The Role of Elective Surgery: Which Patients Should be Selected?

Abstract

Although the incidence of acute diverticulitis (AD) has risen over the past few decades, particularly in younger patients, the rate of emergency surgery has been dropping due to a major paradigm shift toward more conservative management approaches. The long-term management strategy after successful nonoperative treatment of AD remains unclear, and indications for elective resection are a matter of ongoing debate. Most modern professional guidelines advise considering elective surgery in an individualized approach, particularly after recovery of acute complicated diverticulitis (ACD) with abscess and in patients with recurrence, persisting symptoms, and complications such as abscess, fistula, and stenosis, focusing on the patient’s quality of life, where recurrence, severity, and symptoms are major determinants. However, guidelines are still not clearly standardized for appropriate decision-making, with patients being managed very differently from institution to institution, and surgeon to surgeon, mainly due to a lack of risk stratification for recurrence and severity that have been the scope of numerous studies but still need to be clarified. In this chapter, we explore the current surgical indications for AD, considering this disease’s ongoing prognostic factors, for proper decision-making.

1. Introduction

Although the incidence of acute diverticulitis (AD) has risen over the past few decades, particularly in younger patients, with 1/5 of them under 50 years old [1], the rate of emergency surgery has been dropping due to a major paradigm shift toward more conservative management approaches [2, 3, 4]. Evolving data on the natural history of AD has led to increased nonoperative management of the acute episode and long-term expectant strategy [2, 3, 4, 5]. Still, the long-term management strategy after successful nonoperative treatment of AD remains unclear and indications for elective resection are a matter of ongoing debate. Historically, the goal of elective surgery for the long-term management of AD was the treatment of complications like fistula or stenosis, preventing recurrence, namely complicated recurrence, and avoiding the morbidity risk associated with emergency surgery or an eventual stoma. In this order, surgery was advised for the management of fistula or stenosis, after a second episode of acute uncomplicated diverticulitis (AUD), after a solitary episode of acute complicated diverticulitis (ACD) and considered in younger patients after any attack [6]. However, every aspect of colonic diverticulitis has been examined over the last two decades, challenging long-held beliefs. So, data have emerged contesting prior standards to proceed with elective colectomy to prevent relapse [7, 8].

2. Current evidence on long-term outcomes in recurrence and severity

The first evidence to be noticed was that complications were more likely to present in the first episode, decreasing with the number of recurrences [9, 10], and therefore, interval colectomy in recurrent AUD did not decrease the rate of emergency surgery or morbidity [10, 11, 12]. As a result, since 2006, The American Society of Colon and Rectal Surgeons (ACRS) strongly advise that the decision should be individualized in recurrent AUD [13]. In 2014, a systematic review, including 68 studies, reviewed the decision-making data and outcomes of elective surgery from 2000 to 2013 [14]. They reported a low rate of complicated recurrence after recovery of AUD (˂5%), and that early-onset age and two or more prior episodes did not rise complications. In addition, current data announced that recurrence is lower than previously thought [15, 16, 17]. It is estimated to be around 13–36%, with higher recurrence after each bloat of AUD and a single episode of ACD with abscess [9, 18]. In 2016, Devaraj et al. noticed a 60.5% global recurrence rate in ACD, with a 46% increment in the modified Hinchey grade [19]. Later, in 2020, a systematic review from Lee et al. reported a 25–30% recurrence rate, without a rise of complications, namely with emergency surgery need [20]. More importantly, it has been noted that all risks associated with recurrent ACD significantly decreased after the first year of observation. However, the risk of recurrence increases with the number of previous attacks [17]. In particular, Aquina et al. observed a 66% decrease in all recurrence-associated risks after one year of follow-up [21]. In their study with 5412 patients, the overall recurrence lowered from 27.4% to 12.5%, as the complicated recurrence and need for emergency surgery fell off from 18.6% and 11.4%, to 7.6% and 3%, respectively. Other modern studies reported similar results in long-term follow-up of ACD. Garfinkle et al. reported an overall recurrence of 30.1% after observing 78 patients with a two-year median follow-up, with complications in 9.6%, and emergency surgery in 2.7% [2]. Buchwald et al. observed 107 patients with ACD with a median duration of 110 months and noticed recurrence in 20% of the patients, in a median time of 4 months, raising to 27% in patients with percutaneous abscess drainage, although non-significant [22]. Moreover, You et al. in a RCT with 107 patients with abscess or extraluminal air initially managed conservatively, and an aleatory allocation of 1:3 to elective surgery or observation, found treatment failure in only 15 patients, which again had medical treatment [23]. Failure was more significant in patients with ≥20 extraluminal air bullae, and with abscess ≥5 cm or pelvic. Further, a 2020’s meta-analysis summarizes these trends, pointing out similar relapse for ACD and AUD, variating between 25% and 30%, with a low complicated recurrence rate that occurs mainly in the first year [20].

