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Quality of
evidence
M. Bertucci Zoccali and A. Angistriotis
Emergent
surgery
Technical
success of
stenting Outcome SEMS
RR 0.605 High
a
a
30-day mortality RR 0.963
Meta-analysis Morbidity
37% 25.9%
25.3% 15%
a
Systemic recurrence
Overall recurrence
74.3% 39.9% Moderate
a
3-year disease-free survival OR 1.429
3-year overall survival OR 1.659
87.4% Primary anastomosis
Propensity-
28.4% 65.3%
a
Stoma rate
Morbidity 42.8% 41.9%
matched
retrospective
90-day mortality 5.4% 6.3%
9 weeks
Time to adj chemo 6
Need for adjuvant chemo 37.8% 37.2%
weeks
Distant metastases 21.6% 26.6%
3-year disease-free survival 58.8% 52.6%
3-year locoregional recurrence 11.4% 13.6%
3-year overall survival 74% 68.3%
98.1% 30-day complication 8.5% Moderate
Prospective
Perforation 1.9%
Stent migration 1.2%
observational
Primary anastomosis 91.8%
Stoma rate 10.6%
Morbidity 16.9%
Mortality 0.5%
(222 SEMS
226 surgery)
Study Intent N Design
Table 13.2 (continued)
6 Foo 2019 BTS 7 RCT
444 surgery
BTS 222 SEMS
2019
7 Amelung
426 BTS
288 palliative
(only BTS
palliative
8 Tomita 2019 BTS/
were included
in the analysis)
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Quality of
evidence
Emergent
surgery
Technical
success of
stenting Outcome SEMS
13.6% 25.5 High
3.9% 9.4%
14.3% 51.4%
a
a
a
30-day mortality
Stoma rate
287 days
19 days 37 days
23.2% 9.8%
a
a
Time to start adj chemo
Need for adjuvant chemo 70.4% 69.5%
Hospital stay 8 days 15 days
Late complication
Mean survival 259
days
5-year disease-free survival HR 1.08
3-year overall survival HR 0.93
6.5% 8.1%
26.1% 41.4%
a
a
5-year overall survival HR 0.93
30-day mortality
Morbidity
Tumor recurrence RR 1.32
Mean difference -7.2
73.8% 50.8%
40.3% 82.9%
OR 3.179 High
OR 0.385
a
a
a
a
a
Hospital stay
Stoma rate
Primary anastomosis
Stoma rate
OR 0.589
OR 0.557
OR 0.687
Difference 2.5 days
a
a
a
a
Anastomotic leak
Post-op ileus
90-day mortality
Hospital stay
(continued)
Meta-analysis Early complication
prospective
observational /
13 retrospective
(758 SEMS
540 surgery
220
decompressing
Study Intent N Design
9 Veld 2020 Palliative 3 RCT/ 2
stoma)
Meta-analysis 3-year disease-free survival HR 1.15 High
14 RCTs/ 13
NRCTs (18
BTS, 7
palliative, 2
BTS/
palliative
2020
10 Spannenburg
both)
1266 BTS
2628 surgery
Meta-analysis 90% Primary anastomosis
observational
(11,596 surgery
1928 SEMS)
11 Jain 2020 BTS 8 RCT/ 25
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Quality of
evidence
M. Bertucci Zoccali and A. Angistriotis
Emergent
surgery
Technical
success of
stenting Outcome SEMS
69.8% 55.1% High
32.7% 48.2%
a
a
Overall morbidity
Overall recurrence 35.1% 24.7%
3-year disease-free survival 58.7% 63.5%
3-year overall survival 67.8% 73.5%
53% 77.2% Moderate
a
44/49 (89.8) 3-year OS
Meta-analysis 89.3% Primary anastomosis
Propensity
65 months
30.6% 55%
41
a
a
Median OS
5-year OS
matched
retrospective
observational
7.7 days Moderate
months
51% 26.5%
a
Total recurrence rate
Regional recurrence 20.4% 8.2%
3.5
a
Distant metastasis 30.6% 18.4%
100% Hospital stay
Prospective
days
Morbidity 20% 20.7%
observational
386 surgery
BTS 387 SEMS
Study Intent N Design
2021
Table 13.2 (continued)
12 Cirocchi
49 surgery
13 Cao 2021 BTS 49 SEMS
29 surgery
Palliative 35 SEMS
2022
14 Mahfouz
Indicates statistically signicant difference in the outcome
BTS bridge to surgery, RCT randomized controlled trial, RR relative risk, OR odds ratio
a
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Results
Emergency Surgery
In the face of an overall increase in early diagnosis, it is estimated that up to one third of CRC patients would require an emergency intervention upon initial presen­tation [11]. Malignancy represents the leading cause of LBO in adults, and over two thirds of the obstructing tumors occur in the left side of the colon, the majority of which are distal to the splenic exure [12, 13]. Due to the smaller diameter of the bowel, more distal tumors (occurring in the left and sigmoid colon) are more likely to present as an obstruction compared to more proximal cancers. Surgical options in this setting include simple diversion with loop colostomy versus resection with or without primary anastomosis. The creation of a diverting or blowhole colostomy proximal to the tumor presents several advantages: (1) it can be performed quickly, with minimal