Category Archives: Colorectal Surgery

Adjuvant chemotherapy for rectal cancer: The PROCTOR-SCRIPT trial

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A discussion this week included adjuvant chemotherapy for rectal cancer after neoadjuvant and surgery.

Reference: Breugom AJ, et al. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Annals of Oncology. 2015 Apr;26(4):696-701. doi:10.1093/annonc/mdu560.

Summary: Locoregional recurrence rates and survival have significantly
improved with the introduction of total mesorectal excision (TME) for patients with rectal cancer. The addition of preoperative radiotherapy to TME surgery resulted in a more than 50% decrease in locoregional recurrences. However, the combination of preoperative (chemo)radiotherapy and TME surgery did not improve overall or disease-free survival.  Up to 30% of all patients treated with curative intent for localized rectal cancer will develop distant metastases, and distant metastases are still the main cause
of death after rectal cancer.

A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to investigate the value of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME surgery. The primary outcome was overall survival. Secondary outcomes were disease-free survival, overall recurrence rate, and locoregional and distant recurrence rate separately.

METHODS: Patients from 52 hospitals were recruited. Those with histologically proven stage II or III rectal adenocarcinoma were randomly assigned to observation (n=221) or adjuvant chemotherapy (n=216) after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival.

RESULTS: Between 1 March 2000 and 1 January 2013, 470 patients were included, of whom 33 were incorrectly randomized. Therefore, 437 patients (309 Dutch and 128 Swedish patients) were eligible for analyses. The trial was finally closed due to poor patient accrual without reaching the intended inclusion.

  • Survival: A total of 95 patients died. Five-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group.
  • Disease-free survival: No statistically significant difference in disease-free survival was
    observed. Five-year disease-free survival was 55.4% for the observation group and 62.7% for the chemotherapy group.
  • Recurrences: In total, there were 157 recurrences. At 5 years, the cumulative incidence for overall recurrences was 40.3% in the observation group and 36.2% in the chemotherapy group.
  • Locoregional recurrences: The 5-year cumulative incidence for locoregional recurrences was 7.8% in the observation group versus 7.8% in the chemotherapy group. This amounted to 38.5% and 34.7%, respectively, for distant recurrences.

CONCLUSION: The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy regarding overall survival, disease-free survival, and recurrence rates after preoperative (chemo)radiotherapy and TME surgery in ypTNM stage II and III rectal cancer patients. However, this trial did not complete planned accrual.

Helicobacter pylori infection: patient management

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One discussion this week involved the management of patients with helicobacter pylori infection.

Reference: DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. T114484, Helicobacter pylori infection; [updated 2018 Dec 04, cited 2019 Apr 05]. Emory login required. [NOTE: direct link is not functional. Go to DynaMed Plus main page and search “helicobacter pylori infection” to access full content.]

Summary: Management overview (DynaMed Plus, 2018)

  • offer treatment to all patients who test positive for active infection with Helicobacter pylori (ACG Strong recommendation)(1); the clinical efficacy of H. pylori eradication varies among associated conditions
    • peptic ulcer disease
      • in patients with H. pylori-positive duodenal ulcers, H. pylori eradication therapy (alone or in addition to ulcer-healing drugs) may increase ulcer healing, and eradication therapy alone may reduce ulcer recurrence (level 3 [lacking direct] evidence)
      • in patients with H. pylori-positive gastric ulcers, addition of H. pylori eradication therapy to ulcer-healing drugs may not improve ulcer healing but H. pylori eradication therapy alone may reduce ulcer recurrence (level 3 [lacking direct] evidence)
      • peptic ulcer bleeding
        • H. pylori eradication therapy appears more effective than short-term antisecretory therapy or long-term ranitidine in preventing recurrent peptic ulcer bleeding in patients not taking nonsteroidal anti-inflammatory drugs (NSAIDs) (level 2 [mid-level] evidence)
        • H. pylori eradication therapy appears less effective than daily proton pump inhibitor (PPI) for preventing recurrent peptic ulcer bleeding in patients who continue long-term NSAIDs (level 2 [mid-level] evidence)
    • precancerous gastric lesions – H. pylori eradication may reduce progression of lesions (level 3 [lacking direct] evidence)
    • iron deficiency anemia – eradicating H. pylori may improve response to oral iron therapy
    • nonulcer dyspepsia – H. pylori eradication improves but does not eliminate symptoms (level 1 [likely reliable] evidence)
    • chronic gastritis – H. pylori eradication may decrease histologic evidence of gastritis in multiple clinical settings (level 3 [lacking direct] evidence), but may not be associated with improved symptoms in children (level 2 [mid-level] evidence)
    • long-term PPI use – H. pylori eradication reduces healthcare use and may reduce dyspepsia symptoms but not reflux symptoms (level 1 [likely reliable] evidence)
    • long-term NSAID use – H. pylori eradication prevents ulcers and ulcer complications in patients starting NSAIDs (level 1 [likely reliable] evidence) but may be less effective than long-term PPI use (level 2 [mid-level] evidence)
    • immune thrombocytopenia – H. pylori eradication improves platelet count (level 2 [mid-level] evidence)
    • gastroesophageal reflux disease (GERD) – H. pylori eradication does not clearly cause, improve, or worsen GERD symptoms (level 2 [mid-level] evidence)
    • asymptomatic patients – H. pylori eradication may prevent future dyspepsia (level 2 [mid-level] evidence), but low overall risk (< 15%) may not warrant such therapy
  • when choosing therapy, consider all of following(1)
    • patient’s history of penicillin allergy, and history of macrolide exposure
    • patient’s ability to adhere to a multidrug regimen with potential adverse effects
    • sensitivity of regional H. pylori strain to the combination of antibiotics administered (H. pylori clarithromycin resistance is > 15% in many areas of North America); see Antimicrobial resistance considerations in Recommendations section for details

