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Background and Objective: Lactobacillus acidophilus has been widely used for the management of gastrointestinal carcinoma owing to its immunomodulation effect; however, the role of L. acidophilus and its specific mechanism of action in the stomach is not fully comprehended. The present study evaluated the expression profile of MUC-1, GAL-3, IL -1β, and IL-17 in the L. acidophilus treated mice stomach. Methods: The study was conducted utilizing three groups of mice, 6 mice for each group, administered with different doses of L. acidophilus and a control group treated with normal saline. The results were analyzed with the Mann-Whitney Test. Results: The results demonstrated that L. acidophilus elevated IL-1β insignificantly and inhibited the expression of IL-17. The MUC-1 expression is influenced by L. acidophilus and inversely proportional to GAL-3 expression. Conclusion: Lactobacillus acidophilus plays a prominent role against inflammatory responses and has a potential in the treatment of gastrointestinal cancer.

Background: The association between celiac disease (CD) and the development of lymphoid and gastrointestinal (GI) malignancies have been reported. However, data are scarce yet needed to develop evidence-based follow-up programs.Objective: The objective of this article is to assess relative (RR) and absolute risks of lymphoma and GI carcinoma for newly diagnosed patients.Methods: A case-control design to determine RR was performed with cases (lymphoma or GI carcinoma) and controls (melanoma or basal cell carcinoma) diagnosed 1994-2014, retrieved from the Dutch nationwide population-based pathology database (PALGA). Within this population, individuals with histologically proven CD before or simultaneously diagnosed with the malignancy were identified.Results: A total of 349/301,425 cases (0.1%) and 282/576,971 (0.05%) controls were diagnosed with CD. Risk of T-cell lymphoma, predominantly enteropathy-associated T-cell lymphoma (EATL), was strongly associated with CD diagnosis (RR = 35.8 (95% CI 27.1-47.4)). Although most often synchronously diagnosed, T-cell lymphoma RR ≥ 1 year after CD diagnosis was still elevated (RR = 12.7 (95% CI 7.6-21.3)). Other CD-associated malignancies were small bowel adenocarcinoma (RR = 11.9 (95% CI 8.2-17.2)) and esophageal squamous cell carcinoma (RR = 3.5 (95% CI 2.1-5.8)). Absolute risks were relatively low. Other types of lymphomas and GI carcinomas were not associated with CD.Conclusion: Increased risk for specific malignancies in CD should alert physicians for EATL (both intestinal and extraintestinal) and small bowel adenocarcinoma in patients with CD diagnosed at age ≥ 50 years.

This series of 10 articles (eight original articles and two reviews) is presented by international leaders in gastrointestinal cancer research [...]

Purpose: Heat shock protein 90 (HSP90) is a critical molecular chaperone for protein folding, intracellular disposition and regulation of tumor biological behavior in the extracellular space. HSP90 has received much attention due to its specific effect in gastrointestinal cancer. This clinical study sought to determine whether HSP90 in plasma may serve as a biomarker in patients with advanced gastrointestinal carcinoma. Methods: Using human plasma samples of advanced gastrointestinal carcinoma, we investigated the specific value of HSP90 in gastrointestinal cancer from a clinical perspective. Results: In summary, plasma levels of HSP90 were shown to be higher in patients with gastric cancer (GC) or colorectal cancer (CRC) than in controls with benign gastrointestinal diseases. In both GC and CRC patients, HSP90 was significantly associated with live metastasis. Higher HSP90 levels were more frequent in CRC patients with hazardous or harmful alcohol consumption habits. Patients with RAS mutations had higher HSP90 levels in CRC. Compared with Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 19-9 (CA19-9), HSP90 benefited patients by enhancing diagnostic sensitivity and the Youden index. The levels of HSP90 were inversely associated with short-term efficacy in GC patients who had received fluorouracil/platinum-based advanced first-line treatment. When first-line therapy failed, plasma HSP90 levels in patients with GC were significantly increased. In terms of progression-free survival (PFS), patients with GC or CRC who had low levels of HSP90 were not significantly different from those with high levels of HSP90. Univariate and multivariate analyses demonstrated that HSP90 was not an independent prognostic predictor for GC and CRC patients with PFS. However, RAS mutation was an independent prognostic factor for poor PFS in CRC patients. Conclusions: Plasma HSP90 levels have potential diagnostic value in advanced gastrointestinal carcinoma and therapeutic predictive value in GC.

Endoscopic submucosal dissection (ESD) is recognized as an important technique in the nonsurgical management of early gastrointestinal carcinoma and it is continuously undergoing evolution in terms of technique and equipment. The pocket-creation method was recently developed for overcoming various difficulties such as large tumor size and severe fibrosis in ESD. Circumferential ESDs are rare and pose technical difficulties. We present a case of a circumferential rectal ESD using a pocket-creation method with two pockets. The associated planning, strategies, and outcome of the procedure are discussed.

