Friday, December 20, 2013

#Vedolizumab - Favorable Among FDA for Ulcerative #Colitis & #Crohns

Good News!!  The FDA supports the approval of Vedolizumab for the treatment of Crohn's disease and ulcerative colitis.  The treatment looks extremely promising with a safety profile to be recognized.  
Hey, If I would consider the treatment, it has to have minimal/low risks in regard to serious side effects that a lot of biologics have.  Vedolizumab is looking good in the safety department.
The FDA will make the decision to either approve or deny treatment for use among ulcerative colitis (UC) patients by Feb. 18.  The decision for Crohn’s disease (CD) patients will be several months later around June. 




SILVER SPRING, Md. -- Most members of an FDA advisory committee support approval of the investigational biologic agent vedolizumab for Crohn's disease, as well as supporting an additional indication for ulcerative colitis.


In the closest vote of the Gastrointestinal Drugs and Drug Safety and Risk Management joint advisory committee meeting, the members voted 12-9 in favor of recommending approval of the drug for its Crohn's indication as an induction therapy, while the panel voted 20-0, with one abstention, to greenlight the drug as a maintenance therapy for the condition.
"While the data for Crohn's disease don't appear quite as strong, there does appear to be some efficacy and particularly the 10-week data were compelling," noted panelist Linda Feagins, MD, of the University of Texas Southwestern Medical Center in Dallas. She added that "the need for other treatment for Crohn's disease is great and we see that every day treating our patients, and I feel that doing further trials and holding this for patients will increase costs and delay drug availability."
Because the meeting was delayed by 2 hours due to inclement weather, the panel announced early in its Monday session that it would skip a formal vote on the ulcerative colitis indication, citing overwhelming evidence in its favor.
Vedolizumab's manufacturer, Takeda Pharmaceuticals, submitted the drug for approval for the Crohn's disease and ulcerative colitis patient population who had moderate to severely active disease and who were inadequately treated with, did not respond to, or were intolerant of convention therapy or a tumor necrosis factor-alpha antagonist.
Phase III trial data showed the drug was effective in ulcerative colitis patients, but only one of two trials showed drug efficacy at 6 weeks for Crohn's disease. However, data presented during the panel meeting out to 52 weeks of treatment showed significant improvements in remission rates among those who received drug treatment for 4 and 8 weeks.


Another issued raised prior to the panel discussion were concerns over risks for progressive multifocal leukoencephalopathy (PML), a rare but potentially fatal demyelinating condition that can occur in patients receiving natalizumab (Tysabri) and other immunosuppressive medications and who are infected with JC virus.
However, in the only unanimous vote of the session, all 21 panelists voted Yes that Takeda had sufficiently accounted for the risk of PML to support approval; Takeda said that although no cases had occurred during phase III studies, the company would still conduct post-market research and include a warning in its packaging. The panel routinely supported its vote with praise for the risk mitigation strategy and post-market research.
Another vote concerned whether concomitantly administered immunosuppressants should be limited to a specific duration. The panel voted 19-1, with one abstention, against such a limit.
For each condition, the panel voted on whether benefits outweighed risks to support approval of the drug in patients who failed steroid, immunosuppressive, or TNF-alpha antagonists; immunosuppressants or TNF-alpha antagonists; or neither. The vote for ulcerative colitis favored treatment for all conditions, with 14 voting for the first option, seven voting for the second, and none voting for the third. Similarly for Crohn's disease, 14 favored the first option, six favored the second, and one panelist favored neither.
Regarding the vote for the ulcerative colitis indication, committee member Elaine Morrato, DrPH, of the Colorado School of Public Health in Aurora, voted for the least restrictive option, but noted that "the products should be effective, but I worry that a specific requirement for failure of immunosuppressant or anti-TNF would be overly burdensome when you're translating this into clinical practice," adding that she "would rather have those discussions left with the patient and the provider."
Those favoring the middle option preferred a bottom-up approach while waiting for additional data on which patient populations would be best served by the drug with the least risk.
The agency is not required to follow the advice of its advisory committees, though it often does.

Thursday, December 19, 2013

Borody-His Innovative Discoveries on Digestive Disease - #FMT & #RHB104

This is another great article.  I knew that Dr. Borody, a doctor and professor out of Australia, developed FMT's (Fecal Matter Transplants) and was 1st to use the transplants to treat c-diff.  Interesting enough he is also considering FMT's for other digestive problems and even neurological conditions.  It will be interesting to see what illnesses are helped with this procedure.  

Here in the US doesn't even have a billing code for FMT's AND the FDA have only permitted transplants for difficult cases of c-diff, patients who do not respond to the antibiotic, that only around 30% of the patients respond to.  FMT's have a 90% recovery rate.  The question again is why not go with the treatment that has a higher success rate rather than lower.  Very sad that the US is so slow to adopt new and smarter treatments that will get people well.   I won't even go there today. It is an issue that probably raises my blood pressure if I think about it too long.  Not even joking.  

Anyway, after reading this article, I found out that Dr Borody also was the innovator for RHB-104 that is currently in the trial stages at this time. If you have Crohn's and don't know what RHB-104, read up on the treatment.  I have some blog posts that will give a good amount of information about the therapy.  It will make you smile and give you a boost of hope for something that may actually be able to eradicate Crohn's all together.  That is exciting!  

Professor Thomas Borody gets it!  He seems to understand the nature of digestive diseases very well.  He is certainly the man who is making some progress with developing real solutions to treat the actual condition and not just remedy the symptoms of a disease.  His name is one to remember and follow as he implements treatments that seem to be successful so far.  
Part of this article gives a little in depth look at his life and how he chose to dedicate his direction to gastrointestinal diseases.   

Note: I have underlined parts of the article that I felt were things to take note of.

