Wouter Willaert

Lymphatic spread, nodal count and the extent of lymphadenectomy in cancer of the colon

In colon cancer, the biological significance of lymphatic tumour spread remains a matter of debate, which impacts on related questions such as the ideal extent of lymphadenectomy and the prognostic significance of lymph node counts. Several lines of evidence suggest that metastasis to locoregional nodes occurs early and is a stochastic, rather than a stepwise phenomenon, and in essence reflects the tumour-host-metastasis relationship. Not surprisingly, therefore, several clinical trials failed to identify a survival benefit from extensive lymphadenectomy compared to standard resection. The recently described complete mesocolic excision technique, which aims to improve survival by maximizing nodal clearance, should be subjected to a prospective randomized trial. There has been a fairly consistent and intriguing relation between nodal counts and survival in colon cancer. Therapeutic effects of more extensive removal of invaded nodes seem an unlikely explanation for the observed association. Similarly, several findings argue against stage migration as the only or even the most important explanation. The available literature shows an extensive array of factors confounding the nodal count-survival relationship, which are correlated to the patients clinical characteristics, pathology variables, and factors relating to the individual (treating surgeon and pathologist) and institutional healthcare levels. More research into the biology of nodal spread and the nodal count-survival relationship is indicated and may have important implications for therapy such as the further introduction of minimally invasive surgery and the identification of novel and potentially modifiable factors impacting on both nodal counts and survival.

Training models in laparoscopy: a systematic review comparing their effectiveness in learning surgical skills.

Abstract Background : Surgery has traditionally been learned on patients in the operating room, which is time-consuming, can have an impact on the patient outcomes, and is of variable effectiveness. As a result, surgical training models have been developed, which are compared in this systematic review. Methods : We searched Pubmed, CENTRAL, and Science Citation index expanded for randomised clinical trials and randomised cross-over studies comparing laparoscopic training models. Studies comparing one model with no training were also included. The reference list of identified trials was searched for further relevant studies. Results : Fifty-eight trials evaluating several training forms and involving 1591 participants were included (four studies with a low risk of bias). Training (virtual reality (VR) or video trainer (VT)) versus no training improves surgical skills in the majority of trials. Both VR and VT are as effective in most studies. VR training is superior to traditional laparoscopic training in the operating room. Outcome results for VR robotic simulations versus robot training show no clear difference in effectiveness for either model. Only one trial included human cadavers and observed better results versus VR for one out of four scores. Contrasting results are observed when robotic technology is compared with manual laparoscopy. Conclusion : VR training and VT training are valid teaching models. Practicing on these models similarly improves surgical skills. A combination of both methods is recommended in a surgical curriculum. VR training is superior to unstructured traditional training in the operating room. The reciprocal effectiveness of the other models to learn surgical skills has not yet been established.

Nanomedicine-based intraperitoneal therapy for the treatment of peritoneal carcinomatosis — Mission possible?

ABSTRACT Intraperitoneal (IP) drug delivery represents an attractive strategy for the local treatment of peritoneal carcinomatosis (PC). Over the past decade, a lot of effort has been put both in the academia and clinic in developing IP therapeutic approaches that maximize local efficacy while limiting systemic side effects. Also nanomedicines are under investigation for the treatment of tumors confined to the peritoneal cavity, due to their potential to increase the peritoneal retention and to target drugs to the tumor sites as compared to free drugs. Despite the progress reported by multiple clinical studies, there are no FDA approved drugs or formulations for specific use in the IP cavity yet. This review discusses the current clinical management of PC, as well as recent advances in nanomedicine‐based IP delivery. We address important challenges to be overcome towards designing optimal nanocarriers for IP therapy in vivo. Graphical abstract Figure. No Caption available.

Intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis: review of animal models.

The development of suitable animal models is essential to experimental research on intraperitoneal chemotherapy (IPC). This review of the English literature (MEDLINE) presents a detailed analysis of current animal models and gives recommendations for future experimental research. Special consideration should be given to cytotoxic drug dose and concentration, tumor models, and outcome parameters. J. Surg. Oncol. 2014 109:110–116.