3. Revised guidelines on indications for elective surgery

The DIRECT trial compared the results of elective surgery vs. conservative management in patients with recurrent diverticulitis or ongoing symptoms, and found little but significant QoL (Quality of Life) gains in the operative group [24]. The recent LASER trial (LAparoscopic Elective Sigmoid Resection following diverticulitis) found an improved QoL (12.95 points in GIQLI score) after elective surgery but with major complications in 10% [25]. Attending to the new data, international guidelines were revised and adopted a position in which quality of life became the main goal of elective surgery [9, 18]. More precisely, the European Society of Coloproctology (ESCP) guidelines stated that elective surgery to prevent complicated disease is no longer justified, irrespective of the number of previous attacks, with level 2 evidence, and that there is no evidence to support resection in symptomatic patients without radiological or endoscopic signs of ongoing inflammation, stenosis, or fistula [9]. The ESCP also stated that the indication for surgery should be individualized and based on the frequency of recurrences, duration, and severity of symptoms after the attacks and the comorbidity of the patient, independently of being AUD or ACD, based on level 3 evidence. For this matter, ACRS was more cautious and stated that elective resection should typically be considered after successful nonoperative treatment of ACD with abscess, with level Ib evidence [18]. So, most modern professional guidelines advise to consider elective surgery in an individualized approach, particularly after recovery of ACD with abscess, and in patients with recurrence, persisting symptoms, and complications such as fistula and stenosis [9, 18, 26]. This strategy, besides being focused on the patient’s quality of life, regards patients’ preferences, coexisting medical conditions, and surgical risk rather than fear of future life-threatening complications [7, 27]. Moreover, elective surgery can improve quality of life [28, 29], the results are imperfect, with an overall morbidity of 7.6% to 19.6%, namely leak and stoma risk, with persistent symptoms in 25% of the patients, even in the laparoscopic era [8, 30, 31, 32]. It would be interesting to have predictive factors for symptom persistence. It also must be said that elective resection does not decrease the rate of emergency surgery and does not eliminate the risk of recurrence (15 vs. 61%). Considering all this, it is a frequent concern for surgeons to know which patients should be operated on and when, where recurrence and complications are significant surgery determinants.

An issue that remains unclear puts into question which ACD characteristics prone patients to a higher risk of failure in wait-and-see management. It appears that abscess size matters, with abscess ≥5 cm having a relapse rate of about 28% and oscillating between 9.6% and 61% in multiple studies [5, 18, 33, 34]. Due to their frequent early relapse after the index attack, it is suggested that they could be persistent abscesses instead. A distant pelvic abscess was also described to confer a higher risk of relapse, with an almost three times higher failure rate of nonoperative management compared with pericolic location, besides a slight increase in emergency surgery risk (4.3 vs. 1.4) [20, 35]. Regarding percutaneous drainage of abscess at index attack, there is a significant body of literature with some discrepancies and bias due to a high selection rate for elective surgery in this group of patients [19, 33, 36, 37, 38]. However, most recent studies describe that despite the increased risk of recurrence in the first year, the risk of emergency surgery is low [34, 35]. Moreover, unlike abscess size and location, percutaneous drainage did not act as an independent factor in multivariate analysis [5].

