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The rise in the antibiotic resistance rate of Helicobacter pylori has led to an increasing eradication failure of this carcinogenic bacterial pathogen worldwide. This underlines the need for alternative antibacterial strategies against H. pylori infection. Antimicrobial photodynamic therapy (aPDT) is a promising non-pharmacological antibacterial technology. In this study, the selective killing activities of three benzylidene cyclopentanone (BCP) photosensitizers (Y1, P1 and P3) towards H. pylori over normal human gastric epithelial GES-1 cells were evaluated and the ex vivo photodynamic inactivation effect was preliminarily assessed on twelve H. Pylor-infected mice. Results showed that under the irradiation of 24 J/cm 2 532 nm laser, Y1, P1 and P3 at 2.5 μM induced a 3-log 10 reduction of H. pylori CFU (99.9% killing). Confocal images showed that P3, unlike Y1 and P1, could not be uptaken by GES-1 cells. P3 at 2.5 to 20 μM showed not significant (p > 0.05) phototoxicity to GES-1 cells, nevertheless, Y1 and P1 under the same concentrations exhibited remarkable phototoxicity to GES-1 cells. In the co-culture of H. pylori and GES-1 cells, P3 at 2.5 μM led to a complete eradication of H. pylori under the irradiation of 24 J/cm 2 532 nm laser. While for the GES-1 cells, no significant (p > 0.05) phototoxicity was observed under the same aPDT dosage. The ex vivo experiments showed that P3 mediated aPDT resulted in 82.4% to 100% reduction of H. pylori CFU without damaging the gastric mucosa. To sum up, P3 is a promising anti-H. pylori photosensitizer with the ability to selectively photo-inactivate H. pylori while sparing normal gastric tissues., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Prior small reports have postulated a link between gastrointestinal polyposis and childhood and young adulthood cancer (CYAC) treatment (therapy-associated polyposis; TAP), but this remains a poorly understood phenomenon. The aim of this study was to describe the phenotypic spectrum of TAP in a multi-institutional cohort. TAP cases were identified from eight high-risk cancer centers. Cases were defined as patients with ≥10 gastrointestinal polyps without known causative germline alteration or hereditary colorectal cancer predisposition syndrome who had a history of prior treatment with chemotherapy and/or radiotherapy for CYAC. A total of 34 TAP cases were included (original CYAC: 27 Hodgkin lymphoma, three neuroblastoma, one acute myeloid leukemia, one medulloblastoma, one nephroblastoma, and one non-Hodgkin lymphoma). Gastrointestinal polyposis was first detected at a median of 27 years (interquartile range, 20-33) after CYAC treatment. A total of 12 of 34 (35%) TAP cases had ≥50 colorectal polyps. A total of 32 of 34 (94%) had >1 histologic polyp type. A total of 25 of 34 (74%) had clinical features suggestive of ≥1 colorectal cancer predisposition syndrome [e.g., attenuated familial adenomatous polyposis (FAP), serrated polyposis syndrome, extracolonic manifestations of FAP, mismatch repair-deficient colorectal cancer, or hamartomatous polyposis] including 8 of 34 (24%) with features of multiple such syndromes. TAP is an apparently acquired phenomenon that should be considered in patients who develop significant polyposis without known causative germline alteration but who have had prior treatment for a CYAC. Patients with TAP have features that may mimic various hereditary colorectal cancer syndromes, suggesting multiple concurrent biologic mechanisms, and recognition of this diagnosis may have implications for cancer risk and screening., (©2020 American Association for Cancer Research.)

Current conventional endoscopes have restricted the accuracy of treatment delivery and monitoring. Over the past decade, there have been major developments in nanotechnology and light triggered therapy, potentially allowing a better detection of challenging lesions and targeted treatment of malignancies in the gastrointestinal tract. Theranostics is a developing form of personalized medicine because it combines diagnosis and targeted treatment delivered in one step using advances in nanotechnology. This review describes the light-triggered therapies (including photodynamic, photothermal, and photoimmunotherapies), nanotechnological advances with nanopowder, nanostent, nanogels, and nanoparticles, enhancements brought to endoscopic ultrasound, in addition to experimental endoscopic techniques, combining both enhanced diagnoses and therapies, including a developed prototype of a "smart" multifunctional endoscope for localized colorectal cancer, near-infrared laser endoscope targeting the gastrointestinal stromal tumors, the concept of endocapsule for obscure gastrointestinal bleed, and a proof-of-concept therapeutic capsule using ultrasound-mediated targeted drug delivery. Hence, the following term has been proposed encompassing these technologies: "Theranostic gastrointestinal endoscopy." Future efforts for integration of these technologies into clinical practice would be directed toward translational and clinical trials translating into a more personalized and interdisciplinary diagnosis and treatment, shorter procedural time, higher precision, higher cost-effectiveness, and less need for repetitive procedures.

Purpose: The optimal treatment for locally advanced GEJ and cardia adenocarcinoma is controversial. Several studies have shown that treating these patients with neoadjuvant chemoradiotherapy followed by surgery leads to survival benefits, and there are also studies that have declared conflicting results. It seems that there is still room for discussion. We calculated the survival rates and pathologic responses in our patients with characteristics which we mentioned above., Methods: Patients with locally advanced, non-metastatic GEJ and cardia adenocarcinomas (only patients with Siewert's type I and II), who were referred to Imam Khomeini hospital (Institute of cancer) between 2005 and 2014 and received neoadjuvant chemoradiation and underwent surgery were enrolled in this retrospective cohort study. Evaluations were done every 3 months., Results: Thirty-two patients enrolled in this study. Median follow up time was 23 months (Reverse Kaplan-Meier method). The rates of 1-year survival, 2-year survival, 3-year survival, 4-year survival, and 5-year survival were 75%, 52%, 52%, 37%, and 37%, respectively. No local recurrences occurred among patients; however, four patients experienced distal recurrence in the following locations: two cases (6.3%) in the liver, one case (3.1%) in the lung, and one case (3.1%) in the peritoneum. The rate of complete pathologic response (T 0 N 0 ) was 21.9%., Conclusions: Neoadjuvant chemoradiation in patients with locally advanced GEJ and cardia adenocarcinoma will lead to a survival benefit.