He has the stomach for it | JPost | Israel News:

''Prof. Thomas Borody
Prof. Thomas Borody Photo: Courtesy
It’s amazing when in medicine, ideas that had seemed ridiculous – such as a chronic infection instead of an annoying boss causing ulcers – eventually become accepted truisms. Even though stools are considered dirty and something to get rid of, gastroenterologists have discovered that they can transplant feces from healthy donors into patients and very often relieve their chronic bacterial infections, irritable bowel disease (IBD), colitis, constipation and even some neurological conditions.

Prof. Thomas Borody, the founder and current medical director of the Center for Digestive Diseases (CDD) in Sydney, Australia, is a major innovator in these surprising treatments.

The CDD is considered a unique medical institution offering novel approaches in researching, diagnosing and treating gastrointestinal conditions. CDD offers a range of services in the day-procedure unit and houses a research and innovation department for conducting clinical trials in collaboration with universities, pharmaceutical companies and medical societies – all focusing on gastroenterology.




HE RECENTLY visited Israel and gave an interview to The Jerusalem Post about new treatments in the field. “This is my first visit to Israel,” said the world-renowned gastroenterologist.

“I’ve given a gastroenterology lecture to professionals at the Dan Hotel in Tel Aviv. I’ve also done some touring in Jerusalem, the Dead Sea and elsewhere – and I’ve already decided to come back.”

Borody was born in Krakow in 1950. My father was a Seventh-Day Adventist minister of religion,” said Borody. When he was 10, his parents decided to move to Australia, and his mother even wrote a book about their immigration experiences.

Inculcated to learn something that would “help mankind,” he and his siblings studied medicine. “I had thought of becoming a nuclear physicist, but it wasn’t to be,” he recalled. His sister is a general practitioner, his brother is an obstetrician/gynecologist and Thomas decided after getting his MD to specialize in the stomach, intestines and other internal organs.

He was inspired to pick his specialty largely because he worked under Dr. David burns, who was “a nice guy and did gastroscopes, which just came into being, in color.

Gastroenterologists spend much of their time performing colonoscopies (using endoscopes with tiny cameras in them to examine the large intestine for polyps or tumors and other irregularities) and gastroscopies (an endoscope is inserted into the mouth and through the esophagus to the stomach to get a view of the upper part of the gastro system). Since they have to fast and clean out their tubes, the gastro practice usually begins early in the morning.

AS FOR ulcers, it was two Australians who discovered in 1979 that they were not the result of stomach acid, spicy food and stress but a bacterium – Helicobacter pylori (H.

pylori) – that caused a chronic stomach infection. Dr. Barry James Marshall and pathologist Dr. John Robin Warren received the Nobel Prize in Medicine in 2005 for their breakthrough in discovering what causes ulcers.

It had been thought by the medical establishment for many years that no bacteria could survive in stomach acid, so that the painful condition must be caused by something else. But the two Australians found it is a very “clever” pathogen that can hide in the mucous lining protected from the acid, so they could remain alive even for decades.

Borody reasoned that if it was due to an infection, something could be done to cure it. So he and his colleagues developed in 1984 a triple “cocktail” of drugs – bismuth, tetracycline and flagyl – to treat and eliminate stomach ulcers. “We went through about 36 different combinations of drugs, and the best were these three.” When ulcer patients come to thank him that their ulcers have disappeared, he said, he feels “great satisfaction.” But despite proof that this healed the stomach lining, it took many years until the doctors were persuaded and accepted the triple therapy. The bacteria return only very rarely, and if it’s caught early, a recurrence can also be treated.

Today, one of the companies that manufactures the cocktail is RedHill Biopharma, an Israeli company. During his visit here, he met with officials of the company, which is based in Tel Aviv. Borody is an unpaid member of the RedHill’s advisory board.

There are other gastroenterological conditions, he continued, that is through to result from lifestyle that in fact result from chronic inflammation – among them ulcerative colitis and Crohn’s disease, which cause much suffering to many people around the world.

“After practicing for a while, I fell into research and spent year in the Solomon Islands [in Oceania lying to the east of Papua New Guinea] doing tropical med. I was more involved in leprosy and tuberculosis, which also involve bacteria that need a cocktail of drugs to treat it. This led to my getting interested in Crohn’s disease and irritable bowel disease.”

Borody spent three years researching at the Mayo Clinic.

NAMED AFTER Dr. Burrill Crohn, who first described the disease 80 years ago, Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract. It belongs to a group of conditions known as inflammatory bowel diseases (but is not the same as ulcerative colitis, which is another type of IBD. The symptoms of these two conditions are quite similar, but they affect different areas of the gastrointestinal tract. Crohn’s most often affects the end of the small bowel and the beginning of the colon, but it may affect any part of the gastrointestinal tract, from the mouth to the anus. Ulcerative colitis is restricted to the colon, also called the large intestine.

Among the symptoms of Crohn’s, which can be very debilitating and limiting, are persistent diarrhea; rectal bleeding; the urgent need to move bowels; abdominal cramps and pain; constipation; and the sensation of incomplete. It can be accompanied by loss of appetite; weigh loss; fatigue; night sweats; and the loss of a normal menstrual cycle in women. It is not a genetic condition, although some used to think so because of cross-infection in the family. It was also thought to be an autoimmune disease in which the autoimmune system, which is supposed to protect the body against infections, becomes aggressive and uncontrollable and attacks the body itself.
“Crohn’s is a more difficult disease to treat,” noted Borody. Because the bacterial infection develops very slowly. The bacteria involved are the most slowly dividing bacteria known to man. “This process can take 15 months, so medications have to be taken for a long time. It’s a difficult bug to destroy until the inflammatory condition calms down.”

Twenty years ago, Borody was reading The Lancet medical journal. “There as a published reader’s letter I came across that mentioned that a person was treated for tuberculosis, and his Crohn’s also improved. In Crohn’s, you see granulomas in the chest that are surrounded by epithelial cells. It looks like TB, but it’s Crohn’s. So I thought it could be treated with a new type of anti-tuberculosis agents. We started 12 Crohn’s on these drugs and it takes many weeks to get better. The longest time a patient has been on these drugs is 19 years.”