// Yingshi Zhang 1, 2, 3, * , Jun Hou 4, * , Fan Feng 4, * , Dandan Li 2, 3 , Qiyu Jiang 4 , Xiaojuan Li 4 , Qingchun Zhao 2, 3 and Bo-An Li 1 1 Center for Clinical Laboratory, The 302nd Hospital of Chinese PLA, Beijing 100039, P.R. China 2 Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, P.R. China 3 Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China 4 Research Center for Clinical and Transitional Medicine, The 302nd Hospital of Chinese PLA, Beijing 100039, P.R. China * These authors contributed equally to this work Correspondence to: Bo-An Li, email: lba@263.net Qingchun Zhao, email: zhaoqingchun1967@163.com Keywords: UDP-glucuronosyltransferases 1A7, polymorphism, gastrointestinal carcinoma, cancer, network meta-analysis Received: May 16, 2017 Accepted: May 29, 2017 Published: June 27, 2017 ABSTRACT Objective: To identify the association between gastrointestinal carcinomas (GIC) risk and UDP-glucuronosyltransferases (UGTs) 1A7 polymorphisms through a systematic review and network meta-analysis. Results: Seventeen studies were eligible, which included 7738 patients and 18 analyses. First, it was found that compared with non-cancer participants, UGT1A7*1 were significantly decreased in cancer patient groups, especially in hepatocellular carcinoma, colorectal carcinoma, and Asian population groups; UGT1A7*2 was significantly increased in hepatocellular carcinoma and Asian population groups; and UGT1A7*3 was significantly increased in hepatocellular carcinoma, colorectal carcinoma, Caucasian, and Asian population groups. Second, the UGT1A7 polymorphism alleles contrast model and the categorized UGT 1A7 genotypes were compared, and the outcomes revealed that the ratio of UGT1A7*3 vs *2 increased, which may indicate an increased risk for cancer, especially for the pancreatic carcinoma and Caucasian groups. The ratio of Intermediate vs Low increased as well, which may also indicate an increased risk for GIC. Materials and Methods: PubMed, Embase, and the Cochrane library were searched for publications up until May 2017. First, the UGT 1A7 gene polymorphisms genotype in GIC patients were compared with a non-cancer control group, and second, the UGT1A7 polymorphism alleles contrast model and UGT 1A7 genotypes categorized according to enzymatic activity were examined. Conclusions: There is a cancer risk associated with increased UGT1A7 *2 for the hepatocellular carcinoma and Asian groups and with increased UGT1A7 *3 for the hepatocellular carcinoma, colorectal carcinoma, Caucasian, and Asian groups. Moreover, in Caucasian patients with GIC, the ratio of UGT1A7 *3 vs *2 was increased.

Background: High pretreatment plasma D-dimer levels can predict poor prognosis in various types of gastrointestinal carcinomas. Our meta-analysis explored the correlation between plasma D-dimer levels and prognosis in gastrointestinal malignancies. Methods: Two independent reviewers conducted a comprehensive search from PubMed, ScienceDirect, Embase, Web of Science and the Cochrane Library. All articles evaluating the correlation between pretreatment plasma D-dimer levels and prognosis in gastrointestinal malignancies were searched. We chose overall survival (OS) as the primary survival outcome measure and progression-free survival (PFS), disease-free survival (DFS) and cancer-specific survival (CSS) as the secondary survival outcome measures. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) from the eligible publications. Results: We included 30 studies involving 5928 gastrointestinal cancer patients. There was an obvious correlation between high D-dimer levels and poor OS (HR = 2.01, 95% CI = 1.72–2.36, P

Gastrointestinal tract neoplasia is on the third place of death statistics among oncological diseases, which is associated with the difficulty of early diagnosis of this disease. This study aims to evaluate applicability of delta-aminolevulinic acid / protoporphyrin IX photosensitizer (5-ALA / PpIX) as diagnosing agent for detection of small and large intestine neoplasia. The experiments were performed in vivo on white laboratorial rats. The animals were divided into 2 groups: control and experimental (overpopulation social stress and a diet, including nitrites and amines) ones. The results of the studies, averaged for each type of tissue, clearly show significant differences between normal tissues and malignant intestine tissues of the rats useful for fluorescent-based discrimination of the tissue state. The fluorescence from malignant areas in small and large intestine represented bright red fluorescence with specific maxima at 635 and 704 nm, typical for PpIX, due to the high accumulation of this photosensitizer in the affected tissues. The accumulation of protoporphyrin IX in the intestine cancerous tissues was very well pronounced. A contrast achieved between normal and abnormal tissue sites at 635 nm fluorescence emission was more than an order of magnitude in the case of large intestine neoplasia, which allows using the 5-ALA/PpIX as a sensitive indicator of gastrointestinal carcinoma.

Background: The blue laser imaging is a kind of new endoscopic system, sending 2 different wavelengths of laser. Result: It can observed that the gastrointestinal mucosa shallow capillaries and mucosal surface microstructure are shown in bright and high resolution images, thus being helpful to the diagnosis of early digestive tract cancer. It has unique advantages compared with the existing technique. This article reviewed the application of blue laser imaging in diagnosis of early gastrointestinal carcinoma.

