Not quite what Dora's colon looks like... some peoples' sigmoid colon isn't quite that short and straight.
Click on photo for more photos of barium x-ray of Dora's bowel
This page is color coded. Unfortunately, it was not possible to for instance give articles on asacol and inflammation their own section because discussion pops up in many articles.
Yellow pertains to the role of inflammation in diverticulitis.
Green pertains to treatment of diverticulitis with asacol and with boswellia (which has its own section).
Teal/ blue pertains to the risk of recurrence after surgery (substantial but minority) and to the strong role of amount of bowel removed in reducing that risk.
Orange, purple and other colors pertain to other issues that have importance to me.
Jackson GI: Diverticulosis.
EmedicineHealth: Diverticulosis and Diverticulitis
PubMed Health: Diverticulitis.
WebMD: Understanding Diverticulitis: the Basics.
WebMD: Digestive Disorders Health Center - Diverticulits Topic Overview
Coviden: Diverticulitis and Diverticulosis
Advances in the management of uncomplicated sigmoid diverticulitis. Coastal Surgery Specialists. Good if slightly outdated general discussion of diagnosis and medical treatment of diverticulitis; basically a patient handout..
Peter Cartwright. Coping with Diverticulitis (London: Sheldon Press, 2007). Excellent. Even includes chapters on how to plan surgery and how to deal with a colostomy. Also discusses causes of recurrent pain. His discussion of recurrence of diverticulitis after surgery and how to avoid it is below.
Joan McClelland. How to Cope Successfully with Diverticulitis (Wellhouse Publishing, 2009) Not as good, and she seems somewhat possessed by the notion that diverticulitis is psychosomatic, but she does cover the basics of how to treat it.
American Society of Colon & Rectal Surgeons Diverticulitis. Up to date review written for physicians.
Chronic complications of diverticular disease include stricture, fistula and recurrent inflammation. Strictures of the colon result from chronic inflammation and fixed scarring, luminal compromise. Usually patients present with chronic partial obstructive symptoms. Recurrent disease not as common as previously thought. Traditionally recurrence after episode 30-50%. Recurrence rate is 5-20%, with recurrences tending to mimic the severity of the initial attack. Decisions about when to do surgery should be individualized.
Patterns of recurrence in patients with acute diverticitis. Abstract of statistical study. One of the studies behind the notion that an initial attack of uncomplicated diverticulitis is relatively unlikely to blow into a need for emergency surgery.
Family Doctor: What are the complications of diverticular disease? Not as analytical.
The timing of elective colectomy in diverticulitis: A decision analysis. Leon Salem, et al. Journal of the American College of Surgeons. 199 (6), Dec 2004, pp 904-912.
Cited by Tursi (2013) for the risk of recurrent diverticulitis after resection 2.6% to 10.4%, argued that risk of recurrent diverticulitis not eliminated after sigmoid resection. Have abstract only; it's a study of the effect of timing on outcome and cost from elective resection, and it finds the lowest deaths and costs associated with doing a resection after 4 attacks instead of after 2 attacks, which is a completely different issue. Also, 2.6% to 10.4% is not consistent with the view that patients who get resections "just keep getting sicker". Cannot find e-mail for Leon Salem, he is not still at University of Washington.
Practice Parameters for Sigmoid Diverticulitis. Janice Rafferty, MD, et al. 2006. Published online.
Current practice parameters of the Standards Committee, American Society of Colon and Rectal Surgeons. Tursi et al summary; they recommend an individualized approach to decisions on colon resection. This is their recommendation. After 1 attack, 1/3 of patients will have second attack. 1/3 of those will have more attacks. Most who present with complicated diverticulitis do so at their first attack. Decision should be influenced by age and condition of patient, frequency and severity of attacks, whether there are persistent sympotms after acute episode. Younger patients have greater risk of recurrent attacks because of longer life span. Usually enough to remove only the most severely affected segment, not all diverticuli-bearing colon. Distally it should extend to the upper rectum. An important predictor of recurrent diverticulitis is colosigmoid rather than colorectal anastomosis.
Non-steroidal anti-inflammatory drugs and perforated diverticular disease: a case-control study. H Goh, R Bourne. Ann R Coll Surg Engl 2002; 84: 93-96.
Three studies including that cited above have found that patients with diverticular disease, perforated diverticular disease, and hemorrhage, were all atleast twice as likely to be taking NSAIDs, most often for cardiac and for osteoarthritis, as to not be taking them. This study found those who developed perforated diverticular disease were three times more likely to be taking aspirin as to be not taking asprin. Other NSAIDs were not taken very much, and meloxicam was not among them. Aspirin is the most common drug indicated in perforation. NSAIDs inhibit prostaglandins that have protective roles in the digestive tract. COX-1 makes physiological prostaglandins that protect the bowel mucosa. COX-2 is pro-inflammatory. Inhibition of COX-1 may predispose diverticula to perforation. COX-2 is anti-inflammatory and conceivably interferes with fighting an infection. In an animal study COX-2 inhibition caused inflamed colon to perforate within a week. Another possibility is that the reasons to take aspirin and the incidence of diverticulitis are highly correlated, but the study looked specifically only at people who had diverticulitis.
Use of aspirin or nonsteroidal anti-inflammatory drugs increases risk for diverticulitis and diverticular bleeding. Lisa L Strate et al. Gastroenterology 2011 May; 140(5); 1427-1433.
Used data from the Health Professionals Followup Study, men, 40-75 at baseline in 1986. Assed use of asprin, non-aspirin NSAIDs, and other risk factors. Documented 939 cases of diverticulitis and 256 cases of diverticulitis. Men who used aspirin regularly had a relative risk of 1.25 for diverticulitis and of 1.70 for diverticular bleeding, compared with men who did not use NSAIDs. Use of aspirin at 2-6 325 mg tablets per week, and 4-6 days/ week, associated with highest risk (RR -2.32) of bleeding. Regular users of non-aspiring NSAIDs also had an increased risk of diverticulitis (RR-1.72) and diverticular bleeding (RR = 1.74), compared with men who did not use these medications. NSAID's carry a higher risk than aspirin.
Colonic Diverticular Disease. H Nail Aydin et al. Cleveland Clinic Center for Continuing Education. Review article.
Mentions that CT with triple contrast used more frequently as the initial imaging study, esp when moderatly severe disease or abscess is anticipated. Postive value for divericulitis by CT scanning is 73% for sigmoid diverticula, 88% for pericolic inflammation, 85%for wall thickness 7-10 mm, 100% for wall thickness > 10mm. Decisions on surgery made on a case by case basis, based on age, condition, frequency, persistance and severity of attacks. No consensus regarding how many attacks to do surgery; mentions evidence that elective surgery doesn't necessarily decrease likelihood of later emergency surgery or overall mortality. One article he cites is Salem, where that's not what Salem found; see below. He found that after four attacks surgery gave the best and cheapest outcome, and that chances of reoccurrence depended on whether or not they removed all bowel between the immediate diseased portion and the rectum.
Long term outcome of conservative treatment in patients with diverticulitis of the sigmoid colon. Mueller MH. European Journal of Gastroenterology and Hepatology. June 2005 - Vol 17 issue 6, pp 649-654. Abstract only.
Review of 252 patients treated conservatively and 111 who had surgery, among all patients treated for diverticulitis at that institution. At first followup, a third of the patients had died, one from bleeding diverticula. Half of the remainder had recurrence of symptoms. At second followup, one patient died from perforation from recurrence. Over a third reported symptoms, 12 of hte 85 had surgery. At second follow up interivew, 34% of patients initially treated conservatively had recurrence and 10% had surgery. The conclusion is that lethal complications are rare, and surgery should be undertaken to relieve symptoms rather than predict death from complications, again different from what Aydin et al represented them as saying. Also the data support thinking one can delay a decision on surgery after a single initial attack. Noone suggests doing surgery after one initial uncomplicated attack. Note: I have the impression that these patients were to be elderly and this was the main explanation of the high rate of their not being living at followup.
Complicated diverticulitis: Is it time to rethink the rules? Jennifer Chapman et al. Ann Surg 2005 October; 242(4); 576-83.
Argues with practice parameters that recommend resection after 2 episodes of diverticulitis to reduce morbidity and mortality. 375 patients hospitalized for CD were retrospectively analyzed. Looked at patients sick enough to be hospitalized. 47% had atleast one attack before. Most who died presented with their first episodes. 50% to 70% of the time perforation is the first sign of complicated diverticulitis - not from this study. Mortality rates between 6% and 17% after surgery for complicated diverticulitis. They argue that complicated diverticulitis doesn't usually develop from uncomplicated diverticulitis. Nothing else in the study seems to have any bearing on when to actually do surgery. Postoperative mortality of 41% similar to other studies and strongly associated with the patient's general health status. In general, 5.5% of patients who have an initiial episode of nonsurgical diverticulitis progress to needing emergency colectomy or colostomy. Risk of recurrent diverticulitis is reported to be 2.6& to 10.4% - in the literature. They end by pointing out that most of those destined to develop surgical emergencies initially present with surgical emergencies, which pertains to only one of a number of good reasons to do a resection.
Level of anastomosis and recurrent colonic diverticulitis. Paul L Benn et al. American J of Surgery 151(2), Feb 1986, 269-71.
Same study summarized above. Examined 501 patients who had resection and anastomosis for diverticular disease at Mayo Clinic 1970 - 75. Recurrent diverticulitis developed in 12.5% of patients in whom sigmoid colon had been used for distal margin of anastomosis and in 6.7% of those in whom the rectum had been used. Reoperation was required in 3.4% of patients in whom sigmoid colon was used and 2.2% of those in whom rectum had ben used. No increase in perioperative complications or anastomotic leaks in those for whom rectum had been mobilized. Concludes the entire distal sigmoid colon should be removed during resection for diverticulra diseaes and anastomosed to the upper rectum to avoid recurrent diverticulitis.
Clinical and functional results after elective colonic resection in 75 consecutive patients with diverticular disease. Thorn Magnus et al.
75 patients who had colonic resection reviewed and sent a questionnaire about abdominal symptoms and functional results. 13% had major complications including anastomotic leakage. Two thirds classified their final result as excellent or good. Functional symptoms or symptoms suggestive of irriable bowel syndrome before the operation predicted less successful result - they had significantly worse results.
Final study cited as supporting Jennifer Chapman's argument; The 5-Year natural history of complicated diverticular disease. N. Farmakis et al. British Journal of Surgery 81(5), May 1994, pp 733-735.
Questionnaire surveys sent to the doctors who treated 300 pateints in a national audit 1985 - 1988. Abstract only available. Much is muddy, esp the numbers. However, of 77 patients managed by sigmoid resection, only 2 developed recurrent complications compared with 37 of 43 managed conservatively. Unclear how sick they were to begin with, but the data clearly contradicts Chapman's argument.
Complicated Diverticulitis: It is not yet time to rethink the rules! Andreas M Kaiser. Ann. Surg 2006 May; 243(5): 707-8.
Sharply takes issue with above article, which was cited by Aydin as evidence that if you treat diverticulitis surgically the patient only gets sicker. He finds that the concepts and definitions are missing or hazy, and large numbers of the patients were unecessarily subjected to serious complications by delaying surgery.
Diverticular Disease. Chapter 93, Marx: Rosen's Emergency Medicine. MD Consult. The version now online is the 8th edition and it is subscription only. General discussion. Use of diagnostic imaging. Of patients treated medically for their first attack of diverticulitis, 95% remain symptom-free for the next 2 years,and 80 to 90% remain symptom free permanently. Patients with recurrent episodes of diverticulitis should be referred to a surgeon for outpatient consultation for elective resection.
Peter Cartwright, Coping with Diverticulitis - bibliographic information see above. Book.
One of my doctors told me that when people have surgery for diverticulitis, they just keep getting sicker. Some of the articles below also give the actual rate of that. Cartwright says the recurrence rate for symptoms after removing part of the colon is 10 - 25%.
