Complicated question about an unusual adenocarcinoma. By rule 1 would be easy to eliminate, the treatment of colon cancer is surgical (with neoadjuvant in rectal cancer). If biopsies confirm adenocarcinoma, there is no need to repeat them, since it is necessary to have the complete specimen. Most colon cancer develops on adenomas, so we could eliminate this one. Among the other 2, it is important to know that 5 is correct since they almost always present microsatellite instability even without fulfilling the Amsterdam criteria and have a better prognosis than other poorly differentiated colon cancer.

Complicated question about an unusual adenocarcinoma. By rule 1 would be easy to eliminate, the treatment of colon cancer is surgical (with neoadjuvant in rectal cancer). If biopsies confirm adenocarcinoma, there is no need to repeat them, since it is necessary to have the complete specimen. Most colon cancer develops on adenomas, so we could eliminate this one. Among the other 2, it is important to know that [HIDDEN] since they almost always present microsatellite instability even without fulfilling the Amsterdam criteria and have a better prognosis than other poorly differentiated colon cancer.

During a colonoscopy, a 5-cm tumor located in the right colon is detected in a 48-year-old man. No other lesions were found. His maternal grandmother also suffered from colon cancer. The biopsies are superficial and show a poorly differentiated tumor with abundant inflammatory cells in the stroma that is diagnosed as a medullary type carcinoma.

Chemotherapy is the treatment of choice.

Since the biopsy is superficial, it should be repeated before proceeding with treatment.

The prognosis of the tumor depends mainly on its high degree of anaplasia.

It is unlikely that this tumor has developed over a previous adenoma.

Microsatellite instability and DNA error repair genes should be studied.

Signet ring cell carcinoma

Colorectal Primary signet ring cell carcinoma of the colon and rectum (PSRCCR) is rare, with a reported incidence of less than 1 percent. It has a poor prognosis because symptoms often develop late and it is usually diagnosed at an advanced stage. Five-year survival rates in previous studies ranged from nine to 30 percent. Average survival was between 20 and 45 months. It tends to affect younger adults with higher likelihood of lymphovascular invasion. It is worth noting that the overall survival rate of patients with SRCC was significantly poorer than that of patients with mucinous or poorly differentiated adenocarcinoma. In advanced gastric cancers, the prognosis for patients with the SRCCs was significantly worse than for the other histological types, which can be explained by the finding that advanced SRCC gastric cancers have a larger tumor size, more lymph node metastasis, a deeper invasive depth and more Borrmann type 4 lesions than other types. Stomach

Colorectal cancer

The U.S. National Comprehensive Cancer Network and American Society of Clinical Oncology provide guidelines for the follow-up of colon cancer. A medical history and physical examination are recommended every 3 to 6 months for 2 years, then every 6 months for 5 years. Carcinoembryonic antigen blood level measurements follow the same timing, but are only advised for people with T2 or greater lesions who are candidates for intervention. A CT-scan of the chest, abdomen and pelvis can be considered annually for the first 3 years for people who are at high risk of recurrence (for example, those who had poorly differentiated tumors or venous or lymphatic invasion) and are candidates for curative surgery (with the aim to cure). A colonoscopy can be done after 1 year, except if it could not be done during the initial staging because of an obstructing mass, in which case it should be performed after 3 to 6 months. If a villous polyp, a polyp >1 centimeter or high-grade dysplasia is found, it

Histopathology of colorectal adenocarcinoma

Microscopy Adenocarcinoma is a malignant epithelial tumor, originating from superficial glandular epithelial cells lining the colon and rectum. It invades the wall, infiltrating the muscularis mucosae layer, the submucosa, and then the muscularis propria. Tumor cells describe irregular tubular structures, harboring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Sometimes, tumor cells are discohesive and secrete mucus, which invades the interstitium producing large pools of mucus. This occurs in mucinous adenocarcinoma, in which cells are poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus at the periphery, this occurs in "signet-ring cell." Depending on glandular architecture, cellular pleomorphism, and mucosecretion of the predominant pattern, adenocarcinoma may present three degrees of differentiation: well, moderately, and poorly differentiated. Micrographs (H&E stain) Microscopic criteria

[Clinicopathological characteristics and prognosis analysis of colorectal synchronous multiple primary cancer].

To investigate the clinicopathological features and prognosis of colorectal synchronous multiple primary cancer(SMPC). From January 2008 to June 2011, 51 patients diagnosed with colorectal SMPC underwent surgery at Department of General Surgery of Peking University First Hospital. Their clinicopathological features, diagnosis, treatment and prognosis were summarized and analyzed. SMPC was diagnosed according to the following criteria: each tumor must have a definite pathologic picture of malignancy; metastasis or recurrence from another colorectal cancer was excluded; tumors must be distinctly separated by at least 5 cm of all intact bowel wall from each other; SMPC has abnormal cells between tumor and normal mucosa and abnormal gland of transitional zone; each cancer is infiltrating carcinoma except the carcinoma in situ; all the cancers are detected at the same time or within 6 months. Multiple primary colorectal cancer originated from familial colonic polyposis or ulcerative colitis was excluded. These 51 colorectal SMPC patients accounted for 3.5% of 1 452 colorectal cancer patients in the same period at our hospital, with 32 males and 19 females, and mean age of (63±13)(29 to 82) years. Of 51 cases, 46(90.2%) had 2 original carcinoma, 3(5.9%) had 3 original carcinoma and 2(3.9%) had 4 carcinoma; 23(45.1%) complicated with colon polyps, 4(7.8%) complicated with malignancy outside the colorectum. In TNM staging, 7(13.7%), 15(29.4%), 24(47.1%) and 5(9.8%) patients were stage I(, II(, III( and IIII( respectively. Among 51 patients undergoing surgery by different procedures, 16 were subtotal colon resection, 8 were extended right colon resection, 5 were extended left hemicolon resection, 8 were right hemicolon resection plus Dixon procedure, 10 were Dixon, and 4 were right hemicolon resection plus sigmoid colon resection. Adjuvant chemotherapy and support treatment were given according to the condition after operation. A total of 105 tumors were found, including 25(23.8%) tumors in sigmoid colon, 24(22.9%) in rectum, 22(21.0%) in ascending colon and 4 in organs outside the colorectum. Tubular adenocarcinoma (86/105, 81.9%) was the main pathological type in these colorectal SMPC patients. During the follow-up of median 43.5 months, 10 cases presented local recurrence and 6 cases had liver metastasis. Multivariable analysis showed that ≤65 years old (OR=22.757, 95%CI: 1.562-331.543, P=0.002),undifferentiated carcinoma or mucous adenocarcinoma (OR=27.174, 95%CI: 2.834-260.512, P=0.004), stage III(-IIII( (OR=29.626, 95%CI: 3.216-272.884, P=0.003) were independent risk factors of postoperative 5-year recurrence and metastasis, but the number of SMPC lesions and the surgical method were not associated with postoperative 5-year recurrence and metastasis (P=0.564, P=0.513). The 3-year and 5-year survival rates of colorectal SMPC patients were 76.5% and 64.7%. Two-original carcinoma is the most common in colorectal SMPC patients, which mainly distributes in sigmoid colon and rectum. Postoperative monitoring should be strengthened for those patients with younger age, poor pathological types and advanced staging to prevent recurrence and metastasis.

Colorectal cancer

In Stage I colon cancer, no chemotherapy is offered, and surgery is the definitive treatment. The role of chemotherapy in Stage II colon cancer is debatable, and is usually not offered unless risk factors such as T4 tumor, undifferentiated tumor, vascular and perineural invasion or inadequate lymph node sampling is identified. It is also known that the people who carry abnormalities of the mismatch repair genes do not benefit from chemotherapy. For stage III and Stage IV colon cancer, chemotherapy is an integral part of treatment.

Microsatellite instability

Direct and indirect mechanisms contribute to chemotherapy resistance. Direct mechanisms include pathways that metabolize the drug, while indirect mechanisms include pathways that respond to the chemotherapy treatment. The NER DNA repair pathway plays a substantial role in reversing cell damage caused by chemotherapeutic agents such as 5-FU. Discoveries since 2010 In May 2017 the FDA approved an immunotherapeutic called Keytruda (pembrolizumab) (PD-1 inhibitor) for patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment. This indication is independent of PD-L1 expression assessment, tissue type and tumor location. Researchers have found another MSI, called elevated microsatellite alterations at selected tetranucleotide repeats (EMAST). However, EMAST is unique in that it is not derived from MMR, and it is commonly associated with TP53 mutations.

[The role of colonoscopy in early diagnosis of intraluminal recurrences in patients already treated for colorectal cancer].

It is a common opinion that the more often and the more rigorously the colon is examined, the more lesions will be discovered and diagnosed. However it has not been shown which methods of colonic examination and which regimen of surveillance should be used. Chart review was conducted on 481 patients who underwent curative resection for colorectal cancer between 1980 and 1990. Colonoscopy was performed preoperatively, after 12-15 months from surgical treatment, and then at an interval of 12-24 months, or when symptoms appeared. About ten percent of patients developed intraluminal recurrences, and more than 25% adenomatous polyps. More than one half of the metachronous lesions arise within the first 24 months. The median time to diagnosis was 25 months for intraluminal recurrences and 22 months for adenomatous polyps. Patients with left sited tumor at an advanced stage run a higher risk of developing recurrent intraluminal disease, and patients who presented associated polyps at the time of the operation for the index cancer have a higher risk of developing new polyps. About 50% of recurrences were detected when patients were asymptomatic. Colonoscopy must be performed within the first 12-15 months after operation, while an interval of 24 months between each examination seems sufficient to guarantee an early detection of metachronous lesion. Asymptomatic patients are more frequently reoperated for cure and thus have a better survival rate.