BackgroundThe annual incidence of gastrointestinal carcinomas (stomach, small bowel, colon and rectum) is increasing in Western countries, reaching 50,000 new cases each year in France. Peritoneal carcinomatosis (PC) is diagnosed in 15% of these patients. Complete cytoreductive surgery (CCS) plus Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) is the only therapy that can offer patients with PC a chance for long-term survival with a 5 year overall survival (OS) rate of 30–60% versus 0–5% with systemic chemotherapy alone. However, CCS plus HIPEC still presents serious limitations and very few patients (10%) are candidates for these radical treatments. PC remains a palliative setting for 90% of patients with a median survival ranging from 15 to 25 months. Innovative surgical therapies such as Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) therefore need to be developed to improve the prognosis. Potential benefits were obtained after intraperitoneal nebulization of oxaliplatin in patients with advanced PC from colorectal cancer. Innovative surgical therapies such as pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been proposed as palliative locoregional treatment with some promising results. The dose of oxaliplatin currently established by nebulization (PIPAC) is really low at 92 mg/m2. However, the peritoneum acts as a barrier limiting the systemic passage of intraperitoneal drug. Oxaliplatin used at higher doses during PIPAC procedures could be a safe option and allow better intratumoral penetration of chemotherapy.Method and designThe proposed study is a multicenter phase I/II trial of oxaliplatin dose escalation during PIPAC. The aim is to determine the maximum tolerated dose of pressurized oxaliplatin administered by the intraperitoneal route (PIPAC) during two consecutive procedures at a 4–6 week interval for patients with extended peritoneal carcinomatosis from the gastrointestinal tract. Dose started at 90 mg/m2and escalation was in 50 mg/m2steps up to a maximum of 300 mg/m2.DiscussionOxaliplatin is an effective drug in gastrointestinal cancer and high doses given by the intraperitoneal route during HIPEC are well tolerated. In this phase I trial, we hypothesized that high-dose oxaliplatin during PIPAC is feasible and safe. The repeated local administration of high doses of oxaliplatin could improve tumor response and prognosis.Trial registrationProspective study. ClinicalTrials.gov: NCT03294252. EudraCT: 2016-003666-49

PLOD1 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1) is important for extracellular matrix formation and is involved in various diseases, including cancer; however, its role in gastrointestinal cancer is unclear. In this study, the expression of PLOD1 in gastrointestinal carcinoma and its relationships with patient survival were examined.Sample expression profiles were downloaded from the Gene Expression Omnibus database and methylation data were obtained from the Cancer Genome Atlas. Correlations between PLOD1 expression and clinicopathological features were analyzed by chi-square tests. Patient survival was evaluated by a Kaplan-Meier analysis.PLOD1 expression was upregulated in gastric cancer and colorectal cancer compared with that in normal tissues. High PLOD1 levels indicated a poor prognosis. The high methylation group had a significantly lower level of PLOD1 expression.These results indicated that PLOD1 is highly expressed in gastrointestinal carcinoma and is a potential prognostic marker and therapeutic target. The data also indicate that hypomethylation contributes to PLOD1 upregulation in gastric and colon cancers.

In this work, design, synthesis, and screening of thiophene carboxamides 4–13 and 16–23 as dual vascular endothelial growth factor receptors (VEGFRs) and mitotic inhibitors was reported. All compounds were screened against two gastrointestinal solid cancer cells, HepG-2 and HCT-116 cell lines. The most active cytotoxic derivatives 5 and 21 displayed 2.3- and 1.7-fold higher cytotoxicity than Sorafenib against HepG-2 cells. Cell cycle and apoptosis analyses for compounds 5 and 21 showed cells accumulation in the sub-G1 phase, and cell cycle arrest at G2/M phase. The apoptotic inducing activities of compounds 5 and 21were correlated to the elevation of p53, increase in Bax/Bcl-2 ratio, and increase in caspase-3/7.Compounds 5 and 21 showed potent inhibition againstVEGFR-2 (IC50 = 0.59 and 1.29 μM) and β-tubulin polymerization (73% and 86% inhibition at their IC50 values).Molecular docking was performed with VEGFR-2 and tubulin binding sites to explain the displayed inhibitory activities., Graphical Abstract

The robotic system for flexible endoscopy was first developed as a platform enabling tissue triangulation in natural-orifice translumenal endoscopic surgery (NOTES). Then endoscopic submucosal dissection (ESD) was introduced and has widely been employed for the treatment of early gastrointestinal carcinoma. Subsequently, endoscopists became well aware of the limitations of their endoscopic manipulations with the conventional flexible endoscopes developed for diagnostic use, which led to the development of robotic systems for upper/lower gastrointestinal tract endoscopes intended for therapeutic use. Most flexible robotic endoscopes have 2 mechanical arms attached to the head, allowing surgeons to perform endoscopic manipulations, such as grasping, traction, incision, excision, and hemostasis. However, there are still many challenges that remain to be addressed: the ideal robotic endoscope has not yet been realized. This article reviews the ongoing developments and our own efforts in the area of flexible robotic endoscopy.

Background & objectives: Colorectal cancer (CRC) is second only to breast cancer as the leading cause of cancer-related deaths in Malaysia. In the Asia-Pacific area, it is the highest emerging gastrointestinal cancer. The aim of this study was to identify single nucleotide polymorphisms (SNPs) and environmental factors associated with CRC risk in Malaysia from a panel of cancer associated SNPs. Methods: In this case-control study, 160 Malaysian subjects were recruited, including both with CRC and controls. A total of 768 SNPs were genotyped and analyzed to distinguish risk and protective alleles. Genotyping was carried out using Illumina′s BeadArray platform. Information on blood group, occupation, medical history, family history of cancer, intake of red meat and vegetables, exposure to radiation, smoking and drinking habits, etc was collected. Odds ratio (OR), 95% confidence interval (CI) were calculated. Results: A panel of 23 SNPs significantly associated with colorectal cancer risk was identified ( p0

A number of advances in both earlier diagnostic imaging and better treatment options for patients with intra-abdominal malignancies have occurred. Frequently such newer therapies rely on the integration of established surgical and radiation approaches potentially with newer chemotherapies and immunomodulators. Unfortunately, with further study some newer therapies have proven less beneficial than initially suggested. Keeping up with the data supporting newer alternatives, and determining which therapies to provide patients can be a challenge.

