Carcinoma in situ is delimited by the basement membrane, i.e. it is not invasive yet, and therefore the treatment is polypectomy, which is already done. Subsequently, an endoscopic follow-up (with biopsies) should be performed at an interval of 3 to 6 months depending on the patient's history, age and concomitant pathologies.

In a colon cancer screening program, a 52-year-old patient undergoes a colonoscopy. The entire colon is normal except for the finding of a 2 cm pedunculated polyp in the sigma which is removed with a diathermy loop. The anatomopathological result indicates that there is a carcinoma in situ limited to the head of the polyp. She has a thoracoabdominal CT scan reported as normal. Indicate the correct course of action.

Segmental resection of the affected colon.

Local resection of the base of the polyp.

[Our experience of 350 endoscopic polypectomies of the colon].

The authors report their experience of the endoscopic removal of 350 polyps of the colon. Vegetating lesions of doubtful endoscopic appearance and nature were excluded from this study. Indications regarding intestinal cleaning and the most appropriate pharmacological preparation are given on the basis of personal experience. No patient had to be hospitalised and the colon was fully explored in all cases; the cecum was reached in 85% of cases. The maximum limit of endoscopic removal was 5 cm due to the greater risk of complications and presence of cancer on polyps. A total of up to 8 polyps were removed in a single session in cases of multiple polyposis. From 1986 to 1992 350 polypectomies were performed in 177 patients, of which 301 were adenoma (85.9%) and 49 mixed (14.1%). Adenomas were 80.5% tubular, 13.6% tubulo-villous and 4.3% villous. Cancer was found on polyps in 5 cases (1.6%). 146 polyps were found in the rectum (41.8%), 84 in the sigma (24%), 76 in the descending (21.7%), 21 in the transverse (6%), and 23 in the right colon (6.5%). Patients were aged between 3 and 81 years, and the most frequently affected age bracket was between 40-70 years. Follow-up consisted in checks at 6, 12 and 24 months in cases of adenoma and quarterly checks during the first year in the event of carcinoma in situ. The decision to use a diathermic loop or hot biopsy was made in relation to lesion size, reserving the former for polyps with diameters of over 8 mm. All polyps under 5 cm were removed and subjected to histological tests. No cases of early or late complications were reported in the 350 polypectomies performed. The authors indicate the criteria of choice which led to surgical resection of the first instance. In the event of in situ carcinoma, endoscopic removal is considered sufficient provided that it is radical. The following must be evaluated in the case of invasive carcinoma: tumor size, the degree of differentiation, lymphatic or vascular invasion and generic or specific risk factors linked to the individual patient.

Treatment of colonic polyps--practical considerations.

The adenomatous colonic polyp, a neoplastic lesion, is the precursor of most if not all carcinomas of the colon and rectum. Confirmatory evidence is derived from epidemiological, histological and clinical data demonstrating a close parallelism between adenomas and cancer of the colon. Based on current knowledge, all colonic polyps should be removed to prevent the development of colonic cancer. However, since the risk of malignancy within an adenoma is related to its size, histology and the degree of dysplasia, practical considerations dictate that all polyps 1 cm in diameter or larger should be removed upon their detection by barium enema or colonoscopy since such adenomas are the ones most likely to contain malignancy. The endoscopic removal of colon polyps can be efficiently and safely accomplished when established principles of colonoscopy and electrosurgery are followed. This technique requires the proper equipment, a skilled endoscopy assistant, and an experienced endoscopist with the ability to adeptly perform colonoscopy, an understanding of the basic concepts of electrocautery and knowledge of the various structural configurations of colonic polyps. Colonoscopic polypectomy will avoid the need for surgical resection in most instances. Management of the malignant colonic polyp remains controversial. The patient with a sessile or pseudo-pedunculated polyp containing invasive cancer should undergo colonic resection. Surgery is not necessary for the majority of patients whose pedunculated adenomas contain invasive cancer, unless the malignancy is poorly differentiated, the cancer invades lymphatics or vascular channels, or tumour is seen at or near the resection margin. Surveillance colonoscopy after endoscopic polypectomy should be performed in most instances within one year to look for recurrent tumour, missed polyps or a metachronous adenoma. Subsequently, colonoscopy should be performed every two years in patients with multiple index polyps, and every three years after removal of a single index adenoma.

Endoscopic resection of large colorectal polyps.

Endoscopic polypectomy is a common technique, but there are discrepancies over which treatment--surgical or endoscopic--to follow in case of polyps of 2 cm or larger. To analyse the efficacy and complications of colonoscopic polypectomy of large colorectal polyps. 147 polypectomies were performed on 142 patients over an eight-year period. The technique used was that of submucosal adrenaline 1:10000 or saline injection at the base of the polyp, followed by resection of the polyp using a diathermic snare in the smallest number of fragments. Remnant adenomatous tissue was fulgurated with an argon plasma coagulator. Lately, prophylactic hemoclips have been used for thick-pedicle polyps. Complete removal was defined as when a polyp was completely resected in one or more polypectomy sessions. Polypectomy failure was defined as when a polyp could not be completely resected or contained an invasive carcinoma. The mean patient age was 67.9 years (range, 4-90 years), with 68 men and 79 women. There were 74 sessile polyps, and the most common location was the sigmoid colon. The most frequent histology was tubulovillous. Most of the polyps (96.6%), were resected and cured. This was not achieved in four cases of invasive carcinoma, and a villous polyp of the cecum. All pedunculated polyps were resected in one session, whereas the average number of colonoscopies for sessile polyps was 1.35 +/- 0.6 (range, 1-4). The polypectomy was curative in all of the in situ carcinomata except one. As for complications, 2 colonic perforations (requiring surgery) and 8 hemorrhages appeared, which were controlled via endoscopy. There was no associated mortality. Endoscopic polypectomy of large polyps (> or =2 cm) is a safe, effective treatment, though it is not free from complications. Complete resection is achieved in a high percentage, and there are few relapses. It should be considered a technique of choice for this type of polyp, except in cases of invasive carcinoma.

[Endoscopic resection of colonic polyps. A propos of 45 polypectomies].

Endoscopic resection of polyps of the colon is, no doubt, a considerable therapeutic advance. It avoids surgical operation permits histological examination and makes simple biopsy unnecessary. It is indicated in the presence of pediculated polyps of a diameter or less than 3 cm, whatever the site of the polyp. Thus we were able to remove 45 polyps without complications. The method is not indicated in a large size polyp, sessile polyps or diffuse polyposis. The follow-up is still insufficient to assess : 1) the true risk of resection which can only be undertaken after long experience of colonoscopy ; 2) the frequency or recurrent adenomas. Endoscopic resection is at present the simplest method of detection and treatment of carcinoma in situ of the colon of which we observed four cases in our series. The problem of surgical reoperation is discussed.

[Endoscopic excision of malignant colorectal polyps. Study of a series of 82 cases].

The management of malignant colonic polyps removed by endoscopic polypectomy is a controversial subject. We reported a series of 81 patients with 82 malignant polyps removed by endoscopic polypectomy between 1977 and 1984. 15 polyps contained carcinoma in situ and were treated by endoscopic polypectomy alone. 36 polyps contained superficial cancer; 35 were treated by EP alone; 1 was treated by endoscopic polypectomy and colectomy. 26 polyps contained invasive carcinoma and 2 were classified as polypoid adenocarcinomas. 19 had clear resection margins at polypectomy and seven had involved resection margins: 17 were treated by endoscopic polypectomy alone, 9 were treated by endoscopic polypectomy and colectomy. The patients were followed with colonoscopy. Follow-up has been 6 to 74 months (mean 32 months). The patients whose polyps were treated by endoscopic polypectomy alone, had had no evidence of recurrent tumor at the polypectomy site. Of the 12 patients undergoing colectomy, 4 had residual tumor at the polypectomy site. No patients had involved lymph nodes. There was no evidence of recurrence in any of these cases. Polyps containing contained carcinoma in situ and superficial cancer, polyps containing invasive carcinoma and clear resection margins can be treated with endoscopic polypectomy alone. Polyps with invasive carcinoma and involved resection margins should undergo segmental colonic resection. This approach must be weighed against the age of the patient, the medical status and the morbidity and mortality of the surgical procedure.

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.

