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Paget's disease of the breast is a type of cancer of the breast. Treatment usually involves a lumpectomy or mastectomy to surgically remove the tumour. Chemotherapy and/or radiotherapy may be necessary, but the specific treatment often depends on the characteristics of the underlying breast cancer.
Invasive cancer or extensive ductal carcinoma "in situ" is primarily treated with modified radical mastectomies. The procedure consists in the removal of the breast, the lining over the chest muscles and a part of the lymph nodes from under the arm. In cases of noninvasive cancers, simple mastectomies are performed in which only the breast with the lining over the chest muscles is removed.
Patients suffering from cancer that has not spread beyond the nipple and the surrounding area are often treated with breast-conserving surgery or lumpectomy. They usually undergo radiation therapy after the actual procedure to prevent recurrence. A breast-conserving surgery consists in the removal of the nipple, areola and the part of the breast that is affected by cancer.
In most cases, adjuvant treatment is part of the treatment schema. This type of treatment is normally given to patients with cancer to prevent a potential recurrence of the disease. Whether adjuvant therapy is needed depends upon the type of cancer and whether the cancer cells have spread to the lymph nodes. In Paget's disease, the most common type of adjuvant therapy is radiation following breast-conservative surgery.
Adjuvant therapy may also consist of anticancer drugs or hormone therapies. Hormonal therapy reduces the production of hormones within the body, or prevents the hormones from stimulating the cancer cells to grow, and it is commonly used in cases of invasive cancer by means of drugs such as tamoxifen and anastrozole.
Cuffitis is treated with mesalamine suppositories or topical application of lidocaine or corticosteroid medications. Systemic medications are rarely used.
Five bisphosphonates are currently available. In general, the most commonly prescribed are risedronic acid, alendronic acid, and pamidronic acid. Etidronic acid and other bisphosphonates may be appropriate therapies for selected patients but are less commonly used. None of these drugs should be used by people with severe kidney disease.
- Etidronate disodium The approved regimen is once daily for six months; a higher dose is more commonly used. No food, beverage, or medications should be consumed for two hours before and after taking. The course should not exceed six months, but repeat courses can be given after rest periods, preferably of three to six months duration.
- Pamidronate disodium in intravenous form: the approved regimen uses an infusion over four hours on each of three consecutive days, but a more commonly used regimen is over two to four hours for two or more consecutive or nonconsecutive days.
- Alendronate sodium is given as tablets once daily for six months; patients should wait at least 30 minutes after taking before eating any food, drinking anything other than tap water, taking any medication, or lying down (patient may sit).
- Tiludronate disodium are taken once daily for three months; they may be taken any time of day, as long as there is a period of two hours before and after resuming food, beverages, and medications.
- Risedronate sodium tablet taken once daily for 2 months is the prescribed regimen; patients should wait at least 30 minutes after taking before eating any food, drinking anything other than tap water, taking any medication, or lying down (patient may sit).
- Zoledronic acid is given as an intravenous infusion; a single dose is effective for two years. This is recommended for most people at high risk with active disease.
Calcitonin, also called calcitonin-salmon, is a synthetic copy of a polypeptide hormone secreted by the ultimobranchial gland of salmon. Miacalcin is administered by injection, three times per week or daily, for 6–18 months. Repeat courses can be given after brief rest periods. Miacalcin may be appropriate for certain patients, but is seldom used. Calcitonin is also linked to increased chance of cancer. Due to the increased risk of cancer, the European Medicines Agency (EMA) recommended that calcitonin be used only on a short-term basis for 3 conditions for which it had previously been approved in the European Union: Paget's disease, acute bone loss resulting from sudden immobilization, and hypercalcemia caused by cancer.
The EMA said it based its recommendations on a review of the benefits and risks of calcitonin-containing medicines. Conducted by the agency's Committee for Medicinal Products for Human Use (CHMP), the review encompassed available data from the companies that market these drugs, postmarketing safety data, randomized controlled studies, 2 studies of unlicensed oral calcitonin drugs, and experimental cancer studies, among other sources.
CHMP found that "a higher proportion of patients treated with calcitonin for long periods of time develop cancer of various types, compared with patients taking placebo." The increase in cancer rates ranged from 0.7% for oral formulations to 2.4% for the nasal formulation. CHMP concluded that the benefits of calcitonin for osteoporosis did not exceed the risks. The nasal spray's only indication is for osteoporosis, thus justifying the drug's removal from the market.
As a solution for injection or infusion, calcitonin should be administered for no more than 4 weeks to prevent acute bone loss resulting from sudden immobilization, and normally for no more than 3 months to treat Paget's disease, the EMA said. The agency did not specify a time frame for the short-term use of calcitonin for treating hypercalcemia caused by cancer.