Colorectal cancer

Bowel cancer may be diagnosed by obtaining a sample of the colon during a sigmoidoscopy or colonoscopy. This is then followed by medical imaging to determine whether the disease has spread. Screening is effective for preventing and decreasing deaths from colorectal cancer. Screening, by one of a number of methods, is recommended starting from the age of 50 to 75. During colonoscopy, small polyps may be removed if found. If a large polyp or tumor is found, a biopsy may be performed to check if it is cancerous. Aspirin and other non-steroidal anti-inflammatory drugs decrease the risk. Their general use is not recommended for this purpose, however, due to side effects.

Biopsy

There are two types of liquid biopsy (which is not really a biopsy as they are blood tests that do not require a biopsy of tissue): circulating tumor cell assays or cell-free circulating tumor DNA tests. These methods provide a non-invasive alternative to repeat invasive biopsies to monitor cancer treatment, test available drugs against the circulating tumor cells, evaluate the mutations in cancer and plan individualized treatments. In addition, because cancer is a heterogeneous genetic disease, and excisional biopsies provide only a snapshot in time of some of the rapid, dynamic genetic changes occurring in tumors, liquid biopsies provide some advantages over tissue biopsy-based genomic testing. In addition, excisional biopsies are invasive, can’t be used repeatedly, and are ineffective in understanding the dynamics of tumor progression and metastasis. By detecting, quantifying and characterisation of vital circulating tumor cells or genomic alterations in CTCs and cell-free DNA in

Localization, clinical and pathological characteristics and survival in sporadic colon cancer patients younger than 40 and over 65 years of age.

Colorectal cancer is predominantly a disease of older population, but occasionally it affects younger patients, in whom very often diagnosis is overseen and treatment begins late. The aim of our study was to compare localization, clinical and pathological characteristics and survival of sporadic colorectal cancer patients aged up to 40 and over 65 years. The first group (group I) included 19 patients under 40 years and the second group (group II) 28 patients aged over 65 years, treated during 1997-2001. Patients with family history of colon cancer and inflammatory disease of the colon were not included. Arithmetic mean, standard deviation, Fisher's test, Student 's t test, x(2) test and the Kaplan-Meier method were used in the statistical analysis of the results. There was no difference among the tested groups regarding tumor localization. The most frequent localization was in the rectum and left colon. At presentation, in group I patients, besides the metastases in the liver and lymph nodes, colorectal cancer infiltrated also the duodenum, stomach, right kidney capsule in one patient, and adnexa in two patients. In group II patients we registered only liver and lymph node metastases. Pathologically, tubular and mucinous forms were present in all of the patients up to 40 years of age, while only one patient over 65 had tumor with mucinous component. In group I, Astler-Coller stage B was found in 1.5% of the patients, stage C in 72.5% and stage D in 26%; in group II, stage B was found in 1.5%, stage C in 84.5% and stage D in 14%. Grade III was 36.8% in group I and 17.8% in group II. No statistical differences were found in stage distribution (p=0.36) and grade (p=0.06) between group I and II. Five-year overall survival was 57.8% and 28.5% in younger and older patients, respectively (p=0.053). The results obtained showed no difference in clinical symptomatology and tumor localization in both groups. The incidence of more aggressive tumors was higher in younger persons. However, early detection combined with more aggressive therapeutic approach, could enable significant improvement of the 5-year survival of younger patients with colon cancer.

Microsatellite instability

Microsatellite instability diagnostics MSI is a good marker for determining Lynch syndrome and determining a prognosis for cancer treatments. In 1996, the National Cancer Institute (NCI) hosted an international workshop on Lynch Syndrome, which led to the development of the “Bethesda Guidelines” and loci for MSI testing. During this first workshop the NCI has agreed on five microsatellite markers necessary to determine MSI presence: two mononucleotides, BAT25 and BAT26, and three dinucleotide repeats, D2S123, D5S346, and D17S250. MSI-H tumors result from MSI of greater than 30% of unstable MSI loci (>2 or more of the 5 loci). MSI-L tumors result from less than 30% of unstable MSI biomarkers. MSI-L tumors are classified as tumors of alternative etiologies. Several studies demonstrate that MSI-H patients respond best to surgery alone, rather than chemotherapy and surgery, thus preventing patients from needlessly experiencing chemotherapy.

Definitive treatment of "malignant" polyps of the colon.

There has been an unremitting rise in incidence of colonic cancer in this country with no recent improvement in cure rate. As a result the evolution of colorectal cancer has been the focus of considerable attention with an enlarging body of evidence pointing to the common neoplastic polyp as a precursor to malignancy. "Neoplastic" polyps include "adenomatous polyps," "villous adenomas" and, lately recognized, "villo-glandular polyps." Experience with endoscopic removal of over 2,000 colonic polyps (with no mortality) has introduced two questions of prime concern to the surgeon: (1) What constitutes  clinical malignancy in a polyp? AND, (2) When should laparatomy supplant or follow endoscopic removal? Eight hundred and ninety-two consecutive adenomatous (tubular), villous, villoglandular (villo-tubular) and "polypoid cancer" polyps are analyzed, 855 of which have been followed for 6 months to 4 years. Support is offered to the concept that villous and tubular growth patterns are merely variants of a similar base disturbance in cell renewal. Superficial cancer (carcinoma-in-situ) occurred in 6.6% of neoplastic polyps and represents no threat if the polyp is completely removed. Only when the cancer penetrates the muscularis mucosae should it be regarded as "invasive." The term "malignant polyp" should be reserved for this form. Invasive cancer was found in 5.0% of neoplastic polyps in this series. Only in this group need the question of further surgical intervention be raised. Major considerations influencing a decision for subsequent laparotomy are polyp size and gross morphology (i.e. sessile or pedunculated), histologic type (of the polyp and of the cancer itself), adequacy of clearance between depth of invasion and plane of polyp resection, and the patient's age and general condition. These are analyzed. Twenty-five of 46 patients with "malignant polyps" were subjected to abdominal exploration: 17 showed no residual cancer, whereas 8 (5 with recognized incomplete endoscopic removal) had tumor in the bowel wall. Of the remaining 21 patients, for whom endoscopic polypectomy alone was deemed appropriate, none have shown residual or recurrent cancer on clinical and endoscopic followup. Colonoscopy appears to be a most promising approach in terms of the goals of cancer programs, offering both prophylaxis and opportunity for treatment at a favorable stage of disease.

Skin cancer in cats and dogs

Treatment The specific treatment will depend on the tumor's type, location, size, and whether the cancer has spread to other organs. Surgical removal of the tumor remains the standard treatment of choice, but additional forms of therapy such as radiation therapy, chemotherapy, or immunotherapy exist. When detected early, skin cancer in cats and dogs can often be treated successfully. In many cases, a biopsy can remove the whole tumor, as long as the healthy tissues removed from just outside the tumor area do not contain any cancer cells. References External links Skin Cancer in Cats and Dogs from Pet Cancer Center Skin Cancer in Dogs from CanineCancer.com' Types of animal cancers Cancer in dogs Cancer in cats Integumentary neoplasia

[Gastrocolic tumor progression--a possibility or mere supposition?].

The authors examined the five-years postoperative survival rate of fifty patients who suffered from colorectal cancer along with the fact that the large bowel one of the neighbouring organs were resected. The subjects were divided into four groups: the colorectal resection was associated with (1) stomach resection (13 patients); (2) liver metastasectomy (14 patients); (3) small bowel resection (10 patients); (4) the resection of other organs (13 patients). In the first two years of the study they were examined once in every three months, in the next two years once in every six months and then yearly. The following tests were carried out: chest X ray, abdominal sonography, irrigography or colonoscopy and CEA. On condition that the colonoscope reached the caecum and the result was negative, the test was repeated only a year later. The patients were operated on between 1985 and 1997. The statistical analysis was made with the help of the Kaplan-Meier method. During this period fifty-six complex resections were performed. Out of fifty-six patients fifty were followed. Compliance 89%. In group 1, where the average age of patients was sixty-two years, one patient died in the forty-first and the other in the fifty-second month after the surgery. Survival rate: 11/13 (83%). The survival rates for the other groups were as follows: group 2 (average age 64) twelve patients died within five years. Survival rate 2/14 (14%). The difference between the survival rates in the first two groups in significant (P = 0.0001). Group 3 (average age 67) seven died and only three survived. Survival rate: 3/10 (30%). The difference between group 1 and group 3 is significant (P = 0.0022). Group 4 (average age 64) seven patients died. Survival rate 6/13 (46%). Comparing this rate to that of the group 1, the difference is not significant (P > 0.01). Having analysed the results of the four groups it can be concluded that the patients of group 1 lived the longest (stomach resection) and those of group 2 (liver metastasectomy) died the earliest after the operation. It is surprising that the patients of group 3 lived significantly shorter than the ones of group 1 in spite of the fact that they belong by far the greatest number to stage Dukes B (group 1: 12/13 = 92%; group 3: 7/10 = 70%). The authors assume that the partial or the total absence of the stomach keeps back the growth of the tumour (gastro-colic tumour growing dependency). They think that in case of colon cancer which infiltrates the stomach surgeons experienced in gastric and colorectal surgery should be encouraged to take the risk of the double resection providing the fact that the operation is accomplishable.

Biopsy

in understanding the dynamics of tumor progression and metastasis. By detecting, quantifying and characterisation of vital circulating tumor cells or genomic alterations in CTCs and cell-free DNA in blood, liquid biopsy can provide real-time information on the stage of tumor progression, treatment effectiveness, and cancer metastasis risk. This technological development could make it possible to diagnose and manage cancer from repeated blood tests rather than from a traditional biopsy.

[Diagnosis and therapy of colorectal polyps with special reference to adenomas].