surgical trauma, potentially even under local anesthesia in particularly frail patients; (2) itis an effective temporizing measure allowing completion of stag­ing and denition of the most appropriate multidisciplinary treatment strategy, while avoiding a resection in the setting of an unprepped colon; (3) itrepresents an effective treatment when a radical resection is not feasible due to the extent of the disease or the tenuous conditions of the patient [4, 14]. However, colostomies are associated with non-trivial complication rates, including prolapse, herniation, necrosis, and infection, and the risk is demonstrably higher when performed in the emergent setting [15]. A loop colostomy negatively affects overall quality of life (QoL) when meant as denitive palliation, and imposes the need for additional operations when used as a bridge to elective resection [16]. The safety of an emer­gency colectomy, when technically feasible, is suggested by several studies in the literature, with reported equal morbidity, mortality and oncologic outcomes com­pared to loop colostomy, and shorter overall length of stay [17, 18]. A segmental resection is the preferred operation, while a subtotal colectomy– reportedly associ­ated with worse functional outcomes- is reserved for those cases where bowel isch­emia or serosal tear/perforation occurs in the proximal colon, or in the presence of synchronous tumors [19]. In a RCT published in 2014, 75 patient with obstructing rectosigmoid cancer were randomized to either loop colostomy or resection with end colostomy (Hartmann’s procedure); after stratifying patients by age and comor­bidities, the two approaches had comparable surgical and non-surgical complication rates, blood transfusion requirement, length of stay, and mortality [20]. Additionally, although the quality of the data is limited, there seems to be a survival benet in resecting the primary tumor even in the presence of synchronous metastases [21]. The feasibility of an oncologically sound resection in the emergent setting was assessed in a retrospective study by Teixeira etal.; 87 patient had an ES (77% of which for bowel obstruction); while the complication rates were higher than those reported for elective procedures (34% morbidity and 20% mortality), the vast majority of the specimens were adequate in terms of surgical margins and lymph node harvest [22]. While a Hartmann’s procedure leaves open the possibility of restoration of bowel continuity, actual colostomy reversal rates are much lower than
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generally thought, with 95% of patients still having a stoma at 18months in the UK National Bowel Cancer Audit published in 2015 [23]. Furthermore, Hartmann’s reversal is a morbid procedure, as reported in a series of 103 patients from University of Vermont, where nearly one third of the patients experienced a postoperative com­plication; interestingly, during the study period, the number of Hartmann proce­dures exceeded by vefold the take downs, once again suggesting that most of these end colostomies will, in reality, become permanent [24]. Over the last two decades, several retrospective and prospective studies have been conducted asserting the fea­sibility and safety of resection with primary anastomosis in the emergent setting for appropriately selected cases [25]. Bearing in mind the potential for bias inherent to the non-randomized design of the studies, primary anastomosis seems to have more favorable outcomes over a staged approach (14% vs 35% mortality, respectively, in a historical series), with leak rates reported between 2% and 12%, not dissimilar to the leak rates reported for elective left sided resections [2529]. Recognized risk factors for poor outcomes after primary anastomosis are age, comorbidities, advanced cancer stage, and surgeon’s expertise [30, 31]. In a recent international audit on nearly 600 patients, those who received a primary anastomosis experienced a similar major complication rate compared to those managed with end colostomy; interestingly, in the anastomosis group, while a diverting stoma did not decrease the leak rate (12% vs 13% for diverted versus not diverted, respectively), it did decrease the rate of severe complications (75% vs 87%), need for reoperation (50% vs 75%), and postoperative mortality (0% vs 20%) [32].