Objective: to retrospectively characterize changes in the hepatobiliary system in liver cirrhosis (LC) in the clean-up workers of the Chornobyl NPP accident and to determine the factors of disease progression according to the expert materials of the Central Interagency Expert Commission on Establishing the Causal Relationship of the Diseases with the influence of factors of Chornobyl NPP accident., Materials and Methods: Based on the data of 60 cases of the Central Interagency Expert Committee on establishing the causal link of diseases with the impact of the Chornobyl NPP accident, the factors of development, concomitant pathology and indicators of the hepatobiliary system status in 49 deceased and 11 alive clean-up workers with LC were investigated., Results: A retrospective study of the morphological changes of the hepatobiliary system in the clean-up workers with LC showed that the main pathologic anatomical diagnosis in 37.8 % of cases was small-nodal LC, in 8.9 % - micromacronodular, in 4.4 % - large-nodal, in 2.2 % - primary biliary LC, in the other 40 % of cases - LC with uncer- tain nodal structure, as well as 2 (4.4 %) cases of fatty liver and 1 case (2.2 %) of portal cirrhosis against the back- ground of fatty liver. Pathomorphological changes were characterized by expressed growth of fibrous tissue with replacement of the liver parenchyma (fields of fibrosis), increase in size and impaired structure of the liver, thick- ening and tightening of its capsule, fibrotic changes in other organs - gastric mucosa, pancreas, spleen, lungs, heart. Histological examination revealed lobe structure abnormalities, false lobules, periportal fibrosis, lymphoid-lympho- cytic infiltration, diffuse fatty small-sized and large-drop dystrophy, and hepatocyte atrophy. Common inflammato- ry processes and fibrotic changes of other organs and systems: cardiovascular, urinary, bronchopulmonary, stomach, pancreas and spleen made the course of the LC more severe. The most frequent were cardiovascular diseases, signi- ficantly more frequent among the deceased than alive patients: hypertension - 67.3 % and 45.5 %, p < 0.05, coro- nary heart disease - 57.1 % and 18 %, p < 0.05. In most cases, the cause of death in the clean-up workers with LC was hepatic and cellular failure (53.3 %), which together with hepatic-renal failure (17.8 %) made 71.1 %., Conclusion: Changes in the hepatobiliary system of change in in the clean-up workers with LC were characterized by marked growth of fibrotic tissue with replacement of the parenchyma and impaired liver structure, fibrotic changes in other organs, diffuse fatty small and large droplet dystrophy and atrophy of hepatocytes. The severe course of the LC with the manifestation of the disease at the stage of decompensation was due to a vague clinical picture, lack of subjective symptoms of liver disease, slow, steadily progressing development, lack of or inadequate examination and treatment, a significant number of concomitant pathology of other organs and systems. The fac- tors of the development of LC in the clean-up workers were the long course of chronic liver disease, numerous con- comitant pathology, long stay in the accident zone, the effect of ionizing radiation, as well as the lack of dispensa- ry supervision and adequate treatment., (E. O. Sarkisova, V. O. Sushko, A. A. Chumak, L. M. Ovsyannikova, O. V. Nosach, S. M. Alyokhina, T. O. Shyiko.)

Background: Definitive chemoradiotherapy is one of the treatment options for locally advanced esophageal cancer with curative intent. Esophagitis and pharyngitis are well-known adverse events that occur during chemoradiotherapy, but gastric mucosal injury has been less frequently reported compared to mucositis. Importantly, gastric mucosal injury is not well known, hard to manage, and sometimes fatal. Hence, we examined the clinical characteristics and the incidence of gastric mucosal injury after CRT for esophageal cancer., Methods: The medical records of patients who received definitive chemoradiotherapy combined with 5-fluorouracil and cisplatin for stage II/III (nonT4) esophageal squamous cell carcinoma from January 2001 to December 2010 at our institute were reviewed retrospectively., Results: We investigated 256 patients in whom, data for endoscopic abdomen examinations were both before and after CRT were available. Gastric mucosal damage was observed in 90 patients (35%) (grade 1/2/3 = 69/18/3). One of the possible risk factors identified in this study was the irradiation dose to abdomen. Compared to patients with cervical esophagus-upper thoracic esophagus tumor location, patients with middle thoracic esophagus-abdominal esophagus tumor location were more likely to develop gastric mucosal damage, although there was no statistically significant difference., Conclusions: It is important to consider gastric mucosal injury in patients who receive CRT, particularly when the irradiation field includes stomach.

Aim: The objective of this study was to investigate the possible synergy between doxycycline and photodynamic therapy against Helicobacter pylori and to evaluate the possible side effects on adenocarcinoma gastric cells with and without protoporphyrin IX. Materials & methods: Three H. pylori strains (ATCC 700392, 43504 and 49503) were grown on solid medium either with, or without, doxycycline at subinhibitory concentrations, and irradiated for 10, 20 and 30 minutes with a 400 nm-peaked light source. The phototoxicity tests on AGS cells were evaluated by MTT assay. Results: The photodynamic therapy and doxycycline combination showed an antibacterial synergistic effect with no significant toxicities. Conclusion: The synergistic treatment could be considered as an interesting therapeutic option.

Since many years it has been acknowledged that some bacterial species, among which H. pylori, P. aeruginosa, P. acnes accumulate endogenous photosensitizers (PS) in the form of porphyrins. This makes antibacterial photodynamic therapy (PDT) easier to perform due to the possible avoidance of external PS. In this study, we focus on gastric infections associated with the presence of Helicobacter pylori (H. pylori), known to accumulate and release both protoporphyrin IX (PPIX) and coproporphyrins. PDT versus H. pylori can be carried out by modified endoscopes or by new ingestible luminous devices under development. In both cases of in vitro and in vivo applications, either for therapy (PDT) or diagnosis, scientific literature lacks studies on the possible side-effects of light treatments on the surrounding tissues. To this aim we evaluated in vitro side-effects due to a possible intrinsic photosensitivity of gastric mucosa or to a photosensitization by the PS released from the bacterium itself. Photo-toxicity studies were conducted on the AGS cell line (ATCC® CRL-1739™), commonly used as a model for the stomach mucosa tissue, considering PPIX as the photosensitizing agent. After first evaluations of PPIX dark toxicity, its uptake and accumulation sites, photo-toxicity tests were conducted using a LED light source peaked at 400 nm, by varying both PPIX concentration (50 nM - 2 μM) and light dose in the range 0.6-13 J/cm 2 , representing different treatment procedures found in literature. The oxidative stress consequent to irradiation was investigated both in terms of ROS production and assessment of the activity of enzymes involved in ROS-related biological mechanisms. A significant phototoxic effect was found only for PPIX concentration > 100 nM for all tested light doses. This indicates that the evaluated photo-treatments do not cause side effects even with the sensitization due to PPIX released by the bacteria., (Copyright © 2018. Published by Elsevier B.V.)

In the present study, the effects and underlying mechanism of RbAp48 on the radiosensitivity of AGS gastric cancer cells was investigated. Cell proliferation was determined with an MTT assay. Flow cytometry was performed to evaluate the cell cycle and apoptosis. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were performed to detect mRNA and protein expression, respectively, including RbAp48, phosphoinositide 3‑kinase (PI3K) and protein kinase B (Akt). The results revealed that radiation enhanced the expression level of RbAp48 in AGS cells, and that RbAp48 combined with radiation reduced AGS cell proliferation. In addition, RbAp48 combined with radiation resulted in G2 phase arrest and induced apoptosis via regulation of the PI3K/Akt pathway. In conclusion, it was demonstrated that overexpression of RbAp48 enhanced the radiosensitivity of AGS gastric cancer cells via suppression of PI3K/Akt pathway activity, suggesting that RbAp48 may hold potential as a gene therapeutic strategy in the future, aiding in the treatment of gastric cancer.

Aim: To identify the clinical features of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with extra copies of MALT1., Methods: This is a multi-centered, retrospective study. We reviewed 146 patients with MALT lymphoma in the stomach who underwent fluorescence in situ hybridization analysis for t(11;18) translocation. Patients were subdivided into patients without t(11;18) translocation or extra copies of MALT1 (Group A, n = 88), patients with t(11;18) translocation (Group B, n = 27), and patients with extra copies of MALT1 (Group C, n = 31). The clinical background, treatment, and outcomes of each group were investigated., Results: Groups A and C showed slight female predominance, whereas Group B showed slight male predominance. Mean ages and clinical stages at lymphoma diagnosis were not different between groups. Complete response was obtained in 61 patients in Group A (69.3%), 22 in Group B (81.5%), and 21 in Group C (67.7%). Helicobacter pylori (H. pylori) eradication alone resulted in complete remission in 44 patients in Group A and 13 in Group C. In Group B, 14 patients underwent radiotherapy alone, which resulted in lymphoma disappearance. Although the difference was not statistically significant, event-free survival in Group C tended to be inferior to that in Group A (P = 0.10)., Conclusion: Patients with t(11;18) translocation should be treated differently from others. Patients with extra copies of MALT1 could be initially treated with H. pylori eradication, similar to patients without t(11;18) translocation or extra copies of MALT1., Competing Interests: Conflict-of-interest statement: All of the authors declare that they have no conflicts of interest associated with this article.

