Topics = myeloma, hepatitis, colorectal cancer ..... Multiple myeloma or plasmacytoma.

It is a condition resulting from the proliferation of a single clone of neoplastic cells of B lymphocyte nature, differentiated, so to speak, in the sense plasma, with infiltration of the same cells in the bone marrow, spleen, liver. These elements produce a myeloma M protein called monoclonal immunoglobulin and / or light chains that may repertoire in the urine as Bence Jones proteins.
Incidence. The disease affects persons 60 years and constitutes 10% of all cancers attributable to hematologic;
Etiologia.E 'etiology was demonstrated prolonged exposition to ionizing radiation, ie staff in radiology, among the survivors of Hiroshima and Nagasaki, it is considered that chromosomal alterations are the basis of this cancer, eg. trisomies 3, 5,7,9,11 or chromosomal rearrangements 1 and 14, there is increased expression of HLA-B5 locus, increased expression of the c-myc proto-oncogene mutations and ras. Finally, reported cases of multiple myeloma among the staff who came into contact with asbestos (asbestos), pesticides, petroleum products.
And clinical symptoms. The onset of the disease is insidious, for our experience, a subject about 65 years, came to our observation by chance, for a poorly specified pulmonary, filed for about 10 years episodes of lower limb edema, pleural effusion, bone pain and dysproteinaemia state, with significant reduction in blood albumin and increase the proportion of gamma globulin with monoclonal peak. These episodes were suffering from fever, fatigue, weight loss. Radiological investigation of the skull revealed areas osteolytic and similarly, there were additional areas of osteolysis in the spine, pelvis and ribs, presence of opacification as confluent pulmonary interstitial infiltrate. Laboratory investigation, based on the detection of normocytic anemia and monoclonal gammopathy and based on feedback Rx DLE was diagnosed and started treatment with melphan. The skeleton of these individuals has bone deformities and is subject to pathological fractures, including crushed ribs, femur, vertebrae. A sindromne anemic is present in these patients for marrow infiltration by neoplastic elements myeloma and also for renal and myelotoxic action of medicines. And 'this also iperdisprotidemia, hypercalcemia, an elevated ESR.
Other signs and complications.
Infections deficit of neutrophils and the presence of circulating malignant plasma cells secreting immunoglobulins void, between the infections reported by Streptococcus pneumoniae pneumonia, staphylococcus aureus, Pneumocystis carinii.
Bleeding: epistaxis, gengivorragie, retinal hemorrhages to decrease platelet and coagulation abnormalities probably related to the fact that the M proteins interact with the Fab fragment with fibrin monomers, so that the clot becomes gelatinous, with little support and no fibrosis retract. Moreover, it shows decrease of coagulation factors, probably for myeloma infiltration of the liver which is the headquarters of their synthesis.
Effect of blood viscosity: epistaxis, headache, sensory disturbance up all'ottundimento paraproteinemia.
Deposition of amyloid and heart failure, and nephrosis steatorre.
Kidney: hypercalcaemia and Bence Jones proteinuria, recurrent pyelonephritis, obstructive tubulopathy.
Nervous system: pain radicular compression trasverse.Cefalea roots and spinal injuries, deafness, nystagmus, radicolonevriti.
Diagnosis.
Major criteria for diagnosis of bone biopsy findings of plasma cells with more than 30% giant cells, Mott B) rate of serum M protein greater than 3.5 grams / dl for IgG,> 2 g / dl for IgA . C) Bence Jones proteinuria greater than 1 grammo/24 hours for kappa or lambda.

Minor criteria: A) plasmacytosis of the bone between 10 -30% B) C osteolytic lesions) anemia D) reduction of the values of IgG, IgA and IgM.

