although select genetic ablations of PRR signaling may protect against some chronic diseases, the overriding theme of studies performed to date is that perturbations of PRR-microbiota interactions are more likely to promote disease states associated with inflammation.

The gastrointestinal tract (GIT) is the most commonly involved site of extranodal lymphomas. The close association between chronic inflammation and specific GIT lymphomas not only provide interesting insights into the pathobiology of lymphomas but also poses unique diagnostic challenges. A clear understanding of marginal zone and mucosa associated lymphoid tissue (MALT) in health and disease is helpful to place GIT lymphomas in proper context. A wide variety of lymphomas besides MALT lymphomas occur in various parts of the GIT. The characteristic pathological, immunophenotypic, and genetic features of different GIT lymphomas categorized according to World Health Organization (WHO) classification are presented. The epidemiological, clinical, and pathological features of lymphomas occurring in each part of the GIT are summarized and the key points regarding lymphomas at each site are emphasized. A tabular summary of the important differential diagnostic considerations at each site is given and suggestions for a minimal diagnostic work up are provided.

Although malnutrition is known to be frequent in cancer patients, it has not been described in a selected population of patients with gastrointestinal malignancies under chemotherapy only. Physician judgment about malnutrition and risk factors for malnutrition were also evaluated. All consecutive in- and outpatients of 11 centers were prospectively enrolled in a cross-sectional 14-day period study and classified according to the French health recommendations [Haute Autorité de Santé (HAS)]. Among 313 patients enrolled in 11 centers (mean age = 63 yr; range = 21-93; 67% male) mainly with colorectal (58%), pancreatic (15%), gastric (11%), and hepatobiliary (10%) primary tumors, the prevalence of malnutrition was 52%. Moderate and severe malnutrition was present in 27% and 25% of cases, respectively. Physicians considered it in 36% and 6% of cases, respectively, thereby misclassifying 134 patients (43%). The agreement between the HAS definition and the physicians' judgment was very low (κ = 0.30). Most of the patients who were identified as severely malnourished received no nutritional support. Performance status and pancreatic and gastric cancers were independently associated with malnutrition. Malnutrition levels are high, around 50%, unequally distributed according to the primitive tumor. It is still underestimated by physicians. Weight loss remains a clinically relevant, simple, and reliable marker of malnutrition.

Inflammasomes are multi-protein complexes that mediate activation of caspase-1, which promotes secretion of the proinflammatory cytokines interleukin-1β and interleukin-18 and pyroptosis, a form of phagocyte cell death induced by bacterial pathogens. Members of the Nod-like receptor family (including Nlrp1, Nlrp3, and Nlrc4), the DNA sensor Aim2, the adaptor apoptosis-associated speck-like protein (ASC), and pro-caspase-1 are important components of inflammasomes. Stimulation with specific microbial and endogenous molecules leads to inflammasome assembly and caspase-1 activation. Inflammasomes are believed to mediate host defense against microbial pathogens and tissue homeostasis within the intestine, and their dysregulation might contribute to inflammatory diseases and intestinal cancer. Improving our understanding of inflammasome signaling pathways could provide insights into the pathogenesis of many gastrointestinal disorders and the development of therapeutic targets and approaches to treat diseases such as inflammatory bowel diseases and gastrointestinal cancers., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Ano1 is a recently discovered Ca(2+)-activated Cl(-) channel expressed on interstitial cells of Cajal (ICC) that has been implicated in slow-wave activity in the gut. However, Ano1 is expressed on all classes of ICC, even those that do not contribute to generation of the slow wave, suggesting that Ano1 may have an alternate function in these cells. Ano1 is also highly expressed in gastrointestinal stromal tumors. Mice lacking Ano1 had fewer proliferating ICC in whole mount preparations and in culture, raising the possibility that Ano1 is involved in proliferation. Cl(-) channel blockers decreased proliferation in cells expressing Ano1, including primary cultures of ICC and in the pancreatic cancer-derived cell line, CFPAC-1. Cl(-) channel blockers had a reduced effect on Ano1(-/-) cultures, confirming that the blockers are acting on Ano1. Ki67 immunoreactivity, 5-ethynyl-2'-deoxyuridine incorporation, and cell-cycle analysis of cells grown in low-Cl(-) media showed fewer proliferating cells than in cultures grown in regular medium. We confirmed that mice lacking Ano1 had less phosphorylated retinoblastoma protein compared with controls. These data led us to conclude that Ano1 regulates proliferation at the G(1)/S transition of the cell cycle and may play a role in tumorigenesis.