Colonic polypectomy

Colonic polypectomy is the removal of colorectal polyps in order to prevent them from turning cancerous. Gastrointestinal polyps can be removed endoscopically through colonoscopy or esophagogastroduodenoscopy, or surgically if the polyp is too large to be removed endoscopically. The method used to perform colonic polypectomies during colonoscopy depends on the size, shape and histological type of the polyp to be removed. Prior to performing polypectomy, polyps can be biopsied and examined histologically to determine the need to perform polypectomy. Evaluation Prior to resection, assessment of the polyp should include: polyp size, morphology, location, and accessibility. If there are features that suggest of cancer is present in the polyp, then either endoscopic submucosal dissection or surgery should be considered. If the polyp appears benign, but the risk of progression to cancer is negligible, then resection is not necessary.

Polyp (medicine)

While colon polyps are not commonly associated with symptoms, occasionally they may cause rectal bleeding, and on rare occasions pain, diarrhea or constipation. They are a concern because of the potential for colon cancer being present microscopically, and the risk of benign colon polyps becoming malignant over time. Since most polyps are asymptomatic, they are usually discovered at the time of colon cancer screening. Common screening methods are occult blood test, colonoscopy with a modern flexible endoscope, sigmoidoscopy ( usually with the older rigid endoscope), lower gastrointestinal series (barium enema), digital rectal examination (DRE), virtual colonoscopy or Cologuard. The polyps are routinely removed at the time of colonoscopy, either with a wire loop known as a polypectomy snare (first description by P. Deyhle, Germany, 1970), or with biopsy forceps. If an adenomatous polyp is found, it must be removed, since such a polyp is pre-cancerous and has a propensity to become

Endoscopic polypectomy: inadequate treatment for invasive colorectal carcinoma.

Endoscopic polypectomy has greatly decreased the necessity for transabdominal resection of adenomatous polyps of the colon and rectum. In addition, the routine removal of these presumed precancerous lesions may well decrease the incidence of colon cancer in these patients. However, some authors have proposed that endoscopic resection alone of certain pedunculated polyps containing invasive carcinoma is adequate treatment for these lesions. At Columbia-Presbyterian Medical Center this has not been our standard practice, and 729 patients who have undergone endoscopic removal of pedunculated adenomatous polyps of the colon and rectum during the past decade have been reviewed. Forty-seven (6.4%) of these patients had polyps containing carcinoma in situ for which no further resection was performed. Thirty-nine patients (5.3%) had polyps containing carcinoma which had invaded up to or through the muscularis mucosae and were, therefore, considered invasive carcinomas. In this latter group, 24 patients underwent colon resection and 15 underwent endoscopic polypectomy alone. Within the group undergoing resection, six patients (25%) had from one to two lymph nodes within the resected specimen containing metastatic cancer. In review of these lesions, all 24 were able to be resected with an intervening segment of uninvolved stalk. After analyzing the frequently quoted parameters of size, depth of invasion into the stalk, degree of differentiation and involvement of lymphatics within the polyp, it was not possible to predict which lesions would have lymph node metastases at the time of resection. Consequently, it is concluded that all patients with polyps containing invasive carcinoma should undergo standard colon resection if feasible, despite the technical ability to resect these lesions endoscopically with an "adequate" margin of uninvolved stalk. This will eliminate the possibility of undiagnosed Dukes' Stage C lesions, and potentially improve long-term survival rates within this group of patients with an otherwise poor prognosis.

Serrated polyposis syndrome

If polyps are very numerous, very large, or their growth cannot be controlled with colonoscopy, then surgery may be necessary. When surgery is necessary, a total abdominal colectomy with ileorectal anastomosis should be considered to minimize the risk of colon cancer. If surgery is necessary and involvement of polyps is focal or largely confined to a particular section of bowel, then segmental resection may be considered. Segmental resection is also recommended for cancer. In most cases, the rectum is left in place. Any remaining segments of colon or rectum require annual surveillance with colonoscopy.

Polypectomy practices in a real life setting. Do we do enough for our patients? A review of 1061 colonoscopies.

Endoscopic removal of colon polyps is the main tool in colorectal cancer prevention programs. Although several quality indicators and guidelines have been proposed, polypectomy practices are still subject to great variation among endoscopist and little data is available regarding polypectomy practices in real life settings. The records of the 1061 screening colonoscopies performed in 2010 in a tertiary care teaching hospital in Bucharest were reviewed and all colonoscopies where at least one polyp was detected were selected for analysis. The number of detected polyps, the resection rate and method used for polypectomy were studied and compared to colonoscopy quality indicators previously reported in literature. 941 polyps were detected in 395 patients. Invasive colorectal cancer was found in 42 patients. 548 polyps (58.23%) were removed endoscopically, with at least one polyp being resected in 283 patients (71.5%), resulting in a polypectomy rate of 26.67% in the entire study population. Cold forceps resection was the most commonly used method for the resection of polyps less than 5 mm in size, while for larger polyps hot snare was the preferred method. Concomitant invasive carcinoma and a larger number of polyps were predictive of incomplete removal of all detected polyps. Most quality indicators were met in our study group, with suboptimal performance regarding histological documentation of detected polyps and establishing a polyp-free colon.

Patient management after endoscopic removal of the cancerous colon adenoma.

The subject of management of patients after endoscopic removal of cancerous adenomas is controversial. A retrospective review of 126 lesions in 121 patients who had had colonoscopic polypectomy of malignant lesions between 1971 and 1985 was used to determine the criteria for colon resection. Invasive cancer was identified in 80 patients, while 41 patients had carcinoma in situ. A synchronous colon cancer was found in five of the 121 patients. The patients who had carcinoma in situ had no evidence of residual tumor or metastatic disease on subsequent follow-up (colon resection in three patients and endoscopic surveillance in 38 patients). Of the 80 patients with invasive cancer, 44 had subsequent colon resection, and 34 of these had no evidence of tumor in the resected bowel or mesenteric lymph nodes. Ten patients had residual tumor, metastatic cancer to regional lymph nodes, or both. Each of the 10 had at least one of the following indications of inadequate resection or dissemination of disease to local lymph nodes (the first indication is a macroscopic evaluation, while the remaining four are all microscopic): incomplete excision, poorly differentiated tumor, invasion of the line of resection, invasion of the polyp stalk, and invasion of venous or lymphatic channels. Present recommendations for patient management after endoscopic removal of an invasive malignant adenoma should include colon resection with regional lymphadenectomy for patients with one or more of these five criteria. Patients without any of these risk factors should have early repeat endoscopic examination 3 months after initial polypectomy to evaluate the polypectomy site. Total colonoscopic examination is repeated at 1 year to ensure the surveillance program is begun with a colon without neoplasms.

Colonoscopic miss rates determined by direct comparison of colonoscopy with colon resection specimens.

Colonoscopy is an effective method for discovery of adenomas and for colon cancer screening and prevention. Studies evaluating back-to-back colonoscopies have estimated significant miss rates but are limited by the lack of a definitive gold standard. Our study evaluated the sensitivity of colonoscopy compared with examination of surgically resected colon as a gold standard. This was a retrospective analysis of patients who had a portion of colon surgically removed and had lower endoscopy within 5 months. The focus of the review was not for the particular lesion for which the surgery was indicated but, rather, for the synchronous lesions in the portions of bowel that were removed. Sensitivity was determined by counting the number of lesions detected at colonoscopy compared with those found in the surgically resected segment. A total of 73 synchronous lesions were present in the resected segments of 156 patients. Colonoscopy detected 56 of 73 the lesions (sensitivity 76.7%: 95% CI = 67-86). Of the 17 missed lesions, 14 of 17 (82%, 95% CI = 64-100) were < 1-cm polyps. Endoscopy overlooked one 1-cm adenoma in the ascending colon. Two cancers were missed, both in the same patient in whom endoscopy detected a sigmoid cancer but missed synchronous lesions in the cecal and ascending colon. Colonoscopy is an effective method of finding cancers and polyps, but it is associated with significant miss rates for polyps <1 cm. The entire bowel should be carefully evaluated to exclude synchronous tumors in patients with known colorectal cancer. Further improvement of colonoscopic techniques and technologies is warranted.

[Malignant colonic polyps: is polypectomy adequate treatment?].

The management of patients with endoscopically removed malignant intestinal polyps is controversial. The risk of residual disease should be assessed against the risk of a surgical operation. The authors report 35 cases of malignant polyps (5.5% of 641 colonoscopically removed adenomas). Sixteen patients had carcinoma in situ and received no further treatment and 19 had invasive carcinoma (sessile in 6, pedunculated in 13). Of these 19, 7 did not undergo surgery--because of old age in 2, minimal invasion in 3, a low rectal location in 1 and refusal in 1. Twelve patients (3 with sessile, 9 with pedunculated polyps) underwent a surgical resection, and residual disease was present in 3 (25%), 1 with positive nodes. Reported criteria of increased risk of residual disease--cancer in lymphatics or veins, incomplete excision, tumour at resection margin, sessile and villous tumours--were present in nine. All three patients with residual disease had microscopically involved margins of resection. The authors believe that the increased risk of recurrence justifies the risk associated with subsequent surgical resection unless the patient is otherwise a poor operative risk.

