Anastomotic leakage after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer.

BACKGROUND: Anastomotic leakage (AL) after colorectal surgery is well-researched, yet the effect of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) after Cytoreductive Surgery (CRS) is unclear. Assessment of risk factors in these patients may assist surgeons during perioperative decision making. METHODS: This was a single-center, retrospective study of patients who underwent CRS-HIPEC for colorectal peritoneal metastases. Main outcome measures were anastomotic leakage and associated morbidity. RESULTS: AL was observed in 17 of the 234 (7.3%) anastomoses in 17 of the total of 165 (10.3%) of patients. No association was observed between the number and location of anastomoses and AL, although only one in 87 small bowel anastomoses showed leakage. The only factor associated with AL was administration of bevacizumab within 60 days prior to surgery with an odds ratio (OR) of 6.13 (1.32-28.39), P = 0.03. Deviating stomata were not statistically protective of increased morbidity, although more AL occurred in the patients with colocolic and colorectal anastomoses when no concomitant deviating stoma was created. Deviation stomata were reversed in 52.6%, and no AL was observed after stoma reversal. CONCLUSION: The overall AL rate of CRS-HIPEC is comparable to colorectal surgery, and there is no cumulative risk of multiple anastomoses - especially in the case of small bowel anastomoses. Deviating stomata should be considered in patients with colocolic or colorectal anastomosis, although there is a significant chance that the stoma will not be reversed in these patients. Due to increased AL-risk surgeons should be aware of previous bevacizumab treatment, and plan the CRS-HIPEC at least 60 days after the treatment-day.

Psychological effects of the intensified follow-up of the CEAwatch trial after treatment for colorectal cancer.

BACKGROUND: The aim of the study was to evaluate psychological effects of the state-of-art intensified follow-up protocol for colorectal cancer patients in the CEAwatch trial. METHOD: At two time points during the CEAwatch trial questionnaires regarding patients' attitude towards follow-up, patients' psychological functioning and patients' experiences and expectations were sent to participants by post. Linear mixed models were fitted to assess the influences and secular trends of the intensified follow-up on patients' attitude towards follow-up and psychological functioning. As secondary outcome, odds ratios were calculated using ordinal logistic mixed model to compare patients' experiences to their expectations, as well as their experiences at two different time points. RESULTS: No statistical significant effects of the intensified follow-up were found on patients' attitude towards the follow-up and psychological functioning variables. Patients had high expectations of the intensified follow-up and their experiences at the second time point were more positive compared to the scores at the first time point. CONCLUSION: The intensified follow-up protocol posed no adverse effects on patients' attitude towards follow-up and psychological functioning. In general, patients were more nervous and anxious at the start of the new follow-up protocol, had high expectations of the new follow-up protocol and were troubled by the nuisances of the blood sample testing. As they spent more time in the follow-up and became more adapted to it, the nervousness and anxiety decreased and the preference for the frequent blood test became high in replacement of conversations with the doctors.

Predictive performance of TPA testing for recurrent disease during follow-up after curative intent surgery for colorectal carcinoma.

BACKGROUND: The aim of the present study was to investigate the predictive performance of serial tissue polypeptide antigen (TPA) testing after curative intent resection for detection of recurrence of colorectal malignancy. METHODS: Serum samples were obtained in 572 patients from three different hospitals during follow-up after surgery. Test characteristics of serial TPA testing were assessed using a cut-off value of 75 U/L. The relation with American Joint Committee on Cancer stage and the potential additive value of tissue polypeptide antigen testing upon standard carcinoembryonic antigen (CEA) testing were investigated. RESULTS: The area under the receiver operating characteristic curve of TPA for recurrent disease was 0.70, indicating marginal usefulness as a predictive test. Forty percent of cases that were detected by CEA testing would have been missed by TPA testing alone, whilst most cases missed by CEA were also not detected by TPA testing. In the subpopulation of patients with stage III disease predictive performance was good (area under the curve 0.92 within 30 days of diagnosing recurrent disease). In this group of patients, 86% of cases that were detected by CEA were also detected by TPA. CONCLUSIONS: Overall, TPA is a relatively poor predictor for recurrent disease during follow-up. When looking at the specific subpopulation of patients with stage III disease predictive performance of TPA was good. However, TPA testing was not found to be superior to CEA testing in this specific subpopulation.

Strengths and weaknesses of a stepped wedge cluster randomized design: its application in a colorectal cancer follow-up study.