Tongguanteng (Marsdenia tenacissima), which is mainly distributed in the Yunnan and Guizhou provinces of China, was first recorded in Diannanbencao by Lan Mao of the Ming dynasty of China. According to recent pharmacological studies, the chemical composition of Tongguanteng (Marsdenia tenacissima) is complex and contains C 21 steroidal saponins, polysaccharides, alkaloids, and other molecules, which show anti-cancer effects on various tumor cell lines. It inhibits tumor cell proliferation and growth mainly by increasing the expression of apoptosis- and cell cycle-related proteins to promote apoptosis and arrest tumor cells in the G2/M or S phase. Downregulation of the expression of vascular endothelial growth factor-2/A and matrix metalloprotease-2/9 suppresses the formation of the tumor microvasculature, leading to tumor malnutrition, increased expression of interleukin-2, glutathione peroxidase, catalase, and superoxide dismutase, and decreased interleukin-10 and malondialdehyde expression, thereby enhancing immunity and antioxidation in the body.Additionally, inhibition of epidermal growth factor receptor, hepatocyte growth factor receptor, and tyrosine-protein kinase receptor activation enhances the anti-tumor efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors as well as inhibits P-glycoprotein and cytochrome P450 to increase the concentration of anti-tumor drugs in tumor cells.

Rationale:Gastrointestinal carcinoma is rare during pregnancy. It is usually diagnosed at an advanced stage because special gastrointestinal symptoms are generally overlooked during pregnancy, and there are many limitations and contraindications for using diagnostic tools during pregnancy.Pa

SUMMARY After a survey of the literature the author reports 4 new cases of gastric carcinoma and 10 of intestinal carcinoma in the dog. In the discussion the data of all known cases of gastro-intestinal carcinoma are analysed with regard to frequency, age, sex ratio, the site of the tumours in the stomach and intestine, the type of carcinoma, their relationship to ulcers and chronic inflammation and their metastasising disposition.

Objective To investigate the effectiveness of stilamin in malignant bowel obstruction (MBO) due to advanced gastrointestinal carcinoma patients.

The National Cancer Institute (NCI) announced in January 2006 the use of intraperitoneal (IP) combined with IV chemotherapy postoperatively as the preferred treatment method for advanced ovarian cancer. The announcement stimulated the need for oncology nurses to become familiar with IP chemotherapy administration and patient management guidelines. IP administration allows a high concentration of chemotherapy to come into direct contact with tumors and surrounding tissues and organs. IP chemotherapy also is administered in clinical trials and some clinical settings for other histologies, such as low-grade gastrointestinal carcinoma and appendiceal carcinoma, which tend to spread locally before invading the bloodstream. Local-regional chemotherapy potentially is an ideal treatment for local spread of those peritoneal carcinomas. Overall side effects from regional treatment are less severe than with systemic treatment. Oncology nurses can help minimize and alleviate discomfort associated with IP chemotherapy administration. This article focuses on nursing management strategies for patients receiving IP chemotherapy for ovarian cancer and other peritoneal carcinomatosis.

Endoscopic biopsies (EBs) are the gold standard for diagnosing gastrointestinal carcinoma yet no guidelines address EB use for prognostic and predictive molecular testing. This review summarizes the reported quantity and quality of EBs, their relationship with molecular test failure rates and the resultant concordance between EB and resection specimen. Studies reporting molecular testing on gastrointestinal carcinoma EBs published between 2002 and 2014 were identified. Details regarding EB quantity, quality, tumour content, molecular test failure rates as well as causes and concordance with resection specimens were reviewed. Seventy-five studies were identified. Eighteen (24%) reported the mean EB number per patient (median: 2.1, range: 1-6.6 EBs). Sixty-one (81%) reported the frequency of test failure (median: 0%, range: 0-100%). Twenty-two (29%) investigated EB and resection specimen concordance (range: 0-100%). EB quantity and quality affected neither concordance nor failure rate. In summary, few studies currently report EB quantity, EB quality or EB and resection specimen concordance. Reliable molecular testing in EBs appears achievable, and can be representative of resection specimens. Concordance depends upon the testing methodology and biomarker heterogeneity within the tumour. To improve patient care, EB sampling, processing and reporting requires standardization and needs optimization for each biomarker individually.

