Postoperative Diarrhea After Colorectal Cancer Surgery: What Patients Should Know About Risk Factors and Complications

Table of Contents

• Key Points
• Background: Why This Research Matters
• Study Methods: How the Research Was Conducted
• Who Participated in the Study
• Key Findings: How Common Was Postoperative Diarrhea?
• Predictors of Postoperative Diarrhea
• The Link Between Mild Diarrhea and Serious Complications
• Clinical Implications: What This Means for Patients
• Study Limitations: What This Study Couldn't Prove
• Recommendations for Patients
• Frequently Asked Questions
• Source Information

Key Points

• In a Japanese study of 178 patients, postoperative diarrhea occurred in 18.4% of those without a stoma.
• Smoking, hypertension, and rectal cancer surgery were independent predictors of postoperative diarrhea.
• Mild postoperative diarrhea preceded serious complications in 39.3% of patients, versus 14.6% without diarrhea.
• Patients with diarrhea had a 7.1% rate of urinary tract infection, compared to 0% without diarrhea.

Background: Why This Research Matters

Colorectal cancer (CRC) surgery is a life-saving procedure, but recovery can be complicated by a range of postoperative issues. One of the most frequently overlooked problems is postoperative diarrhea—a condition that can negatively affect a patient's nutritional status and overall clinical outcome during the critical recovery period.

Postoperative diarrhea has multiple potential causes. These include bowel stenosis (narrowing) caused by a large tumor, the surgical procedure itself, and medications given during the perioperative period. One well-known culprit is Clostridioides difficile (formerly called Clostridium difficile) infection, commonly abbreviated as CDI—a type of hospital-acquired intestinal infection that causes diarrhea and occasionally severe symptoms.

For patients who undergo surgery requiring a stoma (an opening on the abdomen through which waste leaves the body), there's an additional concern called high-output stoma (HOS). This condition occurs when the stoma produces an excessive amount of output, which can cause dehydration, kidney dysfunction, and electrolyte abnormalities. According to recent reports, HOS occurs in 16–43.3% of patients who have undergone rectal resection and have a diverting ileostomy.

Over the past decade, many retrospective studies (studies that look back at existing data) have examined chronic gastrointestinal complications after CRC surgery, including diarrhea. However, very few prospective studies—those that follow patients forward in time—have focused on acute postoperative diarrhea. The researchers behind the SHISA-1602 study aimed to fill this gap by identifying which patients are most at risk and whether postoperative diarrhea predicts other complications.

Study Methods: How the Research Was Conducted

This study, called SHISA-1602, was a multicenter, prospective, observational study conducted at six hospitals in Japan. Between June 2016 and December 2017, researchers enrolled 178 consecutive patients with colorectal cancer who were scheduled for elective radical surgery (surgery aimed at curing the cancer, not emergency surgery).

Patients were divided into three groups based on whether they received a stoma and what type:

1. Non-stoma group (147 patients)—no stoma was created
2. Colostoma group (17 patients)—a colostomy (stoma from the colon) was created
3. Ileostoma group (14 patients)—an ileostomy (stoma from the small intestine) was created

The study's inclusion criteria required that patients have a confirmed diagnosis of colorectal cancer, be scheduled for curative resection, be at least 20 years old, and have a performance status of 2 or lower on the Eastern Cooperative Oncology Group (ECOG) scale—meaning they were capable of at least some self-care. Patients were excluded if they had diarrhea before surgery, a history of CDI, required emergency surgery, had severe complications, or had a performance status of 3 or higher.

Postoperative diarrhea was defined using the World Health Organization's criteria as "frequent watery bowel movement for more than three times per day within postoperative 30 days." The diarrhea corresponded to type 6 (mild, meaning fluffy pieces with ragged edges or a mushy stool) and type 7 (severe, meaning watery with no solid pieces) on the Bristol stool chart, a widely used scale for classifying stool form.

For patients in the colostoma and ileostoma groups, high-output stoma (HOS) was defined as ostomy excretion of greater than 2000 mL per day within the first 30 days after surgery. If postoperative diarrhea or HOS was diagnosed, doctors performed a Clostridioides difficile toxin assay and fecal culture examinations at their discretion.

All other complications, including surgical site infection (SSI), were assessed using the Clavien–Dindo (C-D) classification system—a standard scale for grading the severity of surgical complications. Grade I complications are mild and don't require specific treatment, while Grade II requires medication, Grade III requires surgical or radiological intervention, and Grade IV involves life-threatening complications.

Who Participated in the Study

The study population comprised 96 men and 82 women, all of whom underwent colorectal cancer surgery at one of the six participating hospitals. The median age of participants was 71 years, and the median body mass index (BMI) was 22 kg/m².