Familial gastrointestinal stromal tumor (GIST) is an extremely rare autosomal dominant disorder, and approximately 20 families have been reported to date. In this article, we present one additional family. A 25-year-old Japanese woman presented with abdominal pain, and subsequent image analyses disclosed multiple tumors measuring 12 cm in maximum diameter in the lower digestive tract. The postoperative histologic examination showed multiple GISTs and diffuse hyperplasia of interstitial cells of Cajal. Her mother had a history of GIST in the digestive tract. Three members of this family including her younger sister and mother had cutaneous hyperpigmentation of external genitalia and axilla. Their DNA samples showed identical missense mutation at exon 11 in the juxtamembrane domain of the KIT gene, and this mutation site was considered to be a hot spot in familial GIST. One year after, her younger sister suffered from multiple GISTs in the digestive tract at the age of 25 years. To correctly diagnose familial GIST, mutual information should be exchanged among clinicians, pathologists, and molecular scientists., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The thyroid hormones control the development and the homeostasis of several organs in vertebrates. Their actions depend, for the most part, on nuclear receptors, the TRs, which are transcription factors whose activity is modulated by the hormone T3. The gastrointestinal tract is a well characterized target of thyroid hormones and TRs, as extensively described in the literature. In fact, its remodeling in amphibians during thyroid hormone-dependent metamorphosis is well characterized at the cellular and the molecular levels. However, whereas a great attention has been paid to the nervous system and to cardiac development and physiology, the function of thyroid hormones and TRs in the mammalian gastrointestinal tract has been, until recently, underestimated. Several studies have described an important conservation of this hormonal signal during intestinal development and have suggested that it may play a role in stem cell physiology in both amphibians and mammals. These findings show the importance of the thyroid hormones and TRs, whose homologous actions are maintained across species. In the present review, we summarize the most recent data on this issue, starting from work that has been conducted on amphibian metamorphosis to results on postnatal development, homeostasis, and tumorigenesis in mammals. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Cachexia has plagued clinicians for centuries. Although all cachexia is related to malnutrition, cachexia associated with malignant diseases differs from starvation cachexia in that it is more recalcitrant to nutritional therapy. All cachexia responds to judicious nutritional support; however, cancer cachexia worsens autonomously as the disease advances and cannot be arrested or reversed by any known form of nutrition, hormonal, or pharmacologic therapy. Cachexia must be treated cautiously to avoid overfeeding syndrome, which may result in serious or dangerous complications or death., (2011 Elsevier Inc. All rights reserved.)

Diabetes and cancer are diseases which take the size of an epidemic spread across the globe. Those diseases are influenced by many factors, both genetic and environmental. Precise knowledge of the complex relationships and interactions between these two conditions is of great importance for their prevention and treatment. Many epidemiological studies have shown that certain types of cancer, especially gastrointestinal cancers (pancreas, liver, colon) and also the urinary and reproductive system cancers in women are more common in patients with diabetes or related metabolic disorders. There are also studies showing the inverse relationship between diabetes and cancer, or the lack of it, but they are less numerous and relate mainly to prostate cancer or squamous cell carcinoma of the esophagus. Epidemiological studies, however, do not say anything about the mechanisms of these dependencies. For this purpose, molecular research is needed on the metabolism of cells (including tumor cells) and on metabolic dysfunctions that arise due to changes in the cell environment taking place in the sick, as well as in the intensely treated human organism.

RAPGEF1 (also known as C3G and GRF2) is a guanine nucleotide exchange factor that releases GDP from the inactive Rap1 protein, facilitating its subsequent activation by the binding of GTP. Rap1 plays regulatory roles in proliferation, differentiation and apoptosis. Amplification and overexpression of RAPGEF1 have been found in small cell lung cancers, suggesting an oncogenic role. In contrast, hypermethylation of a promoter CpG island (CGI-A) of RAPGEF1 has been reported in squamous cervical tumors, suggesting an anti-oncogenic role in these gynecological cancers. In our studies of DNA methylation alterations in gastrointestinal cancer we found somatic demethylation of a relaxed-criterion CpG island (CGI-B) located in the first intron of RAPGEF1 in 40% of colon cancers and 8% of gastric cancers relative to their matching normal tissues that were always methylated. We also found somatic demethylation in 47% of squamous cervical carcinomas as well as 33% of ovarian cancers. This somatic change in methylation, however, did not extend to the strict-criterion CpG island located in the promoter region (CGI-A) that was unmethylated in all normal and tumor tissues analyzed. Thus, promoter hypermethylation of RAPGEF1 seems insignificant in colorectal, cervical and ovarian cancers. In contrast, tumor-specific hypomethylation of the gene appears to be frequent in gastrointestinal and gynecological cancers.

Purpose: Molecular targeting approaches have been an intensive focus of treatment strategies against advanced gastric and colorectal cancers. Recent clinical trials have demonstrated promising survival prolongation of targeted human epidermal growth factor receptors; however, patients harboring mutations in the K-Ras gene (human homolog of the Kirsten rat sarcoma-2 virus oncogene) do not derive benefit from the anti-epidermal growth factor receptor antibodies. K-Ras mutations cause a stimuli-independent activation of a large cohort of downstream effectors that permit cells to acquire a sustained growth. The perpetuated growth activation manifests resistance to molecular targeting therapies., Methods: Literature review has been made to explore the possibilities that, given that K-Ras or downstream effector proteins require farnesyl or geranylgeranyl moiety for their activity (e.g., prenylation), statins are logical candidates to overcome the limitations of or to potentiate the effect of molecular targeting therapies as statins suppress the mevalonate pathway leading to depletion of an end product of mevalonate such as farnesylpyrophosphate and geranylgeranylpyrophosphate, which are used as substrates by their respective transferase enzyme for protein prenylation, and ultimately impair functions of K-Ras and downstream effector proteins., Results: In the last few years, statins have gained interest in therapeutic value for anticancer treatments extending beyond their lipid-lowering effects as single agents or in combined use with other chemotherapeutic agents. This review provides insights into possible anticancer mechanisms of statins and introduces current achievements or ongoing studies of statins in the field of cancer treatment in single or combined uses. This review also offers information to help establish optimal treatment schedules of statins that overcome current limitations of molecular targeting therapies., Conclusions: It is expected that therapeutic scope of statins will expand considerably in the future as anticancer agents in addition to their proven benefits of hyperlipidemia.