Postmortem circulation: A new model for testing endovascular devices and training clinicians in their use

The development of new medical devices, such as aortic valves, requires numerous preliminary studies on animals and training of personnel on cadavers before the devices can be used in patients. Postmortem circulation, a technique used for postmortem angiography, allows the vascular system to be reperfused in a way similar to that in living persons. This technique is used for postmortem investigations to visualize the human vascular system and to make vascular diagnoses. Specific material for reperfusing a human body was developed recently. Our aim was to investigate whether postmortem circulation that imitates in vivo conditions allows for the testing of medical materials on cadavers. We did this by delivering an aortic valve using minimally invasive methods. Postmortem circulation was established in eight corpses to recreate an environment as close as possible to in vivo conditions. Mobile fluoroscopy and a percutaneous catheterization technique were used to deliver the material to the correct place. Once the valve was implanted, the heart and primary vessels were extracted to confirm its position. Postmortem circulation proved to be essential in several of the cadavers because it helped the clinicians to deliver the material and improve their implantation techniques. Due to the intravascular circulation, sites with substantial arteriosclerotic stenosis could be bypassed, which would have been impossible without perfusion. Although originally developed for postmortem investigations, this reperfusion technique could be useful for testing new medical devices intended for living patients. Clin. Anat. 556–562, 2014.

Life-threatening side effects of malabsorptive procedures in obese patients necessitating conversion surgery: a review of 17 cases.

Abstract Background : malabsorptive surgery (MAS) can cause huge weight loss but is also known for its serious side effects. We investigated whether conversion surgery is an effective treatment for MAS-induced complications. Methods : we searched our hospital database for patients who underwent conversion surgery after MAS. Any complication was recorded till time of conversion. The conversion techniques and their effect on the course of the patients were analyzed and compared to the situation after MAS. Results : we identified 17 patients who suffered a wide range of complications after biliopancreatic diversion (BPD) (n = 11), biliopancreatic diversion with duodenal switch (BPD-DS) (n = 4), or distal gastric bypass (D-GBP) (n = 2). After a (mean ± SD) period of 6.0 ± 3.6 years the MAS was either converted to a gastric bypass (GBP) in 6 patients or an elongation of the common limb (ECL) in 9 patients. Two conversions were atypical. After a (mean ± SD) follow-up of 2.4 ± 2.5 years the majority of blood test results improved. The incidence of most complaints diminished except abdominal discomfort, critical illness polyneuropathy, need for total parenteral nutrition (TPN), wheelchair dependency, and asthenia. One patient died of irreversible liver failure after 3 liver transplantations. Two patients died of cachexia. The preferred conversion technique is still unclear. Conclusions : MAS can cause invalidating and life-threatening side effects. If there are signs of incipient deterioration in organ function and/or nutritional status, conversion surgery should not be delayed. Although we have the impression that early conversion causes better outcome, many patients experience lifelong postoperative complications.

BEV-IP: Perioperative chemotherapy with bevacizumab in patients undergoing cytoreduction and intraperitoneal chemoperfusion for colorectal carcinomatosis

BackgroundSelected patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) benefit from cytoreductive surgery (CRS) combined with intraperitoneal chemoperfusion (IPC). However, even after optimal cytoreduction, systemic and locoregional recurrence are common. Perioperative chemotherapy with bevacizumab (BEV) may improve the outcome of these patients.Methods/DesignThe BEV-IP study is a phase II, single-arm, open-label study aimed at patients with colorectal or appendiceal adenocarcinoma with synchronous or metachronous PC. This study evaluates whether perioperative chemotherapy including BEV in combination with CRS and oxaliplatin-based IPC results in acceptable morbidity and mortality (primary composite endpoint). Secondary endpoints are treatment completion rate, chemotherapy-related toxicity, pathological response, progression free survival, and overall survival.DiscussionThe BEV-IP trial is the first prospective assessment of the safety and efficacy of perioperative chemotherapy combined with anti-angiogenic treatment in patients undergoing CRS and IPC for colorectal peritoneal metastases.Trial registrationClinicalTrials.gov Identifier: NCT02399410 EudraCT number: 2015-001187-19 (registered March 9, 2015).

Simultaneous Parenchyma-Preserving Liver Resection, Cytoreductive Surgery and Intraperitoneal Chemotherapy for Stage IV Colorectal Cancer.

