Preface

The purpose of writing this book was to overview recent hot topics in gastroenterology with a focus directed towards information derived from the bench and used at the patient's bedside. To address these issues, scientists who are working on a daily basis in the field of experimental gastroenterology and clinical investigators, with their chapter proposal's being *peer-reviewed*, all have integrated their attempts to summarize the recent advances in the pathophysiology and therapy of upper and lower gastrointestinal tract disorders. Such an integrative approach in basic and clinical gastroenterology seems to be essential for the pathomechanism, proper diagnosis and management of patients who suffer from gastrointestinal disorders. The potential reader will not only find in this book the recent advances in the physiology and pathomechanism of GI tract disorders, but also the treatment options based on pharmacological and surgical intervention and the recent advances in the biological therapy with probiotics and prebiotics, which nowadays is a rapidly growing area of interest. For instance, *Betta and Vitaliti* described in their review, the direct and indirect effects of probiotics in the functional interactions between bacteria, gut epithelium, gut mucosal immune system and systemic immune system. The direct effect of probiotics in the lumen include the competition with pathogens for nutrients, production of antimicrobial substances and in particular organic acids competitive inhibition on the receptor sites, change in the composition of mucin hydrolysis of toxins, receptor hydrolysis, and nitric oxide (NO). The indirect effect of probiotics largely depends on the site of interaction between the probiotic and the effectors of the immune response. *Thantasha et al*., presented the number of specific properties or criteria a microbial strain has to fulfill in order for it to be regarded as a probiotic. These criteria are classified into its safety profile, performance within the GI tract and technological aspects of its development. The criteria are further dependent on the specific purpose of the strain and on the location for the expression of the specific property. With regards to safety, the probiotic strain must be of human origin, isolated from the gastrointestinal tract (GIT) of healthy individuals. The strain itself, its fermentation products or its cell components after its death, should be non-pathogenic, non-toxic, non-allergic, non-mutagenic or non-carcinogenic even when given to immunocompromised individuals. The detailed criteria for the probiotic is underlined with respect to their performance, acid-tolerance and survival in the human gastric juices and bile. Probiotic bacteria must be able to survive in sufficient numbers and

#### X Preface

adhere to the intestinal mucosal surface in order to survive within the gastrointestinal tract.

Preface XI

cells in crypt to the tip of the villous. The GIT motility constituents such as migrating motor complex in the stomach and the one way peristaltic movements in small intestine are significantly influenced by the bacterial colonization. Moreover, the decrease of intestinal motility may cause a small intestinal bacterial overgrowth (SIBO). Therefore the use of *Lactobacillus* or *Bifidobacterium*, which caused an enhancement in intestinal contractility could be of interest in the modification of several functions of the upper GIT including gastric emptying, probiotics-induced normalization of motor disorders associated with IBS causing gastrointestinal

*Rudil and Isaksen* presented a comprehensive overview on the methods of detection, cultivation of the bacteria and pathogens and molecular techniques of laboratory bacterial detection including quantitative PCR. The authors explored the current focus on the human gut microbiota screenings that are based on explorative deep sequencing and by probes targeting the gene encoding 16S ribosomal RNA. The conserved regions provide information for classification of the higher taxa, while the variable regions can be used for differentiation between closely related species. *Mortavasian et al*., have provided an update on the mechanism of delivery of probiotics by food products, which has recently been considered as a physiological way to transport beneficial compounds such probiotic bacteria to the organism of the host. Because of that, this mechanism of probiotics delivery is also termed 'functional foods'. The authors define the viability of probiotic bacteria in food, which depends mostly upon the number of viable and active cells per g or mL of probiotic food products, at the moment of consumption. This is essentially a measure of the transport efficiency discussed in this chapter. It has been documented that the consumption of probiotic bacteria using food products, mainly probiotic dairy products, could be beneficial to the health of the host. The probiotic bacteria must be viable to affect the health, but the non-viable bacteria could also affect the immunological status of the host. It is believed that the arrival of probiotic bacteria with food to different parts of intestine can increase probiotic bacteria adherence and the rate of colonization. Food products may contain many forms of probiotic bacteria, including culture concentrate that is added to a food (dried or deep-freeze form), the fermented or non-fermented food products, and dietary supplements in the form of drug products-powder, capsules or tablet. It is estimated that probiotic foods comprise between 60 and 70% of the total functional food market. Among food products probiotic bacteria is distributed in a variety of products including fermented milks, ice cream, various types of cheese, baby-food milk powder, frozen dairy desserts, whey-based beverages, sour cream, butter milk, normal and flavored milk, and concentrated milk. Currently, yogurt is the major probiotic which is sold to consumers. *Mortavasian et al*. attempted to characterize the probiotic microorganisms used in food products exploring the most common, bifidobacteria and lactic acid bacteria. *Lactobacillus* and *Bifidobacterium* are the probiotic organisms which are the normal constituents of the human intestinal microbiota*.* Some other strains considered by the authors of being equally beneficial are *Lactococcus*, *Enterococcus*, *Saccharomyces* and *Propionibacterium.* The predominant

dysfunction.

The historical background of probiotics can be traced back to when the first definition of probiotic bacteria was given by Russian scientist Elie Metchnikoff who stated that probiotics are considered to exert a beneficial effect on the host. This was confirmed later on by an official statement by FAO/WHO. In their reviews, two group of investigators *Matur et al.* and *Boaventura et al.,* presented the impact of probiotics on the physiology of the GIT and the underlying mechanism of action of this microflora and the benefits derived with the use of probiotics in human and animal nutrition. Until now there is a growing list of probiotic bacteria involved in the regulation of gastrointestinal tract. Among them *Lactobacillus* and *Bifidobacterium* species were most frequently cited and have been implicated in many human GIT disorders and have become commercially promoted to improve the health of the host. The mode of action of probiotics involves a mutual interaction with intestinal cells and other microflora present in the gut. In these two chapters, the influence of probiotics on digestion, absorption and barrier function, secretory functions and the postnatal maturation of intestinal mucosa are described. Probiotics may exert a multidirectional effects affecting the gene expression in intestinal cells. A number of positive effects of probiotics have been indicated, particularly their beneficial effect in the pathologic conditions including antibiotic-associated traveler's diarrhea, irritable bowel syndrome (IBS), lactose intolerance, dental caries, gastroduodenal ulcers due to *Helicobacter pylori,* hepatic encephalopathy, intestinal motility disorders and neonatal necrotizing enterocolitis. Authors evaluated a variety of probiotics functions for the control of morphological characteristics and the proliferation capacity of crypt and villous epithelium as well as their effects on enteric nervous system. Since the microorganisms located within the digestive tract during the postnatal period have been shown to decrease villi length and increased crypt depth in many species, one of the aims was to overview the effects of probiotics on villous and crept depth. Indeed, the evidence from literature indicated that the villous height was increased in piglets inoculated with probiotics, *Lactobacillus fermentum* or *Pediococcus acidilactici* and some *Bifidobacterium* species but it was not the case for another probiotics such as *Saccharomyces boulardii*. Major inconsistency still exist as to whether probiotics could affect the crypt depth because some studies have reported that crypt depth decreased in mice supplemented with moderate and high doses of probiotic, however there were reports to the contrary as some failed to confirm those findings. All this information was important for the determination of the villous height /crypt depth ratio that may indicate the proper development of intestinal epithelia regulated by probiotics. Authors also deliberate on the villous surface area parameter that may contribute to the enhancement of the intestinal absorptive area which seems to be positively regulated by probiotics in a majority of the available evidence. From the perspective of the functionality of the GIT, particularly that which is affected by probiotics the most important being cell proliferation, migration and turnover regulated by apoptosis. Probiotics can increase number of cells in intestinal mucosa and affect the migration of cells in crypt to the tip of the villous. The GIT motility constituents such as migrating motor complex in the stomach and the one way peristaltic movements in small intestine are significantly influenced by the bacterial colonization. Moreover, the decrease of intestinal motility may cause a small intestinal bacterial overgrowth (SIBO). Therefore the use of *Lactobacillus* or *Bifidobacterium*, which caused an enhancement in intestinal contractility could be of interest in the modification of several functions of the upper GIT including gastric emptying, probiotics-induced normalization of motor disorders associated with IBS causing gastrointestinal dysfunction.

