I. H. M. Borel Rinkes

Preoperative MRI and surgical management in patients with nonpalpable breast cancer: The MONET - Randomised controlled trial

BACKGROUND We evaluated whether performing contrast-enhanced breast MRI in addition to mammography and/or ultrasound in patients with nonpalpable suspicious breast lesions improves breast cancer management. METHODS The MONET - study (MR mammography of nonpalpable breast tumours) is a randomised controlled trial in patients with a nonpalpable BIRADS 3-5 lesion. Patients were randomly assigned to receive routine medical care, including mammography, ultrasound and lesion sampling by large core needle biopsy or additional MRI preceding biopsy. Patients with cancer were referred for surgery. Primary end-point was the rate of additional surgical procedures (re-excisions and conversion to mastectomy) in patients with a nonpalpable breast cancer. FINDINGS Four hundred and eighteen patients were randomised, 207 patients were allocated to MRI, and 211 patients to the control group. In the MRI group 74 patients had 83 malignant lesions, compared to 75 patients with 80 malignant lesions in the control group. The primary breast conserving surgery (BCS) rate was similar in both groups; 68% in the MRI group versus 66% in the control group. The number of re-excisions performed because of positive resection margins after primary BCS was increased in the MRI group; 18/53 (34%) patients in the MRI group versus 6/50 (12%) in the control group (p=0.008). The number of conversions to mastectomy did not differ significantly between groups. Overall, the rate of an additional surgical intervention (BCS and mastectomy combined) after initial breast conserving surgery was 24/53 (45%) in the MRI group versus 14/50 (28%) in the control group (p=0.069). INTERPRETATION Addition of MRI to routine clinical care in patients with nonpalpable breast cancer was paradoxically associated with an increased re-excision rate. Breast MRI should not be used routinely for preoperative work-up of patients with nonpalpable breast cancer.

First experience with robot-assisted thoracoscopic esophagolymphadenectomy for esophageal cancer.

BackgroundTransthoracic esophagectomy with extended lymph node dissection is associated with higher morbidity rates than transhiatal esophagectomy. This morbidity rate could be reduced by the use of minimally invasive techniques. The feasibility of robot-assisted thoracoscopic esophagectomy (RTE) with mediastinal lymphadenectomy was assessed prospectively.MethodsThis study investigated 21 consecutive patients with esophageal cancer who underwent RTE using the Da Vinci™ robotic system. Continuity was restored with a gastric conduit and a cervical anastomosis.ResultsA total of 18 (86%) procedures were completed thoracoscopically. The operating time for the thoracoscopic phase was 180 min (range, 120–240 min), and the median blood loss was 400 ml (range, 150–700 ml). A median of 20 (range, 9–30) lymph nodes were retrieved. The median intensive care unit stay was 4 days (range, 1–129 days), and the hospital stay was 18 days (range, 11–182 days). Pulmonary complications occurred in 10 patients (48%), and one patient (5%) died of a tracheoneoesophageal fistula.ConclusionsIn this initial experience, robot-assisted thoracoscopic esophagectomy was found to be feasible, providing an effective lymphadenectomy with low blood loss. Standardization of the technique and increased experience should reduce the complication rate, which is in the range of the rate for open transthoracic dissection.

Mouse Models of Colorectal Cancer and Liver Metastases

Colorectal cancer (CRC) is one of the most common malignancies in the western world. Its high mortality rates are particularly related to the occurrence of liver metastases. Many mouse models have been developed to evaluate the various features of CRC in human. Since none of the existing mouse models mimics all the characteristics of human CRC, it is of crucial importance that the optimal model is chosen for each experiment to resolve a specific experimental question. Currently used mouse models for CRC include chemically induced CRC models, genetically engineered mouse models and models in which colon tumors are implanted in recipient mice. Recently, conditional mouse models have been created in which a gene of interest can be (in)activated in a time- and tissue-specific manner. All models have their advantages and limitations. This review highlights the most commonly used mouse models for CRC and its liver metastases, their usefulness and shortcomings, as well as recent improvements, particularly regarding intravital (tumor) imaging.

Robot‐assisted thoracoscopic oesophagectomy for cancer

Thoracoscopic oesophagectomy was introduced to reduce the morbidity of transthoracic oesophagectomy. The aim was to assess the short‐ and mid‐term results of robot‐assisted thoracoscopic oesophagectomy for oesophageal cancer.

Impaired healing of cutaneous wounds and colonic anastomoses in mice lacking thrombin-activatable fibrinolysis inhibitor.

Summary.  Plasmin and other components of the plasminogen activation system play an important role in tissue repair by regulating extracellular matrix remodeling, including fibrin degradation. Thrombin‐activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase that, after activation, can attenuate plasmin‐mediated fibrin degradation by removing the C‐terminal lysine residues from fibrin, which play a role in the binding and activation of plasminogen. To test the hypothesis that TAFI is an important determinant in the control of tissue repair, we investigated the effect of TAFI deficiency on the healing of cutaneous wounds and colonic anastomoses. Histological examination revealed inappropriate organization of skin wound closure in the TAFI knockout mice, including an altered pattern of epithelial migration. The time required to completley heal the cutaneous wounds was slightly delayed in TAFI‐deficient mice. Healing of colonic anastomoses was also impaired, as reflected by decreased strength of the tissue at the site of the suture, and by bleeding complications in 3 of 14 animals. Together, these abnormalities resulted in increased mortality in TAFI‐deficient mice after colonic anastomoses. Although our study shows that tissue repair, including re‐epithelialization and scar formation, occurs in TAFI‐deficient mice, TAFI appears to be important for appropriate organization of the healing process.