He discusses recurrence of diverticulitis. He gives three likely explanations: symptomatic diverticulosis (IBS-like) mistaken for diverticulitis, diverticula developed elsewhere in large intestine, an insufficient length of the colon was removed. He explains,
"When the sigmoid colon is removed, the lower cut should be in the rectum. This is because the rectum very rarely develops diverticula... The upper cut should be above the point of colonic muscle thickening. sometimes there is muscle thickening without diverticula and the surgeon might not remove that section. It may not be realized that not only is colonic muscle thickening a precursor to the devleopment of diverticula, but also that the thickened muscles may play a part in the spasmodic reactions that are involved in IBS-like symptoms. To be confident of removing all current and future causes of DD symptoms, some surgeons remove the whole of the descending colon as well as the sigmoid colon. To reduce the risk of having recurrent symptoms after surgery, it may be advisable to clarify with your suregon where the cuts in the colon will be made."
Advances in the management of uncomplicated sigmoid diverticulitis. James A. Harris, M.D., FACS Coastal Surgery Specialists.
Surgery usually not needed for one episode of uncomplicated sigmoid diverticulits as recurrent rate is only 30%. However, recurrence rate after two episodes is more than 50%, and surgical treatment should be strongly considered. (Not all studies find the rate of recurrence after two uncomplicated attacks that high, however, after four attacks the situation is explicitly very different.)
Diverticulitis. M. Shane McNevin, MD. American Society of Colon & Rectal Surgeons.
Acquired diverticula of the colon are false or pseudodiverticular because only two layers herniate. Recurrence rate was tradionally thought to be 30-50%, newer data suggests it is 5 - 20%, with recurrences tending to mimic the severity of the initial attack. In patients requiring urgent surgery it is the initial attack in over 80% of cases.
Diverticular Disease of the Colon. Tonia M. Young- Fadok, MD. Mayo Medical School, Division of Colon and Rectal Surgery. American Society of Colon & Rectal Surgeons.
If sigmoid is redundant the tenderness may extend across the suprapubic region and into the right lower quadrant. Normal temperature and white blood count seen in up to 45% of patients. Sterile pyuria indicates adjacent inflammation in the sigmoid. In CT scan, sensitivities range from 85-98% and specificities from 80 - 98%. After a second attack, only 10% subsequently remain asymptomatic. They recommend elective resection after two confirmed attacks.
Patterns of recurrence in patients with acute diverticulitis. Elginton T et al. British Journal of Surgery, 97(6), 952-957, June 2010.
Prophylactic surgery following conservatively managed diverticulitis is increasingly controversial.
Review of charts of all patients admitted with diverticulitis between June 1997 and June 2002. Demographic data, management, recurrence rates, complications and subsequent surgery were recorded. 502 patients; 337 with uncomplicated and 165 with complicated diverticululits. Of 320 patients with uncomplicated diverticulits managed conservatively, 19% had one episode of recurrence, and 5% had two or more episodes. Only 5% developed complicated disease. Recurrences usually happened wihtin 12 months of initial episode. These authors think that is failure of an initial episode to settle, which on the diverticulitis forums proves to be a not uncommon idea, especially with surgeons.
Long-term outcome of patients presenting with acute complications of diverticular disease. Sanjeev Sarin and Paul Boulos. American R Coll Surg Engl 1994; 76: 117-120.
Of 164 patients admitted over an 8 year period with comlicated diverticulular disease. Reviewed outcome. 13 patients required readmission with complications of diverticular disease; none of those who underwent resection of the sigmoid/ descending colon required resection. The authors took this to mean that conservative treatment works as well as surgery. The diagnoses were made by symptoms alone and subsequently confirmed by barium enema and/or colonoscopy, and it's a miracle if either of those procedures confirmed very much. It says a variety of operative procedures were performed, and I could not confirm how mcuh bowel was removed or whether that varied.
Incidence and risk factors of recurrence after surgery for pathology-proven diverticular disease. Caroline Andeweg et al. World Journal of Surgery, July 2008, 32(7), 1501-1506.
Recurrent diverticulitis occurs in about 10% after resection. Pathogenesis for recurrence not completely understood. Medical records of 183 consiecutive patients with pathology-proven diverticulitis examined. Mean follow-up was 7.2 years. Incidence of recurrence was 8.7%, with an estimated risk over a 15 year period of 16%. RIsk factors associatedd with recurrence were younger age, persistence of postoperative pain. Persistent abdominal pain after surgery present in 22%. 80% of patients who needed emergency surgery had no signs of diverticular disease before surgery. Recurrent diverticulitis was not associated with a higher percentage of emergency procedures. Data from 1960's and 1980's showed rates of recurrent diverticulitis after resection from 7% to 11%. Lower rates between 5% and 8% found more recently, explained by the fact that recurrences had to be consistent with barium enema or CT findings. Young people with diverticular disease may have a different pathogenic mechanism. Recent findings of histologic similarity between the colonic wall surrounding diverticula and biopsies of patients with inflammatory bowel disease suggest different pathogenic mechanisms of diverticula formation in young patients. In older people it is presumed to be weakening of the bowel wall. Abdominal symptoms persist after resection in up to 33% of cases and are attributed by most authors to coesxisitng irritable bowel syndrome. IBS would be expected in patients lacking inflammatory changes in the resected specimens. Over 90% of rsected bowel parts had histological signs of inflammation in our series; authors think IBS is unlikely cause for persistent complaints. Postoperative abdominal complaints are an independent risk factor for recurrent diverticulitis. It has been found that recurrence rates are lower if the total sigmoid had been removed and a rectal anastomosis made. They couldn't confirm this. Mean specimen lenght of 19.6 cm and 17.1 cm respectively did not significantly differ between recurrence and nonrecurrence groups; it seems the authors couldn't discern whether the lower cut was made in the rectum. Short lengths suggest those who did not have recurrences may have had good luck, as not much of the colon can have been removed. Hoever the authors find that 1/6 patients had recurrence of diverticulitis, which they think argues for more conservative treatment, especially if the goal is to avoid emergency surgery, as recurrent diverticulitis and complicated diverticulitis evidently don't have alot to do with each other. It is unclear how many of these patients had complicated diverticulitis. (I don't agree; I think that if 5/6 of the patients had their symptoms go away and not come back, that is a very good reason to do the surgery. That's a 17% recurrence rate; consistent with the literature - when the procedure was not done the right way)
New Paradigms in the Management of Diverticular Disease. Hall, J et al. Curr Probl Surg. 2010 Sep; 47(9): 680-735.
Very long review article about diverticulitis; includes very technical discussion of how diverticuli form, etc., that I've not seen elsewhere. His theories of development of diverticulitis are mechanical, as opposed to inflammatory. However, on page 691, they state that inflammation is a newly proposed theory. Supporting it, they review one study that reviewed 47 patients who underwent resection, and reported a syndrome of smoldering diverticulitis that occurred in patients with chronic left lower quadrant pain but did not have associated fever or leukocytosis. They go on to state that 7 of the 47 had previously undetected abscesses, and 76% had evidence of acute and chronic submucosal inflammation. More than 3/4 had resolution of symptoms after surgery (suggesting that nearly 25% did not). He mentions that Morton himself found no evidence of inflammation in 1/3 of his patients and concluded that his evidence was too weak to associate inflammation with diverticulitis. He goes on to discuss a syndrome with mixed aspects of inflammatory bowel disease and diverticulitis, also called segmental colitis, sigmoiditis, and diverticular colitis; as that syndrome is very stringently (and in my view unrealistically) defined its incidence is very low - 0.25 to 1.5% of colonoscopies performed. Then he discusses visceral hypersensitivity and post inflammatory neuronal damage - which I found that some think is part of the inflammatory process and some not; it accounts for the IBS-like syndrome. The large bowel nerves of people with attacks of diverticulitis are structurally, microscopically and chemically different than those of normal people.
He reports the widely cited statistics, specifically using a cohort of 502 patients, that most people who have complicated diverticulitis have it on their first attack, and adds that people with severe diverticulitis on CT scan are far more likely to have recurrent attacks after an initial attack treated with antibiotics (39% vs 14%). (To me, that suggests that if someone who intially had an uncomplicated attack has frequent more attacks, something more than usual is going on, and the CT scan may simply have missed the complication.) He discusses use of CT in detail but does not discuss its accuracy.
He discusses "emerging medical therapies". There has been increased interest in the use of immuno-modulatory agents in the management of diverticular disease. 5-ASA compounds and sulfazalazine are widely used in the management of inflammatory bowel disease. 5-ASA products alter DNA synthesis and cell cycle progression in lymphocytes. 5-ASA compounds are also thought to suppress leukotriene and prostaglandin synthesis, as well as decrease leukocyte adhesion, thus reducing proinflammatory states. 117,118
Because a low-grade proinflammatory state is the proposed mechanism underlying chronic diveriticular disease, a number of small trials have evaluated the effectiveness of mesalamine-like compounds. In virtually all of these studies the outcome of interest was symptom severity and change in bowel habits. In the original description of the use of mesalamine for the management of diverticulitis, Trespi and colleagues demonstrated that patients treated with rifaximin, ampicillin/sulbactam, and mesalamine had decreased symtomatology and were less likely to experience microhemorrhagic phenomenon. 119
Another study randomized patients with at least 2 episodes of acute diverticulitis to a rifaximin-only arm versus a rifaximin/mesalamine arm. Patients in the rifaximin/mesalamine arm demonstrated significantly improved bowel habits, episodes of recurrence, and symptom severity. 120
In another study, mesalamine alone was compared with rifaximin alone. Although there were only 170 patients in the study, the authors compared 11 outcome variables including nausea, emesis, dysuria, general illness, fever, abdominal tenderness, diarrhea, tenesmus, bloating, and abdominal pain/discomfort. Patients treated with mesalamine had statistically significant lower global score than patients treated with rifaximin alone. These authors concluded that mesalamine is an effective medication for preventing recurrence of diverticulitis and maintaining remission. 121
Other authors have demonstrated that daily treatment with mesalamine is more effective than cyclic treament. 122
I found and have included all of the references - or in the case of the Tursi et al studies, on which they have published maybe 50 articles, a suitable group of them.
Other studies have examined rifaximin, an expensive antibiotic used to prevent traveller's diarrheah, and lactobacilli, in combination with each other and with 5-ASA, and found rifaximin highly effective at stopping repeat attacks, and probiotics very helpful. It did not matter what kind of probiotics were used; one study used nonpathogenic e-coli.
When to do resections in patients with complicated disease is controversial. It appears from the discussion that some think that the 40% rate of recurrent sepsis in patients who have ever had to have an abscess drained, is a reason to do resection, but many do not think so. There is also controversy about whether the things should be drained, or merely treated with antibiotics; smaller ones often resolve with antibiotics. They recommend a routine strategy of bowel rest, antibiotics and careful observation.
For uncomplicated diverticulitis they recommend an individualized approach that looks at many factors including the number of attacks, based on the recommendations of the American Society of Colo-Rectal Surgeons, and others.
"The proximal resection margin should be in soft pliable bowel and it is not necessary to resect all proximal diverticula. The distal resection margin is the proximal rectum since anastomosis to the distal sigmoid is associated with a higher risk of recurrent diverticulitis. ... The most established risk factor for recurrent diverticulitis is the level of anastomosis. Although diverticulits may only involve a portion of the sigmoid colon, the entire sigmoid should be resected and anastomosis performed to the proximal rectum. " Two studies mentioned. Benn et al, 501 patients who had sigmoid rsection, recurrence was 6.7% with anastomosis to proximal rectum and 12.5% with anastomosis to distal sigmoid colon. Thaler and colleagues used regression analysis to find that those with a colosigmoid anastomosis had a 4x higher risk of recurrence than those with a colorectal anastomosis.
Several surgical procedures are detailed, with detailed instructions on how to decide what to do and how to mobilize and how to attach to various structures.
NSAID use is twice as common in patients with diverticular disease as those without it. Increased incidence of both uncomplicated and complicated diverticular disease. 23% higher risk of perforating diverticulitis in patients who took NSAIDs regularly compared to patients with diverticulitis who did not take NSAIDs. NSAID use also much higher in patients admitted with diverticular disease than in the population as a whole. Those patients 4 times more likely to develop perforated diverticulitis than patients with no history of NSAID use.
No difference found based on differences in caffeine consumption.