Surgical treatments may be used to treat the condition, and include retro-rectal levatorplasty, post-anal repair, retro-anal levator plate myorrhaphy.
There is no treatment, but because this is a benign condition with no serious clinical complications, prognosis is excellent.
Treatment for proctitis varies depending on severity and the cause. For example, the physician may prescribe antibiotics for proctitis caused by bacterial infection. If the proctitis is caused by Crohn's disease or ulcerative colitis, the physician may prescribe the drug 5-aminosalicyclic acid (5ASA) or corticosteroids applied directly to the area in enema or suppository form, or taken orally in pill form. Enema and suppository applications are usually more effective, but some patients may require a combination of oral and rectal applications.
Another treatment available is that of fiber supplements such as Metamucil. Taken daily these may restore regularity and reduce pain associated with proctitis.
There are several stages to treating an anal fistula:
Definitive treatment of a fistula aims to stop it recurring. Treatment depends on where the fistula lies, and which parts of the internal and external anal sphincters it crosses.
There are several options:
- Doing nothing — a drainage seton can be left in place long-term to prevent problems. This is the safest option although it does not definitively cure the fistula.
- Lay-open of fistula-in-ano — this option involves an operation to cut the fistula open. Once the fistula has been laid open it will be packed on a daily basis for a short period of time to ensure that the wound heals from the inside out. This option leaves behind a scar, and depending on the position of the fistula in relation to the sphincter muscle, can cause problems with incontinence. This option is not suitable for fistulae that cross the entire internal and external anal sphincter.
- Cutting seton — if the fistula is in a high position and it passes through a significant portion of the sphincter muscle, a cutting seton (from the Latin "seta", "bristle") may be used. This involves inserting a thin tube through the fistula tract and tying the ends together outside of the body. The seton is tightened over time, gradually cutting through the sphincter muscle and healing as it goes. This option minimizes scarring but can cause incontinence in a small number of cases, mainly of flatus. Once the fistula tract is in a low enough position it may be laid open to speed up the process, or the seton can remain in place until the fistula is completely cured. This was the traditional modality used by physicians in Ancient Egypt and formally codified by Hippocrates, who used horsehair and linen.
- Seton stitch — a length of suture material looped through the fistula which keeps it open and allows pus to drain out. In this situation, the seton is referred to as a draining seton. The stitch is placed close to the ano-rectal ring – which encourages healing and makes further surgery easy.
- Fistulotomy — till anorectal ring
- Colostomy — to allow healing
- Fibrin glue injection is a method explored in recent years, with variable success. It involves injecting the fistula with a biodegradable glue which should, in theory, close the fistula from the inside out, and let it heal naturally. This method is perhaps best tried before all others since, if successful, it avoids the risk of incontinence, and creates minimal stress for the patient.
- Fistula plug involves plugging the fistula with a device made from small intestinal submucosa. The fistula plug is positioned from the inside of the anus with suture. According to some sources, the success rate with this method is as high as 80%. As opposed to the staged operations, which may require multiple hospitalizations, the fistula plug procedure requires hospitalization for only about 24 hours. Currently, there are two different anal fistula plugs cleared by the FDA for treating ano-rectal fistulae in the United States. This treatment option does not carry any risk of bowel incontinence. In the systematic review published by Dr Pankaj Garg, the success rate of the fistula plug is 65-75%.
- Endorectal advancement flap is a procedure in which the internal opening of the fistula is identified and a flap of mucosal tissue is cut around the opening. The flap is lifted to expose the fistula, which is then cleaned and the internal opening is sewn shut. After cutting the end of the flap on which the internal opening was, the flap is pulled down over the sewn internal opening and sutured in place. The external opening is cleaned and sutured. Success rates are variable and high recurrence rates are directly related to previous attempts to correct the fistula.
- LIFT Technique is a novel modified approach through the intersphincteric plane for the treatment of fistula-in-ano, known as LIFT (ligation of intersphincteric fistula tract) procedure. LIFT procedure is based on secure closure of the internal opening and removal of infected cryptoglandular tissue through the intersphincteric approach. Essential steps of the procedure include, incision at the intersphincteric groove, identification of the intersphincteric tract, ligation of intersphincteric tract close to the internal opening and removal of intersphincteric tract, scraping out all granulation tissue in the rest of the fistulous tract, and suturing of the defect at the external sphincter muscle. The procedure was developed by Thai colorectal surgeon, Arun Rojanasakul, The first reports of preliminary healing result from the procedure were 94% in 2007. Additional ligation of the intersphincteric fistula tract did not improve the outcome after endorectal advancement flap.
