Diverticulosis and Its Complications Flashcards
1
Q
epidemiology of diverticulosis
A
- True incidence difficult to measure as most patients asymptomatic
- No sex predilection generally
- “Disease of Western Civilization” – very much in America, Europe, Australia, etc. (Rare in rural Africa & Asia, Common in US, Europe, Australia, Japanese migrating to Hawaii have rate intermediate b/w native Japanese and mainland born, suggesting ‘westernization’ of colon)
2
Q
incidence of diverticulosis
A
increases with age
3
Q
pathologic anatomy of diverticulosis
A
- Typically arise in 2 or 4 parallel rows:
- Along the mesenteric sides of the anti-mesenteric taenia and along both sides of the mesenteric taenia (Happens where blood vessels go through the walls of the colon, Bands of muscle in the colon are tinea!, Where the blood vessels go through the wall is a weak spot – pouches that happen at very specific places (looks like little pock marks through the colon)
- Corresponds to sites of arterial penetration through smooth muscle
- Pseudo-diverticula in that mucosa and submucosa herniate through the muscle, but diverticulum does not include all layers of wall.
4
Q
western and asian individuals
A
- Western individuals: 90% left-sided, 15% right-sided
- Asian individuals: 25% left-sided, 75% right-sided
- WHY DO WE HAVE LEFT SIDED AND ASIANS HAVE RIGHT SIDED? Probably due to diet
- Vary in number from few to hundreds
- Typically 5-10mm in diameter, although ‘giant’ diverticula described
5
Q
Pathogenesis of diverticulosis
A
-colonic wall resistance, disordered mobility
6
Q
colonic wall resistance
A
- No evidence that atherosclerosis or venous changes predispose
- > 200% increase in elastin deposition, laid down in contracted form, with shortening of taenia and ‘concertina-like’ bunching of circular muscle
- If you have more proteins in your colon that are contracting, you have more contraction and then you have higher pressures which will make more pouches!
- Precocious diverticulosis occurs in patients with connective tissue disorders (Ehlers-Danlos, Marfan’s)
7
Q
Disordered mobility
A
- Increased resting, post-prandial, & neostigmine-induced luminal pressures demonstrated in patients with tics vs. controls without
- Symptomatic pts have higher motility indices than asymptomatic patients –> PRESSURE IS THE PROBLEM!!!
- Higher right-sided pressures seen in Asian patients with right-sided diverticula
- Wynne-Jones: westernized urban lifestyle “impermissive of flatus” -> air retention -> increased intraluminal pressures & tic formation (Impermissive of flatus = afraid to fart, When you fart, you are preventing diverticulitis)
- Diverticulosis (having diverticula), diverticulitis is inflammation, disease state
8
Q
Fiber Deficiency Hypothesis
A
- Evidence for: Worldwide striking geographic correlation with low dietary fiber intake, Developed in the west after the introduction of grain milling, Humans & animals on low-fiber diets: only species to get diverticula, Lower rates diverticular disease in vegetarians
- Burkitt and Painter: stool weights & transit times in Brits (low fiber diet) vs rural Ugandans (high fiber diet)
- Also supported by rodent data (lifelong low vs high fiber diet) –> Low-fiber diet: 45% developed diverticula (right sided), High-fiber diet: 9% developed diverticula
- Popular and logical thesis, but evidence supporting is actually poor, assumes uniform population diet and uncontrolled for lifespan etc
- There is no animal in the wild that has diverticulosis!!
- Vegetarians and vegans have a much lower rate of diverticulosis
9
Q
Can dietary fiber prevent complications?
A
- 2 large prospective cohort studies showing inverse relationship b/w fiber intake and diverticular complications
- HPFU, >43K men, US, 1988-1992, no prior colonic dz (RR for symptomatic disease in highest vs lowest fiber quintiles = 0.63 (.44-.91) (insoluble fiber, esp cellulose))
- EPIC-Oxford Study, 47K M & F, UK, 12 year follow up
- You can’t get rid of diverticulosis but you can reduce risk of diverticulitis
10
Q
Risk of seeds/nuts
A
-ACG Practice Guidelines 19991 (“Controlled studies that support this belief are lacking….no role for ‘elimination’ diet”)
o Not only ‘no association’ but may actually protect
11
Q
Genetic risk factors
A
- Swedish Twin Registry linked to Inpatient Registry1 (>100K twins; 2300 had dx of diverticular disease, OR for developing DD if monozygotic twin affected = 7.15 (4.8-10.6) (3.2 for same gender dizygotic twins), Estimate hereditability at 40%)
- Danish Registry2, >10K siblings, 900+ twins (RR for developing DD if monozygotic twin affected = 14.5 (8.9-23) (5.5 for dizygotic twins), Estimated hereditability at 53%)
12
Q
posture during defecation
A
-Conclusion: “Sitting during defecation (Western type toilet) seems to increase the risk of DD. To optimize the anorectal angle, placing a footstool during defecation may have a protective role against diverticula formation”.
