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Partial

Colectomy P-value

Partial

Colectomy Overall TAC LI

– 32% 40% 17% – 0.002

(21%)

(79%)

– 26% 23% 30% – 1.0

– – 31% 36% – 0.45

(43%)

(57%)

(10%)

(90%)

A. M. Ammann and I. M. Paquette

– 30.1% 31% 26% – 0.28

613

(20%)

– 151 (21%) 35% – 37% 0.58

(80%)

(79%)

Patients (N) Mortality (%)

Total TAC LI

Low 98 77

Years

Studied Quality

2014

Retrospective Multicenter 2011–

etal.

Year Study Design Study Type

Table 32.2 Summary of studies

2017 Ferrada

27 13

Very

low

2011–

2015

center

Retrospective Single

etal

2017 Fashandi

Low 457 410

2011–

2016

(ACS-

NSQIP)

2018 Hall etal. Retrospective Database

Low 3021 2408

Low 733 582

2011–

2015

2007–

(NIS)

Retrospective Database

2019 Juo etal. Retrospective Database

2019 Peprah

2015

(ACS-

etal.

NSQIP)

LI loop ileostomy, TAC Total abdominal colectomy, CDI Clostrioides difcile infection

32 Surgical Management Options inSevere C Dicile Colitis

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(12.9–26.5%). There was no signicant difference in in-hospital mortality between LI and TAC (26% vs. 31%, p=0.28). However, those who underwent LI were signicantly younger (60.4 vs. 68.2, p<0.01), had fewer comorbidities (Elixhauser index, >5; 9.6% vs 13.3%, p=0.03), and occurred more often in hospitals with large bed sizes (76.3% vs 65.4%, p < 0.01) and urban teaching hospitals (84.0% vs.

66.3%, p< 0.01) [14]. Interestingly, Juo etal. also found that signicantly more patients underwent LI compared to TAC on hospital day 0 (23% vs 12%, p<0.01). The authors suggest a bias towards less severe cases of CDI on patients who underwent LI, which may affect mortality in subsequent studies and should be considered.

Finally, Peprah etal. queried the ACS NSQIP (2007–2015) database for patients with a diagnosis of C. difcile colitis who underwent a TAC or partial colectomy [15]. This was the only study comparing these two surgical approaches. The authors found no signicant difference in mortality between TAC or partial colectomy (34.7% vs. 37.1%, p=0.58). After controlling for patient factors, there was no difference for partial colectomy in complication rate (OR 0.92, 95% CI 0.51–1.62) compared with TAC.

367

Recommendations Based ontheData

As stated above, the overall grade of evidence on this subject is low due to the retrospective nature of this data and heterogeneous populations of patients studied. Additionally, only a small number of articles were identied comparing surgical procedures in the management of severe CDI.Overall, the mortality rates following surgical intervention for severe CDI remain high. The surgical management chosen is often patient specic and heavily reliant on individual surgeon’s bias or judgement. None of the new data presented here should change the recommendations suggested in the ASCRS Clinical Practice Guidelines. (1) “Surgery for C. difcile colitis should be typically reserved for patients with colonic perforation or severe colitis who do not improve with medical therapy.” (2) “Subtotal colectomy with end ileostomy is typically the operative procedure recommended for severe complicated fulminant C. difcile colitis.” [3]

Personal View oftheData

The art of being a surgeon lies in selecting the correct operation for a patient and intervening at the correct time. Surgery for C. difcile is no different. As a patient progresses to severe colitis, a surgical team should be consulted to help make these difcult decisions. Though vancomycin and daxomicin have shown promising results, a small proportion of patients will fail medical management. Surgery should be reserved for the most severe, fulminant cases that are progressing towards organ dysfunction. The standard operation in this rare setting is still total abdominal colectomy with end ileostomy. This operation has historically been shown to be superior to any type of segmental colectomy. The concept of a diverting loop ileostomy

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A. M. Ammann and I. M. Paquette

is intriguing and though the original study by Neal did include critically ill patients in the loop ileostomy group, the remaining literature on this topic is subject to selection bias [9]. Many patients with less severe illness were offered diverting ileostomy, leaving the reader to wonder whether they would have recovered with no surgical intervention at all. This is similar to laparoscopic lavage for diverticulitis, where many patients who likely did not need any surgical intervention at all were treated with laparoscopic lavage. Their positive outcomes likely skewed the literature in favor of lavage. The recent EAST study on LI vs. Colectomy was criticized because LI offered no advantage in postoperative sepsis, renal failure, acute lung injury, or overall mortality [10]. More information is needed, ideally in the form of a well-powered randomized trial to make LI the standard practice.