Background Bromelain and N-acetylcysteine are two natural, sulfhydryl-containing compounds with good safety profiles which have been investigated for their benefits and application in health and disease for more than fifty years. As such, the potential values of these agents in cancer therapy have been variably reported in the literature. In the present study, the efficacy of bromelain and N-acetylcysteine in single agent and combination treatment of human gastrointestinal carcinoma cells was evaluated in vitro and the underlying mechanisms of effect were explored. Methods The growth-inhibitory effects of bromelain and N-acetylcysteine, on their own and in combination, on a panel of human gastrointestinal carcinoma cell lines, including MKN45, KATO-III, HT29-5F12, HT29-5M21 and LS174T, were assessed by sulforhodamine B assay. Moreover, the influence of the treatment on the expression of a range of proteins involved in the regulation of cell cycle and survival was investigated by Western blot. The presence of apoptosis was also examined by TUNEL assay. Results Bromelain and N-acetylcysteine significantly inhibited cell proliferation, more potently in combination therapy. Drug-drug interaction in combination therapy was found to be predominantly synergistic or additive. Mechanistically, apoptotic bodies were detected in treated cells by TUNEL assay. Furthermore, Western blot analysis revealed diminution of cyclins A, B and D, the emergence of immunoreactive subunits of caspase-3, caspase-7, caspase-8 and cleaved PARP, withering or cleavage of procaspase-9, overexpression of cytochrome c, reduced expression of anti-apoptotic Bcl-2 and pro-survival phospho-Akt, the emergence of the autophagosomal marker LC3-II and deregulation of other autophagy-related proteins, including Atg3, Atg5, Atg7, Atg12 and Beclin 1. These results were more prominent in combination therapy. Conclusion We report for the first time to our knowledge the growth-inhibitory and cytotoxic effects of bromelain and N-acetylcysteine, in particular in combination, on a panel of gastrointestinal cancer cell lines with different phenotypes and characteristics. These effects apparently resulted from cell cycle arrest, apoptosis and autophagy. Towards the development of novel strategies for the enhancement of microscopic cytoreduction, our results lay the basis for further evaluation of this formulation in locoregional approaches to peritoneal surface malignancies and carcinomatosis.

We created a new clinical staging system for end-stage gastrointestinal (GI) carcinoma to clarify the therapeutic goals for these patients.Data were obtained from a retrospective review of medical charts. Based on daily clinical observation of 144 patients with end-stage GI carcinoma, we classified the terminal stages as A, B, C, and D.The mean durations of terminal stages A, B, C, and D were 19, 16.6, 6.6, and 1.8 days, respectively, in patients with end-stage gastric cancer and 28.5, 9.1, 5.4, and 1.9 days, respectively, in patients with colorectal cancer. Moreover, 88.0% of patients with gastric carcinoma and 82.6% of patients with colorectal carcinoma passed through terminal stages A, B, C, and D sequentially. The patients in terminal stage B experienced temporary relief of symptoms, but those in terminal stage C did not (P0.05).These terminal stages can easily be judged by clinical observation and may be an effective new tool with which to manage patients with end-stage GI carcinoma and their families.

はじめに: 神経因性疼痛あるいはモルヒネ不耐性を示す消化器末期癌の癌性疼痛に対して抗不整脈剤であるリドカインの皮下あるいは静脈内持続注入法を行った症例についてretrospectiveに, 有効性, 安全性について検討した. 方法: 疼痛制御を目的に入院した消化器末期癌患者に対しリドカイン持続注入法を32例に施行した. 効果判定は痛みのアセスメントを行い, Verbal Rating Scale (0-5) で4段階以上改善を著効, 3段階以上改善したものを有効とした. 結果: リドカインの平均維持量は911±411mg/日であり, 投与日数は30±34日であった. 併用オピオイドはモルヒネ25例, フェンタニル9 例であり, 本法併用で低量に維持された. 効果は著効16例, 有効12例であり (有効率87.5%), 無効例あるいは効果が持続しなかった計8例に, 持続クモ膜下ブロックの追加が必要であった. 副作用は, 持続皮下注入例の全例に皮膚刺入部の軽度発赤を認めた. 他に4 例 (12.5%) にせん妄, 失見当識が現れ, リドカインの減量を要したが, 重篤なものは認めなかった. 考察: リドカインの持続注入法は簡便であり, 消化器末期癌の疼痛緩和に有効かつ安全性の高い方法であると考えられた. しかし一方で, 本法の適応と効果には限界があり, 神経ブロックなど他の方法を併用した総合的な対応が必要である.

Monoclonal rat anti-idiotypic antibody (Ab2) BR3E4 mimicking the colorectal carcinoma (CRC)-associated epitope CO17-1A induced antigen-specific humoral and cellular immune responses in mice and rabbits. Ab2 BR3E4 was administered in a phase I trial to CRC patients either as intact IgG or as F(ab′) 2 coupled to keyhole limpet hemocyanin (KLH). There was a trend for the F(ab′) 2 -KLH-immunized patients to show higher immune response rates (18/21 and 5/15 patients with anti-anti-idiotypic antibodies and T cells, respectively) than the IgG-immunized patients (15/23 and 3/15 patients positive). Clinical responses were rare in these patients with liver metastases.

Minimal access techniques in surgery are improving. At the same time, the significance of interventional flexible endoscopy is increasing. Postoperative complications can be treated endoscopically with low rates of morbidity and mortality. Anastomotic strictures after resection of the esophagus, colon or rectum are mostly treated with success by endoscopy. Reoperations are almost never necessary in these cases today. Although the efficient detection of locoregional recurrence of gastrointestinal carcinoma is still the subject of controversial discussion, in contrast, endoscopic therapy for palliation by ablation, dilatation or stenting leads to a clear benefit for many of these patients.