X Preface

tract.

adhere to the intestinal mucosal surface in order to survive within the gastrointestinal

The historical background of probiotics can be traced back to when the first definition of probiotic bacteria was given by Russian scientist Elie Metchnikoff who stated that probiotics are considered to exert a beneficial effect on the host. This was confirmed later on by an official statement by FAO/WHO. In their reviews, two group of investigators *Matur et al.* and *Boaventura et al.,* presented the impact of probiotics on the physiology of the GIT and the underlying mechanism of action of this microflora and the benefits derived with the use of probiotics in human and animal nutrition. Until now there is a growing list of probiotic bacteria involved in the regulation of gastrointestinal tract. Among them *Lactobacillus* and *Bifidobacterium* species were most frequently cited and have been implicated in many human GIT disorders and have become commercially promoted to improve the health of the host. The mode of action of probiotics involves a mutual interaction with intestinal cells and other microflora present in the gut. In these two chapters, the influence of probiotics on digestion, absorption and barrier function, secretory functions and the postnatal maturation of intestinal mucosa are described. Probiotics may exert a multidirectional effects affecting the gene expression in intestinal cells. A number of positive effects of probiotics have been indicated, particularly their beneficial effect in the pathologic conditions including antibiotic-associated traveler's diarrhea, irritable bowel syndrome (IBS), lactose intolerance, dental caries, gastroduodenal ulcers due to *Helicobacter pylori,* hepatic encephalopathy, intestinal motility disorders and neonatal necrotizing enterocolitis. Authors evaluated a variety of probiotics functions for the control of morphological characteristics and the proliferation capacity of crypt and villous epithelium as well as their effects on enteric nervous system. Since the microorganisms located within the digestive tract during the postnatal period have been shown to decrease villi length and increased crypt depth in many species, one of the aims was to overview the effects of probiotics on villous and crept depth. Indeed, the evidence from literature indicated that the villous height was increased in piglets inoculated with probiotics, *Lactobacillus fermentum* or *Pediococcus acidilactici* and some *Bifidobacterium* species but it was not the case for another probiotics such as *Saccharomyces boulardii*. Major inconsistency still exist as to whether probiotics could affect the crypt depth because some studies have reported that crypt depth decreased in mice supplemented with moderate and high doses of probiotic, however there were reports to the contrary as some failed to confirm those findings. All this information was important for the determination of the villous height /crypt depth ratio that may indicate the proper development of intestinal epithelia regulated by probiotics. Authors also deliberate on the villous surface area parameter that may contribute to the enhancement of the intestinal absorptive area which seems to be positively regulated by probiotics in a majority of the available evidence. From the perspective of the functionality of the GIT, particularly that which is affected by probiotics the most important being cell proliferation, migration and turnover regulated by apoptosis. Probiotics can increase number of cells in intestinal mucosa and affect the migration of

*Rudil and Isaksen* presented a comprehensive overview on the methods of detection, cultivation of the bacteria and pathogens and molecular techniques of laboratory bacterial detection including quantitative PCR. The authors explored the current focus on the human gut microbiota screenings that are based on explorative deep sequencing and by probes targeting the gene encoding 16S ribosomal RNA. The conserved regions provide information for classification of the higher taxa, while the variable regions can be used for differentiation between closely related species. *Mortavasian et al*., have provided an update on the mechanism of delivery of probiotics by food products, which has recently been considered as a physiological way to transport beneficial compounds such probiotic bacteria to the organism of the host. Because of that, this mechanism of probiotics delivery is also termed 'functional foods'. The authors define the viability of probiotic bacteria in food, which depends mostly upon the number of viable and active cells per g or mL of probiotic food products, at the moment of consumption. This is essentially a measure of the transport efficiency discussed in this chapter. It has been documented that the consumption of probiotic bacteria using food products, mainly probiotic dairy products, could be beneficial to the health of the host. The probiotic bacteria must be viable to affect the health, but the non-viable bacteria could also affect the immunological status of the host. It is believed that the arrival of probiotic bacteria with food to different parts of intestine can increase probiotic bacteria adherence and the rate of colonization. Food products may contain many forms of probiotic bacteria, including culture concentrate that is added to a food (dried or deep-freeze form), the fermented or non-fermented food products, and dietary supplements in the form of drug products-powder, capsules or tablet. It is estimated that probiotic foods comprise between 60 and 70% of the total functional food market. Among food products probiotic bacteria is distributed in a variety of products including fermented milks, ice cream, various types of cheese, baby-food milk powder, frozen dairy desserts, whey-based beverages, sour cream, butter milk, normal and flavored milk, and concentrated milk. Currently, yogurt is the major probiotic which is sold to consumers. *Mortavasian et al*. attempted to characterize the probiotic microorganisms used in food products exploring the most common, bifidobacteria and lactic acid bacteria. *Lactobacillus* and *Bifidobacterium* are the probiotic organisms which are the normal constituents of the human intestinal microbiota*.* Some other strains considered by the authors of being equally beneficial are *Lactococcus*, *Enterococcus*, *Saccharomyces* and *Propionibacterium.* The predominant organisms in the intestinal tract of breast-fed babies, *L. acidophilus* is so far the most widely used probiotic. The dominant overall flora in human intestines in bifidobacteria, *B. longum.* The information provided by the Authors are very useful in understanding the process of probiotic adaptation with regards to the fermentation conditions, in milk and other food substrates. Among the factors influencing the viability of probiotic microorganisms in food products, the most important are: pH, titrable acidity, molecular oxygen, redox potential, hydrogen peroxide, bacteriocins and short chain fatty acids.