Staging. The disease presents a staging for prognosis, staging more accepted is that of Durie and Salmon is based on the criteria of anemia, hypercalcemia, skeletal lesions and M protein.
STAGE I: Hemoglobin> 10 g / dl, Serum-calcium levels normal skeletal X-ray maximum with a single lesion, low production of M protein: IgG <5 g / dl, IgA <3 g / dl, proteinuria M <4 hours grammi/24 .
STAGE II: internmedio
STAGE III: hemoglobin <8.5 g / dl, serum calcium> 12 mg/100 ml, while several osteolytic lesions, production of M proteins: IgG> 7 g / dl, IgA> 5 g / dl, proteinuria M> 12 grammi/24 hours.
Therapy. It makes use of chemotherapy. The classical scheme involving the use of melphalan (6 mg/m2) + prednisone (60 mg / sqm) for 7 days per month or other alkylating agents like cyclophosphamide and nitrosoureas but the 80 schemes were introduced, combined with adriamici, vincristine and dexamethasone (VAD) or cyclophosphamide, vincristine, melphalan, cyclophosphamide and prednisone. The intent is to achieve remission with reduction of 50-76 on the M protein to <25 g / l in two measurements at 4 weeks; reduction BJ with values of 0.2 g/24 hours and lack of progression of bone lesions with normalization of serum calcium.
In recent years, a hope is given by autologous and allogeneic bone marrow transplantation after ablative therapy by infusion of peripheral blood stem cells and other hematopoietic growth factors (G-CSF and GM-CSF).
The board of Gastroepato is therefore to turn to specialist centers and a good start and quickly with appropriate treatment, not underestimating the risk of infectious complications, to our experience, are allìordine the day including heavy side effects of chemotherapy.
Waldrenstrom macroglobulinemia.
The Waldenstrom's macroglobulinemia (MW) is a neoplastic proliferation of intermediate morphology "lympho-plasma cell, which synthesizes monoclonal immunoglobulin IgM, to neoplastic transformation of a B lymphocyte cell, the symptoms are insidious, with fatigue, adynamia, dyspnoea, from attributed to a syndrome with infiltrative hepatosplenomegaly and haemorrhagic syndrome with mucosal bleeding, and hyperviscosity due to high rate of IgM molecules, we add, as for multiple myeloma, infectious complications. IgM complexes come together to form tetramers with a molecular weight of 1,000,000, responsible for hyperviscosity. The diagnosis relies on the study of marrow biopsy, which is characterized by plasma cell elements, we also Bence Jones proteinuria due to kappa and erythrocyte rouleaux, ie erythrocytes stacked to the slide.
Cryoglobulinemia.
The cryoglobulins are antibodies that precipitate and gel with the cooling and which are divided into:
Monoclonal -> IgM, IgG, IgA, Bence Jones chains
mixed IgM + IgG
polyclonal, more protein
They are due to abnormal production of proteins in the course of multiple myeloma, macroglobulinemia, lymphoproliferative disease, or you can Repertoire in the course of SLE, rheumatoid arthritis, allergic vasculitis, Sjogren syndrome, if you suspect crioglubine is necessary to leave the serum a sample of blood, first in a water bath at 37 ° and then at 4 ° At this point we will observe a precipitate, criocrito. The cryoglobulins are responsible for Raynaud's phenomenon, namely the slow circulation of the extremities and the fridge to vasospasm of the fingers, nose, ear lobes, etc., and urticaria in fridge.

