Colorectal Cancer

Colorectal cancer is a public health problem, considering that in many European countries is first in on the list of malignancies. Although, lung cancer predominates in men and breast cancer in women, adding the two sexes makes colorectal cancer to be the first cause of malignancy in many developed countries. Frequency of colorectal cancer varies by geographic area and is very common in Europe and USA, but less common in South America and Africa. These geographical differences are mainly related to eating habits and to some extent to genetic factors.

Colorectal Cancer

The incidence of colorectal cancer is approximately 30-40 per 100.000 inhabitants. Regarding to the ratio between the sexes, colorectal cancer, it is almost equal, with a slight detriment to men. Men / women ratio is about 1.5 / 1. Colorectal cancer is somehow preventable by endoscopic detection of polyps and their removal. Also is well known the role of genetic factors in the development of colorectal cancer (Lynch syndrome).

Colon Cancer Causes

For colorectal cancer are established several factors involved in its production. So there are:

1. Dietary factors are involved in the development of colorectal cancer, considering that protective factors are vegetable consumption, dietary fiber, calcium and vitamins. Negative dietary factors are considered to be excess dietary fat and protein, red meat, alcohol, smoking and excessive caloric intake.
2. The role of bile acids in colorectal cancer development is debatable, but there are experimental studies that show the involvement of bile acids. Some studies have shown a relationship between cholecystectomy and increased frequency of right colon cancer.
3. States predisposing to colorectal cancer are:

• Colorectal polyps is a common condition in gastroenterology practice, so that about 10% of people over 50 years and 30% of people over 70 years have colorectal polyps. These polyps are adenomatous and hyperplastic. Adenomatous polyps ( real polyps ) have several histological types: tubular, tubulo-villous and villous. The highest potential of malignancy have villous polyps and the lowest, tubular polyps lowest. Hyperplastic polyps have no malignant potential. Evolution of malignant colorectal polyps depends on genetic factors, metabolic factors and dietary factors. Malignant polyps have a greater risk if they have a larger size (usually over 2 cm diameter), are more numerous and present more severe dysplasia at biopsy;
• Familial colic polyposis is a pathological situation with a genetic character characterized by the presence of more than 100 colorectal polyps, which occur before 30 years. Genetic transmission is autosomal dominant and the evolution to malignancy is a rule;
• Inflammatory bowel diseases with long evolution, increase the risk of colorectal cancer. This risk is about 10% after 25 years of evolution of ulcerative colitis. The risk of development of colorectal cancer is lower in case of Crohn’s disease;
• Familial predisposition: descendants of a patient with colorectal cancer, have an increased risk of developing the disease, colorectal cancer rate being 2-3 times more common in first degree relatives;
• Lynch syndrome or hereditary non-polypoid colorectal cancer is characterized by the presence of  colorectal cancer in many members of the same family, the emergence of disease in young age and association with other malignancies such as ovarian cancer and endometrial cancer. Amsterdam criteria for Lynch syndrome diagnosis are:  at least three members of a family diagnosed with colorectal cancer, of which one member to be first-degree relative and at least one diagnosis of colorectal cancer to be put  in a patient under the age of 50.

Morphopathology

More than half of colorectal cancers are located at the rectosigmoid level. In the ascending colon are located about 20% of cases. Histologically, the majority of colorectal cancers are adenocarcinomas.

Staging of colorectal cancer is made after Dukes classification in the following stages:

• Stage A: tumor located in the mucosa;
• Stage B1: tumor reaches the mucosa muscle;
• Stage B2: tumor invades the entire colon wall, but does not include lymph nodes;
• Stage C: tumor includes lymph nodes;
• Stage D: metastases to distant organs.

Colorectal Cancer

Postsurgical survival depends on the stage of the tumor after Dukes classification, being approximately 90% in stage A and 50% in stage C.

Colon Cancer Symptoms

Symptoms of colorectal cancer are suggestive in advanced stages of disease. Most typical signs are:

1. Rectorragia is an important sign and appears in colorectal cancers located in the descending colon. Depending on the location of cancer, blood can be red, or clot can be mixed with the stool. In the elderly people, rectorragia always should be considered a sign of malignancy.
2. Transit disorders can sometimes suggest a colorectal cancer.
3. Partially occlusive syndrome, characterized by intermittent and incomplete stopping of gas transit and fecal transit may raise suspicion of colorectal cancers.
4. Anemic syndrome may be a sign of colorectal cancers. It is a iron deficiency anemia which can be mild or moderate.

Colorectal cancer is often asymptomatic in early stages.

Colon Cancer Diagnosis

Diagnosis of colorectal cancer is through these explorations:

1. Rectoscopy allows diagnosis of colorectal cancer. With digital rectal examination and anoscopy  (which can diagnose the pathology of anal canal), can accurately assess the distal region of the digestive tract.
2. Rectosigmoidoscopy allows accurate evaluation of descending colon, where are located 70% -80% of colorectal cancers.
3. Colonoscopy is the ideal method for examining the colon, it can view any lesion located in the colon and allows taking biopsies. Allows therapeutic measures, such as polypectomy. It is the only method that can detect vascular lesions of the colon and can perform hemostasis.
4. Spiral CT (CT colonography or virtual colonoscopy) allows, using a abdominal CT the virtual reconstruction of the colon and can diagnose colonrectal cancer and colorectal polyps.
5. Echo endoscopy (Transrectal ultrasound) allows assessment of extension of colorectal cancer  in the colonic mucosal layers.
6. Hemocult test, it is used determination of the occult bleeding in the stool. It is a screening test and is aimed at people over 50 years, asymptomatic for diagnose colonrectal cancer. Hemocult II test has a sensitivity greater than Hemocult test and the Immune Hemocult test shows the presence of human hemoglobin in stool.

Colorectal Cancer

Colon Cancer Evolution

Evolution of colon cancer depends on the moment of discovery and the time of surgery. If is a Dukes A stage, then survival at 5 years is 90% and in case of  Dukes C stage, survival at 5 years is 50%. In the case of colorectal cancer with liver metastases, survival is very low.