Preface XIII

the grain of the wood, the weave of a fabric, the pattern of crops in a field, rugae on the mucous membrane of the stomach, the mucosa of colon and small intestine. This structural information and image color property has been proven essential for the purpose of medical image analysis and interpretation, perhaps the eroded ulcerous region or a protruded cancerous tissue is visually distinguished, mainly, by its alternated texture. *Akimov and Bezuglov* described existing models for the evaluation of protein digestibility with a major focus on the evaluation of enzymes involved in protein digestion in stomach and intestine. Moreover, a special emphasis is placed on the characterization of the intestinal wall peptidases (surface as well as intracellular)

with description of their specificities and their role in overall protein digestion.

ischemia and mesenteric occlusive disease.

Thrombosis in the gut is a serious disorder which may have fatal consequences. *Jomha and Schmidt* presented the most common cause of arterial mesenteric ischemia, which is embolization to the SMA. The Authors evaluated the mechanism of arterial emboli, intracardiac mural thrombus and specific circulatory disorders such as mural thrombus in proximal aneurysms within the thoracic or proximal abdominal aorta. Since SMA arises at the lesser acute angle from the abdominal aorta compared with other mesenteric vessels, it appears to be the most common final destination for mesenteric emboli. Arterial thrombosis constitutes the next most common cause of AMI and occurs in 20% to 35% of cases. The authors provided the tools for the diagnostic evaluation in the form of Duplex ultrasonography and color Doppler, scanning used to assess the flow velocities and resistance index. Another method is Computed tomography (CT) and Magnetic resonance angiography (MRA), which provides an accurate, noninvasive imaging modality for diagnosing mesenteric

It is well known that the GIT regulates the absorption of microelements, which are essential for the maintenance of body homeostasis and a failure in natural nutrient absorption in the intestine, resulting in anemic diseases. One of the major functions of intestine is the control of the mechanism of iron uptake and iron loss. In the chapter by *Freiberg et al.*, the pathomechanism of microcytic anemia and the major causes of this blood disorder are described. The physiology of red blood cells (RBC), hemoglobin and gas exchange at the level of tissues and lungs as well as pathology of various anemia's based on the gender and race of the patient are presented. This blood disease is usually attributed to iron deficiency resulting mainly from the dysfunction of iron absorption in the intestine leading to anemia. The reader is informed that apart from nutritional deficiency, the greatest cause of iron deficiency worldwide and in the United States, is a slow or "silent" gastrointestinal bleed. Based on the basic and clinical criteria that categorizes anemia's there are three important pathological processes: decreased or ineffective erythropoiesis, increased hemolysis, and blood loss. Evidence based medicine indicates that especially in poor countries, infestation by hookworm (mostly Necator americanus and Ancylostoma duodenale) is the leading cause of gastrointestinal blood loss causing the iron deficiency and iron deficiency anemia. The authors consistently classified the anemia from a pathological point of view into: 1) iron deficiency anemia, 2) thalassemia trait, 3) lead poisoning, 4) chronic

*Azzaroli et al.* dedicated their chapter to the most prescribed medications worldwide, namely non steroidal anti-inflammatory drugs (NSAIDs). These drugs are prescribed for pain management in musculoskeletal or osteoarticolar pathologies because of their analgesic and anti-inflammatory properties, however, major side effect associated with NSAIDs include gastrointestinal bleedings from both the upper and lower gastrointestinal tract. The authors provided evidence regarding NSAIDs mechanism of action and NSAIDs management including low-dose aspirin therapy. The discovery of safe NSAIDs with reduced upper GI toxicity such as selective COX-2 inhibitors is also presented in this chapter. *Vanaskova et al*., described the functional disorders of the GIT, focusing on swallowing dysfunctions in human beings. It is well known that these disorders are not only difficult to verify and quantify but also difficult to treat. There are a great deal of problems associated with functional disorders related to psychosomatic, morphological and mechanical alterations as the real causative background for these diseases. The authors decided to describe in detail the relationship between the clinical disability of locomotor system and functional dysphagia. They provided detailed anatomic and functional characteristics of the esophagus including the extrinsic and intrinsic innervations. Moreover, they had concentrated on the reflex part of swallowing involving both the afferent and efferent pathways. The afferent signals apparent during the swallowing reflex are directed from sensitive fibers of the trigeminal nerve, *n. glossopharyngeus* and *n. vagus*. The major nerve constituents of the efferent pathway are nerves in the hypoglossal motor fibers, *n. trigeminus*, *n. facialis*, *n. glossopharyngeus* and the *n. vagus*. Subsequent physiology phases of swallowing are listed by *Vanaskova et al*. in proper order and the role of autonomic and enteric system is emphasized. Finally they explore the physiology of the lower esophageal sphincter (LES) and its neurohumoral control. Among the swallowing disorders, dysphagia is the most prevalent and dangerous due to the fact it can lead to tumor formation. The classification of swallowing disorders into obstructive and non-obstructive including e.g. lower motor neuron dysfunction, autoimmune disease and achalasia were discussed in this chapter. The authors also referred to motility disorders in diabetic neuropathy, alcoholism, psychiatric illness and scleroderma – an autoimmune disease that causes weakening of the tissues of the esophagus.

*Charisis et al*. dedicated their review to the various textures which entails substantial information regarding the structural arrangement of surfaces and their relationship to the surrounding environment. Texture is an innate property of virtually all surfaces; the grain of the wood, the weave of a fabric, the pattern of crops in a field, rugae on the mucous membrane of the stomach, the mucosa of colon and small intestine. This structural information and image color property has been proven essential for the purpose of medical image analysis and interpretation, perhaps the eroded ulcerous region or a protruded cancerous tissue is visually distinguished, mainly, by its alternated texture. *Akimov and Bezuglov* described existing models for the evaluation of protein digestibility with a major focus on the evaluation of enzymes involved in protein digestion in stomach and intestine. Moreover, a special emphasis is placed on the characterization of the intestinal wall peptidases (surface as well as intracellular) with description of their specificities and their role in overall protein digestion.

XII Preface

and short chain fatty acids.

esophagus.

organisms in the intestinal tract of breast-fed babies, *L. acidophilus* is so far the most widely used probiotic. The dominant overall flora in human intestines in bifidobacteria, *B. longum.* The information provided by the Authors are very useful in understanding the process of probiotic adaptation with regards to the fermentation conditions, in milk and other food substrates. Among the factors influencing the viability of probiotic microorganisms in food products, the most important are: pH, titrable acidity, molecular oxygen, redox potential, hydrogen peroxide, bacteriocins