The aim of the research was to study the state of melatonin-positive-labeled cells (MPLC) of GM in desynchronosis in rats of different age and gender. 780 sections of the pyloric part of the gastric mucosa were studied in rats of both genders at the age of 9, 15 and 20 months. Animals were divided into intact control groups and the groups of the animals kept under the conditions of continuous light for 14 days - desynchronosis. The study was performed by the method of immunohistochemical staining with the primary antibodies to melatonin (Biorbyt, UK) and the secondary Alexa Fluor 488-conjugated antibody (Abcam, UK). In the course of the research it was found that MPLC in all experimental groups were mainly located in the basal and middle segments of the tubular glands of gastric mucosa and were represented by three types of cells. In desynchronosis the number of melatonin-positive-labeled cells significantly reduced in almost every age group, with the exception of females at the age of 20 months. Thus in elderly males and females the number of melatonin-positive-labeled cells of type III increases, whereas in young and mature males it decreases, and cells of type I predominate.

Yttrium-90 microsphere radioembolization ((90)Y MRE) is a therapy for liver malignancies by permanently implanting (90)Y-containing microspheres into tumors via hepatic artery. The etiology of persistent gastric ulcerations in patients presenting months after treatment remains unclear. Three patients who presented with gastric ulceration 4 to 13 months after (90)Y MRE were examined by esophagogastroduodenoscopy and biopsies. Pathological examinations showed multiple (90)Y microspheres scattered within the lamina propria and submucosa. Most of the microspheres were distributed in a linear fashion, consistent with an intravascular location; however, the vascular lumen and endothelial cells were not present. The microspheres were surrounded by fibrotic tissue infiltrated by chronic inflammatory cells and rare neutrophils. Epithelial granulation without pititis and miniaturized glands with intervening fibrosis were noted, compatible with chronic ischemic changes. These findings suggest that the persistent gastric ulceration is a result of localized ischemic injury in response to (90)Y MRE-induced vascular damage., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To understand the effects of γ-ray irradiation (IR) on the proliferation of gastric mucosal cells and to investigate the possible mechanisms that affect gastric mucosal cell proliferation., Study Design: C57BL/6J mice were exposed to IR at various doses (4, 8, and 15 Gy). We measured the changes of gastric mucosal BrdU-positive cells and the expression of β-catenin protein in the isthmus of fundic glands at days 1, 3, and 5 after irradiation., Results: Our data showed that the mice that received 15 Gy IR died within 4 days. IR caused gastric mucosal injury in mice, and the degree of injury increased along with the increasing doses. Compared with the control group, the proliferation of gastric mucosal cells was inhibited 1 day after irradiation. Cell proliferation was recovered on day 5 after low-dose (4 and 8 Gy) IR, while proliferation was continuously inhibited after high-dose (15 Gy) IR. β-catenin expression was increased and had a translocation in the isthmus of gastric mucosa., Conclusion: These findings suggest that gastric mucosa is sensitive to irradiation. The Wnt/β-catenin pathway is activated and plays a role in cell proliferation of gastric mucosa upon irradiation.

Purpose: To determine the maximum tolerated radiation dose (MTD) of an integrated boost to the tumor subvolume infiltrating vessels, delivered simultaneously with radical dose to the whole tumor and concomitant capecitabine in patients with pretreated advanced pancreatic adenocarcinoma., Methods and Materials: Patients with stage III or IV pancreatic adenocarcinoma without progressive disease after induction chemotherapy were eligible. Patients underwent simulated contrast-enhanced four-dimensional computed tomography and fluorodeoxyglucose-labeled positron emission tomography. Gross tumor volume 1 (GTV1), the tumor, and GTV2, the tumor subvolume 1 cm around the infiltrated vessels, were contoured. GTVs were fused to generate Internal Target Volume (ITV)1 and ITV2. Biological tumor volume (BTV) was fused with ITV1 to create the BTV+Internal Target Volume (ITV) 1. A margin of 5/5/7 mm (7 mm in cranium-caudal) was added to BTV+ITV1 and to ITV2 to create Planning Target Volume (PTV) 1 and PTV2, respectively. Radiation therapy was delivered with tomotherapy. PTV1 received a fixed dose of 44.25 Gy in 15 fractions, and PTV2 received a dose escalation from 48 to 58 Gy as simultaneous integrated boost (SIB) in consecutive groups of at least 3 patients. Concomitant chemotherapy was capecitabine, 1250 mg/m(2) daily. Dose-limiting toxicity (DLT) was defined as any treatment-related G3 nonhematological or G4 hematological toxicity occurring during the treatment or within 90 days from its completion., Results: From June 2005 to February 2010, 25 patients were enrolled. The dose escalation on the SIB was stopped at 58 Gy without reaching the MTD. One patient in the 2(nd) dose level (50 Gy) had a DLT: G3 acute gastric ulcer. Three patients had G3 late adverse effects associated with gastric and/or duodenal mucosal damage. All patients received the planned dose of radiation., Conclusions: A dose of 44.25 Gy in 15 fractions to the whole tumor with an SIB of 58 Gy to small tumor subvolumes concomitant with capecitabine is feasible in chemotherapy-pretreated patients with advanced pancreatic cancer., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Recently, endoscopic submucosal dissection (ESD) has been performed to treat early gastric cancer. The en bloc resection rate of ESD has been reported to be higher than that of conventional endoscopic mucosal resection (EMR), and ESD can resect larger lesions than EMR. However, ESD displays a higher complication rate than conventional EMR. Therefore, the development of devices that would increase the safety of ESD is desired. Lasers have been extensively studied as a possible alternative to electrosurgical tools. However, laser by itself easily resulted in perforation upon irradiation of the gastrointestinal tract. We hypothesized that performing ESD using a CO2 laser with a submucosal laser absorber could be a safe and simple treatment for early gastric cancer. To provide proof of concept regarding the feasibility of ESD using a CO2 laser with submucosally injected laser absorber solution, an experimental study in ex vivo and in vivo porcine models was performed., Methods: Five endoscopic experimental procedures using a carbon dioxide (CO2) laser were performed in a resected porcine stomach. In addition, three endoscopic experimental procedures using a CO2 laser were performed in living pigs., Results: In the ex vivo study, en bloc resections were all achieved without perforation and muscular damage. In addition, histological evaluations could be performed in all of the resected specimens. In the in vivo study, en bloc resections were achieved without perforation and muscular damage, and uncontrollable hemorrhage did not occur during the procedures., Conclusions: Endoscopic submucosal dissection using a CO2 laser with a submucosal laser absorber is a feasible and safe method for the treatment of early gastric cancer.

The efficiency of remaxol for prevention and treatment of chemoradiotherapy toxicity effects in patients with advanced oral cancer was evaluated. Ninety-five oral cancer patients were using remaxol both locally (mouth rinse solution) and by intravenous infusion, 87 patients were included in control group. Intravenous remaxol proved to be effective for mucositis and nephrotoxicity prevention by chemoradiotherapy.

CD24 is expressed in the putative stem cells within several tissues and is overexpressed in gastric and colonic adenocarcinomas. Perturbed CD24 expression may therefore alter the response of gastrointestinal epithelia to damage-inducing stimuli that induce cancer. We have investigated the effects of CD24 deletion on gastric responses to Helicobacter felis infection and γ-irradiation using CD24-null mice. Gastric CD24 expression was determined by immunohistochemistry in C57BL/6 mice. Female CD24-null and C57BL/6 mice were infected with H. felis for 6 wk, and inflammation, proliferation, apoptosis, and parietal cell numbers were assessed in gastric tissue sections. Apoptosis and proliferation were analyzed on a cell-positional basis in stomach, small intestine, and colon of CD24-null and C57BL/6 mice following γ-irradiation. Apoptosis was also assessed in HT29 cells following CD24 siRNA transfection. Of CD24-positive cells in the gastric corpus, 98% were H(+)-K(+)-ATPase-expressing parietal cells. CD24-null mice showed more prominent gastric H. felis colonization than C57BL/6 mice but displayed a marked reduction in corpus inflammation, reduced Ki67 labeling, and less gastric atrophy 6 wk following infection. Corpus apoptosis was elevated in CD24-null mice, but this did not increase further with H. felis infection as observed in C57BL/6 mice. More apoptotic cells were found following γ-irradiation in the stomach, small intestine, and colon of CD24-null mice and following CD24 knockdown in vitro. In conclusion, CD24 is expressed in gastric parietal cells, where it modulates gastric responses to H. felis and γ-radiation. CD24 also regulates susceptibility to apoptosis in the distal murine gastrointestinal tract.