Polyp (medicine)

Colon polyps as they grow can sometimes cause bleeding within the intestine, which can be detected by an occult blood test. According to American Cancer Society guidelines, people over 50 should have an annual occult blood test. People in their 50s are recommended to have flexible sigmoidoscopies performed once every 3 to 5 years to detect any abnormal growth which could be an adenomatous polyp. If adenomatous polyps are detected during this procedure, a colonoscopy is recommended. Medical societies recommend colonoscopies every ten years starting at age 50 as a necessary screening practice for colon cancer. The screening provides an accurate image of the intestine and also allows the removal of the polyp, if found. Once an adenomatous polyp is identified during colonoscopy, there are several methods of removal, including using a snare or a heating device. Colonoscopies are preferred over sigmoidoscopies because they allow the examination of the entire colon and can detect polyps in

Colonic polypectomy

Larger, pedunculated polyps Pedunculated polyps can be removed by snare polypectomy. When the polyp is identified, a polypectomy snare is passed over the polyp and around the stalk of the polyp. The loop of the snare is then tightened to grip the polyp stalk, and the polyp is pulled away from the wall of the colon. An electric current is then passed through the snare loop to cut through the polyp stalk, providing electrocautery at the same time. The polyp can then be retrieved using the snare or an endoscopy basket, and removed by withdrawing the colonoscope. Technique Polyps may be removed using cold biopsy forceps, cold snare polypectomy, hot biopsy forceps, hot snare polypectomy, endoscopic mucosal resection, or endoscopic submucosal dissection. Cold biopsy forceps may be used for small (diminutive) polyps 1-3 mm in size. Cold snare polypectomy has the advantage of avoiding the risk of delayed bleeding, postpolypectomy coagulation syndrome, and perforation.

Colorectal polyp

Gallery NICE classification In colonoscopy, colorectal polyps can be classified by NICE (Narrow-band imaging International Colorectal Endoscopic): Treatment Polyps can be removed during a colonoscopy or sigmoidoscopy using a wire loop that cuts the stalk of the polyp and cauterises it to prevent bleeding. Many "defiant" polyps—large, flat, and otherwise laterally spreading adenomas—may be removed endoscopically by a technique called endoscopic mucosal resection (EMR), which involves injection of fluid underneath the lesion to lift it and thus facilitate endoscopic resection. Saline water may be used to generate lift, though some injectable solutions such as SIC 8000 may be more effective. Minimally invasive surgery is indicated for polyps that are too large or in unfavorable locations, such as the appendix, that cannot be removed endoscopically. These techniques may be employed as an alternative to the more invasive colectomy.

Colonoscopy

Fecal occult blood is a quick test which can be done to test for microscopic traces of blood in the stool. A positive test is almost always an indication to do a colonoscopy. In most cases the positive result is just due to hemorrhoids; however, it can also be due to diverticulosis, inflammatory bowel disease (Crohn's disease, ulcerative colitis), colon cancer, or polyps. Colonic polypectomy has become a routine part of colonoscopy, allowing quick and simple removal of polyps during the procedure, without invasive surgery. Colon cancer screening Colonoscopy is one of the colorectal cancer screening tests available to people in the US who are 45 years of age and older. The other screening tests include flexible sigmoidoscopy, double-contrast barium enema, computed tomographic (CT) colongraphy (virtual colonoscopy), guaiac-based fecal occult blood test (gFOBT), fecal immunochemical test (FIT), and multitarget stool DNA screening test (Cologuard).

Polyp (medicine)

(first description by P. Deyhle, Germany, 1970), or with biopsy forceps. If an adenomatous polyp is found, it must be removed, since such a polyp is pre-cancerous and has a propensity to become cancerous. For certainty, all polyps which are found by any diagnostic modality, are removed by a colonoscopy. Although colon cancer is usually not found in polyps smaller than 2.5 cm, all polyps found are removed since their removal reduces the likelihood of future colon cancer. When adenomatous polyps are removed, a repeat colonoscopy is usually performed three to five years later.

Colon Polyps -- Treatment / Management

Colonic polypectomy is done during colonoscopy for diagnostic and therapeutic purposes using snare polypectomy with electrocautery for pedunculated polyps, or mucosal resection for sessile polyps. Total colectomy with ileorectal anastomosis or proctocolectomy ileal pouch anal anastomosis is done for prophylactic reasons for Familial Adenomatous Polyposis (FAP) and MUTYH-associated polyposis (MAP). They may also be done with persistent bleeding or when there are too many polyps. Guidelines for CRC screening recommend a colonoscopy starting at age 50 for the general population, earlier for at-risk patients, and to stop screening if life expectancy is less than ten years. Risk factors for colon cancer include polyp pathology (adenomatous, serrated, with high-grade dysplasia, with more than 25% villous histology), polyp more than 1 cm in diameter, polyps located in the proximal colon and the number of polyps more than three. Hence, a follow-up colonoscopy is recommended to be done in 10 years if no polyps or distal small hyperplastic polyps are found; in five years if there are small sessile serrated polyps with no dysplasia; in three years if they are large sessile serrated polyp(s) or with dysplasia or traditional serrated adenoma. Other guidelines include screening in five to ten years if one or two small tubular adenomas are seen; in three years if there are three to ten adenomas; in less than three years if there are more than ten adenomas; and in three years if at least one adenoma is ten mm in diameter or more. Alternatively, also screen in three years if one or more adenomas show villous features of any or with high-grade dysplasia. Colectomy is recommended in cases of resected polyps with high-risk features of malignancy (lower third of the submucosa invasion, indeterminate or positive resection margins, margin less than 1 mm, lymphovascular invasion, or poor differentiation) as there is a high incidence of lymph node metastasis. [13] [14]

[Clinical aspects in polyps of the colon].

The colonics polyps according to their number, size, location, age of presentation and mainly, according to their histology, have the potentiality of malignant degeneration, which makes of a continuous study and pursuit susceptible. To evaluate the relation between the histologic type of the colon polyps, its location, the degree of dysplasia, the size, its possible commitment by carcinoma, the age, sex and the handling that has occurred them, in a series of 684 patients of the National Institute of Enfermedades Neoplásicas (INEN) between the 1 of January from 1974 to the 31 of March of the 2004. The revision of clinical histories of 840 patients with the diagnosis of colon polyp was made who attended the service of Gastroenterology of the INEN between the 1 of January from 1974 to the 31 of March of 2004 and a card predesigned for each clinical history filled. The study is of observational, analytical type and of cross section. 1162 resecteds polyps evaluated themselves in this period. 156 patients by diagnosis related to cancer and familiar adenomatouspoliposis did not include themselves. The final sample was of 684 patients, in whom it was 1057 polyps. Other endoscopic findings were: internal hemorrhoids (172), colonic diverticulosis (50), anal fissure (4), and nonspecific ulcerative colitis (2). The statistical processing was made with program SPSS 12. For the qualitative variables the method of the Chi-square was used, for the quantitative variables analyzed the average, the rank and the variance. 1057 polyps extirpated, by means of the endoscopy polipectomy were 1016, with colectomy were 32 and with transanal resection without colectomy they 9. Within the histology of the 1057 polyps, 331 was briefed (31.3%) that were hyperplasic, 448 (42.4%) adenomas, 278 (26.3%) others and 35 (8.2%) adenocarcinomas on adenomas. The average age was of 50 years, was no significant difference with sex. The location but frequence of the adenomas was in the left colon (76.6%). Adenocarcinoma (carcinomas on adenomas), was present mainly in polyps villous type, with dysplasia severe and greater to 10 mm. Nevertheless, in smaller polyps of 5mm with dysplasia severe, was a polyp invaded by cancer, that represents the 0,8% of millimetric polyps. The made handling was mainly endoscopic, with 96% of the resected polyps this way, also slogan transanal resection and segmental colonic resection. The colectomy was necessary in 3% of all the made interventions, dysplasia severe or carcinoma was made in adenomatous polyps with, and in greater percentage in greater polyps of 20 mm (53%). The single polipectomy was sufficient in the level of invasion Haggitt 0. In patients with level of invasion Haggitt 1 and 2, the single polipectomy was the election treatment. On the other hand, in polyps with level of invasion Haggitt 3 and 4, the colectomy was the election treatment. One briefed two complications, one of perforation and peritonitis and another one of digestive hemorrhage loss (both: 0.29%), without mortality events. The Evaluation of colonic polyps in INEN is predominantly by endoscopy. The polyps are more frequent over the 50 years and have preferred location in the left colon. The carcinoma is more probable with severe dysplasia and greater size of the adenoma. All polyps, from the millimetric ones, including the hyperplasic, must be considered marks of neoplasia and extirpated in its totality.

