Extent of surgery in cancer of the colon : is more better?

Since the introduction of total mesorectal excision as the standard approach in mid and low rectal cancer, the incidence of local recurrence has sharply declined. Similar attention to surgical technique in colon cancer (CC) has resulted in the concept of complete mesocolic excision (CME), which consists of complete removal of the intact mesentery and high ligation of the vascular supply at its origin. Although renewed attention to meticulous surgical technique certainly has its merits, routine implementation of CME is currently unfounded. Firstly, in contrast to rectal cancer, local recurrence originating from an incompletely removed mesentery is rare in CC and usually a manifestation of systemic disease. Secondly, although CME may increase nodal counts and therefore staging accuracy, this is unlikely to affect survival since the observed relationship between nodal counts and outcome in CC is most probably not causal but confounded by a range of clinical variables. Thirdly, several lines of evidence suggest that metastasis to locoregional nodes occurs early and is a stochastic rather than a stepwise phenomenon in CC, in essence reflecting the tumor-host-metastasis relationship. Unsurprisingly, therefore, comparative studies in CC as well as in other digestive cancers have failed to demonstrate any survival benefit associated with extensive, additional or extra-mesenteric lymphadenectomy. Finally, routine implementation of CME may cause patient harm by longer operating times, major vascular damage and autonomic nerve injury. Therefore, data from randomized trials reporting relevant endpoints are required before CME can be recommended as a standard approach in CC surgery

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

Background: Selected 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/Design: The 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. Discussion: The 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

Aerosolization of nanotherapeutics as a newly emerging treatment regimen for peritoneal carcinomatosis

Recent advances in locoregional chemotherapy have opened the door to new approaches for the clinical management of peritoneal carcinomatosis (PC) by facilitating the delivery of anti-neoplastic agents directly to the tumor site, while mitigating adverse effects typically associated with systemic administration. In particular, an innovative intra-abdominal chemotherapeutic approach, known as Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC), was recently introduced to the intraperitoneal (IP) therapy regimens as a palliative therapeutic option in patients with PC, presumably providing a better drug distribution pattern together with deeper drug penetration into tumor nodules within the peritoneal space. Furthermore, the progress of nanotechnology in the past few decades has prompted the application of different nanomaterials in IP cancer therapy, offering new possibilities in this field ranging from an extended retention time to sustained drug release in the peritoneal cavity. This review highlights the progress, challenges, and opportunities in utilizing cancer nanotherapeutics for locoregional drug delivery, with a special emphasis on the aerosolization approach for intraperitoneal therapies

Intraperitoneal chemotherapy for peritoneal metastases : an expert opinion

Introduction: The rationale for intraperitoneal (IP) drug delivery for patients with peritoneal metastases (PM) is based on the pharmacokinetic advantage resulting from the peritoneal-plasma barrier, and on the potential to adequately treat small, poorly vascularized PM. Despite a history of more than three decades, many aspects of IP drug delivery remain poorly studied. Areas covered: We outline the anatomy and physiology of the peritoneal cavity, including the pharmacokinetics of IP drug delivery. We discuss transport mechanisms governing tissue penetration of IP chemotherapy, and how these are affected by the biomechanical properties of the tumor stroma. We provide an overview of the current clinical evidence on IP chemotherapy in ovarian, colorectal, and gastric cancer. We discuss the current limitations of IP drug delivery and propose several potential areas of progress. Expert opinion: The potential of IP drug delivery is hampered by off-label use of drugs developed for systemic therapy. The efficacy of IP chemotherapy for PM depends on cancer type, disease extent, and mode of drug delivery. Results from ongoing randomized trials will allow to better delineate the potential of IP chemotherapy. Promising approaches include IP aerosol therapy, prolonged delivery platforms such as gels or biomaterials, and the use of nanomedicine

Occupational safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC)

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/cm(2)). 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/m(3)). 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

Nanomedicine-based intraperitoneal therapy for the treatment of peritoneal carcinomatosis : mission possible?

A

Pressurized intraperitoneal aerosol chemotherapy (PIPAC), a new surgical technique for the treatment of unresectable peritoneal carcinomatosis

C

Postmortem pump-driven reperfusion of the vascular system of porcine lungs: towards a new model for surgical training

PURPOSE: The objective of this experiment is to establish a continuous postmortem circulation in the vascular system of porcine lungs and to evaluate the pulmonary distribution of the perfusate. This research is performed in the bigger scope of a revascularization project of Thiel embalmed specimens. This technique enables teaching anatomy, practicing surgical procedures and doing research under lifelike circumstances. METHODS: After cannulation of the pulmonary trunk and the left atrium, the vascular system was flushed with paraffinum perliquidum (PP) through a heart-lung machine. A continuous circulation was then established using red PP, during which perfusion parameters were measured. The distribution of contrast-containing PP in the pulmonary circulation was visualized on computed tomography. Finally, the amount of leak from the vascular system was calculated. RESULTS: A reperfusion of the vascular system was initiated for 37 min. The flow rate ranged between 80 and 130 ml/min throughout the experiment with acceptable perfusion pressures (range: 37-78 mm Hg). Computed tomography imaging and 3D reconstruction revealed a diffuse vascular distribution of PP and a decreasing vascularization ratio in cranial direction. A self-limiting leak (i.e. 66.8% of the circulating volume) towards the tracheobronchial tree due to vessel rupture was also measured. CONCLUSIONS: PP enables circulation in an isolated porcine lung model with an acceptable pressure-flow relationship resulting in an excellent recruitment of the vascular system. Despite these promising results, rupture of vessel walls may cause leaks. Further exploration of the perfusion capacities of PP in other organs is necessary. Eventually, this could lead to the development of reperfused Thiel embalmed human bodies, which have several applications

Establishment of a rat ovarian peritoneal metastasis model to study pressurized intraperitoneal aerosol chemotherapy (PIPAC)

A