We explored the biocompatible gold nanoparticles (GNPs) with surface modified by chitosan in the applications of cell's response to X-ray irradiation. Substantial amounts of chitosan modified gold nanoparticles (CS-GNPs) were found to be internalized in cell cytoplasm revealed by transmission electron microscopy. Their in vitro cytotoxicity effects on MGC-803 cells and GES-1 cells were observed at 24, 48 and 72 h. The MTT results showed that CS-GNPs own excellent biocompatibility. The dose enhancement based on CS-GNPs induced the damage of MGC-803 cells under X-ray irradiation, monitored by clonogenic cell survival assay. We also investigated their effects on the survival rates of MGC-803 cells during irradiation for a dose up to 10 Gy using a radio-oncology linear accelerator (6 MeV). The survival fraction of cells incubated with different concentration of CS-GNPs was obviously reduced in comparison with that irradiation alone. The result also revealed an increase of cell inhibition with increasing the concentration of CS-GNPs. In conclusion, CS-GNPs can enhance the cell radiation therapeutic sensitivity, and have potential application in tumor irradiation therapy in near future.

Purpose: To study the effect of aqueous propolis extract (AEP) against indomethacin (Indo)-induced gastric ulcers in irradiated and non-irradiated rats., Materials and Methods: Animals were irradiated at different radiation dose levels before the induction of ulcers. AEP was injected orally 1 hour before induction of gastric ulcers and the effects compared with those of lansoprazole (Lanso), which was used as a reference anti-ulcerogenic drug., Results: Pretreatment of rats, either irradiated or non-irradiated, with AEP effectively protected against Indo-induced gastric ulceration. This was associated with a reduction in acid output and peptic activity and an increase in the secretion of mucin. The mucosal prostaglandin E(2) (PGE(2)) level was also increased. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) were suppressed to the same extent after treatment. Both propolis and Lanso were effective in reducing the number of gastric lesions as well as the plasma level of malondialdehyde (MDA)., Conclusions: These findings indicate that the gastroprotective effect of AEP could be of value in the management of excessive gastric damage induced by radiation exposure.

Purpose: To investigate the protective effect of immune-enhanced diet (IED) on chemoradiation-induced injury of the gastrointestinal mucosa., Materials and Methods: Forty-eight Sprague-Dawley rats were divided into control (C, n=6), irradiation (IR, n=14), fluoropyrimidine (5-FU, n=14)-treated, IR + 5-FU (n=14)-treated groups. Half of each irradiated and/or 5-FU-treated groups were previously fed with IED containing arginine, omega-3-fatty acids and RNA fragments, while the other half were fed a standard rat diet (SD) for eight days before the induction of IR or injection of 5-FU. In IR groups, whole abdominal irradiation (11 Gy) was performed with 6 MV photons. In the 5-FU groups, fluoropyrimidine (100 mg/kg) was administered intraperitoneally 30 min prior to irradiation. All animals were sacrificed on the 4th day of IR or 5-FU injection., Results: Bacterial colony counts in the ceca and mesenteric lymph nodes of IED-fed rats, which have received either 5-FU and/or irradiation were significantly lower than the corresponding SD-fed groups. Morphometric results revealed that gastric, ileal and colonic injuries were less in IED-treated IR or IR + 5-FU + IED groups, as compared to SD-fed groups. However, IED did not alter DNA fragmentation ratios., Conclusion: Prophylactic feeding of IED has a protective effect on chemoradiation-induced gastrointestinal injury, which appears to involve the eradication of bacterial overgrowth.

Gastric surface pH (pH(o)) transiently increases in response to focal epithelial damage. The sources of that increase, either from paracellular leakage of interstitial fluid or transcellular acid/base fluxes, have not been determined. Using in vivo microscopy approaches we measured pH(o) with Cl-NERF, tissue permeability with intravenous fluorescent-dextrans to label interstitial fluid (paracellular leakage), and gastric epithelial intracellular pH (pH(i)) with SNARF-5F (cellular acid/base fluxes). In response to two-photon photodamage, we found that cell-impermeant dyes entered damaged cells from luminal or tissue compartments, suggesting a possible slow transcellular, but not paracellular, route for increased permeability after damage. Regarding cytosolic acid/base status, we found that damaged cells acidified (6.63 +/- 0.03) after photodamage, compared with healthy surface cells both near (7.12 +/- 0.06) and far (7.07 +/- 0.04) from damage (P < 0.05). This damaged cell acidification was further attenuated with 20 muM intravenous EIPA (6.34 +/- 0.05, P < 0.05) but unchanged by addition of 0.5 mM luminal H(2)DIDS (6.64 +/- 0.08, P > 0.05). Raising luminal pH did not realkalinize damaged cells, suggesting that the mechanism of acidification is not attributable to leakiness to luminal protons. Inhibition of apical HCO(3)(-) secretion with 0.5 mM luminal H(2)DIDS or genetic deletion of the solute-like carrier 26A9 (SLC26A9) Cl(-)/HCO(3)(-) exchanger blocked the pH(o) increase normally observed in control animals but did not compromise repair of damaged tissue. Addition of exogenous PGE(2) significantly increased pH(o) in wild-type, but not SLC26A9 knockout, animals, suggesting that prostaglandin-stimulated HCO(3)(-) secretion is fully mediated by SLC26A9. We conclude that cellular HCO(3)(-) secretion, likely through SLC26A9, is the dominant mechanism whereby surface pH transiently increases in response to photodamage.

Background: Cancer of unknown primary (CUP) is defined as histologically confirmed metastases in the absence of an identifiable primary tumor. Patients with solely liver metastases from adenocarinomas represent the most frequent subgroup with an unfavourable prognosis. The medium survival averages 6 to 9 months. No chemotherapheutic standard has been established., Case: We present a patient with hepatic CUP. After cycles of chemotherapy and hemihepatectomy the tumor returned and showed hepatic progression. The patient was evaluated for selective internal radiation therapy (SIRT). Three years after diagnosis she is still alive and tumorfree. Despite a good result and disease control our patient suffered radiation-induced ulceration in the oesophagus, stomach, and duodenum. This side effect appears in up to 12 % of patients, often very late after treatment, is refractory to pharmacotherapy and persistent over a long time., Conclusions: SIRT is a new, effective treatment in patients with hepatic CUP. Because of the anticipated increase of this therapy, adverse side effects such as ulcerations in the upper-GI tract secondary to ectopic implantation of microspheres may be seen more commonly. Awareness of this and the recognition of microspheres in biopsies is cardinal for appropriate management and maintenance of the patient's quality of life.