Colon Cancer Complications

The most common complications of colorectal cancer are:

• Metastasis;
• Intestinal obstruction;
• Perforation.

Colon Cancer Treatment

The main treatment of colon cancer is surgery. The intervention of colorectal cancer depends on its location. Preoperative evaluation will include assessing of nodal extension and the existence of metastasis in  lung, liver and peritoneal.

Postsurgical chemotherapy is indicated for patients in  B2 and C Dukes stages. It was observed that postsurgical chemotherapy increases survival time of colorectal cancer patients.

Antiangiogenic therapy, using drugs that inhibit the activity of vascular endothelial growth factor. Clinical studies have shown that the combination of this therapy to chemotherapy, improves survival of metastatic colorectal cancer patients.

Colorectal Cancer

Colon Cancer Prevention

Colorectal cancer prevention is a current requirement, given that colorectal cancer ranks first in the world.

Primary prevention consists of measures which encourage people to eat as many vegetables, a diet rich in fiber (whole grain bread, cereal), calcium and reduce consumption of fats, or proteins.

Secondary prevention consist in removing the causes that can lead to colorectal cancer development, especially the discover of polyps and endoscopic resection of them.

Hemocult tests are recommended at one to two years in patients older than 50 years, followed by colonoscopy at people  found positive to the test.

After surgical resection of a colorectal cancer, can be done carcino-embryonic antigen to highlight any local recurrences. Tracking ultrasound at 3 months and CT at 6-12 months, is done in the first 3-5 years to detect metastases.

Wilson Disease

Wilson disease is a genetic disorder with autosomal dominant transmission, characterized by deposition of copper in tissues and by the appearance of liver, neurological, psychiatric, eyes and other organs (kidney, bone, skin) symptoms.

Causes:

In Wilson disease two major anomalies occur :

1. Decreased synthesis of ceruloplasmin, a serum protein that transports copper.
2. Decreased biliary copper removal.  Wilson disease dose not cause a high absorption of copper, but a decrease in biliary elimination, which explains the positive copper balance.

Wilson Disease

Copper is found in plasma in two forms, linked to ceruloplasmin (90 micrograms%) and free (10 micrograms%). In Wilson disease, copper rises much above this concentrations, broadcasting from the vascular space into the tissues, which will cause cell damage. The liver is the first organ that accumulates copper.

Symptoms:

In half of patients with Wilson disease symptoms first appear in adolescence, only in 1% of patients the onset is after 50 years.

Classic triad of symptoms in Wilson disease is:

1. Liver. Are the first events that occur, but are not specific for Wilson disease. Thus, there are, hepatomegaly, splenomegaly, jaundice, vascular asterisks, ascites and other complications of cirrhosis. Acute fulminant hepatitis with hemolytic anemia is another way that disease can onset, with progressive jaundice, ascites, liver and kidney failure. The phenomenon is similar to acute copper poisoning, the prognosis is severe and death occurs within days.
2. Neuropsychological. Occur in young adults and are represented by coreiform movements, Parkinson’s syndrome, tremors which are worse in deliberate moves. Mental changes may occur suddenly and are manifested by the mismatch in the community, deterioration of intellectual capacity. More rarely may appear: anxiety or schizophrenic events.
3. Eye. Is due to the deposit of copper at the periphery of the cornea and appears as a gray-brown color ring or greenish ring called Kayser-Fleischner ring.

Wilson disease

Diagnosis:

Diagnosis is based on physical signs and paraclinical explorations. Paraclinical examinations are:

• Decreased creuloplasmin, normal 20mg% -40 mg%;
• Increased copper excretion in urine, its normal value is 40 microgram/24h, and over 100 microgram/24h Wilson disease;
• Increased serum copper;
• Increased amount of copper in the liver;
• Nonspecific alteration of liver tests.

Clinical forms:

Are describe three clinical forms of Wilson disease, according to clinical manifestations:

1. Hepatic form of Wilson disease;
2. Hepato-neurological form of Wilson disease;
3. Neurological form of Wilson disease.

Wilson disease

Evolution:

Untreated, Wilson disease has a rapid evolution. Under treatment, liver damage and neurological manifestations are obviously improved. In patients with untreated Wilson disease death occurs after 15 years. Neurologic form is the one with the most severe prognosis.

Wilson disease

Treatment:

Wilson disease treatment is focused on the following:

1. Diet. Copper intake should be  decrease to 1.5 mg / day, by excluding copper-rich foods (shellfish, liver, nuts, cocoa, vegetables and water with high copper content).
2. Drugs. D-penicillamine is used as a chelating agent, which reduces toxic free copper in the blood and increases its urinary elimination. Is associated with vitamin B6. The administration of zinc reduces intestinal absorption of copper.
3. Liver transplant. It is indicated in two situations:

• Acute fulminant hepatitis associated with hemolysis;
• Decompensated liver cirrhosis which is not responding to chelating agents.

Primary Hemochromatosis

Primary hemochromatosis is a systemic genetic disease characterized by deposition of iron in parenchymal organs (especially liver, spleen, etc.)  and by the appearance of liver cirrhosis, diabetes mellitus, skin pigmentation, heart disease and hypogonadism. Is also called tanned diabetes, because the liver disease is associated with diabetes and specific pigmentation of the skin.

Primary Hemocromatosis

Causes:

The etiology of primary hemochromatosis is unknown. It is described a secondary form, which occurs when the body is overload with iron:  red blood cells diseases (sideroblastic anemia, thalassemia major), oral ingestion of iron, liver disease (alcoholic cirrhosis, porphyria cutanea tarda). There may be a secondary iron overload in chronic hemodialysis or blood transfusion.

Storage of iron in liver is correlated with age, hepatotoxicity depends on the concentration of iron in the liver and on the duration of exposure. Liver iron load is progressively and later will appear fibrosis and in the end, cirrhosis.

