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Prostate cancer screening is an attempt to find unsuspected cancers. Initial screens may lead to more invasive follow-up tests such as a biopsy. Options include the digital rectal exam (DRE) and the prostate-specific antigen (PSA) blood test. Such screening is controversial and, in some people, may lead to unnecessary disruption and possibly harmful consequences. Routine screening with either a DRE or PSA is not supported by the evidence as there is no mortality benefit from screening.
The United States Preventive Services Task Force (USPSTF) recommends against the PSA test for prostate cancer screening in healthy men regardless of age. They concluded that the potential benefit of testing does not outweigh the expected harms. The Centers for Disease Control and Prevention shared that conclusion. The American Society of Clinical Oncology and the American College of Physicians discourages screening for those who are expected to live less than ten to fifteen years, while in those with a greater life expectancy a decision should be made by the person in question based on the potential risks and benefits. In general, they concluded, "it is uncertain whether the benefits associated with PSA testing for prostate cancer screening are worth the harms associated with screening and subsequent unnecessary treatment." American Urological Association (AUA 2013) guidelines call for weighing the benefits of preventing prostate cancer mortality in 1 man for every 1,000 men screened over a ten-year period against the known harms associated with diagnostic tests and treatment. The AUA recommends screening decisions in those 55 to 69 be based on shared decision making, and that if screening is performed it should occur no more often than every two years.
In those who are being regularly screened, 5-alpha-reductase inhibitor (finasteride and dutasteride) reduce the overall risk of being diagnosed with prostate cancer; however, there is insufficient data to determine if they have an effect on the risk of death and may increase the chance of more serious cases.
These lymphomas are difficult to differentiate from gastric adenocarcinoma. The lesions are usually ulcers with a ragged, thickened mucosal pattern on contrast radiographs.
The diagnosis is typically made by biopsy at the time of endoscopy. Several endoscopic findings have been reported, including solitary ulcers, thickened gastric folds, mass lesions and nodules. As there may be infiltration of the submucosa, larger biopsy forceps, endoscopic ultrasound guided biopsy, endoscopic submucosal resection, or laparotomy may be required to obtain tissue.
Imaging investigations including CT scans or endoscopic ultrasound are useful to stage disease. Hematological parameters are usually checked to assist with staging and to exclude concomitant leukemia. An elevated LDH level may be suggestive of lymphoma.
The majority of gastric lymphomas are non-Hodgkin's lymphoma of B-cell origin. These tumors may range from well-differentiated, superficial involvements (MALT) to high-grade, large-cell lymphomas. Sometimes, it's hard to differentiate poorly differentiated high grade B-cell gastric lymphoma from gastric adenocarcinoma clinically or radiologically, yet histopathology with immunohistochemistry is recommended to stain specific markers on the malignant cell that favor the diagnosis of lymphoma. Immunohistochemistry stains specific clusters of differentiation that are present on B-cells like CD20. Cytokeratin is also a surface marker that is presented on epithelial cells, is stained histochemically and favors the diagnosis of epithelial tumors like adenocarcinoma.
Differentiating poor gastric lymphoma from adenocarcinoma is essential because the prognosis and modalities of treatment differ significantly.
Other lymphomas involving the stomach include mantle cell lymphoma and T-cell lymphomas which may be associated with enteropathy; the latter usually occur in the small bowel but have been reported in the stomach.
Prognoses and treatments are different for HL and between all the different forms of NHL, and also depend on the grade of tumour, referring to how quickly a cancer replicates. Paradoxically, high-grade lymphomas are more readily treated and have better prognoses: Burkitt lymphoma, for example, is a high-grade tumour known to double within days, and is highly responsive to treatment. Lymphomas may be curable if detected in early stages with modern treatment.
In order to diagnose MALT, a biopsy is needed from the affected tissue. If the abnormal tissue is suspected to be in the stomach or bowel, an endoscopy is done in order to get the biopsy. This requires either a gastroscopy or colonoscopy. If the lymphoma is thought to have spread to other areas in this region, an ultrasound scan is often done at the same time. If the abnormal tissue is thought to be in the lungs, a bronchoscopy is ordered.
In order to determine the correct type of lymphoma and stage it accurately, the physician will also need to do a physical exam, blood tests to determine blood cell counts, a CT scan, an MRI and/or a PET scan. A PET scan is the most important in planning a course of treatment.