Background : The outcome of stage IV colorectal cancer (CRC) has improved with modern systemic therapy. However, the concomitant presence of liver metastases (LM) and peritoneal carcinomatosis (PC) remains associated with a dismal prognosis and surgery in this context remains exceptional. Methods : Stage IV CRC patients with LM and PC undergoing simultaneous cytoreductive surgery, intraperitoneal chemotherapy (IPC) and liver resection/ablation were identified from prospectively collected databases. We assessed response to neoadjuvant chemotherapy (NACT), postoperative complications, progression free survival (PFS), and overall survival (OS). Results : Twenty-one patients with resectable disease were treated between 2007 and 2014. In 16 patients (76%), NACT was administered and tumour response defined their selection. The remaining 5 (24%) were selected according to the pattern of recurrence. Median peritoneal cancer index was 5 (range : 3-10.5). Liver surgery included 34 wedge resections, 5 ablations and one bisectionectomy to treat a total of 45 hepatic lesions with a median of 2 per patient (range : 1-2) and a median size of 1.35 cm (range : 0.8-2). Tumour regression grade 4 (fibrosis but residual cancer cells predominate) was seen in 50% of the resected metastases after NACT. Median hospital stay was 17 days (range : 14-24); severe morbidity (Clavien-Dindo grade 3-4) occurred in 24% and no perioperative mortality (0-90 days) was recorded. The median OS was 44 months (range : 31-57) while the median PFS was 10 months (range : 8-12). Conclusion : Combined parenchyma-preserving liver resection, cytoreductive surgery and IPC in patients with LM and PC from CRC can be performed safely and results in promising mid-term overall survival.

Occupational safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC)

Abstract Background Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel method to treat extensive, small volume peritoneal metastases. The clinical use of chemotherapy containing aerosols represents a potential occupational health hazard. We report the results of toxicological analysis during the first two clinical PIPAC procedures performed at Ghent University Hospital. Methods After extensive preparation and in vitro testing, two patients were treated with PIPAC: the first using doxorubicin (2.86 mg in 51.43 mL) and cisplatin (14.28 mg in 164.3 mL), the second using oxaliplatin (182.10 mg in 186.42 mL). A standardized safety checklist was developed and used. Aerosol delivery was combined with electrostatic precipitation (ePIPAC). The following samples were obtained at several time points and locations: environmental air, floor surface wipes, surgeon’s gloves, surgeon’s hand wipes, circuit filters, and fluid from the water seal collection chamber container placed along the closed aerosol waste evacuating line. Platinum concentration was measured in these samples using voltammetry. Sample collection and analysis were performed by an independent external laboratory. Results Platinum was not detected on the four floor locations after both procedures (detection limit 0.02 ng/cm2). Similarly, no platinum was detected in environmental air during both PIPACs at the surgeon’s or anesthesiologist’s position (detection limit 4.0–27 ng/m3). No platinum contamination was detected on the hands, outer pair of gloves, or inner pair of gloves of the surgeon (detection limit 70 and 50 ng respectively). Platinum was not detected on the filters and in the air-seal container liquid. Conclusions With adequate preparation and precautions, a clinical PIPAC program can be established without measurable chemotherapy exposure to the operating room environment or healthcare workers.

Metabolic surgery in patients over 60 years old: short- and long-term results.

Abstract Purpose: Laparoscopic Roux-en-Y gastric bypass can treat obesity related comorbidities and can prolong life expectancy. It remains unclear whether this type of surgery is also indicated in obese patients with advanced age. Materials and methods: In this retrospective monocentric study, we investigated the morbidity and outcomes of weight and metabolic control of bariatric surgery in patients older than 60 years and compared these findings with those of younger patients. Results: At 18 months after RY gastric bypass, weight losses of respectively 30 ± 11% and 34 ± 9% of total initial body weight were measured in the older and younger patients (p < 0.05). After 12 months, HbA1c dropped below 6.5% in 89% of patients younger and in 81% of patients older than 60 (p = 0.11). There was no mortality in either group, but there were significantly more complications and there was a longer hospital stay in the older patients. Conclusion: RY gastric bypass comes with a significantly higher morbidity and hospital stay in older patients, but weight loss and improvement of DM are similar as in the younger patients.