References

1. Mada PK AM Clostridioides Difcile. 2022.

2. Control CfD.C. diff (Clostridioides difcile). Available at: https://www.cdc.gov/cdiff/what- is.

html. July 3, 2022.

3. Poylin V, Hawkins AT, Bhama AR, Boutros M, Lightner AL, Khanna S, etal. The American Society of Colon and Rectal Surgeons clinical practice guidelines for the Management of Clostridioides difcile infection. Dis Colon Rectum. 2021;64:650–68.

4. Paquette IM, Stwart DB. Clostridium Difcile infection. In: ASCRS textbook of colon and Rectal surgery. Springer; 2022.

5. Stewart DB.Loop ileostomy for Clostridium difcile infection: know thy enemy. J Trauma Acute Care Surg. 2017;83:1214–5.

6. Bhangu A, Nepogodiev D, Gupta A, Torrance A, Singh P, West Midlands Research C. Systematic review and meta-analysis of outcomes following emergency surgery for Clostridium difcile colitis. Br J Surg. 2012;99:1501–13.

7. Steele SR, McCormick J, Melton GB, Paquette I, Rivadeneira DE, Stewart D, etal. Practice parameters for the management of Clostridium difcile infection. Dis Colon Rectum. 2015;58:10–24.

8. Lee DY, Chung EL, Guend H, Whelan RL, Wedderburn RV, Rose KM.Predictors of mortality after emergency colectomy for Clostridium difcile colitis: an analysis of ACS-NSQIP.Ann Surg. 2014;259:148–56.

9. Neal MD, Alverdy JC, Hall DE, Simmons RL, Zuckerbraun BS.Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difcile associated disease. Ann Surg. 2011;254:423–7; discussion 427-9.

10. Ferrada P, Callcut R, Zielinski MD, Bruns B, Yeh DD, Zakrison TL, et al. Loop ileostomy versus total colectomy as surgical treatment for Clostridium difcile-associated disease: an Eastern Association for the Surgery of Trauma multicenter trial. J Trauma Acute Care Surg. 2017;83:36–40.

11. Felsenreich DM, Gachabayov M, Rojas A, Lati R, Bergamaschi R.Meta-analysis of postoperative mortality and morbidity after total abdominal colectomy versus loop ileostomy with colonic lavage for fulminant clostridium difcile colitis. Dis Colon Rectum. 2020;63:1317–26.

12. Hall BR, Leinicke JA, Armijo PR, Smith LM, Langenfeld SJ, Oleynikov D.No survival advantage exists for patients undergoing loop ileostomy for clostridium difcile colitis. Am J Surg. 2019;217:34–9.

13. Fashandi AZ, Martin AN, Wang PT, Hedrick TL, Friel CM, Smith PW, etal. An institutional comparison of total abdominal colectomy and diverting loop ileostomy and colonic lavage in the treatment of severe, complicated Clostridium difcile infections. Am J Surg. 2017;213:507–11.

32 Surgical Management Options inSevere C Dicile Colitis

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14. Juo YY, Sanaiha Y, Jabaji Z, Benharash P. Trends in diverting loop ileostomy vs total abdominal colectomy as surgical management for Clostridium difcile Colitis. JAMA Surg. 2019;154:899–906.

15. Peprah D, Chiu AS, Jean RA, Pei KY.Comparison of outcomes between total abdominal and partial colectomy for the management of severe, complicated clostridium difcile infection. J Am Coll Surg. 2019;228:925–30.

369

Are Antibiotics Needed

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fortheManagement ofUncomplicated

Diverticulitis?

NathanKohrman andGlennT.Ault

Introduction

As colorectal surgeons we are familiar with diverticulitis, its complications, its epidemiology, and its burden on our health system. We are also familiar with the new hypothesis about its etiology: inammation and changes in the colonic microbiome cause micro-perforations, which in turn cause infection [1–7]. Two major randomized control trials, DIABOLO [8] and AVOD [9], offer compelling evidence for this new hypothesis. Both trials showed that patients with acute uncomplicated diverticulitis (AUD) who receive conservative management have clinical outcomes similar to patients who receive antibiotics, long the standard of care.