Now, a new, experimental drug for Crohn’s developed and patented by Red- Hill Biopharma now undergoing Phase III studies is called RHB-104. “Just as tuberculosis and HIV requires taken a drug cocktail to fight them, Crohn’s does too. If you give too-few medications, resistance to them can develop.

RHB-104 is a proprietary and potentially grandbreaking combination antibiotic therapy in oral pill form, with potent intracellular, antimycobacterial and anti-inflammatory properties, RedHill explains.


“The drug is based on increasing evidence supporting the hypothesis that Crohn’s disease is caused by an infection of the Mycobacterium avium subspecies named paratuberculosis in susceptible patients rather than being an autoimmune disease.

Borody notes that the triple drug combination that he invented for Crohn’s have been on the market for years, but the combination he suggested is new. “There are now clinical trials in 40 countries around the world. There are an estimated two or three million Crohn’s patients globally.

The phenomenon is grow- ing in places like China, Hongkong and Japan.”

When the US Food and Drug Administration approves the drug cocktail, “it will explode on the market. There is much need for such a treatment. It is legal to combine separate prescription drugs, but this will be a single capsule.”

The food supply around the world is tainted because of cattle and sheep getting it, both their meat and their milk. So if such animals are infected, some of it can get to people if not properly prepared, said Borody
. The milk has to be pasteurized at very high temperatures but that changes the quality.

It is difficult to detect the bacteria in meat. About 60% of America herds catch it, and they have gotten to poultry as well.

AS FOR stool transplants – known scientifically as fecal microbiota transplantation (FMT), Borody is very enthusiastic. “I read a scientific paper from way back in 1958 about a patient being given feces for mild colitis caused by the Clostridium difficile bacteria. But it didn’t go further.” The bacteria produce anything from diarrhea to Pseudomembranous colitis. More virulent strains have been developing in the last 15 years because the overuse of antibiotics caused resistance to them. In the U.S alone, there are some three million new cases of such infections each year; some of them can even be fatal.

In FMT, a donor with healthy and beneficial bacteria (probiotica) in his gastrointestinal system gives some 150 cc. of feces that are purified and introduced by enema into the recipient. A healthy growth of bacteria in the gastroenterological system is restored. A randomized study on FMT published in the New England Journal of Medicine last January showed a 94% cure rate of pseudomembranous colitis caused by Clostridium difficile, compared to just 31% with the antibiotic vancomycin. The study was stopped prematurely as it was considered unethical not to offer the FMT to all participants of the study due to the outstanding results.

Wednesday, December 18, 2013

Identifying & Destroying the Cause of Crohn's Disease #ibd #MAP

Encouraging and hopeful article!  



'UCF College of Medicine professor Dr. Saleh Naser soon will participate in a clinical trial to test whether a new antibiotic therapy acquired by RedHill Biopharma can be used to treat Crohn’s disease patients.
The FDA-approved phase III trial is expected to commence within weeks by RedHill Biopharma, which licensed Naser’s DNA technology for detecting Mycobacterium avium subspecies paratuberculosis, known as MAP. It is believed to be associated with Crohn’s disease. RedHill Biopharma developed the anti-MAP antibiotic regimen known as RHB 104. Crohn’s disease is a chronic inflammatory disease of the gastrointestinal tract characterized by cramping and diarrhea.
Naser developed and patented a way to detect MAP from milk, blood and tissue clinical samples. The bacterium is known to cause inflammation in the intestines of cows. It is also linked to Crohn’s disease, although its role has been debated for more than a century. Naser believes MAP is an underlying cause of the disease.
“Crohn’s disease affects more than 750,000 Americans, yet traditional treatments only address the symptoms of inflammation and not the cause,” Naser said. “I have seen case studies where patients’ lives have been restored following treatment, which removes MAP. I have high hopes that this clinical trial may lead to finding a cure.”
RedHill will be enrolling 240 subjects from the United States, Canada and Israel in this double blind clinical trial in which blood and intestinal biopsy specimens from Crohn’s patients will be tested for MAP before, during and following the one-year treatment with the antibiotic RHB 104.
“Since we acquired the license to Dr. Saleh Naser’s MAP detection technique in 2011, we have had an excellent collaboration with UCF,” said RedHill’s CEO Dror Ben-Asher. “The UCF team of researchers… is at the forefront of global academic research on MAP and its detection.”
Naser is looking forward to the trial and hopes this will end the academic debate regarding MAP and Crohn’s disease.
“I am ecstatic to be part of a team, which will help determine whether or not MAP is associated with Crohn’s disease; certainly a final answer to a one hundred-year old controversy,” Naser said.
Naser joined UCF in 1995 and has been a faculty member in the medical college since its foundation. He teaches clinical chemistry and infectious processes in the Burnett School of Biomedical Sciences within the medical school. He also serves as the graduate coordinator for three masters programs in the College of Medicine.

Saturday, December 7, 2013

Anorectal Sinuses, Fistulae/ #Fistula #Fissure, Rectal Bleeding

I was searching for some information and happened to run across this "different" online manual that almost explains how you would treat and perform certain surgeries for various gastrointestinal problems. They write it up in laymans terms maybe in order to understand the material.  They give minimal instruction on how to actually do each procedure/surgery (as this is probably a good thing, some of the broad details are difficult to read)  

When I was done reading the Proctology section, I went to the Home page which is states the following about this manual  The manual contains the collective views of an international group of experts. The methods and techniques described correspond to the state of the art with regard to their feasibility in rural hospitals, where sophisticated technical equipment may not be available. These manuals cannot, however, replace personal instruction by a qualified expert. Neither the editors, nor the publisher may be held responsible for any damage resulting from the application of the described methods. Any liability in this respect is excluded.:  http://www.meb.uni-bonn.de/dtc/primsurg/index.html