- Fistula clip closure (OTSC Proctology) is the latest surgical development, which involves the closure of the internal fistula opening with a superelastic clip made of nitinol (OTSC). During surgery, the fistula tract is debrided with a special fistula brush and the clip is transanally applied with the aid of a preloaded clip applicator. The surgical principle of this technique relies on the dynamic compression and permanent closure of the internal fistula opening by the superelastic clip. Consequently, the fistula tract dries out and heals instead of being kept open by continuous feeding with stool and fecal organisms. This minimally-invasive sphincter-preserving technique has been developed and clinically implemented by the German surgeon Ruediger Prosst. First clinical data of the clip closure technique demonstrate a success rate of 90% for previously untreated fistulae and a success rate of 70% for recurrent fistulae.
- PERFACT Procedure is another latest addition to the armamentarium to treat complex and highly complex fistula-in-ano. It is a minimally cutting procedure as both the anal sphincters (internal and external sphincters) are not cut/damaged at all. Therefore, the risk of incontinence is minimal. PERFACT procedure (proximal superficial cauterization, emptying regularly fistula tracts and curettage of tracts) entails two steps: superficial cauterization of mucosa at and around the internal opening and keeping all the tracts clean. The principle is to permanently close the internal opening by granulation tissue. This is achieved by superficial electrocauterization at and around the internal opening and subsequently allowing the wound to heal by secondary intention. Early results of this procedure are quite encouraging for complex fistula-in-ano (86.4% in highly complex anal fistulae). The procedure is effective even in fistula associated with abscess, supralevator fistula-in-ano and fistula where the internal opening is non-localizable.
Non-surgical treatments are recommended initially for acute and chronic anal fissures. These include topical nitroglycerin or calcium channel blockers (e.g. diltiazem), or injection of botulinum toxin into the anal sphincter.
Other measures include warm sitz baths, topical anesthetics, high-fiber diet and stool softeners.
Local application of medication to relax the sphincter muscle, thus allowing the healing to proceed, was first proposed in 1994 with nitroglycerine ointment,
and then calcium channel blockers in 1999 with nifedipine ointment,
and the following year with topical diltiazem.
Branded preparations are now available of topical nitroglycerine ointment (Rectogesic (Rectiv) as 0.2% in Australia and 0.4% in UK and US), topical nifedipine 0.3% with lidocaine 1.5% ointment (Antrolin in Italy since April 2004) and diltiazem 2% (Anoheal in UK, although still in Phase III development). A common side effect drawback of nitroglycerine ointment is headache, caused by systemic absorption of the drug, which limits patient acceptability.
A combined surgical and pharmacological treatment, administered by colorectal surgeons, is direct injection of botulinum toxin (Botox) into the anal sphincter to relax it. This treatment was first investigated in 1993. However, in many cases involving Botox injections the patients eventually had to choose another cure as the injections proved less and less potent, spending thousands of dollars in the meantime for a partial cure. Lateral sphincterotomy is the Gold Standard for curing this affliction.
Combination of medical therapies may offer up to 98% cure rates.
In people presenting with symptoms compatible with radiation enteropathy, the initial step is to identify what is responsible for causing the symptoms. Management is best with a multidisciplinary team including gastroenterologists, nurses, dietitians, surgeons and others.
Medical treatments include the use of hyperbaric oxygen which has beneficial effects in radiation proctitis or anal damage. Nutritional therapies include treatments directed at specific malabsorptive disorders such as low fat diets and vitamin B12 or vitamin D supplements, together with bile acid sequestrants for bile acid diarrhea and possibly antibiotics for small intestinal bacterial overgrowth. Probiotics have all been suggested as another therapeutic avenue.
Endoscopic therapies including argon plasma coagulation have been used for bleeding telangiectasia in radiation proctitis and at other intestinal sites, although there is a rick of perforation. Sucralfate enemas look promising in proctitis.
Surgical treatment may be needed for intestinal obstruction, fistulae, or perforation, which can happen in more severe cases. These can be fatal if patients present as an emergency, but with improved radiotherapy techniques are now less common.
Optimal treatment usually produces significant improvements in quality of life.
Some people will have an active infection when they present with a fistula, and this requires clearing up before definitive treatment can be decided.
Antibiotics can be used as with other infections, but the best way of healing infection is to prevent the buildup of pus in the fistula, which leads to abscess formation. This can be done with a seton.
Treatment for fistula varies depending on the cause and extent of the fistula, but often involves surgical intervention combined with antibiotic therapy.
Typically the first step in treating a fistula is an examination by a doctor to determine the extent and "path" that the fistula takes through the tissue.