Colo-rectal adenoms occur more frequently in the elderly and should be considered as precancerous. The structural changes of the glandular epithelium are known as dysplasia or atypia and are classified into three grades of severity; the "severe epithelial dysplasia" has all the histological characteristics of a malignant tumor which however has not infiltrated the muscularis mucosa and so has not gained access to the lymphatic system. Whenever these structural changes were present the terms focal carcinoma or carcinoma in situ were used. However in 1976 the WHO accepted to change the nomenclature to "severe epithelial dysplasia", as Morson had proposed. Their aim was to avoid superfluous radical surgical intervention. Whenever severe dysplasia is present in an adenoma, the necessary therapy is the local excision of the adenoma together with its pedick. An exact complete histological examination is necessary. Between 1976 and 1980 we saw 201 cases of adenoma of the colon or rectum at the Surgical Clinic, University of Düsseldorf. 27 of these cases showed severe epithelial dysplasia. As described in the literature there was a correlation between the size of the adenoma, the histological picture and the risk of malignancy. The reexamination of 105 patients showed that there was a significant percentage of recurrency at the site of excision or new polyps at a different site. Therefore, regular checkups are a must for all those patients in whom polyps of the large bowel have been removed.

Lipofibromatosis

The diagnosis of LPF depends on its clinical presentation almost exclusively in newborn and young children and, most importantly, its histopathology as determined on biopsied intact tissue or fine-needle aspiration to obtain a sampling of the tumor's cells. Intact tissue samples typical show abundant mature-appearing adipose (i.e. fat) tissue mixed with a minor component of oval-shaped or spindle-shaped fibroblast-like cells some of which have a pseudolipoblast-like morphology. Needle biopsies should show these cells. However, LPF histopathology can vary widely between cases. The cited gene abnormalities in the above section are insufficient to support a diagnosis of LPF although further study of these and discoveries of other gene abnormalities may do so. The histopathology of lipofibromatosis-like neural tumors (LPF-NT) can closely resemble LPF tumors. Unlike LPF tumors, however, LPF-NT tumors have been diagnosed in adults in more than 27% of cases with the remaining cases diagnosed

[Synchronous and metachronous tumors of the colon and rectum].

Three hundred and seventy-two patients with colorectal tumours treated by curative resection between January 1982 and January 1992 were reviewed in order to determine the role of colonoscopy and the outcome of patients with multiple tumours. Thirty (8.1%) of them with a mean age of 57 (35-79) years (20 males, 10 females) had synchronous (19 cases) or metachronous (11 cases) lesions. Rectum and sigmoid colon were the most frequent site of multiple lesions, accounting for 73% of all lesions. Accurate pre-operative diagnosis was performed in 14 of the 19 patients with synchronous lesions, and in the remaining 5 cases failure to perform an intra-operative colonoscopy was the cause of missing the lesions. Three of them had over-looked lesions on the previous barium enema. Synchronous lesions has the tendency to be less invasive as compared to metachronous ones. Five-year survival rates (Kaplan-Meier method) were 45% and 58% for patients with multiple and single lesions respectively (not significant). For patients with colorectal carcinoma a thorough examination of the whole colon by intra-operative colonoscopy should be accomplished in order to rule out the possibility of associated lesions as well as to decrease the incidence of "early" metachronous lesions.

Benign tumor

Tumors are formed by carcinogenesis, a process in which cellular alterations lead to the formation of cancer. Multistage carcinogenesis involves the sequential genetic or epigenetic changes to a cell's DNA, where each step produces a more advanced tumor. It is often broken down into three stages; initiation, promotion and progression, and several mutations may occur at each stage. Initiation is where the first genetic mutation occurs in a cell. Promotion is the clonal expansion (repeated division) of this transformed cell into a visible tumor that is usually benign. Following promotion, progression may take place where more genetic mutations are acquired in a sub-population of tumor cells. Progression changes the benign tumor into a malignant tumor. A prominent and well studied example of this phenomenon is the tubular adenoma, a common type of colon polyp which is an important precursor to colon cancer. The cells in tubular adenomas, like most tumors that frequently progress to

Circulating tumor DNA

The emergence of drug-resistant tumors due to intra- and inter-tumoral heterogeneity an issue in treatment efficacy. A minor genetic clone within the tumor can expand after treatment if it carries a drug-resistant mutation. Initial biopsies can miss these clones due to low frequency or spatial separation of cells within the tumor. For example, since a biopsy only samples a small part of the tumor, clones that resides in a different location may go unnoticed. This can mislead research that focuses on studying the role of tumor heterogeneity in cancer progression and relapse. The use of ctDNA in research can alleviate these concerns because it could provide a more representative 'screenshot' of the genetic diversity of cancer at both primary and metastatic sites. For example, ctDNA has been shown to be useful in studying the clonal evolution of a patient’s cancer before and after treatment regimens. Early detection of cancer is still challenging but recent progress in the analysis of

[A thousand total colonoscopies: what is the relationship between distal and proximal findings?].

Flexible sigmoidoscopy is indicated for colorectal cancer screening. The decision about who needs total colonoscopy based on distal findings is still controversial because of the uncertainty of the associations between distal and proximal findings. The purpose of the study was to characterize distal findings in patients with total colonoscopy, to investigate its importance as markers of advanced proximal lesions and to evaluate the usefulness of a clinical Predictive Index, already published in the literature, in the identification of these lesions. Retrospective analysis of the patients submitted to total colonoscopy between January 2006 and February 2007, with selection of 1000 consecutive cases with reference to polyps. We analysed demographic data, indication for the exam and morphological and histological characteristics of the polyps. Advanced lesion was defined as any adenoma larger than 10 mm or any polyp with villous characteristics, high grade dysplasia or cancer. The Predictive Index was obtained through the assignment of points to 3 categories: sex, age and distal findings, which result in 3 groups: low, intermediate and high risk. The mean age of patients was 64,69 years and 65,1% were male. Distal and proximal polyps were identified in 829 (82,9%) and 369 (36,9%) patients, respectively. Advanced distal lesion was found in 342 patients (34,2%) and advanced proximal lesion in 98 (9,8%). 587 patients (58,7%) were in the high risk group. In the group of patients with advanced proximal lesion, a third presented low and intermediate risk, 52% had no distal polyps, 88,7% had less than three distal polyps and 71,4% had no advanced distal lesion. Sensitivity values for these four categories ranged between 11,2% and 66,6%. If the decision to perform total colonoscopy is based on distal colonic findings or on the Predictive Index, the ability to identify advanced proximal lesion is markedly reduced, endangering the aim of a screening program.

Endoscopic mucosal resection

For the esophagous Endoscopic mucosal resection has been advocated for early esophageal cancers (that is, those that are superficial and confined to the mucosa only) and has been shown to be a less invasive, safe, and effective therapy for early squamous cell carcinoma. It has also been shown to be safe and effective for early adenocarcinoma arising in Barrett’s esophagus. The prognosis after treatment with this method is comparable to surgical resection. This technique can be attempted in patients who have no evidence of nodal or distant metastases, with differentiated tumors that are slightly raised and less than 2 cm in diameter, or in differentiated tumors that are ulcerated and less than 1 cm in diameter. The most commonly employed modalities of endoscopic mucosal resection include strip biopsy, double-snare polypectomy, resection with combined use of highly concentrated saline and epinephrine, and resection using a cap.

A potentially brighter prognosis for colon carcinoma in the third and fourth decades.

In contrast to earlier studies that suggested that colon carcinoma is unusually lethal in the young, 69 patients, ages 20 to 39 years, had a relatively good prognosis. Fifty-nine percent lived over 5 years after diagnosis, and 51% were cured. Furthermore, 67% were cured if they did not have distant spread of the carcinoma at the time of the initial operation. Neither age, sex, tumor size, location, mere presence of lymph node metastases, depth of tumor invasion, nor predisposing disease of the colon was a strong prognostic factor. Metastases to six or more lymph nodes and distant spread of the tumor at the time of initial surgery were ominous findings. Mucinous carcinoma was relatively frequent (28%) and was also an ominous feature (only 5 of 20 patients cured as opposed to 26 of 43 with classical adenocarcinoma).

Skin cancer in cats and dogs

Cytology is an important tool that can help the veterinarian distinguish a tumor from inflammatory lesions. The biopsy technique used will largely depend on the tumor's size and location. Small masses are usually completely excised and sent to the pathology lab to confirm that the surrounding healthy tissues that were excised along with the tumor do not contain any cancer cells. If the tumor is larger, a small sample is removed for analysis and depending on the results, appropriate treatment is chosen. Depending on the tumor type and its level of aggressiveness, additional diagnostic tests can include blood tests to assess the pet’s overall health, chest X-rays to check for lung metastasis, and abdominal ultrasound to check for metastasis to other internal organs.

[Clinical and macroscopic variables that influence the prognosis of colorectal carcinoma].

The paradoxical evolution of approximately one third of patients with neoplasms cataloged in Dukes stages B and C demonstrates the desirability of utilizing other prognostic criteria that are capable of broadening the information provided by these two important variables. Only a small number of investigators have dedicated themselves to the study of the prognostic value of clinical and macroscopic parameters of colorectal neoplasms, and the results obtained have been shown to be controversial. The principal aim of this work was to evaluate the prognostic importance of these parameters. A study was made of 320 patients with colorectal cancer who underwent curative extirpation. They had a median age of 58 years, and there were 199 females (62.2%) and 121 males (37.8%). The patients were divided into three age groups: under 40 years old, between 40 and 60 years old and over 60 years old. The tumors were distributed in three intestinal segments: right colon, left colon and rectum. The neoplasms were classified as small (diameter less than or equal to 35 mm) and large (diameter greater than 35 mm). With regard to their form, they were classified as exophytic, when characterized by luminal growth, and endophytic, when there was intramural growth. The involvement of the intestinal circumference at the site of the neoplasm was considered as partial or total. Of the 320 patients, 22 (6.9%) were aged under 40 years, 159 (49.7%) from 40 to 60 years and 139 (43.4%) presented an age of over 60 years. Seventy-three (22.8%) of the neoplasms were located in the right colon, 130 (40.6%) in the left colon and 117 (36.6%) in the rectum. Regarding the size, 280 (87.5%) were large and 40 (12.5%) small; exophytic lesions predominated over endophytic ones - 173 (54.1%) vs 147 (45.9%). A greater number of tumors presented total involvement of the intestinal circumference - 216 (67.5%) - while 104 (32.5%) presented partial involvement. The 5-year survival of the patients was not influenced by their age and sex, or by the location and size of the neoplasms. Exophytic lesions conferred greater survival on their sufferers (65.9%), in comparison with endophytic lesions (49.0%). The survival of patients with lesions partially involving the intestinal circumference was greater than for those with total involvement - 72.1% vs. 51.4%. Clinical variables had no influence on the patients' prognosis. Among the macroscopic variables, the form of the neoplasia and its involvement in the intestinal circumference did influence the patients' prognosis. These last two variables are important data capable of contributing to the identification of patient subpopulations with greater or lesser prognostic risk.