Finally, recent studies on diverticulitis in alleged high-risk groups such as young and immunosuppressed patients did not confirm the same risks of complications as previous studies. More specifically, research comparing patients younger and older than 50 years of age, namely a 2020’s meta-analysis, have determined that although a relative increase in the recurrence rate was possible in the younger, the cumulative risks of complications and emergency surgery were similar [35, 39, 40, 41, 42]. Therefore, guidelines were updated and recommended to manage young patients as the older ones based on level 1C evidence [9, 18]. In relation to immunosuppressed patients, a group with significantly more comorbidities, the discussion is still burning. The 2020ESCP’s guidelines stated that the decision for elective resection in immunocompromised patients should follow the same principles as for the immunocompetent patients and was not recommended routinely. In a similar way, the 2020-ACRS suggested an individualized decision for this group of patients. In the other hand, the 2020 guidelines of the World Society of Emergency Surgery (WSES) were more cautious and suggested that all immunocompromised patients should be planned for surgery after recovery from an episode with successful nonoperative management, based on level 2D evidence [32]. It is generally accepted that AD has a higher incidence in immunocompromised patients and worse outcomes in ACD after medical or surgical management. A study by Biondo et al. analyzed the relationship between the different causes of immunosuppression and diverticulitis. Immunocompromised patients were divided into five groups according to the reasons of immunosuppression: chronic corticosteroid therapy, transplant patients, malignant neoplasm disease, chronic renal failure, and other immunosuppressant treatments [37]. The authors observed that the emergency surgery rate in the first episode was high (39.3%) and needed more frequently in the chronic corticosteroid therapy group. The overall postoperative mortality was 31.6%, and recurrence after successful non-operative management occurred in 27.8%, with no differences among groups. So, the authors concluded that elective surgery in immunosuppressed patients should be individually indicated according to the persistence of symptoms or early recurrences, with a low threshold in patients with chronic corticosteroid therapy. Sugrue et al. compared the outcomes between 20 renal transplant patients and 134 immunocompetent patients with AD [43]. The authors observed similar results for AUD and concluded that the nonoperative management in this situation was safe. However, the optimal treatment for renal transplant patients with ACD remained unclear, as they were more likely to undergo an emergency operation with additional complications. Another study by Lee et al. did not find differences in the morbidity and mortality of renal transplant patients that underwent elective colectomy after index or recurrent episodes and concluded that the fear of postoperative complications from recurrent diverticulitis should not be a reason to recommend elective colectomy after an initial attack [44].

A meta-analysis published in 2022 by Yeow et al., including 7415 patients from 11 studies, three of them RCTs, compared the outcomes between elective surgery and nonoperative treatment for the long-term management of ACD. The authors reported significantly increased odds of recurrence in the conservatively treated group, as it would be expected (OR = 0.24). However, the stoma rate (OR = 2.34) and the morbidity rate (OR = 4.29) were significantly higher in the elective surgery group, although with an increase in QoL and cost-effectiveness [45].

Regarding the approach, laparoscopy is safe in the setting of elective surgery for diverticular disease and is associated with reduced rates of morbidity and length of stay compared to open surgery [46]. So, laparoscopic colectomy is recommended when feasible and when there is expertise available [18, 46]. The timing is still unclear, and limited evidence suggests no difference in morbidity or mortality when comparing early (< 6 weeks) versus late (> 6 weeks) elective resection for diverticular disease, although with a trend to a higher rate of conversion in early surgery. Thus, EAES-SAGES guidelines recommend delaying elective interval sigmoid resection for a minimum of six weeks from the previous episode of AD.

Considering all these, it is a frequent concern for surgeons to know which patients should be operated on and when, with recurrence and complications being major determinants. Asymptomatic patients with recurrent AUD and following an episode of ACD with abscess are managed very differently from institution to institution, and surgeon to surgeon, addressing the paramount need to improve and standardize guidelines in decision-making with better stratification of risk for recurrence and severity [47].

4. Assessment of predictive factors for severity and recurrence

Although recent evidence has emerged, AD’s natural history and pathophysiology remain unclear. Current evidence highlights the role of genetic susceptibility, environment, colonic dysmotility, visceral hypersensitivity, chronic inflammation, and gut microbiota imbalance in the pathogenesis of this disease, and further studies are needed to identify more potential targets for medical or surgical decision-making and establish well-defined preventive strategies [1, 8, 48, 49]. To know upfront which patients are more prone to have complicated or recurrent diseases and which patients are more likely to maintain symptoms after surgery could enormously contribute to tailored decision-making for elective surgery. The identification of risk factors for recurrence and severity has been the scope of numerous studies over the past few decades, but still needs to be clarified [7, 50]. Despite high-level evidence is lacking, several risk factors for AD have been found, falling into some broad categories, including anthropometric and anatomic features, diet, lifestyle, medications, genetics, and others, however, with little value in predicting the course of this disease [7, 51]. Current systematic reviews suggested that recurrence is associated with younger age, female gender˃50 years, smoking, obesity, Charlson comorbidity index score (CCI) ≥ 3, dyslipidemia, first ACD with abscess, number of previous episodes, as well with the extension of the disease, and pancolonic diverticula [7, 16, 50]. On the other hand, severity has been associated with obesity, lifestyle, drugs, comorbidities, previous ACD with abscess, and high C-reactive protein (CRP) or leucocytes (LCT) on admission [51, 52, 53, 54, 55, 56, 57, 58]. There are numerous studies addressing this subject, and Table 1 lists the most frequently suggested predictive factors for severity and recurrence.