Background & Aims: The nuclear factor kappaB (NF-kappaB)/IkappaB-kinase-beta (IKKbeta) pathway has been shown to represent a key link between inflammation and cancer, inducing pro-inflammatory cytokines in myeloid cells and anti-apoptotic pathways in epithelial cells. However, the role of NF-kappaB pathway in gastric carcinogenesis and injury has not been well-defined. We derived mice with a conditional knockout of IKKbeta in gastric epithelial cells (GECs) and myeloid cells, and examined responses to ionizing radiation (IR) and Helicobacter felis infection., Methods: Ikkbeta(Deltastom) mice were generated by crossing Foxa3-Cre mice to Ikkbeta(F/F) mice. Cellular stress was induced with IR and H felis in Ikkbeta(Deltastom), Ikkbeta(F/F), and cis-NF-kappaB-enhanced green fluorescent protein (GFP) reporter mice. Gastric histopathology, apoptosis, proliferation, necrosis, reactive oxygen species, and expression of cytokines, chemokines, and anti-apoptotic genes were assessed. The role of myeloid IKKbeta in these models was studied by crosses with LysM-Cre mice., Results: NF-kappaB activity was upregulated in myeloid cells with acute H felis infection, but in GECs by IR or long-term H felis infection during progression to dysplasia. Deletion of IKKbeta in GECs led to increased apoptosis, reactive oxygen species, and cellular necrosis, and resulted in up-regulation of interleukin-1alpha and down-regulation of anti-apoptotic genes. Loss of IKKbeta in GECs resulted in worse inflammation and more rapid progression to gastric preneoplasia, while loss of IKKbeta in myeloid cells inhibited development of gastric atrophy., Conclusions: The loss of IKKbeta/NF-kappaB signaling in GECs results in increased apoptosis and necrosis in response to cellular stress, and accelerated development of dysplasia by Helicobacter infection., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Context: Selective internal radiation (SIR) therapy (SIRT) with yttrium 90 microspheres is increasingly used as an alternative therapeutic modality for patients with inoperable liver tumors. During administration of microspheres via the hepatic artery branches, some may on occasion be misdirected and be caught in the capillary bed of the duodenal and/or stomach., Objective: To better characterize the histopathologic features of these complications., Design: We report herein our experience with 3 patients who received SIR and developed gastroduodenal complications., Results: SIR-microsphere-induced gastroduodenitis was diagnosed from 10 days to 5 months after treatment. In all 3 cases, purple particles measuring about 40 microm in diameter were observed. An array of changes ranging from mucosal ulceration to epithelial changes were seen. Fibrinopurulent exudate was admixed with granulation tissue and reactive stromal cells. Epithelial changes included apoptosis and mucin depletion. Glandular cystic dilatation and epithelial flattening were also common as well as foveolar hyperplasia, suggestive of reparative changes in one case. Capillary ectasia and prominent plump endothelial cells were also present., Conclusion: The spectrum of the alterations is consistent with radiotherapy-induced changes. Given the recent approval by the US Food and Drug Administration for the use of SIRT, it is anticipated that more patients will be treated with this modality. Pathologists should become aware of the adverse effects associated with its use.

Gastrointestinal ulcers occur frequently and are mainly caused by H. pylori infection. In this report, we present a rare case of gastro-duodenal ulcer following selective internal radiation therapy (SIRT). SIRT is a palliative treatment for unresectable liver tumours. During SIRT, (90)Y-microspheres are infused into the hepatic artery. Pre-treatment evaluation for the presence of arterial shunts to neighbouring organs should be determined in order to avoid complications of SIRT.

Plasma concentrations of the hormone gastrin are elevated by Helicobacter pylori infection and by gastric atrophy. It has previously been proposed that gastrin acts as a cofactor during gastric carcinogenesis and hypergastrinemic transgenic INS-GAS mice are prone to developing gastric adenocarcinoma, particularly following H. pylori infection. We hypothesised that the increased risk of carcinogenesis in these animals may partly result from altered susceptibility of gastric epithelial cells to undergo apoptosis. Gastric corpus apoptosis was significantly increased 48 h after 12Gy gamma-radiation in mice rendered hypergastrinemic by transgenic (INS-GAS) or pharmacological (omeprazole treatment of FVB/N mice) methods and in both cases the effects were inhibited by the CCK-2 receptor antagonist YM022. However, no alteration in susceptibility to gamma-radiation-induced gastric epithelial apoptosis was observed in mice overexpressing progastrin or glycine-extended gastrin. Apoptosis was also significantly increased in gastric corpus biopsies obtained from H. pylori-infected humans with moderate degrees of hypergastrinemia. We conclude that hypergastrinemia specifically renders cells within the gastric corpus epithelium more susceptible to induction of apoptosis by radiation or H. pylori. Altered susceptibility to apoptosis may therefore be one factor predisposing to gastric carcinogenesis in INS-GAS mice and similar mechanisms may also be involved in humans.

Cyclooxygenase-1 (Cox-1) contributes to gastric defense of healthy tissue, but the role in the protection of the gastric epithelium after minor, acute damage has been difficult to study in vivo. Using 710-nm two-photon light absorption to create microscopic gastric damage in anesthetized mice with the gastric mucosal surface surgically exposed and perfused on the microscope stage, the acute response of surface cells to injury could be monitored using in vivo microscopy within seconds after injury. Using exogenous (Cl-NERF) and endogenous fluorophores, extracellular pH and cell death were monitored in real time during the entire damage and repair cycle. Two-photon damage was initiated by scanning approximately 200 microm(2) of gastric surface cells with high laser intensity, causing rapid bleaching of NAD(P)H fluorescence in optically targeted cells. In both Cox-1(+/-) and Cox-1(-/-) mice, a similar initial damage area expanded to include bystander epithelial cells over the next 2-5 min, with larger maximal damage noted in Cox-1(-/-) mice. The maximal damage size seen in Cox-1(-/-) mice could be reduced by exogenous dimethyl-PGE(2). All damaged cells exfoliated, and the underlying epithelium was coincidently repaired over a time interval that was briefer in Cox-1(+/-) (12 +/- 2 min, n = 12) than in Cox-1(-/-) (24 +/- 4 min, n = 14) mice. Directly after damage, pH increased transiently in the juxtamucosal layer (maximal at 3-6 min). A smaller peak pH change was noted in Cox-1(-/-) mice (DeltapH = 0.3 +/- 0.04) than in Cox-1(+/-) mice (DeltapH = 0.6 +/- 0.2). Recovery to normal surface pH took longer in Cox-1(-/-) mice (27 +/- 5 min) than in Cox-1(+/-) mice (12 +/- 1 min). In conclusion, constitutive loss of Cox-1 leaves the gastric mucosa more prone to damage and slowed repair of microlesions.

Unlike the small intestine and colon where gamma-radiation-induced apoptosis has previously been well characterized, the response of murine gastric epithelium to gamma-radiation has not been investigated in detail. Apoptosis was therefore assessed on a cell positional basis in gastric antral and corpus glands from adult male mice following gamma-radiation. Maximum numbers of apoptotic cells were observed in both antrum and corpus at 48 h and at radiation doses greater than 12 Gy. However, the number of apoptotic cells observed in the gastric epithelium was much lower than observed in the small intestine or colon after similar doses of radiation. Hematoxylin and eosin, caspase 3 immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling detected similar numbers and cell positional distributions of apoptotic cells, hence hematoxylin and eosin was used for subsequent studies. The highest numbers of apoptotic cells were observed at cell positions 5-6 in the antrum and cell positions 15-18 in the corpus. These distributions coincided with the distributions of PCNA-labeled proliferating cells, but not with the distributions of H(+)-K(+)-ATPase-labeled parietal cells or TFF2-labeled mucous neck cells. Decreased numbers of apoptotic gastric epithelial cells were observed in p53-null, bak-null, and bax-null mice compared with wild-type counterparts 6 and 48 h after 12 Gy gamma-radiation. Significantly increased numbers of apoptotic gastric epithelial cells were observed in bcl-2-null mice compared with wild-type littermates 6 h after 12 Gy gamma-radiation. Radiation therefore induces apoptosis in the proliferative zone of mouse gastric epithelium. This response is regulated by the expression of p53, bak, bax, and bcl-2.