Pancreatic neuroendocrine tumor

In functioning PanNETs, octreotide is usually recommended prior to biopsy or surgery but is generally avoided in insulinomas to avoid profound hypoglycemia. PanNETs in Multiple endocrine neoplasia type 1 are often multiple, and thus require different treatment and surveillance strategies. Some PanNETs are more responsive to chemotherapy than are gastroenteric carcinoid tumors. Several agents have shown activity. In well differentiated PanNETs, chemotherapy is generally reserved for when there are no other treatment options. Combinations of several medicines have been used, such as doxorubicin with streptozocin and fluorouracil (5-FU) and capecitabine with temozolomide. Although marginally effective in well-differentiated PETs, cisplatin with etoposide has some activity in poorly differentiated neuroendocrine cancers (PDNECs), particularly if the PDNEC has an extremely high Ki-67 score of over 50%.

[Cancers of the colon. Results of surgical treatment. Presentation of a series of 234 patients].

This report is a retrospective analysis of the results of surgical treatment in 234 consecutive cases of adenocarcinoma of the colon; 56.4 p. 100 of patients were male with a mean age of 66. Sixty per cent of the carcinoma were situated in the sigmoid. Carcinoma was complicated in 26.1 p. 100 of cases. The tumor was confined to the bowel wall in 14.3 p. 100 of cases (stage A), involved the serosa in 36.3 p. 100 of cases (stage B), lymph nodes in 25.5 p. 100 of cases (stage C), and distal organs in 23.8 p. 100 of cases (stage D). Global operative mortality was 10 p. 100. Obvious anastomotic leakages occurred in two patients with one death. The overall five year survival rate was 35 p. 100. The stage-by-stage 5-year survival rates depended mainly on the differentiation and on the extension of the tumor: 59.2 p. 100 in patients with stage A lesions, 54.8 p. 100 in those with stage B lesions, 30.2 p. 100 in those with stage C lesions, 3.9 p. 100 in those with stage D lesions. On the other hand, survival was not significantly related to the duration of symptoms. This suggests that early diagnosis of symptomatic disease does not guarantee a better prognosis. This can only be achieved by prevention of the disease.

[Association between microsatellite instability and clinico-pathological characteristics in sporadic colon cancer].

Currently, colon cancer is a leading cause of cancer death world-wide. It progresses according to three molecular pathways, named suppressor, mutador and methylator. Microsatellite instability is a hallmark of the lack of reparation, of DNA mismatches and it characterizes a subset of colon tumors (unstable tumors, MSI). MSI-H patients (high degree of microsatellite instability) seem to share clinico-pathological differences with MSS (microsatellite stable) and MSI-L (low degree of microsatellite instability) patients. In this study, associations between high degree of microsatellite instability and pathological (location, mucinous content, differentiation grade, stages T3N0, stages II and III) and clinical features (response to chemotherapy, disease-free survival and overall survival) were evaluated. 117 patients with sporadic colon cancer were classified into two populations (MSS/MSI-L and MSI-H) by using PCR and electrophoresis of seven microsatellites, according to the National Cancer Institute recommendations. MSI-H tumors tended to be located in the right colon (p = 0.022) and were of mucinous histologic type (p = 0.04). No differences in disease-free survival and overall survival between group of stage II and III patients with MSS/ MSI-L and corresponding ones with MSI-H colon cancer were found (p = 0.54, p = 0.37, respectively). Conversely, MSI-H patients with stage II colon cancer had a favourable prognosis (p = 0.027). Nevertheless, response to 5-fluorouracil (5-FU) and leucovorin was similar in MSS/ MSI-L and MSI-H groups (p = 0.38). MSI-H patients are characterized by certain pathological features; those MSI-H patients with a stage II seem to have a better prognosis than MSS/ MSI-L patients.

Surgical pathology

polyps are very common. The pathologist's interpretation of a biopsy is critical to establishing the diagnosis of a benign or malignant tumor, and can differentiate between different types and grades of cancer, as well as determining the activity of specific molecular pathways in the tumor. This information is important for estimating the patient's prognosis and for choosing the best treatment to administer. Biopsies are also used to diagnose diseases other than cancer, including inflammatory, infectious, or idiopathic diseases of the skin and gastrointestinal tract, to name only a few.

Synchronous colorectal carcinomas.

Eighteen (5.0%) out of 358 patients who underwent resection of a colorectal carcinoma during the period 1978 through 1990 had synchronous colorectal carcinomas, and were 5.6 years younger on average than those with a single carcinoma. The distance between synchronous lesions was less than 10 cm in 69.6% of all the patients in the study. Among the synchronous carcinomas there was a higher incidence of ascending colon involvement, mucinous carcinoma, family history of malignant diseases, multiple malignant neoplasms associated with other organs and benign neoplastic polyps of the colorectum, and it is suggested that hereditary oncogenic factors influence these carcinomas. The synchronous lesions were detected pre-operatively in 14 of 18 patients with synchronous carcinomas, and the most common reason why synchronous lesions were missed was that the lesions on the anal side prevented the lesions on the proximal side from being examined. The prognosis in the synchronous lesion group was worse than in the solitary lesion group. Since it is difficult to predict synchronous colorectal carcinomas, careful pre-operative examination, including that of other organs, is necessary, and intra-operative colonoscopy should be carried out when pre-operative examination was insufficient.

Pembrolizumab

In May 2017, pembrolizumab received an accelerated approval from the US FDA for use in any unresectable or metastatic solid tumor with DNA mismatch repair deficiencies or a microsatellite instability-high state (or, in the case of colon cancer, tumors that have progressed following chemotherapy). This approval marked the first instance in which the FDA approved marketing of a drug based only on the presence of a genetic mutation, with no limitation on the site of the cancer or the kind of tissue in which it originated. The approval was based on a clinical trial of 149 patients with microsatellite instability-high or mismatch repair deficient cancers who enrolled on one of five single-arm trials. Ninety patients had colorectal cancer, and 59 patients had one of 14 other cancer types. The objective response rate for all patients was 39.6%. Response rates were similar across all cancer types, including 36% in colorectal cancer and 46% across the other tumor types. Notably, there were 11

Synchronous and 'early' metachronous carcinomas of the colon and rectum.

In a review of cases of colorectal cancer presenting to St. Mark's Hospital over the 16-year period 1970-85, 59 patients were found to have a synchronous carcinoma (3.4 per cent). Although 82 per cent of these synchronous tumours were distal to the splenic flexure (and hence within reach of a 60 cm flexible sigmoidoscope) only 42 per cent were detected pre-operatively: the remaining tumours were noted at surgery (24 per cent) or found incidentally on pathological examination of the resected specimen (34 per cent). Histological examination of these synchronous lesions revealed a high proportion with favourable stage (Dukes' A-75 per cent) and grade (well or moderate differentiation-90 per cent). Over the same 16-year period, 10 patients presented with an 'early' metachronous lesion (less than 3 years from initial surgery). Review of these cases noted negative findings on the initial barium studies in four patients and a failure to conduct full examination of the colon at initial presentation in the remaining six. It is concluded that full examination of the colon in all patients presenting with primary colorectal cancer is mandatory and that, in the light of this experience and recent reports in the literature, this should be by pre- or peroperative colonoscopy.


In the presence of acute gouty arthritis (the presence of intracellular crystals with negative birefringence confirms this) in a hyperuricemic patient previously treated with allopurinol, an NSAID should be added until the crisis subsides. No changes should be made in the hypouricemic treatment during this period because the uric acid metabolic chain is altered and the situation may worsen.

A hyperuricemic patient who usually takes 100 mg of allopurinol daily comes to the ED with acute pain and inflammatory signs in the right knee. Arthrocentesis is performed and polarized light microscopy shows intracellular crystals with negative birefringence. Which of the following therapeutic approaches is the most appropriate in this case?

Discontinue allopurinol and start colchicine treatment.

Discontinue allopurinol and start NSAIDs.

Increase the dose of allopurinol to 300 mg/day.

Substitute allopurinol for uricosuric acid.

Does starting allopurinol prolong acute treated gout? A randomized clinical trial.

Traditionally, allopurinol is not initiated during an acute gout attack to avoid prolonging the painful arthritis. The 2012 American College of Rheumatology Guidelines for the Management of Gout suggest that urate-lowering therapy can be started during an acute attack, based on "consensus opinion of experts, case studies, or standard of care." The aim of this study was to determine whether initiating allopurinol will adversely affect the resolution of acute, treated gout. We conducted a 28-day, placebo-controlled, double-blind study of allopurinol initiation in patients with acute gout. Patients with crystal-proven gout by arthrocentesis were enrolled if they presented to the rheumatology clinic with an acute gout attack within 72 hours from initial therapy. The patients were also required to meet at least 1 additional criterion for urate-lowering therapy including (1) the presence of gouty tophi, (2) more than 1 acute gout attack per year, (3) a history of nephrolithiasis, or (4) urate overproduction (>1000 mg in 24-hour urine collection). Patients were excluded from the study if they had a glomerular filtration rate of less than 50 or liver function test of greater than 1.25 times the upper limit of normal. The treating physician determined therapy for the acute gout attack. Standard prophylaxis, with colchicine or nonsteroidal anti-inflammatory drugs, was prescribed. Allopurinol or placebo was initiated at 100 mg daily for the first 14 days and then increased to 200 mg daily for the next 14 days. The primary end point was protocol defined days to resolution of acute gout, incorporating patient-rated joint pain and physician examination. Secondary measures included Physician Global Assessment, patient-rated pain, adverse effects of therapy, and serum uric acid. Thirty-one patients (17 on placebo, 14 on allopurinol) completed the study. Both intent-to-treat and completer analyses showed only a statistically insignificant difference in days to resolution (15.4 days in the allopurinol group completers vs 13.4 days in the placebo group; P = 0.5). The secondary measures revealed that the acute phase of pain rapidly improved in both groups. We initiated allopurinol at low doses during an acute gout attack in patients who met criteria for starting urate-lowering therapy and did not have abnormal kidney or liver function. In this cohort, allopurinol did not prolong the acute, treated attack.