M. Bertucci Zoccali and A. Angistriotis
SEMS asBridge toSurgery
For patients with resectable disease who are t for surgery, SEMSs have been used to avoid ES and allow for denitive treatment in a more controlled environment with a one-step resection, thus acting as a bridge to surgery (BTS). This section of the chapter summarizes the current literature by reported outcomes.
Success Rate Overall, the reported clinical and technical success rates for SEMSs are excellent. Atukorale etal., in their systematic review, dened technical success as satisfactory placement and deployment of the SEMS, and clinical success as improvement of obstructive symptoms within 48h and resumption of bowel func­tion and oral intake. Over the 6 studies included in their review (2 RCTs and 4 non­randomized comparative studies), technical and clinical success were observed in 91% and 89% of the patients, respectively. The need for reintervention due to recur­rent obstruction was reported in 4 studies, and this occurred in 17% of the patients [33]. The CReST study (246 patients with left-sided colonic obstruction random­ized to either endoluminal stenting as a bridge to surgery or surgical decompression, 92% of which treated with curative intent), reported a success rate of 82% after stenting [34]. In a more recent pooled analysis from 2 prospective multicenter trials (426 patients total), technical and clinical success rates were found to be 98% and 94% respectively [35]. Lastly, in a meta-analysis that included 8 RTC and 25 obser-
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vational studies (15,224 patients total), SEMSs had technical and clinical success rates of 90% (1426 patients) and 81% (860 patients), respectively [36].
Morbidity and Mortality The safety aspect of the use of SEMS has been exten­sively scrutinized in the literature. Arezzo et al., in a meta-analysis of 8 RCTs, reported an overall 60-day morbidity rate of 34%, not statistically different com­pared to ES [37]. The ESCO RTC published in 2017 reported 8 cases of stent­related complications in the 56 patients treated with SEMS, the most common being perforation at the tumor site (9%) [38]. Perforation remains the most feared stent­related complication, with a reported incidence ranging from 2% to 10%, followed by stent migration (reported rates 1–10%) [35, 36, 39]. In a meta-analysis by Van Halsema etal., chemotherapy regimen including bevacizumab was an independent risk factor for perforation following SEMS placement (incidence 12% vs 7% for non-bevacizumab based regimens) [40]. Many studies have been published investi­gating whether the use of SEMSs improves surgical outcomes at the time of resection when compared to emergent operations. A recent updated meta-analysis comparing the two approaches demonstrated signicantly lower overall postopera­tive complications rates inthe SEMS group (33%) than in the ES group (48%), along with a higher rate of successful primary anastomosis formation (70% vs 55%, respectively) [41]. In a meta-analysis of seven RCTs by Huang etal., patients man­aged with SEMS achieved signicantly better rates of primary anastomoses (OR
2.01, p=0.007), wound infection (OR 0.31, p=0.004)] and overall complication
(OR 0.30, p=0.03); no difference was demonstrated in anastomotic leak rate fol­lowing curative resection (OR 0.74, p= 0.47), mortality (OR 0.88, p =0.76), or organ space infections (OR 0.62, p=0.57)] [42]. Similar ndings were reported in a propensity matching study by Harvey etal. based on NHS data, where the rate of anastomotic leak, wound dehisce and sepsis were comparable between stenting and ES [43]. Across the most recent literature, the reported rates of successfulprimary anastomosis and overall post-operative complications are consistently more favor­able in patients treated with SEMS [10, 37, 41, 42]. Procedure-related mortality is more difcult to assess, as many studies do not distinguish between procedure- and disease-related mortality, making survival a more reliable indicator, which will be discussed later in the chapter. Nonetheless, Amelung et al. reported a procedure­related mortality of 1.6%, most commonly secondary to bowel perforation [44]. While an earlier meta-analysis failed to demonstrate a difference in overall 60-day­mortality,[37] subsequent studies have shown signicant lower 30-day, 90-day and 1-year mortality in subjects undergoing stenting prior to surgery [10, 36, 43].