Symptoms:

Symptoms occur most often after 40 years in men, the ratio men / women is 5-8/1.

Classic triad of symptoms of primary hemochromatosis is:

1. Hepatomegaly. Hepatic manifestations occur early, especially hepatomegaly, which appears in asymptomatic phase of the disease. In terminal stages of primary hemochromatosis, the patient will develop cirrhosis, splenomegaly and jaundice.
2. Diabetes. At 50% – 60% of cases of primary hemochromatosis, diabetes is the result of iron toxicity over the pancreatic beta-cells.
3. Skin pigmentation. Occurs in late stages of primary hemochromatosis and especially affects the exposed areas of the skin. It is due to excess of melanin and not due to iron storage in the skin.

Other events associated with primary hemochromatosis are:

• Cardiac: congestive heart failure, as an expresion of dilated cardiomyopathy;
• Symmetrical arthropathy, usually affects proximal interphalangeal and metacarpofalngeal joints, spine and knees.
• Endocrine: gonads failure, decreased libido and amenorrhea.

Primary Hemocromatosis

Diagnosis:

Diagnosis is mainly based on laboratory exploration. Paraclinical exploration which are used for the diagnosis of primary hemochromatosis are addressed to iron metabolism:

• Increased transferrin saturation coefficient, over 45%;
• Increased serum ferritin over 200 ng / ml in men and 250 ng / ml in women;
• Increasing levels of iron in the blood over 175 mg%.

The excess of iron from the tissues can be tracked by MRI or biopsy.

Evolution:

Primary hemochromatosis has a long-term evolution, survival from the moment of diagnosis, is usually for 5 years. Death ocuurs due to liver failure or due to heart failure, through the complications of diabetes or liver cancer, because there is an increased risk for the development liver cancer. Prognosis is favorable in case of early diagnosis and treatment and is reserved in the advanced stages associated with cirrhosis.

Treatment:

Are excluded foods rich in iron (spinach, liver, etc.)  and alcohol.  Drugs which are containing iron are contraindicated.

Phlebotomy is most efficiently therapy and should be done 1 or 2 sessions per week in order to remove 250 mg iron / session. In symptomatic patients are needed about 70 phlebotomies in 2-3 years.

Primary Hemocromatosis

Criteria for assessment of phlebotomy are:

• Hematocrit decreased by 5% – 10% below normal;
• Coefficient of transferrin saturation below 45%;
• Serum ferritin below 50 ng / ml.

After reaching these goals will be done 2 to 3 phlebotomies per year for maintenance.

Iron chelating agents are indicated in patients with anemic syndromes or chronic kidney failure.

 Alcoholic Steatohepatitis

Alcoholic steatohepatitis is a liver disease characterized by fibrosis and necrosis of the liver tissue induced by excessive alcohol consumption.

Causes:

Excessive consumption of alcohol has various effects on the body. From unknown causes one third of chronic alcohol consumers, do not develop alcoholic staetohepatitis . Others develop fatty liver or cirrhosis and chronic pancreatitis, dilating cardiomyopathy and neuro-psychiatric disorders.

Alcoholic Steatohepatitis

There are several risk factors for alcoholic staetohepatitis:

1. Duration of alcohol consumption and alcohol consumption itself: it is considered toxic, a dose of 60 -80 ml ??of pure alcohol / day in men and 40-50 ml of pure alcohol / day in women. Is also important is the duration of alcohol consumption, because there is a higher risk for the development of alcoholic steatohepatitis if  the length of this behavior is more than 5 years. Daily consumption of alcohol is more dangerous than occasional use. Changes occurring in the liver does not depend on the type of alcoholic beverage, but its alcohol content.
2. Gender: women are more likely to develop alcoholic steatohepatitis than men. For men to develop the disease, they must consume a higher quantity of alcohol in function than women and the metabolism of alcohol in stomach and liver is slower in women than in men.
3. Genetics: Although not demonstrated a clear genetic markers that have a clear susceptibility to alcoholism, it seems that exist some inherited behavioral patterns related to alcohol consumption.
4. The existence of a chronic hepatitis B or chronic hepatitis C;
5. Nutritional factors. Protein malabsorption favors the development of alcoholic steatohepatitis and was noticed that protein malabsorption is very common in alcoholics. It was demonstrated that a balanced diet can protect the individual who consume alcohol, at least for a while.

There are three histological types of alcoholic steatohepatitis:

• Alcoholic fatty liver;
• Alcoholic hepatitis;
• Alcoholic cirrhosis, which is the last stage of alcoholic statohepatitis, in which the fibosis affects the entire liver.

Alcoholic fatty liver:

It is characterized pathologically by lipid loading with more than 5% of hepatocytes. Macroscopic liver is enlarged, firm, pale yellow.

Clinically is observed asymptomatic hepatomegaly and sometimes signs of chronic liver disease such as Dupuytren’s contracture, testicular atrophy, palmar erythema, gynecomastia and vascular asterisks. Later physical fatigue can occur, cachexia, fever, anorexia, nausea, vomiting, jaundice, painful  hepatomegaly, splenomegaly andascites. A complication of alcoholic fatty liver can be Zieve syndrome, characterized by hyperlipidemia, hemolytic anemia, jaundice and abdominal pain.

Paraclinical, can be observed an increase in transaminases, with a  AST / ALT report greater or equal to 2, and 80% of cases there is an increase in gamma-glutamyl-transpeptidase.

Alcoholic fatty liver positive diagnosis is on account of symptoms, clinical history, due to laboratory and ultrasound liver steatosis highlighting.

A particular form of alcoholic fatty liver is represented by focal steatosis, which often pose problems of diagnosis with liver tumors.

Complications that can occur are the sudden death due to fatty embolism, alcohol withdrawal and hypoglycemia.

Treatment involves permanent stop of alcohol consumption, correction of protein deficiencies and administration of hepatoprotective drugs.