Several health characteristics of the study population are important for understanding the results:

• Smokers: 72 patients (40.4%) had a smoking habit
• Hypertension (high blood pressure): 69 patients (38.8%)
• Diabetes mellitus: 28 patients (15.7%)
• Preoperative antibiotic use: 12 patients (6.7%)
• Preoperative antacid use: 32 patients (18.0%)
• Preoperative chemotherapy: 11 patients (6.2%)

Notably, no patients in the study underwent perioperative radiation therapy. The median preoperative hospital stay was 3 days. Before surgery, 157 patients (88.2%) underwent mechanical bowel preparation (using laxatives or enemas to empty the bowel), while 61 patients (34.3%) underwent chemical bowel preparation (using oral antibiotics to reduce bacteria in the gut).

Tumor locations among all 178 patients were as follows: right colon (60 patients), left colon (42 patients), rectum (75 patients), and both right colon and rectum (1 patient). The cancer stages, based on the TNM classification system, were distributed as follows: stage 0 (1 patient), stage I (45 patients), stage II (32 patients), stage III (74 patients), and stage IV (26 patients).

Most patients—127 out of 178 (71.3%)—underwent laparoscopic (minimally invasive) surgery. The median operation time was 240 minutes, and the median blood loss was 50 mL. Eleven patients (6.2%) required a blood transfusion during the operation.

Key Findings: How Common Was Postoperative Diarrhea?

The incidence of postoperative diarrhea varied significantly depending on whether patients had a stoma and what type of stoma they had.

In the non-stoma group (147 patients), the incidence of postoperative diarrhea was 18.4%—meaning 27 out of 147 patients experienced diarrhea within 30 days of surgery. This means that nearly one in five patients who had colorectal surgery without a stoma developed postoperative diarrhea.

In the ileostoma group (14 patients), high-output stoma occurred in 28.6% of patients (4 out of 14). This is a substantial proportion, highlighting the risk of dehydration and electrolyte imbalance for patients with this type of stoma.

In the colostoma group (17 patients), no cases of high-output stoma were observed (0%).

Among the 31 patients who experienced postoperative diarrhea or HOS, 17 patients (54.8%) underwent rapid CD toxin testing and fecal culture examinations. Here's what the testing revealed:

• All 17 patients tested negative for the CD toxin
• However, 2 patients (11.8%) showed CD-antigen positivity
• One of these two patients also had a positive fecal culture

Both patients with positive antigen tests were clinically diagnosed with mild Clostridioides difficile infection—one on the third postoperative day and the other on the fourth postoperative day. They were treated with metronidazole, a standard antibiotic for CDI, in accordance with clinical practice guidelines.

The other 29 patients with diarrhea (from causes other than CDI) all had mild symptoms that did not require special treatments such as antibiotics. They were classified as having C-D grade I postoperative complications—the mildest category.

For context on timing, the median onset of diarrhea was postoperative day 4, with a range from day 1 to day 20 after surgery. Interestingly, the median duration of postoperative hospitalization was 13 days in both patients who had diarrhea (range, 10–58 days) and those who did not (range, 7–90 days). This means that mild diarrhea itself didn't lengthen the hospital stay on average.

It's also worth noting that no patients in this study took postoperative laxatives (aperients) before the onset of diarrhea, ruling out medication-induced diarrhea as a contributing factor.

Predictors of Postoperative Diarrhea

Because the number of patients with high-output stoma in the stoma groups was too small for statistical analysis, the researchers focused their risk factor analysis on the non-stoma group of 147 patients. They performed both univariate analysis (examining each factor individually) and multivariable analysis (examining factors together to identify independent predictors).

Univariate Analysis: Individual Risk Factors

The univariate analysis identified three factors significantly associated with postoperative diarrhea:

• Smoking habits: 29.1% of smokers (16 out of 55) developed diarrhea, compared to only 12% of non-smokers (11 out of 92)—this difference was statistically significant (P = 0.0146)
• Hypertension: 26.7% of patients with high blood pressure (16 out of 60) developed diarrhea, compared to 12.6% of patients without hypertension (11 out of 87)—statistically significant (P = 0.0497)
• Tumor location (rectum): 28.3% of patients with rectal cancer (13 out of 46) developed diarrhea, compared to 13.9% of patients with colon cancer (14 out of 101)—statistically significant (P = 0.042)

Other factors—including gender, age, BMI, performance status, diabetes, preoperative medications, bowel preparation type, cancer stage, surgical approach, operation time, blood loss, and intraoperative transfusion—were not significantly associated with postoperative diarrhea in the univariate analysis.