Diverticular Disease: Reconsidering Conventional Wisdom. (Abstract) Anne F. Peery, Robert S. Sandler. Division of Gastroenterology and Hepatology, Dept of Medicine, U North Carolina, Chapel Hill, NC.
Colonic diverticula are common in developed countries and complications of colonic diverticulosis are responsible for a significant burden of disease. Several recent publications have called into question long-held beliefs about diverticular disease. Contrary to conventional wisdom, studies have not shown that a high-fiber diet protects against asymptomatic diverticulosis. The risk of developing diverticulitis among individuals with diverticulosis is lower than the 10% to 25% proportion that commonly is quoted, and may be as low as 1% over 11 years. Nuts and seeds do not increase the risk of diverticulitis or diverticular bleeding. It is unclear whether diverticulosis, absent diverticulitis, or overt colitis is responsible for chronic gastrointestinal symptoms or worse quality of life. The role of antibiotics in acute diverticulitis has been challenged by a large randomized trial that showed no benefit in selected patients. The decision to perform elective surgery should be made on a case-by-case basis and not routinely after a second episode of diverticulitis, when there has been a complication, or in young people. A colonoscopy should be performed to exclude colon cancer after an attack of acute diverticulitis but may not alter outcomes among individuals who have had a colonoscopy before the attack. Given these surprising findings, it is time to reconsider conventional wisdom about diverticular disease.
Note: This section relies on the research on inflammation below under prescribing Asacol. This is not the same thing as diverticulitis, like diverticulosis, as part of the same disease process as irritable bowel syndrome.
Researchers describe new form of irritable bowel syndrome. (Abstract) MedicalXpress.
Abstract of report by Breenan Spiegel, Assc Prof of Medicine at David Geffen School of Medicine, about "Post-Diverticulitis Irritable Bowel Syndrome", in Clinical Gastroenterology and Hepatology, 5 Sep 2013. Compared 1000 patient records, including matched patents with and without acute diverticulitis. The groups were followed for "many" years for irritable bowel syndrome and mood disorders. Found that "many" patients experience symptoms long after they got over diverticulitis. Suggests that diverticulitis is a chronic disease, or atleast leaves residual damage that causes an inflammatory process. The authors think that the changes are neurological, and have a psychological and a physiological theory of how this leads to depression. (Breenan Spiegel belongs to LL Strate's team, and coauthored Diverticulitis as a chronic illness: evolving epidemiologic and clinical insights")
Increased Risk for Irritable Bowel Syndrome After Acute Diverticulitis (received article from author) Erica Cohen et al, includes Brennan Spiegel, appears to report on the same study. Request copies from Brennan Spiegel, Dept of Gastroenterology, VA Medical Center, LA. email@example.com Clinical Gastroenterology and Hepatology, 11 (12), Dec 2013, pp 1614-1619.
Probably the same study as above. Examined long term bowel dysfunction and affective disorders in subsequent to having diverticulitis. Examined 1102 VA patients who had diverticulitis and 1102 carefully matched VA patients who did not have diverticulitis, followed for average of 6.3 years. Those who had had diverticulitis were 4.7 x more likely to later be diagnosed with IBS, 2.4x more likely to be diagnosed with a functional bowel disorder, and 2.2x more likely to develop a mood disorder, than controls.
This article appears to be part of a debate; there is also an article titled, "Limited evidence of postdiverticulitis irritable bowel syndrome".
Diverticular disease is often conceived as consisting of acute attacks surrounded by periods of clinical silence; this is not true for everyone. Recent studies have reframed the paradigm of diverticular disease from an acute surgical illness to a chronic disorder with symptoms persisting for a long time. Symptomatic uncomplicated diverticular disease implies that chronic gastrointestinal symptoms co-occur with diverticulitis in the abscense of overt complications or macroscopic inflammation. Research suggests a potential role for low-grade peridiverticular inflammation. Evolving research implicates altered motility and altered intestinal microbiota, in a pathophsyiologic picture similar to irritable bowel syndrome. Far from a self-limited episode, actue diverticulitis may become a chronic disorder in some patients.
Diverticulosis appears to exist on a continuum with irritable bowel syndrome. More people with diverticulosis have frequent lower abdominal pain and altered bowel habits than people without it.
The development of PDV-IBS is biologically plausible. Research has shown potentially shared pathophysiologic mechanisms between IBS and symptomatic diverticular disease. There are reports that some IBS patients show low-grade colonic inflammation in the absence of macroscopic colitis. Moreover, inflammation may alter gastrointestinal reflexes, amplify visceral sensitivity, render the bowel more susceptible to negativeeffects of microbiota, and alter motility in IBS. Similarly, some small studies have shown chronic microscopic infammation in biopsy specimens taken from within and around diverticula inpatients with symptomatic diverticular disease. Similar to IBS, patients with diverticular disease have heightened visceral pain perception in response to luminal distension comparedwith controls. Another putative mechanism of chronic diverticular disease involves shifts in intestinal microbiota leading to chronic inflammation, similar to theoretical models for IBS. Several lines of evidence support a potential association be-tween the intestinal microbiota and diverticular disease. Gutdirected antibiotics may reduce attacks of recurrent diverticulitis and treat gastrointestinal symptoms in patients with symptomatic diverticular disease. Data also have shown modest benefits of antibiotics in IBS. Low dietary fiber intake, a putative risk factor for chronic diverticular disease and IBS with constipation, is also associated with alterations in the gutmicrobial composition; these changes might lead to bacterial overgrowth or even precipitate acute diverticulitis. In a study of 90 patients with a history of acute diverticulitis, 60% met criteria for small intestinal bacterial overgrowth, a condition also purported to occur in many patients with IBS.
Finally, there is a strong and consistent link between acute bacterial gastroenteritis and PI–IBS, a condition in which chronic bowel symptoms persist long after the infectious agent has cleared. Analogous to the postinflammatory model of PI–IBS, it is possible that acute diverticular inflammation may trigger PDV-IBS.
Postinfectious irritable bowel syndrome. (abstract) Robin Spiller, Klara Garsed. Gastroenterology. 136(6) 1797-1988.
Approximately 1 in ten patients with irritable bowel syndrome (IBS) believe their IBS began with an infectious illness. Prospective studies have shown that 3% to 36% of enteric infections lead to persistent new IBS symptoms; the precise incidence depends on the infecting organism. Whereas viral gastroenteritis seems to have only short-term effects, bacterial enteritis and protozoan and helminth infections are followed by prolonged postinfective IBS (PI-IBS). Risk factors for developing PI-IBS include, in order of importance, prolonged duration of initial illness, toxicity of infecting bacterial strain, smoking, mucosal markers of inflammation, female gender, depression, hypochondriasis, and adverse life events in the preceding 3 months. Age older than 60 years might protect against PI-IBS, whereas treatment with antibiotics has been associated with increased risk. The mechanisms that cause PI-IBS are unknown but could include residual inflammation or persistent changes in mucosal immunocytes, enterochromaffin and mast cells, enteric nerves, and the gastrointestinal microbiota. Adverse psychological factors contribute to persistent low-grade inflammation. The prognosis for patients with PI-IBS is somewhat better than for those with unselected IBS, but PI-IBS can still take years to resolve. There are no specific treatments for PI-IBS; these should be tailored to the predominant bowel disturbance, which is most frequently diarrhea
Recent studies have overthrown the dogma that irritable bowel syndrome is characterized by no abnormality of structure by demonstrating low-grade lymphocytic infiltration in the gut mucosa, increased permeability and increases in other inflammatory components including enterochromaffin and mast cells. Furthermore, increased inflammatory cytokines in both mucosa and blood have been demonstrated in irritable bowel syndrome. While steroid treatment has proved ineffective, preliminary studies with probiotics exerting an anti-inflammatory effect have shown benefit.
The study of post-infectious irritable bowel syndrome has revealed the importance of low-grade inflammation in causing irritable bowel syndrome symptoms. It has suggested novel approaches to irritable bowel syndrome including studies of serotonin and histamine metabolism which may be relevant to other subtypes of the disease.
Role of infection in irritable bowel syndrome. (abstract) Robin C. Spiller. Journal of Gastroenterology. January 2007, 42(17), Suppl, 41-47.
Infection by pathogenic organisms leads to mucosal damage and disruption of the gut's extensive commensal flora, factors which may lead to prolonged bowel dysfunction. Six to 17% of unselected irritable bowel syndrome (IBS) patients believe their symptoms began with an infection, which is supported by prospective studies showing a 4%–31% incidence of postinfectious IBS-(PI) sfollowing bacterial gastroenteritis. The wide range of incidence can be accounted for by differences in risk factors, which include in order of magnitude; severity of initial illness > bacterial toxigenicity > hypochondriasis, depression and neuroticism, and adverse life events in the previous 3 months. PI-IBS has been reported after Campylobacter, Salmonella, and Shigella infections. Serial biopsies after Campylobacter jejuni gastroenteritis show an initial inflammatory infiltrate, with an increase in enterochromaffin (EC) cells, which in most cases subsides over the next 6 months. Those who go on to develop IBS show increased numbers of EC and lymphocyte cell counts at 3 months compared with those who do not develop IBS. Interleukin-1β mRNA levels are increased in the mucosa of those who develop PI-IBS, who also show increased gut permeability. Recover can be slow, with approximately 50% still having symptoms at 5 years. Recent studies suggest an increase in peripheral blood mononuclear cell cytokine production in unselected IBS, an abnormality that may be ameliorated by probiotic treatment. The role of small-bowel bacterial overgrowth in IBS is controversial, but broad-spectrum antibiotics do have a temporary benefit in some patients. More acceptable long-term treatments altering gut flora are awaited with interest.
Post inflammatory damage to the enteric nervous system in diverticular disease and its relationship to symptoms. J. Simpson. Neurogastroenterology and Motility. 21(8), pp 847-e58, Aug 2009.
A previous survey of symptoms in patients with diverticulitis attending University Hospital Nottingham, showed that previous episodes of presumed acute diverticulitis doubled the risk of recurrent, often daily, transient (1–3 h) bouts of pain.2 A follow up study using multivariable analysis identified a history of acute diverticulitis (odds ratio 3.98) and a raised score on the Hospital Anxiety and Depression Scale (odds ratio 2.40) as the best predictors of recurrent pain.3 Several recent studies have documented that pain in diverticulitis is related temporally to contractions in the sigmoid colon, particularly high pressure propagated contractions (HAPCs).4,5 This is most obvious after a meal,6 when many patients experience pain. However, there is also an element of visceral hypersensitivity, as HAPCs of similar amplitude do not evoke pain in controls.5 Recent studies using rectal balloon distension confirm visceral hypersensitivity in symptomatic but not asymptomatic diverticular disease.7
These clinical observations have been supported by numerous animal studies which show long lasting visceral hypersensitivity associated with pronounced circular muscle hypertrophy following induction of colitis with the hapten, trinitrobenzene sulphonic acid (TNBS), an effect which can last more than 100 days.8,9 Given the similarities with the pathology in diverticular disease which also exhibits muscular hypertrophy and hypersensitivity, we hypothesized that in painful diverticular disease postinflammatory changes in enteric nerves and muscles contribute to the development of symptoms.
Previous studies in ulcerative colitis and Crohn’s disease suggest postinflammatory alterations in tackykinins and VIP.10–14 Our own studies using the animal model of TNBS colitis have shown that this induces a remodelling of enteric nerves and a change in the neurochemical coding with increased expression of a number of markers of neural injury including tachykinins, pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal peptide (VIP) and galanin in both mucosa and myenteric plexus.15 These mucosal changes gradually returned to normal over 14 weeks apart from a persistent elevation of mucosal galanin. However the increase in myenteric and mucosal tachykinins substance P (SP) and neuropeptide K (NPK) persisted for at least 14 weeks as did the increase in circular muscle thickness. These studies suggested that mucosal tachykinins and galanin might be good mucosal markers of both previous postinflammatory neural damage and persistent increase in myenteric tachykinins, which might in turn relate to visceral hypersensitivity as recent animal studies have suggested.16–18
As in most cases patients do not come to colonic resection, one of the aims of our study was to validate the use of the more readily available mucosal markers as an indication of neuropeptide changes within the myenteric plexus. With this aim in mind, we undertook two studies. The first used colonic specimens from patients undergoing colonic resection for both acute and chronic diverticular disease and examined how the changes observed in myenteric plexus related to those in the mucosa. The second part of our study compared mucosal biopsies from patients with symptomatic and asymptomatic diverticular disease for the expression of the neuropeptides, SP, NPK, PACAP, VIP and galanin which we had previously shown to change their expression after acute inflammation.