The aim of this study was to investigate the location of photodegradable nitric oxide (NO) store using a pharmacological approach in mouse gastric fundus. The ultraviolet light irradiation (UV; 360 nm, 60 s), electrical field stimulation (EFS; 4 Hz, 25 V, 1 ms, 15s-train), exogenous nitric oxide (NO; 10 microM), nitroglycerin (100 microM) and isoproterenol (5 nM) induced relaxation in mouse gastric fundus preparations in the absence or presence of an intact mucosa. The NO scavenger, haemoglobin (20 microM), significantly inhibited the relaxation of intact and denuded mucosa stomach fundus to UV light irradiation, EFS and NO, but not to nitroglycerin and isoproterenol. The superoxide anion generator, pyrogallol (50 microM), inhibited relaxation of intact and denuded mucosa stomach fundus induced by UV light irradiation, EFS, NO, but not to nitroglycerin and isoproterenol. The inhibition observed with pyrogallol was prevented by exogenous Cu/Zn superoxide dismutase (SOD; 100 U/ml), a membrane impermeable antioxidant. The Cu/Zn SOD inhibitor, diethyldithiocarbamic acid (DETCA; 8 mM), inhibited the relaxation of intact and denuded mucosa stomach fundus to UV light irradiation, EFS, NO and nitroglycerin but not those to isoproterenol. Exogenous SOD (100 U/ml) partially prevented the inhibitory effect of DETCA on relaxation to UV light irradiation, EFS, NO but not to nitroglycerin. DETCA-induced inhibition of the nitroglycerin-induced relaxation was partially prevented by the cell-permeable polyethylene-glycol-superoxide dismutase (100 U/ml). These results indicate that photodegradable NO store is, at least in part, unlikely to be within smooth muscle cells, and furthermore, that UV light-induced relaxation is not dependent on gastric mucosal layer.

Purpose: The aim of this study was to assess the tolerance dose of gastric mucosa for single-fraction computed tomography (CT)-guided, high-dose-rate (HDR) brachytherapy of liver malignancies., Methods and Materials: A total of 33 patients treated by CT-guided HDR brachytherapy of liver malignancies in segments II and/or III were included. Dose planning was performed upon a three-dimensional CT data set acquired after percutaneous applicator positioning. All patients received gastric protection post-treatment. For further analysis, the contours of the gastric wall were defined in every CT slice using Brachyvision Software. Dose-volume histograms were calculated for each treatment and correlated with clinical data derived from questionnaires assessing Common Toxicity Criteria (CTC). All patients presenting symptoms of upper GI toxicity were examined endoscopically., Results: Summarizing all patients the minimum dose applied to 1 ml of the gastric wall (D(1 ml)) ranged from 6.3 to 34.2 Gy; median, 14.3 Gy. Toxicity was present in 18 patients (55%). We found nausea in 16 (69%), emesis in 9 (27%), cramping in 13 (39%), weight loss in 12 (36%), gastritis in 4 (12%), and ulceration in 5 patients (15%). We found a threshold dose D(1 ml) of 11 Gy for general gastric toxicity and 15.5 Gy for gastric ulceration verified by an univariate analysis (p = 0.01)., Conclusions: For a single fraction, small volume irradiation we found in the upper abdomen a threshold dose D(1 ml) of 15.5 Gy for the clinical endpoint ulceration of the gastric mucosa. This in vivo assessment is in accordance with previously published tolerance data.

The age-dependent series of stylized computational phantoms developed at the Oak Ridge National Laboratory in the late 1970's to early 1980's has found wide applicability in dosimetry studies ranging from dose coefficient compilations for external and internal photon emitters, simulations of patient radiological exams, and dose reconstruction activities. In the present study, we report on a series of revisions to the Oak Ridge National Laboratory series for their intended use within the MIRD schema of medical internal dosimetry. These revisions were made to (1) incorporate recent developments in stylized models of the head, brain, kidneys, rectosigmoid colon, and extra-pulmonary airways; (2) incorporate new models of the salivary glands and the mucosa layer of the urinary bladder, alimentary tract organs, and respiratory airways; (3) adopt reference values of elemental tissue compositions and mass densities from ICRP Publication 89 and ICRU Report 46; (4) provide for explicit treatment of left and right organs within organ pairs; (5) provide for a systematic tabulation of electron absorbed fractions as a function of energy and subject age for all internal organs; and (6) provide for methods of deriving patient-specific values of the specific absorbed fraction for both electrons and photons through interpolation/extrapolation of their phantom-derived values. While tomographic computational phantoms provide improved anatomic realism given the CT or MR image sets used in their construction, there does not yet exist a comprehensive series of reference pediatric tomographic phantoms, nor the ability to simulate very fine anatomic structures as can be modeled via mathematical approximation. Consequently, stylized pediatric phantoms will continue to fill this data need in medical dosimetry.

Backgrounds and Aims: Most low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas respond to eradication of H. pylori, however, some are refractory. The effectiveness of radiotherapy for MALT lymphoma refractory to H. pylori eradication has been demonstrated. However, the long-term outcome and associated late radiation morbidity of radiotherapy for gastric MALT lymphoma are unclear. We evaluated the efficacy of radiotherapy and the radiation-associated adverse effects for gastric MALT lymphoma refractory to H. pylori eradication therapy., Methods: Eighteen patients with H. pylori-positive gastric MALT lymphoma received H. pylori eradication therapy, of which three patients refractory to eradication of H. pylori were subsequently treated with irradiation (median 39 Gy, range 36-40 Gy). Efficacy of radiotherapy and associated radiation morbidity were evaluated. Adverse events were evaluated according to RTOG and NCI-CTC criteria., Results: Radiation was well tolerated. All three patients treated with radiotherapy achieved complete remission, which was sustained for a median follow-up period of 42.0 months (range, 24-72 months). As acute radiation side effects, all patients experienced mild nausea (Grade 1 by RTOG and 1 point [1 category] in NCI-CTC). One patient had Grade 1 appetite loss. There were no severe late adverse events. One patient had left kidney atrophy of approximately 10%, but none had renal dysfunction., Conclusions: Radiotherapy for patients with gastric MALT lymphoma refractory to H pylori eradication was effective without any critical acute or late adverse events.

This study sought to explore the effects of He-Ne laser irradiation on the gastric mucosa of experimental chronic atrophic gastritis (CAG) in rat. Fifty-two male adult Wistar rats were randomly divided into five groups including normal control group, model group and three different doses He-Ne laser groups. The CAG model in rats was made by administering (per gastrogavage) a compositus liquor, including 2% sodium salicylate and 30% alcohol, for 8 weeks to stimulate the rat's gastric mucosa, combined with irregular fasting and compulsive sporting as pathogenic factors. He-Ne laser therapy was used at different doses of He-Ne laser, once a day for twenty days, then the morphological changes and the expression of cyclinD1 were observed. Compared with untreated group, the gastric mucosa of 3.36J x cm(-2) He-Ne laser group was significantly thicker (P < 0.01), the inflammatory cells of gastric mucosa were decreased (P < 0.05), the morphology, structure and volume of the cells were restored or nearly normal and the expressions of cyclinD1 were higher (P < 0.05). In a word, small dose He-Ne laser (3.36 J x cm(-2)) has a good adjuvant therapeutic effect on rat's CAG.

