The Delphi and GRADE methodology used in the PSOGI 2018 consensus statement on Pseudomyxoma Peritonei and Peritoneal Mesothelioma

Pseudomyxoma Peritonei (PMP) and Peritoneal Mesothelioma (PM) are both rare peritoneal malignancies. Currently, affected patients may be treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy offering long-term survival or even cure in selected patients. However, many issues regarding the optimal treatment strategy are currently under debate. To aid physicians involved in the treatment of these patients in clinical decision making, the PSOGI executive committee proposed to create a consensus statement on PMP and PM. This manuscript describes the methodology of the consensus process. The Delphi technique is a reliable method for attaining consensus on a topic that lacks scientific evidence through multiple voting rounds which feeds back responses to the participants in between rounds. The GRADE system provides a structured framework for presenting and grading the available evidence. Separate questionnaires were created for PMP and PM and sent during two voting rounds to 80 and 38 experts, respectively. A consensus threshold of 51.0% was chosen. After the second round, consensus was reached on 92.9%–100.0% of the questions. The results were presented and discussed in the plenary session at the PSOGI 2018 international meeting in Paris. A third round for the remaining issues is currently in progress. In conclusion, using the Delphi technique and GRADE methodology, consensus was reached in many issues regarding the treatment of PM and PMP amongst an international panel of experts. The main results will be published in the near future

Primary and metastatic peritoneal surface malignancies

Peritoneal surface malignancies comprise a heterogeneous group of primary tumours, including peritoneal mesothelioma, and peritoneal metastases of other tumours, including ovarian, gastric, colorectal, appendicular or pancreatic cancers. The pathophysiology of peritoneal malignancy is complex and not fully understood. The two main hypotheses are the transformation of mesothelial cells (peritoneal primary tumour) and shedding of cells from a primary tumour with implantation of cells in the peritoneal cavity (peritoneal metastasis). Diagnosis is challenging and often requires modern imaging and interventional techniques, including surgical exploration. In the past decade, new treatments and multimodal strategies helped to improve patient survival and quality of life and the premise that peritoneal malignancies are fatal diseases has been dismissed as management strategies, including complete cytoreductive surgery embedded in perioperative systemic chemotherapy, can provide cure in selected patients. Furthermore, intraperitoneal chemotherapy has become an important part of combination treatments. Improving locoregional treatment delivery to enhance penetration to tumour nodules and reduce systemic uptake is one of the most active research areas. The current main challenges involve not only offering the best treatment option and developing intraperitoneal therapies that are equivalent to current systemic therapies but also defining the optimal treatment sequence according to primary tumour, disease extent and patient preferences. New imaging modalities, less invasive surgery, nanomedicines and targeted therapies are the basis for a new era of intraperitoneal therapy and are beginning to show encouraging outcomes

A bronchogenic cyst, presenting as a retroperitoneal cystic mass

Bronchogenic cysts are mostly benign, congenital abnormalities originating from the remnants of the primitive foregut. A retroperitoneal location is rare. Due to the mostly asymptomatic behavior and the historical confusion regarding histology, an exact prevalence is not known. We present here a case report of a retroperitoneal bronchogenic cyst. A literature review was performed for cases of retroperitoneal bronchogenic cysts written in English. Anatomopathological criteria for inclusion were pseudo stratified, ciliated, columnar epithelium together with the presence of at least one of the following: cartilage, smooth muscle or seromucous glands. In addition, the embryology, pathogenesis, radiological, clinical and suggested treatment modalities are reviewed. We report the surgical excision of a retroperitoneal bronchogenic cyst that presented as a non-functioning left adrenal mass. Our review of literature revealed only 62 potential cases of retroperitoneal bronchogenic cysts. After applying the strict anatomopathological criteria, only 30 cases of true retroperitoneal bronchogenic cysts could be identified. Retroperitoneal location of a bronchogenic cyst is rare. Despite the rarity of this pathologic entity, bronchogenic cysts should be considered in the differential diagnosis of retroperitoneal cystic lesions. Only histology can confirm definitive diagnosis. Surgery remains the recommended treatment of choice

Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges

The presence of peritoneal metastases (PM) in patients with colorectal cancer (CRC) is associated with an extremely poor prognosis. The diagnosis of PM is challenging, resulting in an underestimation of their true incidence. While surgery can be curative in a small percentage of patients, effective treatment for non-operable PM is lacking, and clinical and pre-clinical studies are relatively sparse. Here we have defined the major clinical challenges in the areas of risk assessment, detection, and treatment. Recent developments in the field include the application of organoid technology, which has generated highly relevant pre-clinical PM models, the application of diffusion-weighted MRI, which has greatly improved PM detection, and the design of small clinical proof-of-concept studies, which allows the efficient testing of new treatment strategies. Together, these developments set the stage for starting to address the clinical challenges. To help structure these efforts, a translational research framework is presented, in which clinical trial design is based on the insight gained from direct tissue analyses and pre-clinical (organoid) models derived from CRC patients with PM. This feed-forward approach, in which a thorough understanding of the disease drives innovation in its clinical management, has the potential to improve outcome in the years to come