*Azzaroli et al.* dedicated their chapter to the most prescribed medications worldwide, namely non steroidal anti-inflammatory drugs (NSAIDs). These drugs are prescribed for pain management in musculoskeletal or osteoarticolar pathologies because of their analgesic and anti-inflammatory properties, however, major side effect associated with NSAIDs include gastrointestinal bleedings from both the upper and lower gastrointestinal tract. The authors provided evidence regarding NSAIDs mechanism of action and NSAIDs management including low-dose aspirin therapy. The discovery of safe NSAIDs with reduced upper GI toxicity such as selective COX-2 inhibitors is also presented in this chapter. *Vanaskova et al*., described the functional disorders of the GIT, focusing on swallowing dysfunctions in human beings. It is well known that these disorders are not only difficult to verify and quantify but also difficult to treat. There are a great deal of problems associated with functional disorders related to psychosomatic, morphological and mechanical alterations as the real causative background for these diseases. The authors decided to describe in detail the relationship between the clinical disability of locomotor system and functional dysphagia. They provided detailed anatomic and functional characteristics of the esophagus including the extrinsic and intrinsic innervations. Moreover, they had concentrated on the reflex part of swallowing involving both the afferent and efferent pathways. The afferent signals apparent during the swallowing reflex are directed from sensitive fibers of the trigeminal nerve, *n. glossopharyngeus* and *n. vagus*. The major nerve constituents of the efferent pathway are nerves in the hypoglossal motor fibers, *n. trigeminus*, *n. facialis*, *n. glossopharyngeus* and the *n. vagus*. Subsequent physiology phases of swallowing are listed by *Vanaskova et al*. in proper order and the role of autonomic and enteric system is emphasized. Finally they explore the physiology of the lower esophageal sphincter (LES) and its neurohumoral control. Among the swallowing disorders, dysphagia is the most prevalent and dangerous due to the fact it can lead to tumor formation. The classification of swallowing disorders into obstructive and non-obstructive including e.g. lower motor neuron dysfunction, autoimmune disease and achalasia were discussed in this chapter. The authors also referred to motility disorders in diabetic neuropathy, alcoholism, psychiatric illness and scleroderma – an autoimmune disease that causes weakening of the tissues of the

*Charisis et al*. dedicated their review to the various textures which entails substantial information regarding the structural arrangement of surfaces and their relationship to the surrounding environment. Texture is an innate property of virtually all surfaces; Thrombosis in the gut is a serious disorder which may have fatal consequences. *Jomha and Schmidt* presented the most common cause of arterial mesenteric ischemia, which is embolization to the SMA. The Authors evaluated the mechanism of arterial emboli, intracardiac mural thrombus and specific circulatory disorders such as mural thrombus in proximal aneurysms within the thoracic or proximal abdominal aorta. Since SMA arises at the lesser acute angle from the abdominal aorta compared with other mesenteric vessels, it appears to be the most common final destination for mesenteric emboli. Arterial thrombosis constitutes the next most common cause of AMI and occurs in 20% to 35% of cases. The authors provided the tools for the diagnostic evaluation in the form of Duplex ultrasonography and color Doppler, scanning used to assess the flow velocities and resistance index. Another method is Computed tomography (CT) and Magnetic resonance angiography (MRA), which provides an accurate, noninvasive imaging modality for diagnosing mesenteric ischemia and mesenteric occlusive disease.

It is well known that the GIT regulates the absorption of microelements, which are essential for the maintenance of body homeostasis and a failure in natural nutrient absorption in the intestine, resulting in anemic diseases. One of the major functions of intestine is the control of the mechanism of iron uptake and iron loss. In the chapter by *Freiberg et al.*, the pathomechanism of microcytic anemia and the major causes of this blood disorder are described. The physiology of red blood cells (RBC), hemoglobin and gas exchange at the level of tissues and lungs as well as pathology of various anemia's based on the gender and race of the patient are presented. This blood disease is usually attributed to iron deficiency resulting mainly from the dysfunction of iron absorption in the intestine leading to anemia. The reader is informed that apart from nutritional deficiency, the greatest cause of iron deficiency worldwide and in the United States, is a slow or "silent" gastrointestinal bleed. Based on the basic and clinical criteria that categorizes anemia's there are three important pathological processes: decreased or ineffective erythropoiesis, increased hemolysis, and blood loss. Evidence based medicine indicates that especially in poor countries, infestation by hookworm (mostly Necator americanus and Ancylostoma duodenale) is the leading cause of gastrointestinal blood loss causing the iron deficiency and iron deficiency anemia. The authors consistently classified the anemia from a pathological point of view into: 1) iron deficiency anemia, 2) thalassemia trait, 3) lead poisoning, 4) chronic disease, 5) sideroblastic anemia. Since iron deficiency anemia is almost always due to chronic blood loss, they also made the distinction between acute and chronic blood loss that can occur externally by any route or internally into any anatomical space, including intracranial, intrathoracic, retroperitoneal and abdominal spaces. The paper is logically divided into sections concerning epidemiology of iron deficiency in children affecting large population worldwide, health conditions of population suffering from iron deficiency and clinical cases of the genetic disorders affecting the uptake of iron and the formation of hemoglobin.

Preface XV

countries. Interestingly, several reports before revealed that the chronic inflammation seen in IBD itself may be the cause of lymphoma and also the drugs possessing immunosuppressive effects used in the treatment of IBD were suspected to confer this risk. Other diseases that might be associated with a risk of lymphoma are rheumatoid arthritis (RA), primary Sjogren's syndrome, systemic lupus erythematosus (SLE) and Hashimoto's thyroiditis. These authors focused on pathogenesis and etiology of IBD discussing the bacterial aspect and enteric microflora including potential microbial triggers, which have been studied in the past such as the enteroadherent *Escherichia coli* and *Mycobacterium paratuberculosis.* There is no doubt that the particular combination of susceptible genes and environmental triggers which greatly vary between individuals with IBD and can lead to different patterns and severity of disease. The pharmacological treatment mainly with anti-inflammatory and immunomodulatory drugs has been indicated to majority of IBD patients. This include corticosteroids, 5-aminosalicylates, azathioprine, mercaptopurine, methotrexate and cyclosporine A, which have been the most commonly used medications. Since recently the biological therapy with infliximab and adalimumab were recommended, the advantages and disadvantages of the treatment with these agents is emphasized. Later part of this review is dedicated to the cancer risk associated with IBD and the classification of lymphomas. An increased risk of certain non-colorectal malignancies has been shown amongst IBD patients. There is also literature disputing the malignancies associated with thiopurines therapy, which needs a final clarification. In the last part of the review by *Prasada et al.*, a broad spectrum of lymphomas appearing in the form of a variety of neoplasm's due to proliferation of lymphoid cells is discussed. The terminology difference between *leukemia* and *lymphoma* is clearly presented for the readers. Furthermore, the historical background for the classification of various type of lymphoma based on the morphological and functional features of the neoplastic cells is presented. The authors describe in details non-Hodgkin's Lymphoma and the pathogenic factors associated with its formation, such as infectious agents, immunosuppressive therapy, autoimmune conditions and the genetic susceptibility. Finally, they point out the recent global factors, mainly the chemical carcinogen exposure of human beings and problems of diet and obesity are implicated

*Lee et al.,* have focused their review on medications recommended to treat cancer currently, such as paclitaxel, which at present seems to be an effective anticancer drug belonging to the taxane family. This drug has been successfully used in the treatment of a wide variety of cancers including breast and ovarian cancers. The current formulation of this drug could induce adverse patient reactions such as hypersensitivity, the nonlinear pharmacokinetic behavior and paclitaxel-induced precipitation during infusion procedure. This group of investigators have been looking for more effective and convenient ways to administer paclitaxel with less formulation-related toxicities than the parent drug. For this purpose, paclitaxel and its analogs have been prepared in many different ways for various intravenous

in NHL.

administration.