The DIABOLO Trial was conducted at 22 clinical sites across the Netherlands and included patients over 18years old who met the Hinchey classication of 1a or 1b or the Ambrosetti classication of ‘mild.’ All diagnoses were conrmed with a CT within 24h of admission. The AVOD trial was conducted across 10 surgical departments in Sweden and one in Iceland. It included patients over 18years old based on clinical criteria such as lower abdominal pain with tenderness, temperature >38°C, elevated WC, and signs of diverticulitis on CT. The trials used different inclusion criteria because there are several ways to diagnose AUD, which is a source of heterogeneity in the way colorectal surgeons approach the disease. Patients in both trials were randomly assigned treatment with antibiotics or conservative

N. Kohrman Keck School of Medicine of USC, Los Angeles, CA, USA

G. T. Ault (*) Keck School of Medicine of USC, Los Angeles, CA, USA

Division of Colon and Rectal Surgery, Keck School of Medicine, Los Angeles, CA, USA e-mail: ault@med.usc.edu

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 K. Umanskiy, N. Hyman (eds.), Difcult Decisions in Colorectal Surgery, Difcult Decisions in Surgery: An Evidence-Based Approach,

https://doi.org/10.1007/978-3-031-42303-1_33

371

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N. Kohrman and G. T. Ault

management, and then followed upon discharge to track complications, readmission, or other adverse events.

The trials found no statistically signicant difference in clinical outcomes, and subsequent meta-analyses and retrospective studies supported the ndings reported by the AVOD and DIABOLO trials. Two noteworthy studies, by Bolkenstein etal. [10] and Emile et Al [11], evaluated potential causes of conservative management failure, and found associations with two factors: elevated inammatory markers and comorbidities. As such, there are still instances where antibiotics are appropriate.

Many colorectal surgeons still prescribe oral and IV antibiotics for all cases of AUD, in line with decades of personal experience, as well as the ASCRS clinical practice guidelines published 2014 [12]. However, current ASCRS clinical practice guidelines published in 2020 state that in majority of cases of AUD, antibiotics are not indicated [13]. As for those of us who treat less healthy patients, choosing between conservative management or prescribing antibiotics is not so straightforward.

Search Strategy

A comprehensive literature search of Cochrane Database of Collected Research [14], EMBASE, MEDLINE, and PubMed was performed to identify all the Englishlanguage publications related to acute uncomplicated diverticulitis, antibiotic use, conservative management, and rates of treatment failure from 2010 to 2020. Key search terms included “diverticulitis,” “diverticulosis,” “diverticular,” “colonic,” “colon diverticulosis,” “surgery,” “medical therapy,” and “antibiotics,” in line with the search performed in the 2020 ASCRS clinical practice guidelines on the topic [13]. Studies were excluded if they did not refer specically to uncomplicated diverticulitis. Complicated diverticulitis was dened as diverticular disease resulting in an uncontained perforation, stula, stricture, or abscess formation. Table33.1 summarizes the population, intervention, comparator and key outcomes (PICO) for the patient population.

Table 33.1 PICO table

Patients Patients with acute

uncomplicated diverticulitis

Intervention Comparator Conservative

management with NSAIDs

Antibiotics (oral or IV) with NSAIDs

Outcome Resolution of symptoms,

treatment failure, subsequent surgery, cost, subsequent antibiotics, hospitalization

33 Are Antibiotics Needed fortheManagement ofUncomplicated Diverticulitis?

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373

Results

In the past decade, DIABOLO and AVOD, two randomized controlled trials (RCTs) conducted across several institutions in Northern Europe, showed there was no difference in outcomes between patients with AUD who received NSAIDs and antibiotics (oral and IV) and those treated conservatively with just NSAIDs [8, 9]. The measured outcomes included recurrence of diverticulitis, development of complicated diverticulitis, subsequent surgery, readmission, or other complications [15–

19]. There was no statistically signicant difference in these ndings in the long or

short term. Of note, van Dijk etal. [20] found that patients who received observational treatment had a higher rate of sigmoid colon resection at 2years (9.0% compared to 5.0%), but those ndings were not statistically signicant (p=0.085). As the authors noted, this may be because the study sample was under powered. However, van Dijk’s meta-analyses of patient records two years after the initial episode of AUD found no difference in the rates of diverticulitis recurrence, complications, or surgical intervention [20]. After more than 10year follow up of patients in the AVOD trial, there was no difference in rates of recurrent diverticulitis or quality of life between patients who received antibiotics and those who did not [21]. Table33.2 summarizes these key studies.