Resection specimens from patients with colonic diverticula were studied. Our control group, Group A had undergone a colonic resection for a non-obstructing colonic malignancy or polyp. Group B (acute diverticulitis; AD) had undergone emergency colonic resection for acute perforated diverticular disease with associated peritonitis. Sections demonstrating diverticulitis were selected. Group C (chronic complication of diverticular disease; CD) had undergone an elective colonic resection for a chronic inflammatory complication of diverticular disease, namely stricture, fistulation or abscess formation.
The microscopic damage score in Group A specimens was 0 (normal) compared with 4.7 ± 0.26 (P < 0.0001) in Group B specimens which demonstrated acute transmural inflammation with marked ulceration. Group C specimens demonstrated a spectrum of histological changes from minor focal inflammation to chronic inflammatory changes with fibrosis, microscopic damage score being 2.1 ± 0.43, P < 0.0001 compared with both Groups A and B. There was also significant muscle thickening in all the diseased specimens,
Immune markers PGP9.5 and NFP was often found, with muscle thickening, and evidence of physical disorganization of nerve fibers.
The CD specimens showed significant increases in the immunoreactivity of SP, NPK and galanin in both mucosal and circular muscle layer compared with controls. Vasoactive intestinal polypeptide immunoreactivity was also significantly increased compared with controls, but only in the circular muscle layer. Although there were rises in PGP9.5 and NFP in the circular muscle of AD specimens, galanin was the only neuropeptide found to demonstrate such a rise in this part of the results (0.02% in controls vs 0.07% in AD specimens, P < 0.0001).
Expressing the neuropeptide stains as a % of the morphological marker PGP9.5 allows detection of specific upregulation of the different markers. When this is done in the mucosa, only galanin showed a specific increase while other markers such as VIP and PACAP actually declined (Table 2, Fig. 4). By contrast in the muscle layer, there was a specific increase only in tachykinin staining (SP and NPK) in group C when compared with control values. There was also a specific rise in galanin within the circular muscle in the AD group and a significant fall in VIP and PACAP but these all were normal in Group C.
Difference in neural staining between symptomatic and asymptomatic patients The % area staining of PGP9.5 and NFP in the lamina propria was found to be equal in both groups studied (see Table 3). However, striking differences were found in the staining for the neuropeptides under study. The level of VIP, galanin, SP, PACAP and NPK staining was significantly increased within the mucosal nerves of the symptomatic compared with asymptomatic patients when expressed by the % area staining of lamina propria. In the combined study population, there was no correlation between galanin and SP expression and frequency of pain. However, there was a significant correlation between the expression of galanin in the mucosal nerves and the frequency of defecation. (Spearman ρ = 0.38, P = 0.016).
Our studies clearly show important alterations in the enteric nervous system which can be related to the presence of symptoms in patients with diverticulitis. We report for the first time, a selective increase in a range of neuropeptides, the most notable increase being shown by galanin and the tachykinins. Importantly, in the chronic phase of the illness, the total amount of nerves as shown by staining for the pan-neuronal markers PGP 9.5 and neurofilament protein were unchanged in the mucosa, while levels of galanin were increased nearly 10-fold in symptomatic patients.
Interpretation of the significance of these findings is considerably aided by reference to the first part of the study in which full thickness sections of the diverticular containing colon were available. These show a close parallel between the neuropeptide changes in the mucosa and that within the circular muscle layer. As these were archival material, inevitably the clinical history was limited to what was recorded in the notes and thus linkage to clinical features could not reliably be performed. However, the main point of this part of the study was to establish the link between mucosal and deeper changes in the muscular layers. We were able to show that substance P and neuropeptide K were significantly increased in both mucosa and circular muscle layer of patients with chronic diverticular disease. Changes in mucosal galanin were likewise reflected by changes in the circular muscle layer, though interestingly VIP was not increased in the mucosa thought it was increased twofold in the circular muscle layer. Detailed morphology of the nerves suggested a very active process of remodelling. Both mucosal and circular muscle layer PGP9.5 was increased as was the nerve density within the longitudinal muscle. The muscle layer showed an increase in thickness (1.3-fold) so the total amount of nerves calculated from nerve density times muscle layer thickness would have been increased three- to fourfold. Thus as muscular hypertrophy occurs, so new nerves sprout to innervate them. This process, together with structural distortions found in chronic diverticular disease, may well account for the increased nerve angulation that we noted. In patients operated on for acute diverticulitis, there was an increase in small diameter nerves, though in patients with more chronic disease this was no longer a feature. This would be compatible with sprouting of new nerves during recovery from acute inflammation as is observed for example in the reparative process in dental abscesses 26 and also in the TNBS colitis model.27
Our observations of increased mucosal tachykinins agree with numerous studies suggesting that both in animals and man, mucosal inflammation initially destroys nerves but is then followed by a proliferation of tachykinin-containing axons. These are an important part of the inflammatory response, mediating both visceral hypersensitivity, vasodilatation and inflammatory changes via axonal reflexes. Tachykinin antagonists inhibit visceral hypersensitivity and in some models inhibit inflammation markedly.28,29 The changes in peripheral nerves are also paralleled by changes within the dorsal root ganglia30 and are likely to contribute to visceral hypersensitivity, as tachykinin antagonists can inhibit colitis induced visceral hypersensitivity.16,18 This is supported by the increased expression of SP in another condition of postinflammatory hypersensitivity, namely dental caries, where the % of PGP 9.5 positive nerves in dental pulp co-staining for SP has been shown to correlate with the occurrence of pain.31
he decrease in 5HT staining enterochromaffin cells has not been previously reported in diverticular disease but reduced serotonin concentration has been reported in inflammatory bowel disease.32 By contrast in patients with postinfective irritable bowel syndrome following a Campylobacter enteritis an increased turnover was noted with reduced 5HT content per cell and increased cell counts.33 Recent animal studies suggest that whether inflammation decreases or increases enterochromaffin cells depends on whether the immune response shows Th1 or Th2 predominance.34 Reduced enterochromaffin cell counts have been reported in Citrobacter rodentium infections35 associated with a Th1 predominant immune response while Trichinella spiralis infection associated with a predomiantly Th2 response causes an increase.36 Thus interpretation of this new finding in diverticular disease will require better characterization of the immune response profile in this particular condition.
The cause of increases in the neuropetide markers is not entirely clear but increased VIP has certainly been noticed in Crohn’s colitis.12 Both VIP and PACAP have general anti-inflammatory effects and may be part of the down regulation of inflammation.37 Vasoactive intestinal polypeptide also controls vasodilatation in the rectum and may be an important part of the mucosal defence,38 being markedly increased after radiotherapy affecting the rectal mucosa.39
The increase in galanin in both mucosa and circular muscle layer of patients with chronic diverticular disease in Study 1 and in the mucosa in symptomatic patients in Study 2 was the most striking abnormality. Galanin has a range of activities which are likely to be different in specific parts of the enteric nervous system. Galanin receptors coupled to inhibitory G proteins are predominately inhibitory in the CNS. Galanin is often co-secreted with substance P and calcium gene related peptide (CGRP) in sensory neurones and transported to the superficial lamina of the dorsal horn where it has a possible antinociceptive role. Upregulation in the circular muscle layer including the myenteric plexus may well have important effects on both spinal afferents and motor responses since galanin-1 receptor knockout mice fail to show increased spinal nociceptive reflex excitability in response to inflammation.40 Galanin has an important role in the increased intestinal chloride secretion which develops in response to inflammation,41 which upregulates the galanin-1 receptor acting via NFκB42. The persistent increase we observed in galanin in the mucosal biopsies did correlate with a significant increase in diarrhoeal symptoms and frequency of defecation, which may be causally relevant
Diverticular disease of the colon: New perspectives in symptom development and treatment. Antonio Colecchia, et al. U Bologna, Italy. World Journal of Gastroenterology 2003 Jul; 9(7): 1385-1389.
Hypertrophic muscle and elastin accumulation may contribute to the development of diverticula.
They pose a model in wihch intestinal bacterial overgrowth leads to mucosal low-grade inflammation, wihch leads to abnormal activation of intrinsic and extrinsic primary afferent neurons, which leads to neural and muscle dysfunction, which leads to abdominal symptoms.
The causes of symptom development, in some patients, are still unclear. Since it has been observed that DD patients who have a history of diverticulitis have more episodes of recurrent abdominal pain and impaired bowel function[6, 51, 52], a possible role of previous episodes of intestinal inflammation may be hypothesised. This finding is not unlike that which has been recently demonstrated in other gastrointestinal diseases such as infectious enteritis and inflammatory bowel disease[53, 54] and, as also speculated in irritable bowel syndrome (IBS). In these patients, the presence of a chronic, low-grade intestinal inflammation would induce a sensory-motor dysfunction, leading to symptom development and/or persistence[53-56].
Changes in intestinal microflora could be one of the putative mechanisms responsible for low grade inflammation, at least in IBS . In patients with DD, bacterial overgrowth may be present. This bacterial overgrowth aided by the faecal stasis inside the diverticula, could contribute to chronic low-grade inflammation which sensitises both intrinsic primary efferent and extrinsic primary afferent neurons. These alterations could lead to smooth muscle hypertrophy, and increased sensitivity to abdominal distension[56,58], and finally, to symptom development. This hypothesis is based mainly on experimental studies, investigation in man, being limited at present. However, an increased level of the neuropeptide substance P, which may be related to impaired visceral sensation, has been demonstrated in patients with DD with abdominal pain but without inflammation. This finding is not unlike that observed by Di Sebastiano et alwho documented a role of neuroproliferation within the appendix, associated with an increased concentration of substance P and vasoactive intestinal polypeptide, in the pathophysiology of right iliac fossa pain in the absence of inflammation. Moreover, in patients with diverticulitis, abnormal nerves with axonal sprouting have been observed, suggesting previous injury. These findings would appear to be compatible with post-inflammatory neural and muscle dysfunction, probably induced also by intestinal bacterial overgrowth, which would contribute to symptom development.
Further studies, both experimental and inman, are obviously needed to confirm the pathogenetic role (which is summarized in Figure 1) of intestinal infection and low grade inflammation, in the development of symptoms in patients with DD.
Role of nerves in enteric infection. R.C. Spiller. Gut. 2002 December 51(6): 759-62.
Spiller explains how and why the gut nerves aid defense against disease.
The gut is richly innervated containing approximately 108 neurones, as many as the entire spinal cord. Nerves interacting with enteric infections can be conveniently divided into four groups: (1) intrinsic enteric, (2) extrinsic afferent, (3) extrinsic efferent, and (4) CNS. Intrinsic nerves comprise the bulk of gut nerves. Their cell bodies lie in the submucous and myenteric plexuses, which can be simplistically thought of as controlling mucosal secretory and longitudinal/circular muscle functions, respectively. Predominant excitatory neuromediators are acetylcholine, substance P, 5-hydroxytryptamine (5-HT), and vasoactive intestinal peptide (VIP), with nitric oxide (NO) being the main inhibitory mediator. The extrinsic sensory nerves have cell bodies in the dorsal root ganglia of the spinal cord and the nodose ganglia. Major neuromediators are calcitonin gene related peptide (CGRP), substance P, and glutamine. Their main function is higher order integration of digestion via their input to the brain centres which control such functions as gastric emptying, eating behaviour, pancreaticobiliary secretion, and colonic transit via extrinsic motor nerves to the gut. Postganglionic sympathetic (adrenergic) neurones exert a largely inhibitory influence on secretion and inhibition of this sympathetic “brake” increases the secretory response. Finally, the relevant CNS nerves responding to infection are mainly in the brainstem from where they can influence extrinsic motor nerve output. We can consider the role of these nerves in infection under five major functional headings (see table 1 ).