Permanent Stoma Rate In the ESCO RCT, the stoma formation rate was 22.2% vs 39% (P=.031) for SEMS and ES, respectively; at the time the study was published, the overall stoma reversal rate was 30% [38]. Similar results were reported by Amelung in a propensity score-matched analysis from the Netherlands (stoma rate 24% for SEMS vs 45% for ES; p<0⋅001) [45]. This nding was conrmed in 2
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recent meta-analyses of RTCs, thus minimizing the possibility that the observed difference is affected by selection bias [37, 41].
Recurrence Rates Since the introduction of stents for the management of malig­nant colonic obstruction, oncologic safety has represented the primary concern [46,
47]. Amelung etal., both in their propensity score-matched retrospective study and
in their meta-analysis, showed comparable local (11% vs 14%) and overall (27% vs 26%) recurrence rates between SEMS and ES, respectively [44, 45]. Similarly, no difference in recurrence rates was observed in the ESCO RCT (17% vs 20%, median follow-up of 36months) and a more recent meta-analysis (25 vs 35%) [38, 41]. Conversely, Cao etal., in their propensity-matched study published in 2021, showed higher rates of perineural invasion (51% vs 26%, p= 0.013) and worse overall recurrence rates for the SEMS group (51% vs 26%, p=0.013) [9]. Along the same lines, in a 2019 meta-analysis of 7 RCTs, the overall recurrence rate was higher in the stent group (37% vs 26%; p = 0.049), although this did not translate into a signicant difference in 3-year disease-free and overall survival [48]. In terms of risk factors for recurrence, a 2020 meta-analysis specically looking at the negative effects of procedural complications, stent-related perforation (reported incidence 9%) was signicantly associated with higher locoregional (27% vs 12%; p=0.004) and global recurrence rates (41 vs. 31%; p=0.04), although 3- and 5-year survival was not affected [49].
M. Bertucci Zoccali and A. Angistriotis
Long Term Survival and Quality Of Life Notwithstanding the considerations regarding the previously discussed outcomes, the literature is rather consistent in reporting comparable long-term survival between the two approaches. Huang etal. observed no difference in 3- (65 vs 75%; p=0.25) and 5-year overall survival (48 vs. 58%, p=0.38), in keeping with the results from the ESCO trial and the meta­analysis by Cirocchi etal.[38, 41, 42]. It is worth reporting that a handful of retro­spective studies have observed worse long-term outcomes associated with SEMS [46, 50]. Particularly, in the propensity-matched study by Cao, 3-year overall sur­vival (53% vs 77%, p=0.039) and 5-year overall survival (31 vs 55%, p=0.025) were signicantly worse in the stent group; stenting was an independent predictor of poorer survival on multivariable analysis (hazard ratio=2.309, p=0.037) [9]. Lastly, the CReST trial is one of the few studies looking at quality of life metrics and did not demonstrate signicant differences at the 3 and 12months between the patients treated with SEMS when compared to ES [34].
SEMS asDefinitive Palliation
Owing to a lesser concern regarding oncologic safety, the use of SEMSs in the pal­liative setting has been more rapidly and broadly accepted; however, the volume and
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quality of the data is limited when compared to that available for patients treated with curative intent.