Predictive factors	Possible predictive factors for recurrence	Possible predictive factors for severity
Demographics	Younger age; Female gender˃50 years
Anthropometric features	Obesity	Obesity; BMI
Anatomic features	Pancolonic diverticula
Lifestyle	Smoking	Smoking
Diet	Low fiber intake
Drugs		NSAID’s; Aspirin; Corticosteroids; Opioids
Comorbidities	CCI ≥ 3; Dyslipidemia	CCI ≥ 3; Immunosuppression
Related to the disease	First ACD with abscess; Number of previous episodes; Extension of the disease	Previous ACD with abscess; Severe disease on radiological imaging
Biochemical markers	High CRP on admission; FC?	High CRP and LCT on admission; FC?; PCT?
Genetic markers		TNFSF15, LAMB4?; ARHGAP15, COLQ , FAM155A?

Table 1.

Possible predictive factors for severity and recurrence of AD.

AD—acute diverticulitis; BMI—body mass index; NSAID’s—non-steroidal anti-inflammatory drugs; CCI—Charlson comorbidity index score; ACD—acute complicated diverticulitis; CRP—C-reactive protein; LCT—leucocytes; FC—fecal calprotectin; PCT—procalcitonin; TNFSF15—tumor necrosis superfamily 15 gene; LAMB4—laminin β4 gene; ARHGAP15—Rho-GTPase-activating protein 15; COLQ—collagen-like tail subunit of asymmetric acetylcholinesterase; FAM155A—family with sequence similarity 155A.

Particularly, there has been increasing interest in the role of biological markers as non-invasive and reliable tools, able to support physicians in diagnosis, assessment of activity, monitoring the potential development of complications, and predicting recurrence in AD, as already reported widely for inflammatory bowel disease (IBD), and grounded on recent data suggesting continuous chronic inflammation in patients after an episode of AD [7, 52, 59, 60, 61, 62]. LCT count was not found to be sensitive nor specific for the diagnosis of AD and its severity, while CRP has been demonstrated to be the best laboratory marker for diagnosis and prognosis [46]. In fact, countless studies indicated that CRP levels correlate with the disease’s severity and recurrence rates [52, 59, 63, 64, 65, 66, 67]. The optimal cut-off of CRP that discriminates AUD from ACD is not yet well-defined and ranges between 50 mg/L and 175 mg/L in different studies. Particularly, a cut-off of 150 mg/L was associated with a specificity of 75–91% for ACD [64, 66, 68]. Interestingly, levels over 240 mg/L during the index episode of AUD have been related to recurrence in the first six months [63]. Other studies have demonstrated that elevated fecal calprotectin (FC), an inflammatory colonic mucosal marker, was associated with diverticulitis recurrence and severity as long as symptomatic uncomplicated diverticular disease (SUDD) [69, 70, 71, 72]. Moreover, Tursi et al. showed that abnormal FC values at least once during the follow-up strongly correlated with recurrence, thus confirming the eventual role of persisting subclinical inflammation in causing it [70, 72]. Finally, procalcitonin (PCT), a biomarker of bacterial infections has been proposed as an accurate marker to differentiate AUD from ACD [73].

Additional studies are needed to establish the role of biomarkers and identify appropriate cut-off values that could be integrated into prediction models of severity, recurrence, and its timing, as long as appropriate decision-making algorithms for patients with AD.