A bone marrow biopsy may be ordered to test for lymph node involvement. If the lymphoma is in the stomach, the physician will test for H.pylori infection through a stool sample. This infection would be necessary to treat in conjunction to treating the cancer.
Biopsy of affected lymph nodes or organs confirms the diagnosis, although a needle aspiration of an affected lymph node can increase suspicion of the disease. X-rays, ultrasound and bone marrow biopsy reveal other locations of the cancer. There are now a range of blood tests that can be utilised to aid in the diagnosis of lymphoma. Flow cytometry detects antibodies linked to tumour cell surface antigens in fluid samples or cell suspensions. Polymerase chain reaction (PCR) for antigen receptor rearrangements (PARR) identifies circulating tumour cells based on unique genetic sequences. The canine Lymphoma Blood Test (cLBT) measures multiple circulating biomarkers and utilises a complex algorithm to diagnose lymphoma. This test utilises the acute phase proteins (C-Reactive Protein and Haptoglobin). In combination with basic clinical symptoms, it gives in differential diagnosis the sensitivity 83.5% and specificity 77%. The TK canine cancer panel is an indicator of general neoplastic disease. The stage of the disease is important to treatment and prognosis. Certain blood tests have also been shown to be prognostic.
The stage of the disease is important to treatment and prognosis.
- Stage I - only one lymph node or lymphoid tissue in one organ involved.
- Stage II - lymph nodes in only one area of the body involved.
- Stage III - generalized lymph node involvement.
- Stage IV - any of the above with liver or spleen involvement.
- Stage V - any of the above with blood or bone marrow involvement.
Each stage is divided into either "substage a", those without systemic symptoms; or "substage b", those with systemic symptoms such as fever, loss of appetite, weight loss, and fatigue.
Splenic MZL is difficult to diagnose and can look similar to other types of lymphoma. Tests include a physical examination, blood tests to determine overall health and detect infections (ex. hepatitis C), a bone marrow biopsy, CT scan, and a PET scan. Sometimes a splenectomy is necessary during the diagnosis process in order to determine the exact type of lymphoma. If the spleen is removed, you will be at a larger risk of infection.
HGPIN in isolation does not require treatment. In prostate biopsies it is not predictive of prostate cancer in one year if the prostate was well-sampled, i.e. if there were 8 or more cores.
The exact timing of repeat biopsies remains an area of controversy, as the time required for, and probability of HGPIN transformations to prostate cancer are not well understood.
After a diagnosis and before treatment, a cancer is staged. This refers to determining if the cancer has spread, and if so, whether locally or to distant sites. Staging is reported as a grade between I (confined) and IV (spread). Staging is carried out because the stage of a cancer impacts its prognosis and treatment.
The Ann Arbor staging system is routinely used for staging of both HL and NHL. In this staging system, I represents a localized disease contained within a lymph node, II represents the presence of lymphoma in two or more lymph nodes, III represents spread of the lymphoma to both sides of the diaphragm, and IV indicates tissue outside a lymph node.
CT scan or PET scan imaging modalities are used to stage a cancer.
Age and poor performance status are established poor prognostic factors, as well.
HGPIN is diagnosed from tissue by a pathologist, which may come from:
- a needle biopsy taken via the rectum and,
- surgical removal of prostate tissue:
- transurethral resection of the prostate - removal of extra prostate tissue to improve urination (a treatment for benign prostatic hyperplasia),
- radical prostatectomy - complete removal of prostate and seminal vesicles (a treatment for prostate cancer).
Blood tests for prostate specific antigen (PSA), digital rectal examination, ultrasound scanning of the prostate via the rectum, fine needle aspiration or medical imaging studies (such as magnetic resonance imaging) are "not" useful for diagnosing HGPIN.
Hodgkin's lymphoma must be distinguished from non-cancerous causes of lymph node swelling (such as various infections) and from other types of cancer. Definitive diagnosis is by lymph node biopsy (usually excisional biopsy with microscopic examination). Blood tests are also performed to assess function of major organs and to assess safety for chemotherapy. Positron emission tomography (PET) is used to detect small deposits that do not show on CT scanning. PET scans are also useful in functional imaging (by using a radiolabeled glucose to image tissues of high metabolism). In some cases a Gallium scan may be used instead of a PET scan.