Excess body weight (EBW) is an independent risk factor for many human malignancies, including cancers throughout the gastrointestinal and hepatobiliary tract from the esophagus to the colorectum. The relative risk of gastrointestinal cancer in obese individuals is approximately 1.5-2.0 times that for normal weight individuals, with organ-specific and gender-specific differences for specific cancers. The association between EBW and risk of premalignant stages of gastrointestinal carcinogenesis, such as colorectal adenoma and Barrett esophagus, is similar, implying a role for EBW during the early stages of carcinogenesis that could be relevant to preventative strategies. EBW also impacts negatively on gastrointestinal cancer outcomes. The mechanistic basis of the association between EBW and carcinogenesis remains incompletely understood. Postulated mechanisms include increased insulin and insulin-like growth factor signaling and chronic inflammation (both linked to the metabolic syndrome), as well as signaling via adipokines, such as leptin. The role of obesity-related changes in the intestinal microbiome in gastrointestinal carcinogenesis deserves further attention. Whether weight loss leads to reduced future gastrointestinal and liver cancer risk has yet to be fully explored. There is some support for the idea that weight loss negatively regulates colorectal carcinogenesis. In addition, data suggest a reduction in risk of several cancers in the first 10 years after bariatric surgery.

Gastrointestinal tract is the most common extranodal site involved by lymphoma with the majority being non-Hodgkin type. Although lymphoma can involve any part of the gastrointestinal tract, the most frequent sites in order of its occurrence are the stomach followed by small intestine and ileocecal region. Gastrointestinal tract lymphoma is usually secondary to the widespread nodal diseases and primary gastrointestinal tract lymphoma is relatively rare. Gastrointestinal lymphomas are usually not clinically specific and indistinguishable from other benign and malignant conditions. Diffuse large B-cell lymphoma is the most common pathological type of gastrointestinal lymphoma in essentially all sites of the gastrointestinal tract, although recently the frequency of other forms has also increased in certain regions of the world. Although some radiological features such as bulky lymph nodes and maintenance of fat plane are more suggestive of lymphoma, they are not specific, thus mandating histopathological analysis for its definitive diagnosis. There has been a tremendous leap in the diagnosis, staging and management of gastrointestinal lymphoma in the last two decades attributed to a better insight into its etiology and molecular aspect as well as the knowledge about its critical signaling pathways.

The endoscopic ultrasonography (EUS) is considered to be the leading method of diagnostic of the submucous gastrointestinal tumors. Results of diagnostics and treatment of submucous tumors of the upper gastrointestinal tract in 38 patients were analyzed. EUS was performed in 37 (97,4%) of patients, which allowed to detect the origin, size and localization of the tumor. The differential diagnostic algorithm was suggested together with certain indications for various surgical treatment modalities. Thereby, endoscopic ablation is reasonable when the tumor invades not deeper than muscle plate of mucosa or the submucose layer. Laparoscopic full-layer resection of the organ wall is necessary when the tumor invades the muscle layer. Larger tumors or those of any size, but with preoperative signs of high malignancy must be eradicated through laparotomy, meeting all principles of oncology.

Gastrointestinal stromal tumors are very rare. The diagnosis is difficult because there are no typical clinical and laboratory signs, as well as specific data of the radiologic and instrumental investigations. Surgical treatment is most important for gastrointestinal stromal tumors, but about nonresecable cases the method of election is the therapy with Imatinib.

Increasing evidence suggests that thiazolidinediones (TZDs) could have a therapeutic potential for patients with cancers. Here, the evidence on the mechanisms by which TZDs could contribute to different steps of cancer biology in the digestive system is summarized. According to studies, TZDs induce anti-cancer actions through 3 main pathways: (1) cell growth arrest, (2) induction of apoptosis, and (3) inhibition of cell invasion. Cell growth arrest is induced by an increased level of p27(Kip1). p27(Kip1) accumulation results from the inhibition of the ubiquitin-proteasome system and/or inhibition of MEK-ERK signaling. TZDs induce apoptosis through increased levels of apoptotic molecules, such as p53 and PTEN and/or decreased level of anti-apoptotic molecules, such as Bcl-2 and survivin. Inhibition of MEK-ERK signaling-mediated up-regulation of E-cadherin and claudin-4, and/or decreased expression of matrix metalloproteinases (MMPs) such as MMP-2 and MMP-9, play a role in the TZD-induced inhibition of cancer cell invasion. Thus, TZDs are capable of inducing anti-tumor action in a variety of ways in gastrointestinal cancers.