Peritoneal changes due to laparoscopic surgery.

BackgroundLaparoscopic surgery has been incorporated into common surgical practice. The peritoneum is an organ with various biologic functions that may be affected in different ways by laparoscopic and open techniques. Clinically, these alterations may be important in issues such as peritoneal metastasis and adhesion formation.MethodsA literature search using the Pubmed and Cochrane databases identified articles focusing on the key issues of laparoscopy, peritoneum, inflammation, morphology, immunology, and fibrinolysis.ResultsLaparoscopic surgery induces alterations in the peritoneal integrity and causes local acidosis, probably due to peritoneal hypoxia. The local immune system and inflammation are modulated by a pneumoperitoneum. Additionally, the peritoneal plasmin system is inhibited, leading to peritoneal hypofibrinolysis.ConclusionSimilar to open surgery, laparoscopic surgery affects both the integrity and biology of the peritoneum. These observations may have implications for various clinical conditions.

Virtual reality training for endoscopic surgery: voluntary or obligatory?

IntroductionVirtual reality (VR) simulators have been developed to train basic endoscopic surgical skills outside of the operating room. An important issue is how to create optimal conditions for integration of these types of simulators into the surgical training curriculum. The willingness of surgical residents to train these skills on a voluntary basis was surveyed.MethodsTwenty-one surgical residents were given unrestricted access to a VR simulator for a period of four months. After this period, a competitive element was introduced to enhance individual training time spent on the simulator. The overall end-scores for individual residents were announced periodically to the full surgical department, and the winner was awarded a prize.ResultsIn the first four months of study, only two of the 21 residents (10%) trained on the simulator, for a total time span of 163 minutes. After introducing the competitive element the number of trainees increased to seven residents (33%). The amount of training time spent on the simulator increased to 738 minutes.ConclusionsFree unlimited access to a VR simulator for training basic endoscopic skills, without any form of obligation or assessment, did not motivate surgical residents to use the simulator. Introducing a competitive element for enhancing training time had only a marginal effect. The acquisition of expensive devices to train basic psychomotor skills for endoscopic surgery is probably only effective when it is an integrated and mandatory part of the surgical curriculum.

Vacuum-assisted breast biopsy: a critical review

Vacuum-assisted biopsy is an image-guided technique introduced in 1995 that is thought to be superior to 14G automated-needle biopsy for the evaluation of non-palpable breast lesions. However, prospective randomised studies evaluating its accuracy are unavailable. We conducted a critical review of the currently available literature on the accuracy of vacuum-assisted biopsy and compared it with published data on the accuracy of 14G automated-needle biopsy. The diagnostic performance of vacuum-assisted biopsy was evaluated by reviewing all available English-language literature published in Medline between 1995 and November 2001. Four independent reviewers used standard forms to extract the data. Twenty-two published studies were included. High-risk and DCIS underestimate rates, as well as the miss-rate of cancer, were assessed. High-risk and DCIS underestimate rates for 11G vacuum biopsy were 16% (95% Confidence Interval (CI) 12-20%) and 11% (95% CI 9-12%), respectively, and both were lower than the rates reported for 14G automated-needle biopsy (40% (95% CI 26%;56%) and 15% (95% CI 8%;26%), respectively). Due to incomplete follow-up of the benign lesions, it was impossible to calculate the miss-rates and the sensitivity rate. The results of this review indicate that vacuum-assisted biopsy can decrease the high-risk and DCIS underestimate rates, but it is unclear whether it can also decrease the miss-rates of cancer.

Systematic review of five feeding routes after pancreatoduodenectomy

Current European guidelines recommend routine enteral feeding after pancreato‐duodenectomy (PD), whereas American guidelines do not. The aim of this study was to determine the optimal feeding route after PD.

Immunosuppression promotes reovirus therapy of colorectal liver metastases

Mortality due to colorectal cancer (CRC) is high and is associated with the development of liver metastases. Approximately 40% of human CRCs harbor an activating mutation in the KRAS oncogene. Tumor cells with activated KRAS are particularly sensitive to Reovirus T3D, a non-pathogenic oncolytic virus. The efficacy of virus-based therapies may be positively or negatively modulated by the host immune system. This study was designed to assess the effect of immunosuppression on Reovirus T3D oncolysis of established colorectal micrometastases in the liver. Mouse C26 CRC cells harbor a mutant Kras gene and are susceptible to Kras-dependent oncolysis by Reovirus T3D in vitro. Isolated C26 liver tumors were established in syngenic immunocompetent BALB/c mice by intrahepatic injection. Reovirus T3D therapy was given as a single intratumoral injection in control mice and in cyclosporin A-treated immunosuppressed mice. Tumor growth was analyzed over time by non-invasive bioluminescence imaging. The outgrowth of established CRC liver metastases in immunocompetent mice was efficiently but temporarily inhibited with a single injection of Reovirus T3D. Immunosuppression with cyclosporin A markedly increased and prolonged the therapeutic effect and allowed complete Reovirus T3D-induced tumor eradication in a subpopulation of the mice. We conclude that Reovirus T3D is an effective therapeutic agent against established C26 colorectal liver metastases and that immunosuppression enhances treatment efficacy.