Surgery_Schwartz

if a lesion is discovered.Computed Tomography Colonography (Virtual Colonos-copy). Advances in imaging technology have created a num-ber of less invasive, but highly accurate tools for screening. CT colonography makes use of helical CT technology and three-dimensional reconstruction to image the intraluminal colon. At present, patients require a mechanical bowel preparation. The colon is then insufflated with air, a spiral CT is performed, and both two-dimensional and three-dimensional images are gener-ated. In the hands of a qualified radiologist, sensitivity appears to be as good as colonoscopy for colorectal cancers and polyps greater than 1 cm in size.103 Colonoscopy is required if a lesion is identified. CT colonography has also been used for imag-ing the proximal colon in cases of obstruction or if a colonos-copy cannot be completed in selected patients. Limitations of this technique include false-positive results from retained stool, diverticular disease, haustral folds, motion

Polyp (medicine)

It has been statistically demonstrated that screening programs are effective in reducing the number of deaths caused by colon cancer due to adenomatous polyps. The risk of complications associated with colonoscopies is approximately 0.35 percent, compared to a lifetime risk of developing colon cancer of around 6 percent. As there is a small likelihood of recurrence, surveillance after polyp removal is recommended. Endometrial polyp

Polyp (medicine)

There are three types of adenomatous polyp: Tubular adenomas (tube-like shape) are the most common of the adenomatous polyps; they may occur everywhere in the colon and they are the least likely colon polyps to develop into colon cancer Tubulovillous Villous adenomas are commonly found in the rectal area and they are normally larger in size than the other two types of adenomas. They tend to be non-pedunculated, velvety, or cauliflower-like in appearance and they are associated with the highest morbidity and mortality rates of all polyps. They can cause hypersecretory syndromes characterized by hypokalemia and profuse mucous discharge, and can harbor carcinoma in situ or invasive carcinoma more frequently than other adenomas.

Colon cancer staging

Colon cancer staging is an estimate of the amount of penetration of a particular cancer. It is performed for diagnostic and research purposes, and to determine the best method of treatment. The systems for staging colorectal cancers depend on the extent of local invasion, the degree of lymph node involvement and whether there is distant metastasis. Definitive staging can only be done after surgery and histopathology of colorectal carcinoma. An exception to this principle would be after a colonoscopic polypectomy of a malignant pedunculated polyp with minimal invasion. Preoperative staging of rectal cancers may be done with endoscopic ultrasound. Adjunct staging of metastasis include abdominal ultrasound, MRI, CT, PET scanning, and other imaging studies.

Polyp (medicine)

Risks The risks of progression to colorectal cancer increase if the polyp is larger than 1 cm and contains a higher percentage of villous component. Also, the shape of the polyps is related to the risk of progression into carcinoma. Polyps that are pedunculated (with a stalk) are usually less dangerous than sessile polyps (flat polyps). Sessile polyps have a shorter pathway for migration of invasive cells from the tumor into submucosal and more distant structures, and they are also more difficult to remove and ascertain. Sessile polyps larger than 2 cm usually contain villous features, have a higher malignant potential, and tend to recur following colonoscopic polypectomy. Although polyps do not carry significant risk of colon cancer, tubular adenomatous polyps may become cancerous when they grow larger. Larger tubular adenomatous polyps have an increased risk of malignancy when larger because then they develop more villous components and may become sessile.

Endoscopic mucosal resection

For the colon and rectum Endoscopic mucosal resection and submucosal dissection are also highly effective methods for resection or large, non-malignant colorectal polyps and superficially (stage T1a) invasive colorectal cancers. The largest study of endoscopic mucosal resection by the Australian Consortium included 1000 cases and long term surveillance. After exclusion of 79 unresectable lesions, the remainder were treated by endoscopic mucosal resection. Overall 98.1% were disease free at the end of two rounds (typically at 6 and 18 months) of follow up. Endoscopic mucosal resection has been shown to be less expensive and safer compared to surgical resection of large, non-invasive polyps of the bowel. Endoscopic mucosal resection requires training to achieve proficiency. The Mayo Clinic Florida group reported that at least 100 procedures are needed to achieve proficiency. Many centers in the United States now offer high-quality, high-volume colorectal endoscopic mucosal resection.

Rapid progression of submucosal invasive micropapillary carcinoma of the colon in progressive systemic sclerosis: report of a case.

A 71-year-old woman presented with hematochezia and narrowing of the stool. She suffered from progressive systemic sclerosis for 12 years and underwent home oxygen therapy due to pulmonary fibrosis and moderate pulmonary hypertension. Colonoscopy revealed a pedunculated, cauliflower-like polyp with a depressed surface in the sigmoid colon. The polyp was regarded as early colon cancer with possible submucosal invasion, and subsequent computed tomographic (CT) scans showed no evidence of lymph node involvement or distant metastases. Because of perioperative risks due to moderate pulmonary hypertension, she underwent an endoscopic resection of the early colon cancer. Pathological examination of the resected specimen of 20 mm diameter revealed the peculiar morphology of an adenocarcinoma with moderate lymphatic invasion. Immunohistochemical analysis for epithelial membrane antigen showed the specific 'inside-out growth pattern' indicative of invasive micropapillary carcinoma (IMPC). Taking the perioperative risks into consideration, she opted to undergo close follow-ups without an additional sigmoidectomy. At 6 months after the resection, the follow-up colonoscopy revealed a local recurrence of the colon cancer, and subsequent CT scans revealed multiple distant metastases including the lung, liver, lymph nodes and spleen. This is a rare case of a pure, submucosal IMPC of the colon. Furthermore, pure IMPC of the colon may represent a reliable predictor of lymphogenous and/or hematogenous metastases. Therefore, one should recommend an additional colectomy after endoscopic mucosal resection treatment when pathological findings confirmed IMPC of the colon and should continue a close follow-up for IMPC patients even when curative resections were performed at an early stage.

[Colonic polyps: clinical and practical implications].

Among colorectal polyps, various forms of neoplastic or non-neoplastic lesions are distinguished by histology. Most accumulated knowledge suggests that the majority of cancer of the colon arise in pre-existing benign neoplastic polyps (adenoma-carcinoma sequence). Because of the risk of cancer being already present, all adenomatous polyps must be removed in toto. The carcinoma may occupy only a small area of the polyp, and therefore, forceps biopsies are inappropriate due to the sampling error. Since patients with polyps detected by rectosigmoidoscopy often have further polyps in the remaining part of the colon, complete examination of the whole colon is required. Follow-up examinations are indicated, because the risk of developing new polyps is high. Studies of the life history of the adenoma-carcinoma sequence suggest that interval of complete large-bowel follow-up may be about 5 years. The policy of polypectomy and follow-up examinations should be possible to prevent the development of colorectal cancer.

[Oncological supervision of patients after colonoscopic polypectomy].

The high frequency of development of new adenomas in patients after colonoscopic polypectomy (30-50%) suggests the need for periodic control examinations of the whole large bowel. The diagnostic value of rectoscopy and routine diagnostic enema is limited and these methods are not suitable for periodic control of the bowel. An important method is fiberoptic sigmoidoscopy (FSS), but it is also insufficient because neoplasms are present frequently in proximal parts of the colon. The best method for evaluation of the whole colon is coloscopy, moreover, this method makes possible removal of the found polyps. In particular cases an alternative of coloscopy may be a combination of FSS and double contrast radiological examination of the colon. The frequency of control examinations of the large bowel depends primarily on the number of removed polyps. The patients after removal of a single polyp should undergo control examinations at intervals of 4-5 years. In cases with multiple adenomas removed during the first procedure or with one large adenoma (over 2 cm in diameter) should have control examinations repeated every 2-3 years.

Malignant colon polyps--cure by colonoscopy or colectomy?