*Turki and Kallel* dedicated their work to malabsorption, which could be defined as a state arising from abnormalities in the absorption of food nutrients across the GIT. Depending on the abnormality, impairment can be of single or multiple nutrients leading to malnutrition and a variety of anemia's. General symptoms may include loss of appetite (anorexia), weight loss, fatigue, shortness of breath, dehydration, low blood pressure, and swelling (edema). The authors describe the nutritional disorders that may cause anemia such as lack of iron, foliate and vitamin B12, bleeding tendency such as lack of vitamin K, or bone disease due to deficiency of vitamin D. Gastrointestinal symptoms include flatulence, stomach distention, discomfort, diarrhea, steatorrhea (excessive fat in stool) and frequent bowel movements. Intestinal malabsorption may result in mucosal damage (enteropathy), congenital or acquired reduction in absorptive surface, defects of specific hydrolysis, defects of ion transport, impaired enterohepatic circulation or pancreatic insufficiency. Their major focus was directed towards fat malabsorption caused by severe pancreatic insufficiency. These authors provide the drawbacks of therapeutic use of currently available lipase preparations, as a new oral enzyme substitution that will be helpful in the treatment of intestinal fat malabsorption caused by exocrine pancreatic insufficiency.

*Kota et al*. attempted in their chapter to describe the development of traditional remedies as a alternative to mainstream pharmaceuticals. In recent years, a number of research papers have been published on herbal medicines to provide experimental evidence for their traditional claims. Authors provide the experimental (animal and human studies) evidence for the plants that have been traditionally used to treat most notable gastrointestinal diseases, namely, peptic ulcer, diarrhea and inflammatory bowel syndrome. Besides the medical usefulness, some of this knowledge on herbal medicine is updated constantly and transferred from one generation to another generations.

It is know that inflammatory bowel disease (IBD) consists of ulcerative colitis (UC) and Crohn's disease (CD) but the role of lymphoma genesis in the pathogenesis of IBD has not been thoroughly investigated. *Prasada et al*. have focused on several lower GIT disorders attributed to UC, the non-Hodgkin's lymphoma (NHL) known as hepatosplenic T-cell lymphoma (HSTCL) and CD and the potential treatment modalities linked to commonly used drugs for the management of IBD, namely thiopurines and tumor necrosis factor (TNF) antagonists. IBD is a global disease affecting a number of Western population and the highest prevalence in developed countries. Interestingly, several reports before revealed that the chronic inflammation seen in IBD itself may be the cause of lymphoma and also the drugs possessing immunosuppressive effects used in the treatment of IBD were suspected to confer this risk. Other diseases that might be associated with a risk of lymphoma are rheumatoid arthritis (RA), primary Sjogren's syndrome, systemic lupus erythematosus (SLE) and Hashimoto's thyroiditis. These authors focused on pathogenesis and etiology of IBD discussing the bacterial aspect and enteric microflora including potential microbial triggers, which have been studied in the past such as the enteroadherent *Escherichia coli* and *Mycobacterium paratuberculosis.* There is no doubt that the particular combination of susceptible genes and environmental triggers which greatly vary between individuals with IBD and can lead to different patterns and severity of disease. The pharmacological treatment mainly with anti-inflammatory and immunomodulatory drugs has been indicated to majority of IBD patients. This include corticosteroids, 5-aminosalicylates, azathioprine, mercaptopurine, methotrexate and cyclosporine A, which have been the most commonly used medications. Since recently the biological therapy with infliximab and adalimumab were recommended, the advantages and disadvantages of the treatment with these agents is emphasized. Later part of this review is dedicated to the cancer risk associated with IBD and the classification of lymphomas. An increased risk of certain non-colorectal malignancies has been shown amongst IBD patients. There is also literature disputing the malignancies associated with thiopurines therapy, which needs a final clarification. In the last part of the review by *Prasada et al.*, a broad spectrum of lymphomas appearing in the form of a variety of neoplasm's due to proliferation of lymphoid cells is discussed. The terminology difference between *leukemia* and *lymphoma* is clearly presented for the readers. Furthermore, the historical background for the classification of various type of lymphoma based on the morphological and functional features of the neoplastic cells is presented. The authors describe in details non-Hodgkin's Lymphoma and the pathogenic factors associated with its formation, such as infectious agents, immunosuppressive therapy, autoimmune conditions and the genetic susceptibility. Finally, they point out the recent global factors, mainly the chemical carcinogen exposure of human beings and problems of diet and obesity are implicated in NHL.

XIV Preface

generations.

disease, 5) sideroblastic anemia. Since iron deficiency anemia is almost always due to chronic blood loss, they also made the distinction between acute and chronic blood loss that can occur externally by any route or internally into any anatomical space, including intracranial, intrathoracic, retroperitoneal and abdominal spaces. The paper is logically divided into sections concerning epidemiology of iron deficiency in children affecting large population worldwide, health conditions of population suffering from iron deficiency and clinical cases of the genetic disorders affecting the

*Turki and Kallel* dedicated their work to malabsorption, which could be defined as a state arising from abnormalities in the absorption of food nutrients across the GIT. Depending on the abnormality, impairment can be of single or multiple nutrients leading to malnutrition and a variety of anemia's. General symptoms may include loss of appetite (anorexia), weight loss, fatigue, shortness of breath, dehydration, low blood pressure, and swelling (edema). The authors describe the nutritional disorders that may cause anemia such as lack of iron, foliate and vitamin B12, bleeding tendency such as lack of vitamin K, or bone disease due to deficiency of vitamin D. Gastrointestinal symptoms include flatulence, stomach distention, discomfort, diarrhea, steatorrhea (excessive fat in stool) and frequent bowel movements. Intestinal malabsorption may result in mucosal damage (enteropathy), congenital or acquired reduction in absorptive surface, defects of specific hydrolysis, defects of ion transport, impaired enterohepatic circulation or pancreatic insufficiency. Their major focus was directed towards fat malabsorption caused by severe pancreatic insufficiency. These authors provide the drawbacks of therapeutic use of currently available lipase preparations, as a new oral enzyme substitution that will be helpful in the treatment of intestinal fat

*Kota et al*. attempted in their chapter to describe the development of traditional remedies as a alternative to mainstream pharmaceuticals. In recent years, a number of research papers have been published on herbal medicines to provide experimental evidence for their traditional claims. Authors provide the experimental (animal and human studies) evidence for the plants that have been traditionally used to treat most notable gastrointestinal diseases, namely, peptic ulcer, diarrhea and inflammatory bowel syndrome. Besides the medical usefulness, some of this knowledge on herbal medicine is updated constantly and transferred from one generation to another

It is know that inflammatory bowel disease (IBD) consists of ulcerative colitis (UC) and Crohn's disease (CD) but the role of lymphoma genesis in the pathogenesis of IBD has not been thoroughly investigated. *Prasada et al*. have focused on several lower GIT disorders attributed to UC, the non-Hodgkin's lymphoma (NHL) known as hepatosplenic T-cell lymphoma (HSTCL) and CD and the potential treatment modalities linked to commonly used drugs for the management of IBD, namely thiopurines and tumor necrosis factor (TNF) antagonists. IBD is a global disease affecting a number of Western population and the highest prevalence in developed

uptake of iron and the formation of hemoglobin.

malabsorption caused by exocrine pancreatic insufficiency.

