The role of Hartmann’s procedure in the elective management of rectal cancer: results of a Brazilian cohort study

ABSTRACT Background: although preservation of bowel continuity is a major goal in rectal cancer surgery, a colorectal anastomosis may be considered an unacceptably high-risk procedure, particularly for patients with multiple comorbidities. We aimed to assess rates of surgical complications in rectal cancer patients according to the type of procedure they had undergone. Materials and Methods: this cohort included all rectal cancer patients undergoing elective resection at a referral academic hospital over 16 years. There were three study groups according to the type of performed operation: (1) rectal resection with anastomosis without defunctioning stoma (DS); (2) rectal resection with anastomosis and DS; and (3) Hartmann’s procedure (HP). Postoperative complications and clinical outcomes were assessed. Results: four-hundred and two patients were studied. The 118 patients in group 3 were significantly older (>10 years), had higher Charlson Comorbidity Index scores, and more ASA class ≥3 than patients in the other two groups. Sixty-seven patients (16.7%) had Clavien-Dindo complications grade ≥ III, corresponding to an incidence of 11.8%, 20.9%, and 14.4% in groups 1, 2, and 3, respectively (p=0.10). Twenty-nine patients (7.2%) had major septic complications that required reoperation, with an incidence of 10.8%, 8.2% and 2.5% in groups 1, 2 and 3, respectively (p=0.048). Twenty-one percent of the group 2 patients did not undergo the stoma closure after a 24-month follow-up. Conclusion: HP was associated with a lower incidence of reoperation due to intra-abdominal septic complications. This procedure remains an option for patients in whom serious surgical complications are anticipated.


INTRODUCTION
A nastomotic leak (AL) is still a critical issue in rectal cancer surgery.Despite all recent surgical advances, such as the performance of total mesorectal excision and minimally invasive techniques, the rates of AL remain relatively high (5% to 19%) 1 , with negative impact on morbimortality [2][3][4] , and cancer recurrence 5 .
The primary method to prevent anastomotic dehiscence after a low anterior resection is to create a DS.Although this strategy may not reduce the incidence of leaking, it can mitigate its consequences, reducing the need for urgent abdominal reoperation 6 .The systematic use of a DS, however, remains controversial, in part because many patients with a "temporary" stoma will never undergo stoma reversal.According to a metaanalysis of ten studies, including 8,568 rectal cancer patients, the nonclosure rate of DSs is 19% 7 .Three variables were significantly associated with nonclosure: older age, ASA score >2, and presence of comorbidities.
Several risk factors for AL have been identified, including systemic conditions such as anemia, diabetes mellitus, and hypoalbuminemia.Local factors have also been implicated, including irradiation of bowel, intestinal ischemia, and a more distal location of the rectal tumor.
So, the crucial decision of performing or not a colorectal anastomosis, particularly in elderly individuals, should take into account the general clinical condition of the patient, including comorbidities and capability to overcome the life-threatening consequences of an AL 8 .The management of rectal cancer patients should include a thorough preoperative discussion with the patient and family about the potential risk of AL, its consequences, and the possibility of having a permanent Lazzaron The role of Hartmann's procedure in the elective management of rectal cancer: results of a Brazilian cohort study stoma at the end of the treatment.A more conservative approach, such as the performance of a Hartmann procedure, which does not include the construction of a colorectal anastomosis, can be alternatively considered in the critical cases.
To this date, despite the extensive literature on the surgical treatment of rectal cancer, very few studies have investigated the role of HP in the routine management of patients at a high risk for AL.Our study aimed to assess, in a strictly elective clinical setting, the rates of postoperative complications in patients with rectal cancer according to the type of operations they underwent (with or without colorectal anastomosis) and the presence of risk factors for AL.The exclusion criteria were synchronous distant metastases, palliative surgery, multivisceral resection (pelvic exenteration or partial resection of adjacent organs), and history of primary malignant neoplasm five years before the rectal operations.Abdominoperineal resections of the rectum were also excluded.We did not include patients for whom HP was not initially planned but ended up being performed due to intraoperative complications (such as massive bleeding with hemodynamic instability), which, according to the surgeon, precluded the construction of an anastomosis.

This
Initially, patients undergoing a colorectal anastomosis were compared with those undergoing a HP.Then, patients were further subdivided in three study groups according to the type of performed operation.Group 1: proctectomy with primary anastomosis without diversion; group 2: proctectomy with primary anastomosis with diversion (transverse colostomy or loop ileostomy); and group 3: HP.All procedures were decided consensually in the preoperative period after extensive discussion with the patient and family considering the potential surgical risks.The type of operation to be performed was routinely registered in the medical record before hospital admission.Tumor staging was determined according to the AJCC TNM Classification of Malignant Tumors, eighth edition 13 .

