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26 Who Needs aLoop Ileostomy After Low Anterior Resection forRectal Cancer?
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on 78 patients undergoing LAR for rectal tumors 4–12cm from the anal verge at a
single hospital in India, who were randomized to ileostomy vs. no ileostomy. The
authors focused on stoma-related outcomes, but unfortunately did not include information on use of neoadjuvant or adjuvant radiation therapy. Data revealed a lower
leak rate in the diverted group (6% vs. 11%). Ileostomy predisposed patients to
electrolyte imbalance in the postoperative period, as well as a signicant overall
stomal complication rate of 25.4%. The authors also found stoma closure to be
associated with an overall complication rate of 67.7%.
More recent studies have examined the effects of wholesale policy changes on
AL and diverting stoma formation. Blok et al. compared outcomes of patients
undergoing LAR for low to mid rectal tumors at a single Dutch university hospital
in an era of “highly selective diversion” vs. historical controls who underwent “routine diversion” [26]. The data are heterogeneous, as selection of diversion was left
up to the surgeon, who selected for lower risk patients (e.g., higher tumors, no neoadjuvant long course radiation, healthy patient) to leave undiverted. The authors
also incorporated a new practice pattern, transanal total mesorectal excision
(TaTME), during the course of the data collection, which may confound results.
They reported that stoma-related readmission and reoperation rate (including reversal) were signicantly lower in their study group than in their control group (17%
and 17%; vs. 84% and 86%; p<0.001), and total hospital stay within 1year was
median 5 vs. 11days, p<0.001. AL rate was higher in the historical control group
(20% vs. 8%), which also more frequently underwent long course chemoradiation
(50% vs. 25%, p=0.016). The ndings do suggest that, when looking at the big
picture of policy (mandatory vs. selective diversion), allowing surgeons to utilize
diversion selectively might have signicant benets for patients.
Taken together, these data overall demonstrate that fecal diversion offers a clear
benet in LAR in lowering anastomotic leak rate and need for reoperation. While
early retrospective studies arrived at varying conclusions, prospective randomized
trials have all demonstrated a clear benet to fecal diversion. Therefore, at this
point, it is clear that at a population level, fecal diversion should be the default
operation in combination with LAR.However, what these studies fail to address is
which patients are at decreased risk of anastomotic leak and therefore could avoid
defunctioning stoma placement.
311
Who Is at Highest Risk forDeveloping aLeak?
Patient factors associated with poor wound healing increase the risk of developing
an anastomotic leak. Patients who are malnourished, on steroids, and obese, are at
higher risk for developing an anastomotic leak [27]. Early retrospective analyses
found specic rectal cancer factors associated with increased risk of AL: distance
from anal verge was found to have the strongest association with leak rate
(OR=5.4–6 for anastomosis 5cm from anal verge) [28, 29]. Further operative factors related to anastomotic leak included male gender (OR=2.36), and intraoperative blood loss (OR=1.05) [29]. Predictive risk score calculators may be useful in

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L. Cunningham and E. Huang
assessing patient and cancer-related factors. The REAL (REctal Anastomotic Leak)
score was proposed by a collaborative study group based on meta-analysis of studies including 9735 patients, and utilizes 12 preoperative factors (interval from neoadjuvant therapy to surgery, short course radiotherapy, TNM staging, anastomotic
distance from anal verge, patient age, gender, smoking status, BMI, diabetes, ASA
grade, prior abdominal surgery, and hemoglobin) to calculate a patient’s risk of
AL [30].
Intraoperative assessment of the anastomosis may play an important role in
reducing the leak rate and in deciding on the need for proximal diversion. Common
methods of evaluating a colorectal anastomosis include air leak testing, saline leak,
methylene blue leak tests and endoscopic assessment. Two randomized trials have
evaluated the validity of performing an intraoperative leak test and have found that
the risk of leak in those tested was signicantly lower than the untested controls
(5.8% versus 16%, p<0.05) [31, 32]. Therefore, intraoperative leak testing should
be performed and patients found to have concerning ndings on exam should
undergo repair, revision, and possibly fecal diversion.