[ERRORS IN THE DIAGNOSTICS AND TREATMENT OF PATIENTS WITH GOUT AND THE ALGORITHM OF THERAPEUTIC TACTICS IN DIFFERENT PERIODS OF THE DISEASE (CLINICAL CASE)].

Difficulties and errors in the treatment of patients with the gout arise, mainly, during urate-lowering therapy. The article discusses possible medical errors in acute gouty arthritis and during chronic tophaceous gout in the light of the updated international recommendations of the American College of Rheumatology (ACR) and the European Antirheumatic League (EULAR 2018). As an example of inadequate treatment, the authors describe a case of a patient with chronic tophaceous gout. Errors in the diagnosis and treatment of the patient caused various complications and unjustified surgical intervention - amputation of the right finger and removal of a large tophus in the left forearm. Based on the analysis of mistakes made in the diagnosis and treatment of gout, the authors propose an algorithm for therapeutic tactics in different periods of the disease. So, for the relief of exacerbation in acute gouty arthritis, it is recommended to take the following drugs at starting doses: colchicine at a dose of 1.8 mg/day (1.2 mg immediately followed by 0.6 mg 1 hour later during 7-10 days or until complete relief of the gout attack), non-steroidal anti-inflammatory drugs (nimesulide up to 200 mg/day) or glucocorticosteroids (prednisolone at a dose of 30 mg/day for 3-5 days with subsequent withdrawal). The first-line urate-lowering drugs for chronic tofaceous gout are xanthine oxidase inhibitors - allopurinol and febuxostat. Allopurinol is prescribed no earlier than 2 weeks after the arthritis attack has stopped at a starting dose of no more than 100 mg/day, the dose is gradually increased to the minimum effective. The starting dose of febuxostat is 40 mg/day. Also, together with allopurinol or febuxostat, it is recommended to take uricosuric drugs (probenecid 500 mg/day or benzbromarone 50-200 mg/day). At the same time, the authors draw attention to the inadmissibility of the combination of allopurinol and febuxostat. In case of gout that does not respond to the main methods of therapy, treatment with pegloticase is recommended. When prescribing urate-lowering therapy, dose titration is necessary, to avoid the development of toxic effects.

Initiation of allopurinol at first medical contact for acute attacks of gout: a randomized clinical trial.

Streamlining the initiation of allopurinol could result in a cost benefit for a common medical problem and obviate the perception that no treatment is required once acute attacks have resolved. Our objective was to test the hypothesis that there is no difference in patient daily pain or subsequent attacks with early versus delayed initiation of allopurinol for an acute gout attack. A total of 57 men with crystal-proven gout were randomized to allopurinol 300 mg daily or matching placebo for 10 days. All subjects received indomethacin 50 mg 3 times per day for 10 days, a prophylactic dose of colchicine 0.6 mg 2 times per day for 90 days, and open-label allopurinol starting at day 11. Primary outcome measures were pain on visual analogue scale (VAS) for the primary joint on days 1 to 10 and self-reported flares in any joint through day 30. On the basis of 51 evaluable subjects (allopurinol in 26, placebo in 25), mean daily VAS pain scores did not differ significantly between study groups at any point between days 1 and 10. Initial VAS pain scores for allopurinol and placebo arms were 6.72 versus 6.28 (P=.37), declining to 0.18 versus 0.27 (P=.54) at day 10, with neither group consistently having more daily pain. Subsequent flares occurred in 2 subjects taking allopurinol and 3 subjects taking placebo (P=.60). Although urate levels decreased rapidly in the allopurinol group (from 7.8 mg/dL at baseline to 5.9 mg/dL at day 3), sedimentation rates and C-reactive protein levels did not differ between groups at any point. Allopurinol initiation during an acute gout attack caused no significant difference in daily pain, recurrent flares, or inflammatory markers.

Gout: modern management of an ancient malady.

If Dr. Sydenham could have benefited from today's therapy, he likely would not have had to endure thirty years of "violent ... torture" that gave birth to his most elegant and classic description of acute gout. The five key points to remember in management of the gouty spectrum are: (1) Establish the diagnosis as clearly as possible or as clearly as seems necessary under the clinical circumstances (i.e. arthrocentesis with crystal analysis to establish diagnosis is not always necessary with reliable patients when septic joint seems highly unlikely). (2) Treat acute attacks with NSAIDs alone or perhaps steroids--or rarely IV colchicine under special circumstances. (3) DO NOT START ALLOPURINOL OR PROBENECID DURING AN ACUTE FLARE OF GOUT--IT MAY MAKE THE EPISODE WORSE. (4) The pattern of disease over time (frequency and severity of attacks) determines whether or not one decides to use an agent such as allopurinol, probenecid, or prophylactic colchicine chronically once a patient is over the acute attack--the mere presence of increased uric acid and a single or rare gouty attack would not usually require any other than the appropriate acute therapy. (5) The presence of visible tophi, uric acid renal calculi and destructive gouty arthritis nearly always warrant uric acid lowering therapy.

Managing problem gout.

For the management of acute gouty arthritis, non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs of choice. In recent years, the use of colchicine has declined because of its frequent adverse reactions, and its reduced efficacy when administered more than 24 hours after onset of an acute attack. Intra-articular corticosteroid therapy (e.g. methylprednisolone acetate) is indicated for the treatment of acute mono or oligoarticular gouty arthritis in aged patients, and in those with co-morbid conditions contraindicating therapy with either NSAIDs or colchicine. Oral corticosteroids (e.g. prednisone), and both parenteral corticotrophin (ACTH) and corticosteroids (e.g. intramuscular triamcinolone acetonide) are valuable, relatively safe alternate treatment modalities in those with polyarticular attacks. For the treatment of hyperuricaemia and chronic gouty arthritis, allopurinol is the preferred urate-lowering drug. Its toxicity in elderly individuals, those with renal impairment, and in cyclosporine-treated transplant patients can be minimised by adjusting the initial dose according to the patient's creatinine clearance. In those experiencing cutaneous reactions to allopurinol, cautious desensitisation to the drug can be achieved using a schedule of gradually increasing doses. The therapeutic usefulness of uricosuric drugs is limited by the presence of renal impairment, occurrence of intolerable side-effects, or concomitant intake of salicylates. They are particularly indicated in patients allergic to allopurinol and in those with massive tophi requiring combined therapy with both allopurinol and a uricosuric.

Crystal arthritides - gout and calcium pyrophosphate arthritis : Part 3: Treatment.

The treatment of gout is based on several principles. Symptom control and termination of the inflammatory process are important early goals, whereas the urate level should be lowered in the long term to prevent further gout attacks and complications. The non-pharmacological approach is based on individually informing the patient on dietary measures and changes of life style. Besides physical measures, such as cold applications on the affected joint, various medications are available for treatment of an acute gout attack. The choice of drug depends on the individual risk profile. If non-steroidal anti-inflammatory drugs (NSAID) and coxibs are chosen it should be taken into account that the use is restricted in patients with renal insufficiency. Moreover, these drugs may have gastrointestinal side effects and are associated with increased cardiovascular morbidity and mortality. Colchicine has gastrointestinal side effects at high dosages but can also be used for differential diagnostics if there is a quick response to treatment. Steroids are an effective alternative and can be given orally or parenterally in patients with dysphagia. Moreover, steroids can be used in cases of renal insufficiency. After symptoms of the acute attack have subsided, urate lowering therapy should be initiated to prevent further attacks. Low-dose urate lowering therapy can be started during an acute gout attack when acute therapy is initiated. Allopurinol is still the medication of choice but its use is restricted in patients with renal insufficiency. A rare but serious side effect is allopurinol hypersensitivity syndrome. Febuxostat can be an alternative in patients who do not tolerate allopurinol. In February 2016, lesinurad, an URAT-1 and OAT-4 inhibitor, was approved in combination with allopurinol or febuxostat. Data on the effectiveness and safety of synthetic uricases and biologicals are still sparse for elderly patients. These substances are reserved for severe cases of gout.

Allopurinol for chronic gout.

