Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
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.
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.
While most cases require no treatment, therapy options include cryotherapy, application of a topical salicylic acid compound, surgical and laser ablation.
Treatment for CIN 1, which is mild dysplasia, is not recommended if it lasts fewer than 2 years. Usually when a biopsy detects CIN 1 the woman has an HPV infection which may clear on its own within 12 months, and thus it is instead followed for later testing rather than treated.
Treatment for higher grade CIN involves removal or destruction of the neoplastic cervical cells by cryocautery, electrocautery, laser cautery, loop electrical excision procedure (LEEP), or cervical conization. Therapeutic vaccines are currently undergoing clinical trials. The lifetime recurrence rate of CIN is about 20%, but it isn't clear what proportion of these cases are new infections rather than recurrences of the original infection.
Surgical treatment of CIN lesions is associated with an increased risk of infertility or subfertility, with an odds ratio of approximately 2 according to a case-control study.
The treatment of CIN during pregnancy increases the risk of premature birth.
Wide, radical, complete surgical excision is the treatment of choice, with free surgical margins to achieve the best outcome and lowest chance of recurrence. Radiation is only used for palliation. In general, there is a good prognosis, although approximately 50% of patients die from disease within 3–10 years of presentation.
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).
Primary treatment for this cancer, regardless of body site, is surgical removal with clean margins. This surgery can prove challenging in the head and neck region due to this tumour's tendency to spread along nerve tracts. Adjuvant or palliative radiotherapy is commonly given following surgery. For advanced major and minor salivary gland tumors that are inoperable, recurrent, or exhibit gross residual disease after surgery, fast neutron therapy is widely regarded as the most effective form of treatment.
Chemotherapy is used for metastatic disease. Chemotherapy is considered on a case by case basis, as there is limited trial data on the positive effects of chemotherapy. Clinical studies are ongoing, however.
a) Surgical resection is mainstay of treatment, whenever possible. If tumor is completely removed, post-operative radiation therapy is typically not needed since acinic cell is considered a low-grade histology. Post-operative radiation therapy for acinic cell carcinoma is used if: 1) margins are positive, 2) incomplete resection, 3) tumor invades beyond gland, 4) positive lymph nodes.
b) Neutron beam radiation
c) Conventional radiation
d) Chemotherapy
This type of carcinoma is commonly managed by local resection, cryotherapy, topical chemotherapy, and radiotherapy. Multimodal therapy has been shown to improve both visual prognosis and survival.
Mohs micrographic surgery has become the treatment of choice for this form of cancer. When used as the primary treatment modality for sebaceous carcinoma of the eyelid, Mohs surgery is associated with significantly lower local and distant recurrence rates.
Treatment may include the following:
- Surgery with or without radiation
- Radiotherapy
Fast neutron therapy has been used successfully to treat salivary gland tumors, and has shown to be significantly more effective than photons in studies treating unresectable salivary gland tumors.
- Chemotherapy
Cisplatin is a chemotherapy drug that is injected into the tumor itself; this drug is commonly used along with surgical removal. That being said, this drug has been shown to resolve tumors with or without surgical removal for at least 2 years.
Cimetidine works by slowing tumor growth; it is a histamine blocker that maintains the body’s immune response which aids in the killing of tumor cells. Cimetidine has not been proven to efficiently resolve tumors completely.
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.
Treatment involves biopsy of the lesion to identify extent of dysplasia. Complete excision of the lesion is sometimes advised depending on the histopathology found in the biopsy. Even in these cases, recurrence of the erythroplakia is common and, thus, long-term monitoring is needed.
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.
MASC is currently treated as a low-grade (i.e. Grade 1) carcinoma with an overall favorable prognosis. These cases are treated by complete surgical excision. However, the tumor does have the potential to recur locally and/or spread beyond surgically dissectible margins as well as metastasize to regional lymph nodes and distant tissues, particularly in tumors with histological features indicating a high cell growth rate potential. One study found lymph node metastasis in 5 of 34 MASC patients at initial surgery for the disease; these cases, when evidencing no further spread of disease, may be treated with radiation therapy. The treatment of cases with disease spreading beyond regional lymph nodes has been variable, ranging from simple excision to radical resections accompanied by adjuvant radiotherapy and/or chemotherapy, depending on the location of disease. Mean disease-free survival for MASC patients has been reported to be 92 months in one study.