Italian Claudio

Autoimmune hepatitis.
It 'a chronic inflammation of the liver due to unknown, which is characterized by a) periportal hepatitis (inflammation of the portal space), b) movement of autoantibodies c) exclusion of other chronic liver disease and hepatitis (eg. Virus HCV, HBV, hemochromatosis, Wilson's disease, etc.., primary biliary cirrhosis, alcoholic steatohepatitis). The disease affects women (71%), typically before age 40. It 'a process, said autoimmune, and thus is associated, sometimes, other autoimmune frameworks (ie characterized by movements of antibodies directed towards the very structures of the body!) Such as ulcerative colitis, Graves' disease (see link), the synovitis.
Classification. It is usual to classify autoimmune hepatitis based on the finding of autoantibodies, which are Type I represented chiefly by the ANA (antinuclear) and SMA (antimuscolo smooth), as well as in the U.S. and Europe, followed by the TYPE II where antibodies LKM1 are not coexist with the first mentioned, and is associated with diseases like thyroid autoimmune (see link), vitiligo, insulin-dependent diabetes and ulcerative-colitis. Autoimmune hepatitis type 3 is characterized by anti-SLA. 11% of patients with autoimmune hepatitis type 1 has anti-SLA.
Diagnosis. Diagnostic criteria for autoimmune hepatitis is an increase of immunoglobulin> 1.5 times the upper limit of normal serum and titles of SMA and ANA and LKM1> of 1:80. There must have been using alcohol, or chronic hepatitis B and C virus related, or Epstein-Barr virus, or cytomegalovirus; antibodies antimuscolo smooth reflect the presence of antibodies against actin, tubulin, vimentin, desmin and scheletina. Anti-microsomal liver / kidney type I reactive against microsomal antigen of 50 kDa liver and kidney identified as the P450 citocromossigenasi IID6. Other types of antibodies detected are directed against liver and pancreas, non-LP, and against the asialoglycoprotein receptors (anti-ASGPR), compared to liver cytosol type 1 (anti-LC1), granulocyte Perinuclear cytoplasmic antibodies (ANCA) have been found especially in primary sclerosing cholangitis (see link).
Pathogenesis of hepatic dannoi. The mechanisms underlying the hepatic damage are represented by A) antibody-dependent cell-mediated cytotoxicity B) direct cytotoxicity, ie mediated by cytotoxic lymphocytes. In case A) are autoantibodies directed against the normal protein and the hepatocyte membrane antigen-antibody complex on the surface dell'epatocito becomes the target for lymphocytes that have receptors for the Fc antibody molecules (natural killer cells). In case B), however, an autoantigen-specific disease is exposed to an unreasonable extent on the surface dell'epatocita in association with HLA antigens (ie histocompatibility) it follows that the lymphocytes (lymphocyte cytotoxic) no longer recognizes the self as structure and is activated to destroy it. The cytokines that are, for the occasion released, facilitate communication between cells and promote expression of HLA class II neoantigen. So in both cases there is an increase in cell-immunoreactivity.
When the cure. The severity of inflammatory activity is assessed on the basis of biochemical indices of cytolysis, Peres. an increase in AST at least 10 times (10X) or more the norm, or AST> 5X associated with hypergammaglobulinemia. The decks highlight histological necrotic or necrobiosis confluent. Instead, it will not be necessary if the care AST are <a 5X and histology does not bode for periportal hepatitis or activity is low.
Therapy. Is based on cycles of steroids for 4 weeks followed by cycles of maintenance, but can be a combination therapy with steroid + azathioprine, from medium to high doses which then reduce weekly and after 4-5 weeks you need to maintenance.


Colorectal cancer, from personal notes of Dr.. Italian Claudio

It 's the most common cancer in developed countries and is responsible for about 10% of deaths from malignant. It occurs at all ages but is most affected in the sixth and seventh decades. It affects both sexes almost with the same frequency, but is more common in males. In 2000, 37,733 new cases in Italy in 20,457 males and 17,276 females. It 'was responsible for 16,646 deaths, with 73% of cases the cancer occurred in 27% colon and rectum. With regard to age in 3% of cases were patients with <49 aa; 9% aa 50-29, 60-69 AA. 20% 70-79 34%, 80% and + 33.
No single cause has been identified but research has led to important acquisitions. Genetics of familial polyposis adenomatous (FAP) and knowledge of oncogenes and tumor suppression genes led to understand that the p53 locus on chromosome 17 is abnormal in 70% of cases. In most tumors are at least two chromosomal alterations. Other conditions associated with risk of colorectal cancer are: Peutz-Jeghers, juvenile polyposis.
Ambentali factors also play their role, physical activity is important and leads to reduced risk of cancer, nutrition has important role in the prevention of colon-rectal cancer, and contain fibers, as confirmed by a European study (EPIC), where RR = 0.75; (see the link on the diet of this site). For alcohol, only heavy drinkers increased incidence of cancer is 1.41 to 1, but alcohol consumption is> 30 g / day. Smoking is associated with increased cancer risk of at least 2 times (Giovannucci et al.) Regarding sex and hormones, it would seem that women have a aminore incidence of cancer, on the other hand, does not seem that hormone therapy in postmenopausal women Possoni play a role in this respect. Instead an important role in aprevenzione appropriate therapy is given by NSAIDs, such as aspirin. A study of the American Cancer Society is a 40% reduction in risk, and a Swedish study of 37%, UC and Crohn's disease are at high risk of cancer. Subjects with primary sclerosing cholangitis and a family history of rectal cancer may have a greater risk of developing cancer if they have an inflammatory bowel disease. The same applies to that Acromegaly is associated with cancer risk, RR = 2.04. Infection with human papilloma virus in anal sex is at risk for cancer.
Intermediate incidence in Western populations to about 2 / 3 of tumors are localized in the sigmoid colon and rectum, and the rest evenly in the rest of the colon. Tumors spread by local invasion, spread to distant crosses the blood vessels and lymphatic and / or directly into the peritoneal cavity. The affected organ par excellence by metastases is the liver. Dukes' classification, proprosta already in 1932, was amended and updated, but the most popular. The classification provides a breakdown at times A, B, C1 and C2. In A, the tumor is confined to the intestinal wall, with B extending through the muscle, but does not involve lymph nodes, affects the lymph nodes proximal to C1, C2 also in the distal.
Symptoms: those are classic beehive while rettorragia data alteration occurs in the more distal, proximal to have a late onset, sometimes even with anemia. Therefore only the search for the fecal occult blood can rappresenatre a valid population screening.
Diagnosis. The diagnosis relies on physical examination is usually normal, except for the presence of a 'anemia or a palpable abdominal mass, the digital rectal examination and sigmoidoscopy are the examinations of choice, sometimes preceded by a double contrast barium enema, today less used. In this case it is clear from reading the sheet looks at apple core, or polypoid lesion or aplacca or saddle. At diagnosis the tumors are small, with rounded edges and detected, or if you have large protruding into the lumen (the blind) and / or may give stenosis pinch.