Volume One: Non-trauma

Nelson AworiAnne BayleyAlan BeasleyJames BolandMichael CrawfordFrits DriessenAllen FosterWendy GrahamBrian HancockBranwen HancockGerald HankinsNeville HarrisonIan KennedyJulius KyambiSamiran NundyJoe SheperdJohn StewartGrace WarrenMichael Wood 
Edited by Maurice King, Peter C. Bewes, James Cairns, Jim Thornton
Online Edition on special wish of the editors Maurice King and Peter C. Bewes expressed on the 8th. DTC Symposium in Jena 1999;
realisation by : Bernd Michael Schneider, Gustav Quade, Jürgen Quade, H. Woltering, P. Sommer, and B.D. Domres

The production of this manual on Surgery was sponsored by the German Federal Ministry for Economic Co-operation within the scope of the Technical Co-operation Agreement with the Republic of Kenya, under project number 78.2048.3-01.100. It was compiled by Maurice King Peter Bewes, James Cairns, and Jim Thornton in close collaboration with Kenyan and other experts. 
The manual contains the collective views of an international group of experts. The methods and techniques described correspond to the state of the art with regard to their feasibility in rural hospitals, where sophisticated technical equipment may not be available. These manuals cannot, however, replace personal instruction by a qualified expert. Neither the editors, nor the publisher may be held responsible for any damage resulting from the application of the described methods. Any liability in this respect is excluded.

Das Copyright © und alle Rechte für 'Primary Surgery' liegen bei der Deutsche Gesellschaft für Technische Zusammenarbeit (GTZ) GmbH und bleiben unberührt.

"GTZ does not accept any liability or give any guarantee for the validity, accuracy and completeness of the information provided in this title. GTZ assumes no legal liabilities for damages, material or immaterial in kind, caused by the use ore non-use of provided information or the use of erronenous or incomplete information."
we thank GTZ for giving us the revocable rigth for distributing this information for non-profit purpose according to the above mentioned wishes of the editors M. King and P.Bewes as expressed on the general assembly of the 8th DTC Symposium in Jena on 13th 11.1999 and thank the team of AGKM Uni Tuebingen; for the support during the implementation and G. Quade for the technical support provided during the realisation of this online - project.


Primary Surgery: Volume One: Non-trauma  - Anorectal sinuses and fistulae:


The anorectal abscesses in Section 5.13, and the sinuses and fistulae described here, are part of the same disease process. An abscess is the acute phase, and a sinus or fistula the chronic one. Both sinuses and fistulae are tracks lined by granulation tissue, which open on to the skin near the anus. The difference between them is that a sinus has no internal opening, whereas a fistula opens into the patient's anal canal, or occasionally into his rectum. Usually, there is only one internal opening, but he may have several external ones. These can either be insignificant little holes, or prominent little nodules of granulation tissue, which heal over temporarily. The treatment of sinuses and fistulae is similar.
Typically, a patient with a fistula starts by having an abscess, which either bursts and fails to heal, or is not drained properly (see Section 5.13), after which he complains of a chronic painless discharge which soils his clothes. His fistula is only painful when it becomes temporarily blocked, so that pus builds up inside it.
Fistulae can take any of the paths shown in Fig. 22-5; they can be subcutaneous (common), low anal, high anal, or intermuscular (rare).
A fistula seldom heals spontaneously, and almost always needs surgery. Cut down on it, deroof it, expose it, and let the wound you have made heal from the bottom by granulation during several weeks. A fistula nearly always goes through the anal sphincters, so that in cutting down on it, you have to cut them. Fortunately, a patient usually has some sphincter capacity to spare, and as his fistula usually goes through his sphincters quite superficially, you can cut the superficial part of them without making him incontinent. But if his fistula goes deep, and you cut too much of his sphincters, he will become incontinent. If, on the other hand, you make the opposite mistake of not cutting deeply enough, you may leave part of the track behind, with the result that his fistula recurs.
You have a 50% chance of finding the internal opening quite easily, by passing a probe from the external opening towards his anal canal. One of the worst mistakes is to create an internal opening, where there was none before, in the process of looking for it, by forcing a probe through into his anal canal. This makes a sinus into an iatrogenic fistula, opens up healthy tissue to infection, and makes cure more difficult.
The key landmarks are his pectinate line, and his anorectal ring. If necessary, you can cut both his sphincters below his pectinate line. In doing so, you preserve his anorectal ring (formed by his puborectalis muscle), and he remains continent, although he may have some incontinence of watery stools. Cutting his anorectal ring makes him completely incontinent. Fortunately, fistulae which go deep to the anorectal line are rare. If you find he has one, and cannot refer him, all you can do is to lay open the superficial tracks, curette the deep ones and hope for the best. This is difficult surgery, so examine him carefully and only operate if he has an easier fistula[md]incontinence is worse than the intermittent discharge from a fistula!
Fistulae which have external openings in front of a transverse line across the anus enter directly into it by the shortest path. Fistulae behind this line usually curve round, so that they enter the anus posteriorly at 6 o'clock (Goodsall's rule, Aa, 22-6). In doing so they follow a horseshoe path, and are often bilateral, one side communicating with the other. There are exceptions, and very superficial fistulae behind the line may occasionally track directly into the anus.
You will find that the track of a horseshoe fistula hugs the puborectalis part of the levator ani muscle, as it forms a sling round the sides and back of the anorectal junction, external to the external sphincter. Fortunately, the internal opening of such a horseshoe fistula is usually at the pectinate line, although the fistula itself may go much deeper.
Provided you trim the wound edges well, the common straight superficial fistulae heal with only minimal postoperative care, but this is critical for deep ones. The wound must be laid open widely, and it must granulate from the bottom up. If it heals leaving pockets, it will recur. So try to prevent the opposing granulating walls of the wound, or its skin edges, from touching one another, uniting, and leaving an unhealed pocket underneath them. Your main difficulty in treating these patients is likely to be to persuade them to stay long enough in hospital. If you are short of beds, a relative or the staff of a health centre will have to manage the wound.
PERIANAL ABSCESSES, SINUSES, AND FISTULAE ARE NOT HELPED BY ANTIBIOTICS! Fig. 22-5. PATTERNS OF FISTULAE. A, two subcutaneous fistulae, one opening at the pectinate line, and one just below it. B, two low anal fistulae. C, several high ones. D, some more high fistulae. Fistula (1) is the commonest high fistula; it goes high towards the levator ani, but does not penetrate it. The high extension is often missed, but it must be explored and laid open. Fistulae (2) and (3) penetrate the levator ani. E, high intermuscular fistulae (rare) may exist alone (4), or be an extension of a low anal fistula (5). After Goligher JC, ''Surgery of the Anus, Rectum and Colon', (4th edn 1980) Figs. 121 to 126. Bailli[gr]ere Tindall, with kind permission.
ANORECTAL FISTULAE X-RAY. X-ray the patient's chest: his fistula may be tuberculous (uncommon). If it is tuberculous, surgery is usually unnecessary. He may or may not have an obvious chest lesion.
EXAMINATION IN THE THEATRE. Prepare him for anaesthesia, if necessary. Before you start, warn him that you are going to examine him under anaesthesia to try to find where his fistula runs. Explain that if he has one of the easier fistulae, you are going to operate. Otherwise, you may have to leave it (unusual). Further indications are given below.
If the opening is less than 5 cm from his anus, his fistula is perianal, if it is more than 5 cm away, it is probably high. Multiple openings suggest a horseshoe fistula. Record the position of all external openings carefully on a copy of diagram A, in Fig. 22-4.
Feel for the thickened track which runs from the external opening(s) towards his anus. If a fistula is superficial, you can usually feel its firm, fibrous track quite easily. As you press it pus may exude from the external opening.
Put a finger into his anus and try to feel the internal opening: you may be able to feel an induration at its internal end. Feel the entire circumference of his rectum, as far as your finger can reach. Determine particularly where the fistula might be in relation to his anorectal ring and his pectinate line. Try to feel the track between your two fingers. Does it appear to come to an end low down, or high up in his anus? If you feel induration at the level of his puborectalis or above (rare), he has a complex high fistula.
PROCTOSCOPY. Examine his anal canal with a proctoscope. You may be able to see the internal opening of his fistula, usually at 6 o'clock on his pectineal line. Insert the proctoscope as far as it will go, withdraw the obturator, and then gradually withdraw the instrument itself. As soon as its end becomes obstructed and closed by his anorectal ring, stop. If you can still see the opening of the fistula, it is safely below the critical level of his anorectal ring.
You may be able to feel the track of a horseshoe fistula as a thick horizontal indurated rod, hugging his puborectalis sling.
In 50% of cases you will find the opening easily, in the other 50%, it will be present but tiny. A probe may show it, but if it does not, inject methylene blue (or boiled milk) into the external opening, and look for this flowing into his anus[md]finding the internal opening is the key to all fistula operations!
PROBING. Don't do this until you have finished your initial inspection. You may need to wait until he is anaesthetized. Decide where a track is probably going to go before you start probing. Pass the probe as far as possible towards his anal canal, and feel for its end in his anus. It may pass through into the lumen, or it may stop before getting there. If his fistula is superficial it will pass horizontally, if it is deep, the probe will pass almost vertically, parallel to his anus.
CAUTION ! (1) If the probe passes vertically, and not towards his mid anal canal (even though there is an opening there), he probably has a high complex fistula or a deep sinus. (2) Only pass a probe into the rectum through a fistulous track[md]don't force it through normal tissues.
DEROOFING [s7]AN ANAL FISTULA INDICATIONS. You should now know where the fistula runs. Only operate on the easier and more superficial fistulae. The main risk is incontinence. Refer him if: (1) His fistula has multiple openings, unless you have had some experience with the operation. (2) He has had previous unsuccessful operations. (3) The probe passes vertically upwards. (4) His fistula is palpable in his upper anal canal, or above his anorectal ring (rare).