Alcoholic Steatohepatitis

Alcoholic hepatitis:

Unlike the alcoholic fatty liver, in alcoholic hepatitis occur in necrosis, inflammation and fibrosis of the liver.

Clinically, patients may be asymptomatic, or  may have the usual events like anorexia, nausea, asthenia, physical fatigue, abdominal pain, jaundice, fever, weight loss or may have symptoms that arise during complications: encephalopathy, upper gastrointestinal bleeding and ascites, complications  that progress rapidly to death.

Clinical examination reveals hepatomegaly, liver tenderness, signs of portal hypertension (splenomegaly, ascites), signs of alcoholism (palmar erythema, bruising, vascular asterisks, gynecomastia).

Paraclinical may reveal anemia due to vitamin B12 deficiency or folic acid deficency, leukocytosis or leukopenia and thrombocytopenia. Always transaminases are increase over the amount of 300 U / l, report AST / ALT is 2 / 1, increase in gamma-glutamyl-transpeptidase and alkaline phosphatase. Sometimes may occur a increases in bilirubin occur.

Alcoholic hepatitis may be complicated by: portal hypertension, which may be reversible after stopping the alcohol consumption or irreversible if the liver presents fibrosis. Cirrhosis is another complication which can lead to death.

Steatohepatitis

Ascites is another complication of alcoholic hepatitis, which is being difficult to control.

Hepatic encephalopathy may appear in advanced forms of the disease.

Mortality in alcoholic hepatitis is between 20% and 80%, patients with the worse prognosis are those who have associated severe jaundice, hepatic encephalopathy, renal failure and gastrointestinal bleeding.

Treatment consists of permanently interruption of alcohol consumption and correcting protein deficiencies by administering amino acid, because was observed that the degree of protein deficiency is associated with mortality. Corticosteroids may also be administered, because have imunosupersor and anti-inflammatory role and can inhibit the fibrosis.

Despite medication, mortality remains high in alcoholic hepatitis.

Non Alcoholic Steatohepatitis

Non alcoholic steatohepatitis is an entity characterized by the presence of an association of steatosis with inflammation and fibrosis that occurs in people who do not consume alcohol. Histological lesions are very similar to those of alcoholic hepatitis.

Causes:

Non alcoholic steatohepatitis main causes of are:

• Obesity;
• Diabetes mellitus;
• Hypertriglyceridaemia;
• Jejuno-ileal bypass for obesity;
• Prolonged parenteral nutrition;
• Some drugs (amiodarone, diltiazem, tamoxifen);
• Occupational exposure to solvents.

In clinical practice most frequent factors in the development of non alcoholic steatohepatitis are obesity, diabetes mellitus and hypertriglyceridaemia.

1. Obesity is a major problem recognized worldwide. In a few countries, such as USA up to 25% of the population is obese. A body mass index greater than 30kg/m² predispose to the emergence of non alcoholic steatohepatitis. Meanwhile, not all patients with non alcoholic steatohepatitis are obese, some of them are normal weight.
2. Type 2 diabetes is often associated with obesity and hypertriglyceridemia, all generating causes of non alcoholic steatohepatitis.

NASH

Symptoms:

Most often patients with non alcoholic steatohepatitis are asymptomatic and the disease is discovered accidentally during a medical exam. In some cases, patients with non alcoholic steatohepatitis may experience fatigue, pain in right upper quadrant and in advanced stages of illness, cirrhosis may occur with typical signs such as jaundice or ascites.

Clinical examination revealed a patient often obese, sometimes with diabetes mellitus and dyslipidemia, a patient who presents a large liver with a high consistency, the spleen may also be increased in advanced stages of disease.

To remember is that most often patients with non alcoholic steatohepatitis are completely asymptomatic and the disease is discovered incidentally.

Paraclinical examination:

Laboratory tests that can be modified are:

• Fasting blood glucose increased, relevant for diabetes;
• Hypertriglyceridemia;
• Elevated transaminases (ALT, AST) typically increase by 1.5 to 3 times their normal value. ALT is more increased than AST;
• May be a slight increase in alkaline phosphatase;
• Gamma-glutamyl-transpeptidase is normal, which differentiate non alcoholic steatohepatitis from the alcoholic steatohepatitis.

Liver ultrasound is the simplest method that can diagnose fatty liver. If is an advance stage of non alcoholic steatohepatitis which can lead to cirrhosis, ultrasound can demonstrate specific signs of the disease, such as ascites, splenomegaly, signs of portal hypertension.

CT can estimate semiquantitatively the liver fat content;

Liver biopsy is the best method (gold standard) that allows a accurate staging of non alcoholic steatohepatitis. However, routine use of liver biopsy in patients with non alcoholic statoheaptitis is questionable because of high frequency of this disease, relatively good prognosis of these patients, but also because biopsy result does not change therapy. May be useful for staging of the disease and determining the exact prognosis.

Non Alcoholic Steatohepatitis

Treatment:

Non alcoholic steatohepatitis treatment will have a dietary component and a medication component.

1. On diet in obese patients weight loss is recommended as a first stage of therapy. Weight loss should be done gradually and physical activity is essential, because both reduce insulin resistance. Often reaching a normal weight will resolve the liver disease. Is very important in diabetic patients a tight glucose control in the long run. In case of hypertriglyceridemia, a low-fat diet is mandatory.
2. Drug treatment includes multiple medications that can be used:

• Metformin, which decreases insulin resistance, may be administered in people who are not suffering from diabetes;
• Ursodeoxycholic acid;
• Vitamin E as antioxidant;
• Glitazones.

Steatohepatitis Treatment

None of the above drugs has proven a clear efficiency in non alcoholic steatohepatitis. Simple medication without solving causal factors (obesity, dyslipidemia) will not lead to an improvement in liver function. In conclusion, diet is essential in the treatment of non alcoholic steatohepatitis.