Furthermore, recent studies highlighted the role of genetic markers in recurrence and severity. According to the 2021 American Gastroenterological Association clinical practice update, approximately 50% of the risk for AD is attributable to genetic markers based on conclusive evidence [30]. However, few genes have yet been implicated in disease pathogenesis. In silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and impaired connective fiber support, while an additional diverticulitis risk might be conferred by epithelial dysfunction [74]. Reports of early onset and severe AD in otherwise healthy families have led to the association still not confirmed with variants in the tumor necrosis superfamily 15 gene (TNFSF15) and the laminin β4 gene (LAMB4), supporting a role for collagen vascular disorder combined with an immunologically based susceptibility [75]. Genome-wide association studies (GWAS) have identified more than 200 risk loci for diverticulosis and diverticulitis, containing genes that regulate immunity, connective tissue integrity, cell adhesion, membrane transport, and intestinal motility. Of these, ten variants have been associated with AD phenotype. The most frequently addressed are in genes ARHGAP15 (Rho-GTPase-activating protein 15), COLQ (collagen-like tail subunit of asymmetric acetylcholinesterase), FAM155A (family with sequence similarity 155A) [76, 77]. Finally, research in therapeutic strategies aimed to modulate gut microbiota and reduce mucosal inflammation on its way [27, 78, 79, 80, 81, 82, 83, 84, 85]. More studies designed to assess risk factors for recurrence and severity could greatly improve stratification along with tailored treatment and prevention strategies in patients with AD.

5. Discussion

Considering actual data, the goals of elective surgery for AD are the improvement of QoL in symptomatic patients with ongoing chronic inflammation or recurrent boats and the management of complications such as abscess, fistula, or stenosis [9, 18, 26]. This decision should be individualized, keeping in mind that although surgery can improve a patient’s QoL and treat complications, the results are imperfect, with an overall morbidity of 7.6% to 19.6%, namely with leak and stoma, with persisting symptoms in at least 25% of the patients [8, 30, 31, 32]. In addition, while a significant reduction in the need for emergency surgery is no longer expected, it also does not eliminate the risk of relapse [14, 33]. Thus, while the indication is mostly linear for the treatment of complications such as enduring abscess, fistula, and stenosis, the remaining indications are personalized, taking into account the comorbidities, symptoms, QoL, degree of active inflammation, or severity of the episode [9, 18]. In symptomatic patients, besides the frequency, duration, and severity of the attacks, there should be disease-specific QoL measures, namely quantifying the negative impact in work [9]. Further, for surgery to be beneficial in persistently symptomatic patients with low QoL, active inflammation must be associated with translation on computed tomography (CT) scan, colonoscopy, or biochemical markers such as CRP or FC. After successful nonoperative treatment of ACD in asymptomatic patients, decision-making is more challenging since professional guidelines based on different data are discordant [9, 18]. The risk of a recurrent bloat needing emergency surgery is low, especially after the first year. However, it appears that size matters as the location. Abscesses ≥5 cm relapse more frequently (28%), ranging between 9.6 and 61%, looking like refractory episodes [34, 35, 86] and pelvic or distant abscesses have a higher rate of emergency surgery (4.3 vs. 1.4%), with previous percutaneous drainage not functioning as an independent variable, but in association with size and location [36]. Finally, surgery should be considered after recovery of Hinchey III episodes and contained perforations with distant or voluminous extraluminal air [87, 88].

Lastly, the decision for resection in young or immunocompromised follows the same principles as in other patients, though with a recommendation of a lower threshold [9, 18]. More specifically, immunosuppressed patients, with a higher risk of complicated recurrence, should be individually indicated according to the persistence of symptoms or early recurrences. The threshold in patients with chronic corticosteroid therapy is even lower, especially after an episode of ACD, where a close follow-up with a CT scan should be considered [26, 38]. On the other hand, the strategy can be more expectant in kidney transplant patients [38, 44, 45].

6. Conclusions

Currently, the main indication for elective surgery in AD, besides complications, is the persistence of symptoms with low QoL after recovery of successful conservative management. Most modern professional guidelines advise considering elective surgery in an individualized approach, particularly after recovery of ACD with abscess, and in patients with recurrence, persisting symptoms, and complications such as abscess, fistula, and stenosis, focusing on the patient’s quality of life, where recurrence, severity, and symptoms are significant determinants. However, we still struggle in the decision-making of alleged high-risk patients, namely with previous ACD with abscess ≥5 cm, or pelvic location needing percutaneous drainage, contained perforations with large and distant bullae of pneumoperitoneum, as long with young and immunocompromised patients. The guidelines still need to be standardized for appropriate decision-making, with patients being managed very differently from institution to institution, and surgeon to surgeon, mainly due to a lack of risk stratification for severity and recurrence. Further studies are needed to identify more potential targets for surgical decision-making to implement a stratified-management approach with the selection of patients for elective surgery tailored to the risk of recurrence, its timing, and severity.

Conflict of interest

The authors declare no conflict of interest.