Treatment options vary and depend on the type and stage of cancer. Common treatments include surgery, chemotherapy, radiation therapy, amputation, and immunotherapy. A combination of therapies may be used. Knowledge and treatment of cancer have increased significantly in the past three decades. Survival rates have also increased due to the increase prevalence of canine cancer treatment centers and breakthroughs in targeted drug development. Canine cancer treatment has become an accepted clinical practice and access to treatment for owners has widely expanded recently. Cancer-targeting drugs most commonly function to inhibit excessive cell proliferation by attacking the replicating cells. However, there is still a prevalent pharmacy gap in veterinary oncology.
There is one canine tumor vaccine approved by the USDA, for preventing canine melanoma. The Oncept vaccine activates T-cell responses and antibodies against tumor-specific tyrosinase proteins. There is limited information about canine tumor antigens, which is the reason for the lack of tumor-specific vaccines and immunotherapy treatment plans for dogs.
Success of treatment depends on the form and extent of the cancer and the aggressiveness of the therapy. Early detection offers the best chance for successful treatment. The heterogeneity of tumors makes drug development increasingly complex, especially as new causes are discovered. No cure for cancer in canines exist.
Some dog owners opt for no treatment of the cancer at all, in which case palliative care, including pain relief, may be offered. Regardless of how treatment proceeds following a diagnosis, the quality of life of the pet is an important consideration. In cases where the cancer is not curable, there are still many things which can be done to alleviate the dog's pain. Good nutrition and care from the dog's owner can greatly enhance quality of life.
The staging is the same for both Hodgkin's and non-Hodgkin's lymphomas.
After Hodgkin lymphoma is diagnosed, a patient will be "staged": that is, they will undergo a series of tests and procedures that will determine what areas of the body are affected. These procedures may include documentation of their histology, a physical examination, blood tests, chest X-ray radiographs, computed tomography (CT)/Positron emission tomography (PET)/magnetic resonance imaging (MRI) scans of the chest, abdomen and pelvis, and usually a bone marrow biopsy. Positron emission tomography (PET) scan is now used instead of the gallium scan for staging. On the PET scan, sites involved with lymphoma light up very brightly enabling accurate and reproducible imaging. In the past, a lymphangiogram or surgical laparotomy (which involves opening the abdominal cavity and visually inspecting for tumors) were performed. Lymphangiograms or laparotomies are very rarely performed, having been supplanted by improvements in imaging with the CT scan and PET scan.
On the basis of this staging, the patient will be classified according to a staging classification (the Ann Arbor staging classification scheme is a common one):
- Stage I is involvement of a single lymph node region (I) (mostly the cervical region) or single extralymphatic site (Ie);
- Stage II is involvement of two or more lymph node regions on the same side of the diaphragm (II) or of one lymph node region and a contiguous extralymphatic site (IIe);
- Stage III is involvement of lymph node regions on both sides of the diaphragm, which may include the spleen (IIIs) or limited contiguous extralymphatic organ or site (IIIe, IIIes);
- Stage IV is disseminated involvement of one or more extralymphatic organs.
The absence of systemic symptoms is signified by adding "A" to the stage; the presence of systemic symptoms is signified by adding "B" to the stage. For localised extranodal extension from mass of nodes that does not advance the stage, subscript "E" is added. Splenic involvement is signified by adding "S" to the stage. The inclusion of "bulky disease" is signified by "X".
Gastric MALT lymphoma is frequently associated (72–98%) with chronic inflammation as a result of the presence of "Helicobacter pylori", potentially involving chronic inflammation, or the action of "H. pylori" virulence factors such as CagA.
The initial diagnosis is made by biopsy of suspicious lesions on esophagogastroduodenoscopy (EGD, upper endoscopy). Simultaneous tests for "H. pylori" are also done to detect the presence of this microbe.
In other sites, chronic immune stimulation is also suspected in the pathogenesis (e.g. association between chronic autoimmune diseases such as Sjögren's syndrome and Hashimoto's thyroiditis, and MALT lymphoma of the salivary gland and the thyroid).
The factors of poor prognosis for patients with thyroid lymphoma are advanced stage of the tumor, large size (>10 cm) as well as spreading to mediastinum. The overall survival for primary thyroid lymphoma is 50% to 70%, ranging from 80% in stage IE to less than 36% in stage IIE and IVE in 5 years.