The effect of 3- or 6-Gray (Gy) whole-body gamma irradiation on basal and stimulated gastric acid secretion was studied in pylorus-ligated rats. Different groups of rats were irradiated with a single 3- or 6-Gy fraction and examined 7 days after irradiation. Exposure to 3-Gy fraction led to marked increase in basal (nonstimulated) gastric acid output in the 4-h pylorus-ligated rat (47.5% compared with unirradiated controls). After exposure to 6 Gy, only 18.2% increase in gastric acid output was noted compared with unirradiated controls. Under pentagastrin or histamine stimulation, gastric acid secretion in those irradiated with 3- or 6-Gy fraction was markedly reduced compared to that of unirradiated controls. Exposure to 3- or 6-Gy gamma irradiation intensified the degree of gastric mucosal injury evoked by indomethacin or 50% ethanol in a dose-dependent manner. It is concluded that in the pylorus-ligated rat model, lower doses of gamma irradiation increase basal gastric acid secretion and impair the gastric mucosal barrier with marked increase in its permeability to H+ following stimulation of acid secretion or exposure to barrier breakers. Exposure to irradiation is likely to result in failure of the parietal cell to respond to direct stimulation with histamine or pentagastrin.

The aim of the study was to evaluate the influence of non-invasive laser therapy on the efficacy of gastric ulcer therapy. The study revealed shortening of the time to ulcer cicatrization in patients who were treated with laser emission of the organospecific iridic zones and immunocompetent body parts in addition to standard drug therapy.

We scored oral mucositis and gut toxicity and measured sugar permeability testing among 56 recipients of a haematopoietic stem cell transplant (HSCT) given myeloablative conditioning with idarubicin, cyclophosphamide and TBI, and a group of 18 patients given cytotoxic chemotherapy for newly diagnosed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Gut integrity was already disturbed in the AML/MDS group as measured by the lactulose/rhamnose ratio (L/R ratio=0.09) before therapy and was severely perturbed (L/R ratio >0.13) for a month after HSCT. Oral mucositis and to a lesser extent gut toxicity was only significantly correlated with disturbed permeability in the transplant group. The data suggest that sugar permeability, oral mucositis and gut toxicity measure different features of mucosal damage after intensive cytotoxic therapy.

In an effort to find an effective concentration that could minimize the side effect for clinical applications, and to understand the potential synergistic effect of hyperosmotic agents on optical clearing of gastric tissues, porcine stomach tissues (pyloric mucosa) applied with a mixed solution of glycerol and dimethyl sulfoxide (DMSO) are investigated with near infrared reflectance spectroscopy. Five chemical solutions, containing 80% glycerol, 50% DMSO, 50% glycerol with 10% DMSO, 20% DMSO and 30% DMSO, respectively, are prepared and studied; all of which show significant improvement in light transmittance, and thus reduction of the light scattering of tissue. It is found that, among the solutions investigated, 50% glycerol with 30% DMSO achieves the best clearing effect on the improvement of light penetration. Light transmittance is increased approximately 29% and diffuse reflectance decreased approximately 31% at 30 min after the topical application of 50% glycerol with 30% DMSO. This solution shows significantly stronger effect than 80% glycerol on optical clearing even though they have the same osmolarity. 80% glycerol leads to 23% increase of light transmittance and 24% decrease of diffuse reflectance. The mixed solution of 50% glycerol and 20% DMSO has less osmolarity than the solution of 80% glycerol, but they achieve a similar degree of optical clearing. In other words, the clearing effect of glycerol is enhanced by adding DMSO into it. It is suggested that membrane penetration and carrier effect of DMSO probably accounts for this synergistic effect.

The study included 52 patients after gastrectomy for carcinoma of the proximal part of the stomach. Endoscopic laser therapy was made in 32 patients to reduce inflammation in the anastomosis zone 2-3 weeks after surgery. Drug therapy was made in 20 patients within the same time period. Histochemical study of the biopsy material of esophageal and intestinal part of the anastomosis was carried out. It is revealed that application of copper vapor laser early after surgery reduces edema and inflammation in the anastomosis zone for 2 weeks as well as accelerates the growth of granulation tissue forming a delicate scar thus preventing formation of scar stenosis.

Gastric mucosa and blood plasm were studied in 82 patients with gastroduodenal ulcer for content of adenylic nucleotides (AMP, ADP and ATP), histamine, amino acids. It was found that the above nucleotides occurred in the examinees in subnormal quantities. The necessary substrates, aspartate in particular, were deficient. This may lead to impairment of biosynthetic processes, to imbalance of defense factors. Photon therapy of gastroduodenal ulcer corrects bioenergetic metabolism in gastric mucosa thus producing a marked therapeutic effect.

The initial concept of delivering RF energy to the gastroesophageal junction for the treatment of GERD was based on the well-established safety profile and scientific clinical evidence supporting the effectiveness of this technology in other disease states. As described in this article, the Stretta procedure is an endoluminal procedure inducing collagen tissue contraction, remodeling, and modulation of the triggering threshold for transient LES relaxations. The preclinical experience with this device included feasibility studies to determine optimal treatment parameters and device design. This was followed by longitudinal animal studies to elucidate the mechanism of safety and effect of this intervention as it relates to LES physiology and histopathology. In these studies, RF elevated the LES pressure and gastric yield pressure in a porcine model of botulinum toxin induced LES hypotension. The elevation in GYP more than 6 months was confirmed in a subsequent evaluation. Thickening of the LES after RF delivery has been demonstrated using histopathological evaluation and EUS. Additionally, using a canine model of triggered transient LES relaxations (tLESR), RF significantly reduced the frequency of tLESRs and reflux events. Additional evaluation was performed in human subjects undergoing esophagectomy, confirming feasibility and Histopathologic results of the treatment. Subsequent clinical trials confirm the safety and mechanism of action data of these pre-clinical studies and are presented in this publication.

The benchmarks in GERD therapy comprise the commonly prescribed anti-secretory drugs (H2RAs and PPIs) and anti-reflux surgery. Although drugs are typically safe, cost and patient compliance are challenges to long-term management. Furthermore, while heartburn may be controlled with aggressive medical therapy, other symptoms such as regurgitation may persist, reducing patient satisfaction and adversely affecting quality of life. Surgical anti-reflux procedures, most commonly laparoscopic Nissen fundoplication, improve GERD symptoms and normalize esophageal acid exposure in most patients. Patient perception of the potential risk of abdominal surgery and general anesthesia may limit willingness to undergo surgery resulting in only a small portion of GERD sufferers that actually undergo anti-reflux surgery each year. Overall, the Stretta procedure is well tolerated, with an acceptably low incidence of complications and obviates the need for anti-secretory drug therapy for most patients at the 6- and 12-month follow-up. GERD symptom scores, heartburn, satisfaction, and SF-36 scores significantly improve over the baseline and this effect lasts at least 12 months. The symptomatic improvement after Stretta at 12 months in one trial (GERD score, 27 to 9) is similar to that reported by Velanovich after fundoplication (GERD score, 27 to 3). Furthermore, the significant reduction in median esophageal acid exposure time (distal 10.6% to 6.2%, proximal 1.9% to 0.9%), provides objective evidence of an anti-reflux effect. Although the reported studies have been non-randomized, the objective improvement observed in esophageal acid exposure and the persistence of GERD symptom score improvement with repeated measure analysis over a course of 12 months make a significant placebo effect unlikely. Stretta is a promising new technology for the treatment of GERD that should be considered for patients who wish to discontinue a lifelong anti-secretory medication regimen or who have incomplete GERD symptom control on drugs, but are not yet accepting anti-reflux surgery.

