title: An investigation into the relationship between the perioperative systemic inflammatory response and postoperative complications in patients undergoing surgery for colorectal cancer
Creators: name: Ramanathan, Michelle L.
Publisher: name: University of Glasgow
Year: 2015
Subjects: subject: colorectal cancer, systemic inflammatory response, infective complications, C-reactive protein.

description: Colorectal cancer is the second most common cause of cancer death in the western world. Despite improvements in diagnosis and treatment, 50% of patients still die from this disease. It is now recognised that postoperative infective complications contribute to poor cancer specific survival following resection for colorectal cancer. The basis of this observation is not clear. One hypothesis is that the presence of a raised systemic inflammatory response may be responsible. Whether a raised postoperative inflammatory response is the result of an early underlying infection at a preclinical stage, or whether a raised inflammatory response leads to increased susceptibility to subsequent infection is not known. If the former proves true, it is possible that targeting at risk patients with preemptive antibiotics may reduce infective complications and improve patient outcomes. Conversely, if the latter is the case, perioperative intervention to reduce the postoperative inflammatory response may reduce infective complications and hence improve outcomes, both short and long term, for patients undergoing colorectal cancer resection.

The work presented in this thesis further examines the relationship between the systemic inflammatory response and postoperative infective complications following resection for colorectal cancer, determines predictive thresholds for the development of postoperative infective complications, assesses the impact of the peak systemic inflammatory response on these thresholds and investigates the determinants of the peak response. Finally, the question as to whether a raised postoperative systemic inflammatory response is the cause or consequence of infective complications is examined.

Patients with colorectal cancer who have a raised systemic inflammatory response prior to surgery have been shown to have poorer long term and short term outcomes. The presence of an ongoing systemic inflammatory response in these patients may be due to impaired cortisol production. Chapter 3 examines the relationship between the perioperative systemic inflammatory response and endogenous cortisol production by assessment of adrenocortical function preoperatively in 80 patients undergoing resection for colorectal cancer.

Infective complications particularly in the form of surgical site infections including anastomotic leak represent a serious morbidity after colorectal cancer surgery. Systemic inflammation markers, including C-reactive protein and white cell count, have been reported to provide early detection. However their relative predictive value is unclear. Chapter 4 examines the diagnostic accuracy of serial postoperative white cell count, albumin and C-reactive protein in detecting infective complications in 454 patients undergoing surgery for colorectal cancer. It demonstrates that postoperative C-reactive protein measurement, particularly a threshold of 170 mg/l on day 3 postoperatively, is clinically useful in predicting surgical site infective complications, including an anastomotic leak, in patients following colorectal cancer resection.

Chapter 5 compares the value of daily C-reactive protein concentrations in the prediction of postoperative infective complications in patients undergoing open versus laparoscopic resection for colon cancer. Although the magnitude of the systemic inflammatory response, as evidenced by C-reactive protein, following surgery was greater in open compared with laparoscopic resection, the threshold concentrations of C-reactive protein for the development of postoperative infective complications were remarkably similar on days 3 and 4.

The postoperative systemic inflammatory response, as evidenced by C-reactive protein on days 3 and 4, is shown in chapters 4 and 5 to be associated with the development of infective complications following surgery for colorectal cancer. However, patients in enhanced recovery after surgery programmes require earlier assessment at day 2, at the peak inflammatory response to surgery. Chapter 6 assesses the impact of day 2 C-reactive protein, on concentrations at days 3 and 4. A day 2 C-reactive protein concentration &gt;190 mg/L was associated with day 3 and 4 concentrations above established thresholds for the development of infective complications.

Chapter 7 examines the clinicopathological determinants of the postoperative systemic inflammatory response, as evidenced by C-reactive protein concentrations on day 2, day 3 and day 4 in patients following resection of colorectal cancer. Chapter 7 demonstrates that several clinical factors are independently associated with the peak systemic inflammatory response, as evidenced by postoperative day 2 C-reactive protein concentration and threshold, following resection of colorectal cancer. In particular, emergency presentation, socioeconomic deprivation and preoperative systemic inflammation are associated with a higher peak systemic inflammatory response. In contrast, laparoscopic surgery is associated with a lower peak systemic inflammatory response.

Enhanced Recovery After Surgery (ERAS) programmes aim to attenuate the stress response to surgery, reduce the length of hospital stay and have been proposed to be associated with reduced morbidity and mortality. However, data on the effect of enhanced recovery on the systemic inflammatory response and infective complications remains limited. Chapter 8 examines the impact of enhanced recovery on the systemic inflammatory response and the rate of infective complications following elective surgery for colorectal cancer. Enhanced recovery was associated with a significant reduction in length of hospital stay. In contrast, the postoperative systemic inflammatory response was similar to that of conventional care. Overall complication rates, both non-infective and infective, were also similar.

Chapter 9 examines the relationships between postoperative predictive thresholds of Creactive protein and infective complications, in the context of the administration of preemptive antibiotic therapy, for patients undergoing resection for colorectal cancer. The administration of pre-emptive antibiotics guided by C-reactive protein thresholds predictive of infective complications did not reduce infective complication rates or the magnitude of the postoperative inflammatory response following elective resection for colorectal cancer.

In summary, the objective measurement of the postoperative systemic inflammatory response and its relationship with postoperative outcomes has profound implications for assessment and treatment of the surgical stress response in patients with colorectal cancer.