The gut mucosa contains numerous free nerve endings whose cell bodies lie in the submucous and myenteric plexuses. Intrinsic primary afferent nerves (IPANs) have free nerve endings in the mucosa and express a number of receptors, including 5-HT1p.1 They form the afferent arm of reflexes which control secretion and motility. Stimulating them by stroking or puffs of nitrogen elicits secretory responses which involve cholinergic interneurones and cholinergic or VIPergic secretory effector neurones.2 Infecting organisms stimulate IPANs both directly and indirectly; the neural networks then spread the secretory response, changing it from a localised response to one which is widespread and capable of flushing the entire gut. This amplification is vital for luminal stimuli to activate the main secretory cells which lie deep in the crypts and hence are not directly exposed to luminal factors. The importance of this amplification can be seen from the effect of VIP antagonists. These block the effector neurones and virtually abolish the secretory response to cholera toxin (CT) in an intact animal,3 in spite of the fact that the local secretory effect of CT on individual enterocytes, which acts via stimulation of adenyl cyclase, is probably unaffected.
Many disease causing microorganisms stimulate teh gut nerves to flush them out, partly as an adaptive mechanism of the invaders. Gut nerves also react in ways that help clear the body of the invaders. Infection also triggers the production of white blood cells and immune system chemicals, including TNF-a and leuikotriene. Nerves interact with the production of these chemicals, which also help to control the nerves. The effect is to clear the germs from the body. For instance, substance P receptors are upregulated on epithelial cells and other tissue; enhances immune chemical production.
It can take the neurotransmitters a long time to return from normal from the state that flushed germs and toxins from the body.
While most of the inflammatory response rapidly subsides, gastrointestinal function may remain disturbed for months and in some cases years. Postinfectious bowel dysfunction is seen in up to 25% of patients following Campylobacter enteritis27,28 and is characterised by persistent low grade chronic mucosal inflammation28 and increased numbers of serotonin containing enteroendocrine cells.29 Persistent changes in gut nerves and muscle are seen in mice following Trichinella spiralis infection. This animal model of postinfectious bowel dysfunction has been extensively studied. It is associated with visceral hypersensitivity, muscle wall thickening, and increased responsiveness to cholinergic stimuli. There is an increase in substance P labelled neurones30 and enhanced afferent firing in response to colorectal distension. Mucosal injury as in chemical colitis has been shown to induce initial nerve lost followed by hyperinnervation, the new nerves showing significant differences in morphology and density.31 Changes such as this may also underlie the features of the postinfectious syndrome described following bacterial enteritis.27,28 These patients with “postinfective irritable bowel syndrome” suffer from diarrhoea and abdominal cramps and are characterised by accelerated transit and increased sensitivity to visceral distension. These changes may be adaptive to individuals living in areas where bacterial infection is common as they are likely to accelerate transit and hence
there are also acute behavioural responses which include thermogenesis, anorexia, lethargy, and withdrawal from normal behaviour, all responses designed to inhibit pathogen survival and divert the host’s energy to fighting infection. Many of these behavioural responses are mediated by cytokines such as interleukin 1β, interleukin 6, TNF-α, and interferon which are initially produced locally at the site of inflammation where they stimulate afferent nerves and are later produced in the brain.32
Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorders. Robin Spiller. Neurogastroenterology and Motility. Published online, 6 Jul 2007. 19 (Issue Suppl s2, 25-31, Aug 2007.
Serotonin (5-hydroxytryptamine, 5-HT) is present in abundance within the gut, most stored in enterochromaffin cell granules. It is released by a range of stimuli, most potently by mucosal stroking. Released 5-HT stimulates local enteric nervous reflexes to initiate secretion and propulsive motility. It also acts on vagal afferents altering motility and in large amounts induces nausea. Rapid reuptake by a specific transporter (serotonin transporter, SERT) limits its diffusion and actions. Abnormally increased 5-HT is found in a range of gastrointestinal disorders including chemotherapy-induced nausea and vomiting, carcinoid syndrome, coeliac disease, inflammatory bowel disease and irritable bowel syndrome (IBS) with diarrhoea (IBS-D), especially that developing following enteric infection. Impaired SERT has been described in IBS-D and might account for some of the increase in mucosal 5-HT availability. 5-HT3 receptor antagonists inhibit chemotherapy-induced nausea and diarrhoea associated with both carcinoid syndrome and IBS. While IBS-D is associated with increased 5-HT postprandially, IBS with constipation (IBS-C) is associated with impaired 5-HT response and responds to 5-HT4 agonists such as Prucalopride and 5-HT4 partial agonists such as Tegaserod.
Inflammatory bowel diseases cause the same changes in serotonin and other neurotransmitters, that diseases do, with similar effects on bowel motility.
5-Hydroxytryptamine excess may be responsible for many features in IBS-D which would explain the success of 5-HT3 antagonists. It may also be true that in constipation, impaired release of serotonin contributes to the symptoms which may be alleviated in some patients by 5-HT4 agonists such as Prucalopride52 and Tegaserod.53 The precise site of action of these 5-HT-modulating agents remains uncertain as autoreceptors on the EC cells may themselves modulate endogenous 5-HT release. MKC-733, for example, has a very short half-life in plasma and is relatively poorly absorbed. Its prolonged duration of action may therefore be due to action of unabsorbed drug on 5-HT3 receptors on the mucosal EC cells as it passes down the gut. Similarly, Tegaserod, also has a bioavailability of only 10% implying that most of the drug is available to act locally on EC cells. Modulating the availability of 5-HT induces many changes with receptor desensitization which may reduce its efficacy with chronic usage. Nevertheless, both agonists and antagonists have proven clinical efficacy, though in both cases, the large number needed to treat suggests that improved ways are needed to target and characterize patients who are likely to respond. Simple biomarkers of responsiveness to these treatments remain to be discovered.
Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. R C Spiller et al. Gut 2000 47: 804-811 47(6) (The article is there but the abstract contains enough information.)
Post-dysenteric irritable bowel syndrome (PD-IBS) develops in up to 25% of patients followingCampylobacter enteritis. Our aim was to define the pathological basis of this subgroup of IBS.
Twenty one patients (group 1) underwent serial rectal biopsy and gut permeability testing following acute Campylobacterenteritis as did 10 PD-IBS patients (group 2) and 12 asymptomatic controls.
In group 1, enteroendocrine cell (EC) numbers were markedly increased initially and at six and 12 weeks (p<0.001) compared with controls. Gut permeability, as assessed by the lactulose/mannitol ratio, was significantly elevated, initially and at 12 weeks (p<0.005). CD3, CD4, and CD8 lymphocyte counts in the lamina propria and intraepithelial lymphocytes (IEL) were significantly increased initially compared with controls. At visit 1, EC numbers were positively correlated with CD3 counts (r=0.6, p=0.01). At one year, seven subjects (five with persistent loose stools) had rectal biopsies which showed significantly elevated EC, CD3, and IEL counts. In group 2, EC and IEL counts were significantly increased compared with controls (p<0.001), as was gut permeability (p<0.01).
Increased EC, T lymphocytes, and gut permeability are acute changes followingCampylobacter enteritis which can persist for more than a year and may contribute to PD-IBS.
Activation of the mucosal immune system in irritable bowel syndrome. Vinton S Chadwick. Gastroenterology 122(7) June 2002, 1778-1783.
These people looked into the role of inflamation in irritable bowel syndrome, but it appears to me that they actually suggest an underlying mechanism by which irritable bowel syndrome and diverticulitis might represent the same disease process. The above articles suggest that for instance what started as neurotransmitter imbalance could become an inflammatory process. It also appears that there is more than one form or course of IBS.
A role for the mucosal immune system in the pathogenesis of irritable bowel syndrome is suggested by its association with intestinal infections. Methods: To investigate this, we performed histologic and immunohistologic studies on colonoscopic biopsy specimens from 77 patients with symptoms satisfying the Rome criteria and 28 asymptomatic control patients. Results: Histologic assessment of biopsy specimens from symptomatic patients indicated 3 different groups. The first (38 of 77) had normal conventional histology; however, immunohistology showed increased intraepithelial lymphocytes (median, 1.8-fold; range, 1.74–1.86), lamina propria CD3+ cells (2-fold; range, 1.55–2.91), and CD25+ cells (6.5-fold; range, 4.98–8.13) compared with asymptomatic controls. The second group (31 of 77) had nonspecific microscopic inflammation and on immunohistology showed similar increases in lymphocyte populations (not significant vs. the uninflamed group) as well as increased numbers of neutrophil leukocytes and mast cells (P < 0.0001 vs. controls and the uninflamed group). The third group (8 of 77) fulfilled histologic and immunohistologic criteria for classic lymphocytic colitis. Conclusions: Examination of colonoscopic biopsy specimens from patients meeting the Rome criteria for a clinical diagnosis of irritable bowel syndrome showed subgroups with normal and abnormal conventional histology. All groups showed increased numbers of activated immunocompetent cells in the intestinal mucosa on quantitative immunohistology, implicating the mucosal immune system in pathogenesis.
Visceral hypersensitivity in symptomatic diverticular disease and the role of neuropeptides and low grade inflammation. Humes, DJ (Spiller) et al. Neurogastroenterol Motil 2012 Apr 24(4) 318-e163.
Recurrent abdominal pain is reported by a third of patients with diverticulosis, particularly those with previous episodes of acute diverticulitis. The current understanding of the etiology of this pain is poor. Our aim was to assess visceral sensitivity in patients with diverticular disease and its association with markers of previous inflammation and neuropeptides.
Patients with asymptomatic and symptomatic diverticular disease underwent a flexible sigmoidoscopy and biopsy followed 5-10 days later by visceral sensitivity testing with barostat-mediated rectal distension. Inflammation was assessed by staining of serotonin (5HT) and CD3 positive cells. mRNA levels of tumor necrosis factor alpha (TNF α) and interleukin-6 (IL-6) were quantitated using RT-PCR. Neuropeptide expression was assessed from percentage area staining with substance P (SP) and mRNA levels of the neurokinin 1 & 2 receptors (NK1 & NK2), and galanin 1 receptor (GALR1).
Thirteen asymptomatic and 12 symptomatic patients were recruited. The symptomatic patients had a lower first reported threshold to pain (28.4 mmHg i.q.r 25.0-36.0) than the asymptomatic patients (47 mmHg i.q.r 36.0-52.5, P < 0.001). Symptomatic patients had a higher median overall pain rating for the stimuli than the asymptomatic patients (P < 0.02). Symptomatic patients had greater median relative expression of NK1 and TNF alpha mRNA compared with asymptomatic patients. There was a significant correlation between barostat VAS pain scores and NK 1 expression (Figure 4, r(2) 0.54, P < 0.02).
Patients with symptomatic diverticular disease exhibit visceral hypersensitivity, and this may be mediated by ongoing low grade inflammation and upregulation of tachykinins.
Relative importance of abnormalities of CCK and 5-HT (serotonin) in Giardia-induced post-infectious irritable bowel syndrome and functional dyspepsia. Dizdar, V (and Spiller) et al. Aliment Pharmacol Ther 2010 Apr; 31(8): 883-91.
Background Post-infectious irritable bowel syndrome (PI-IBS) and functional dyspepsia (FD) have been described after both Campylobacter jejuni gastroenteritis and Giardia infection. After C. jejuni, there is increased rectal serotonin (5-HT)-containing EC cells and postprandial plasma 5-HT, while a pilot study suggested increased plasma cholecystokinin (CCK) after Giardia infection. Aim To determine changes in plasma and duodenal mucosal 5-HT and CCK in Giardia-induced PI-IBS. Methods A total of 32 patients previously infected with Giardia and 19 who had recovered fully (controls) completed symptom questionnaires. Endoscopic duodenal biopsies were obtained from all subjects and immunohistochemically stained for CCK, 5-HT and CgA containing entero-endocrine cells and mast cells. 5-HT content was also assessed. Twenty-one of 32 patients and 19 controls consumed a high-carbohydrate meal, while fasting and postprandial plasma CCK and 5-HIAA were measured. Results Post-infectious irritable bowel syndrome patients had increased numbers of CCK cells (P = 0.02), but lower numbers of EC cells (P = 0.009). Plasma CCK did not differ significantly between the groups, but correlated significantly with postprandial dyspepsia scores (r = 0.5, P = 0.05). PI-IBS patients had significantly lower plasma 5-HIAA, before and after meal (P = 0.05) as well as more dyspepsia (P < 0.0001) compared with recovered subjects. Conclusions Post-infectious bowel dysfunction following Giardia infection is associated with increased duodenal mucosal CCK. Postprandial dyspeptic symptoms correlate better with CCK than measures of 5-HT metabolism.