Multivariable Analysis: Independent Predictors

The researchers then included the three significant variables from the univariate analysis in a multivariable logistic regression analysis using backward stepwise regression. This statistical method helps determine which factors are independently associated with the outcome, after adjusting for the influence of other factors.

The results revealed the following independent predictors of postoperative diarrhea:

• Smoking habits: Odds ratio (OR) of 3.14, with a 95% confidence interval of 1.29–7.66 (P = 0.012). This means that smokers were more than three times more likely to develop postoperative diarrhea than non-smokers, even after accounting for other factors.
• Hypertension: Odds ratio of 2.74, with a 95% confidence interval of 1.12–6.70 (P = 0.0274). Patients with high blood pressure were nearly three times more likely to develop postoperative diarrhea.
• Rectal cancer surgery: Odds ratio of 2.45, with a 95% confidence interval of 1.00–6.02 (P = 0.0501). This was borderline statistically significant, suggesting that rectal cancer surgery tends to be associated with postoperative diarrhea more than colon cancer surgery.

In plain language, a P-value of 0.012 means there's only a 1.2% chance that the association between smoking and diarrhea occurred by random chance. The odds ratio of 3.14 means smokers had 214% higher odds of developing postoperative diarrhea compared to non-smokers.

The Link Between Mild Diarrhea and Serious Complications

One of the most clinically important findings of this study concerns the relationship between mild postoperative diarrhea and the development of more serious complications. The researchers investigated whether patients with C-D grade I diarrhea (including HOS) were more likely to subsequently develop complications classified as C-D grade II (requiring medication) or higher.

They combined patients from the non-stoma and ileostoma groups who had undergone bowel reconstruction, totaling 158 patients for this analysis. Patients with diarrhea of C-D grade II or higher at the outset, and those who developed diarrhea after other complications (which could be antibiotic-induced), were excluded.

The results were striking:

Patients with mild (C-D grade I) diarrhea had a complication rate of 39.3% (11 out of 28 patients) for C-D grade II or III complications. In contrast, patients without postoperative diarrhea had a complication rate of only 14.6% (19 out of 130 patients). This difference was highly statistically significant (P = 0.0061).

Breaking down the types of complications:

• C-D grade II complications (requiring medication): 25% (7 out of 28) in patients with diarrhea vs. 11.5% (15 out of 130) in patients without—this difference approached but didn't reach statistical significance (P = 0.0741)
• C-D grade III complications (requiring surgical or radiological intervention): 14.3% (4 out of 28) in patients with diarrhea vs. 3.1% (4 out of 130) in patients without—statistically significant (P = 0.0337)

Here is the complete breakdown of complications observed in both groups:

Among patients with mild diarrhea (n = 28):

• Incisional surgical site infection: 2 patients (7.1%)
• Ileus (intestinal blockage): 2 patients (7.1%)
• Anastomotic leakage (leak at the surgical connection): 1 patient (3.6%)
• Intra-abdominal abscess: 1 patient (3.6%)
• Neurogenic bladder (bladder dysfunction): 1 patient (3.6%)
• Delirium (confusion): 1 patient (3.6%)
• Heart failure: 1 patient (3.6%)
• Urinary tract infection (UTI): 2 patients (7.1%)

Among patients without diarrhea (n = 130):

• Incisional surgical site infection: 6 patients (4.6%)
• Ileus: 4 patients (3.1%)
• Anastomotic leakage: 3 patients (2.3%)
• Intra-abdominal abscess: 1 patient (0.8%)
• Pneumonia: 2 patients (1.5%)
• Chyle leak (lymphatic fluid leak): 1 patient (0.8%)
• Port site hernia (hernia at incision site): 1 patient (0.8%)
• Postoperative transfusion: 1 patient (0.8%)

The most notable individual difference was in urinary tract infections: 7.1% of patients with postoperative diarrhea (2 out of 28) developed a UTI, compared to 0% in patients without diarrhea (P = 0.0305). Both patients who developed UTIs were men with rectal cancer and a smoking habit, and their UTIs occurred one day after the onset of postoperative diarrhea.

During the entire study period, there were no C-D grade IV (life-threatening) complications or C-D grade V complications (death related to surgery). Additionally, no patients experienced simultaneous C-D grade II and III complications.

Clinical Implications: What This Means for Patients

These findings carry several important messages for patients preparing for colorectal cancer surgery and for the medical teams caring for them.