Table 33.2 Results summary table

Patients (N) observation v.

Study Megge [16] 1394 v 927 Treatment failure

Daniels [8] 262 v. 266 Median time to recovery

Chabok [9] 309 v. 314 Complications

Desai [15] 1346 v. 895 Length of hospital stay

antibiotics Outcome measure

Emergency surgery Recurrence

Complications Recurrence Sigmoid resection Readmission Adverse events Mortality

Recurrence within 1year Readmission Length of hospital stay

Recurrence Complications Readmission Treatment failure Sigmoid resection Mortality

Results observation v. antibiotics

Comparable Comparable Comparable

Comparable Comparable Comparable Comparable Comparable Comparable Comparable

Comparable Comparable Comparable Comparable

Comparable Comparable Comparable Comparable Comparable Comparable Comparable

Quality of evidence

Moderate

High

Moderate

(continued)

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Table 33.2 (continued)

Patients (N) observation v.

Study Au [17] 1663 v. 842 Length of hospital stay

Van Dijk [18] 545 v. 564 Ongoing diverticulitis at

Mocanu [19] 1626 v. 843 Recurrence within 1month

Isacson [21] 275 v. 281 Recurrence rate at 10years

Van Dijk [20] 262 v. 266 Recurrence at 2years

antibiotics Outcome measure

Additional treatment Recurrence Complications

1year Recurrence Sigmoid resection

Treatment failure Complications Elective or emergent surgery

Complication rate at 10years Surgery rate at 10years Cancer rate at 10years Quality of life at 10years

Complications at 2years Sigmoid resection at 2years

N. Kohrman and G. T. Ault

Results observation v. antibiotics

−0.68; p=0.04 Comparable Comparable Comparable

Comparable Comparable Comparable

Comparable Comparable Comparable Comparable

Comparable Comparable Comparable Comparable Comparable

Comparable Comparable Comparable

Quality of evidence

Moderate

Other meta-analyses, by Bolkenstein etal. and Emile etal. found associations between conservative treatment failure and a CRP of >170 [10], and between conservative treatment failure and comorbidities, especially immunosuppressive comorbidities such as diabetes [11]. The study by Emile etal. did not address specic comorbidities that may have put patients at elevated risk, or the risk posed by nonimmunosuppressive conditions such as heart failure. While Bolkenstein etal. [10] did nd a statistically signicant relationship between elevated CRP and conservative treatment failure, Emile etal. [11] failed to nd one. Both meta-analyses are sufciently powered to support their contradictory conclusions. While it seems intuitive that elevated CRP would correlate with an increased rate of conservative treatment failure, other measures of inammation and infection such as white blood cell count and temperature had no relationship with treatment failure in any of the meta-analyses we reviewed.

Among the studies looking at the consequences of antibiotic use, Au etal. [17] found an association between antibiotics and a prolonged hospital stay, while Megge etal. [16] found that for AUD patients treated with antibiotics, a short course of oral antibiotics had similar outcomes compared to a longer course of IV antibiotics. These ndings were consistent with a randomized prospective trial performed by Schug-Pass etal. [22] which found that a 4-day dose of ertapenem was as effective as a 7-day course. The DIVER trial performed by Biondo

33 Are Antibiotics Needed fortheManagement ofUncomplicated Diverticulitis?

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etal., [23] found that AUD can be safely treated in an outpatient setting at a third of the cost of treating AUD in the hospital setting. Estrada Ferrer etal. [24] found that 88% of patients with AUD who received conservative treatment in an outpatient setting successfully completed their treatment. They also found that many patients who did require antibiotics for acute diverticulitis could be managed outpatient as well.

375

Recommendations

• Patients with AUD who have no comorbidities can be safely treated with obser-

vation and NSAIDs. (Evidence: strong; Recommendation: strong)

• Patients with AUD who are immunosuppressed or have comorbidities affecting

their immune function can receive oral antibiotics and can be safely treated out-

patient. (Evidence: moderate; Recommendation: moderate)

• Patients with AUD and other poorly controlled comorbidities should be seriously

considered for inpatient antibiotics.