Although malignant sessile colon polyps usually require colectomy for proper treatment, the vast majority of malignant pedunculated polyps can be removed colonoscopically for cure. The author's experience with 83 consecutively encountered malignant polypoid lesions is reviewed and is the basis for the discussion herein. All 49 malignant pedunculated polyps were removed colonoscopically. Eight of these patients also underwent colectomy because of questionable or definite presence of cancer cells within the stalk portion of the polyp; no residual cancer was identified at the polypectomy site, and all lymph nodes were negative in these patients. Of 34 patients with malignant sessile polypoid lesions, 13 underwent colectomy because of obvious malignancy at colonoscopy. Twenty-one sessile lesions were removed colonoscopically; with malignancy documented, nine of the 21 patients underwent colectomy. Positive findings (either cancer at the polypectomy site or in lymph nodes) at surgery were identified in two of these nine patients. Colonoscopic polypectomy can be considered curative for malignant pedunculated polyps provided the stalk portion of the lesion is totally uninvolved with the malignant process, provided there is no lymphatic or vascular invasion, the malignancy is well differentiated, and follow-up endoscopic examination of the polypectomy site reveals no residual or recurrence. These four criteria must be satisfied in order to consider a malignant pedunculated polyp curatively removed by colonoscopic polypectomy alone. The risk of colectomy in patients satisfying these four criteria is believed to be greater than the risk of metastatic disease and death from this lesion. Colectomy is recommended for all patients with malignant sessile polypoid lesions, provided their general medical condition provides an acceptable operative risk. Although colonoscopic polypectomy is not recommended for obviously malignant sessile polyps, there are instances where sessile lesions are removed colonoscopically and found microscopically to contain focal or minute areas of invasive cancer. In certain of these patients, the risk of colectomy may exceed the risk of recurrence or metastasis, if the polypoid lesion has been totally removed colonoscopically and completeness of the polypectomy has been documented by follow-up colonoscopy. Each patient's clinical history, general condition, and histopathology must be reviewed individually by a clinician experienced in this field in order to reach a wise and proper decision regarding the potential need for colectomy, and limit colectomy to those patients in whom it is absolutely necessary.

A hard look at colonoscopy.

The fiberoptic colonscope represents a significant diagnostic and therapeutic acheivement in the management of colonic disease. Despite some claims to the contrary, it is not universally simple, rapid, thorough, reliable, and inexpensive or without morbidity and mortality. Until these goals are achieved through future refinements, modifications, and new instrumentation, it is strongly recommended that the indications for colonscopy be sharply defined to include the following: (1) Investigation of colonic lesions seen on two successive or one air-contrast barium enema examination. Pedunculated polyps less than 1 cm in diameter can be observed. (2) Preoperative investigation of patients with demonstrable colorectal cancer (to rule out synchronous lesions). (3) Postoperative evaluation after colectomy for carcinoma where the anastomosis is above the reach of a sigmoidoscope. (4) Evaluation of patients with inflammatory bowel disease of the colon. (5) Investigation of persistent occult or gross rectal bleeding when anoscopy, sigmoidoscopy, and barium studies are negative. Patients who represent prohibitive surgical risks because of age or systemic disease should not be considered as candidates for colonoscopy without compelling indications. The decision to biopsy rather than remove or fulgerate a detected lesion must be left to the judgment and experience of the endoscopist. The morbidity that follows polypectomy or fulgeration of sessile lesions less than 0.5 cm in diameter probably exceeds the incidence of carcinoma.


Allopurinol is always the treatment of choice, especially in the case of tophaceous gout. Moreover, in this case, uricosuric acid could worsen urolithiasis by increasing uricosuria (sorry for the redundancy...).

A 62-year-old man with a history of arterial hypertension under treatment with captopril, duodenal ulcer and uric acid urolithiasis. He consults for typical podagra crisis similar to others presented in the last two years. Examination showed tophi in both pinnae. Analyses show uric acid 10.1 mg/dl, creatine 1.5 mg/dl. Indicate which of the following answers is FALSE in relation to his possible treatment with allopurinol.

Its use is second choice when uricosurics have failed.

Its prolonged use is practically obligatory because there are tophi.

Its introduction should be delayed until the current attack has resolved with anti-inflammatory drugs or colchicine.

Its introduction should be gradual up to a dose that achieves a uricemia below 6 mg/dL.

In the first months of treatment it is advisable to associate low doses of colchicine to prevent new attacks.

Gout: an update.

Arthritis caused by gout (i.e., gouty arthritis) accounts for millions of outpatient visits annually, and the prevalence is increasing. Gout is caused by monosodium urate crystal deposition in tissues leading to arthritis, soft tissue masses (i.e., tophi), nephrolithiasis, and urate nephropathy. The biologic precursor to gout is elevated serum uric acid levels (i.e., hyperuricemia). Asymptomatic hyperuricemia is common and usually does not progress to clinical gout. Acute gout most often presents as attacks of pain, erythema, and swelling of one or a few joints in the lower extremities. The diagnosis is confirmed if monosodium urate crystals are present in synovial fluid. First-line therapy for acute gout is nonsteroidal anti-inflammatory drugs or corticosteroids, depending on comorbidities; colchicine is second-line therapy. After the first gout attack, modifiable risk factors (e.g., high-purine diet, alcohol use, obesity, diuretic therapy) should be addressed. Urate-lowering therapy for gout is initiated after multiple attacks or after the development of tophi or urate nephrolithiasis. Allopurinol is the most common therapy for chronic gout. Uricosuric agents are alternative therapies in patients with preserved renal function and no history of nephrolithiasis. During urate-lowering therapy, the dose should be titrated upward until the serum uric acid level is less than 6 mg per dL (355 micromol per L). When initiating urate-lowering therapy, concurrent prophylactic therapy with low-dose colchicine for three to six months may reduce flare-ups.

Gout treatment: should we aim for rapid crystal dissolution?

Monosodium urate crystal deposition in gout precedes the first attack and, while hyperuricaemia persists, it grows and expands to other sites. Fortunately, it is reversible and slowly dissolves when serum uric acid (SUA) is lowered below its saturation point of about 6.8 mg/dl and with certainty below 6 mg/dl. Crystals finally disappear from joints, taking longer in those patients with longer disease duration, probably because of a larger accumulated load of crystals. The SUA level achieved affects the velocity of crystal dissolution and tophi reduction. Accordingly, by deciding the SUA level cut-off point to be achieved by treatment we are determining the time of crystal disappearance and cure of gout. 6 mg/dl is the usual target level, but lower levels appear appropriate to us, particularly in certain situations.

[Summary of the Dutch College of General Practitioners' "Gout" Standard].

The typical form of acute gout can be clinically diagnosed. The term 'complicated gout' is used if there are more than three acute attacks of gout per year, tophi or urate stones in the urinary tracts. In the case of recurrent probable acute gout, a diagnostic fine needle aspirate from the joint during an attack is indicated. First choice treatment of acute gout consists of NSAIDs. Colchicine is the second choice treatment and the third choice treatment consists of corticosteroids. Excessive alcohol use should be limited. Treatment of chronic gout depends on the uric acid excretion in the 24-hour urine. If the level of excretion is too low, the first choice should be benzbromarone, and if the uric acid output is too high, allopurinol should be the treatment of first choice. Increased fluid intake is recommended; maintenance treatment with colchicine is not advised. Consultation with or referral to a rheumatologist is indicated in the case of doubt about the diagnosis of 'acute gout' or 'complicated gout', or (suspected) bacterial arthritis and insufficient treatment effect.

Evaluating appropriate use of prophylactic colchicine for gout flare prevention.

American College of Rheumatology and European League Against Rheumatism guidelines recommend colchicine to prevent gout flares in patients initiating and increasing uric acid–lowering therapy until serum uric acid is maintained at ≤6 mg/dl. We aimed to evaluate how well colchicine prescribing practices adhere to these guidelines and to examine factors associated with improved prescribing. Electronic medical records were reviewed for 126 patients with active colchicine prescriptions for prophylaxis of gout flares. Colchicine prescribing was defined as inappropriate if 1) no concurrent urate-lowering therapy was prescribed, 2) uric acid was not at goal and urate-lowering therapy had not been increased in the past 3 months, or 3) uric acid goals were met for >1 year and flares had resolved in the absence of tophi. Colchicine use was considered inappropriate in 93 patients (73.8%). Thirty-four were prescribed no urate-lowering therapy, 50 were above the uric acid goal without urate-lowering therapy increase in the prior 3 months, and 9 were at the uric acid goal for >1 year without flares or tophi. Patients appropriately prescribed colchicine were younger and were more likely to have been seen by a rheumatologist. Allopurinol dose and allergy, uric acid level, and renal function were similar in the 2 groups. We found a high prevalence of what we considered inappropriate prophylactic colchicine use, driven largely by failure to prescribe concurrent urate-lowering therapies or adequately increase these medications. Rheumatology consultation was associated with improved colchicine prescribing.

