Klaas Havenga

Avoiding long-term disturbance to bladder and sexual function in pelvic surgery, particularly with rectal cancer.

Urinary and sexual dysfunction are common problems after rectal cancer surgery, and the likely cause is damage to the pelvic autonomic nerves during surgery. In recent years, attention has been focused on preserving the autonomic nerves through a technique which is usually combined with total mesorectal excision or radical pelvic lymphadenectomy. The autonomic nerves consist of the paired sympathetic hypogastric nerve, sacral splanchnic nerves, and the pelvic autonomic nerve plexus. We will demonstrate the anatomy of the pelvic autonomic nerves and the relation of these nerves to the mesorectal fascial planes, and review the medical literature on sexual and urinary dysfunction after rectal cancer surgery with and without autonomic nerve preservation.

Risk factors for anastomotic leakage and leak-related mortality after colonic cancer surgery in a nationwide audit

Surgical resection with restoration of bowel continuity is the cornerstone of treatment for patients with colonic cancer. The aim of this study was to identify risk factors for anastomotic leakage (AL) and subsequent death after colonic cancer surgery.

Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab, capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer

BACKGROUND To evaluate the efficacy and tolerability of preoperative short-course radiotherapy followed by capecitabine and oxaliplatin treatment in combination with bevacizumab and subsequent radical surgical treatment of all tumor sites in patients with stage IV rectal cancer. PATIENTS AND METHODS Adults with primary metastasized rectal cancer were enrolled. They received radiotherapy (5 × 5 Gy) followed by bevacizumab (7.5 mg/kg, day 1) and oxaliplatin (130 mg/m2, day 1) intravenously and capecitabine (1000 mg/m2 twice daily orally, days 1-14) for up to six cycles. Surgery was carried out 6-8 weeks after the last bevacizumab dose. The percentage of radical surgical treatment, 2-year survival and recurrence rates, and treatment-related toxicity was evaluated. RESULTS Of 50 included patients, 42 (84%) had liver metastases, 5 (10%) lung metastases, and 3 (6%) both liver and lung metastases. Radical surgical treatment was possible in 36 (72%) patients. The 2-year overall survival rate was 80% [95% confidence interval (CI) 66.3%-90.0%]. The 2-year recurrence rate was 64% (95% CI 49.8%-84.5%). Toxic effects were tolerable. No treatment-related deaths occurred. CONCLUSIONS Radical surgical treatment of all tumor sites carried out after short-course radiotherapy, and bevacizumab-capecitabine-oxaliplatin combination therapy is a feasible and potentially curative approach in primary metastasized rectal cancer.BACKGROUND To evaluate the efficacy and tolerability of preoperative short-course radiotherapy followed by capecitabine and oxaliplatin treatment in combination with bevacizumab and subsequent radical surgical treatment of all tumor sites in patients with stage IV rectal cancer. PATIENTS AND METHODS Adults with primary metastasized rectal cancer were enrolled. They received radiotherapy (5 × 5 Gy) followed by bevacizumab (7.5 mg/kg, day 1) and oxaliplatin (130 mg/m(2), day 1) intravenously and capecitabine (1000 mg/m(2) twice daily orally, days 1-14) for up to six cycles. Surgery was carried out 6-8 weeks after the last bevacizumab dose. The percentage of radical surgical treatment, 2-year survival and recurrence rates, and treatment-related toxicity was evaluated. RESULTS Of 50 included patients, 42 (84%) had liver metastases, 5 (10%) lung metastases, and 3 (6%) both liver and lung metastases. Radical surgical treatment was possible in 36 (72%) patients. The 2-year overall survival rate was 80% [95% confidence interval (CI) 66.3%-90.0%]. The 2-year recurrence rate was 64% (95% CI 49.8%-84.5%). Toxic effects were tolerable. No treatment-related deaths occurred. CONCLUSIONS Radical surgical treatment of all tumor sites carried out after short-course radiotherapy, and bevacizumab-capecitabine-oxaliplatin combination therapy is a feasible and potentially curative approach in primary metastasized rectal cancer.