Additional Reading: Chey WD, et al. ACG Clinical Guideline: Treatment of Helicobactor pylori infection. American Journal of Gastroenterology. 2017 Feb;112(2):212-239. doi: 10.1038/ajg.2016.563.

Management of elective surgery for diverticulitis

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One discussion this week was on the management of elective surgery for acute diverticulitis.

Reference: Wieghard N, Geltzeiler CB, Tsikitis VB. Trends in the surgical management of diverticulitis. Annals of Gastroenterology. 2015 Jan-Mar;28(1):25-30.

Summary: Wieghard et al (2015) state that sigmoid diverticulitis is an increasingly common Western disease associated with a high morbidity and cost of treatment. Improvement in the understanding of the disease process, along with advances in the diagnosis and medical management has led to recent changes in treatment recommendations. The natural history of diverticulitis is more benign than previously thought and despite current recommendations of more restrictive indications for surgery, practice trends indicate an increase in elective operations for the treatment of diverticulitis. Due to diversity in disease presentation, in many cases, optimal surgical treatment of acute diverticulitis remains unclear with regard to patient selection, timing, and technical approach in both elective and urgent settings.

The table below (Wieghard et al, 2015, p.28) provides direct comparison between ASCRS and ACPGBI recommendations for surgical treatment:

diverticulitis 1

diverticulitis 2

Additional Reading: Xai J, Paul Olson TJ, Rosen SA. Robotic-assisted surgery for complicated and uncomplicated diverticulitis: a single-surgeon case series. Journal of Robotic Surgery. 2019 Jan 23. doi: 10.1007/s11701-018-00914-x. [Epub ahead of print]

Risk of acute kidney injury in patients on vancomycin

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One discussion this week included the use of vancomycin in the setting of acute kidney injury (AKI).

Reference: Navalkele B, et al. Risk of acute kidney injury in patients on concomitant vancomycin and piperacillin-tazobactam compared to those on vancomycin and cefepime. Clinical Infectious Diseases. 2017 Jan 15;64(2):116-123. doi:10.1093/cid/ciw709.

Summary: In a retrospective, matched, cohort study of 558 patients, Navlkele et al (2017) compared the incidence of AKI among patients receiving combination therapy with vancomycin + piperacillin-tazobactam (VPT) to a matched group receiving vancomycin + cefepime (VC).

AKI rates were significantly higher in the VPT group than the VC group (81/279 [29%] vs 31/279 [11%]). In multivariate analysis, therapy with VPT was an independent predictor for AKI (hazard ratio = 4.27; 95% confidence interval, 2.73-6.68). Among patients who developed AKI, the median onset was more rapid in the VPT group compared to the VC group (3 vs 5 days P =< .0001).

Types of perirectal abscesses

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One discussion this week involved perirectal abscesses.

Reference: Calandrella C, La Gamma N. Abscess, Perirectal. In StatPearls [NCBI Bookshelf]. Last updated: 2018 Oct 27.

Summary: Although often thought of as the same, perianal abscess and perirectal abscesses differ in both complexity and care options. Except for perianal abscess which can be simply incised and drained as definitive care, all others usually require intravenous antibiotics, surgical evaluation, and drainage. A majority of abscesses are diagnosed clinically based on skin findings and palpitation of the affected area alone, but some require advanced imaging to determine the extent of infiltration.

A perirectal abscess can be further divided into a category based on anatomical location: ischiorectal abscess, intersphincteric abscess, and supralevator abscess. Given the variability in location and severity of the abscess, it is important to consider the presence of fistulas or tracts which may contribute to the spread of the infection. Perianal abscesses are the most common type, followed by ischiorectal, and intersphincteric abscesses.

Alternatively, the Park’s classification system which groups the fistulas into 4 types based on the course of the fistula and the relationship to the anal sphincters.