Context: The Patient Care Monitor (PCM) is a review of systems survey delivered by means of an electronic patient-reported outcomes (ePRO) data capture system that uses wireless tablet computers. Although the PCM 1.0 is validated, the updated PCM 2.0 has not been validated nor tested in the academic setting., Objectives: To validate and test the PCM 2.0 in three cancer populations., Methods: Two hundred seventy-five individuals participated in three clinical trials enrolling breast (n=65), gastrointestinal (n=113), and lung (n=97) cancer patients. Internal consistency was evaluated using Cronbach's alpha coefficients calculated for six PCM subscales (general physical symptoms, treatment side effects, distress, despair, impaired performance, and impaired ambulation) and a Quality-of-Life Index. Construct validity was evaluated through Pearson's correlation between PCM subscales and subscales of the Functional Assessment of Cancer Therapy--General (FACT-G), the M.D. Anderson Symptom Inventory (MDASI), and the Functional Assessment of Chronic Illness Therapy--Fatigue (FACIT-F). The participants had the following characteristics: mean age was 58 years (standard deviation: 11), 52% were females, 79% were whites, 17% were blacks, 62% had no college degree, and 78% had metastatic or recurrent disease., Results: Raw and normalized scores for PCM 2.0 subscales were internally consistent across study cohorts. PCM 2.0 subscales correlated significantly (P<0.05) with the corresponding subscales on FACT-G, MDASI, and FACIT-F, with the exception of FACT-G social well-being, particularly for the lung cancer population. These correlations demonstrated construct validity. PCM 2.0 results followed expected patterns by cancer etiology. Prior reports demonstrate patient satisfaction with PCM 2.0., Conclusion: Within three unique academic oncology populations, PCM 2.0 is a valid ePRO instrument for assessing symptoms with seven patient-centered subscale or index domains., (Copyright © 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

The aim of palliative chemotherapy is to increase survival whilst maintaining optimal quality of life for the individual patient. While the best use of traditional chemotherapeutical agents continues to be explored, the introduction of targeted therapies has significantly broadened the therapeutic options. Yet it is interesting to note that the results of current trials did not always confirm the underlying molecular concepts. Recent data have suggested that altered pathways underlie the development of cancer, not just altered genes. Thus an effective therapeutic agent will have to target pathophysiologically relevant signalling networks, rather than individual proteins. This review presents current concepts and problems of cancer treatment, highlighting results from recent clinical trials of colorectal and pancreatic cancer patients and to discuss the current understanding of the underlying mechanisms., (Georg Thieme Verlag KG Stuttgart-New York.)

Inflammation is a primary defense process against various extracellular stimuli, such as viruses, pathogens, foods, and environmental pollutants. When cells respond to stimuli for short periods of time, it results in acute or physiological inflammation. However, if the stimulation is sustained for longer time or a pathological state occurs, it is known as chronic or pathological inflammation. Several studies have shown that tumorigenesis in the gastrointestinal (GI) tract is closely associated with chronic inflammation, for which abnormal cellular alterations that accompany chronic inflammation such as oxidative stresses, gene mutations, epigenetic changes, and inflammatory cytokines, are shared with carcinogenic processes, which forms a critical cross-link between chronic inflammation and carcinogenesis. Transforming growth factor (TGF)-beta is a multi-potent cytokine that plays an important role in regulation of cell growth, apoptosis and differentiation. Most importantly, TGF-beta is a strong anti-inflammatory cytokine that regulates the development of effector cells. TGF-beta has a suppressive effect on carcinogenesis under normal conditions by inhibiting abnormal cell growth, but on the other hand, many GI cancers originate from uncontrolled cell growth and differentiation by genetic loss of TGF-beta signaling molecules or perturbation of TGF-beta adaptors. Once a tumor has developed, TGF-beta exerts a promoting effect on the tumor itself and stromal cells to enhance cell growth, alter the responsiveness of tumor cells to stimulate invasion and metastasis, and inhibited immune surveillance. Therefore, novel development of therapeutic agents to inhibit TGF-beta-induced progression of tumor and to retain its growth inhibitory activities, in addition to anti-inflammatory actions, could be useful in oncology. In this review, we discuss the role of TGF-beta in inflammation and carcinogenesis of the GI tract related to abnormal TGF-beta signaling.

Gastrointestinal follicular lymphoma (GI-FL) is a relatively rare disease, accounting for only 1%-3.6% of gastrointestinal non-Hodgkin's lymphoma. Although the duodenum and terminal ileum are considered to be the most common sites of origin, the development of wireless capsule endoscopy and double-balloon enteroscopy has increased the detection of GI-FL in every part of the small intestine. Approximately 70% of patients with GI-FL are estimated to have multiple lesions throughout the entire gastrointestinal tract. FL is a low-grade lymphoma that usually develops very slowly. If the lymphoma causes no symptoms, immediate treatment may not be necessary. Standard therapy has not yet been established for GI-FL, but chemotherapy, radiotherapy, monoclonal antibody therapy, or a combination of these therapies, is sometimes performed based on the therapeutic regimens for nodal FL. Regimens including conventional chemotherapy with rituximab, which achieve high response rates in nodal FL, are commonly used for GI-FL. The long-term clinical outcome of GI-FL is unclear. The results of a few series on the long-term outcomes of patients with GI-FL treated with conventional therapy indicate a median relapse-free time ranging from 31 to 45 months. On the other hand, in patients with GI-FL who were followed without treatment, the median time to disease progression was 37.5 months. Thus, whether to initiate aggressive therapy or whether to continue watchful waiting in patients with GI-FL is a critically important decision. Ongoing research on biomarkers to guide individualized GI-FL therapy may provide invaluable information that will lead to the establishment of a standard therapeutic regimen.