The tyrosine kinase activity of NTRK3 as well as the ETV6-NTRK3 protein is inhibited by certain tyrosine kinase inhibitory drugs such as Entrectinib and LOXO-101; this offers a potential medical intervention method using these drugs to treat aggressive MASC disease. Indeed, one patient with extensive head and neck MASC disease obtained an 89% fall in tumor size when treated with entrectinib. This suppression lasted only 7 months due to the tumor's acquirement of a mutation in the "ETV6-NTRK3" gene. The newly mutated gene encoded an entrectinib-reisistant "ETV6-NTRK3" protein. Treatment of aggressive forms of MASC with NTRK3-inhibiting tyrosine kinase inhibiting drugs, perhaps with switching to another type of tyrosine kinase inhibitor drug if the tumor acquires resistance to the initial drug, is under study.STARTRK-2
Surgical treatments may be used to treat the condition, and include retro-rectal levatorplasty, post-anal repair, retro-anal levator plate myorrhaphy.
Complete radical surgical resection is the treatment of choice for EMECL, and in most cases, results in long-term survival or cure.
Dietary modification may be important for successful management. Both diarrhea and constipation can contribute to different cases, so dietary advice must be tailored to address the underlying cause or it may be ineffective or counter productive. In persons with disease aggravated by diarrhea or those with rectal loading by soft stools, the following suggestions may be beneficial: increase dietary fiber; reduce wholegrain cereals/bread; reduce fruit and vegetables which contain natural laxative compounds (rhubarb, figs, prunes/plums); limit beans, pulses, cabbage and sprouts; reduce spices (especially chilli); reduce artificial sweeteners (e.g. sugar free chewing gum); reduce alcohol (especially stout, beer and ale); reduce lactose if there is some degree of lactase deficiency; and reduce caffeine. Caffeine lowers the resting tone of the anal canal and also causes diarrhea. Excessive doses of vitamin C, magnesium, phosphorus and/or calcium supplements may increase FI. Reducing olestra fat substitute, which can cause diarrhea, may also help.
Pharmacological management may include anti-diarrheal/constipating agents and laxatives/stool bulking agents Stopping or substituting any previous medication that causes diarrhea may be helpful in some (see table). There is not good evidence for the use of any medications however.
In people who have undergone gallbladder removal, the bile acid sequestrant cholestyramine may help minor degrees of FI. Bulking agents also absorb water, so may be helpful for those with diarrhea. A common side effect is bloating and flatulence. Topical agents to treat and prevent dermatitis may also be used, such as topical antifungals when there is evidence of perianal candidiasis or occasionally mild topical anti-inflammatory medication. Prevention of secondary lesions is carried out by perineal cleansing, moisturization, and use of a skin protectant.
It used to be thought that cases of CIN progressed through these stages toward cancer in a linear fashion.
However most CIN spontaneously regress. Left untreated, about 70% of CIN-1 will regress within one year, and 90% will regress within two years. About 50% of CIN 2 will regress within 2 years without treatment.
Progression to cervical carcinoma in situ (CIS) occurs in approximately 11% of CIN1 and 22% of CIN2. Progression to invasive cancer occurs in approximately 1% of CIN1, 5% in CIN2 and at least 12% in CIN3.
Progression to cancer typically takes 15 (3 to 40) years. Also, evidence suggests that cancer can occur without first detectably progressing through these stages and that a high grade intraepithelial neoplasia can occur without first existing as a lower grade.
It is thought that the higher risk HPV infections, have the ability to inactivate tumor suppressor genes such as the p53 gene and the RB gene, thus allowing the infected cells to grow unchecked and accumulate successive mutations, eventually leading to cancer.
Treatment does not affect the chances of getting pregnant but does increase the risk of second trimester miscarriages.
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.
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.
Bartholin glands were described in cattle by Casper Barthlin in 1677. Their existence in humans was postulated at that time.
Treatment can be a vulvectomy that results in the removal of the growth along with an extensive removal of adjacent tissue. An iguinal lympenectomy often accompanies the vulvectomy. The tissue that is removed sometimes includes sections of the vagina and rectum.
The Adenoid cystic carcinoma of the Bartholin gland is another uncommon malignancy with symptoms that include local painful intermittent recurrences. The disease is slow to progress but it can result in lung cancer after a long time after the initial treatment. Treatment consists of surgical removal of the growth. Sometimes radiation and chemotherapy is performed.
Normally found in children or young adults, a common cause of conjunctival squamous cell papilloma is during childbirth, when the mother passes the virus to her child.