Preoperative Chemoradiotherapy with Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer. A Phase I–II Multicenter Study of the Dutch Colorectal Cancer Group

BackgroundWe studied the maximum tolerated dose (MTD) and efficacy of oxaliplatin added to capecitabine and radiotherapy (Capox-RT) as neoadjuvant therapy for rectal cancer.MethodsT3-4 rectal cancer patients received escalating doses of oxaliplatin (day 1 and 29) with a fixed dose of capecitabine of 1000 mg/m2 twice daily (days 1–14, 25–38) added to RT with 50.4 Gy and surgery after 6–8 weeks. The MTD, determined during phase I, was used in the subsequent phase II, in which R0 resection rate (a negative circumferential resection margin) was the primary end point.ResultsTwenty-one patients were evaluable. In the phase I part, oxaliplatin at 85 mg/m2 was established as MTD. In phase II, the main toxicity was grade III diarrhea (18%). All patients underwent surgery, and 20 patients had a resectable tumor. An R0 was achieved in 17/21 patients, downstaging to T0-2 in 7/21 and a pCR in 2/21.ConclusionCombination of Capox-RT has an acceptable acute toxicity profile and a high R0 resection rate of 81% in locally advanced rectal cancer. However the pCR rate was low.

Calcium score: a new risk factor for colorectal anastomotic leakage.

BACKGROUND Anastomotic leakage (AL) is the most feared complication of colorectal surgery. Atherosclerosis is suggested to have a detrimental effect on anastomotic healing. This study aimed to analyze the calcium score, a measure for atherosclerosis, as a risk factor for AL. STUDY DESIGN The calcium scores of colorectal patients operated on in 2 Dutch university medical centers were determined using a computed tomography scan and calcium scoring software. The aorta, common iliac arteries, internal and external iliac arteries were studied. Additionally, patient- and operation-related factors were scored. RESULTS A total of 122 patients were included. In patients with AL, calcium scores were significantly higher in the left common iliac artery (561.4 vs 156.0, P = .028), right common iliac artery (542.0 vs 144.4, P = .041), both common iliac arteries together (1,103.3 vs 301.9, P = .046), and the left internal iliac artery (716.3 vs 35.3, P = .044). CONCLUSIONS Patients with higher calcium scores in the iliacal arteries have an increased leakage risk.

Intensified follow-up in colorectal cancer patients using frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging : Results of the randomized "CEAwatch" trial

AIM The value of frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging for detecting recurrent disease in colorectal cancer (CRC) patients was investigated in search for an evidence-based follow-up protocol. METHODS This is a randomized-controlled multicenter prospective study using a stepped-wedge cluster design. From October 2010 to October 2012, surgically treated non-metastasized CRC patients in follow-up were followed in eleven hospitals. Clusters of hospitals sequentially changed their usual follow-up care into an intensified follow-up schedule consisting of CEA measurements every two months, with imaging in case of two CEA rises. The primary outcome measures were the proportion of recurrences that could be treated with curative intent, recurrences with definitive curative treatment outcome, and the time to detection of recurrent disease. RESULTS 3223 patients were included; 243 recurrences were detected (7.5%). A higher proportion of recurrences was detected in the intervention protocol compared to the control protocol (OR = 1.80; 95%-CI: 1.33-2.50; p = 0.0004). The proportion of recurrences that could be treated with curative intent was higher in the intervention protocol (OR = 2.84; 95%-CI: 1.38-5.86; p = 0.0048) and the proportion of recurrences with definitive curative treatment outcome was also higher (OR = 3.12, 95%-CI: 1.25-6.02, p-value: 0.0145). The time to detection of recurrent disease was significantly shorter in the intensified follow-up protocol (HR = 1.45; 95%-CI: 1.08-1.95; p = 0.013). CONCLUSION The CEAwatch protocol detects recurrent disease after colorectal cancer earlier, in a phase that a significantly higher proportion of recurrences can be treated with curative intent.