Afshin Amini, Anahid Ehteda, Samar Masoumi Moghaddam, Javed Akhter, Krishna Pillai, David Lawson Morris Department of Surgery, St George Hospital, University of New South Wales, Sydney, NSW, Australia Background: Bromelain is a pineapple stem extract with a variety of therapeutic benefits arising from interaction with a number of different biological processes. Several preclinical studies and anecdotal clinical observations have reported the anticancer properties of bromelain. In the present study, we investigated the cytotoxic effects of bromelain in four human cancer cell lines of gastrointestinal origin and the mechanisms involved. Methods: The gastric carcinoma cell lines (KATO-III and MKN45) and two chemoresistant subpopulations of the HT29 colon adenocarcinoma cell line (HT29-5M21 and HT29-5F12) were treated with a range of concentrations of bromelain, as well as with cisplatin as a positive control. The effect of bromelain on the growth and proliferation of cancer cells was determined using a sulforhodamine B assay after 72 hours of treatment. Expression of apoptosis-associated proteins in MKN45 cells treated with bromelain was analyzed by Western blotting. Results: Data from our sulforhodamine B assay showed that bromelain inhibited proliferation of HT29-5F12, HT29-5M21, MKN45, and KATO-III cells, with respective half maximal inhibitory concentration values of 29, 34, 94, and 142 µg/mL. Analyzing the expression of proapoptotic and antiapoptotic proteins in bromelain-treated MKN45 cells, we observed activation of the caspase system, cleavage of PARP and p53, overexpression of cytochrome C, attenuation of phospho-Akt and Bcl2, and removal of MUC1. Apart from the caspase-dependent apoptosis observed, emergence of cleaved p53 supports a direct, extranuclear apoptotic function of p53. Moreover, interrupted Akt signaling and attenuation of Bcl2 and MUC1 oncoproteins suggest impaired survival of cancer cells. Conclusion: Our findings collectively indicate that bromelain exerts cytotoxic effects in a panel of human gastric and colon carcinoma cells. Our study of MKN45 cells implicated different mechanisms in bromelain-induced cell death. While promoting apoptosis with involvement of the caspase system and extranuclear p53, bromelain also appears to impair cancer cell survival by blocking the Akt pathway and attenuating Bcl2 and MUC1 oncoproteins. Keywords: bromelain, cytotoxicity, gastrointestinal carcinoma, MKN45, KATO-III, HT29

Diagnosis of hepatocellular carcinoma (HCC) on the basis of digital images is a challenging problem because, unlike gastrointestinal carcinoma, strong structural and morphological features are limited and sometimes absent from HCC images. In this study, we describe the classification of HCC images using statistical distributions of features obtained from image analysis of cell nuclei and hepatic trabeculae. Images of 130 hematoxylin-eosin (HE) stained histologic slides were captured at 20X by a slide scanner (Nanozoomer, Hamamatsu Photonics, Japan) and 1112 regions of interest (ROI) images were extracted for classification (551 negatives and 561 positives, including 113 well-differentiated positives). For a single nucleus, the following features were computed: area, perimeter, circularity, ellipticity, long and short axes of elliptic fit, contour complexity and gray level cooccurrence matrix (GLCM) texture features (angular second moment, contrast, homogeneity and entropy). In addition, distributions of nuclear density and hepatic trabecula thickness within an ROI were also extracted. To represent an ROI, statistical distributions (mean, standard deviation and percentiles) of these features were used. In total, 78 features were extracted for each ROI and a support vector machine (SVM) was trained to classify negative and positive ROIs. Experimental results using 5-fold cross validation show 90% sensitivity for an 87.8% specificity. The use of statistical distributions over a relatively large area makes the HCC classifier robust to occasional failures in the extraction of nuclear or hepatic trabecula features, thus providing stability to the system.

The nomenclature, definition and clinicopathological features of ovarian serous and mucinous tumours of borderline malignancy are reviewed. The reasons are considered for the proposal that serous neoplasms of borderline type should be subdivided into fully benign forms and low-grade adenocarcinomas. Because even the apparently benign forms can recur and can eventually give rise to a frank adenocarcinoma, it is suggested that they should still be considered as a distinct entity. Enteric type borderline mucinous tumours localized to the ovary do appear to be benign, but those associated with pseudomyxoma peritonei are probably metastases from a gastrointestinal carcinoma.

The value of lymphadenectomy in most localized gastrointestinal (GI) malignancies is well established. Our objectives were to evaluate the time trends of lymphadenectomy in GI cancer and identify factors associated with inadequate lymphadenectomy in a large population-based sample.Using the National Cancer Institute's Surveillance Epidemiology and End Results Database (1998-2009), a total of 326,243 patients with surgically treated GI malignancy (esophagus, 13,165; stomach, 18,858; small bowel, 7,666; colon, 232,345; rectum, 42,338; pancreas, 12,141) were identified. Adequate lymphadenectomy was defined based on the National Cancer Center Network's recommendations as more than 15 esophagus, 15 stomach, 12 small bowel, 12 colon, 12 rectum, and 15 pancreas. The median number of lymph nodes removed and the prevalence of adequate and/or no lymphadenectomy for each cancer type were assessed and trended over the ten study years. Multivariate logistic regression was employed to identify factors predicting adequate lymphadenectomy.The median number of excised nodes improved over the decade of study in all types of cancer: esophagus, from 7 to 13; stomach, 8-12; small bowel, 2-7; colon, 9-16; rectum, 8-13; and pancreas, 7-13. Furthermore, the percentage of patients with an adequate lymphadenectomy (49 % for all types) steadily increased, and those with zero nodes removed (6 % for all types) steadily decreased in all types of cancer, although both remained far from ideal. By 2009, the percentages of patients with adequate lymphadenectomy were 43 % for esophagus, 42 % for stomach, 35 % for small intestine, 77 % for colon, 61 % for rectum, and 42 % for pancreas. Men, patients65 years old, or those undergoing surgical therapy earlier in the study period and living in areas with high poverty rates were significantly less likely to receive adequate lymphadenectomy (all p 0.0001).Lymph node retrieval during surgery for GI cancer remains inadequate in a large proportion of patients in the USA, although the median number of resected nodes increased over the last 10 years. Gender and socioeconomic disparities in receiving adequate lymphadenectomy were observed.