Other factors which increase the risk of subsequent incontinence are: (1) The liability to attacks of diarrhoea, or a history of soiling, which might indicate reduction of his sphincter capability. (2) A female patient, particularly if she is old.
EQUIPMENT. This includes a medium-sized malleable silver probe, or a probe-pointed director.
ANAESTHESIA. (1) Ketamine. (2) Light general anaesthesia. Avoid relaxants and subarachnoid anaesthesia. You want to be able to feel the anorectal ring, so as not to cut it. Muscular relaxation makes feeling it more difficult, but does provide better exposure.
Fig. 22-6 A LOW ANAL FISTULA can have several tracks, as in A, and B, or only one, as in the remainder of these figures. Aa, Goodsall's rule. Fistulae above a horizontal line across the anus usually pass directly into it; fistulae behind the line usually curve round it to enter at 6 o'clock. C, passing a probe-pointed director along the track from the external to the internal opening, and out through the patient's anus. D, cutting down on the director. E, scraping away the granulation tissue with a sharp spoon. F, trimming the edges of the wound. G, the final pear-shaped guttered wound. If there is much fibrous tissue round the track, excise it. H, packing the wound with gauze soaked in hypochlorite. After Goligher JC, ''Surgery of the Anus, Rectum and Colon', (4th edn 1980). Figs. 139 and 140, Bailli[gr]ere Tindall, with kind permission.
A SUBCUTANEOUS OR LOW ANAL FISTULA. Carefully confirm the findings you obtained before you anaesthetized him. If you thought that his fistula was blind at the inner end (a sinus), confirm this. Pass a probe or director through the track, from the external opening towards his anal canal, either completely through to its lumen, or as far as it will go. It may enter his anal canal, or it may stop before doing so.
If the probe enters his anus superficial to his pectinate line, cut down on all structures superficial to it, and lay the track open. If you are using a director, cut down to the groove in it. Look at the velvety track of the opened fistula. If there is no such track, you have probably opened up a false passage. Look carefully for any side openings, and feel among the fatty tissue for nodules of induration, that might be offshoots of the fistula. As a general rule, all fistulous tracks communicate with one another. Using a sharp spoon, curette the tracks, so as to leave only healthy tissue, and trim away any overhanging skin.
Alternatively, make a narrow pear-shaped incision to include both the internal and external openings. Excise both of them, and the track of tissue that still clings to the probe.
If the probe enters his anus deep to his pectinate line, leave the fistula untreated, or refer him. Even experts find these fistulae difficult.
CAUTION ! (1) Don't cut deep to his pectinate line, or you will cut too much sphincter. (2) When you cut down on to a probe or director, do so by the most direct route.
If the probe does not enter his anal canal, he has a sinus. Lay it open in the same way, but without opening into his anus.
With all sinuses and fistulae, look, feel, and probe for other track openings and areas of induration. If you find any, open them and curette them. Curette the granulation tissue.
Control bleeding with diathermy, or tie off bleeding vessels with 2/0 plain catgut. Excise the skin edges and bevel them, so as to leave a conical or pear-shaped concave raw area. Be sure that there will be no pockets or overhanging edges, when muscle tone returns. If a fistula is complex, you will have to make a deep, wide wound.
Always send tissue for histology to exclude tuberculosis. Apply flat squares of gauze soaked in hypochlorite, or salt solution, pad it with plenty of gauze, and hold it in place with a T-bandage. Avoid vaseline gauze because it may cause a foreign body granuloma (''paraffinoma').
Fig. 22-7 A HIGH POSTERIOR HORSESHOE FISTULA[md]ONE. A, the fistula shown on a standard diagram of the anus. B, a coronal section. C, a sagittal section. This is the fistula that is being operated on in the next diagram. After Goligher JC, ''Surgery of the Anus, Rectum and Colon', (4th edn 1980). Fig. 128, Bailli[gr]ere Tindall, with kind permission.
ISCHIORECTAL (horseshoe) FISTULAE usually have two or more external openings. Pass a director into an opening, and lay open one side at a time.
Point the director forwards, make it project against his skin at the side of his anus, and cut down on it. The track will be deeply overhung by fat; trim this. Turn the director posteriorly, and see if you can follow the track across to the other side, and then forwards on that side.
Now see if you can find the opening into his anus posteriorly. If you have seen a definite opening below his anorectal ring, encourage the director to follow it there, and lay the fistula open.
CAUTION ! (1) Most of these fistulae have a posterior opening close to the pectinate line, and if you miss it and don't lay it open, the fistula will recur. If you don't find such an opening, make one. (2) Lay open all side tracks.
If oozing is a problem, apply pressure from adrenalin soaked gauze. Gutter, trim and dress the wound as above. If his fistula is complex and deep, feel it with your gloved finger each day, to keep the edge of the granulating wound smooth, and to make sure that no deep pockets are left, which would lead to recurrent infection. Lay a flat gauze square on it. If you are worried about the way it is healing, take him back to the theatre and further lay the wound open.
POSTOPERATIVE CARE is the same as for any granulating anal wound, with daily, or twice daily, salt baths (sitting in a bowl of saline), regular dressing changes, and measures to ensure soft stools. Warn him that a perianal fistula may take 2 weeks to heal, and an ischiorectal one 4 weeks. An extensive horseshoe fistula may take 12 weeks. If necessary, trim away any excess granulation tissue.
Fig. 22-8 A HIGH POSTERIOR HORSESHOE FISTULA[md]TWO. This is the fistula in Fig. 22-7. A, passing the director forwards. B, cutting down on the track on the left side. C, passing the director along the posterior part of the track towards the right. D, exposing the track on the right side. E, passing the director forwards through the posterior communication into the patient's anus. G, the final horseshoe-shaped wound, with part of his sphincter divided. After Goligher JC, ''Surgery of the Anus, Rectum and Colon', (4th end 1980). Fig. 147, Bailli[gr]ere Tindall, with kind permission.
DIFFICULTIES [s7]WITH ANAL FISTULAE If a FISTULA PASSES FORWARDS from his (or her) anus, it may be an URETHRAL FISTULA (23.8), or originate in Bartholin's glands (23.4).
If a FISTULA IS POSTERIOR, don't confuse it with a PILONIDAL SINUS (22.8). If it is low and immediately behind his anus, it may have arisen in an anal fissure.
If the EXTERNAL OPENING IS SOME DISTANCE FROM HIS ANUS, look out for a long curved fistula, or a high one. Its thickened track will usually show you its course and destination. Probe it, but don't expect it to enter his anus.
If his FISTULA EXTENDS UP THROUGH A HOLE IN HIS LEVATOR ANI, and you cannot refer him, pass a haemostat through the hole and stretch it. Enlarge the opening to provide free drainage. If necessary, cut backwards, laterally or forwards, but not medially. Enlarge the external wound by wide trimming, especially posteriorly, to provide a wide gutter, extending backwards towards the side of his coccyx. Provided there is no internal opening above his levator ani, or chronic pelvic disease, such as regional ileitis, his prognosis is good.
CAUTION ! Don't look for an opening in his rectum, there almost never is one, unless the cause of the fistula was a penetrating injury.
If you find a HIGH INTERMUSCULAR FISTULA (submucous fistula, unusual), leave it. If it really is submucous, it can be opened into his rectum, but if it happens to be outside his rectal wall, and you cut into it, this will be a disaster.
If he also has PILES, excise them, or they may thrombose and bleed postoperatively. Or, if they are first- degree, do Lord's procedure (22.5), and leave his anus packed.
If he has RECURRENT DISCHARGE FROM THE TRACK, his wound has healed over externally, without healing from below. Operate again. It will not heal with antibiotics. Also consider the possibility of tuberculosis.
If he has ULCERATIVE COLITIS, or CROHN'S DISEASE (both uncommon in the developing world), he is a special case, so refer him.
If there is GREAT NODULAR THICKENING of his subcutaneous tissue, purplish discoloration (in a white skin), numerous sinuses which seldom discharge much pus, and no real cavity or track, suspect SUPPURATIVE HIDRADENITIS (rare).
If he, or more likely she, has MULTIPLE FISTULAE with much scarring and skin bridges between them, suspect LYMPHOGRANULOMA VENEREUM (22.10) or colloid carcinoma of the anus.