*Lee et al.,* have focused their review on medications recommended to treat cancer currently, such as paclitaxel, which at present seems to be an effective anticancer drug belonging to the taxane family. This drug has been successfully used in the treatment of a wide variety of cancers including breast and ovarian cancers. The current formulation of this drug could induce adverse patient reactions such as hypersensitivity, the nonlinear pharmacokinetic behavior and paclitaxel-induced precipitation during infusion procedure. This group of investigators have been looking for more effective and convenient ways to administer paclitaxel with less formulation-related toxicities than the parent drug. For this purpose, paclitaxel and its analogs have been prepared in many different ways for various intravenous administration.

The chapter by *Gancarcikova et al.,* was designed to evaluate the effects of age and various diets including natural feeding, artificial feeding and gnotobiotic conditions on the development of microflora, and the production of short-chain fatty acids (SCFAs). Moreover, authors studied the postnatal morphological development and disaccharidase enzymes activity in the small intestine in piglets reared under the sow, piglets fed on milk replacement, as well as in gnotobiotic piglets. Important information on the mechanism of stress in the early postnatal period and just after weaning affecting gut development, the microbial colonization of the digestive tract and the absorption capacity. The changes in colostrums, that contains a high levels of several hormones and growth promoting peptides like insulin, epidermal growth factor (EGF), insulin-like growth factor-I and II (IGF-I and II), transforming growth factor-β (TGF- β), glucagon-like peptide-2 (GLP-2) and leptin are discussed. These factors were proved to play an important role in the postnatal development of the digestive tract in newborn animals. On the other hand, the morphologic changes combined with certain types of enterobacteria, can be responsible for post-weaning *diarrhea*. It has recently been recognized that probiotics such as *Lactobacillus*, *Bifidobacterium*, *Bacillus*, *Enterococcus* and S*treptococcus* may be effective in preventing various forms of diarrheic diseases of dietetic and bacterial origin. In the experimental part of the chapter, the authors collected sections of jejunum, ileum and caecum and processed them for microbial counting and short-chain fatty acids (SCFAs) determinations. These experiments were carried out in the contents from jejunum, ileum and colon of gnotobiotic and conventionally bred piglet*s.* Furthermore, the association between the digestive enzyme activity in relation to pH and other constituents of the intestinal contents in various breeds of pigs were studied and suggested that the gnotobiotic animals are a very useful model in studying the physiology of the digestive tract, based on established microbial population affecting the postnatal intestinal development. The authors gave insight into the mechanism of the beneficial effects of probiotic microorganisms that may interact with colostrums, milk containing growth factors, hormones and other bio-active compounds to maintain the proper growth and development of GIT.

Preface

was appendicitis and the patient underwent laparoscopic appendectomy using the three-trocar technique. The authors recommend simple appendectomy as a first line treatment that also endoscopic surveillance seems to be essential for control of a low

The review by *Burmeister et al.* was dedicated to the pathogenesis and therapy of chronic pancreatitis (CP), which has been defined as a continuing inflammatory disease of the pancreas. This disease is characterized by irreversible morphological changes, often associated with pain and loss of exocrine and endocrine function, which may be clinically relevant. The mechanism of pancreatitis involves multiple factors including excessive generation of reactive oxygen-derived metabolites (ROM), tissue hypoxia and acidosis. The development of pancreatitis includes tissue inflammatory infiltration, accompanied by impaired transmission of pain sensation *via* neural ascending pathway and the development of pancreatic ductal and tissue fluid hypertension. Pancreatic disorders are the most difficult diseases to treat, and there is a lot of concerns regarding how to manage the pancreatitis patients from the first symptoms to hospital admission and proper handling those patients either symptomatically or surgically. Pain together with pancreatic insufficiency may have a significant deleterious effect on a patient's quality of life as well as their ability to work and contribute to society, often leading to a loss of their' social support network. *Burmeister et al.* proposed surgery of the pancreatic head containing altered neural fibrotic tissue and diseased ducts as an option to bring relief of pain, due to a resection of inflamed pancreatic tissue and the prevention of the glycoprotein plug formation that may calcify leading to pancreatic ductal hypertension. They also critically analyzed their own surgical attempts and data on pancreatic surgery in humans that exists so far in the literature, and paid major attention to the risk of post-operative pancreatic functional insufficiency and in some cases the surgically related morbidity and mortality for the patient. Furthermore, *Burmeister et al*. described the pathophysiology of pain in CP, and discussed the rationale and indications for

surgical intervention and detailed the procedures currently available.

*Uchiyama-Tanaka* have addressed his review of colonic hydrotherapy with a major focus on colonic irrigations. These procedures are performed using an instrument in combination with abdominal massage, but without drugs or mechanical pressure. The Author explored the events associated with colonic irrigation, for instance, a lymphocyte transmigration from gut-associated lymphoid tissue (GALT) into the circulation, which may improve the functions of both the colon and immune system. Colonic irrigation was developed approximately 40 years ago with no serious complications associated with its use being reported. The author made a substantial contribution to the field of colonic irrigation and shares with readers his experience with this method, which is employed in subjects with no history of malignant or inflammatory disease. The impact of this method, which uses a large amount of water, on the function of intestinal microbiota and serum electrolytes remains, however,

XVII

unknown.

grade MALToma that can progress into IBD.

*Sophia and Bashir* described what mostly occurs in adolescent or young adults and is classified as a rare disorder, termed superior mesenteric artery syndrome (SMAS). This syndrome was first described by the Von Rokitansky in 1842 and since then about 400 cases has been reported in literature. In their overview, Sophia and Bashir have underlined the epidemiology of this disorder, and have reported it to be around 0.013- 0.3 %. The Authors refer to the high rate of morbidity caused by this syndrome and the difficulty in diagnosing it, and convincingly warned clinicians to be aware of this disorder.

*Marte Antonio et al*. presented a case report on the mucosa associated lymphoid tissue (MALT) lymphoma involving the appendix in a 6-year-old girl, a rather rare disease in the children in young age. The complications appearing after MALT lymphomas includes approximately 40% of adult developing non-Hodgkin lymphomas (NHL), with the disease being more prevalent in females than males. The primary diagnosis was appendicitis and the patient underwent laparoscopic appendectomy using the three-trocar technique. The authors recommend simple appendectomy as a first line treatment that also endoscopic surveillance seems to be essential for control of a low grade MALToma that can progress into IBD.