In order to understand the mechanisms of intestinal injuries due to ionizing radiation, various groups of rats have been whole-body irradiated by gamma-rays at two dose rates (1 Gy/min and 1 Gy/hr), three doses (1, 2 and 4 Gy) and two post-irradiation times (24 and 48 hr). Duodenum samples of the animals were prepared for light microscopy, according to classical methods for histology and TUNEL reaction. A small number of morphological differences were observed within the mucosa between the two dose rates used. The extent and the number of lesions were more important at the slower dose rate (1 Gy/hr) and increased with the total dose. Clear cavities were seen inside the lamina propria which appeared like capillaries free of blood cells. The mitotic index calculated from crypt cells showed a regular decrease with the dose, which was exacerbated at 48 hr post-irradiation. On the other hand, the apoptotic index increased with the dose and the postirradiation time. Our results lead to hypothesize another mechanism of intestinal mucosa renewal allowing to explain mucosa denudations observed after radiotherapy. Thus we propose a new concept in which the duodenal mucosa renewal may occur by whole villi shedding into the duodenal lumen.

Object of the investigation were effects of elevated radiation background on specific body systems in two generations of rats that had been chronically exposed to radiation in the most badly polluted areas of the Kaluga district and eaten local food. Findings included some compensatory deviations in the white blood count, decrease in karyocytes and increase in chromosomal aberration rate in nucleus-containing cells from the femoral bone marrow in younger animals of several groups, morphologic and histochemical shifts in mucous membrane of the esophagus and the stomach, and morphofunctional changes in neurons and glia of the cerebral cortex. These changes are compensatory-adaptive by nature and indicative of destabilization of homeostasis in experimental animals.

The efficacy of allogeneic, haemopoietic stem cell transplantation (HSCT) is limited by concomitant toxicity. This has led to the development of less toxic, reduced intensity conditioning (RIC) protocols, whose therapeutic benefit is largely related to an associated, immunity-mediated graft-versus-malignancy effect rather than by the cytotoxic treatment itself. Murine HSCT models suggests that acute graft-versus-host disease (GVHD) increases with the intensification of the conditioning regimen mediated by loss of integrity of the gut mucosa barrier. The present study was undertaken to investigate gastro-intestinal (GI) permeability during allogeneic HSCT with RIC. In 17 patients (myeloablative conditioning in nine, RIC in eight), intestinal permeability was assessed by a (51)Cr-EDTA absorption test before the start of cytotoxic treatment the day before stem cell infusion (day -1) and 4, 7 and 14 days after stem cell infusion. Patients receiving RIC did not develop any significant increase in intestinal permeability during the transplantation course but in myeloablatively conditioned patients there was a significant increase in intestinal permeability the day before the stem cell infusion (P < 0.005), on day 4 (P < 0.005), on day 7 (P < 0.01) and on day 14 (P < 0.005) after stem cell infusion, compared with the baseline. Myeloablative conditioning also revealed increased intestinal permeability on day 7 compared with the RIC (P < 0.05). The finding of preserved intestinal-barrier function during allogeneic HSCT with RIC is discussed, with reference to the hypothesis that GI tract damage may be an important initiating event of GVHD.

Background: A new technique of 805 nm semiconductor diode laser-tissue interaction potentiation using indocyanine green (ICG) as an exogenous chromophore has been assessed for use in the palliation of advanced gastrointestinal malignancy., Materials and Methods: The tissue effects of ICG potentiated 805 nm laser were assessed both in-vivo using rat stomach and colon, and in vitro using normal and neoplastic human gastric and colonic mucosa., Results: Intravenous ICG did not potentiate the laser-tissue effects of the 805 nm laser in in-vivo studies. Local techniques of ICG application (submucosal injection +/- surface painting of 0.1% ICG solution) enhanced the total depth and diameter of laser induced thermal injury in all in-vitro tissues. Without ICG enhancement thermal tissue injury was minimal in normal gastric and colonic mucosa., Conclusion: Local techniques of ICG application enhance laser induced thermal injury in normal and neoplastic gastric and colonic mucosa. This may permit targeting of 805 nm laser-tissue effects with minimal collateral damage during endoscopic laser palliation of advanced gastrointestinal malignancy., (Copyright Harcourt Publishers Limited.)

Preoperative chemotherapy combined with radiotherapy (chemrad) is a common type of neoadjuvant treatment for esophageal adenocarcinoma or squamous cell carcinoma. The purpose of this study was to describe the clinical, histologic, proliferative (MIB-1), and oncogenetic (p53) features of 15 patients with gastric dysplasia-like epithelial atypical changes associated with preoperative chemrad for esophageal cancer. Two of these cases were initially misinterpreted as dysplasia, which led to partial gastrectomy. The findings were compared with 12 age- and sex-matched patients with known gastric dysplasia. Cases with gastric dysplasia-like epithelial atypia were significantly associated with a flat gross appearance, a patchy distribution, foveolar and gland involvement, surface maturation, an open nuclear chromatin pattern with prominent nucleoli, retention of nuclear polarity, mitoses confined to the pits, lack of atypical mitoses, cytoplasmic hypereosinophila and/or vacuolization, a lack of association with intestinal metaplasia, and finally, irregular glandular microcystic change, in comparison to the dysplasia controls. Furthermore, the study cases showed MIB-1 positivity restricted to the deep foveolar epithelium and an absence of p53 staining in 14 of 15 cases, in contrast to the dysplasia controls, in which MIB-1 stained both the deep and superficial foveolar epithelium and surface epithelium, and p53 was positive in all cases (100%). In summary, a number of histologic and immunohistochemical features may distinguish gastric dysplasia-like epithelial atypia associated with chemrad for esophageal cancer from true dysplasia. Pathologists should be aware of this entity and its histologic and immunohistochemical features to avoid misinterpretation and prevent unnecessary treatment.

Shown in the paper are pathogenetic mechanisms of peptic ulcer of the stomach and duodenum that can be subjected to curative correction with the aid of EHF-therapy. Results are submitted of treatment and examination of 72 patients with peptic ulcer in whom EHF-therapy was instituted to deal with their condition. Recommendations are given on optimization of methodological approaches to the conduction of EHF-procedures, on combination of EHF-therapy with other methods for treating peptic ulcer.

Background: The spectral irradiance delivered by a variety of gastrointestinal endoscopes was measured as a function of wavelength and used to estimate the amount of light delivered to the mucosal surface during routine endoscopic procedures., Methods: Spectral irradiances from seven different endoscopes were measured using a commercial spectroradiometer calibrated against a National Institute of Standards and Technology traceable source., Results: The largest maximum irradiance was 8.0 W/cm2 obtained from an endoscope used in transillumination mode. In the typical viewing mode, the largest maximum irradiance measured was 1.6 W/cm2. The majority of the light energy delivered by these gastrointestinal endoscopes was in the visible wavelength region (400 to 700 nm)., Discussion: The measurements revealed surprisingly high light exposures in the visible wavelength range. In fact, the estimated tissue exposures can exceed by 40-fold the standards established for skin exposure to light set forth by the American National Standards Institute. Because gastrointestinal endoscopy is widely viewed to be safe, it is probable that the gastrointestinal tract has significant tolerance to light exposure.

This study assessed a novel approach using defocused carbon dioxide (CO2) laser irradiation on the gastric mucosal surface to reduce gastric acid output. Ninety-six Sprague-Dawley rats were randomised to three groups: control, surgical highly selective vagotomy (surgical-HSV), and gastric mucosal irradiation (laser-M). Cysteamine-induced peptic ulceration was studied, including ulcer index (product of the total number of ulcers by the sum of the ulcer length), at 4 weeks and 20 weeks. The mean ulcer index in the surgical-HSV group was significantly reduced compared with controls at 4 weeks and at 20 weeks. The mean ulcer index in the laser-M group was significantly reduced compared with controls at 4 weeks but not at 20 weeks. Histologic analysis did not reveal any mucosal changes in parietal cell mass at 4 weeks and at 20 weeks. The results show a transient antiulcer effect produced by the gastric mucosal irradiation seen at 4 weeks and abolished by 20 weeks. This data supports the feasibility of endoscopic management of peptic ulcer disease.