Postoperative Complications
Postoperative complications were analyzed according to the Clavien-Dindo (CD) classification system 14 .Grade III, IV, and V complications are the most severe and relevant, being this cutoff point widely used in previous studies 15,16  We also assessed the incidence of major abdominal septic complications, which included abdominal and pelvic infections (abscess/peritonitis) that required surgical reintervention by laparotomy or laparoscopy.
These are the most relevant surgical complications directly resulting from AL or rectal stump leak, representing the main interest of the study.Minor revision procedures, such as pelvic abscess drainage via anal and percutaneous puncture of abdominal collections, or purely mechanical complications (evisceration, bowel obstruction) were not classified as major abdominal septic complications.Finally, in those patients who had a DS, the stoma closure rate was analyzed.

Sample size
The sample size was calculated based on the study conducted by Jonker et al.The one-tailed Student's t-test was used to estimate differences in the incidence of major abdominal septic complications between patients with anastomosis and patients without anastomosis (HP).
With significance level of 5% and a power of 80%, 392 subjects would be needed.

Statistical analysis
Pearson's chi-squared and

RESULTS
A total of 548 patients with rectal cancer underwent proctectomy during the study period.Onehundred fourty-six of them were excluded according to the exclusion criteria, resulting in a study population of 402 patients.Their clinical characteristics are shown in Table 1.Patients who underwent HP (group 3) were significantly older (>10 years), had a higher CCI score, and a higher proportion of ASA class ≥3 than patients in the other two study groups.In contrast, group 2 had more distal tumors, underwent more neoadjuvant therapies, and there was a higher percentage of men.Table 2 shows the incidence of comorbidities between patients undergoing a HP and those who underwent a colorectal anastomosis and protective stoma.The median followup of the study was 38 months (interquartile range = 41 months).Postoperative complications according to Clavien-

Major abdominal septic complications
Twenty-nine patients (7.2%) had major abdominal septic complications.When all patients with anastomosis (groups 1 and 2) were compared with those who underwent HP, the incidences of major septic complications were 9.1% and 2.5%, respectively (p = 0.034).When the patients were further subdivided in the three study groups, the incidence was 10.8%, 8.2% and 2.5% in Groups 1, 2 and 3, respectively (p = Lazzaron The role of Hartmann's procedure in the elective management of rectal cancer: results of a Brazilian cohort study 0.048).When only patients with CCI ≥3 were analyzed, this difference was even more marked (Table 5).While 7 patients with CCI ≥3 in group 2 (15.2%) had major abdominal septic complications requiring abdominal reoperation, none in the Hartmann group presented this complication (< 0.001).Overall, the 30-day mortality was 2.9%, 1.1% and 3.4% in Groups 1, 2 and 3, respectively (p = 0.31).

Proctectomies with a protective stoma
A total of 182 patients had a DS.We analyzed all patients within a minimum postoperative follow-up of 24 months, resulting in 147 patients.Of these, 115 (78.2%) underwent stoma reversal.In three cases, the stoma had to be constructed again: two due to AL after the reversal operation, and one because of severe fecal incontinence (rediversion required after 14 months).The reasons why the other 32 patients (21.8%) did not undergo the reversal operation are presented in Table 6.Table 7 has the information regarding patients who did or did not undergo reversal surgery.The median time for the reversal was 12 months (interquartile range = 8 months).

DISCUSSION
The current article approaches one of the most crucial dilemmas of the colorectal surgeon: to perform or not an anastomosis in a patient with a high risk for AL.Our study is, to our knowledge, the first to compare surgical results between the preoperatively planned HP and the colorectal anastomosis in patients undergoing elective rectal resections.
Due to the observational nature of the study, a retrospective cohort, there was a series of significant differences between the study groups.As expected, patients undergoing HP were older, had higher CCI scores and ASA classes, reflecting the selective decision regarding rectal anastomosis our team has adopted over the years.The high proportion of HP in our series (29.3%) seems to be related with the low socioeconomic status of the study population.All the patients were using the governmental health system, and they usually have only limited access to specialized health services and proper diagnostic checkups.As a consequence, many of them present with more advanced tumors and multiple poorly managed comorbidities.Despite their significantly worse clinical conditions, patients in group 3 did not present increased CD ≥III complications.This result suggests that the strategy of avoiding an anastomosis in patients with multiple comorbidities might have reduced their chance of presenting severe postoperative complications.As previously demonstrated, higher ASA scores have been associated with increased postoperative morbidity, including a higher incidence of AL 17 .
We also decided to analyze a second primary endpoint: major septic abdominal complications, which included abdominal and pelvic infections (abscess/ peritonitis) that demanded surgical reintervention, were significantly older, had more comorbidities, and were more often classified as ASA 3 or 4. Thirty-day mortality was higher after HP (3.2% vs. 1.3% and 1.3% for low anterior resection with or without DS, p<0.001), but HP was not an independent predictor of mortality in the multivariable analysis.HP and low anterior resection with DS were associated with a lower rate of intra-abdominal infections (6.5% and 10.1% vs.16.2%, p<0.001) and reoperations (7.3% and 8.1% vs.16.5%, p<0.001).HP also had the lowest rate of an endpoint described as "any postoperative complication".
Our study is distinct from the previous reported studies because we only analyzed patients operated on with a curative intent for whom the type of operation (with or without anastomosis) was defined preoperatively.
Patients for whom HP was not initially planned but was performed due to intraoperative complications (such as massive bleeding, hemodynamic instability or perfuration) were excluded from the analysis since their procedures are usually longer and technically more complex.So, we analyzed the results of the three different operations in a strictly elective setting.
The AL rate in Groups 1 and 2 was 17.9%.
Previous studies have found post-proctectomy AL rates ranging from 5 to 19% 1,20 .Our relatively high rate of AL can be explained, in part, by our rigid definition of AL, which included any perianastomotic collection or abscess 11 .Also, we routinely follow a strict protocol of AL detection, which included C-reactive protein measurement on the fourth postoperative day, followed by abdominal CT-scan whenever the protein level was elevated.With this sequence, we can eventually detect pelvic abscesses that result from infected hematomas or intraoperative contamination, not from a true AL.
Another relevant aspect of our study is the analysis of the patients who had a DS.After 24 months, about 22% of patients did not have the stoma One issue that should not be underestimated is the morbidity of the stoma closure 15,22 .A metaanalysis assessed 6,107 patients undergoing the closure of loop ileostomy.Overall morbidity was 17.3%, with a mortality rate of 0.4%.Almost 4% of patients required a laparotomy to close the ileostomy.The most common postoperative complication was small bowel obstruction (7.2%) 23 .
Another important point to be considered is the chance of developing low anterior resection syndrome (LARS), a condition known for its highly negative impact on patients' quality of life.A recent meta-analysis of 11 studies found that the estimated prevalence of major LARS was 41%.Radiotherapy and low tumor height were the most consistently assessed variables, both presenting a negative effect on bowel function.DS was found to have a significant negative impact on bowel function in 4 of 11 studies 24 .
We strongly believe that the type of operation to be performed in rectal cancer should be decided preoperatively.Patients with multiple comorbidities must be informed about their increased risk of AL and the severe associated consequences, including a higher chance of undergoing surgical reintervention and death.