Gout--current diagnosis and treatment.

Because of the changing dietary habits of an aging population, hyperuricemia is frequently found in combination with other metabolic disorders. Longstanding elevation of the serum uric acid level can lead to the deposition of monosodium urate crystals, causing gout (arthritis, urate nephropathy, tophi). In Germany, the prevalence of gouty arthritis is estimated at 1.4%, higher than that of rheumatoid arthritis. There are no German guidelines to date for the treatment of gout. Its current treatment is based largely on expert opinion. Selective literature review on the diagnosis and treatment of gout. Asymptomatic hyperuricemia is generally not an indication for pharmacological intervention to lower the uric acid level. When gout is clinically manifest, however, acute treatment of gouty arthritis should be followed by determination of the cause of hyperuricemia, and long-term treatment to lower the uric acid level is usually necessary. The goal of treatment is to diminish the body's stores of uric acid crystal deposits (the intrinsic uric acid pool) and thereby to prevent the inflammatory processes that they cause, which lead to structural alterations. In the long term, serum uric acid levels should be kept below 360 micromol/L (6 mg/dL). The available medications for this purpose are allopurinol and various uricosuric agents, e.g., benzbromarone. There is good evidence to support the treatment of gouty attacks by the timely, short-term use of non-steroidal anti-inflammatory drugs (NSAID), colchicine, and glucocorticosteroids.

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.

Prevention and management of gout.

Gout is a common disease with a worldwide distribution. The major risk factor for the development of gout is sustained asymptomatic hyperuricaemia. Although pharmacological therapy of asymptomatic hyperuricaemia is not recommended, primary prevention of gout can be achieved through lifestyle changes including weight loss, restricting protein and calorie intake, limiting alcohol consumption, avoiding the use of diuretics in the treatment of hypertension, and avoiding occupational exposure to lead. The arthritis of gout can be readily managed with the use of nonsteroidal anti-inflammatory drugs (NSAIDs); systemic steroids or corticotrophin (adrenocorticotrophic hormone; ACTH) should be used in patients with contraindications to NSAIDs, or who are intolerant of them. Because of potential toxicity, colchicine should not be used to treat acute gout, but should be used in low dosage (0.6 to 1.2 mg/day) for prophylaxis of recurrent attacks of gout. The other cornerstone of prevention of recurrent gouty attacks is control of hyperuricaemia, which can be effectively accomplished with antihyperuricaemic therapy. The choice of agents, either uricosuric drugs or xanthine oxidase inhibitors, is based on the level of urinary uric acid excretion, renal function, age of patient, history of renal calculi and presence of tophi. Treatment and prevention of gout are exceedingly effective and patients can usually be managed by their primary care physician.

Drugs to lower uric acid levels. How to avoid misuse in gouty arthritis.

Several points regarding the use of drugs to lower uric acid levels deserve emphasis. First, these agents are not useful in the management of acute gout. Second, all forms of the drugs should be initiated at low dose with gradual increments to achieve a serum uric acid level between 5 and 6 mg/dL. There are no data to support the widely presumed notion that dropping the uric acid level to a very low range (1 to 3 mg/dL) hastens resorption of tophi or improves joint function. Third, the uricosuric agents probenecid (Benemid) and sulfinpyrazone (Anturane) interact with a number of drugs, and both the patient and physician should be aware of this. Finally, and most important, careful and frequent monitoring is needed during the first several months of therapy with these drugs.

Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout?

To determine if lowering of serum uric acid (SUA) concentrations below 6 mg/dl or longer duration of lowered SUA will result in depletion of urate crystals from the knee joints and prevent further attacks of gout. A prospective study was initiated 10 years ago at Philadelphia VA Medical Center to attempt to maintain SUA levels of patients with crystal proven gout at < 6.0 mg/dl. We recalled all 57 patients who were available during 1999. Patients were divided into 2 groups: Group A, with SUA still > 6 mg/dl, and Group B, with SUA < or = 6 mg/dl. A knee joint aspirate was requested from all asymptomatic Group B patients and many in Group A. Aspirates were examined by polarized light microscopy for identification of crystals. There were no differences between the groups in age, sex, duration of gout, or serum creatinine. Group A (n = 38) had a mean of 6 attacks of gout for the recent year, those with tophi having the most frequent attacks. Among the 16 patients in this group who agreed to knee aspiration, monosodium urate (MSU) crystals were found in 14, although they were asymptomatic at the time. Nineteen patients (Group B) were able to maintain serum urate levels < or = 6 mg/dl for > 12 months. Nearly half of them had no attack of gout for 2 or more years, with a mean of 1 attack in the last year for the whole group. Three patients in whom tophi were found did not have major flares of gout within the past year. Knee joint aspiration was done on 16 asymptomatic patients. Seven (44%) still had MSU crystals present in their knees. Patients in this group who were taking prophylactic colchicine did not differ with respect to the character of synovial fluid from those who had discontinued it for up to several years, although the frequency of attacks was less in those who continued colchicine. A majority of patients were able to deplete urate crystal stores in their knee joint fluids when their SUA levels were kept to < or = 6 mg/dl for several years. The mechanisms for persistence in some patients, and whether such crystals have clinical implications, are not known. Patients with chronic gout need serum urate concentrations to be kept low to prevent further attacks.

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.

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.

Treatment Options for Gout.

1-2% of adults in Germany suffer from gout. Gout is one of the few rheumatological diseases that can be cured. It arises through the deposition of uric acid crystals in joints as a result of hyperuricemia. Painful redness and swelling of the affected joints are typical findings. Multiple pertinent guidelines and treatment recommendations have been published, but there is reason to believe that patients with gout are not always treated accordingly. This review is based on relevant publications from the years 2000-2016 that were retrieved by a selective search in the Cochrane and PubMed databases. In a person with normal renal function, asymptomatic hyperuricemia is not an indication for treatment to lower the serum uric acid level. The drugs of first choice for acute gouty arthritis are nonsteroidal antiinflammatory drugs (NSAID), corticosteroids, and colchicine. Treatment with xanthine oxidase inhibitors (XOI) or uricosuric drugs is indicated for patients with a recurrent or severe course; the target uric acid value is <6 mg/dL. Long-term treatment should be initiated only after resolution of the acute attack. For patients with refractory gout, lesinurad (approved in February 2016) in combination with XOI is a new treatment option that can be considered. Comprehensive patient education and counseling is an important component of the treatment of patients with gout. Regular laboratory follow-up is necessary as well. The prevalence of gout is rising around the world. Patients with gout could benefit greatly from consistent implementation of the existing treatment guidelines and recommendations. In the future, controlled trials should be conducted to determine the best time to start treatment and the optimal target level for the serum uric acid concentration in terms of a risk/benefit analysis.

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.

Diagnosis, treatment, and prevention of gout.

Gout is characterized by painful joint inflammation, most commonly in the first metatarsophalangeal joint, resulting from precipitation of monosodium urate crystals in a joint space. Gout is typically diagnosed using clinical criteria from the American College of Rheumatology. Diagnosis may be confirmed by identification of monosodium urate crystals in synovial fluid of the affected joint. Acute gout may be treated with nonsteroidal anti-inflammatory drugs, corticosteroids, or colchicine. To reduce the likelihood of recurrent flares, patients should limit their consumption of certain purine-rich foods (e.g., organ meats, shellfish) and avoid alcoholic drinks (especially beer) and beverages sweetened with high-fructose corn syrup. Consumption of vegetables and low-fat or nonfat dairy products should be encouraged. The use of loop and thiazide diuretics can increase uric acid levels, whereas the use of the angiotensin receptor blocker losartan increases urinary excretion of uric acid. Reduction of uric acid levels is key to avoiding gout flares. Allopurinol and febuxostat are first-line medications for the prevention of recurrent gout, and colchicine and/or probenecid are reserved for patients who cannot tolerate first-line agents or in whom first-line agents are ineffective. Patients receiving urate-lowering medications should be treated concurrently with nonsteroidal anti-inflammatory drugs, colchicine, or low-dose corticosteroids to prevent flares. Treatment should continue for at least three months after uric acid levels fall below the target goal in those without tophi, and for six months in those with a history of tophi.