In some cases the fistula is temporarily covered, for example a fistula caused by cleft palate is often treated with a palatal obturator to delay the need for surgery to a more appropriate age.
Surgery is often required to assure adequate drainage of the fistula (so that pus may escape without forming an abscess). Various surgical procedures are commonly used, most commonly fistulotomy, placement of a seton (a cord that is passed through the path of the fistula to keep it open for draining), or an endorectal flap procedure (where healthy tissue is pulled over the internal side of the fistula to keep feces or other material from reinfecting the channel). Treatment involves filling the fistula with fibrin glue; also plugging it with plugs made of porcine small intestine submucosa have also been explored in recent years, with variable success. Surgery for anorectal fistulae is not without side effects, including recurrence, reinfection, and incontinence. High rate of recurrence and more chances of complications like incontinence are always there in fistula surgeries (Anal Fistula).
It is important to note that surgical treatment of a fistula without diagnosis or management of the underlying condition, if any, is not recommended. For example, surgical treatment of fistulae in Crohn's disease can be effective, but if the Crohn's disease itself is not treated, the rate of recurrence of fistula is very high (well above 50%).
10 to 20% of patients treated for anal cancer will develop distant metastatic disease following treatment. Metastatic or recurrent anal cancer is difficult to treat, and usually requires chemotherapy. Radiation is also employed to palliate specific locations of disease that may be causing symptoms. Chemotherapy commonly used is similar to other squamous cell epithelial neoplasms, such as platinum analogues, anthracyclines such as doxorubicin, and antimetabolites such as 5-FU and capecitabine. JD Hainsworth developed a protocol that includes Taxol and Carboplatinum along with 5-FU. Median survival rates for patients with distant metastases ranges from 8 to 34 months.
Aggressive surgical removal of the tumor and any enlarged sublumbar lymph nodes is essential for treatment of the tumor and associated hypercalcaemia. There is a high recurrence rate, although removal of lymph nodes with metastasis may improve survival time. Radiation therapy and chemotherapy may be helpful in treatment. Severe hypercalcaemia is treated with aggressive IV fluid therapy using sodium chloride and medications such as loop diuretics (increased kidney excretion of calcium) and aminobisphosphonates (decreased calcium release from bones). A poorer prognosis is associated with large tumor size (greater than 10 cm), hypercalcaemia, and distante metastasis. Early, incidental diagnosis of small anal sac masses may lead to a better prognosis with surgery alone (ongoing study).
Localised disease (carcinoma-in-situ) and the precursor condition, anal intraepithelial neoplasia (anal dysplasia or AIN) can be ablated with minimally invasive methods such as Infrared Photocoagulation.
Previously, anal cancer was treated with surgery, and in early-stage disease (i.e., localised cancer of the anus without metastasis to the inguinal lymph nodes), surgery is often curative. The difficulty with surgery has been the necessity of removing the internal and external anal sphincter, with concomitant fecal incontinence. For this reason, many patients with anal cancer have required permanent colostomies.
Current gold-standard therapy is chemotherapy and radiation treatment to reduce the necessity of debilitating surgery. This "combined modality" approach has led to the increased preservation of an intact anal sphincter, and therefore improved quality of life after definitive treatment. Survival and cure rates are excellent, and many patients are left with a functional sphincter. Some patients have fecal incontinence after combined chemotherapy and radiation. Biopsies to document disease regression after chemotherapy and radiation were commonly advised, but are not as frequent any longer. Current chemotherapy consists of continuous infusion 5-FU over four days with bolus mitomycin given concurrently with radiation. 5-FU and cisplatin are recommended for metastatic anal cancer.
Colostomy is recommended by most surgeons, and has a good prognosis, with 90% of patients regaining normal bowel control. Since the rectal opening and anal orifice in a vestibular fistula tend to be short and narrow, a colostomy is usually performed to allow decompression of the bowel unless the orifice is wide enough to allow normal defecation. Colostomy is often followed by posterior sagittal anorectoplasty (PSARP), a surgical procedure to repair the anal orifice, at a later date. Some surgeons prefer to perform an immediate PSARP without a colostomy first, while others perform neither a colostomy nor a PSARP and instead opt for a simple dilatation of the orifice to allow stool to pass and the bowel to decompress. It has been suggested that only experienced surgeons should perform repair without an initial colostomy.
Prevention of radiation injury to the small bowel is a key aim of techniques such as brachytherapy, field size, multiple field arrangements, conformal radiotherapy techniques and intensity-modulated radiotherapy. Medications including ACE inhibitors, statins and probiotics have also been studied and reviewed.