Allopurinol, a xanthine oxidase inhibitor, is considered one of the most effective urate-lowering drugs and is frequently used in the treatment of chronic gout. To assess the efficacy and safety of allopurinol compared with placebo and other urate-lowering therapies for treating chronic gout. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE on 14 January 2014. We also handsearched the 2011 to 2012 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts, trial registers and regulatory agency drug safety databases. All randomised controlled trials (RCTs) or quasi-randomised controlled clinical trials (CCTs) that compared allopurinol with a placebo or an active therapy in adults with chronic gout. We extracted and analysed data using standard methods for Cochrane reviews. The major outcomes of interest were frequency of acute gout attacks, serum urate normalisation, pain, function, tophus regression, study participant withdrawal due to adverse events (AE) and serious adverse events (SAE). We assessed the quality of the body of evidence for these outcomes using the GRADE approach. We included 11 trials (4531 participants) that compared allopurinol (various doses) with placebo (two trials); febuxostat (four trials); benzbromarone (two trials); colchicine (one trial); probenecid (one trial); continuous versus intermittent allopurinol (one trial) and different doses of allopurinol (one trial). Only one trial was at low risk of bias in all domains. We deemed allopurinol versus placebo the main comparison, and allopurinol versus febuxostat and versus benzbromarone as the most clinically relevant active comparisons and restricted reporting to these comparisons here.Moderate-quality evidence from one trial (57 participants) indicated allopurinol 300 mg daily probably does not reduce the rate of gout attacks (2/26 with allopurinol versus 3/25 with placebo; risk ratio (RR) 0.64, 95% confidence interval (CI) 0.12 to 3.52) but increases the proportion of participants achieving a target serum urate over 30 days (25/26 with allopurinol versus 0/25 with placebo, RR 49.11, 95% CI 3.15 to 765.58; number needed to treat for an additional beneficial outcome (NNTB) 1). In two studies (453 participants), there was no significant increase in withdrawals due to AE (6% with allopurinol versus 4% with placebo, RR 1.36, 95% CI 0.61 to 3.08) or SAE (2% with allopurinol versus 1% with placebo, RR 1.93, 95% CI 0.48 to 7.80). One trial reported no difference in pain reduction or tophus regression, but did not report outcome data or measures of variance sufficiently and we could not calculate the differences between groups. Neither trial reported function.Low-quality evidence from three trials (1136 participants) indicated there may be no difference in the incidence of acute gout attacks with allopurinol up to 300 mg daily versus febuxostat 80 mg daily over eight to 24 weeks (21% with allopurinol versus 23% with febuxostat, RR 0.89, 95% CI 0.71 to 1.1); however more participants may achieve target serum urate level (four trials; 2618 participants) with febuxostat 80 mg daily versus allopurinol 300 mg daily (38% with allopurinol versus 70% with febuxostat, RR 0.56, 95% CI 0.48 to 0.65, NNTB with febuxostat 4). Two trials reported no difference in tophus regression between allopurinol and febuxostat over a 28- to 52-week period; but as the trialists did not provide variance, we could not calculate the mean difference between groups. The trials did not report pain reduction or function. Moderate-quality evidence from pooled data from three trials (2555 participants) comparing allopurinol up to 300 mg daily versus febuxostat 80 mg daily indicated no difference in the number of withdrawals due to AE (7% with allopurinol versus 8% with febuxostat, RR 0.89, 95% CI 0.62 to 1.26) or SAE (4% with allopurinol versus 4% with febuxostat, RR 1.13, 95% CI 0.71 to 1.82) over a 24- to 52-week period.Low-quality evidence from one trial (65 participants) indicated there may be no difference in the incidence of acute gout attacks with allopurinol up to 600 mg daily compared with benzbromarone up to 200 mg daily over a four-month period (0/30 with allopurinol versus 1/25 with benzbromarone, RR 0.28, 95% CI 0.01 to 6.58). Based on the pooled results of two trials (102 participants), there was moderate-quality evidence of no probable difference in the proportion of participants achieving a target serum urate level with allopurinol versus benzbromarone (58% with allopurinol versus 74% with benzbromarone, RR 0.79, 95% CI 0.56 to 1.11). Low-quality evidence from two studies indicated there may be no difference in the number of participants who withdrew due to AE with allopurinol versus benzbromarone over a four- to nine-month period (6% with allopurinol versus 7% with benzbromarone, pooled RR 0.80, 95% CI 0.18 to 3.58). There were no SAEs. They did not report tophi regression, pain and function.All other comparisons were supported by small, single studies only, limiting conclusions. Our review found low- to moderate-quality evidence indicating similar effects on withdrawals due to AEs and SAEs and incidence of acute gout attacks when allopurinol (100 to 600 mg daily) was compared with placebo, benzbromarone (100 to 200 mg daily) or febuxostat (80 mg daily). There was moderate-quality evidence of little or no difference in the proportion of participants achieving target serum urate when allopurinol was compared with benzbromarone. However, allopurinol seemed more successful than placebo and may be less successful than febuxostat (80 mg daily) in achieving a target serum urate level (6 mg/dL or less; 0.36 mmol/L or less) based on moderate- to low-quality evidence. Single studies reported no difference in pain reduction when allopurinol (300 mg daily) was compared with placebo over 10 days, and no difference in tophus regression when allopurinol (200 to 300 mg daily) was compared with febuxostat (80 mg daily). None of the trials reported on function, health-related quality of life or participant global assessment of treatment success, where further research would be useful.

Desensitization to allopurinol after allopurinol hypersensitivity syndrome with renal involvement in gout.

This is a case report of a 36-year-old male with tophaceous gout for 16 years. He started therapy with 300 mg/day of allopurinol. He had received variable dexamethasone doses by self-prescription for 16 years. When allopurinol was initiated, he had hyperuricemia and normal renal function. Twenty days after starting allopurinol, he presented diffuse maculopapular rash, conjunctivitis, increase in serum creatinine values, leukocytosis and eosinophilia and the diagnosis of allopurinol hypersensitivity (AH) syndrome was made. He completely recovered from the AH and renal function normalized. However, the gout worsened over the following years in spite of treatment with benzobromarone, low doses of prednisone, and colchicine. Allopurinol desensitization was successful beginning with an oral low dose scheme (6.5 mug/day) until we reached 300mg/day. Today the patient receives allopurinol with no side effects. We believe that this is the first reported example of successful desensitization in full-blown AH with renal involvement. Our cautious regimen might be tried in other such patients.

Colchicine

Medical uses Gout Colchicine is an alternative for those unable to tolerate NSAIDs when treating gout. Low doses appear to be well tolerated and may reduce gout symptoms and pain (1.2 mg in one hour, followed by 0.6 mg an hour later). This low dose may have a similar effectiveness to NSAIDS (low quality evidence). At high doses, side effects (primarily diarrhea, nausea, or vomiting) limit its use, however may be effective against pain. In addition, there is preliminary evidence that daily colchicine (0.6 mg twice daily) may be effective as a long-term prophylaxis when used with allopurinol to reduce the risk of increased uric acid levels and acute gout flares, although adverse gastrointestinal effects may occur. For treating gout symptoms, colchicine is used orally with or without food, as symptoms first appear. Subsequent doses may be needed if symptoms worsen.

Gout

Treatment The initial aim of treatment is to settle the symptoms of an acute attack. Repeated attacks can be prevented by medications that reduce serum uric acid levels. Tentative evidence supports the application of ice for 20 to 30 minutes several times a day to decrease pain. Options for acute treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and Glucocorticoids. While glucocorticoids and NSAIDs work equally well, glucocorticoids may be safer. Options for prevention include allopurinol, febuxostat, and probenecid. Lowering uric acid levels can cure the disease. Treatment of associated health problems is also important. Lifestyle interventions have been poorly studied. It is unclear whether dietary supplements have an effect in people with gout.

Gout

While it has been recommended that urate-lowering measures should be increased until serum uric acid levels are below 300–360 µmol/l (5.0–6.0 mg/dl), there is little evidence to support this practice over simple putting people on a standard dose of allopurinol. If these medications are in chronic use at the time of an attack, it is recommended that they be continued. Levels that cannot be brought below 6.0 mg/dl while attacks continue indicates refractory gout. While historically it is not recommended to start allopurinol during an acute attack of gout, this practice appears acceptable. Allopurinol blocks uric acid production, and is the most commonly used agent. Long term therapy is safe and well-tolerated and can be used in people with renal impairment or urate stones, although hypersensitivity occurs in a small number of individuals.

Ultrasonography shows disappearance of monosodium urate crystal deposition on hyaline cartilage after sustained normouricemia is achieved.

This study aimed at determining whether lowering serum urate (SU) to less than 6 mg/dl in patients with gout affects ultrasonographic findings. Seven joints in five patients with monosodium urate (MSU) crystal proven gout and hyperuricemia were examined over time with serial ultrasonography. Four of the five patients were treated with urate lowering drugs (ULDs) (allopurinol, n = 3; probenecid, n = 1). One patient was treated with colchicine alone. Attention was given to changes in a hyperechoic, irregular coating of the hyaline cartilage in the examined joints (double contour sign or "urate icing"). This coating was considered to represent precipitate of MSU crystals. Index joints included metacarpophalangeal (MCP) joints (n = 2), knee joints (n = 3), and first metatarsophalangeal (MTP) joints (n = 2). The interval between baseline and follow-up images ranged from 7 to 18 months. Serial SU levels were obtained during the follow-up period. During the follow-up period, three patients treated with ULD (allopurinol, n = 2; probenecid, n = 1) achieved a SU level of <6 mg/dl. In two patients, SU levels remained above 6 mg/dl (treated with allopurinol, n = 1; treated with colchicine, n = 1). At baseline, the double contour sign was seen in all patients. In those patients who achieved SU levels of <6 ml/dl, this sign had disappeared at follow-up. Disappearance of the double contour sign was seen in two knee joints, two first MTP joints, and one MCP joint. In contrast, disappearance of the double contour sign was not seen in patients who maintained a SU level > or =7 mg/dl. In one patient treated with allopurinol, SU levels improved from 13 to 7 mg/dl during the follow-up period. Decrease, but not resolution of the hyperechoic coating was seen in this patient. In the patient treated with colchicine alone, SU levels remained >8 mg/dl, and no sonographic change was observed. In our patients, sonographic signs of deposition of MSU crystals on the surface of hyaline cartilage disappeared completely if sustained normouricemia was achieved. This is the first report showing that characteristic sonographic changes are influenced by ULDs once SU levels remain < or =6 mg/dl for 7 months or more. Sonographic changes of gout correlate with SU levels and may be a non-invasive means to track changes in the uric acid pool. Larger prospective studies are needed to further assess these potentially important findings.

Lesinurad/allopurinol

Lesinurad/allopurinol (trade name Duzallo) is a fixed-dose combination drug for the treatment of gout. It contains 200 mg of lesinurad and 300 mg of allopurinol. In August 2017, the US Food and Drug Administration approved it for the treatment of hyperuricemia associated with gout in patients for whom target serum uric acid levels have not been achieved with allopurinol alone. It was approved for medical use in the European Union in August 2018. In February 2019, it was discontinued by its manufacturer for business reasons and is no longer available. References Antigout agents Combination drugs AstraZeneca brands Withdrawn drugs

Management of acute and chronic gouty arthritis: present state-of-the-art.