  • Intersphincteric (70%): Between the internal and external sphincters
  • Trans-sphincteric (25%): Extends thru the external sphincter into the ischiorectal fossa
  • Suprasphincteric (5%): Lasses from the rectum to the skin through the levator ani
  • Extrasphincteric (1%): Extends from the intersphincteric plane through the puborectalis

EPIDEMIOLOGY: The incidence of anorectal abscesses is 1:10,000, resulting in approximately 68,000 to 96,000 cases in the United States per year with a male prevalence of 3:1 during the third and fourth decades of life. The condition is seen more in the summer and spring months. Although often a concern of the patient, data does not support that there is an increased risk from hygiene, anal-receptive intercourse, diabetes, obesity, race, or altered bowel habits.

Laparoscopic entry techniques

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One discussion this week involved laparoscopic entry techniques.

Reference: Ahmad G, et al. Laparoscopic entry techniques. The Cochrane Database of Systematic Reviews. 2019 Jan 18;1:CD006583. doi: 10.1002/14651858.CD006583.pub5

Summary: In their updated systematic review on the topic, Ahmed et al (2019) included 57 RCTs including four multi-arm trials, with a total of 9865 participants, and evaluated 25 different laparoscopic entry techniques.

Overall, evidence was insufficient to support the use of one laparoscopic entry technique over another. Researchers noted an advantage of direct trocar entry over Veress needle entry for failed entry. Most evidence was of very low quality; the main limitations were imprecision (due to small sample sizes and very low event rates) and risk of bias associated with poor reporting of study methods.

Open-entry vs closed-entry: Evidence was insufficient to show whether there were differences between groups for:

  • vascular injury (Peto OR 0.14, 95% CI 0.00 to 6.82; 4 RCTs; n=915; I²=N/A)
  • visceral injury (Peto OR 0.61, 95% CI 0.06 to 6.08; 4 RCTs; n=915: I²=0%)
  • failed entry (Peto OR 0.45, 95% CI 0.14 to 1.42; 3 RCTs; n=865; I²=63%)

Direct trocar vs Veress needle entry: Trial results show a reduction in failed entry into the abdomen with the use of a direct trocar in comparison with Veress needle entry (Peto OR 0.24, 95% CI 0.17 to 0.34; 8 RCTs; n=3185; I²=45%; moderate-quality evidence).

Direct vision entry vs Veress needle entry: Evidence was insufficient to show whether there were differences between groups in rates of:

  • vascular injury (Peto OR 0.39, 95% CI 0.05 to 2.85; 1 RCT; n=186)
  • visceral injury (Peto OR 0.15, 95% CI 0.01 to 2.34; 2 RCTs; n=380; I²=N/A)

Direct vision entry vs open entry: Evidence was insufficient to show whether there were differences between groups in rates of:

  • visceral injury (Peto OR 0.13, 95% CI 0.00 to 6.50; 2 RCTs; n=392; I²=N/A)
  • solid organ injury (Peto OR 6.16, 95% CI 0.12 to 316.67; 1 RCT; n=60)
  • failed entry (Peto OR 0.40, 95% CI 0.04 to 4.09; 1 RCT; n=60)

Radially expanding (STEP) trocars vs non-expanding trocars: Evidence was insufficient to show whether there were differences between groups in rates of:

  • vascular injury (Peto OR 0.24, 95% Cl 0.05 to 1.21; 2 RCTs; n=331; I²=0%)
  • visceral injury (Peto OR 0.13, 95% CI 0.00 to 6.37; 2 RCTs; n=331)
  • solid organ injury (Peto OR 1.05, 95% CI 0.07 to 16.91; 1 RCT; n=244)

(Ahmed et al, 2019, p.2)

PROSPER trial: A comparison of treatments for rectal prolapse

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One discussion this week involved the PROSPER trial of treatment for rectal prolapse.

References: Senapati A, et al. PROSPER: a randomised comparison of surgical treatments for rectal prolapse. Colorectal Disease. 2013 Jul;15(7):858-868. doi:10.1111/codi.12177

Summary: The PROSPER randomised control trial is a pragmatic, factorial (2 × 2) design trial in which 293 patients were randomised between abdominal and perineal surgery (i) (n=49), suture vs resection rectopexy for those receiving an abdominal procedure (ii) (n=78), or Altemeier’s vs Delorme’s for those receiving a perineal procedure (iii) (n=213). Primary outcome measures were recurrence of the prolapse, incontinence, bowel function and quality of life scores measured up to 3 years.

Recurrence rates were not significant in any comparisons:

  • abdominal vs perineal surgery: 20% vs 26%
  • suture vs resection rectopexy: 13% vs 26%
  • Altemeier’s vs Delorme’s: 24% vs 31%

It was noted that substantial improvements from baseline in quality of life following all procedures. Additionally, Vaizey, bowel thermometer and EQ-5D scores were not significantly different in any of the comparisons (Senapati et al, 2013).

Additional Reading: Bordeianou L, et al. Clinical practice guidelines for the treatment of rectal prolapse. Diseases of the Colon and Rectum. 2017 Nov;60(11):1121-1131. doi:10.1097/DCR.0000000000000889