Success Rates Overall, SEMSs are very effective in the symptomatic management of malignant LBO, with clinical success rates reported above 90% across the litera­ture [5153]. In a 2020 meta-analysis by Veld etal., pooled clinical success rate from 10 studies including 406 SEMS procedures was 94% [54]. Lower success rates (86%) were reported in a meta-analysis by Ribeiro etal., however the inclusion of rectal cancer patients might have represented a confounding factor, since this tumor location appears to be associated with worse outcomes, as discussed later in this chapter [55].
Morbidity Dependingon the studies and denitions, overall stent-related compli-
cation rates are reported between 23% and 36%, with the most common adverse events being restenosis/migration (15–21%), perforation (5–16%), and bleeding (3%) [51, 55, 56]. Several studies, some of which randomized, have compared adverse event rates between SEMSs and ES for palliation, without demonstrating any statistically signicant differences [51, 55, 57]. The use of SEMS for palliation is consistently associated with shorter hospital stay and earlier resumption of oral nutrition [51, 55, 57, 58]. When looking at long-term morbidity, Siddiqui et al. reported stent occlusion (10%), stent migration (5%), and colonic ulcer (6%) as the most common occurrences in the SEMS group, at a median follow up of 26weeks [58]. In this RCT, patients managed with stenting experienced worse long term maintenance of decompression (until death or latest follow-up) compared to surgi­cal patients (74% vs 97%; respectively, p=0.003), while overall long-term compli­cation rate was higher (21% vs 11%, respectively; p=0.27) [58].
Similarly, a retrospective series on 114 patients described shorter patency dura­tion after SEMS compared to surgery (163 vs 349days; p<0.001), even after addi­tional intervention (202 vs 349days; p<.001); the presence of carcinomatosis has been signicantly associated with long term stent failure and need of re-intervention [59, 60].
In a recent retrospective population based study, Abelson et al. showed that, compared to those palliated surgically, patients undergoing SEMS had similar or fewer complications (major events: OR 0.81; p=0.68; procedural complications: OR 0.57; p=0.10) with no signicant difference between the groups in terms of 90-day and 1-year hospital readmission (OR 0.93; p=.83; OR 0.72; p=.30 respec­tively); SEMS patient had a higher risk of requiring an additional intervention at 1year (OR 2.93; p=0.03), most commonly re-stenting [61].
Long Term Survival and Quality of Life Most of the published studies suggest no signicant difference in long-term survival between SEMS and ES [55, 56, 62]. One retrospective study, however, showed that surgery was an independent predictor of better survival in patients with good performance status (ECOG 0-1), emphasizing
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the importance of patient selection in the treatment decision making [59]. Quality of life is arguably the most important outcome of treatment in the palliative setting. Data is scarce, however, Fiori etal,. in their 2019 RCT, observed a bimodal distribu­tion of outcomes; at one month, QoL was signicantly better in patients treated with stenting, whereas, at 6months, patients who had surgical treatment reported higher scores [57]. The authors speculated that this may be due to stent-related late side effects such as tenesmus and minor rectal bleeding, in line with the evidence avail­able in the literature demonstrating higher long term morbidity associated with stenting as compared to ES [59, 62, 63]. Lastly, in an RCT published in 2017, Young etal., while unable to demonstrate any signicant difference in QoL at 4weeks, found stenting signicantly more cost effective compared to surgery, with an esti­mated incremental cost-effectiveness ratio of about $22.000 [64].