Rectal bleeding

A patient who bleeds severely from his stomach or duodenum, usually vomits the blood, if he bleeds fast. If he bleeds more slowly, it appears as black tarry melaena stools. The higher the source of the blood, the longer it takes to reach his rectum, and the more likely is it to be converted into melaena stools. Although a melaena stool is usually the result of bleeding from his stomach or his duodenum, it can follow bleeding from his small gut. Dark red ''burgundy-coloured' blood mixed with stool can come from the stomach, the duodenum, the small or the large gut, but fresh bright-red blood usually comes from the rectum or anus. Not all dark stools are the result of bleeding, so remember the possibility of iron medication (negative occult blood test), or nose bleeds (often positive for occult blood).
Bleeding from the upper gut is often severe, is usually more serious than it looks, and frequently threatens his life (11.3). Bleeding from the lower gut is often mild, and even a small quantity of bright blood can be alarming. He is usually not as ill as he seems, and you have more time to investigate him.
Rectal bleeding is common everywhere, but its causes differ geographically. In the developing world, where carcinoma is still comparatively unusual, you can treat most patients with rectal bleeding quite easily.
If he continues to bleed from his rectum, and you are not sure why, you will have to decide: (1) if you are going to operate, (2) when, and (3) what you are going to do when you get inside. In most areas, the commonest cause of massive rectal bleeding is a peptic or duodenal ulcer; but in some tropical areas it is bleeding from the terminal ileum, or ascending colon, due to typhoid or amoebiasis.
The major mistakes are: (1) To misjudge the severity of his bleeding. (2) To fail to use your finger, a proctoscope and a sigmoidoscope, to label him as having ''piles' without examining him properly, to fail to investigate him, and so to miss a carcinoma. (3) To miss the more treatable diseases, such as tuberculosis and amoebiasis, as the following case shows.
POUL (53) had passed several bloody stools since the morning, but had no other gastrointestinal symptoms. He was neither anaemic nor hypotensive, but during the next few days he continued to bleed, and his haematocrit fell to 23%. Sigmoidoscopy showed friable, oedematous, reddish-yellow areas in his rectum, but no obvious ulcers. A smear from his rectal mucosa showed amoebae. Metronidazole cured him dramatically. LESSONS (1) Amoebiasis is readily treatable[md]if you diagnose it. (2) A severe bleed in the absence of previous symptoms of amoebiasis is unusual.
THE GENERAL METHOD [s7]FOR RECTAL BLEEDING See also Section 11.3.
COMMON CAUSES (other than piles 22.4). Peptic ulcer (11.3). Typhoid ulcers of the ileum (bleeding may be severe, 31.8). Amoebiasis (31.10). Schistosomiasis mansoni. Bacillary dysentery (diarrhoea with blood and mucus, 31.10). Anal fissures (which may bleed at defaecation, 22.7). Lymphogranuloma (22.10). Polyps, especially juvenile polyps (usually producing a little fresh blood, see below). Intussusception (''red currant jelly stools', 10.8). Also causes of high gastrointestinal bleeding (11.3).
UNCOMMON CAUSES. Carcinomas of the colon, rectum, or anal canal (32.27), tuberculous ulcers of the gut (29.5), non-specific ulcers of the gut (see below), pigbel disease (31.9), Meckel's diverticulum (episodic massive bleeding in the young, 28.5), rectal prolapse (22.9).
RARE CAUSES. Ulcerative colitis, ischaemic colitis, diverticulitis, haemangiomas of the small gut, blood dyscrasias, villous adenomas of the rectum (bright blood with much watery mucus). A foreign body in the rectum.
EXAMINATION. (1) Assess the degree of the patient's hypovolaemia (53.2), and the severity of his anaemia. Does sitting him up in bed make him feel faint, or exercise make him breathless? Examine him for epigastric tenderness, distension, the signs of subacute gut obstruction (10.3), and abdominal masses.
Examine his rectum with your finger and a proctoscope, and don't forget to look at his stool.
CAUTION ! Never forget to do a sigmoidoscopy if an adult presents with rectal bleeding.
DIFFERENTIAL DIAGNOSIS. Bleeding related to defaecation? (an anal or rectal lesion). Blood mixed with stool? (some lesion higher than the rectum). Painful bleeding? (a lesion below the pectinate line; piles arise above this line and are painless, unless they prolapse or strangulate). A feeling of something prolapsing from the rectum? (piles, prolapse, or polyps). Dyspepsia, heartburn, etc.? (peptic ulceration, 11.1). High fever for a week or two? (typhoid fever, 31.8). Loss of weight, anorexia, night sweats, and fatigue? (abdominal tuberculosis; rectal bleeding is unusual 29.5). Vague lower abdominal pain followed by the passage of much dark blood? (non-specific ulceration of the gut, 22.10). Abdominal pain, diarrhoea, fever, prostration? (non-occlusive infarction of the gut, pigbel disease, 31.9).
THE INDICATIONS FOR LAPAROTOMY. (1) Loss of [mt]1500 ml of blood. If he is in extremis, surgery may be life saving. (2) The presence of a mass. The treatment of most causes of rectal bleeding is discussed elsewhere. Most colonic bleeding stops on its own, so don't operate too early.
RESUSCITATION. Replace the blood he has lost, with due regard to the dangers of HIV (28a.2).
ANAESTHESIA. General anaesthesia.
LAPAROTOMY. Enter his abdomen through a long midline incision. Exclude more common causes of bleeding, such as peptic ulceration, then examine his entire gut from his duodeno[nd]jejunal junction down to his rectum. Note the colour of the contents of his gut. What is the highest site in his gut to show bleeding? Look for abnormal vessels going to the bleeding area, and feel for induration or an ulcer. If necessary, do a gastrotomy and enterotomies (open his gut, 9.3) to find the level of the bleeding.
If he is bleeding severely from his right colon, you don't find a lesion, and there is no bleeding more proximally, consider doing a ''blind' right hemicolectomy (66-20). This will not be easy, so don't do it lightly. Afterwards, open the specimen to see where the blood is coming from.
DIFFICULTIES [s7]WITH RECTAL BLEEDING If a CHILD HAS INTERMITTENT CONTINUING RECTAL BLEEDING, he may have a JUVENILE POLYP. This is a friable, proliferative mass, which lies on his mucosa to begin with, and then develops a stalk. On rectal examination you can usually feel a soft, mobile, pedunculated mass, and see a strawberry-like lesion through a proctoscope or sigmoidoscope. If examination is difficult, you may have to anaesthetize him to examine it.
If a polyp is small, remove it through his anus, tie the stalk, and cut it off. If you cut the stalk without tying it first, it may bleed massively. Or, if tying it is impracticable, leave it to undergo spontaneous strangulation, necrosis, and sloughing.
If the cause of a patient's RECTAL BLEEDING IS NOT IMMEDIATELY OBVIOUS, consider the possibility of NON-SPECIFIC ULCERATION OF THE GUT (uncommon). In the tropics patients sometimes bleed from small punched-out ulcers of unknown cause in the mucosa of their distal ileum and proximal colon. They are usually middle-aged adults of either sex, who present with lower abdominal pain and fever, followed by the passage of a quantity of dark blood rectally. He may be tender in his right iliac fossa; sigmoidoscopy is normal, except for blood coming from above. If bleeding does not stop and you are sufficiently skilled, a right hemicolectomy may save him, because the source of the bleeding is nearly always in his distal ileum, or proximal colon. In good hands he has a 10% chance of death.
His distal ileum and colon are likely to be discoloured by contained blood, and feel slightly oedematous and thickened. The ulcers in his mucosa are rarely palpable.
If you have established the source of the bleeding, and think you could remove it, do an extended right hemicolectomy, and take the last 20 cm of his ileum, his ascending colon, and his entire transverse colon up to his splenic flexure. Do an end to end ileo-transverse anastomosis in two layers.
Open the specimen, and you will find numerous punched-out ulcers in his terminal ileum and right colon, one of which may contain a bleeding artery. Histology shows non-specific changes only, with very little inflammation round the ulcers.
If he has RECTAL BLEEDING ACCOMPANIED BY SEVERE DIARRHOEA, PROSTRATION, vomiting, and fever, consider the possibility of pigbel disease, and see Section 31.9.
Fig. 22-9 LORD'S ANAL STRETCH[md]ONE will cure many cases of piles and anal fissures. First, do a digital examination with your right index finger, then introduce two fingers, side by side. Stretch hard, and then put four fingers in. [f10]Dilate the patient's anus gradually over 3 or 4 minutes, [f11]so that the sphincters of his anus are stretched, and not torn. Finally, put six or eight of your fingers in. 