First, smoking and hypertension are red flags. While the exact biological mechanisms linking these conditions to postoperative diarrhea remain unknown, the statistical association is strong. For smoking, previous research has shown that it's a risk factor for inflammatory bowel diseases like Crohn's disease and collagenous colitis. Nicotine can affect the immune system, cytokine levels, gut permeability, intestinal motility, and blood flow in the digestive tract. For hypertension, certain blood pressure medications—particularly beta-blockers and angiotensin II receptor blockers—are known to cause diarrhea as a side effect, though this study didn't analyze which specific antihypertensive drugs patients were taking.

Second, rectal cancer surgery carries additional risk. Patients undergoing surgery for rectal cancer tended to experience postoperative diarrhea more frequently than those having colon cancer surgery (28.3% vs. 13.9%). The researchers suggest this may relate to the reduced rectal reservoir capacity and the surgical sacrifice of the hypogastric nerve, which plays a role in bowel function.

Third, and most critically, mild diarrhea should not be dismissed. The finding that patients with mild (grade I) diarrhea had a 39.3% rate of subsequent serious complications—compared to 14.6% in patients without diarrhea—suggests that postoperative diarrhea may be an early warning sign. The researchers note that postoperative diarrhea is frequently overlooked due to its mild symptoms and the assumption that it will resolve on its own. This study suggests that even mild diarrhea deserves attention and monitoring.

The possible connection between diarrhea and urinary tract infections is particularly interesting. The researchers hypothesize that dehydration from diarrhea, combined with fecal contamination of the urinary tract, may explain why two patients developed UTIs shortly after diarrhea onset. However, they caution that with only two UTI cases, the data are insufficient to draw definitive conclusions.

Prior research supports the idea that postoperative diarrhea has real clinical consequences. A study by Gaertner and colleagues found that postoperative diarrhea—whether or not it was caused by CDI—was associated with superficial surgical site infections. Baker and colleagues reported that CDI significantly increased the likelihood of anastomotic leakage (leaking at the surgical connection site) in patients who had a colectomy. The SHISA-1602 researchers had also previously reported that early postoperative diarrhea might predict the development of symptomatic anastomotic leakage after laparoscopic low anterior resection.

Interestingly, this study did not find a significant correlation between postoperative diarrhea and ileus (bowel blockage) or acute kidney injury (AKI) of C-D grade II or higher, though these are theoretical concerns given that diarrhea can cause dehydration and reduced intestinal motility.

Study Limitations: What This Study Couldn't Prove

Every scientific study has limitations, and the SHISA-1602 study is no exception. Understanding these limitations helps put the findings in proper context.

Small sample size: With only 178 patients total—and just 14 patients in the ileostoma group and 17 in the colostoma group—the statistical power to detect differences, especially in the stoma groups, was limited. The researchers acknowledge that the small number of patients reduces the generalizability of the results.

Varied surgical procedures: The study included patients undergoing many different types of operations, from right hemicolectomy to abdominoperineal resection to total pelvic exenteration. Different procedures carry different risks and physiological impacts, which could influence results.

No standardized bowel preparation: Bowel preparation was left to the discretion of each hospital, meaning some patients received mechanical preparation, others received chemical preparation, and the protocols may have varied. This could have introduced confounding variables.

Challenges in diagnosing CDI: The CD toxin assay used in this study has relatively low sensitivity, meaning some cases of CDI may have been missed. This is a known limitation of these tests.

Non-standardized definition of HOS: There is no universally agreed-upon definition of high-output stoma. Definitions range from excretion of 1500 mL to more than 2000 mL per day, sometimes requiring the elevated output to persist for 2 consecutive days. The definition used in this study (over 2000 mL per day) may have influenced the results.

Antihypertensive drugs not analyzed: The study didn't record which specific blood pressure medications patients were taking, even though certain antihypertensive agents are known to cause diarrhea as a side effect. This means the association between hypertension and diarrhea could partially reflect medication effects rather than hypertension itself.

Observational design: As an observational study, this research can identify associations but cannot prove cause and effect. The researchers note that "the courses and mechanisms of postoperative diarrhea are diverse and complex" and call for further basic physiological and pathological studies along with clinical research.