A 2014 meta-analysis by Qin etal. included seven randomized controlled trials
evaluating the role of preoperative radiotherapy as a risk factor for AL after LAR
[33]. In the pooled studies, 1660 patients were included in the preoperative radiotherapy group and 1715 patients were included in the control group. In this analysis,
rates of anastomotic leak were not increased in the preoperative radiotherapy group
(OR=1.02; CI 0.80, 1.30; p=0.88). This analysis, however, is limited by the use of
clinically detected anastomotic leaks in the individual trials making up the analysis,
which may underreport anastomotic leaks that would be clinically signicant if no
defunctioning stoma were in place. Because it is not possible to directly measure the
rate of clinically signicant leaks in the presence of a defunctioning stoma, making
strong recommendations in patients who received preoperative radiotherapy remains
difcult. Short course chemoradiotherapy (delivery of neoadjuvant therapy over the
course of 5days vs. 25 fractions) has gained in popularity. The most direct comparison of relevant outcomes, a randomized controlled trial in which patients with T3
rectal adenocarcinoma within 12cm of the anal verge were randomized to short
course radiotherapy vs. long course chemoradiotherapy, demonstrated no signicant difference in AL rate [34].
A new and growing body of evidence also points to the role gut microbiome in
AL.A study by Shogan etal. in 2015 was one of the rst to demonstrate the contribution of specic bacteria in development of AL [35]. This group noted that matrix
metalloproteinase enzymes produced by Enterococcus faecalis were responsible for
tissue degradation at the anastomosis in rats and found the same strains in anastomotic samples of patients undergoing colon resections. While research in this area
is still ongoing, a substantial and growing body of literature suggests that environmental factors, including diet, antibiotics, bowel prep, and physiological stress from
surgery, alter the microbiome to cause AL or worsened oncologic outcomes after
colorectal surgery [36]. Upcoming microbiome sequencing technology may thus
inform decisions about AL risk and diversion.

26 Who Needs aLoop Ileostomy After Low Anterior Resection forRectal Cancer?
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313
What Type ofDiverting Ostomy Should WeUse?
When considering fecal diversion, the two common options are loop ileostomy and
loop colostomy. Four randomized trials have compared these two options to each
other, with two studies favoring the use of loop colostomy [37, 38] and two favoring
loop ileostomy [39, 40]. A 2007 Cochrane review found ve randomized studies
involving 334 patients: 168 undergoing loop Ileostomy and 166 undergoing loop
colostomy [41]. There was a large and signicant difference in stomal prolapse
rates, with a rate of 2% in the ileostomy group vs. 19% in the colostomy group
(p<0.01); however, there were no other differences noted. Given the large difference in rates of prolapse, current recommendations are to create a loop ileostomy
when possible.
Are There Benefits toEarly Ileostomy Closure?
Most surgeons close a diverting ileostomy at 2–3months after the initial LAR.Under
traditional models of neoadjuvant chemoradiation and possible adjuvant chemotherapy, this occasionally caused considerable delay in closure, as patients might
need to undergo uninterrupted adjuvant chemotherapy. Conversely, patients who
developed stoma-related complications might be prevented from undergoing needed
adjuvant therapy. There was thus signicant interest in the possibility of early closure of diverting ileostomy, within 2weeks of LAR.One multicenter randomized
controlled trial from Denmark and Sweden addressed this question, nding that the
mean number of complications up to 12months of follow up after LAR was actually
signicantly lower in the early closure group vs. the control group undergoing ileostomy closure at 12weeks (1.2 vs. 2.9, p<0.0001) [42]. Cost analysis from this same
trial demonstrated a mean cost savings of $3608in favor of early closure [43].
Given the known functional impacts of delayed ileostomy closure including
impaired bowel function, delaying ileostomy closure no longer than 6months is
recommended [44]. Total neoadjuvant therapy, in which both chemoradiotherapy
and consolidation chemotherapy are delivered up-front before surgery, may help
prevent prolonged interval to ileostomy closure after LAR.
Personal View oftheData
While proximal diversion is not without risks, the consequences of an anastomotic
leak are signicant enough that the benets usually outweigh the risks. Therefore,
proximal fecal diversion following anterior resection for rectal cancer should be
considered standard practice in most patients. Some patients may be at low risk for
developing an anastomotic leak, and consideration of patient factors such as age,
sex, weight and smoking status, tumor factors, and intraoperative factors; as well as
utilization of a risk calculator, may help determine those patients who are candidates for non-diversion. After creation, all colorectal anastomoses should be tested

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L. Cunningham and E. Huang
for the presence of an anastomotic leak. A positive test may necessitate a revision of
the anastomosis and/or repair followed by proximal fecal diversion.