Importance of the Field: In recent years, scientific work has been intensified to unravel new (patho-) physiological insights, particularly regarding the functional role of somatostatin (SRIF) receptor subtype 5 (sst) and the development of novel sst(5)-targeted SRIF analogues, in order to broaden medical therapeutic opportunities in patients suffering from neuroendocrine diseases., Areas Covered in This Review: The scope of this review is primarily focused upon recent insights in sst(5)-receptor physiology, novel sst(5)-targeted treatment options predominantly directed towards pituitary adenomas, and gastroenteropancreatic neuroendocrine tumours., What the Reader Will Gain: An understanding of the potential that novel sst(5)-targeted SRIF analogues might have in the medical treatment of Cushing's disease and acromegaly, as demonstrated by translational research, based on pathophysiological data combined with results from clinical trials., Take Home Message: The role of targeting sst(5) in gastroenteropancreatic neuroendocrine tumours remains to be established. The sst(5) subtype might function as sst(2) modulator in terms of receptor internalization and desensitization, and seems less important compared with sst(2)-preferring SRIF analogues in the regulation of human insulin secretion by the pancreas. Finally, absence of sst(5) in corticotroph adenomas could be related to tumour aggressiveness in Cushing's disease.

Purpose of Review: Chronic infection of the gastric mucosa with Helicobacter pylori has long been recognized as a significant risk factor for gastric cancer, and indeed, this model represents the prototypical inflammation-associated cancer. In this review, we present the latest clinical and experimental evidence showing that gastrin peptides and their receptors [the cholecystokinin (CCK2) receptors] potentiate the progression of gastric cancer and other gastrointestinal malignancies in the presence of inflammation., Recent Findings: We highlight the feed-forward mechanisms by which gastrin and CCK2 receptor expression are upregulated during inflammation and in gastrointestinal cancers, summarize gastrin's proinflammatory role by inducing the production of cyclooxgenase-2 (COX-2) and interleukin-8 (IL-8), and relate evidence suggesting that gastrin and their receptors modulate the function of immune cells and fibroblasts following cellular stress, injury, repair, as well as during cancer progression., Summary: We discuss trends for future studies directed toward the elucidation of gastrin peptides' role in regulating intercellular molecular signaling mechanisms between local and circulating immune cells, fibroblasts, epithelial cells, and other cell types in the microenvironments of inflammation-related cancers. Elucidation of the molecular and cellular pathways that relate inflammation with cancer may provide additional opportunities to develop complementary therapies that target the inflammatory microenvironment of the cancer.

Background and Aims: Insulin-like growth factor (IGF)-I receptor (IGF-IR) signaling plays important parts in both the tumorigenicity and progression of digestive/gastrointestinal malignancies. In this study, we sought to test the effectiveness of a practical approach to blocking IGF-IR signaling using RNA interference delivered by recombinant adenoviruses., Methods: We constructed a recombinant adenovirus expressing short hairpin RNA targeting IGF-IR (shIGF-IR) and assessed its effect on signal transduction, proliferation, and survival in digestive/gastrointestinal cancer cell lines representing colorectal, gastric, and pancreatic adenocarcinoma, esophageal squamous cell carcinoma, and hepatoma. We analyzed the effects of shIGF-IR alone and with chemotherapy in vitro and in nude mouse xenografts, as well as on insulin signaling and hybrid receptor formation between IGF-IR and insulin receptor., Results: shIGF-IR blocked expression and autophosphorylation of IGF-IR and downstream signaling by the IGFs, but not by insulin. shIGF-IR suppressed proliferation and carcinogenicity in vitro and up-regulated apoptosis in a dose-dependent fashion. shIGF-IR augmented the effects of chemotherapy on in vitro growth and apoptosis induction. Moreover, the combination of shIGF-IR and chemotherapy was highly effective against tumors in mice. shIGF-IR reduced hybrid receptor formation without effect on expression of insulin receptor., Conclusions: shIGF-IR may have therapeutic utility in human digestive/gastrointestinal cancers, both alone and in combination with chemotherapy.

Similar to growing and metabolically active tissues, tumors require a dense vasculature to gain access to oxygen and nutrients. However, blood vessels in tumors differ from vessels in normal tissues in many respects. In particular, the tumor vasculature is in an active state of angiogenesis or vasculogenesis, and it is immature and leaky. Blood vessels are multicellular tubes formed by polarized endothelial cells, which face the patent vascular lumen with their apical cell surface, whereas their basal cell surface faces extracellular matrix on the outside of the vessels. The same cell polarity can be found in other tubular structures, such as in the bronchial tubes of the lung or the kidney tubules. In contrast, blood vessels in invertebrates often have a vascular lumen lined by basal cell surfaces. These vessels are often formed by a process named 'ancestral vascular tube formation'. Here, we discuss the hypothesis that the supply of tumors with blood can be achieved by both endothelial cell-lined tubes as well as tubes formed by the tumor cells themselves using the ancestral vascular tube formation mechanism. We discuss this hypothesis with a particular focus on gastrointestinal tumors.