New imaging techniques, the role of cromoendoscopia.
The evidence that in the colon, the flat lesions, namely flat mucosal lesions are much more frequent and dangerous than previously thought because they represent those adenomas and depressed lesions are advanced, the fact that it is now possible to evaluate the pit patterns ", that can discern between hyperplastic and adenomatous lesions that can degenerate into malignant, this has enabled the development of cromoendoscopia. Until now the traditional endoscopy could see only the surface lining of the colon, and low resolution, not being able to obtain information on the fine structure or the histological features of mucosal and submucosal layer. The development of 'a magnification endoscope has made the accurate assessment of the mucosal surface. The fact is, however, that this technique is currently more widespread in the East, although spreading rapidly in Western countries. With the recent introduction of these new technologies that use mainly high resolution, the "magnification" (ie the magnification of the new endoscopes with more pixels solving, up to 850,000 against 200,000 of the old endoscopes) and the interaction between some chemicals (or light) and the tissues will be possible soon make biopsies more targeted, increasing the efficiency of diagnostic endoscopy. The term "cromoendoscopia" means the use of a foreign substance on the surface of the gastrointestinal tract to enhance visualization of one or more characteristics of the mucosa. The dyes used are chemical substances which react with the elements present in the mucosa (vital dyes) or they stay in small structures on the mucosal surface (contrast dyes). The vital dye commonly used in colon methylene blue, which is absorbed from the cytosol of tissues like small intestine, the colonic mucosa and epithelia affected by intestinal metaplasia. The technique of vital staining is based on the principle that dysplasia and cancer account for methylene blue to a lesser extent. Indigo carmine is an example of a counterstain. The dye is sprayed onto the mucosa with a special catheter. At present, the maximum capacity is reached magnification of 170x. With the color contrast and magnification, the mucosa of the colon appears as a set of numerous pits (pits) that really correspond to the openings of the crypts of Lieberkühn. These can be seen only with an endoscopic instrument magnification. The tiny grooves on the mucosal surface, the smallest observable detail with a standard endoscope, circumscribe areas that contain 40 to 60 pits. Several systems have been proposed for the classification of pit pattern. The best known classification recognizes six types and was developed by Kudo This classification is based on a close correlation between the pit pattern, other endoscopic features and histology of the lesions. The same author, in a study published in 2001, achieved a sensitivity of 93.8% and a specificity of 64.6% in differentiating lesions containing adenocarcinoma or less.