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19. Graffner H, Fredlund P, Olsson S-Å, Oscarson J, Petersson B-G. Protective colostomy in
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22. Chude GG, Rayate NV, Patris V, Koshariya M, Jagad R, Kawamoto J, Lygidakis
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24. Montedori A, Cirocchi R, Farinella E, Sciannameo F, Abraha I.Covering ileo- or colostomy
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25. Thoker M, Wani I, Parray FQ, Khan N, Mir SA, Thoker P.Role of diversion ileostomy in low
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30. Arezzo A, Migliore M, Chiaro P, etal. The REAL (REctal anastomotic leak) score for prediction of anastomotic leak after rectal cancer surgery. Tech Coloproctol. 2019;23:649–63.
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32. Ivanov D, Cvijanovic R, Gvozdenovic L.Intraoperative air testing of colorectal anastomoses.
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33. Qin C, Ren X, Xu K, Chen Z, He Y, Song X.Does preoperative radio(chemo)therapy increase
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34. Ansari N, Solomon MJ, Fisher RJ, et al. Acute adverse events and postoperative complications in a randomized trial of preoperative short-course radiotherapy versus long-course
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35. Shogan BD, Belogortseva N, Luong PM, et al. Collagen degradation and MMP9 activation by enterococcus faecalis contribute to intestinal anastomotic leak. Sci Transl Med.
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36. Gaines S, Shao C, Hyman N, Alverdy JC.Gut microbiome inuences on anastomotic leak and
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37. Gooszen AW, Geelkerken RH, Hermans J, Lagaay MB, Gooszen HG.Temporary decompression after colorectal surgery: randomized comparison of loop ileostomy and loop colostomy.
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41. Güenaga KF, Lustosa SA, Saad SS, Saconato H, Matos D. Ileostomy or colostomy
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42. Danielsen AK, Park J, Jansen JE, Bock D, Skullman S, Wedin A, Marinez AC, Haglind E,
Angenete E, Rosenberg J.Early closure of a temporary ileostomy in patients with rectal cancer: a multicenter randomized controlled trial. Ann Surg. 2017;265:284–90.
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L. Cunningham and E. Huang

Reoperative Surgery forLocally
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Recurrent Rectal Cancer
NicholasP.McKenna andRobertR.Cima
Introduction
Locoregional rectal cancer recurrence rates have decreased from as high as 30% to
less than 10% since the widespread adoption of total mesorectal excision along with
administration of neoadjuvant or adjuvant chemoradiotherapy [1–4]. Locoregional
recurrences treated with chemoradiation alone have poor outcomes, with a median
survival of only 12 to 24months [5–7]. However, the combination of preoperative
chemoradiation or re-irradiation, an R0 resection, and intraoperative radiation therapy (IORT) when indicated can signicantly improve outcomes. Patients with
locoregional recurrences undergoing this multimodal treatment approach have
5-year survival between 37% and 57% [7, 8].
Reoperative surgery for locally recurrent rectal cancer is associated with major
morbidity rates ranging from 15% to 68% and mortality rates of up to 10% [9].
Therefore, patient selection is critical to ensure that only patients with a reasonable
chance for an R0 resection undergo such an extensive operation. Additional important considerations are ensuring the patient is optimized from a nutritional standpoint, is not smoking, the resection of local recurrence is technically feasible, and
that any metastatic disease is controlled or controllable. The latter two factors inuence whether the operation is curative or palliative. Optimally, the patient’s case is
reviewed by a multidisciplinary team to ensure that appropriate preoperative therapy is provided. Given the complexity of these cases, care should provided at a
tertiary referral center with the resources and experience to perform an R0 multivisceral resection as well as manage potentially signicant postoperative complications [10].