Prognosis:

Non alcoholic steatohepatitis has a good prognosis in cases of mild steatosis, and in case of cirrhosis, the prognosis is reserved. Progressive weight loss, along with physical activity, control of diabetes and of hypertriglyceridemia are solutions to improve the liver function.

Evolution:

Non alcoholic steatohepatitis evolution depends primarily on the causal factors, their importance (severity of obesity) and solving of the causal factors (weight loss, total control of diabetes or of hypertriglyceridemia). Fibrosis lesions of the liver, show that the disease is irreversible.

Autoimmune Hepatitis

Autoimmune hepatitis is an immune disease that is found predominantly in women, characterized by chronic liver damage and systemic manifestations. Autoimmune hepatitis is a relatively rare disease, given the fact that the diagnosis is often missed. Generally the discovery of autoimmune hepatitis is usually in a patient with chronic liver pain, marked hypergammaglobulinemia with fever, arthralgia and negative viral markers. In these cases, immunological markers such as ANA, LKM 1, SMA are positive.

Autoimune Hepatitis

Causes:

The exact cause of autoimmune hepatitis is not know, but it is assumed that due to a genetic predisposition or exogenous factors, there is a loss of immune tolerance to the liver tissue,  transforming it from self to non-self. Among the exogenous factors, hepatitis C often trigger an autoimmune hepatitis, rarely hepatitis B can determine this disease. Some drugs can trigger autoimmune hepatitis (alpha methyldopa). Immune response target is a membrane protein called liver specific protein, which by some mechanism it is turning from self, into non-self and will become cytotoxic.

Symptoms:

Symptoms are generally noisier than in chronic hepatitis B, but the symptoms may also be absent.

The onset of autoimmune hepatitis occurs in young women or over 40 years old and it is characterized by fatigue, asthenia, fever, arthralgia.

Immune manifestations are variable and consist of:

• Autoimmune thyroiditis;
• Amenorrhea;
• Autoimmune hemolytic anemia;
• Rheumatoid arthritis;
• Autoimmune glomerulonephritis;
• Thrombocytopenic purpura.

Autoimune Hepatitis

Paraclinical examination:

Laboratory tests show signs of liver damage and immune signs:

Signs of liver damage are:

• Elevated transaminases (AST, ALT);
• Slightly decreased serum albumin;
• Normal bilirubin;
• Gammaglobulins greatly increased.

Specific immune changes in  autoimmune hepatitis are:

• Antinuclear Antibodies (ANA);
• Smoth Muscle Antibodies (SMA);
• Liver Kidney Microsomal Antibodies (LKM 1);
• Liver Specific Protein Antibodies (LSP).

Autoimmune hepatitis is divided into several types, depending on the antibodies that appear as follows:

1. Autoimmune hepatitis type 1: is characterized by the presence of ANA and SMA, this type represent many of  the cases of autoimmune hepatitis, around 70% . It is often associated with other autoimmune disease and often progresses to cirrhosis.
2. Autoimmune hepatitis type 2: characterized by presence LKM 1. This type of autoimmune hepatitis occurs in both sexes, often in childhood. This type is associated with infection with hepatitis C and will progress to cirrhosis in 80% of cases.
3. Autoimmune hepatitis type 3: a very rare form and is associated with the presence of LSP.

Treatment:

Autoimune Hepatitis

Treatment of autoimmune hepatitis is based on immunosuppressive medication and focused on the following:

• use of immunosuppressive and anti-inflammatory drugs;
• preventing and treating side effects of therapy;
• autoimmune hepatitis prevention and treatment of complications, including autoimmune cirrhosis.

Basic medication is represented by corticosteroids, which are used for a period of approximately six months. May be associated with immunosuppressive drugs such as azathioprine. This combination is recommended in terms of postmenopausal osteoporosis, diabetes mellitus, obesity, hypertension.

The occurrence of relapse after stopping therapy, makes it to be used for life.

Crohn’s Disease

Crohn’s disease, along with ulcerative colitis is an inflammatory bowel disease. In the past it was called terminally ileitis, but it has been shown that Crohn’s disease affects the terminally portion of the ileum in 30% of cases, in about 50% of cases the disease is located both in the ileum, and the colon, and sometimes Crohn’s disease can affected only the colon. In fact, the disease may affect any segment of the digestive tract, including the esophagus and stomach. The exact cause of the disease is not know, but there are several theories. A number of bacteria, viruses and dietary factors are considered to be involved. Genetic predisposition in developing Crohn’s disease has a very important role.

Crohn’s Disease

Crohn’s Disease Symptoms

Symptoms can sometimes be absent, and other times may be suggestive for Crohn’s disease. Usually, are divided into digestive symptoms and extradigestive symptoms.

Digestive symptoms:

• Diarrhea but without blood, which can differentiate this disease from ulcerative colitis;
• Diffuse abdominal pain;
• Malabsorption;
• Perianal lesions (perianal fistulas, characteristic for Crohn’s disease).

Extradigestive symptoms:

• Fever or low grade fever;
• Asthenia;
• Weight loss;
• Arthritis;
• Nodosum eritema;
• Uveitis.

The context that can lead to clinical diagnosis of Crohn’s disease is the chronic diarrhea with low grade fever, fatigue, and perianal lesions.

Clinical examination may reveal a painful abdomen to touch, sometimes can be  palpated a mass in right iliac fossa and  the presence of cutaneous fistulas.

Crohn’s Disease

Crohn’s Disease Diagnosis

Diagnosis is not always easy, often can be done intraoperatively or during the occurrence of complications, such as a digestive fistula.

Positive diagnosis is based on endoscopy with biopsy.

Endoscopy will reveal mucosal lesions with deep, liniar ulceration. Mucosa has a cobblestoning aspect.

Biopsy is mandatory, it shows that inflammation includes the entire thickness of the intestinal wall, and the presence of fibrosis and stenosis.

Ultrasound examination will show thickening of the intestinal wall in the area of inflammation and can thus evaluate extending the inflammation . It may reveal the presence of complications such as perforation or the presence of fistulas.

