Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase 3 CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group.

BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase 3 trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1:1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n= 103 without upfront PTR, n=101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (IQR 59-71). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% CI 16.0-22.2) compared to 20.1 months (95% CI 17.0-25.1) in the upfront PTR arm (p = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (p=0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSION: of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.

Comparison of extended hemicolectomy versus transverse colectomy in patients with cancer of the transverse colon.

BACKGROUND: Cancer of the transverse colon is rare and postoperative mortality tends to be high. Standard surgical treatment involves either extended hemicolectomy or transverse colectomy, depending on the location of the tumour. The aim of the present study was to compare postoperative mortality and five-year survival between these types of surgery. METHODS: For this observational study, data on patients with a tumour of the transverse colon, treated by open resection in the Dordrecht Hospital from 1989 through 2003, were derived from the database of the regional cancer registry. Information on type of resection, tumour stage, complications, postoperative mortality (30-day) and survival was abstracted from the medical files. Patients with multi-organ surgery, (sub)total colectomy or stage IV disease were excluded from the analysis, leaving a total series of 103 patients. RESULTS: Transverse colectomy comprised one third of operations, predominantly involving partial resections. Postoperative mortality was 6% (2/34) after transverse colectomy and 7% (5/69) after extended hemicolectomy. Five-year survival was slightly higher for the hemicolectomy group (61% versus 50%), but this difference did not reach statistical significance (p = 0.34). CONCLUSION: Our results confirm the high postoperative risk after surgery for cancer of the transverse colon and show that this risk does not depend on the type of surgery. Considering the satisfactory results after partial transverse colectomy, segmental resections may be considered as an option for the treatment of localised tumours of the transverse colon.

Outcome of surgery for colovesical and colovaginal fistulas of diverticular origin in 40 patients.

INTRODUCTION: According to literature, colonic resection with a primary anastomosis and no defunctioning ileostomy is a safe treatment for colovesical or colovaginal fistula of diverticular origin. This study investigates the outcome of surgery for this patient group in a regional hospital. METHODS: Patients were obtained from a prospective database in the period 2004-2011. Several variables were investigated for their relation with surgical outcome. RESULTS: A colovesical (n = 35) or colovaginal (n = 5) fistula was diagnosed in 18 men and 22 women. The mean age was 69 years (range, 45-90). A rectosigmoid resection with primary anastomosis was performed in 32 patients. Fourteen patients received a defunctioning ileostomy. Eight patients were treated with a Hartmann procedure. Overall 30-day treatment-related morbidity and mortality was 48 and 8 %, respectively. Major morbidity, because of anastomotic leakage, was mainly observed in the primary anastomosis group without a defunctioning ileostomy. Morbidity and mortality were associated with high body mass index, diabetes, use of corticosteroids, and American Society of Anesthesiologists classification, though not significantly. CONCLUSIONS: One should be liberal in the use of a defunctioning ileostomy in case of a primary anastomosis after colonic resection for a diverticular fistula, in order to prevent high morbidity rates due to anastomotic leakage.

Treatment of grade 2 and 3 hemorrhoids with Doppler-guided hemorrhoidal artery ligation.

AIM: We evaluated the results of the Doppler-guided hemorrhoidal arterial ligation (DG-HAL) method in the management of symptomatic grade 2 and 3 hemorrhoids. PATIENTS AND METHODS: Between June 2005 and March 2006, 110 consecutive patients with symptomatic grade 2 and 3 hemorrhoids according to the DG-HAL method were treated. All procedures were performed in daycare under spinal anesthesia. The primary objective was the reduction in hemorrhoidal gradation as determined by proctoscopy; the secondary was patient satisfaction. This was measured by interviewing patients over the telephone. RESULTS: The average age was 47.6 years. 42 patients had grade 2 hemorrhoids, 68 grade 3. An average of 7.3 ligations were placed. Proctoscopy showed that, after 6 weeks, 97 (88%) patients had a significant improvement in their hemorrhoidal gradation. After an average follow-up of 37 weeks, 93 of the 110 (84.5%) patients were satisfied with the postoperative result. Mortality was 0% and morbidity 3%. CONCLUSION: DG-HAL is a safe and effective treatment in the management of symptomatic grade 2 and 3 hemorrhoids.

Effects of brain death on stress and inflammatory response in the human donor kidney.

BACKGROUND: After kidney transplantation, a decreased graft survival is seen in grafts from brain dead donors compared to living donors, possibly related to a progressive inflammatory reaction in the graft. In this study, we focused on the effects of brain death on the inflammatory response (adhesion molecules, leukocyte infiltration, and gene expression) and stress-related heat shock proteins in the human kidney. Research outcomes and clinical donor parameters were linked to outcome data after transplantation. METHODS: Human kidney biopsy specimens were obtained during organ retrieval from brain dead and living organ donor controls. On these specimens, immunohistochemistry and semiquantitative RT-PCR were performed. Regression analyses were performed connecting results to outcome data of kidney recipients. RESULTS: In brain death, immunohistochemistry showed an increase of E-selectin and interstitial leukocyte invasion versus controls; RT-PCR showed an increase of gene expression of HO-1 and Hsp70. One and 3 years after transplantation, high ICAM and VCAM expression proved to have a negative effect on kidney function in brain dead and living kidneys, while HO-1 proved to have a strongly positive effect, but only in kidneys from living donors. CONCLUSIONS: E-selectin expression and interstitial leukocyte accumulation in brain dead donor kidneys indicate an early phase inflammatory state prior to organ retrieval. Also, brain death causes a stress-related response resulting in upregulation of potentially protective heat shock proteins. The upregulation of HO-1 is beneficial in living donor kidneys, but might be inadequate in brain death.