27
N. P. McKenna · R. R. Cima (*)
Mayo Clinic, Division of Colon and Rectal Surgery, Rochester, MN, USA
e-mail: McKenna.Nicholas@mayo.edu; cima.robert@mayo.edu
© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
K. Umanskiy, N. Hyman (eds.), Difcult Decisions in Colorectal Surgery,
Difcult Decisions in Surgery: An Evidence-Based Approach,
https://doi.org/10.1007/978-3-031-42303-1_27
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Table 27.1 PICO question search strategy for the chapter
Patients
Patients with recurrent rectal cancer Surgery Palliative treatment
Intervention Comparator
Non-treatment
N. P. McKenna and R. R. Cima
Outcomes
Survival
Cure
Morbidity
Quality of life
Search Strategy
PubMed was utilized to conduct a review of the English literature on recurrent rectal
cancer. Search terms used included “recurrent rectal cancer,” “locally recurrent rectal cancer,” and “intraoperative radiation therapy.” Original studies were used where
possible and supplemented by meta-analyses. Reference lists in systematic reviews
were used to identify additional manuscripts. Manuscripts published between 1986
and 2022 were assessed with a focus on the last 10years (Table27.1).
Results
Diagnosis
Data on diagnosis of locoregional recurrence of rectal cancer is heterogeneous, with
some studies describing over 65% of patients diagnosed due to symptoms [7, 11],
while others describe the majority of recurrences diagnosed based on routine surveillance imaging and carcinoembryonic antigen (CEA) levels [12]. All patients
with a conrmed recurrence require a full staging workup, including cross-sectional
imaging, a colonoscopy, and a CEA level. Cross-sectional imaging should include
CT scan of the chest, abdomen, and pelvis, as well as a pelvic MRI. Chest and
abdominal imaging are useful for the detection of distant recurrence, while CT and
MRI of the pelvis dene the anatomic relationships of the locoregional recurrence.
MRI is particularly useful since it allows better soft-tissue resolution and can distinguish recurrent rectal cancer from presacral scar [13]. Tissue diagnosis via colonoscopy if a luminal recurrence or via CT-guided biopsy is important before committing
to an operation. If biopsies are non-diagnostic, PET CT is also often helpful to distinguish brosis from recurrence. It may also detect distant metastatic disease
missed by CT scan.
Classification Systems andOutcomes
Once a recurrence is diagnosed, there are numerous classication systems to
describe the recurrence pattern without clear superiority of one system [14]. The
Memorial Sloan Kettering system is based on anatomical compartments (axial,
anterior, posterior, or pelvic sidewall). Axial recurrences can be anastomotic
(patients status post low anterior resection), perineal (patients status post

27 Reoperative Surgery forLocally Recurrent Rectal Cancer
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abdominoperineal resection), or local recurrence after transanal or transsphincteric
excision. Anterior recurrences involve the urogenital structures while posterior
recurrences involve the sacrum and/or coccyx. Lateral recurrences involve the pelvic sidewall bones, musculature, or sidewall structures [15]. In studies that have
used the Memorial Sloan Kettering system to evaluate surgical outcomes, R0 resections were more common for axial recurrences compared all other compartments
[15–17]. Iliac vessel involvement was also specically associated with decreased
R0 resections rates [15]. Yamada etal. proposed a system based on the pattern of
pelvic invasion– localized type, sacral invasive type, and lateral invasive type [18].
Like the Memorial Sloan Kettering system axial compartment recurrence type, survival was best with the local invasive type [18–20]. The Mayo Clinic system uses
sites of xation [from 0 sites of xation (F0) to 3–4 sites of xation (F3)] and symptoms [no symptoms or pain (S0) to symptomatic and painful (S2)] to classify recurrence [21]. Survival has been shown to decrease with both increasing sites of xation
and increasing symptoms and pain [8, 21–23]. Additional classication systems
exist and are largely based on the pattern of pelvic invasion [23, 24]. The common
theme amongst all recurrence classication systems is that axial or local recurrences
and therefore less points of xation are associated with either improved rates of R0
resection, survival, or both. No comparisons between the classication systems
exist to determine whether one is more prognostic than others.
319
Treatment andOncologic Outcomes
Since an R0 resection is the most consistent favorable factor for survival, it is critically important to maximize the chances of this. Multimodal therapy with a combination of chemotherapy, chemoradiotherapy, and surgery have shown the best
outcomes compared to surgery alone or radiotherapy alone [25–27]. Specic treatment received and the sequence of treatment depends on several factors related to
the extent of the local recurrence and prior treatment received.