The Medical and Nonoperative Treatment of Diverticulitis. Heath Beckham and Charles B. Whitlow. Clinics in Colon Rectal Surg. 2009 August, 22(3): 156-160.
Study of outpatient treatment of 70 patients with acute diverticulitis up to and including abscess <2 cm in size. 10 days of oral 3rd generation cephalosporin. Study of 317 patients with diverticulits; 186 of 193 of the less seriously ill patients were successfully treated with no antibiotics. Two-agent treatment; fluoroquinolone or bactrim plus flagyl or clindamycin. Single-agent regimens include agumentin, doxycycline or moxifloxacin. Abscess < 2 cm in diameter may resolve with antibiotics alone. Other studies supported draining abscesses > 4 or 5 cm in size.
One study found that remission longer with probiotic than without it (14.1 months vs 2.43 months). In another study, on egroup got mesalamine daily, a second got probiotics plus vitamin B, and a 3rd received mesalamine plus probiotics; the 3rd group did better than the other two groups. Mesaaline alone has been shown to be useful in the treatment of uncomplicated diverticular disease.
What are the Different Antibiotics for Diverticulitis? WiseGeek
Another of the commonly prescribed antibiotics for diverticulitis is metronidazole. Like ciprofloxacin, it is a broad spectrum antibiotic and is often used for abdominal infections. Most patients tolerate metronidazole very well, with only mild side effects like loss of appetite, nausea, and headache, though some people can experience more severe effects such as numbness in their hands or feet.
Doxycycline is also one of the antibiotics for diverticulitis that doctors often use to treat patients. This drug is also a broad spectrum antibiotic and is very good for treating a wide variety of infections. It is well tolerated by the majority of people, though like many other antibiotics, it can lead to nausea or vomiting. It also tends to make people taking it sensitive to sunlight.
Cephalexin is another antibiotic that may be used to treat diverticulitis. This drug is in the class of antibiotics known as cephalosporins. These antibiotics are similar to penicillin, so people who are allergic to that medication may not be able to take cephalexin. Side effects are typically mild and similar to other antibiotics, and can include nausea, diarrhea, and headache.
When a patient is suffering from a severe infection from diverticulitis, intravenous antibiotics may be necessary. Patients will need to stay in a hospital so doctors can administer the drugs and monitor how effectively they are fighting the infection. A variety of different antibiotics may be used; some possibilities can include aztreonam, cefoxitin, or ertapenem.
What antibiotics are used to treat diverticulitis? Ehow. By Andrea Helaine, eHow Contributor.
Some of the common antibiotics prescribed for diverticulitis include ciprofloxacin, metronidazole, cephalexin and doxycycline. Antibiotics will help to kill bacteria that are present in the gastrointestinal tract.
Diverticular Disease - a patient's guide. FamilyDoctor.co.nz Dr. Cliff Tasman-Jones, Gastroenterologist.
Diverticulosis and diverticulitis. Health24. 10 February 2011.
Antibiotics are usually needed. Oral antibiotics are sufficient when symptoms are mild. Commonly prescribed antibiotics include ciprofloxacin, metronidazole, cephalexin and doxycycline. People with severe diverticulitis accompanied by high fever and pain are hospitalised and given a combination of three drugs intravenously.
Oral antibiotic therapy for acute uncomplicated diverticulitis. Paul S. Auerbach MD. Healthline. Sep 29, 2011.
Antibiotics (metronidazole, metronidazole combined with doxycycline, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, cefixime, ciprofloxacin, or cefpodoxime) should be administered if help is more than 24 hours away
Gastroenterology Associates. Diverticulitis.
When diverticulitis occurs, antibiotics are usually needed. Oral antibiotics are sufficient when symptoms are mild. Some examples of commonly prescribed antibiotics include: • ciprofloxacin (Cipro), • metronidazole (Flagyl), • cephalexin (Keflex), and • doxycycline (Vibramycin).
These focus on mesalzine (asacol, 5-ASA, 5-aminosalycilic acid), rifaxaimin, and probiotics. The use of asacol and probiotics comes from a new understanding of the nature of diverticulitis, especially diverticulitis that recurs and causes problems between attacks. The possiblity exists that people who ever get just one or two attacks of diverticulitis have a different disease; it is very common in medicine for several causes to cause diseases that have highly similar symptoms.
Mesalazine Aspirin variant aimed at colitis and diverticulitis. Asacol has the part of sulphasalazines removed that causes the worst side effects and causes reactions in people allergic to sulfa.
Rifaximin - Wikipedia article.
Rifaximin is a nonabsorbable antibiotic used to treat treaveler's diarrhea and hepatic encephalopathy. May be effective with irritable bowel syndrome.
Drug of the Month: Mesalazine Mesalzine or Asacol widely used for inflammatory bowel disease.
Potential for causing major kidney problems. Causes kidney and urinary tract reactions. People taking the drug more likley to develop nephritis - several months after starting treatment. Only 1/3 of cases can be reversed if diagnosis not made for 18 months. Other reactions include headaches, gut problems, nausea, abdominal pain, diarrheah, even exacterbate colitis.
Mesalazine. What Doctors don't tell you. Asacol is Smith Klein and French's answer to sulphasaline; has fewer side effects.
Diverticular disease and diverticulitis. Anish A Sheth et al. American J of Gastroenterology, 2008; 103: 1550-1556.
Colonic diverticula are pseudodiverticula because only two layers herniate. Visceral hypsensitivity caused by altered nerve regeneration and neurotransmitter release may result in increased pain. Low level mucosal inflammationmay cause chronic diverticular symptoms such as abdominal pain and diarrheah. Increase in relative levels of proinflammatory cytokines, TNF, triggered in part by altered peridivercular microfora, can give rise to mucosal inflammatoin, cause lower abdominal pain, bloating, etc. Recent studies demonstrate the efficacy of 5-ASA (aminosalicylate) compounds in symptom relief. Mesalamine signifcantly improved patients' symptoms and global sense of well being, and a decrease in recurrent episodes of diverticulitis. This suggests that low-level chronic inflammation plays a role in the development of acute diverticulitis.
Floch MH Management of diverticular disease is changing. World J Gastroenterol 2006 May 28; 12(20); 3225-8. (Article received from Dr. Floch.)
Cause of diverituclitis is uncertain, new observations and hypotheses suggest it is due to chronic inflammation in the bowel wall. Preliminary observations found microscopic colitis associated with mucosa of the colon adjacent to the diverticula. Their studies and others have found decreased and altered bacteria in subjects eating low fiber diet compared to those eating high fiber. Very mild colitis may occur and progress to more focal acute diverticulits. Sigmoid colon has smallest diameter of colon and different motility pattern. Very small number have all the endoscopic criteria for segmental colitis in addition to diverticula.
Anti-inflammatories and possibly antibiotics may be helpful in shortening the course and perhaps preventing recurrences.
Efficacy of mesalazine in the treatment of symptomatic diverticular disease. De Mario F. Dig Dis Sci. 2005 Mar; 50(3): 581-6. 170 outpatients, 4 schedules, with rifaximin and mesalazine, 2 dosages each. At baseline and after 3 months symptoms scored. The lowest scores were those on mesalazine.
Takes time for abscess to form so may be missed on initial CT.
Most guidelines treating elective or non-urgent cases recommend that the resection must remove all thickened diseased colon. It may be accepatble to retain proximal diverticular colon as long as the remaining bowel is not hypertrophied. In almost all cases, all of the sigmoid colon should be removed.
Clinical Review, Management of diverticulitis. Letters to editor. Clinical management of colonic diverticulitis. 30 June 2006. Antonio Tursi.
Comments on a review by Simon Janes et al on management of diverticulitis. Colonoscopy has yielded surprising results. A common finding in clinical practice that colonoscopy shows acute diverticular inflammation in patients complaining of mild nonspecific symptoms such as abdominal pain. A recent retrospective study of 5266 patients undergoing colonoscopy, 0.8% showed evidence of acute diverticular inflammation (erthethema and edema of the opening, pus, poolypoid mass, or granulation tissue in the diverticulum) but surprisingly none of them complained of symptoms. Quite common in clinical practice to find patients affected by diverticular disease with increased inflammatory indices (C reactive protein, etc.) and endoscopic picture of inflamed diverticula but no complications. Recent observations suggest understanding diverticular disease as a chronic inflammatory bowel disease. Low fiber diets result in altered microecology. Wheat bran alters anaerobic/ aerobic bacterial ratios. Altering the flora changes the immune response of the hose and the colon. Some recent studies reveal chronic inflammation associated to diverticula formation, and this chronic inflammation seems related to the severity fo the disease. (Naryan et al, Microscopic colitis as part of the natural history of diverticular disease, Morini et al, Epithelial cell proliferation of the colonic mucosa in diverticular disease, and Tursi, Epithelial cell proliferation of the colonic mucosa in different degrees of colonic diverticular disease) Altered microecology may be associated with decreased colon mucosal immune response, and evidence that chronic inflammation occurs in the mucosa associated with diverticula. Long term history of chronic inflammation may lead to diverticulitis.
Diverticular disease as a chronic illness: evolving epidemiologic and clinical insights. Lisa L. Strate et al. Am J Gastroenterol, 2012. (Article received from Dr. Strate.)
Patients with diverticular disease often experience lower health-related quality of life. For some patients true diverticulitis persists beyond overt flares and evolves into more chronic illness. Others develop irritable bowel syndrome symptoms in the setting of diverticular disease. If diverticular disease causes long-standing pain, discomfort, IBS symptoms, the condition may become a chronic bowel disorder in some patients. Traditional view of diverticular disease as a relatively asymptomatic disorder punctuated by acute, self-limited attacks of diverticulitis, reframed as potentially chronic illness with everyday outpatient practive implications. SUDD - subtype of diverticular disease with persistent abdominal symptoms without macroscopically overt colitis or diverticulitis. Chronic form of diverticulits. Patients have recurrent bouts of low-grade or overt diverticulitis. Small subset of patients develop SCAD - segmental colitis associated with diverticulitis.
Shifts in intestimal microbiota leads to chronic inflammation. Fecal statis may lead to chronic dysbiosis, promoting abnormal metabolits that cause longstanding inflammatoin. Rifaximin, may reduce attacks of recurrent diverticulitis and treat GI symptoms in patients with SUDD. Low fiber intake, associated with alterations in gut microibial composition. Study of 90 patients with history of acute diverticulitis, 60% appeared to have small bowel overgrowth using lactulose hydrogen breath test, though that isn't the most reliable test.
Visceral hypersensitivity. Heightened pain perception can affect the unaffected rectum as well as the sigmoid colon. An IBS-like process of hyperalgesia. The mechanism of hypersensitivity may related to increased neuropeptides and alterations in enteric innervation, a post-inflammatory consequence that persists after acute diverticulitis.37 . Simpson J , Sundler F , Humes DJ et al. P o s t i n fl ammatory damage to the enteric nervous system in diverticular disease and its relationship to symptoms . Neurogastroenterol Motil 2009 ; 21 : 847 – e58 . (exerpts below)
Growing body of literature indicates that low grade inflammation may have role in diverticular disease. 1976, Kealy et al, higher density of lymph node aggregates in macroscopically disease-free portions of colonic mucosa in subjects with vs without diverticulosis. Floch – abnormal pathology in random biopsies taken from 16 of 17 patients with diverticulosis, with most demonstrating lymphocytic infiltrate without overt colitis. Horgan et al, series of 930 patients undergoing surgery for SUDD but not overt diverticulits, chronic inflammation in and around diverticula in three-quarters of resected specimens. Extent of inflammation did not correlate well with symptom intensity. Together the evidence suggests that microscopic inflammation occurs in diverticulosis.