Computer tomography and MRI are methods that allow a good visualization of lesions.

Crohn’s disease stadialization:

Stadialization of Crohn’s disease is done after several parameters that form  CDAI (Crohn’s Disease Activity Index) indexes. These parameters are:

• Number of stools per day;
• Abdominal pain;
• General condition;
• Extradigestive symptoms (fever, arthritis);
• Use of antidiarrheal medication;
• Palpation of an abdominal mass;
• Presence of anemia;
• Weight loss.

Based on CDAI is estimated the severity of a flare.

Crohn’s Disease

Montreal classification of Crohn’s disease is based on the age at which the disease began, the location of lesions and lesion behavior (ABL):

A (Age):

• A1 <16 years;
• A2: 17-40 years;
• A3> 40 years.

L (Location):

• L1: the last part of the ileum;
• L2: colon;
• L3: contain both ileum and colon;
• L4: isolated disease only in upper digestive tract;

B (Behavior):

• B1: non-stenosing and non-penetrating form of Crohn’s disease;
• B2: stenosing form of Crohn’s disease;
• B3: penetrating form, fistulising of Chron’s disease;
• P: perianal manifestations.

Crohn’s Disease Complications

Complications of Crohn’s disease are:

• Stenosis;
• Internal or external fistulas;
• Perforation;
• Abscess;
• Sepsis.

Crohn’s Disease

Crohn’s Disease Treatment

In the acute phase of disease is recommended to use corticosteroids for a period of about six weeks. Corticosteroid therapy may be associated with the use of Mesalazine, Metronidazole and Imuran.

In severe forms of Crohn’s disease is generally recommended the administration of anti TNF (tumor necrosis factor) medications, because it has been observed that this type of medication cause remission of severe forms of the disease.

Surgical treatment is aimed primarily to the complications or to the unresponsive to drug therapy forms of disease . Sometimes is attempted the recalibration of stenosis by endoscopic procedures.

Ulcerative Colitis

Ulcerative colitis, an inflammatory bowel disease is characterized by recurrent attacks of diarrhea with mucus and blood, alternating with periods of calm.

Symptomatology

Symptomatology of ulcerative colitis is characterized by digestive and extradigestive manifestations.

1. Digestive manifestations are represented by diarrhea with blood, mucus and pus. Also may appear abdominal pain, tenesmus and abdominal cramps. Palpation of the abdomen is painful in hypogastrium or on colic trajectory. Diarrhea episodes usually occur in a total of 3 to 10 bloody stools per day, and in severe forms can occur only emission of blood, mucus and pus.
2. Extra-digestive manifestations are represented by anemia, secondary to blood loss, fever, weight loss and fatigue.
3. Other conditions that may occur simultaneously, but in connection with ulcerative colitis are:

• Sclerosing colangite;
• Liver disease;
• Secondary amyloidosis;
• Ankylosing spondylitis.

Ulcerative Colitis

Paraclinical examination. Paraclinical explorations that help diagnose ulcerative colitis are biological investigations and investigations which highlights morphological changes.

Laboratory tests appear altered in active periods of illness and are:

• Iron deficiency anemia;
• Hypoalbuminaemia;
• ESR increased;
• Increased C-reactive protein.

Endoscopy is useful in highlighting the damage. Typical of ulcerative colitis is affecting the rectum, but the continuous character of  lesions which are seen at endoscopy. Therefore with a simple endoscopy, the diagnosis may be suggested and then confirmed by biopsy. The typical endoscopic appearance of mucosa is full of blood. The mucosa is friable with superficial ulcers, diffuse erythema and loss of vascular typical design. The mucosa is covered with pus and mucus.

Colonoscopy is used to assess the degree of extension of ulcerative colitis in the colon.

Biopsy of the colic mucosa is mandatory for diagnosis, assessing severity of injuries in this way.

Positive diagnosis will put on the presence of diarrhea with blood, mucus and pus and also by  the appearance of the colic mucosa seen at endoscopy, followed by confirmation, which is done by biopsy.

Ulcerative Colitis

Classification ulcerative colitis is based on clinical forms, on the assessing of the severity of lesions and based on the localization of the lesions.

Clinical forms of ulcerative colitis:

• Fulminant form of ulcerative colitis;
• Intermittent chronic form of ulcerative colitis, characterized by the occurrence of acute episodes on the background of almost complete remission;
• Chronic continuous form of ulcerative colitis, very rare.

The assessing of the severity of the lesions is done after Trulove’s classification, which is  based on the number of stools and intensity of clinical signs:

1. Mild form of ulcerative colitis: characterized by up to 4 stools / day with blood and mucus, and the patient’s general condition is good, without fever or denutrition and anemia is discreet;
2. Medium form of ulcerative colitis: with 4-6 stools / day, anemia and low grade fever;
3. Severe form of ulcerative colitis: more than 6 stools / day, high fever, anemia and hypoalbuminemia, blood in large amounts in stool and malaise.

After localization, ulcerative colitis is classified as follows:

• Proctitis, this form of injury occurs in the rectum or at rectosigmoid level;
• Left colitis, lesions affecting the entire descending colon;
• Pancolitis, lesions affecting the entire colon.

Ulcerative Colitis

Complications:

• Toxic megacolon;
• Perforation with secondary peritonitis;
• Intestinal stenosis;
• Massive bleeding with severe anemia;
• Colon cancer.

Treatment

Treatment begins with some dietary measures, by which should be avoided if possible milk and milk products, raw vegetables and fruits, especially those with seeds and concentrated sweets.

Drug treatment depends on the intensity of the disease:

• In severe forms of ulcerative colitis, nutrition will be done parenteral, will begin fluid and electrolyte correction. Corticosteroid is administered in high doses for several weeks. After treatment with corticosteroids are administered 5-aminosalicylates acid or salazopirin. In toxic forms of disease will be administrated antibiotics;
• In mild forms of ulcerative colitis are administered 5-aminosalicylates acid or salazopirin.