The review by *Burmeister et al.* was dedicated to the pathogenesis and therapy of chronic pancreatitis (CP), which has been defined as a continuing inflammatory disease of the pancreas. This disease is characterized by irreversible morphological changes, often associated with pain and loss of exocrine and endocrine function, which may be clinically relevant. The mechanism of pancreatitis involves multiple factors including excessive generation of reactive oxygen-derived metabolites (ROM), tissue hypoxia and acidosis. The development of pancreatitis includes tissue inflammatory infiltration, accompanied by impaired transmission of pain sensation *via* neural ascending pathway and the development of pancreatic ductal and tissue fluid hypertension. Pancreatic disorders are the most difficult diseases to treat, and there is a lot of concerns regarding how to manage the pancreatitis patients from the first symptoms to hospital admission and proper handling those patients either symptomatically or surgically. Pain together with pancreatic insufficiency may have a significant deleterious effect on a patient's quality of life as well as their ability to work and contribute to society, often leading to a loss of their' social support network. *Burmeister et al.* proposed surgery of the pancreatic head containing altered neural fibrotic tissue and diseased ducts as an option to bring relief of pain, due to a resection of inflamed pancreatic tissue and the prevention of the glycoprotein plug formation that may calcify leading to pancreatic ductal hypertension. They also critically analyzed their own surgical attempts and data on pancreatic surgery in humans that exists so far in the literature, and paid major attention to the risk of post-operative pancreatic functional insufficiency and in some cases the surgically related morbidity and mortality for the patient. Furthermore, *Burmeister et al*. described the pathophysiology of pain in CP, and discussed the rationale and indications for surgical intervention and detailed the procedures currently available.

*Uchiyama-Tanaka* have addressed his review of colonic hydrotherapy with a major focus on colonic irrigations. These procedures are performed using an instrument in combination with abdominal massage, but without drugs or mechanical pressure. The Author explored the events associated with colonic irrigation, for instance, a lymphocyte transmigration from gut-associated lymphoid tissue (GALT) into the circulation, which may improve the functions of both the colon and immune system. Colonic irrigation was developed approximately 40 years ago with no serious complications associated with its use being reported. The author made a substantial contribution to the field of colonic irrigation and shares with readers his experience with this method, which is employed in subjects with no history of malignant or inflammatory disease. The impact of this method, which uses a large amount of water, on the function of intestinal microbiota and serum electrolytes remains, however, unknown.

XVI Preface

The chapter by *Gancarcikova et al.,* was designed to evaluate the effects of age and various diets including natural feeding, artificial feeding and gnotobiotic conditions on the development of microflora, and the production of short-chain fatty acids (SCFAs). Moreover, authors studied the postnatal morphological development and disaccharidase enzymes activity in the small intestine in piglets reared under the sow, piglets fed on milk replacement, as well as in gnotobiotic piglets. Important information on the mechanism of stress in the early postnatal period and just after weaning affecting gut development, the microbial colonization of the digestive tract and the absorption capacity. The changes in colostrums, that contains a high levels of several hormones and growth promoting peptides like insulin, epidermal growth factor (EGF), insulin-like growth factor-I and II (IGF-I and II), transforming growth factor-β (TGF- β), glucagon-like peptide-2 (GLP-2) and leptin are discussed. These factors were proved to play an important role in the postnatal development of the digestive tract in newborn animals. On the other hand, the morphologic changes combined with certain types of enterobacteria, can be responsible for post-weaning *diarrhea*. It has recently been recognized that probiotics such as *Lactobacillus*, *Bifidobacterium*, *Bacillus*, *Enterococcus* and S*treptococcus* may be effective in preventing various forms of diarrheic diseases of dietetic and bacterial origin. In the experimental part of the chapter, the authors collected sections of jejunum, ileum and caecum and processed them for microbial counting and short-chain fatty acids (SCFAs) determinations. These experiments were carried out in the contents from jejunum, ileum and colon of gnotobiotic and conventionally bred piglet*s.* Furthermore, the association between the digestive enzyme activity in relation to pH and other constituents of the intestinal contents in various breeds of pigs were studied and suggested that the gnotobiotic animals are a very useful model in studying the physiology of the digestive tract, based on established microbial population affecting the postnatal intestinal development. The authors gave insight into the mechanism of the beneficial effects of probiotic microorganisms that may interact with colostrums, milk containing growth factors, hormones and other bio-active compounds to

maintain the proper growth and development of GIT.

disorder.

*Sophia and Bashir* described what mostly occurs in adolescent or young adults and is classified as a rare disorder, termed superior mesenteric artery syndrome (SMAS). This syndrome was first described by the Von Rokitansky in 1842 and since then about 400 cases has been reported in literature. In their overview, Sophia and Bashir have underlined the epidemiology of this disorder, and have reported it to be around 0.013- 0.3 %. The Authors refer to the high rate of morbidity caused by this syndrome and the difficulty in diagnosing it, and convincingly warned clinicians to be aware of this

*Marte Antonio et al*. presented a case report on the mucosa associated lymphoid tissue (MALT) lymphoma involving the appendix in a 6-year-old girl, a rather rare disease in the children in young age. The complications appearing after MALT lymphomas includes approximately 40% of adult developing non-Hodgkin lymphomas (NHL), with the disease being more prevalent in females than males. The primary diagnosis *Nguyen* have overviewed the pancreato-biliary cancers that may arise from cancer of the pancreas, bile duct and major ampullae. These tumors uniformly carry a poor prognosis due to its late presentation. Despites many medical advances in imaging diagnosis, chemo-radio-therapy, surgical technique and post-operative care over the last 2 decades, the overall survival of patients with pancreato-biliary neoplasm has not improved significantly. Surgical resection is only possible in less than 20% of patients. The Author's discussed in his review the current techniques and approaches to the diagnosis and management of pancreato-biliary neoplasm. The aim of the chapter by *Jablonska and Lampe* was to present different types of biliary reconstructions used in the surgical treatment of iatrogenic bile duct injuries (IBDI). IBDI remain a critical issue in gastrointestinal surgery due to the fact its a frequent cause of laparoscopic cholecystectomy, which is one of the most commonest surgical procedure in gastroenterology. The early and proper diagnoses of IBDI is very important for surgeons and gastroenterologists, because unrecognized IBDI can lead to serious complications such as biliary cirrhosis, hepatic failure and in some cases to death. The authors refer to the non-invasive, percutaneous radiological and endoscopic techniques as a recommended options for the initial treatment of IBDI. When endoscopic treatment is not effective, surgical management is considered. The major goal of surgical treatment is to reconstruct the proper bile flow to the alimentary tract.

Preface XIX

clinical problem recognition and management of the most common drugs affecting the gastrointestinal tract. Moreover, they attempted to identify epidemiology, the true incidence in hospitalized and non-hospitalized patients and the main concerns about their causes and the treatment modalities. The problem is of great clinical interest because less common and, usually less severe disorders such as liver disease and

In the overview by *Rakus-Andersso,* the subject of Computational Intelligence development in recent years is described. Computational Intelligence has been divided into five main regions, namely, neural networks, evolutionary algorithms, swarm intelligence, immunological systems and fuzzy systems. The author's attention has been attracted by the possibilities of medical applications provided by immunological computation algorithms. Immunological computation systems are based on immune reactions of living organisms in order to defend the bodies from pathological substances. Especially, the mechanisms of T-cell reactions to detect strangers, have been converted into artificial numerical algorithms. In this chapter, another hybrid between the NS algorithm and the chosen solutions coming from fuzzy systems is proposed. This hybrid constitutes their own model of adapting the NS algorithm to the

operation decisions "operate" contra "do not operate" in gastric cancer surgery.

therapeutic options offered by conventional and interventional medicine.