Pain relief is administered concomitantly to the treatment of the primary disease causing tenesmus. Methadone has been shown to be an effective pain-reliever.
Initially, an evaluation of malignancy is always indicated. If no abnormality is found, then a surgical duct excision may resolve the symptoms. Treatment also depends on whether single-duct or multiple-duct discharge is present, and whether the symptoms of nipple discharge are distressing to the patient. In some cases, there may be no need for any further intervention; in others, microdochectomy or a total duct excision may be appropriate. If the patient wishes to conserve the ability to breastfeed and only single-duct discharge is present, then ductoscopy or galactography should be considered in view of performing a localised duct excision. Once the cause of the nipple discharge is found, it will be treated by the health provider who will evaluate:
- Whether changing any medicine that has caused the discharge is appropriate
- Whether any lumps should be removed
- Whether some or all of the breast ducts should be removed
- If a prescription for cream to treat skin changes around the nipple will be helpful
- If medicines to treat a health condition are required
If all the tests are normal, treatment may not be necessary. A follow up mamogram mammogram and physical exam may be prescribed within 1 year.
Extramammary Paget's disease is usually seen in isolation and is associated with an underlying invasive malignancy about 12% of the time. It is associated with an underlying adnexal malignancy about 24% of the time. Paget's disease of the breast is almost always associated with an underlying invasive malignancy, i.e. breast cancer (e.g. mammary ductal carcinoma).
Paget's disease of the vulva, a rare disease, may be a primary lesion or associated with adenocarcinoma originating from local organs such as the Bartholin gland, the urethra, or the rectum and thus be secondary. Patients tend to be postmenopausal.
Paget's disease of the penis may also be primary or secondary, and is even rarer than genital Paget’s disease in women. At least one case has been misdiagnosed as Bowen's disease. Isolated Paget's disease of the penis is extremely rare.
The presence of three factors for the prognosis has been suggested, whether there is a palpable mass of the disease, whether lymph nodes are positive and whether there is an underlying malignant cancer.
If there is none of these, the five- and 10-year survival is 85% and 80% respectively, with adjuvant chemotherapy even 95% and 90%. If there is a palpable mass, it is 32% and 31% respectively, with adjuvant chemotherapy (40% and 35%).
Positive lymph-nodes have been positively associated with a palpable mass and affect the prognosis to be now just 28% survival after 10 years (vs 79% without palpable mass and without affected lymph-nodes). Involvement of the lymph nodes does not directly cause any harm, but is merely an indicator of systemic spread.
Furthermore, patients with an identifiable associated underlying breast tumor have a survival rate of 38-40% at five years and a survival rate of 22-33% at 10 years. The death rate of metastatic breast carcinoma in patients with mammary Paget's disease and underlying cancer is 61.3%, with a 10-year cumulative survival rate of 33%.
Anal abscesses are rarely treated with a simple course of antibiotics. In almost all cases surgery will need to take place to remove the abscess. Treatment is possible in an emergency room under local anesthesia, but it is highly preferred to be formally admitted to a hospital and to have the surgery performed in an operating room under general anesthesia.
Generally speaking, a fairly small but deep incision is performed close to the root of the abscess. The surgeon will allow the abscess to drain its exudate and attempt to discover any other related lesions in the area. This is one of the most basic types of surgery, and is usually performed in less than thirty minutes by the anal surgical team. Generally, a portion of the exudate is sent for microbiological analysis to determine the type of infecting bacteria. The incision is not closed (stitched), as the damaged tissues must heal from the inside toward the skin over a period of time.
The affected individual is often sent home within twenty-four hours of the surgery, and may be instructed to perform several 'sitz baths' per day, whereby a small basin (which usually fits over a toilet) is filled with warm water (and possibly, salts) and the affected area is soaked for a period of time. Another method of recovery involves the use of surgical packing, which is initially inserted by the surgical team, with redressing generally performed by hospital staff or a District Nurse (however, following the results of several double-blind studies, the effectiveness of surgical packing has come into question). During the week following the surgery, many patients will have some form of antibiotic therapy, along with some form of pain management therapy, consistent with the nature of the abscess.
The patient usually experiences an almost complete relief of the severe pain associated to his/her abscess upon waking from anesthesia; the pain associated with the opening and draining incision during the post-operative period is often mild in comparison.
The only potentially curative treatment for complete rectal prolapse is surgery, however in those patients with medical problems that make them unfit for surgery, and those patients who have minimal symptoms, conservative measures may benefit. Dietary adjustments, including increasing dietary fiber may be beneficial to reduce constipation, and thereby reduce straining. A bulk forming agent (e.g. psyllium) or stool softener can also reduce constipation.