Due to the causal relationship between "H. pylori" infection and MALT lymphoma, identification of the infection is mandatory. Histological examination of GI biopsies yields a sensitivity of 95% with five biopsies, but these should be from sites uninvolved by lymphoma and the identification of the organism may be compromised by areas of extensive intestinal metaplasia. As proton-pump inhibition can suppress infection, any treatment with this class of drug should be ceased 2 weeks prior to biopsy retrieval. Serology should be performed if histology is negative, to detect suppressed or recently treated infections. Following the recognition of the association of gastric MALT lymphoma with "H. pylori" infection, it was established that early-stage gastric disease could be cured by "H. pylori" eradication, which is now the mainstay of therapy. Fifty to 95% of cases achieve complete response (CR) with "H. pylori" treatment.
A t(11;18)(q21;q21) chromosomal translocation, giving rise to an "API2-MLT" fusion gene, is predictive of poor response to eradication therapy.
Treatment with dose-adjusted EPOCH with rituximab has shown promising initial results in a small series of patients (n=17), with a 100% response rate, and 100% overall survival and progression-free survival at 28 months (median follow-up).
Due to the high risk of recurrence and ensuing problems, close monitoring of dogs undergoing chemotherapy is important. The same is true for dogs that have entered remission and ceased treatment. Monitoring for disease and remission/recurrence is usually performed by palpation of peripheral lymph nodes. This procedure detects gross changes in peripheral lymph nodes. Some of the blood tests used in diagnosing lymphoma also offer greater objectivity and provide an earlier warning of an animal coming out of remission.
Complete cure is rare with lymphoma and treatment tends to be palliative, but long remission times are possible with chemotherapy. With effective protocols, average first remission times are 6 to 8 months. Second remissions are shorter and harder to accomplish. Average survival is 9 to 12 months. The most common treatment is a combination of cyclophosphamide, vincristine, prednisone, L-asparaginase, and doxorubicin. Other chemotherapy drugs such as chlorambucil, lomustine (CCNU), cytosine arabinoside, and mitoxantrone are sometimes used in the treatment of lymphoma by themselves or in substitution for other drugs. In most cases, appropriate treatment protocols cause few side effects, but white blood cell counts must be monitored.
Allogeneic and autologous stem cell transplantations (as is commonly done in humans) have recently been shown to be a possible treatment option for dogs. Most of the basic research on transplantation biology was generated in dogs. Current cure rates using stem cell therapy in dogs approximates that achieved in humans, 40-50%.
When cost is a factor, prednisone used alone can improve the symptoms dramatically, but it does not significantly affect the survival rate. The average survival times of dogs treated with prednisone and untreated dogs are both one to two months. Using prednisone alone can cause the cancer to become resistant to other chemotherapy agents, so it should only be used if more aggressive treatment is not an option.
Isotretinoin can be used to treat cutaneous lymphoma.
The most common chemotherapy used for non-Hodgkin lymphoma is R-CHOP.
Thyroid lymphoma shows a diagnostic and therapeutic challenge in many cases, because some manifestation patterns are similar to anaplastic thyroid cancer (ATC). Performance of fine-needle aspiration (FNA) has helped to distinguish these between two entities preoperatively.
Radiotherapy is the most effective treatment for local disease either as the sole treatment for low-grade lymphoma or in combination with chemotherapy for intermediate- and high-grade lymphoma. Radiotherapy dose in range of 30-45 Gy administered in fractions are advised in treating the local orbital lymphomas.
Of all cancers involving the same class of blood cell (lymphoproliferative disorders), 22% of cases are follicular lymphomas.
Median survival is around 10 years, but the range is wide, from less than one year, to more than 20 years. Some patients may never need treatment. The overall survival rate at five years is 72–77%. Recent advances and addition of Rituximab, improved median survival. Recent reports for the period 1986 and 2012 estimates median survival of over 20 years.
Nevertheless, the Working Formulation and the NHL category continue to be used by many. To this day, lymphoma statistics are compiled as Hodgkin's versus non-Hodgkin lymphomas by major cancer agencies, including the US National Cancer Institute in its SEER program, the Canadian Cancer Society and the IARC.