Aim: To investigate the role of subjective global assessment (SGA) in nutritional assessment and outcome prediction of Chinese patients with gastrointestinal cancer., Methods: A total of 751 patients diagnosed with gastrointestinal cancer between August 2004 and August 2006 were enrolled in this study. Within 72 h after admission, SGA, anthropometric parameters, and laboratory tests were used to assess the nutritional status of each patient. The outcome variables including hospital stay, complications, and in-hospital medical expenditure were also obtained., Results: Based on the results of SGA, 389 (51.8%), 332 (44.2%), and 30 (4.0%) patients were classified into well nourished group (SGA-A), mildly to moderately malnourished group (SGA-B), and severely malnourished group (SGA-C), respectively. The prevalence of malnutrition classified by SGA, triceps skinfold thickness (TSF), mid-upper arm muscle circumference (MAMC), albumin (ALB), prealbumin (PA), and body mass index (BMI) was 48.2%, 39.4%, 37.7%, 31.3%, 21.7%, and 9.6%, respectively. In addition, ANOVA tests revealed significant differences in body mass index (BMI), TSF, PA, and ALB of patients in different SGA groups. The more severely malnourished the patient was, the lower the levels of BMI, TSF, PA, and ALB were (P < 0.05). Chi2 tests showed a significant difference in SGA classification between patients receiving different types of treatment (surgery vs chemotherapy/radiotherapy). As the nutritional status classified by SGA deteriorated, the patients stayed longer in hospital and their medical expenditures increased significantly. Furthermore, multiple regression analysis showed that SGA and serum ALB could help predict the medical expenditures and hospital stay of patients undergoing surgery. The occurrence of complications increased in parallel with the increasing grade of SGA, and was the highest in the SGA-C group (23.3%) and the lowest in the SGA-A group (16.8%)., Conclusion: SGA is a reliable assessment tool and helps to predict the hospital stay and medical expenditures of Chinese surgical gastrointestinal cancer patients.

Background: Opioids are key drugs for cancer pain relief, but some patients, especially those who have gastroenterological cancers, suffer from severe opioid-induced bowel dysfunction (OBD), which reduces their quality of life. In order to achieve better pain relief, efforts to minimize OBD are required., Methods: Between September 2006 and December 2007, 18 patients were enrolled in this feasibility study. All patients had gastroenterological cancer pain. The patients received direct fentanyl patch introduction starting from 12.5 microg/h, with additional opioid treatment for the first 12 h. Adverse events, changes of medications, pain scale, and patients' satisfaction scores were recorded for 9 days after fentanyl patch introduction., Results: All patients completed the protocol treatment without interruption by adverse events. Eight patients (44%) showed adverse events that were presumed to be related to the treatment. However, all events were grade 1 and had a minimal effect on patients' quality of life. According to subjective evaluation on day 9, only 4 patients (22%) mentioned that they had felt adverse events during the treatment course. Seventeen patients (94%) had pain score scale improvements evaluated on day 9. Satisfaction scores on days 9 and day 27 were excellent or good for all but one of the patients., Conclusion: This prospective study showed the safety and efficacy of direct fentanyl patch introduction in Japanese gastroenterological cancer patients, and the treatment had good feasibility. This model should help cancer pain management for patients with a high risk of features of OBD such as constipation, subileus, or postabdominal surgery.

Aim: To ascertain from patients and their relatives the advice they would like to receive on dealing with the post-operative symptoms associated with oesophagectomy and gastrectomy. The findings would be used by the Oesophageal Patients Association to update its information booklet., Method: A literature review was undertaken to investigate what information is available. Qualitative methodology using focus groups with patients and healthcare professionals informed the study. The focus group proceedings were tape recorded and transcribed. Inductive thematic analysis was used, with words being grouped into categories to explore recurrent themes and overlapping concepts. Themes were labelled and the transcripts re-explored for items relevant to each theme., Findings: The literature search produced 604 articles. Many were irrelevant to upper gastrointestinal (GI) cancer but useful information was obtained from others, leading to a first draft of the updated booklet. The focus groups' data were crucial in developing the booklet., Conclusion: The updated booklet will assist patients who have had surgery for upper GI cancer to manage their nutrition.

Purpose: This study examines the rate and prediction of referral for specialized psychosocial oncology care in 326 patients with metastatic GI or lung cancer., Patients and Methods: Referral information was abstracted from medical records and hospital databases. Patients completed measures of psychosocial and physical distress and functioning., Results: Routine referral occurred in 33% of patients, and in 42% and 44%, respectively, of those scoring high on measures of depression (Beck Depression Inventory [BDI]-II >or= 15) and hopelessness (Beck Hopelessness Scale >or= 8). Univariate analyses indicated that referral was associated with younger age, unmarried status, living alone, presence of more depressive symptoms, hopelessness, and attachment anxiety, and with less social support, self-esteem, and spiritual well-being (all P < .05). Among the significantly depressed (BDI-II >or= 15), 100% of those less than 40 years of age, but only 22% of those age 70 years or older were referred. Multivariate analyses indicated that referral was associated with younger age, unmarried status, and presence of more depressive symptoms. Moreover, increasing age was associated with a progressively lower likelihood of referral independent of the level of distress., Conclusion: Routine referral of patients with metastatic cancer for psychosocial oncology care was predicted by presence of more severe depressive symptoms, younger age, and unmarried status. The rate of referral progressively declined with each decade of age, even among those with significant distress. These findings are consistent with some aspects of Andersen's model of health care utilization. The extent to which referred patients represent those who are most likely to benefit deserves further investigation.

Objectives: To review the normal anatomy and physiology of the gastrointestinal (GI) tract, the malignant transformations in GI cancers, and the rationale for targeted therapy for these cancers., Data Sources: Published articles, book chapters and web sources., Conclusion: Oncology nurses require an understanding of normal GI anatomy and physiology, along with an understanding of malignant transformations at the cellular and molecular level, to effectively educate and care for the patient with a diagnosis of a GI cancer., Implications for Nursing Practice: Challenges for the oncology nurse include continuing education related to GI cancer, the development of effective patient education skills, ensuring safe administration of oral agents and remaining current regarding GI clinical trial opportunities. Education of nursing colleagues, development of an area of expertise through specialization, and development of leadership skills are opportunities associated with practicing in the dynamic environment of oncology nursing.