13
Q
uncomplicated diverticulosis: the asymptomatic patient
A
- The majority of patients with diverticula (80%) will remain asymptomatic.
- There is no justification of any specific therapy or follow-up to be offered to such patients, other than a higher fiber diet.
- Incidentally discovered diverticulosis requires no intervention or treatment.
14
Q
Symptomatic Uncomplicated Diverticular Disease (SUDD)
A
- SUDD: lower abdominal symptoms in absence of overt inflammation (by vital signs, labs, CT)
- Now recognizing a continuum of inflammation, with evidence for a middle ground of subclinical inflammation in SUDD patients
- Possible mechanisms: Inflammatory damage to enteric nerves (and aberrant re-innervation leading to visceral hypersensitivity), Altered neuropeptides, Muscle hypertrophy with increased intraluminal pressure, Microbiota alterations
15
Q
emerging treatments for SUDD
A
- If there is indeed a symptomatic state of DD marked by low-grade inflammation, and/or visceral hypersensitivity or abnormal motor function or abnormal biome, can we intervene in such patients?
- Historically, we’ve prescribed fiber or anti-spasmodics, although data in support is weak
- ? Antibiotics, ? Probiotics ? Anti-inflammatories
- Cyclic Rifaximin in SUDD (400mg BID, 7 d/month)
16
Q
probiotics for diverticulitis
A
- The addition of the probiotic produced longer intervals of disease quiescence and a greater degree of symptom relief than the antibiotic/absorbent regimen alone
- The second study investigated the efficacy of Lactobacillus casei DG in combination with mesalamine in patients with symptomatic uncomplicated diverticular disease that was in remission
- The third study evaluated a high-potency probiotic in combination with balsalazide. in patients with acute uncomplicated diverticulitis in remission, respectively
- In both studies, the probiotic/5 ASA combination was associated with greater symptom improvement and fewer relapses compared to the 5-ASA regimen
- USE FERMENTED FOOD!!! Not probiotics (The way to put good bugs in you is with FOOD!!!)
17
Q
Mesalamine in DD
A
- At least 6 Italian studies have evaluated 5-ASA either after acute diverticulitis (3) or in SUDD (3)
- Generally favorable results (Daily superior to cyclic, But data very heterogeneous, Not double blinded, not placebo controlled, Subjective endpoints, Dose / regimen unclear)
18
Q
DIVA trial
A
- 52 week, randomized, multi-center, double-blind, placebo-controlled, proof-of-concept study (first in US)
- Required CT scan confirmed AD, excluded IBS Dx
- Patients randomized to: Standard care (abx, dietary advice as per local MD), Standard care, plus mesalamine 2.4gm QD, Standard care, plus mesalamine 2.4gm QD plus B. infantis QD)
- 12 week Rx with 40 week additional f/u (Lower GSS at all time points with 5ASA but NS (no effect probiotics), Significant increase in symptom responders (GSS=0 or 1) at some (but not all) time points, No effect on acute diverticulitis recurrence rates or surrogate markers)
19
Q
5ASA: the final answer
A
- Phase III RDBPC (PREVENT 1 and 2)
- > 1000 patients with >1 episode of acute uncomplicated diverticulitis
- Randomized to receive mesalamine (1.2, 2.4, or 4.8 g/d) or placebo
- Primary endpoint: proportion of patients free of recurrent diverticulitis, defined as surgical intervention or positive CT scan
- No dose of 5ASA superior to PBO placebo for reducing diverticulitis at 104 weeks
- No decrease in symptoms or time to recurrence
20
Q
5-ASA for AD
A
- Systematic review of five RCTs of 5-ASA to prevent recurrent AD (not SUDD)
- Pooled OR was 0.95 (95% CI 0.60 to 1.49)
- Quality of evidence by GRADE approach was “moderate”.
- Conclusion: “We have found no evidence to support a role for mesalamine in the prevention of recurrent diverticulitis”
21
Q
complicated diverticulosis: Diverticulitis
A
- Inflammation and/or infection associated w/ diverticula
- Affects <15% of patients with diverticula (Its porbably even lower than this (more like 10%))
- 450,000 US admissions / year
- 2 million outpatient visits US / year
- Generally the result of perforation of a single diverticulum, probably due to obstruction by inspissated stool. (Diverticulitis is microperforation, Bacteria breach mucosa, through wall, and cause (often limited) perforation.)
22
Q
risk of acute diverticulitis
A
- Estimates based on older data, true denominator unknown
- Retrospective review LA-VAMC 1996-2011
- 2222 pts with baseline diverticulosis (97% men)
- Diverticulitis during 11 year follow up: Liberal criteria: 4.3%, Strict criteria: 1.0% (CT or surgery confirmed)
- Median time to event (AD): 7.1 years
- Risk highest in younger patients
23
Q
clinical features of complicated diverticulosis - diverticulitis
A
- Pain and tenderness, usually LLQ, but in Asians or those with redundant sigmoids, can be RLQ or suprapubic.