R E S U M O R E S U M O
retrospective cohort included all patients with rectal adenocarcinoma who underwent elective proctectomy at the Division of Coloproctology between January 1st, 2003, and December 31st, 2018.Medical records were reviewed for demographic, clinical, surgical, and pathological data.All tumors were located up to 15cm from the anal verge.Open, laparoscopic, and robotic tumor-specific mesorectal excisions were performed.All procedures were performed by experienced board certificated colorectal surgeons.When neoadjuvant treatment was used, it was always chemoradiation, using conventional doses of 2 Gy per fraction throughout five to six weeks for a total 50.4Gy with concurrent 5-fluorouracil-based chemotherapy 9 .Except for the individuals dying of early surgical complications, all patients had a minimum postoperative follow-up of six months.
Fisher's exact tests were used to determine the association between categorical variables, while ANOVA, Student's t-test, Kruskal-Wallis, and the Mann-Whitney U test were used to compare the distribution of continuous variables.Categorical variables are presented as frequencies or percentages, and continuous variables are presented as means or medians, depending on the distribution Lazzaron The role of Hartmann's procedure in the elective management of rectal cancer: results of a Brazilian cohort study type.Variables independently associated with CD ≥III were determined by the Poisson regression with robust variance.The significance level was set at 5%.This study was approved by our Institutional Ethics Committee under the number 60630116.0.0000.5327.
reversed.The only factor significantly associated with the nonreversal was a more distal tumor location.Previous authors have identified specific characteristics that reduce the chance of closing temporary stomas.Pan et al. 21investigated 296 patients who underwent anterior resection of the rectum with protective ileostomy.After a mean follow-up of 29 months, the ileostomy could not be closed in 17.2% of the patients.Metastatic disease, a CCI score >1, and complications during the initial operation were independent risk factors for non-reversal of ileostomies.More recently, a meta-analysis aimed to identify the risk factors associated with the nonclosure of DS after rectal cancer surgery 7 .Ten studies with 8,568 patients were reviewed.The nonclosure rate was 19%.Three demographic factors were associated with nonclosure: older age, ASA score >2 and comorbidities.Besides, surgical complications, AL, stage IV tumor, and local recurrence were strong risk factors for nonclosure.

Table 1 .
Demographic and clinical characteristics of the patients (N = 402).

Table 2 .
Differences in comorbidities between patients in groups 2 and 3.
* Chi-square with Yates correction.**Fisher'sexact test.All others: Chi-square with Yates correction.LazzaronThe role of Hartmann's procedure in the elective management of rectal cancer: results of a Brazilian cohort study

Table 4 .
Postoperative complications according to the study groups.

Table 6 .
Reasons for not performing the stoma closure (n=32).

Table 7 .
Characteristics of patients in group 2 (24-month follow-up, n = 147) according to the reversal of the stoma.
LazzaronThe role of Hartmann's procedure in the elective management of rectal cancer: results of a Brazilian cohort study LazzaronThe role of Hartmann's procedure in the elective management of rectal cancer: results of a Brazilian cohort study they recognized, could be the reason for the surgeon to perform the HP.