Recommendations for Patients

Based on this research, here are some practical takeaways for patients preparing for colorectal cancer surgery:

1. Discuss smoking cessation with your healthcare team. If you smoke, consider trying to quit before your surgery. Smoking was the strongest predictor of postoperative diarrhea in this study, with smokers facing more than three times the risk of non-smokers. Even if the exact mechanism isn't fully understood, reducing this risk factor may help improve your recovery.
2. Talk to your doctor about your blood pressure medications. If you have hypertension, ask whether any of your current medications could contribute to diarrhea. Some blood pressure drugs (like beta-blockers and angiotensin II receptor blockers) are known to cause diarrhea in some patients. Your doctor may be able to adjust your regimen, but never stop or change blood pressure medications without medical supervision.
3. Be aware that rectal cancer surgery carries higher diarrhea risk. If you're having surgery for rectal cancer, know that 28.3% of patients in this study experienced postoperative diarrhea. Understanding this risk ahead of time can help you and your care team monitor for it proactively.
4. Report any diarrhea to your medical team—even if it seems mild. This study suggests that mild diarrhea may be an early warning sign of more serious complications to come. Don't dismiss it as a normal part of recovery. Tell your nurses and doctors about any loose or frequent stools, and ask them to monitor you closely for complications.
5. Ask about probiotics or synbiotics. The researchers mention that some studies have shown promising results for probiotics after CRC surgery. Yang and colleagues found that the incidence of diarrhea after CRC surgery was significantly lower in a probiotics group (26.7%, or 8 out of 30 patients) compared to a placebo group (53.3%, or 16 out of 30 patients). However, a larger randomized controlled trial by Komatsu and colleagues with 362 patients found no significant difference in postoperative complications between a synbiotic group and a control group. The evidence is mixed, but for patients with rectal cancer who smoke or have hypertension, the researchers suggest a week of prophylactic oral synbiotics (a combination of probiotics and prebiotics) might be worth trying. Discuss this with your surgeon.
6. If you have a stoma, learn about high-output stoma. The study confirms that HOS is a real concern for ileostomy patients, occurring in 28.6% of cases. If you have an ileostomy, ask your healthcare team what output volume should trigger concern and what to do if you notice excessive output. Watch for signs of dehydration, including dark urine, dizziness, and extreme thirst.
7. Monitor for urinary symptoms after diarrhea. Given the potential link between postoperative diarrhea and urinary tract infections, be aware of symptoms like burning during urination, frequent urination, or lower abdominal pain—especially in the days after a diarrhea episode—and report them promptly.

Remember that this study represents the experience of 178 patients at six Japanese hospitals. Individual outcomes can vary widely based on many factors, including your overall health, the specifics of your surgery, and the expertise of your surgical team. Always discuss your individual risk factors and concerns with your own healthcare providers.

Frequently Asked Questions

What factors increase the risk of postoperative diarrhea?

The study found that smoking, hypertension, and rectal cancer surgery were linked to higher diarrhea risk. Smokers had over 3 times the odds compared to non-smokers, and patients with high blood pressure had nearly 3 times the odds. These were independent predictors in the analysis.

Is mild diarrhea after colorectal cancer surgery something to worry about?

Yes, the study suggests mild diarrhea may be an early warning sign. Among patients with mild diarrhea, 39.3% later developed more serious complications, compared to 14.6% of those without diarrhea. Even mild diarrhea deserves close monitoring and should be reported to your medical team.

Should I stop smoking before colorectal cancer surgery to reduce diarrhea risk?

The study found smoking was the strongest predictor of postoperative diarrhea, with smokers facing more than three times the risk of non-smokers. Discuss smoking cessation with your healthcare team before surgery. Quitting may help improve your recovery, but always talk to your doctors first.

Can blood pressure medications contribute to postoperative diarrhea?

The study found hypertension was an independent predictor of postoperative diarrhea. Some blood pressure medications, like beta-blockers and angiotensin II receptor blockers, can cause diarrhea as a side effect. Ask your doctor whether any of your current medications could contribute. Never stop or change blood pressure medicines without medical supervision.

What should I do if I develop diarrhea after colorectal cancer surgery?

Report any loose or frequent stools to your nurses and doctors, even if it seems mild. The study found that mild diarrhea can be followed by more serious complications, including urinary tract infections. Your care team can monitor you closely and check for complications. Don't dismiss diarrhea as a normal part of recovery.

Source Information

Original Article Title: Predictors and clinical impact of postoperative diarrhea after colorectal cancer surgery

Authors: Hiroyuki Ohta, Toru Miyake, Tomoyuki Ueki, Masatsugu Kojima, Masayasu Kawasaki, Takeshi Tatsuta, Takekazu Iuchi, Sumihiro Kamitani, Tomoharu Shimizu, Eiji Mekata, Masaji Tani

Journal: International Journal of Colorectal Disease (2022) 37:657–664

DOI: https://doi.org/10.1007/s00384-022-04097-8

Study Registration: UMIN Clinical Trials Registry (UMIN 000,022,206)

This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and should not replace professional medical advice. Patients should always consult their healthcare providers regarding their individual medical situations.