Most patients diagnosed with gastrointestinal carcinomas are older people. The above-mentioned fact may lead to an erroneous finding that the problem does not concern patients aged between 20 and 30 years. Unfortunately, this assumption is often the reason for late diagnosis and delayed treatment of these malignancies. The study presented an example of three patients subject to surgical management of gastrointestinal carcinomas at the II Department of General and Gastroenterological Surgery, Medical University in Białystok.

SummaryCancer increases the risk of venous thromboembolism (VTE). Here, we investigated the contribution of microparticle (MP)-dependent procoagulant activity to the prothrombotic state in these patients. In 43 cancer patients without VTE at study entry and 22 healthy volunteers, markers of in vivo and MP-dependent coagulation were measured and patients were prospectively followed for six months for the development of VTE. Procoagulant activity of MPs was measured in vitro using a tissue factor (TF)-independent phospholipid dependent test, a factor Xa-generation assay with and without anti-TF, and a fibrin generation test (FGT) with and without anti-factor VII(a). Markers of in vivo coagulation activation and total number of MPs at baseline were significantly elevated in cancer patients compared to controls (F1+2 246 vs. 156 pM, thrombin-antithrombin complexes 4.1 vs. 3.0 mg/l, D-dimer 0.76 vs. 0.22 mg/l and 5.53 x 106 vs. 3.37 x 106 MPs/ml). Five patients (11.6%) developed VTE. Patients with VTE had comparable levels of coagulation activation markers and phospholipid-dependent MP pro-coagulant activity. However, median TF-mediated Xa-generation (0.82 vs. 0.21 pg/ml, p=0.016) and median VIIa-dependent FGT (13% vs. 0%, p=0.036) were higher in the VTE group compared with the non-VTE group. In this exploratory study the overall hypercoagulable state in cancer patients was not associated directly with the MP phospholipid-dependent procoagulant activity. However, in the patients who developed VTE within six months when compared to those who did not, an increased MP procoagulant activity was present already at baseline, suggesting this activity can be used to predict VTE.

Patients with inflammatory bowel disease, including both ulcerative colitis (UC) and Crohn's disease, are at increased risk for the development of gastrointestinal carcinoma, particularly colorectal adenocarcinoma. The current options to reduce this cancer risk include prophylactic colectomy, periodic endoscopic screening with colectomy performed in those patients found to have dysplastic colonic mucosa, or expectant management with no routine surveillance regimen. Despite the lack of data demonstrating effectiveness of surveillance colonoscopy, this approach has become the standard of care in most communities in the United States. Although it has fallen out of fashion in recent years, prophylactic colectomy remains a good option for reducing cancer risk for select patients with UC.

Immunotherapy-based strategies for gastrointestinal carcinomas (GIC) have been exploited so far, but these approaches have to face strong mechanisms of immune escape induced by tumours. We previously demonstrated that sub-therapeutic doses of an adenovirus expressing IL-12 genes (AdIL-12) mediated a potent antitumour effect against subcutaneous (s.c.) colorectal carcinomas (CRC) in mice pre-treated with low doses of cyclophosphamide (Cy). In our study we used this combination to assess its impact on the immunosuppressive microenvironment. In s.c. CRC model we demonstrated that non-responder mice failed to decrease Tregs in tumour, spleen and peripheral blood. Reconstitution of Tregs into tumour-bearing mice treated with combined therapy abolished the antitumoural effect. In addition, Cy + AdIL-12 modified Tregs functionality by inhibiting the in vitro secretion of IL-10 and TGF-β and their ability to inhibit dendritic cells activation. Combined treatment decreased the number of myeloid-derived suppressor cells (MDSCs) in comparison to non-treated mice and, interestingly, administration of Tregs restored splenic MDSCs population. Furthermore, combined therapy potently generated specific cytotoxic IFN-γ-secreting CD4+ T cells able to eradicate established CRC tumours after adoptive transfer. Finally, we evaluated the combination on disseminated CRC and pancreatic carcinoma (PC). Cy + AdIL-12 were able to eradicate liver metastatic CRC (47%) and PC tumour nodules (40%) and to prolong animal survival. The results of this study support the hypothesis that Cy + AdIL-12 might be a valid immunotherapeutic strategy for advanced GIC. Fil: Malvicini, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina Fil: Ingolotti, Mariana. Universidad Austral; Argentina Fil: Piccioni, Flavia Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina Fil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina Fil: Bayo Fina, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina Fil: Atorrasagasti, María Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina Fil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina Fil: Aquino, Jorge Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina Fil: Espinoza, Jaime A.. Universidad Adolfo Ibañez; Chile. Universidad de La Frontera; Chile Fil: Gidekel, Manuel. Universidad Adolfo Ibañez; Chile Fil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: Matar, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina

Many esophageal granular cell tumors (GCT) diagnosed incidentally during endoscopic examinations are less than 10 mm in diameter and can be treated endoscopically for histological examination of the entire lesion. However, it is difficult to remove them with sufficient surgical margins by conventional endoscopic methods because GCT, even if small in diameter, lie in the submucosal layer and lesions in the esophagus make it difficult to manipulate cutting devices. To overcome these drawbacks we tried using a ligating device that has recently been employed for endoscopic resection of early gastrointestinal carcinoma. Two patients diagnosed with GCT by biopsy, and with lesions confirmed to be in the submucosal layer by endoscopic ultrasonography, were treated easily and completely by this method without any complications. The tumors measured 5 × 5 mm and 8 × 6 mm. Endoscopic resection with the ligating device is thought to be the simplest and most effective endoscopic treatment for GCT.

We conducted this randomized trial to compare the LigaSure Vessel Sealing System with conventional methods in gastrointestinal carcinoma surgery at five specialty cancer hospitals.Patients with resectable stomach or colorectal cancers were randomized to the LigaSure (n = 100) or conventional surgery (n = 74) groups according to sealed envelopes. The operative data were compared.There were no significant differences in operating times, blood loss, postoperative complications, or hospital stay. However, at the hospital where most of the procedures took place, the LigaSure was associated with a shorter operating time (173 ± 43 min for gastric carcinoma and 157 ± 43 min for colorectal carcinoma vs 211 ± 55 min and 202 ± 55 min for conventional surgery; P = 0.0046 and P = 0.0200, respectively) and less blood loss (300 ± 196 ml and 150 ± 133 ml, respectively, vs 453 ± 387 ml and 382 ± 444 ml; P = 0.0482 and P = 0.0465, respectively).The LigaSure is safe for both gastric and colorectal cancer surgery with extended lymph node dissection. Used effectively, the device appears to reduce operating times and blood loss, although this requires confirmation in a larger series.

Gastrointestinal carcinoma was induced in male Wistar rats by administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). During the carcinogenic process, blood polyamine levels were measured, and pathological investigation was conducted simultaneously.The results were as follows : 1) Polyamine levels increased with the advancement of tumors.2) When tumors invaded to the submucosal layer or deeper, the blood polyamine levels became higher than those in control rats ; the increases in spermidine and spermine levels were especially remarkable.3) The level of each polyamine was significantly higher in tumor-bearing rats than in control rats.These results suggest the usefulness of blood polyamine assay as a marker of carcinogenesis.

Endosonography has been reported to be effective in the staging of gastrointestinal carcinoma. Pancreatic carcinoma is included in the new (1987) TNM classification. Resectability is abandoned in favour of depth of tumour invasion. In the author's preoperative study, endosonography was accurate for staging of tumour categories, and early stages of disease could be distinguished from advanced carcinomas. The presence or absence of regional lymph nodes can be detected. Tissue diagnosis by biopsy and endosonographyguidcd cytology is now possible. This imaging technique will become the standard procedure for the staging of pancreatic carcinoma.

KANO, Y., TANIGUCHI, T., UEMURA, Y., YOKOYAMA, K., OHYANAGI, H. and SAITOH, Y. Selection of Monoclonal Antibodies Detecting KM01 Antigen. Tohoku J. Exp. Med., 1990, 162 (2), 127-136 - Monoclonal antibodies (MoAbs) were selected for specific binding inhibition of KM01 to the KM01 antigen, which was detected in the serum of colorectal and other gastrointestinal carcinoma patients. Out of 91 MoAbs tested, 8 were found to have the inhibiting activity. The reactivity of these MoAbs with glycolipid antigen, which was isolated from cancer cell line, corresponded well with that of cancer patients sera. These monoclonal antibodies are thought to be useful in combination with KM01 for the construction of the second generation of the KM01 antigen-detecting system.

Letters to the Editor: The extension of disease is associated to an increased risk of venous thromboembolism (VTE) in patients with gastrointestinal (GI) carcinoma

Objective. To compare the detection rate of conventional ultrasonography and contrast-enhanced wide-band harmonic ultrasonographic imaging in the detection of small liver metastases. Methods. Consecutive patients with histologically proved gastrointestinal carcinoma liver metastases were studied. Biphasic helical computed tomography, conventional ultrasonography, and contrast-enhanced wide-band harmonic imaging were performed on all patients within a 5-day period. The biphasic helical computed tomographic scans were reviewed and interpreted by a skilled radiologist. The number of lesions and their descriptive characteristics were recorded for analysis. In addition, videotape recordings of the conventional ultrasonography and contrast-enhanced wide-band harmonic imaging were blindly reviewed, after which the number of detected lesions and their characteristics were then compared with those detected on biphasic helical computed tomography, considered the standard of reference. Results. Twenty-eight patients (10 female and 18 male; age range, 45-72 years) were studied. Conventional ultrasonography detected 37 (59%) of all lesions visualized by biphasic helical computed tomography. The detection rate for contrast-enhanced wide-band harmonic imaging was significantly higher (61 [97% of 63). In our series, two 10-mm lesions near the diaphragm were not visualized by wide-band harmonic imaging. Conclusions. The use of contrast-enhanced imaging techniques significantly improves the ultrasonographic detection of liver metastases. Our results achieved the sensitivity of biphasic helical computed tomography.