There are three stages in the management of gout: (i) treating the acute attack; (ii) lowering excess stores of uric acid to prevent flares of gouty arthritis and to prevent tissue deposition of urate; and (iii) providing prophylaxis to prevent acute flares. It is important to distinguish between therapy to reduce acute inflammation in acute gout and therapy to manage hyperuricaemia in patients with chronic gouty arthritis. During the acute gouty attack nonpharmacological treatments such as topical ice and rest of the inflamed joint are useful. NSAIDs are the preferred treatment in acute gout. The most important determinant of therapeutic success is not which NSAID is chosen, but rather how soon NSAID therapy is initiated. Other treatments include oral and intravenous colchicine, intra-articular and systemic corticosteroids, and intramuscular corticotropin. Optimal treatment of chronic gout requires long-standing reduction in serum uric acid. The urate-lowering drugs used to treat chronic gout are the uricosuric drugs, the uricostatic drugs, which are xanthine oxidase inhibitors, and the uricolytic drugs. Xanthine oxidase inhibitors such as allopurinol, oxipurinol and febuxastat should be used as first-line treatment in patients with renal calculi, renal insufficiency, concomitant diuretic therapy and ciclosporin (cyclosporine) therapy, and urate overproduction. Uricosuric drugs include probenecid, benzbromarone, micronised fenofibrate and losartan. They are the urate-lowering drugs of choice in allopurinol-allergic patients and underexcretors with normal renal function and no history of urolithiasis. The use of recombinant urate oxidase in patients with chronic gout is limited by the need for parenteral administration, the potential antigenicity and production of anti-urate oxidase antibodies, and declining efficacy. The effectiveness of colchicine prophylaxis as an isolated therapy is still to be confirmed by placebo-controlled trials. Another issue is prophylaxis with NSAIDs. There are no comparative studies with colchicine.

Adherence to the 2012 American College of Rheumatology (ACR) Guidelines for Management of Gout: A Survey of Brazilian Rheumatologists.

To describe the current pharmacological approach to gout treatment reported by rheumatologists in Brazil. We performed a cross-sectional survey study using an online questionnaire e-mailed to 395 rheumatologists, randomly selected, from among the members of the Brazilian Society of Rheumatology. Three hundred and nine rheumatologists (78.2%) responded to the survey. For acute gout attacks, combination therapy (NSAIDs or steroid + colchicine) was often used, even in monoarticular involvement, and colchicine was commonly started as monotherapy after 36 hours or more from onset of attack. During an acute attack, urate-lowering therapy (ULT) was withdrawn by approximately a third of rheumatologists. Anti-inflammatory prophylaxis (98% colchicine) was initiated when ULT was started in most cases (92.4%), but its duration was varied. Most (70%) respondents considered the target serum uric acid level to be less than 6 mg/dl. Approximately 50% of rheumatologists reported starting allopurinol at doses of 100 mg daily or less and 42% reported the initial dose to be 300 mg daily in patients with normal renal function. ULT was maintained indefinitely in 76% of gout patients with tophi whereas in gout patients without tophi its use was kept indefinitely in 39.6%. This is the first study evaluating gout treatment in a representative, random sample of Brazilian rheumatologists describing common treatment practices among these specialists. We identified several gaps in reported gout management, mainly concerning the use of colchicine and ULT and the duration of anti-inflammatory prophylaxis and ULT. Since rheumatologists are considered as opinion leaders in this disease, a program for improving quality of care for gout patients should focus on increasing their knowledge in this common disease.

Management of Gout: A Systematic Review in Support of an American College of Physicians Clinical Practice Guideline.

Gout is a common type of inflammatory arthritis in patients seen by primary care physicians. To review evidence about treatment of acute gout attacks, management of hyperuricemia to prevent attacks, and discontinuation of medications for chronic gout in adults. Multiple electronic databases from January 2010 to March 2016, reference mining, and pharmaceutical manufacturers. Studies of drugs approved by the U.S. Food and Drug Administration and commonly prescribed by primary care physicians, randomized trials for effectiveness, and trials and observational studies for adverse events. Data extraction was performed by one reviewer and checked by a second reviewer. Study quality was assessed by 2 independent reviewers. Strength-of-evidence assessment was done by group discussion. High-strength evidence from 28 trials (only 3 of which were placebo-controlled) shows that colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids reduce pain in patients with acute gout. Moderate-strength evidence suggests that low-dose colchicine is as effective as high-dose colchicine and causes fewer gastrointestinal adverse events. Moderate-strength evidence suggests that urate-lowering therapy (allopurinol or febuxostat) reduces long-term risk for acute gout attacks after 1 year or more. High-strength evidence shows that prophylaxis with daily colchicine or NSAIDs reduces the risk for acute gout attacks by at least half in patients starting urate-lowering therapy, and moderate-strength evidence indicates that duration of prophylaxis should be longer than 8 weeks. Although lower urate levels reduce risk for recurrent acute attacks, treatment to a specific target level has not been tested. Few studies of acute gout treatments, no placebo-controlled trials of management of hyperuricemia lasting longer than 6 months, and few studies in primary care populations. Colchicine, NSAIDs, and corticosteroids relieve pain in adults with acute gout. Urate-lowering therapy decreases serum urate levels and reduces risk for acute gout attacks. Agency for Healthcare Research and Quality. (Protocol registration: http://effectivehealth-care.ahrq.gov/ehc/products/564/1992/Gout-managment-protocol-141103.pdf).

Febuxostat: a new treatment for hyperuricaemia in gout.

Febuxostat is a new non-purine xanthine oxidase inhibitor that is more potent than allopurinol 300 mg daily. In two Phase III trials, significantly more febuxostat-treated gout patients met the primary endpoint [serum urate (sUA) <6 mg/dl (<360 mumol/l) at the last three visits] (48 and 53% with 80 mg; 65 and 62% with 120 mg), compared with those receiving allopurinol 300 mg (22 and 21%; P < 0.001 in both studies). Febuxostat was more effective than allopurinol in the subset with impaired renal function; no dose adjustment is required in mild-to-moderate renal impairment. Long-term extension studies confirmed the efficacy and tolerability of febuxostat. In patients who achieved the sUA target of 6 mg/dl (360 mumol/l), the incidence of gout flares fell steadily and tophi resolved in many patients. The incidence of adverse events such as dizziness, diarrhoea, headache and nausea with febuxostat was similar to allopurinol. The incidence of cardiovascular side-effects (Antiplatelet Trialists Collaboration events) was numerically higher with febuxostat than with allopurinol, but this was not statistically significant. Co-administration of febuxostat with AZA or 6-mercaptopurine is not recommended. Prophylaxis (colchicine and/or NSAIDs) against acute attacks should be used for at least the first 6 months, since early mobilization flares were observed in the clinical trials. In conclusion, febuxostat is more effective than allopurinol 300 mg daily in reducing sUA levels <6 mg/dl (360 mumol/l), the target recommended by EULAR, and offers a new option for the long-term treatment of gout.

Allopurinol

It is also used to treat kidney stones caused by deficient activity of adenine phosphoribosyltransferase. Tumor lysis syndrome Allopurinol was also commonly used to treat tumor lysis syndrome in chemotherapeutic treatments, as these regimens can rapidly produce severe acute hyperuricemia; however, it has gradually been replaced by urate oxidase therapy. Intravenous formulations are used in this indication when people cannot take medicine by mouth. Inflammatory bowel disease Allopurinol cotherapy is used to improve outcomes for people with inflammatory bowel disease and Crohn's disease who do not respond to thiopurine monotherapy. Cotherapy has also been shown to greatly improve hepatoxicity side effects in treatment of IBD. Cotherapy invariably requires dose reduction of the thiopurine, usually to one-third of the standard dose depending upon the patient's genetic status for thiopurine methyltransferase.

Preventing acute gout when starting allopurinol therapy. Colchicine or NSAIDs?

Acute gout is a well known complication of the commencement of allopurinol therapy. Prophylaxis is needed for some months, even after serum urate levels have returned to normal. Colchicine is usually preferable to NSAIDs for this purpose, being cheaper, and better tolerated, especially in patients with peptic ulcer, gastrointestinal bleeding or dyspepsia or who are taking anticoagulants.

Gout

Medications As of 2020, allopurinol is generally the recommended preventative treatment if medications are used. A number of other medications may occasionally be considered to prevent further episodes of gout, including probenecid, febuxostat, benzbromarone, and colchicine. Long term medications are not recommended until a person has had two attacks of gout, unless destructive joint changes, tophi, or urate nephropathy exist. It is not until this point that medications are cost-effective. They are not usually started until one to two weeks after an acute flare has resolved, due to theoretical concerns of worsening the attack. They are often used in combination with either an NSAID or colchicine for the first three to six months.

Gout

Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, or colchicine improves symptoms. Once the acute attack subsides, levels of uric acid can be lowered via lifestyle changes and in those with frequent attacks, allopurinol or probenecid provides long-term prevention. Taking vitamin C and eating a diet high in low-fat dairy products may be preventive. Gout affects about 1 to 2% of the Western population at some point in their lives. It has become more common in recent decades. This is believed to be due to increasing risk factors in the population, such as metabolic syndrome, longer life expectancy, and changes in diet. Older males are most commonly affected. Gout was historically known as "the disease of kings" or "rich man's disease". It has been recognized at least since the time of the ancient Egyptians. Signs and symptoms

[Evaluation of a 12-week allopurinol-lowering therapy in combination with the non-steroidal anti-inflammatory drug meloxicam in patients with gout].