Altered motility has a role in IBS, and also associated with chronic symptoms in diverticular disease. Patients with SUDD displayed increased duration of rhythmic, low frequency, contractile activity, esp in segments bearing diverticulitis - spastic colon. Abnormal motor and propulsive activites. Patients with diverticulosis have fewer interstitial cells of Cajal - "pacemaker" cells of instestine, compared w normal controls. Aso shifts in chemical mediators.
Discusses fiber supplements, mesalamine (randomized controlled studies underway), rifaxin, probiotics. Lactobacillus acidophilus and bifidobacterium.
Preventing recurrent acute diverticulitis with pharmacological therapies. Antonio Tursi. Thereapeutic Advances in Chronic Disease. 2013. Not yet published, I got a copy from Dr. Tursi.
I note sources if I do NOT have them. The literature review in this paper is far more informative than the studies, which examined the effect of mesalazine on anything but recurrent diverticulitis.
Since for good reason conservative management has become the preferred approach to recurrent diverticulitis, Tursi focuses on identifying the correct approach to preventing relapses. In other words, one of his goals is to use pharmaceutical and lifestyle changes to avoid surgery where possible.
He discusses high fiber diet and the use of nonabsorbable antibiotics, of which only one, rifaximin, seemingly exists. Rifaximin and fiber alone results in a 10% rate of recurrence compared to 19% in those getting high fiber alone. Populations of disease causing bacteria in the gut recover within 2 weeks of ending antibiotic therapy.
5-Aminosalycilic Acid. The mechanisms that underlie the development of inflammation in diverticulitis may be similar to those that drive the inflammation in inflammatory bowel disease - cites Lahat et al, 2013, not an article I have. Five findings support this:
1. Diverticular disease shows an inflammatory infiltrate linked to the severity of the disease (Tursi et al 2008, 2010)
2. Diverticular disease shows an enhanced expression of proinflammatory cytokines as tumor necrosis factor a (Turse et al, 2012a, 2012b, Humes et al 2012) (I don't believe I cared what happens to tumor necrosis factor)
3. Obesity os a risk factor for diverticulits recurrence due to the pronflammatory effect of adipokynes and chemokynes (may once have been my problem but has not been in some time)
4. Both persisting endoscopic and histological inflammation have been identified as important risk factors for diverticulitis recurrence (Tursi et al 2013)
5. Up to 20% of patients complain of persistent abdominal pain after surgical treatment of diverticulitis, and quality of life for pateients is significantly worse after surgery. One hypothesis is that persistent symptoms are linked to increased neuropeptides in mucosal biopsies (a cause of irritable bowel like syndrome) which may reflect resolved prior acute inflammation and persistent chronic inflammation (Scarpa et al 2009, Bargellini et al 2013)
Mesalazine and its prodrug balsalizide, have been found effective in preventing diverticulitis recurrence (cites several of his own papers). Mesalazine also seems to be able to reduce endoscopic and histological inflammation after an attack of acute diverticulitis. (Smith et al 2012, Kruis et al 2013)
DIVA trial. mesalazine (Eudragit L enteric coating) after acute attack of diverticulitis. 1-year double blind, randomized trial. 117 patients with CT scan confirmed acute diverticuliits. Some received probiotics as well. Global Symptom score of 10 symptoms. Note that given the selection method, the great majority of these patients would have had no further problems without any treatment, since 4 of 5 patients never do. The difference was not statistically significant; however, scores were consistently lower for mesalazine at all timepoints, and the probiotics did not add to the effect.
Another study looked at the possible effect of mesalazine in the symptom scores of people who only had diverticulosis, and had never had diverticulitis, and unsurprisingly, they did not find one. This study is consistent with the idea that the inflammation that drives recurrent diverticulitis did not cause the diverticula to form. There were actually weak findings, consistent with the notion that mesalazine may do something for some process that is present to some degree or in some people at that point, and diverticula may often form as a result of irritabowel syndrome. .
Note: I haven't included all of Tursi et al's review articles.
Use of mesalazine in diveriticular disease. De Mario F et al. J Clin Gastroentrol. 2006 Aug; 40 Suppl 3: S155-9. Inflammation plays a role in all forms of diverticular disease. Inflammation seems generatied by prinflammatory cytokines, reduced ant-inflammatory cytokines, and enhanced intramucosal synthesis of nitric oxide. Mechanims of action of mesalezine not well understood. Inhibits factors of the inflammatory cascade (such as cyclooxygenase) and free radicals, antioxidant effect. Some recent studies confirm efficacy in diveritculitis both in relief of symptoms in uncomplicated forms and prevention of recurrence of symptoms and main complications.
Prevention of complications and sympotmatic recurrences in diverticular disease with mesalazine: a 12-month follow-up. Comparato G et al. Dig Dis Sci 2007 Nov; 52 (11): 2934-41. Efficacy of mesalazine for relief of symptoms of uncomplicated diverticulitis. 268 people; random controlled, 4 treatment schedules. Some got only rifaxim, two doses, some got mesalazine instead, two doses, noone got none. Those treated with mesalazine had fewer symptoms than those treated with rifaximin. Cyclic administration; 800 mg bid. caused greater improvement than smaller doses.
Mesalazine and/or Lactobacillus casei in preventing recurrence of symptomatic uncomplicated diverticular disease of the colon; a prospective, randomized, open-label study. Tursi, A et al. firstname.lastname@example.org 90 patients previously stabilized on 800 mg/d rifaximin plus mesalazine 2.4 tg/d for 01 d, followed by mesalazine 1.6 g/d for 8 wk, 12 month followup. Mesalazine and L. Casei DG. Both are effective in preventing recurrence of symptomatic uncomp-licated diverticular disease. It does not say how they compared their success rates to rates of recurrent symptoms if they did nothing.
Mesalzine for diverticular disease of the colon - a new role for an old drug. A. Tursi. Expert Opin. Pharacother. 2005 Jan; 6(1); 69-74. Discussion. Mesalazine with or without antibiotics significant superiority in improving severity of symptoms and preventing symptomatic recurrence of diverticulits over antibiotics alone.
Gatta L. Efficacy of 5-ASA in the treatment of colonic diverticular disease. J Clin Gastroenterol. 2010 Feb; 44(2): 113-9. Systemic review of literature. 6 randomized control trials or a controlled clinical trial with parallel group design using 5-ASA as 1 treatment arm. Patients had uncomplicated diverticulitis in all studies. Those treated with 5-ASA had significantly better outcomes. Daily mesalazine better than cyclic administration to prevent relapse.
Long term treatment with mesalazine and rifaximin vs rifaximin alone - Tursi A. Dig Liver Sis. 2002 Jul; 34(7); 510-5. Compared patients treated with 400 mg rifaxoin bid plus mesalazine 800 mg tid for 7 days, then rifaximin 400 mg bid plus mesalzine 800 mg bid for 7 days/ month. Group B got only rifaxin. Group A had significantly less recurrence of diverticulitis.
Petruzziello L et al. Review article: Uncomplicated diverticular disease of the colon. Alment Pharmacol Ther. 2006 May 15; 23(10); 1379-91. Pathophysiology of divertiuclar disease complex and related to abnormal colonic motility, changes in the colonic wall, chronic mucosal low-grade inflammation,imbalance in colonic microflora and visceral hypersensitivity. May be genetic factors. Use of nonabsorable antibiotics . Mesalazine acts as a local mucosal immunomodulator, improves symptoms, prevents recurrence of diverticulitis.
Strate, LL Diverticular disease as a chronic illness: Evolving epidemiologic and clinical insights. Am J Gastroenterol, 2012 Oct: 107(10) 1486-93. From low dietary fiber and fecalith obstruction model, growing knowledge shifting paradigm of diverticular disease from acute surgical illness to chronic bowel disorder. Role for low grade inflammation, sensory-motor nerve damage, dysbiosis, in clinical picture that mimics irritable bowel syndrome. These developments prompt shift from widespread antimicrobials and supportive care to use of probiotics, mesalamine, and gut-directed antibiotics. I got this article from the author, and it is summarized above, as well as I can privately e-mail it to people.
Cohen HD, The metabolism of mesalamine and its possible use in colonic diverticulitis as an anti-inflammatory agent. J Clinc Gastroenterol 2006 Aug; 40 Suppl 3. 5-aminosalicylic acid (5-ASA) is the mainstay of therapy for inflammatory bowel disease (IBD). 5-ASA is active moiety in sulfasalazine. Many of side effects linked to sulapyridine, several druges that contain 5-ASA but lack sulfasalzine developed. Several recent studies have suggested that 5-ASA drugs are useful for treating uncomplicated acute diverticulitis.
Tomita R Role of nitric oxide in the left-sided colon of patients with diverticular disease. Hepatogastroenterology. 2000 May-Jun; 47(33); 692-6. Non-adrenergic non-cholinergic inhibitory nerves the most important nerves in the enteric nervous system of human gut. They release nitric oxide. Diverticular colon more strongly innervated by them than the normal colon. They act on the normal colon and to a lesser extent in the diverticular colon. Nitric oxide mediates the relaxation reaction of non-adrenergic non-cholinergic inhibitory nerves in the normal colon and to a lesser extent in the diverticular colon. Cholinergic nerves are dominant in the left-sided colon with diverticula. This may add to high intraluminal pressure by colonic segmentation observed in left sided colon with diverticula.
Nitric oxide-releasing mesalamine: potential utility for treatment of inflammatory bowel disease. Dig Liver Dis. 2003 May; 35 Suppl 2. Nitric oxide can accelerate ulcer healing and exert anti-inflammatory effects. Addition of a nitric oxide-releasing moiety to mesalamine significantly boosts its anti-inflammatory activity. NOreleasing mesalamine suppresses inflammatory cytokine production and reduces leukocyte infiltration.
Tursi, A. Effectiveness of different therapeutic strategies in preventing diverticulitis recurrence. Eur Rev Med pharmacol Sci, 2013 Feb; 17(3): 342-8. Similar to his other studies, but he did clinical, endoscopic and histological studies, both before (after treatment of acute episode) and after to demonstrate that mesalazine decreased endoscopic and histological inflammation.
Colecchia A, Efficacy of long term cyclic administration of the poorly absorbed antibiotic Rifaximin in symptomatic, uncomplicated colonic diverticular disease. World J Gastroeneterol. 2007 Jan 14; 13(2): 264-9. Compared dietary fiber alone to dietary fiber plus rifaximin, for 24 months. Both treatments reduced symptom frequency, but Rifaximin more so. Long term administration was well tolerated by patients.
Management of diverticular disease: is there room for rifaximin? C. Papi et al. Chemotherapy 2005; 51 Suppl 1:110-4. Review.
Diverticulitis forum at Topix: User reports on mesalazine for diverticulitis
Patients testifying that it worked well for them. Doctors are increasingly just prescribing it for their patients, and so far, every patient who has reported on diverticulitis forums that they tried it, reported that it helped.
Ulcerative colitis: Boswellia for Ulcerative Colitis.
Review of studies on boswellia and ulcerative studies. Shows that boswellia is slightly more effective on ulcerative colitis than sulfasalzine. Possible mechanisms are that Boswellia serrata is a potent 5-LOX inhibitor, and it has COX-2 inhibiting activity. Binds to 5-lipoxygenase. Reduces recruitment of platelets and leukocytes into inflamed mucosa. Limits leukotriene synthesis by inhibiting 5-lox.
Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Gupta I. Eur J Med Res. 1997 Jan; 2(1): 37-43.
Abstract of the key study where patients were given Boswllia serrata gum resin preparation 350 mg 3x/ day for 6 weeks (strength not given), on stool properties, histolopathology and scan microscopy of rectal biopsies, blood parameters, total leukocytes and eosinophils. Controls given sulfasalazine, 1g 3x/day. 82% of those treated with Boswellia went into remission compared to 75% of those on sulfasalazine. Authors think that leukotrienes play an important role in keeping colon inflammation active, and boswellia inhibits 5-lipogxygenase, the key enzyme of leukotriene synthesis.