• (Evidence: moderate; Recommendation; moderate)

Personal View

Most colorectal surgeons have been taught to prescribe antibiotics for AUD.Despite available evidence, surgeons may be reluctant to change the treatment approaches they have relied on over the course of their career. However, the evidence is overwhelming that immunocompetent patients can be treated effectively with conservative management. While the outcomes are similar, the benets of observational management are substantial. Many patients are spared the discomfort and logistical difculty of taking another drug and are spared the potential side effects of antibiotics. While not specifally addressed by this chapter, avoiding antibiotics will result in decreasing healthcare costs. The patient will face less risk from antibiotic resistance and C.Difcile infection. For physicians who treat AUD in healthy patient populations, this will streamline care. The patients can be followed on an outpatient basis with phone calls, electronic messaging or video visits. The timeframe for follow up can be left to individual provider’s clinical judgment.

The recommendations are not as clear-cut for management patients with AUD who have comorbidities. Emile etal. [11], a metanalysis of 2565 patients, found that comorbidities were the only variable signicantly associated with treatment failure in the non-antibiotic group. While this group was small—85 patients out of 1671— it makes sense that immunosuppressive conditions such as diabetes could impede the healing process. Since Bolkenstein etal. and Emile etal. had different ndings on the relationship between elevated CRP and treatment failure, we defer to individual provider’s judgment whether to use this value in managing of AUD.In our opinion, because it is a non-specic marker, elevated CRP value alone should not inform the decision for or against an antibiotic treatment.

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N. Kohrman and G. T. Ault

Would we discharge a patient with AUD without antibiotics if they have prediabetes or take low-dose steroids? What if they have a serious but nonimmunosuppressive disease like congestive heart disease? Additional research is necessary to answer these questions. In the meantime, we will have to use our individualized clinical judgment.

The AVOD and DIABOLO studies were conducted in European countries with patient populations that are healthier than the patients we serve at LAC+USC Medical Center, which is a large public safety net hospital. Our patients often have low health literacy and comorbidities, both diagnosed and undiagnosed. Many are low-income and Latino, which according to the CDC means between one in four and one in ve of our patients have diabetes [25]. These rates likely grow as patients get older—which is also when AUD is more likely to present. Many patients also have cirrhosis and inammatory conditions for which they must take steroids. These patients need antibiotics when they present with AUD.Treating our patient population on an outpation basis would be challenging. Even with coaching, patients with low health literacy often struggle to ll prescriptions and take their medications as prescribed.

So where does this leave us? We would feel comfortable using conservative management to treat a patient with AUD and DM with an A1c below 7.0, the threshold above which patients develop an increased risk of infection [26]. As for patients with AUD and non-immunosuppressive comorbidities, we would use conservative management if the comorbid condition is well controlled, such as asymptomatic heart failure. For patients with AUD and uncontrolled comorbidities, we would, despite the ndings of Schug-Pas etal. [22] and Estrada Ferrer etal. [24] admit the patient for a 4-day course of antibiotics to reduce the risk of treatment failure or non-adherence. Each surgeon will likely have a different approach based on his or her patient population. Treating acute uncomplicated diverticulitis is, well, complicated.

References

1. Strate LL, Modi R, Cohen E, Spiegel BM.Diverticular disease as a chronic illness: evolving epidemiologic and clinical insights. Am J Gastroenterol. 2012 Oct;107(10):1486–93. https://

doi.org/10.1038/ajg.2012.194. Epub 2012 Jul 10. PMID: 22777341.

2. Espín F, Rofes L, Ortega O, Clavé P, Gallego D.Nitrergic neuro-muscular transmission is upregulated in patients with diverticulosis. Neurogastroenterol Motil 2014 Oct;26(10):1458–1468.

https://doi.org/10.1111/nmo.12407. Epub 2014 Aug 11. PMID: 25109425.

3. Floch MH. A hypothesis: is diverticulitis a type of inammatory bowel disease? J Clin Gastroenterol 2006 Aug;40 Suppl 3:S121–S125. https://doi.org/10.1097/01.

mcg.0000225502.29498.ba. PMID: 16885694.

4. Simpson J, Sundler F, Humes DJ, Jenkins D, Scholeeld JH, Spiller RC.Post inammatory damage to the enteric nervous system in diverticular disease and its relationship to symptoms. Neurogastroenterol Motil 2009 Aug;21(8):847-e58. https://doi.org/10.1111/

j.1365- 2982.2009.01308.x. Epub 2009 May 14. PMID: 19453515.

5. Humes DJ, Simpson J, Smith J, Sutton P, Zaitoun A, Bush D, Bennett A, Scholeeld JH, Spiller RC.Visceral hypersensitivity in symptomatic diverticular disease and the role of neu-

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