Purpose: Cancer-related cachexia is an obscure syndrome leading to muscle wasting, reduced physical fitness and quality of life. The aim of this study was to assess morphology, metabolism, and microcirculation in skeletal muscles of patients with cancer-related cachexia and to compare these data with matched healthy volunteers., Methods: In 19 patients with cancer-induced cachexia and 19 age-, gender-, and body-height-matched healthy volunteers body composition and aerobic capacity (VO(2max)) were analyzed. Skeletal muscle fiber size and capillarization were evaluated in biopsies of the vastus lateralis muscle. The cross-sectional area (CSA) of the quadriceps femoris muscle was measured by magnetic resonance imaging as well as its isokinetic and isometric force. The energy and lipid metabolism of the vastus lateralis muscle was quantified by (31)P and (1)H spectroscopy and parameters of its microcirculation by contrast-enhanced ultrasonography (CEUS)., Results: Morphologic parameters were about 30% lower in cachexia than in volunteers (body mass index: 20 +/- 3 vs. 27 +/- 4 kg m(-2), CSA: 45 +/- 13 vs. 67 +/- 14 cm(2), total fiber size: 2854 +/- 1112 vs. 4181 +/- 1461 microm(2)). VO(2max) was reduced in cachexia (23 +/- 9 vs. 32 +/- 7 ml min(-1) kg(-1), p=0.03), whereas histologically determined capillary density and microcirculation in vivo were not different. Both concentrations of muscular energy metabolites, pH, and trimethyl-ammonium-containing compounds were comparable in both groups. Absolute strength of quadriceps muscle was reduced in cachexia (isometric: 107 +/- 40 vs. 160 +/- 40 Nm, isokinetic: 101 +/- 46 vs. 167 +/- 50 Nm; p=0.03), but identical when normalized on CSA (isometric: 2.4 +/- 0.5 vs. 2.4 +/- 0.4 Nm cm(-2), isokinetic: 2.2 +/- 0.4 vs. 2.5 +/- 0.5 Nm cm(-2))., Conclusions: Cancer-related cachexia is associated with a loss of muscle volume but not of functionality, which can be a rationale for muscle training.

Important deteriorations in body composition and strength occur and need to be accurately measured in advanced cancer patients (ACPs). The aim of this study was to establish the relationship between a single-frequency bioimpedance analyzer (BIA) and the dual-energy X-ray absorptiometer (DXA), as well as the Jamar handgrip dynometer and the Biodex handgrip attachment, and to determine the precision of each of these instruments in ACPs. Eighty-one ACPs with non-small-cell lung cancer and gastrointestinal cancer were recruited from the McGill University Health Centre (Montreal, Que.). Consecutive paired measurements, with repositioning between measurements, were obtained for total-body DXA, BIA, Biodex handgrip, and BIA plus Jamar handgrip. The total-body percent coefficient of variation (%CV) for the BIA and DXA were 1.34 and 1.56 for fat mass (FM), respectively, and 0.42 and 0.72 for fat free mass (FFM), respectively. The %CV for the Jamar and Biodex handgrips were 6.3 and 16.7, respectively. Bland-Altman plots were used to characterize the limits of agreement between DXA and BIA for FM (4.60 +/- 7.80 (-3.19 to 12.39) kg) and FFM (-1.87 +/- 7.16 (-9.03 to 5.29) kg). Both DXA and BIA demonstrate good short-term precision in ACPs. However, given its poor accuracy, it remains to be determined if BIA can be used to monitor ACPs for changes in total-body tissue composition as a function of time, whether for observation or response to treatment. Furthermore, because of wide limits of agreement, the DXA and BIA cannot be used interchangeably in research or clinical settings. The Jamar handgrip dynamometer shows more consistency than the Biodex handgrip attachment in ACPs, and should therefore be the preferred measure of changes in strength over time.

A novel peptide combination consisting of four synthetic neuropeptide analogs of Vasoactive Intestinal Peptide (VIP), Bombesin, Substance P and Somatostatin has been found to have potent anticancer activity in vitro and in vivo. The receptors of these four neuropeptides are known to be over expressed in various cancers. We have found the presence of native neuropeptides in the culture supernatant of the primary tumor cells of human colon adenocarcinomas. It was further demonstrated by receptor-ligand assays that not only do these tumor cells synthesize and secrete four peptide hormones but also possess specific high affinity receptors on their surface. Screening a large panel of analogs to the four peptide hormones on tumor cell proliferation led to the identification of four cytotoxic analogs, the combination of which was code-named DRF7295. The design and synthesis of the peptide analogs have been described in this paper. In vitro anticancer activity of DRF7295 was studied in a large panel of human tumor cells. Gastrointestinal tumor cells of the colon, pancreas and duodenum were found to be most sensitive to DRF7295 with moderate activity seen in glioblastoma, prostate, leukemia and those of oral cancer cells. Efficacy studies in xenograft models of colon and duodenum resulted in T/C% of less than 40%, which is indicative of strong tumor regressing potential of DRF7295 in gastrointestinal cancers. Acute and long-term toxicity studies as well as safety pharmacology studies conducted indicate the safety of the drug upon systemic administration with no significant adverse pharmacological effects.