The patients who are radiation naïve, should receive a full course of chemoradiation following the same protocols used for locally advanced rectal cancer with 50 to
50.4Gy in 25–28 fractions with radiosensitizing chemotherapy [28]. Patients who
previously received radiation can typically receive up to 30.4–39Gy in additional
radiation with acceptable toxicity [29–31]. Re-irradiation may be better tolerated
moving forward with increased use of intensity-modulated radiation therapy [32],
which allows precise dose delivery [33]. Hyperfractionated radiotherapy may also
reduce the late toxicity of reirradiation [34].
Receipt of radiation or re-irradiation is essential as pooled data from the Mayo
Clinic, Rochester and the Catharina Hospital, Eindhoven showed lower rates of R0
resections in patients who never received either radiation or re-irradiation (25.9%)
versus those who received full course (50.2%) or re-irradiation (43.0%) in the largest series to date (n=565) [25]. Additionally, neoadjuvant chemoradiation and reirradiation are associated with improved 3-year overall survival (full course 49.3%,
re-irradiation 47.6%, no radiation 25.0%) and 3-year local control (full course

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N. P. McKenna and R. R. Cima
69.0%, re-irradiation 48.9%, no radiation 37.6%) compared to patients who were
not re-irradiated [35]. Lastly, in a recent systematic review of studies from 1999 to
2021, the highest proportion of R0 resections were observed in patients treated with
neoadjuvant chemoradiotherapy compared to neoadjuvant radiotherapy or adjuvant
chemoradiotherapy [36].
Recently, Catharina Hospital, Eindhoven published their results of adding induction chemotherapy to the treatment regimen for recurrent rectal cancer with the goal
of improved downsizing the local recurrence and increasing pathologic complete
response rates. The regimen consists of either 3cycles of CAPOX (capecitabine and
oxaliplatin) or 4 cycles of FOLFOX (leucovorin, 5-uorouraicl, oxaliplatin) followed by radiation or re-irradiation as described above. If on restaging imaging a
patient had a good response to chemotherapy, consolidation chemotherapy is considered during the interval between radiation and surgery.
With this regimen, they achieved a 17% completely pathologic response [37, 38].
This is better than reported complete pathologic response rates of 8%–12% with
radiotherapy alone [39–41]. Mayo Clinic employs a similar protocol with 4cycles
of FOLFOX followed by re-staging imaging with PET-CT and musculoskeletal protocol MRI followed by radiation or re-irradiation [42].
With respect to long-term outcomes, patients in the Catharine Hospital experience with a complete pathologic response had a 3-year overall survival of 92%.
Since all patients with a complete response have an R0 resection, by denition, the
authors also studied patients with a good response to neoadjuvant therapy and R0
resection. These patients did better than patients with a poor response and R0 resection in both overall survival and local disease-free interval. Interestingly, patients
with a poor response but an R0 resection had outcomes similar to patients without
an R0 resection for both local-recurrence free survival and metastasis-free survival.
Toxicity from chemotherapy was acceptable with 10% of patients experiencing
grade 3–4 toxicity and no grade 5 events.
No other institutions have reported outcomes of induction chemotherapy for
locally recurrent chemotherapy yet, but the results from Catharina Hospital are
promising. They also are in line with the increasing utilization of total neoadjuvant
therapy for primary locally advanced rectal cancer [43], which is addressed in a
separate chapter. Randomized controlled trials comparing neoadjuvant chemotherapy followed by pelvic re-irradiation versus neoadjuvant chemotherapy alone
(GRECCAR 15) and neoadjuvant chemotherapy followed by pelvic re-irradiation
versus neoadjuvant chemoradiotherapy (PelvEx II) are currently recruiting patients
with recurrent rectal cancer [44, 45]. Therefore, higher-level evidence on preoperative therapy for recurrent rectal cancer may be available in the future.
Intraoperative radiation therapy can be added after surgical resection to overcome the dose tolerance of normal tissue to external beam radiation and reirradiation. Outcomes with the use of IORT are generally favorable in terms of local
control and survival without a concomitant increase in morbidity [25, 46–50]. At the
Mayo Clinic and Catharina Hospital, IORT is delivered via a dedicated linear accelerator in the operating room [25, 51]. The IORT dose is determined intraoperatively
based on frozen section pathologic margins and the radiation dose the patient
received preoperatively. For patients who received 45–54Gy preoperatively, IORT
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