Can intraluminal devices prevent or reduce colorectal anastomotic leakage : A review

Colorectal anastomotic leakage is a serious complication of colorectal surgery, leading to high morbidity and mortality rates. In recent decades, many strategies aimed at lowering the incidence of anastomotic leakage have been examined. The focus of this review will be on mechanical aids protecting the colonic anastomosis against leakage. A literature search was performed using MEDLINE, EMBASE, and The Cochrane Collaborative library for all papers related to prevention of anastomotic leakage by placement of a device in the colon. Devices were categorised as decompression devices, intracolonic devices, and biodegradable devices. A decompression device functions by keeping the anal sphincter open, thereby lowering the intraluminal pressure and lowering the pressure on the anastomosis. Intracolonic devices do not prevent the formation of dehiscence. However, they prevent the faecal load from contacting the anastomotic site, thereby preventing leakage of faeces into the peritoneal cavity. Many attempts have been made to find a device that decreases the incidence of AL; however, to date, none of the devices have been widely accepted.

Definition of Total Mesorectal Excision, Including the Perineal Phase: Technical Considerations

Background: Total mesorectal excision (TME) has contributed to a decline in local recurrence. The operation is difficult because of the complicated anatomy of the pelvis and the narrow spaces in the pelvis. We review the anatomy related to TME and we present our surgical technique. Anatomy: The pelvis can be divided into a parietal compartment and a visceral compartment. Both compartments are covered by a fascial layer: the parietal and the visceral fascia. A space between these fascial layers can be opened by dividing loose areolar tissue. The pelvic autonomic nerves consist of the sympathetic hypogastric nerve and the parasympathetic sacral splanchnic nerve. At the pelvic sidewall these nerves join in the inferior hypogastric plexus. Surgery: We present our surgical technique based on careful dissection under direct vision and describe our approach to abdominoperineal resection in the knee-chest position. This position enables en bloc resection of the levator ani muscle with the mesorectum, preventing positive circumferential margins in distal rectal tumor. Conclusion: TME is a difficult and challenging operation. Continuous attention to surgical technique and anatomy is important to keep up the high standards of contemporary rectal surgery.

Late anastomotic leakage in colorectal surgery: a significant problem.

Reported incidence rates of colorectal anastomotic leakage (AL) vary between 2.5 and 20%. There is little information on late anastomotic leakage (LAL). The aim of this study was to determine the incidence of LAL after colorectal resection.

Anastomotic leakage as an outcome measure for quality of colorectal cancer surgery

Introduction When comparing mortality rates between hospitals to explore hospital performance, there is an important role for adjustment for differences in case-mix. Identifying outcome measures that are less influenced by differences in case-mix may be valuable. The main goal of this study was to explore whether hospital differences in anastomotic leakage (AL) and postoperative mortality are due to differences in case-mix or to differences in treatment factors. Methods Data of the Dutch Surgical Colorectal Audit were used. Case-mix factors and treatment-related factors were identified from the literature and their association with AL and mortality were analysed with logistic regression. Hospital differences in observed AL and mortality rates, and adjusted rates based on the logistic regression models were shown. The reduction in hospital variance after adjustment was analysed with Levenes test for equality of variances. Results 17 of 22 case-mix factors and 4 of 11 treatment factors related to AL derived from the literature were available in the database. Variation in observed AL rates between hospitals was large with a maximum rate of 17%. This variation could not be attributed to differences in case-mix but more to differences in treatment factors. Hospital variation in observed mortality rates was significantly reduced after adjustment for differences in case-mix. Conclusions Hospital variation in AL is relatively independent of differences in case-mix. In contrast to ‘postoperative mortality’ the observed AL rates of hospitals evaluated in our study were only slightly affected after adjustment for case-mix factors. Therefore, AL rates may be suitable as an outcome indicator for measurement of surgical quality of care.