We have reported earlier a novel combination of four structurally designed synthetic neuropeptide analogs of vasoactive intestinal peptide (VIP), bombesin, substance P and somatostatin, code-named DRF 7295 which have anti-tumor efficacy for adenocarcinomas in vitro and in vivo (Jaggi et al., Invest New Drugs, 2008). The discovery, synthesis, in vitro and in vivo efficacy was reported (Jaggi et al., Invest New Drugs, 2008). Gastrointestinal tumor cells of the colon, pancreas and duodenum were found to most sensitive to DRF7295 in vitro and in vivo (Jaggi et al., Invest New Drugs, 2008). We have further investigated and report here the modulation of cellular signaling in gastrointestinal carcinomas by DRF 7295, which may be mediating its observed anticancer activity in these cancer types. DRF 7295 inhibits the binding of specific neuropeptides initiating a cascade of cellular signaling events leading to programmed cell death. It down regulates the second messenger cAMP, epidermal growth factor (EGF) dependent proliferation and the phosphorylated MAP Kinase pERK1/2 in gastrointestinal carcinomas, thus depriving the tumour cells of critical pro-proliferative cellular signals. It triggers bcl2 and Caspase 3 dependent apoptotic cell death and induces p53 tumor suppressor protein in the treated carcinoma cells in vitro. It has significant anti-angiogenic potential as reflected in the inhibition of tube like formation in the endothelial cells and down regulation of VEGF levels. Tumour xenograft studies confirmed the in vivo efficacy of DRF 7295 for gastrointestinal carcinomas (Jaggi et al., Invest New Drugs, 2008). The Phase I clinical trials have shown DRF 7295 to be well tolerated and devoid of systemic toxicities of the conventional cytotoxics (Mukherjee et al., Phase I dose escalating study of DRF7295: a new class of peptide based drugs. "Abstract" ASCO ID:948, 2003). The drug may have a promising role in disease stabilization in colorectal and other cancers. Thus DRF 7295 is a novel targeted drug in the class of signal transduction modulators, with potential for treatment of gastrointestinal carcinomas.

Objective: To observe the influence of chemotherapy with FOLFOX protocol (CT-F) on sex hormones of male patients, and the protective and detoxifying effect of herbal medicines for reinforcing Shen and supplementing qi (HM) on it., Methods: The randomized block control and self-control design was adopted to retrospectively investigate the changes of sex hormones in 61 patients with cancer of colon, rectum or stomach. They were assigned to four groups, A: treated simply with HM; B: treated with CT-F; C: treated with CT-F combined with HM; D: the blank control group. One course of CT-F composed of 1 month treatment, and 6 courses totally were applied on each patients. The levels of luteinizing hormone (LH), estradiol (E2), prolactin (PRL), progesterone (P), testosterone (T) and follicle-stimulating hormone (FSH) were determined before treatment (T0), at the end of the 6th month treatment (T1) and the 12th month (T2) after starting treatment., Results: Levels of LH, PRL and T were significantly lowered in the group B at T1, being 4.6 +/- 0.4 IU/L, 8.6 +/- 0.7 microg/L and 13.1 +/- 1.4 IU/L, respectively, which were significantly different to those in the other 3 groups at the corresponding time; they were somewhat raised after chemotherapy but still lower at T2 than those at T0, being 5.0 +/- 0.4 IU/L, 9.9 +/- 1.1 microg/L and 14.1 +/- 1.4 IU/L respectively, also lower than the corresponding levels in the other 3 Groups (P<0.05 or P<0.01). In group C, LH significantly lowered at T1 (P<0.05) to 5.1 +/- 0.4 IU/L, but it was restored to the levels of T0 and that in Group D, reaching 6.1 +/- 0.5 IU/L; while PRL and T were changed insignificantly in the chemotherapeutic course, and restored at T2 to the level of T0, comparable to that in group D. Contrarily, levels of E2 and FSH increased significantly (P <0.01) in group B after chemotherapy (at T1) to 135 +/- 14 pmol/L and 9.1 +/- 1.1 IU/L respectively, and till T2, being 140 +/- 15 pmol/L and 9.1 +/- 1.o IU/L, they were lower than those at T0 and higher than those in group D, A and C ( all P <0.01), but the two indexes were not significantly increased in group C, being 116 +/- 12 pmol/L and 7.1 +/- 0.9 IU/L at T1. However, all the parameters showed no significant change in group A and D, and the level of P showed insignificant change in all the groups in the whole observation period., Conclusion: CT-F could induce multiple sex hormonal abnormalities in male patients with post-operational gastrointestinal cancer, and HM shows protective and detoxifying effects on them in different degrees.

To assess the association between nutrition status and prognosis of patients with digestive system cancer, epidemiological investigations were conducted in 2 periods to obtain information about the patients' nutrition status, survival time, and quality of life. Relative risks and 95% confidence intervals were estimated by logistic regression. Among the patients with esophagus, stomach, and colorectal cancers, nutritional indicators at time 1 did not affect relative risk for survival at time 2. At time 2, relations between quality of life and albumin, daily intake of calories, and daily intake of protein were statistically significant (P < .05). This study offers evidence that nutrition status shortly after operation does not affect 1-year survival rate and that nutritional status at 1 year is associated with quality of life.