Botanicals in the treatment of Crohn's Disease, from Crohn's.net
Cited small controlled trial of Boswellia extract and mesalamine in total of 102 Chron's patients. Change in "CDAI" between baseline and end of study. People on boswellia did twice as well than those on mesalamine. Difference not statistically significant, but boswellia appeared to perform better than mesalamine. Authors thought the effect is that Boswellia inhibits 5-lipoxygenase product LTB4, which has been implicated in Crohn's Disease.
Boswellia; from WholeHealthMD. Boswellia, Indian frankincense, grows in dry hills of India. Called Guggai.
Modern preparations made form purified extract of this resin and packaged in pill or cream form. Specific anti-inflammatory effects: They deter inflammatory white cells from infiltrating damaged tissue; they improve blood flow to the joints, and they block chemical reactions that set the stage for inflammation to occur in chronic intestinal disorders such as Crohn's disease and ulcerative colitis. Several small studies confirm that Boswellia performs atleast as well as mesalazine, and Boswellia is increasingly prescribed for this use, but more controlled trials are needed. 300 mg of Boswellia gum resin three times daily has been used - strength not given.
Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data. Abdel-Tawab M. Clin Pharmacokinet. 2011 Jun;50(6):349-69 Abstract.
Gum resin of Boswellia serrata, a traditional ayurvedic medicine, increasingly popular in western countries. BSE is associated with better tolerability than NSAIDs. Benefits were thought mainly due to suppression of leukotriene formation via inhibition of 5-lipoxygenase (5-LO) by two boswellic acids - KBA and AKBA. However, they failed to inhibit leukotriene formation in human whole blood. Very low concentrations found in plasma, far below effective concentrations for bioactivity in vitro. Permeability studies suggest poor absorption of AKBA. On the other hand, 100-fold higher plasma concentrations found for B-boswellic acid, which inhibits microsomal prostaglandin E synthase-1 and serine protease cathepsin G.
Boswellia serrata. Alternative Medicine Review 13(2) 2008.
Boswellia serrata (frankincense, there are two other kinds) is a full sized tree, height 12 feet, found in India, N Africa, and the Middle East (where it isn't the main kind of frankincense). Trips of bark are peeled away, yielding a gummy oleo-resin. Extracts traditionally used in the Ayrvedic system of medicine. Contains oils, terpenoids, sugars and volatile oils. Four pentacyclic triterpene acids, beta-boswellic acid the major constituent. Animal studies in India show ingestion of defatted alcoholic extract decreased polymorphonuclear leukocyte infiltration, decreased primary antibody synthesis, almost totally inhibited the classical complement pathway. In an in vitro study of b-boswellic acid, the extract demonstrated a marked inhibitory effect on both the classical and alternate complement pathways. Also shows marked sedative and analgesic effects in animal models. In vitro testing shows boswellic acids isolated from Boswellia, in dose-dependant manner, block synthesis of proinflammatory t-lipoxygenase products, incl 5-HETE and leukotriene B4 (LTB4), which cause bronchoconstriction, chemotaxis, and increased vascular permeability. An animal study found that Boswellia extract and one of its constituents, AKBA (above) decreased "rolling", adherent leukocytes, attenuated tissue injury scores, and reduced macroscopic and microscopic inflammation of gut mucosa, in dose dependent manner, in rats with induced ileitis. Two studies of Boswellia and ulcerative colitis. The one that found 82% of boswellia patients went into remission compared with 75% on sulfasalazine, and another that found 900 mg of gum resin of Boswellia/ day, for 6 weeks, had 70% went into remission compared to 40% treated with 3g/ day of sulfasalazine. Of 44 Chrohn's Disease patients treated with boswellia vs 39 patients treated with mesalazine, there was absolutely no statistically significant difference, meaning that the Boswellia extract was as effective as mesalazine.
Ancient Herb Suppresses Inflammation. Vicki Brower. Life Extension Magazine. March 2007.
Boswellia inhibits lipoxygenase (LOX) enzymes that are powerful contributors to inflammation and disease. 5-LOX contribute to formation of leukotrienes. May counter atherosclerosis. An advanced boswellia formulation called 5-LOXIN displays particular efficacy in inhibiting 5-LOX's inflammatory effects. Survey of German patients with inflammatory bowel disease showed that over a third used complementary and alternative medicines. Those who used boswellia extract reported better results than those who used other approaches. Review same studies as above. Also, researchers tested animal model of ulcerative colitis. Found boswellia extract protected the colon by significantly reducing disease activity, measured by decreased recruitment and adherence of white blood cells and platelets in the inflamed colon. Boswellia decreased the presence of P-selectin, that plays a role in active colitis. The protective effects similar to those seen in patients on steroids to reduce symptoms of colitis. AKBA binds directly to 5-LOX and inhibits its activity. Other boswellia derived compounds partially and incompletely inhibit 5-LOX. However even in standardized extracts, biologically active AKBA makes up only a small fraction of total composition. 5-LOXIN is made with a patented process that contains a concentration of AKBA greater than 30%. Animal study comparing 5-LOXIN to ibuprofen, 5-LOXIN produced 27% reduction in inflammation, compared to 35% for ibuprofen. Another study found 5-Loxin produced 55% reduction in inflammation, and so did prednisone.
Frankincense - Wikipedia article. Four species of Boswellia; most attention is given to the other three, which are used for their scent. .
Frankincense resin is edible and is used in traditional medicines in Asia. Often chewed like gum. In India Boswellia serrata used for a long time to treat arthritis, healing wounds, strengthening female hormone system and purifying the air.
Boswellia Serrata - The Indian Frankincense. Posted by Melodie Munro Jan 30, 2013 in Herbs, Plants and Spices for your Health. City of Shamballa.net Review.
Until recently research on boswellia has focused almost exclusively on boswellic acids, esp AKBA. Most supplements have looked to maximize that component. More recent research suggests some of the water soluble polysaccharides in boswellia are essential components; initiate and support the anti-inflammatory activity, while the lipid-soluble boswellic acids help provide a sustained action. A particular boswellin polysaccharide extract called Polysal has demonstrated a dose dependent anti-inflammatory potential similar to the boswellic acids.
Boswllin PS contains Polysal. Polysal primarily consists of galactose, arabinose, D-glucuronic acid, and 4-o-methyl-glucuronarabino-galactan.
Boswellia (Boswellia serrata). Livingnaturally.com Natural Standard (www.naturalstandard.com)
Monograph on safety of Boswellia. As opposed to nonsteroidal anti-inflammatory drugs (NSAIDS) long term use of Boswellia has demonstrated minimal side effects. Safety not well studied in humans. Gastrointestinal side effects and liver toxicity have been reported in humans. Dermatitis (itchy, inflamed skin) has been reported in clinical trials using Articulin-F, a combination product. Not clear if Boswellia responsible. Gastrointestinal side effects, including mild stomach upset, abdominal fullness, diarrhea, nausea, epigastric pain, abdominal cramps, and a bezoar, have been reported. Reflux and stomach pain have been associated with use of Boswellia; use with caution in those with pre-existing gastritis or GERD. Boswellia may interfere with the way the body processes certain drugs, herbs, or supplements using the liver's cytochrome P450 enzyme system. As a result, the levels of these agents may change in the blood and may cause increased or decreased effects or potentially serious adverse reactions. Patients taking any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions. Use cautiously in patients with liver function or liver damage. Liver damage with pronounced liver enlargement and steatosis is possible with high doses of Boswellia. Avoid in individuals with known allergy or hypersensitivity to Boswellia, its constituents, or members of the family Burseraceae. Allergic contact dermatitis has been associated with the use of a naturopathic cream containing Boswellia serrata extract. Theoretically, Boswellia may act additively with analgesics (pain relievers), antiarthritic agents, antibiotics, anticancer agents, antifungals, anti-inflammatory agents, cholesterol- and triglyceride-lowering agents, drugs that cause liver damage, immunosuppressants, leukotriene receptor antagonists (such as zafirlukast (Accolate®) and montelukast (Singulair®)), and tumor necrosis factor (TNF)-blocking agents.
Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction. Frank A et al. J Chromatogr A 2006 Apr 21; 1112(1-2); 255-62.
In our search for herbal remedies with inhibitory activity on cytochrome P450 (CYP) enzymes, we identified extracts of the gum-resin of Boswellia carteri, Boswellia frereana, Boswellia sacra and Boswellia serrata as equally potent, non-selective inhibitors of the major drug metabolising CYP enzymes 1A2/2C8/2C9/2C19/2D6 and 3A4. LC/LC/ESI-MS fingerprint analyses of the boswellic acids 11-keto-beta-boswellic acid, alpha-boswellic acid, beta-boswellic acid and their 3-O-acylated derivatives were used for the authentication of the commercially obtained frankincense samples. Although the boswellic acids could be identified as moderate to potent inhibitors of the applied CYP enzymes, they are not the major CYP inhibitory principle of frankincense.
Benefits of Boswellia. Narda G. Robinson.
Triterpines in boswellic acid reduce synthesis of leukotrienes by inhibiting -lipoxgenase, the key enzyme involved in synthesis of leukotrienes in intact neutrophils. Colitis and bronchial asthma are characterized by increased concentrations of leukotrienes. Boswellia cause immunomodulation by inhibiting TH1 and promoting TH2 cytokine production. Regulate vascular responses to inflammation and stabilize mast cells. In intestinal inflammation boswellic acids may modulate adhesive interactions between leukocytes and endothelial cells. Boswellia is perceived to be a safe and effective remedy for a number of conditions. Germans with inflammatory bowel disease placed Boswellia serrata extract among the top three most beneficial CAM treatments, along with probiotics and acupuncture. Mentions one of the IBD/ colitis studies. Half life of boswellia is 6 hours; needs dosing every 6 to 8 hours. Presence of food in stomach and type of food eaten dramatically alters bioavailablity of boswellic acids, and bile acids affect their absorption. When human subjects ingested boswellic acids with a high fat meal, the areas under the plasma concentration-time curves and peak concentrations totaled several times higher than when the herbal preparations are taken in the fasting condition. Combining certain boswellic acid extracts with ethanol only produces significant cellular toxicity. Side effects of boswellic acids include abdominal discomfort, nausea, epigastric pain, hyperacidity, and diarrhea. Frankincense extracts, as well as boswellic acids themselves, display moderate to potent inhibition of human drug-metabolizing cytochrome P450 enzymes.
Ulcerative Colitis; University of Maryland Medical Center. Patient handout on ulcerative colitis. Boswellia is discussed under herbal remedies.
Boswellia (Boswellia serrata, 550 mg 3 times per day for up to 6 weeks) -- Boswellia has anti-inflammatory properties. One small study suggests that people who took boswellia had similar improvement as people who took the prescription drug sulfasalazine. More research is needed. Boswellia may interact with other drugs and supplements, so talk to your doctor before taking it. (The dose is sky high, though it may not assume 67% concentration of boswellic acids. )
Research on best treatments for Krohn's disease and IBS recommend the following, with notes that people vary in their need for (as I milk substitutes) and ability to tolerate various things on the list. For instance, if I want to see my lower digestive system go bonkers I can try more than 3 eggs in a week.
Oatmeal, well cooked
Vegetable soups, pureed
Salmon, shrimp, white fish (tilapia and flounder)
Papaya and mango, bananas
Avocado (soluble fiber)
Pureed chickpeas and lentils - allegedly this doesn't cause gas. I personally find that highly alleged. One of them is the ingredient of hummus, which I've seen recommended elsewhere.
Chicken and turkey
Butter lettuce (
Roasted red peppers, skinned.
Smooth nut butters
Herbs for inflammatory bowel disease
We tong ning (Traditional Chinese medicine)
Turmeric/ Curcumin – antibiotic as well as anti-inflammatory
Marshmallow (herb) – may also reduce stomach acid and protect stomach lining
Golden seal 1500 mg/day
Essential oils – oregano and anise, to reduce pathogenic bacteria in the gut. Fresh, crushed garlic cloves or garlic powder product.
Tablets containing boswellia 1200 mg, turmeric 2000 mg, celery 1000 mg, and ginger 300 mg, 4 per day.