To evaluate a 12-week course of combined alloturinol-lowering therapy with a prophylactic anti-inflammatory dose of movalis for the frequency of exacerbations and the quality of life of patients with gout. Allopurinol was administered orally, 1 time per day. Every 3 weeks, the dosage of the drug was increased by 50 mg to 300 mg per day under the control of the level of serum uric acid (sUA). The total daily dose of the drug movalis, used in the form of different dosage forms, was 7.515 mg. The clinical effectiveness of the treatment was evaluated after 3, 6, 9 and 12 weeks according to physical examination, the dynamics of joint pain at rest, during movement and palpation, according to the visual analogue scale (VAS) in millimeters, Likert scale, EuroQol-5D-5L questionnaire, care for oneself, habitual daily activities, the presence of anxiety and depression, assessment of satisfaction with treatment (on a scale of 1 to 5, where 1 is the complete absence of improvement or worsening, and 5 is a very good result); took into account the period of remission, as well as the time before the onset of relapse of gouty arthritis. An adverse event (AE) was recorded. On the background of treatment with movalis 7.5 mg per day more than two-thirds of patients showed no worsening of the articular syndrome with an increase in the dose of allopurinol to 300 mg per day. By the 12th week of observation, a significant difference was found between the severity of gouty arthritis characteristics in the direction of improving mobility, self-care, normal daily activities, reducing soreness, reducing anxiety and depression (p0.05). In addition, the ESR and sUA levels were significantly different initially and at the final observation point (p0.05), which indicates a positive effect on the inflammatory process. A 3-month course of combination therapy was not accompanied by significant increases in blood pressure, changes in creatinine clearance in blood serum. There were no adverse events from the gastrointestinal tract. 90.9% of patients rated the treatment result as very good. AE in the form of a skin allergic rash was observed in one patient; it did not require interruption of treatment and completely stopped without consequences after completion of the course. 12 a week-long combined therapy of the allopurinol-reducing drug with the anti-inflammatory dose movalis prevents the exacerbation of the articular syndrome and improves the quality of life of patients with gout.

Kidney stone disease

Allopurinol For people with hyperuricosuria and calcium stones, allopurinol is one of the few treatments that have been shown to reduce kidney stone recurrences. Allopurinol interferes with the production of uric acid in the liver. The drug is also used in people with gout or hyperuricemia (high serum uric acid levels). Dosage is adjusted to maintain a reduced urinary excretion of uric acid. Serum uric acid level at or below 6 mg/100 ml) is often a therapeutic goal. Hyperuricemia is not necessary for the formation of uric acid stones; hyperuricosuria can occur in the presence of normal or even low serum uric acid. Some practitioners advocate adding allopurinol only in people in whom hyperuricosuria and hyperuricemia persist, despite the use of a urine-alkalinizing agent such as sodium bicarbonate or potassium citrate.

Mercaptopurine

Mercaptopurine causes changes to chromosomes in animals and humans, though a study in 1990 found, "while the carcinogenic potential of 6-MP cannot be precluded, it can be only very weak or marginal." Another study in 1999 noted an increased risk of developing leukemia when taking large doses of 6-MP with other cytotoxic drugs. Drug interactions Allopurinol inhibits xanthine oxidase, the enzyme that breaks down mercaptopurine. Those taking allopurinol (often used to prevent gout) are at risk for mercaptopurine toxicity. The dose should be reduced or allopurinol should be discontinued. Several published studies have demonstrated that the use of allopurinol in combination with low dose 6-MP helps reduce 6-MP levels, which are toxic to liver tissue, whilst increasing the therapeutic levels of 6-MP for some inflammatory conditions. Mechanisms of action

First_Aid_Step1

tREatmEnt Acute: NSAIDs (eg, indomethacin), glucocorticoids, colchicine. Chronic (preventive): xanthine oxidase inhibitors (eg, allopurinol, febuxostat). Previously called pseudogout. Deposition of The blue P’s—blue (when Parallel), Positive calcium pyrophosphate crystals within the birefringence, calcium Pyrophosphate, joint space. Occurs in patients > 50 years old; Pseudogout both sexes affected equally. Usually idiopathic, sometimes associated with hemochromatosis, hyperparathyroidism, joint trauma. Pain and swelling with acute inflammation (pseudogout) and/or chronic degeneration (pseudo-osteoarthritis). Most commonly affected joint is the knee. Chondrocalcinosis (cartilage calcification) on x-ray. Crystals are rhomboid and weakly ⊕ birefringent under polarized light (blue when parallel to light) A . Acute treatment: NSAIDs, colchicine, glucocorticoids. Prophylaxis: colchicine. MUSCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE ` pathology SECTION III 468

Management of hyperuricemia in gout: focus on febuxostat.

Gout is the most common inflammatory arthritis in an elderly population, and can be diagnosed with absolute certainty by polarization microscopy. However, diagnosis may be challenging because atypical presentations are more common in the elderly. Management of hyperuricemia in the elderly with gout requires special consideration because of co-medication, contra-indications, and risk of adverse reactions. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used sensibly in the elderly, especially when renal function impairment is present. However, if used at the lowest dose that maintains the serum urate level below 5.0 to 6.0 mg/dL (0.30 to 0.36 mmol/L), the excess urate in the body will eventually be eliminated, acute flares will no longer occur, and tophi will resolve. Febuxostat, a new xanthine oxidase inhibitor, is welcomed, as few alternatives for allopurinol are available. Its pharmacokinetics and pharmacodynamics are not significantly altered in patients with moderate renal function or hepatic impairment. Its antihyperuricemic efficacy at 80 to 120 mg/day is better than "standard dosage" allopurinol (300 mg/day). Long-term safety data and efficacy data on tophus diminishment and reduction of gout flares have recently become available. Febuxostat may provide an important option in patients unable to use allopurinol, or refractory to allopurinol.

Allopurinol-induced granulomatous hepatitis with cholangitis and a sarcoid-like reaction.

A 36-year-old man had pain in both knees and an elevated uric acid concentration; his liver function was normal. Allopurinol therapy was started, 100 mg twice daily. After one month fever, lethargy, and severe polyarthralgia developed. On admission to our hospital liver function was abnormal, and a liver biopsy specimen showed granulomas with cholangitis and pericholangitis. He also had lymphopenia with a reduced number of T cells and granulomas in the bone marrow. One month after discontinuation of allopurinol therapy the patient was clinically well with normal liver function and a normal lymphocyte count. A repeated liver biopsy specimen showed normal liver tissue with no granulomas. The onset of the symptoms and findings shortly after the initiation of allopurinol therapy, and their disappearance after the discontinuation of therapy suggest a drug-induced hypersensitivity.

Allopurinol -- Adverse Effects

Due to the destabilization of intra-articular uric acid microtophi on initiating any urate-lowering therapy, there is an increased incidence of acute gouty flares, especially during the initial few months. To prevent this, patients should start an anti-inflammatory agent such as colchicine, nonsteroidal anti-inflammatory drug (NSAID), or low-dose prednisone (only in patients who cannot take colchicine or NSAIDs) before or at the same time as initiating allopurinol. [10]

Clinical manifestations of gout and their management.

Gout is an inflammatory response to deposition of monosodium urate crystals in and around joints. It is primarily a disease of adult men. In acute gout, treatment options include non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and corticosteroids, administered either intra-articularly, orally or parenterally. Asymptomatic hyperuricaemia does not require specific treatment, but should prompt screening for atherosclerosis risk factors, and general lifestyle modification to reduce serum urate levels. Gout presents differently in the elderly. Both women and men are affected, attacks are frequently polyarticular and in the upper limbs, and the gout may be associated with diuretic use, hypertension and renal impairment. In patients with peptic ulcer disease, selective COX-2 inhibitors provide another treatment option. In the presence of renal impairment, allopurinol is the treatment of choice for urate lowering therapy, but doses of allopurinol and colchicine must be adjusted. Urate lowering therapy should only be used if recurrent episodes of gout occur despite aggressive attempts to reverse or control the underlying causes. It should not be introduced or discontinued during an acute episode of gout, and gout prophylaxis (NSAIDs or colchicine) should be prescribed during the introduction of urate lowering therapy.

Images in clinical medicine: Tophi.

Tophi (plural of tophus, Latin for "stone") are stone-like deposits of monosodium urate in the soft tissues, synovial tissues, or in bones near the joints. They are pathognomonic for gout, the most common inflammatory arthritis in the United States, with an estimated lifetime prevalence of 4%. It is usually the end result of loss of the balance between uric acid production and excretion. It can be found anywhere in the body especially in areas of friction or trauma. It is usually painless and rarely to present as the initial manifestation of gout. It is diagnosed mainly clinically. Imaging is mainly used to assess the complication like bony erosions. The American College of Rheumatology (ACR) guidelines currently indicate that urate-lowering therapy should be initiated in patients with the presence of tophi visible on examination or imaging (ACR Evidence A). First-line therapy for urate lowering remains the xanthine oxidase inhibitor allopurinol. The ACR currently recommends colchicine, 0.6 mg (or 0.5 mg) once or twice daily, or low dose NSAIDs should be continued to reduce gout flare incidence for six months after resolution of the tophus. Daily prednisone ≤10 mg has been endorsed as an acceptable second-line prophylactic agent. <bAbbreviations:</b ACR: American College of Rheumatology; NSAID: non-steroidal anti-inflammatory drug.

Allopurinol

Allopurinol should not be given to people who are allergic to it. Drug interactions Drug interactions are extensive, and are as follows: Azathioprine and 6-mercaptopurine: Azathioprine is metabolised to 6-mercaptopurine which in turn is inactivated by the action of xanthine oxidase - the target of allopurinol. Giving allopurinol with either of these drugs at their normal dose will lead to overdose of either drug; only one-quarter of the usual dose of 6-mercaptopurine or azathioprine should be given; Didanosine: plasma didanosine Cmax and AUC values were approximately doubled with concomitant allopurinol treatment; it should not be co-administered with allopuroinol and if it must be, the dose of should be reduced and the person should be closely monitored.

Allopurinol -- Administration

To prevent tumor lysis syndrome, allopurinol shall be initiated 2 to 3 days before starting chemotherapy and continued until 3 to 7 days after chemotherapy. Doses for oral allopurinol are 300 mg/m^2/day in three divided doses every 8 hours, a maximum of 800 mg daily, and IV allopurinol is 200 to 400 mg/m2 daily single doses or 2 to 3 divided doses. Allopurinol dosing is 300 mg oral daily for the prevention of recurrent uric acid or calcium nephrolithiasis.