OBJECTIVES: To determine the advantages and disadvantages of a stepped wedge design for a specific clinical application. STUDY DESIGN AND SETTING: The clinical application was a pragmatic cluster randomized surgical trial intending to find an increased percentage of curable recurrences in patients in follow-up after colorectal cancer. Advantages and disadvantages of the stepped wedge design were evaluated, and for this application, new advantages and disadvantages were presented. RESULTS: A main advantage of the stepped wedge design was that the intervention rolls out to all participants, motivating patients and doctors, and a large number of patients who were included in this study. The stepped wedge design increased the complexity of the data analysis, and there were concerns regarding the informed consent procedure. The repeated measurements may bring burden to patients in terms of quality of life, satisfaction, and costs. CONCLUSION: The stepped wedge design is a strong alternative for pragmatic cluster randomized trials. The known advantages hold, whereas most of the disadvantages were not applicable to this application. The main advantage was that we were able to include a large number of patients. Main disadvantages were that the informed consent procedure can be problematic and that the analysis of the data can be complex.

Detection of recurrences during follow-up after liver surgery for colorectal metastases: both carcinoembryonic antigen (CEA) and imaging are important.

BACKGROUND: The follow-up of patients treated for colorectal liver metastases (CRLM) is not standardized. The accuracy of an increase in carcinoembryonic antigen (CEA) levels for finding recurrences after treatment for CRLM is compared in this retrospective cohort study with the accuracy of routine imaging modalities of liver and chest. METHODS: Data from all patients in follow-up after intentionally curative treatment for CRLM from 1990 to 2010 were analyzed. All patients underwent the same follow-up schedule. The way in which recurrences became apparent (i.e., CEA increase, routine imaging, or both) was registered. The specificity and sensitivity of increases in CEA before finding recurrent disease were calculated by receiver operating characteristic (ROC) curves. An economic evaluation of the cost per resectable tumor recurrence was performed. RESULTS: ROC curves showed that a significant CEA increase was defined as a 25 % increase from the previous value. Recurrences were detected in 46 % of the procedures through CEA increase concomitant with positive imaging, in 23 % through CEA increase without positive findings on routine imaging, and in 31 % through positive imaging without an increase in CEA. The resectability of recurrences did not differ between triggers. Cost per curable recurrence was 2,196 for recurrences found via CEA alone and 6,721 for recurrences found with imaging and CEA. CONCLUSIONS: In the follow-up of patients after liver surgery for CRLM, a 25 % increase in CEA serum level can accurately detect recurrences, but routine imaging is indispensable. In patients with CRLM, we advocate both CEA monitoring and imaging in the follow-up after liver surgery.

Evaluation of the use of decision-support software in carcino-embryonic antigen (CEA)-based follow-up of patients with colorectal cancer.

BACKGROUND: The present paper is a first evaluation of the use of "CEAwatch", a clinical support software system for surgeons for the follow-up of colorectal cancer (CRC) patients. This system gathers Carcino-Embryonic Antigen (CEA) values and automatically returns a recommendation based on the latest values. METHODS: Consecutive patients receiving follow-up care for CRC fulfilling our in- and exclusion criteria were identified to participate in this study. From August 2008, when the software was introduced, patients were asked to undergo the software-supported follow-up. Safety of the follow-up, experiences of working with the software, and technical issues were analyzed. RESULTS: 245 patients were identified. The software-supported group contained 184 patients; the control group contained 61 patients. The software was safe in finding the same amount of recurrent disease with fewer outpatient visits, and revealed few technical problems. Clinicians experienced a decrease in follow-up workload of up to 50% with high adherence to the follow-up scheme. CONCLUSION: CEAwatch is an efficient software tool helping clinicians working with large numbers of follow-up patients. The number of outpatient visits can safely be reduced, thus significantly decreasing workload for clinicians.

The Role of High Frequency Dynamic Threshold (HiDT) Serum Carcinoembryonic Antigen (CEA) Measurements in Colorectal Cancer Surveillance: A (Revisited) Hypothesis Paper.

Following curative treatment for colorectal cancer (CRC), 30% to 50% of patients will develop recurrent disease. For CRC there are several lines of evidence supporting the hypothesis that early detection of metachronous disease offers a second opportunity for cure. This paper revisits the potential role of serum carcinoembryonic antigen (CEA) in follow-up. A comprehensive review of the literature (1978-2008) demonstrates that the initial promise of serum CEA as an effective surveillance tool has been tarnished through perpetuation of poorly designed studies. Specific limitations included: testing CEA as only an 'add-on' diagnostic tool; lack of standardization of threshold values; use of static thresholds; too low measurement frequency. Major changes in localizing imaging techniques and treatment of metastatic CRC further cause a decrease of clinical applicability of past trial outcomes. In 1982, Staab hypothesized that the optimal benefit of serum CEA as a surveillance tool is through high-frequency triage using a dynamic threshold (HiDT). Evidence supporting this hypothesis was found in the biochemical characteristics of serum CEA and retrospective studies showing the superior predictive value of a dynamic threshold. A multi-centred randomized phase III study optimizing the usage of HiDT against resectability of recurrent disease is commencing recruitment in the Netherlands.