Anal fissure

An anal fissure causes suffering out of all proportion to its size. It starts as a crack in the lower part of a patient's anal canal, which makes defaecation, and the half-hour following it, acutely painful. Even the thought of a bowel movement may fill him with such fear that he ignores the urge, so that the hard constipated stools that he eventually passes make his fissure worse, and may occasionally make it bleed.
You will almost always find his fissure posteriorly in the 6 o'clock position, between his anal verge and his pectinate line, directly over the distal end of his internal sphincter. A small oedematous skin tag commonly forms on his anal verge, just posterior to the fissure. This is the ''sentinel skin tag'. Later, his fissure may become indurated and infected, and may lead to a low perianal abscess (5.13), which may discharge through the fissure, and externally, to produce a low anal fistula. His internal sphincter lies directly under his fissure, and after several months of exposure this becomes fibrosed and spastic.
ANAL FISSURE DIAGNOSIS. A fissure is acutely painful, so don't do a rectal examination, or pass a proctoscope, until the patient is under general anaesthesia. Alternatively, and less satisfactorily, smear his anus with 10% amethocaine ointment for 10 minutes. Can you see a sentinel skin tag? Look for a triangular or pear-shaped slit posteriorly, just inside his anus.
DIFFERENTIAL DIAGNOSIS Other obvious skin changes and cracks? (pruritus ani). Diarrhoea with multiple fistulae away from the midline? (the skin changes following some forms of colitis). More induration than in a fissure, a larger ulcer, and perhaps enlarged inguinal nodes? (carcinoma). Indurated margins, a symmetrical lesion on the opposite margin of his anal canal, and no pain? (primary chancre). The whole region is moist and pruritic, with flat, slightly-raised lesions, which are usually symmetrical on both sides? (secondary syphilis).
TREATMENT depends on how long he has had his fissure. Early presentation is unusual in the developing world.
If it is acute (less than 10 days old), only his epithelium is involved. It may heal, if you keep his stools soft for a week or two with liquid paraffin. When it has healed, warn him that it may return, if he allows himself to become constipated. He may have to continue this treatment indefinitely. Warn him that he must not keep his stools too loose, or they will never dilate his anus, so that it stenoses.
If you give him a local anaesthetic ointment (5% lignocaine), ask him to smear it over the sphincter inside his anus, not outside it.
If, his fissure fails to heal after you have kept his stools soft for 3 weeks, stretch his anus (22.5). Unfortunately the relapse rate with non-operative treatment is high, even if a fissure does heal at first.
If his fissure is chronic (more than 10 days), fibrosed, has a sentinel skin tag, and especially if you can see the exposed fibres of his internal sphincter under it, it will probably not respond to non-operative treatment. First try stretching his anus (22.5). After a day or two, there is a 95% chance that he will be completely free of pain. There is a 15% chance that his fissure will recur later. If it does, don't repeat the stretching, refer him for sphincterotomy.