Ulcerative Colitis

Surgery is rarely practiced, in case of perforation of the colon, in case of toxic megacolon or if the bleeding can not be controlled therapeutically.

Development of colon cancer can occur in more than 10 years of disease, if is affected the entire colon and if severe epithelial dysplasia exist. Because of this, endoscopic surveillance is mandatory in patients with ulcerative colitis which has a long evolution.

Chronic Pancreatitis

Chronic pancreatitis is a chronic inflammatory disease of the pancreas, with progressive evolution, characterized by the destruction of  exocrine and endocrine pancreatic tissue evolving finally to pancreatic failure. Chronic pancreatitis is a disease that occurs slowly, as a different condition from acute pancreatitis and not as a consequence of it.

Symptoms

Symptoms that may suggest a chronic pancreatitis are generally dominated by abdominal pain, localized in the epigastric region or around the navel, it can sometimes be triggered by heavy meals and can last for a few days, nausea, fever, swollen abdomen which is very sensitive to the touch, fatigue, headaches. The presence of steatorrhea (bulky, paste and rancid odor stools) is a very late sign, when the disease is already accompanied by malabsorption and weight loss. The presence of a case history of chronic alcoholism is an important element for diagnosis.

Man with pancreatitis

Causes

1. Chronic alcoholism is the most important cause of chronic pancreatitis, generating over 90% of cases of chronic pancreatitis. Toxic dose of pure alcohol is 60 -70 ml / day in men and 40 ml / day in women. At autopsy 45% of chronic alcoholics show morphological changes of chronic pancreatitis, even if they had no clinical signs of disease. Clinical symptoms of chronic pancreatitis usually are installed later, after 10-20 years of important use of alcohol. At some patients may occur an ethanol liver damage (steatosis, alcoholic hepatitis or ethanolic cirrhosis).
2. Gallstones, although it is certainly a factor for acute pancreatitis, is not a generator factor for chronic pancreatitis. Thus, a cholecystectomy in asymptomatic patients to prevent chronic pancreatitis is unjustified, as well as a correlation between chronic pancreatitis and gallstones.
3. Hypercalcemia of hyperparathyroidism, is another possible etiologic factor of acute pancreatitis, but certainly not one for chronic pancreatitis.
4. Ductal obstructions given by pancreatic trauma, pancreatic tumors, stenosis of Oddi’s sphincter, presence of stones in Wirsung duct.
5. Hereditary pancreatitis involves the presence of a gene that is transmitted autosomal reigned. In this case the family history is important.
6. Various conditions such as malnutrition (tropical chronic pancreatitis in India, Africa and Southeast Asia), hemochromatosis (tanned diabetes – cause is iron deposition in the liver, pancreas and myocardium).

Chronic Pancreatitis

In conclusion, the cause of chronic pancreatitis is almost exclusively represented by chronic alcoholism.

Pathogenesis:

In conditions of chronic alcoholism, the pancreas secretes a pancreatic juice with higher protein content than normal. These proteins will precipitate in the form of protein plugs, which will cause obstruction of small ducts of the pancreas and will activate the pancreatic enzymes. Some of the protein plugs will calcify by impregnation with calcium carbonate. Stone formation is favored by the alteration done by the alcohol over the synthesis of litostatin, a pancreatic enzyme known in the past as pancreatic stone protein. This enzyme prevents the precipitation of calcium carbonate in the pancreatic juice. Following obstruction some ducts will broke, others will suffer o process of fibrosi, leading in the final to the appearance of stenosis. Finally, will  appear pancreatic tissue destruction and deposition of calcium in the pancreatic cells.

Diagnosis:

Chronic pancreatitis have most often inisidios onset, sometimes difficult to differentiate from repetitive acute pancreatitis alcoholic relapse. Chronic pancreatitis is 3-4 times more common in men than in women. Diagnosis is usually after age 40 years, but sometimes can occur in cases diagnosed around the age of 30 years, in these cases is possible the existence of a genetic factor.

Symptomatology is dominated by epigastric pain or around the navel, often with radiation to back. Pain can be dragged, annoying, less occasionally, sometimes may be intense, permanent, disabling. Often the pain is caused by diet and therefore, patients with chronic pancreatitis prefer not to eat, but only to consume alcohol, which can have an analgesic effect for them. At 10% – 20% of chronic pancreatitis, painful symptoms may be absent, the diagnosis being made at the laboratory of exploration.

Other symptoms may include obstructive jaundice made by the compression of the pancreatic head over the coledoc, malabsorption with steatorrhea or diabetes mellitus (occurs in 50% – 70% of chronic pancreatitis calcified).

Chronic Pancreatitis

Paraclinical examination:

1. Laboratory tests may show a slight increase in amylase, lipase or amylase of the urine. Values of this enzymes are not so high as in acute pancreatitis, but there are severe forms of chronic pancreatitis which have normal levels of these parameters.
2. Determination of fat in the stool may show steatorrhea (more 7g/ day lipid) and protein determination in the stool can show creatorrhea (less than 2.5 g / day protein), a sign of protein malabsorption.
3. Blood glucose levels may be increased because of secondary diabetes, is useful a oral glucose tolerance test.
4. Imaging currently is the most useful diagnostic methods for chronic pancreatitis:

• Abdominal radiography may reveal the presence of calcifications in 30% of cases of chronic pancreatitis;
• Abdominal ultrasound, can identify calcification of the pancreas, dilation of Wirsung duct, stones in Wirsung duct,  pancreatic cysts. Not all cases of chronic pancreatitis have these signs, but they often are linked;
• Computer tomography is the most accurate method of diagnosing chronic pancreatitis. At the same time is useful for monitoring the disease;
• Endoscopic retrograde pancreatography, highlights aspects of morphological pancreatic duct, stenosis and dilatation, as occurs in chronic pancreatitis.