M. Bertucci Zoccali and A. Angistriotis
Special Considerations
Proximal Tumors Because of the larger caliber of the proximal colon, right sided malignant obstructions are less common. Even in those uncommon instances, emer­gency resections tend to be less challenging compared to left sided procedures and, except for the frailest patients, a primary anastomosis can be safely performed, in spite of a more advanced age and stage at presentation [65]. Anastomotic leak rates after emergency right colectomy for obstruction are reported in the range of 1–5%, signicantly lower compared to emergent distal colocolonic and colorectal anasto­moses, and not far off from the rates commonly reported for ileocolostomies per­formed in the elective setting (~1%) [4]. In order to minimize metabolic derangements and improve quality of life, a surgical ileocolonic bypass is the preferred palliation in patients with unresectable right sided tumors, with surgical/percutaneous cecos­tomy reserved for extremely unt patients [66]. The use of SEMS in the right colon is technically more challenging, which, along with the favorable outcomes after ES, have hampered the diffusion of endoscopic stenting for obstructing proximal tumors. A 2016 retrospective multicenter retrospective study from South Korea comparing ES versus stenting as bridge to surgery for obstructing right colon cancer suggests the safety of the latter approach, with comparable short- and long-term results for all the assessed outcomes [67]. An earlier metanalysis on 14 studies showed better outcomes when resection was performed after initial stent placement, with statistically signicant less major morbidity (1% vs 24%) and mortality (0% vs 11%), and a trend towards less anastomotic leaks (0% vs 9%); these results must be interpreted with caution due to the limited quality and the high heterogeneity of the included studies (mostly retrospective) [44]. In a more recent retrospective multi­center trial where SEMSs were used both for denitive palliation (15%) and as bridge to surgery (85%), stenting achieved clinical success in 78% of the casesand long term maintenance of patency in 74%, with 21% long term complication rate (compared to 11% for patients undergoing ES upon presentation) [58]. Lastly, in a retrospective study from China, the use of SEMSs in the acute setting not only pro­vided better short-term outcomes compared to emergent colectomy (intensive care
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admission 11.4% vs. 34.7%, p= 0.011; overall complications 11.4% vs. 29.2%, P=0.042; length of stay 8.23±6.50 vs. 11.18±6.71days, p=0.033) but, in the stage IV subgroup, patients treated with stent were 3 times more likely to undergo a synchronous liver metastasis resection at the time of surgery (85.7% vs 14.3%, p=0.029; HR=3.26, p=0.041) [68].
Extraperitoneal Rectal Cancer Tumors involving the mid and distal rectum pres­ent some distinctive features that call for a different approach compared to more proximal CRCs. A distal rectal cancer causing an obstruction is almost always locally advanced at presentation, hence best managed with neoadjuvant chemora­diation [69]. A diverting colostomy represents the treatment modality of choice in the acute setting, as it reliably manages the obstruction with minimal trauma, allow­ing from prompt initiation and minimal interruptions of oncologic treatments. While a loop ileostomy is the preferred diversion modality after low anterior resection, it should be used with caution in the emergent setting, as it does not represent a suit­able option in the presence of complete obstruction or of a competent ileocecal valve [70]. The choice of type and placement of the colostomy should be based on the anticipated denitive surgery. Vermeer etal., in a paper from 2016, suggested to perform a right sided transverse colostomy or very distal loop sigmoid colostomy if an eventual lower anterior resection (LAR) is anticipated, while an end sigmoid colostomy is preferred in those cases where an abdominoperineal resection will be required; left sided colostomies should be avoided as they could compromise the future conduit in case of an LAR [71]. The use of SEMSs for lower rectal cancers (<5cm from the anal verge) is limited by the potential for pain, tenesmus and incon­tinence, ultimately worsening patients’ quality of life; additionally, stent migration and bleeding are common complications during neoadjuvant treatment [72]. In a meta-analysis including 32 articles, technical success was reported in 97% of the cases, however, the clinical success rate was only 69%, with a considerable rate of complications (28%) [73].
Extracolonic Malignancies Conicting results have been reported in the literature on the safety and efcacy SEMs for the management of LBO cause by advanced ECM, with earlier series documenting higher morbidity as well as lower success rates when compared to primary CRC [72, 74]. More recent reports have mitigated those concerns, with comparable technical and clinical success rates as well as com­plications, irrespective of the underlying malignancy, when used both as denitive palliation or BTS; one study reported signicant shorter long term patency for extracolonic primaries in the palliative setting, however, this was not of clinical relevance given the shorter life expectancy of this cohort [7577]. Because of the rarity of this presentation, high quality data is lacking, nonetheless, based on the current evidence, SEMSs are a viable option for the treatment of LBO second­ary to ECM.