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.

Diagnosis and treatment of gout in primary care.

The prevalence of gout increases with age. Up to 7% of men > 65 and 3% of women > 85 have gout. Risk of gout increases significantly with increasing serum uric acid levels. Alcohol consumption and purine-rich foods such as red meat and seafood increase the risk of incident gout significantly. Loop and thiazide diuretics are also associated with increased risk. Gout is frequently associated with the metabolic syndrome. Dehydration, increasing creatinine levels, and surgery are also known to precipitate flares. Acute gout manifests as severe joint pain, of rapid onset, reaching maximal intensity within a few hours. Gout has a predilection for lower extremity joints. It often starts at the first metatarsophalangeal joint, a condition termed podagra. Other common sites of gouty flares include: tarsal and subtalar joints; ankle; knee; wrist; small joints of the hands; Achilles tendon; and olecranon bursae. The joint affected is usually hot, red, swollen and very painful. This is often associated with skin erythema. Identification of MSU crystals in the synovial fluid of an inflamed joint or from tophi allows a definite diagnosis of gout to be made. Hyperuricaemia does not confirm or exclude gout as most people with hyperuricaemia are asymptomatic, while serum uric acid levels tend to decrease during acute attacks. Short-acting NSAIDs should be used at maximal dose as first drug of choice if not contraindicated. In patients at risk of GI complications, co-prescription of a proton pump inhibitor or the use of COX-2 selective agents should be considered. Colchicine can be particularly useful in patients with heart failure in whom NSAIDs are contraindicated but should be avoided in patients with severe renal impairment. Joint aspiration and injection of intra-articular steroids is one of the most effective ways of treating acute monoarthritic gout. Uric acid lowering therapy is initiated if a patient suffers two or more attacks in one year. Many rheumatologists will start this therapy in hyperuricaemic patients whose first attack is very severe or in polyarticular gout.

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.

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.

Gout: a review of its aetiology and treatment.

To review the current understanding of the causes and the management of gout. Publications on all peer-review literature from MEDLINE from 1965 to January 2004. Selected and evaluated by the author. Extracted and evaluated by the author. The underlying metabolic disorder in gout is hyperuricaemia. Most patients with hyperuricaemia remain asymptomatic throughout their lifetime. The phase of asymptomatic hyperuricaemia ends with the first attack of gouty arthritis or urolithiasis. The risk of gout and stone formation is increased with the degree and duration of hyperuricaemia. Drugs available for the treatment of acute gouty arthritis, such as non-steroidal anti-inflammatory drugs, selective cyclo-oxygenase 2 inhibitors, systemic corticosteroids, or colchicine, are effective. For periods between attacks, prophylactic therapy, such as low-dose colchicine, is effective. In those with recurrent attacks of more than two to three times yearly, a uric acid-lowering agent as a long-term therapy should be considered to avoid recurrence and the development of tophaceous gout. Effective management of gout can be achieved through better understanding of the causes of the condition, preventive measures as well as drug treatment.

Treatment of hyperuricemia, gout and other crystalline arthritidies.

Gout is a very common joint disease which is due to chronic hyperuricemia and its related articular involvements. Yet it can be cured when appropriately managed. Comprehensive management of gout involves correct identification and addressing all causes of hyperuricemia, treating and preventing attacks of gouty inflammation (using colchicine NSAIDs, and/or steroids), and lowering serum urate (SUA) to an appropriate target level indefinitely. The ideal SUA target is, at a minimum, less than 6 mg/dL (60 mg/L or 360 μmol/L), or even less than 5 mg/dL in patients with tophi. The SUA target should remain at less than 6 mg/dL for long in all gout patients, especially until tophi have resolved. Patient education and adherence to therapy are key point to the optimal management of gout, aspects which are often neglected. Adherence can be monitored in part by continuing, regular assessment of the SUA level. More difficult cases of gout often need a combination of urate lowering therapy (ULT) for both refractory hyperuricemia and chronic tophaceous arthritis. Chronic tophaceous gouty arthropathy which do not respond adequately to optimized oral ULT might benefit from the use of pegloticase, when this is available in, for example, Italy and other European countries. By contrast, in calcium pyrophosphate (CPP) crystal deposition disease (CPPD), as evidenced by pseudo gout attacks or chronic polyarthritis, similar anti-inflammatory strategies have been recommended, but there have as yet been no controlled trials. Of note, there is no treatment for the underlying metabolic disorders able to control the CPPD. Management of crystal-induced arthropathies (CIA) depends not only on clinical expression, namely acute attacks or chronic arthropathy, but also on the underlying metabolic disorder. We will mainly focus on gout as an archetype of CIA.

Gout

Probenecid appears to be less effective than allopurinol and is a second line agent. Probenecid may be used if undersecretion of uric acid is present (24-hour urine uric acid less than 800 mg). It is, however, not recommended if a person has a history of kidney stones. Pegloticase is an option for the 3% of people who are intolerant to other medications. It is a third line agent. Pegloticase is given as an intravenous infusion every two weeks, and reduces uric acid levels. Pegloticase is useful decreasing tophi but has a high rate of side effects and many people develop resistance to it. Using lesinurad plus febuxostat is more beneficial for tophi resolution than lesinural with febuxostat, with similar side effects. Lesinural plus allopurinol is not effective for tophi resolution. Potential side effects include kidney stones, anemia and joint pain. In 2016, it was withdrawn from the European market.

[How to select and use urate lowering agents for hyperuricemia].

Two classes of urate lowering agents, i.e. uricosuric agents and allopurinol, are available for the treatment of hyperuricemia. To prevent the formation of urinary urate stones and possible damage to liver function, it is recommended to use uricosuric agents in those patients with underexcretion of urate, and allopurinol in those with overproduction. Urinary uric acid/creatinine ratio is a convenient index to determine these phenotypes. These agents should be started to prescribe from the minimal dose to prevent the gouty arthritis which is easily evoked in the first several months after the introduction of these agents. An uric acid level between 5.0 and 6.4 mg/dl had minimal occurence of gouty attack during the first six months of the drug therapy.

2011 Recommendations for the diagnosis and management of gout and hyperuricemia.

Gout is a major health problem in the United States; it affects 8.3 million people, which is approximately 4% of the adult population. Gout is most often diagnosed and managed in primary care physician practices. Primary care physicians have a significant opportunity to diagnose and manage patients with gout and improve patient outcomes. Following publication of the 2006 European League Against Rheumatism (EULAR) gout guidelines, significant evidence on gout has accumulated and new treatments for patients with gout have become available. It is the objective of these 2011 recommendations for the diagnosis and management of gout and hyperuricemia to update the 2006 EULAR guidelines, paying special attention to the needs of primary care physicians, who manage most patients with gout. The revised 2011 recommendations are based on the Grading of Recommendations Assessment, Development, and Evaluation approach as an evidence-based strategy for rating quality of evidence and grading strength of recommendation in clinical practice. A total of 26 key recommendations for diagnosis (n = 10) and management (n = 16) were evaluated. Presence of tophus (proven or suspected) and response to colchicine had the highest clinical diagnostic value (likelihood ratio [LR], 15.56 [95% CI, 2.11-114.71] and LR, 4.33 [95% CI, 1.16-16.16], respectively). The key aspect of effective management of an acute gout attack is initiation of treatment within hours of onset of first symptoms. Low-dose colchicine is better tolerated than and is as effective as high-dose colchicine (number needed to treat [NNT], 5 [95% CI, 3-13] and NNT, 6 [95% CI, 3-72], respectively). For urate-lowering therapy, allopurinol in combination with probenecid was shown to be more effective than either agent alone (effect size [ES], 5.51 for combination; ES, 4.46 for probenecid; and ES, 2.80 for allopurinol). Febuxostat, also a xanthine oxidase inhibitor, has a slightly different mechanism of action and can be prescribed at unchanged doses for patients with mild-to-moderate renal or hepatic impairment. Febuxostat 40 mg versus 80 mg (NNT, 6 [95% CI, 4-11]) and 120 mg (NNT, 6 [95% CI, 3-26]) both demonstrated long-term efficacy. The target of urate-lowering therapy should be a serum uric acid level of ≤ 6 mg/dL. For patients with refractory and tophaceous gout, intravenous pegloticase is a new treatment option.

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.

[Treat to target in gouty arthritis].