5.  Pancreatic secretory tests, evaluates the functional reserve of the pancreas, they are:

• Lundh test, which consists of dose pancreatic enzymes in pancreatic juice which is obtained through duodenal tubing after food stimulation;
• Secretin test, pancreatic secretion is stimulated after the administration of secretin. In case of chronic pancreatitis decrease both secretory volume and bicarbonate flow;
• Fecal elastase 1 test, a functional test, which highlights the early pancreatic failure, it is the gold test for the diagnosis of chronic pancreatits used nowadays.

Classification of chronic pancreatitis:

Classification of chronic pancreatitis is made by clinical and pathological forms.

Clinical forms of chronic pancreatitis:

• Chronic pancreatitis with pain;
• Asymptomatic chronic pancreatitis;

Pathological forms of chronic pancreatitis:

• Chronic obstructive pancreatitis, Wirsung duct dilatation is dominant;
• Calcified chronic pancreatitis, dominated by calcifications of the pancreatic tissue;
• Mixed chronic pancreatitis with pancreatic tissue calcification and dilatation of the duct.

Evolution:

Chronic pancreatitis is a disease of long evolution and relapse of exacerbation. At first it may be asymptomatic, but in time the symptoms will appear of which the most important is pain. Stopping alcohol consumption may have a beneficial effect on pain. In time will come malabsorption.

Chronic Pancreatitis

Complications:

Complications of chronic pancreatitis are:

• pancreatic pseudocyst sometimes can cause compression;
• pancreatic abscess, which is produced by infecting a pancreatic pseudocyst;
• ascites;
• obstructive jaundice;
• splenic vein or portal vein thrombosis caused by inflammation.

Treatment:

Treatment should begin with some dietary measures, the most important is the final and complete suppression of alcohol consumption. Should be avoided heavy meals, rich in fat and protein because it stimulates pancreatic secretion and may cause exacerbation of pain.

Chronic Pancreatitis

Drug treatment of chronic pancreatitis is to:

• Analgesics for painful episodes (Metamizol, Fortral);
• Pancreatic enzyme replacements, which can relieve symptoms of chronic pancreatitis. Doses of these drugs have to be large, even in the absence of malabsorption. Drugs with a high lipase concentration will be used (Creon, Mezym Forces, Nutryzym, etc.). Enterosoluble drugs are preferred due toneutralization of the lipase by gastric juice.

Endoscopic treatment consists of:

• Papilotomy;
• Prosthesis of the Wirsung duct or gallbladder;
• Stone extraction from the Wirsung duct.

Surgery is recommended in forms with intense pain

Functional Dyspepsia

Functional dyspepsia is a functional distress (does not have an organic substrate), characterized by symptomatology located in the upper abdomen, which has the manifestations of epigastric pain, fullness, bloating or discomfort. About 70% – 80% of patients that have seen a gastroenterologist doctor, have a symptomatology  located in upper abdomen, but paraclinical explorations can not reveal the presence of organic lesions (peptic ulcer, gastric cancer, gallstones, chronic pancreatitis). These patients are classified as having functional dyspepsia. The remaining 20% – 30% of patients with upper abdominal symptomatology have an organic dyspepsia.

Functional Dyspepsia

Functional dyspepsia etiopathogenesis:

Concerning on functional dyspepsia etiopathogenesis, there are many poorly understood aspects. Thus, for cases with ulcer-like symptoms may be incriminated the role of Helicobacter pylori or the hypersecretion status , while those with symptoms of bloating can criminalize a type of gastric emptying disorder or sensory perception digestive disorders (the patient perceives as abnormal a regular amount of gas which is located in the digestive tract).

Functional dyspepsia classification:

It is achieved after the dominant symptom:

• ulcer-like dyspesia, dominated by epigastric pain, discomfort, painful hunger, but the paraclinical examination reveal the absence of digestive ulcers;
• dismotility dyspepsia, the patient complains of fullness, epigastric heaviness, bloating, belching, but paraclinical explorations will reveal the absence of lesions;
• essential dyspepsia, which includes a mixture of symptoms belonging to the two types of functional dyspepsia described above.

Functional dyspepsia diagnosis:

Clinical diagnosis, consists of an epigastric symptomatology more or less noisy, but weight loss, digestive bleeding or anemia are missing, in the presence of these symptoms, attention should be directed to an organic distress. The type of symptoms that predominate will enable the hiring in one of the forms of functional dyspepsia.

Laboratory diagnosis will consist of a series of explorations that will demonstrate the absence of organic lesions:

• Abdominal ultrasound will demonstrate a gallbladder without stones, a normal looking pancreas, a liver without modification;
• Digestive endoscopy will show an normal esophagus, stomach and duodenum;
• Colonoscopy does not reveal changes in the mucosa of the colon.

So, the character of functional dyspepsia is shown by the absence of organic lesions.

Functional Dyspepsia

Treatment of functional dyspepsia:

Regarding to functional dyspepsia treatment, it generally addresses to the symptoms and will be administered at their appearance.

1. Treatment of ulcer-like dyspepsia is done with antisecretory drugs, like  histamine H2 blockers(ranitidine, famotidine), administered in periods with symptoms or proton pump inhibitors (omeprazole, lansoprazole). There are discussions about the usefulness of eradication of Helicobater pylori infection, when is present in ulcer-like dyspesia patients and microbe can be found by direct or indirect tests. Half of patients in whom triple therapy works for the eradication of Helicobacter pylori, the symptoms disappear or are reduced, but at the rest of the patients symptoms remain;
2. Treatment of dismotility functional dyspepsia is  using prokinetic, like metoclopramide or domperidone. Also can be used digestive ferments, such as digestion or festive and sinks of intestinal gas, as dimethicone;
3. Essential functional dyspepsia treatment will be done with medication which addresses to the dominant symptom, considering that in this form of functional dyspepsia symptoms include the first two entities.

Functional Dyspepsia

In all cases of functional dyspepsia, if stress plays a role in symptoms, should be given a mild sedative or resorting to psychotherapy.