De novo cancer "
This means the development of colorectal cancer without adenoma-carcinoma sequence (lesion type IIc) The depressed colorectal cancers are often referred to Kudo disease 15 years ago. They represent 03.02% of all colorectal cancers, but not in tumors with submucosal invasion of the percentage of depressed type was 33%. If we look at very small lesions, ie below 10 mm, then you can say I'm 66%. For pattner type III L, IV and VI shows the endoscopic polypectomy, as a first treatment and the investigation shows that if histological invasion of the submucosa and the muscle wall, lymph nodes and vessels, then by an absolute indication for surgery (SM1-a, + ly or v + sm1c, sm3), and if the lesion is limited to the mucosa or just simply extended to the submucosa, with negative lymph nodes and vessels, you can do follow-up (sm1a-b, ly - and v-). The conventional endoscopy allows the identification of polyps and small, in fact, cancer depressed or flat, but now we see more, thanks to cromoendoscopia, so in 59-62% of cases vs 41-43% traditional endoscopy found in it depressed cancer, representing 23 and even 30% of total cases delel cancerous lesions, as indicated by a recent Swedish series. The lesions are flat on average 16 mm but are already talking about cancer or invasive lesions with high grade dysplasia, especially in the right colon (56% vs 42% of cases of polypoid lesions)
Other techniques in development.
CTC or the colongrafia TC, ie, a reconstruction of virtual colonoscopy survey prepared by the PC after TAC. It displays the polyps <6 mm with a sensitivity of 88, 7%, and specificity of 79.6%.
EUS.
Already established technique that allows visualization of the 5 layers of the wall of the colon, with mucosal and submucosal invasion display (T1), the muscular layer (T2), perirectal T3, T4 and parenchyma. In addition you can view or not lymph nodes (N0 or N1) If the nodes are not obvious, that are isoecoici context with no evidence of their tissue metastasis.


Colonic polyps
Colon polyps can be neoplastic, inflammatory or hyperplastic, but lipomas. The hamartomatous polyps are characteristic of juvenile polyposis and Peutz-Jeghers. Inflammatory and hyperplastic polyps than are found in inflammatory bowel disease.
Adenomatous polyps: rettorragie can cause cancer and have potential, especially if tewndono hairy appearance (frayed) or are larger than 2 cm. Must be removed as soon as identified during endoscopy. The tubular adenoma of 15 mm in size and pedunculated, villous adenoma is large and sessile, ie without stem. Adenomas have metaplastic potential until the dysplastic epithelium not through the muscularis mucosae into the submucosa. In this case terms are used for malignant polyp or carcinoma in early stage (!)
metaplastic or hyperplastic polyps are often found, even multiple, although harmless, sometimes hiding the risk of adenomas elsewhere.

Gastric cancer.
The cancers of the stomach in most cases are malignant and represent 15% of all deaths from cancer, it is mostly adenocarcinomas, and lymphomas, liposarcomas represent a minority. Benign tumors are represented by polyps (adenomatous and hyperplastic hamartomas), leiomyomas and lipoma.

Endoscopic examination can save the life of the patient who complains dyspepsia: in fact in Japan early gastric cancer, which is one aspect of ulcerated tumor initial (differential diagnosis with gastric ulcer!), Is diagnosed in time, we have the diagnosis is unfortunately the later.

The endoscopic picture of gastric cancer-is-said to neoplastic ulcer margins detected, or an ulcer or a benign tumor or nodular vegetans. Less common is the infiltrative type, known as linitis plastica, where the tumor extends to the whole gastric wall.

Then, the gastric cancer is divided into:
polypoid type
type diffuse infiltrative
The ulcerated type
From the perspective of histological (tissue):
gastric cancer may have a glandular pattern and bowel cancer has the appearance of a vegetating mass in the lumen and expansive, this being the most common form.
Preneoplastic
Gastric polyps can be considered as precancerous lesions at high risk! The other precancerous conditions are pernicious anemia, adenomatous polyps and intestinal metaplasia and gastric previous surgery. It 'been called into question even the chronic gastritis associated with H. pylori. The importance of Barrett's esophagus in the pathogenesis of gastroesophageal junction dell'adenocarcinoma is indisputable.
Gastric polyps are classified in types:
hamartomatous
Regenerative
hyperplastic
adenomas (they have malignant potential, with high risk when they are multiples or when the diameter exceeds 2 cm).
Other cancers:
The leiomyomas are the most common benign tumors of the stomach and autopsy studies have shown that the most frequenri tumors of the gastrointestinal tract. Originate from smooth muscle of the stomach are large, pedunculated, polypoid appearance, ulcers and bleeding, the problem is whether there is any possible potential malignancy, which is sometimes confirmed by the presence of metastases.
Gastric lymphomas that can be isolated or part of a disseminated process, has been associated with AIDS and biopsy is essential for diagnosis.
Other gastric cancers, in metastatic lesions to pancreatic adenocarcinoma, ovarian or breast cancer. Kaposi's sarcoma can occur not infrequently in patients with AIDS in the stomach. In this case the appearance is pseudopolipoide, sessile, pointed, deep red, which stands on the mucosa of salmon pink.
 

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