In summary, we hope that this book with divergent thematic gastroenterology chapters will be beneficial to all those who share our interest in basic and clinical medicine, translational medicine and health care as well as it serving to trigger the attention of medical students, and potential patients to understanding the recent advancements in the field of gastroenterological disorders of human beings, and the

Professor of Medicine, Chairman, Department of Physiology,

Jagiellonian University Medical College, Cracow

**Tomasz Brzozowski** 

Poland

pancreatitis can be induced by adverse drug reactions.

*Parkash et al.* explored in their review, the most common liver diseases, namely, acute liver failure (ALF) and the chronic liver disease (cirrhosis), however, these authors also considered herein the extra hepatic manifestations of liver disease such as hepatic encephalopathy (HE). This latter occurs in 50-70% of patients with chronic liver disease indicating decompensated chronic liver disease. Among symptoms of HE, the most important are alterations in psychomotor functions, personality changes, cognitive impairment and disturbed sleep patterns. Authors provide the recent standings on classification of HE into 3 types: A, B and C, respectively. Type A is associated with acute liver failure; type B observed mainly in patients with portosystemic bypass and no intrinsic hepatocellular disease; and type C is linked with cirrhosis or portal-hypertension or porto-systemic shunts, respectively. The proposed mechanism of pathophysiology for HE includes the generation of ammonia, inflammatory cytokines, benzodiazepine among them manganese like substances, which impair neuronal function. The ammonia hypothesis includes dietary nitrogenous components producing ammonia, bacterial metabolism of these nitrogenous products in the colon and in small intestine from glutamine by glutaminase enzyme. Ammonia can activate peripheral type benzodiazepine receptor (Trasnslocator proteins) giving rise to neurosteroids and the GABA/benzodiazepine receptor complex theory. Other mechanisms include the contribution to HE of the microelements such as zinc and manganese as well as oxidative and the nitrosative stress effects *via* a mechanism involving their effect on translocator proteins. Overall, other possible mechanisms of HE have been also carefully analyzed and explained.

*Hernandez et al.* have focused their review on common adverse drug reactions of the GIT, mainly hemorrhages and peptic ulcer disease. These Authors propose proper clinical problem recognition and management of the most common drugs affecting the gastrointestinal tract. Moreover, they attempted to identify epidemiology, the true incidence in hospitalized and non-hospitalized patients and the main concerns about their causes and the treatment modalities. The problem is of great clinical interest because less common and, usually less severe disorders such as liver disease and pancreatitis can be induced by adverse drug reactions.

XVIII Preface

*Nguyen* have overviewed the pancreato-biliary cancers that may arise from cancer of the pancreas, bile duct and major ampullae. These tumors uniformly carry a poor prognosis due to its late presentation. Despites many medical advances in imaging diagnosis, chemo-radio-therapy, surgical technique and post-operative care over the last 2 decades, the overall survival of patients with pancreato-biliary neoplasm has not improved significantly. Surgical resection is only possible in less than 20% of patients. The Author's discussed in his review the current techniques and approaches to the diagnosis and management of pancreato-biliary neoplasm. The aim of the chapter by *Jablonska and Lampe* was to present different types of biliary reconstructions used in the surgical treatment of iatrogenic bile duct injuries (IBDI). IBDI remain a critical issue in gastrointestinal surgery due to the fact its a frequent cause of laparoscopic cholecystectomy, which is one of the most commonest surgical procedure in gastroenterology. The early and proper diagnoses of IBDI is very important for surgeons and gastroenterologists, because unrecognized IBDI can lead to serious complications such as biliary cirrhosis, hepatic failure and in some cases to death. The authors refer to the non-invasive, percutaneous radiological and endoscopic techniques as a recommended options for the initial treatment of IBDI. When endoscopic treatment is not effective, surgical management is considered. The major goal of surgical treatment is to reconstruct the proper bile flow to the alimentary tract.

*Parkash et al.* explored in their review, the most common liver diseases, namely, acute liver failure (ALF) and the chronic liver disease (cirrhosis), however, these authors also considered herein the extra hepatic manifestations of liver disease such as hepatic encephalopathy (HE). This latter occurs in 50-70% of patients with chronic liver disease indicating decompensated chronic liver disease. Among symptoms of HE, the most important are alterations in psychomotor functions, personality changes, cognitive impairment and disturbed sleep patterns. Authors provide the recent standings on classification of HE into 3 types: A, B and C, respectively. Type A is associated with acute liver failure; type B observed mainly in patients with portosystemic bypass and no intrinsic hepatocellular disease; and type C is linked with cirrhosis or portal-hypertension or porto-systemic shunts, respectively. The proposed mechanism of pathophysiology for HE includes the generation of ammonia, inflammatory cytokines, benzodiazepine among them manganese like substances, which impair neuronal function. The ammonia hypothesis includes dietary nitrogenous components producing ammonia, bacterial metabolism of these nitrogenous products in the colon and in small intestine from glutamine by glutaminase enzyme. Ammonia can activate peripheral type benzodiazepine receptor (Trasnslocator proteins) giving rise to neurosteroids and the GABA/benzodiazepine receptor complex theory. Other mechanisms include the contribution to HE of the microelements such as zinc and manganese as well as oxidative and the nitrosative stress effects *via* a mechanism involving their effect on translocator proteins. Overall, other possible mechanisms of HE have been also carefully analyzed and explained.

*Hernandez et al.* have focused their review on common adverse drug reactions of the GIT, mainly hemorrhages and peptic ulcer disease. These Authors propose proper In the overview by *Rakus-Andersso,* the subject of Computational Intelligence development in recent years is described. Computational Intelligence has been divided into five main regions, namely, neural networks, evolutionary algorithms, swarm intelligence, immunological systems and fuzzy systems. The author's attention has been attracted by the possibilities of medical applications provided by immunological computation algorithms. Immunological computation systems are based on immune reactions of living organisms in order to defend the bodies from pathological substances. Especially, the mechanisms of T-cell reactions to detect strangers, have been converted into artificial numerical algorithms. In this chapter, another hybrid between the NS algorithm and the chosen solutions coming from fuzzy systems is proposed. This hybrid constitutes their own model of adapting the NS algorithm to the operation decisions "operate" contra "do not operate" in gastric cancer surgery.

In summary, we hope that this book with divergent thematic gastroenterology chapters will be beneficial to all those who share our interest in basic and clinical medicine, translational medicine and health care as well as it serving to trigger the attention of medical students, and potential patients to understanding the recent advancements in the field of gastroenterological disorders of human beings, and the therapeutic options offered by conventional and interventional medicine.

> **Tomasz Brzozowski**  Professor of Medicine, Chairman, Department of Physiology, Jagiellonian University Medical College, Cracow Poland

**Section 1** 

**Emerging Impact of** 

**Probiotics in Gastroenterology** 