- Altered bowel habits
- Anorexia, nausea, vomiting
- Hematochezia rare
- Dysuria: sympathetic cystitis
- Fever common; shock or hypotension unusual
- WBC common; no other labs routinely useful
- Differential Diagnosis
- Acute Appendicitis
- Crohn’s Disease
- Colonic carcinoma
- Pseudomembranous or ischemic colitis
- Ovarian cyst / abscess / torsion
- Ectopic pregnancy
24
Q
diagnostic modalities - diverticulitis
A
-CT scanning - most accurate (Abd & Pelvic scans; oral / rectal / IV contrast, Findings: pericolic infiltration of fatty tissues, wall thickening, abscess, Sensitivity and Specificity: 85-95%, Severe disease predicts complications and poor prognosis)
25
diverticulitis treatment
- Determine need for hospitalization: Mild symptoms, no peritoneal signs, tolerating POs, & supportive home networks: may be candidates for outpatient Rx.; Elderly, immunosuppressed, comorbid illness, or evidence of severe disease (high WBC or fevers): inpatient Rx.
- Antibiotics: cover gut organisms (eg GNRs & anaerobes, esp E. coli and bacteroides) – these are the bugs that live in the poop!
- Little data to guide choice.
- Oral: consider T/S or cipro plus flagyl (Single agent: Augmentin)
- IV: aminoglycoside/aztreonam/3rd gen ceph plus metronidazole or clindamycin. (Single agent: Unasyn)
- Sxs should ß w/in 2-3 days, advance diet.
- Continue Rx for 7-10 days
26
logic against routine abx in AD
- Abx overused, AEs (eg quinolones), drug resistance increasing.
- White House / CDC 2015 announce National Strategy to Combat Antibiotic Resistance ($1.2B)
- We’re creating ‘superbugs’ with multiple resistance
- Could some “acute diverticulitis” be Rx’d without Abx?
27
complicated diverticulosis - diverticulitis - tx
- Majority will respond to medical Rx; up to 25% will require surgery during admission.
- For those who respond, a complete colonic evaluation is required after resolution of clinically diagnosed case, to exclude other diagnoses, such as CA.
- Surgery to prevent recurrence?
28
when to consider surgery
- Prior guidelines recommended ‘considering’ prophylactic surgical resection after 2nd attack’
- Most recent ASCRS recommendations1 (“The decision to recommend elective sigmoid colectomy after recovery from uncomplicated acute diverticulitis should be individualized.”, “Routine elective resection based on young age (<50 years) is no longer recommended.”)
- Markov Model (WA State database)2 (Colectomy after fourth (rather than 2nd) episode → 0.5% fewer deaths and saved $1,035/patient.)
29
complicated diverticulosis: abcess
- Suggested by persistent fever or WBC
- CT scan: diagnose & follow course
- Stage I (small pericolic abscesses): 70-80% success with medical tx alone
- Stage II (distant abscesses): CT-guided percutaneous drainage, Allows for rapid control of sepsis without operative risk, allows for temporary drainage and single-stage procedure in 3-4 weeks, 15-25% may still require primary surgical therapy if multiloculated or inaccessible.
30
Fistulas
- Occur when phlegmon/abscess extends or ruptures into adjacent organ.
- Colovesicular: (65%) 2:1 M:F (fecaluria - pathognemonic, pneumaturia - suggestive)
- Colovaginal: (25%) stool / flatus per vagina
- Coloenteric, colouterine, colocutaneous: rare
- Treatment: single-stage resection / closure
31
Complicated diverticulosis: hemorrhage
- Most common cause of LGIB (30-50%)
- 5-10% of patients with diverticula bleed
- While most tics in left colon, bleeding may occur more often from right colonic tics.
- Arterial bleed from vasa recta coursing over dome of tic.
- Increased risk with NSAID use.
32
complicated diverticulosis clinical features of hemorrhage
- Rarely occurs with diverticulitis
- Abrupt, painless onset of maroon / red blood or clots; melena uncommon
- Mild lower abd cramps / urge to defecate
- Never consider tics as cause of Heme+ stool
- 75-80% stop bleeding spontaneously
- 25-35% recurrent bleeds; consider surgery after recurrent episodes.
33
complicated diverticulosis diagnosis/management
- Fluid & blood product resuscitation
- Exclude UGIB with NGT or EGD
- Urgent Flex Sig, if negative for source: Tagged RBC Nuclear Scan Þ angiography OR “Rapid Purge” and colonoscopy; although endoscopic Rx much less effective than in UGIB
- Surgery if endoscopy or angiography fails- segmental vs. subtotal colectomy.