Gout is a crystal-induced, metabolically determined inflammatory rheumatic disease with increasing prevalence. In clinical practice, gout causes frequent diagnostic as well as therapeutic problems. The golden diagnostic standard is crystalographic analysis and evidence of monosodium urate crystals in the polarization microscope; if this is not available, the diagnosis can be established through a combination of clinical, laboratory and imaging techniques. The acute gouty attack must be treated by quick administration of anti-inflammatory medicines, with available alternatives being nonsteroidal antirheumatic drugs (NSA), colchicine and glucocorticoids. When the attack subsides, hypouricemic therapy is initiated which should combine the regimen and diet measures and pharmacological treatment. Recommendations for the treatment of gout were published by the EULAR and the Czech Society for Rheumatology. Recently a new strategy appeared known as Treat to target - T2T. This principle has been successfully used in the treatment of rheumatiod arthritis and spondyloarthritis. The publication is structured as four overarching principles and nine Recommendations. The recommendations emphasize long-term maintenance of serum levels of uric acid below 360 μmol/l as the basic gout-related target in all patients, and below 300 μmol/l for patients with tophies. It is recommended to administer prophylactic small doses of colchicine for at least 3-6 months on the commencement of hypouricemic therapy. The Recommendations further emphasize the need for regular monitoring of comorbidities and the kidney function. A separate recommendation is concerned with necessary education of patients and their motivation toward compliance with regimen measures and increased physical activity.Key words: colchicine - gouty arthritis - treat to target principle.

Lesch–Nyhan syndrome

It is essential that the overproduction of uric acid be controlled in order to reduce the risk of nephropathy, nephrolithiasis, and gouty arthritis. The drug allopurinol is utilized to stop the conversion of oxypurines into uric acid, and prevent the development of subsequent arthritic tophi (produced after having chronic gout), kidney stones, and nephropathy, the resulting kidney disease. Allopurinol is taken orally, at a typical dose of 3–20 mg/kg per day. The dose is then adjusted to bring the uric acid level down into the normal range (<3 mg/dL). Most affected individuals can be treated with allopurinol all through life. No medication is effective in controlling the extrapyramidal motor features of the disease. Spasticity, however, can be reduced by the administration of baclofen or benzodiazepines.

Gout -- Treatment / Management -- Prophylaxis For Acute Gout

The subclinical joint inflammation in gout forms the basis for colchicine prophylaxis. An acute gout flare is the most common adverse effect of urate-lowering therapy. For prophylaxis, low-dose colchicine therapy is the first choice. It is commenced 1 or 2 weeks before using urate-lowering drugs and continued for up to 6 months after normalization of the uric acid levels or until the clinically visible tophi resolve. Low-dose NSAIDs and low-dose corticosteroids are rarely used. The recommended dosage of colchicine is 0.5mg once or twice daily in the absence of any renal or hepatobiliary compromises.

[Gout and Its Management in Clinical Practice].

Gout and Its Management in Clinical Practice <bAbstract.</b Resolution of an acute attack is usually the prime objective in routine clinical management of gout. Crystal identification in synovial fluid by polarised light microscopy is considered the diagnostic gold standard. Imaging procedures such as high-resolution ultrasonography are also useful. Non-steroidal anti-inflammatory drugs, steroids and colchicine (not approved in Switzerland, available from pharmacies) are used to treat an acute gout attack. Just as important as the diagnosis and treatment of an acute attack is the long-term management of hyperuricaemia in order to prevent further gout attacks as well as possible renal, cardiac or metabolic complications. Therefore, patients with a confirmed diagnosis of gout should, apart from non-pharmacologic interventions, receive hypouricaemic therapy with a target uric acid level of <360 µmol/l (<6 mg/dl). Drugs of first choice are xanthine oxidase inhibitors. Achievement of the therapeutic objective should be periodically reviewed, adjusting therapy as necessary.

Management of gout in older adults: barriers to optimal control.

Gout, a common inflammatory arthritis, can be diagnosed with absolute certainty. Gout results from the body's reaction to urate crystals deposited in tissues, and this pathophysiology is well understood. If used appropriately, available therapies can be entirely effective in not only treating the symptoms of gout, but also in eliminating the excess urate from the body, thereby eradicating the disease. Because of these facts, management of patients with gout should be successful. However, management of gout is particularly challenging in the elderly, even though the principles of management are the same for all age groups. The purpose of this article is to review these principles and discuss them as they pertain to the elderly. The classic gout attack is acute in onset, extremely painful and associated with marked swelling, warmth, erythema and tenderness of a single joint. However, the diagnosis of gout may be challenging in the elderly because atypical presentations are more common in this group. Treatment of acute gout involves the use of NSAIDs, colchicine, corticosteroids or corticotropin (adrenocorticotropic hormone). Unfortunately, co-morbid conditions such as chronic kidney disease, peptic ulcer disease and congestive heart failure may make the use of these agents dangerous or contraindicated. Thus, it is important to try to treat an acute flare of gout at the earliest sign, because the sooner treatment is initiated, the faster the inflammation will resolve. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used judiciously in the elderly. However, if used at the lowest dose that maintains the serum urate level below 5.0-6.0 mg/dL, the excess urate in the body will be eliminated, acute flares will no longer occur and tophi will resolve. Gout is often seen in association with hypertension, excessive alcohol consumption, obesity and hypertriglyceridaemia. These conditions and the medications used to treat them may contribute to the hyperuricaemia. Treating these conditions and using medications that do not promote hyperuricaemia will aid in the management of gout. Despite the challenges that often complicate the management of gout in the elderly, an understanding of the pathophysiology of the disease and both the indications and limitations of the medications used should allow successful treatment.

Therapeutic perspectives on uricases for gout.

Available recombinant uricases (rasburicase, pegloticase) are potent hypouricaemic agents for tophaceous gout, but their long-term use is in question. We have performed a literature review on uricases, using Scirus, PubMed, Science Direct, and several other search engines. We have also consulted the records of drug regulatory authorities and patents on uricases. Rasburicase (Fasturtec(®)) was approved in Europe for tumour lysis syndrome induced by chemotherapy, in a single daily infusion dose for a maximum of 7 days. A retrospective study (n=10) conducted in patients with gout and three clinical cases have shown that infusions spaced over time, over several months, ensure the control of serum uric acid and help to eliminate or significantly reduce the size of tophi. However, repeated gout attacks (despite colchicine) and hypersensitivity reactions (despite corticosteroids) have dampened enthusiasm for its use in gout. Pegloticase was recently approved by the Food and Drug Administration (FDA) for patients with chronic gout, refractory or intolerant to conventional hypouricaemic therapy. A 6 month study versus placebo showed that pegloticase (infused at 8 mg every 2 weeks), induced a significant decrease in plasma uric acid in about 40% of patients (associated with a tendency for tophi dissolution). However, the remaining patients were non-responders, which correlated with the formation of pegloticase antibodies and infusion reactions. Research efforts are needed to develop less immunogenic uricases. In conclusion, some uricases could have an important role in the treatment of gout, for instance as a first-line treatment and over a short period of several months in patients with severe and tophaceous gout to allow rapid tophi dissolution.

InternalMed_Harrison

may be cost-effective after two attacks), serum uric acid levels (progression is more rapid in patients with serum uric acid >535 μmol/L [>9.0 mg/dL]), the patient’s willingness to commit to lifelong therapy, or the presence of uric acid stones. Urate-lowering therapy should be initiated in any patient who already has tophi or chronic gouty arthritis. Uricosuric agents such as probenecid can be used in patients with good renal function who underexcrete uric acid, with <600 mg in a 24-h urine sample. Urine volume should be maintained by ingestion of 1500 mL of water every day. Probenecid can be started at a dose of 250 mg twice daily and increased gradually as needed up to 3 g per day to achieve and maintain a serum uric acid level of less than 6 mg/dL. Probenecid is generally not effective in patients with serum creatinine levels >177 μmol/L (2 mg/dL). These patients may require allopurinol or benzbromarone (not available in the United States). Benzbromarone is another uricosuric drug

Colchicine

Colchicine is typically prescribed to mitigate or prevent the onset of gout, or its continuing symptoms and pain, using a low-dose prescription of 0.6 to 1.2 mg per day, or a high-dose amount of up to 4.8 mg in the first 6 hours of a gout episode. With an oral dose of 0.6 mg, peak blood levels occur within one to two hours. For treating gout, the initial effects of colchicine occur in a window of 12 to 24 hours, with a peak within 48 to 72 hours. It has a narrow therapeutic window, requiring monitoring of the subject for potential toxicity. Colchicine is not a general pain-relief drug, and is not used to treat pain in other disorders.