The emergence of pressurized intraperitoneal aerosol chemotherapy as a palliative treatment option for patients with diffuse peritoneal metastases: a narrative review

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an emerging palliative treatment for patients with unresectable peritoneal metastases. Potential advantages of PIPAC over current treatment options are a homogeneous intraperitoneal distribution, low local and systemic toxicity, and enhanced tumour penetration. Given these possible benefits, PIPAC is increasingly implemented in many centres worldwide. Scientific research into PIPAC is currently available from in vitro/in vivo/in animal studies, retrospective cohorts in humans, and phase I and II studies in humans. There are no results from randomised trials comparing PI PAC with conventional treatment, such as palliative systemic therapy. This narrative review aimed to provide an overview of the currently available literature on PIPAC. In general, repetitive PIPAC was feasible and safe for patients and operating room personnel. Primary and secondary non-access rates varied from 0-17% and 0-15%, respectively. Iatrogenic bowel injury was observed in 0-3% of PIPAC procedures. CTCAE grade 1-2 complications were common, mostly consisting of abdominal pain, nausea, vomiting, and fatigue. CTCAE grade 3-4 complications were uncommon, occurring on 0-15% of PIPAC procedures. Post-operative mortality rates of 0-2% were reported. The risk of occupational exposure to cytotoxic drugs was very low when strict safety guidelines were followed. Clinical heterogeneity was high in most studies, since, in general, patients with unresectable peritoneal metastases from a variety of primary tumours were included. Also, patients received either PIPAC monotherapy or PIPAC combined with concomitant systemic therapy, and were able to receive PIPAC in any line of palliative treatment. Since the results were generally not stratified for these three important factors, this severely complicates the interpretation of results. Based on the current literature, PIPAC may be regarded as a promising palliative treatment option in patients with diffuse peritoneal metastases. Initial results show that it is feasible and safe. However, well designed and (ideally) randomized controlled trials are urgently needed to determine the additional value of PIPAC in this setting. Until then, PIPAC should preferably be performed in the setting of clinical trials

Pharmacokinetics of the Perioperative Use of Cancer Chemotherapy in Peritoneal Surface Malignancy Patients

Background. The peritoneal surface is an acknowledged locoregional failure site of abdominal malignancies. Previous treatment attempts with medical therapy alone did not result in long-term survival. During the last two decades, new treatment protocols combining cytoreductive surgery with perioperative intraperitoneal and intravenous cancer chemotherapy have demonstrated very encouraging clinical results. This paper aims to clarify the pharmacologic base underlying these treatment regimens. Materials and Methods. A review of the current pharmacologic data regarding these perioperative chemotherapy protocols was undertaken. Conclusions. There is a clear pharmacokinetic and pharmacodynamic rationale for perioperative intraperitoneal and intravenous cancer chemotherapy in peritoneal surface malignancy patients

The emergence of pressurized intraperitoneal aerosol chemotherapy as a palliative treatment option for patients with diffuse peritoneal metastases: a narrative review

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an emerging palliative treatment for patients with unresectable peritoneal metastases. Potential advantages of PIPAC over current treatment options are a homogeneous intraperitoneal distribution, low local and systemic toxicity, and enhanced tumour penetration. Given these possible benefits, PIPAC is increasingly implemented in many centres worldwide. Scientific research into PIPAC is currently available from in vitro/in vivo/in animal studies, retrospective cohorts in humans, and phase I and II studies in humans. There are no results from randomised trials comparing PI PAC with conventional treatment, such as palliative systemic therapy. This narrative review aimed to provide an overview of the currently available literature on PIPAC. In general, repetitive PIPAC was feasible and safe for patients and operating room personnel. Primary and secondary non-access rates varied from 0-17% and 0-15%, respectively. Iatrogenic bowel injury was observed in 0-3% of PIPAC procedures. CTCAE grade 1-2 complications were common, mostly consisting of abdominal pain, nausea, vomiting, and fatigue. CTCAE grade 3-4 complications were uncommon, occurring on 0-15% of PIPAC procedures. Post-operative mortality rates of 0-2% were reported. The risk of occupational exposure to cytotoxic drugs was very low when strict safety guidelines were followed. Clinical heterogeneity was high in most studies, since, in general, patients with unresectable peritoneal metastases from a variety of primary tumours were included. Also, patients received either PIPAC monotherapy or PIPAC combined with concomitant systemic therapy, and were able to receive PIPAC in any line of palliative treatment. Since the results were generally not stratified for these three important factors, this severely complicates the interpretation of results. Based on the current literature, PIPAC may be regarded as a promising palliative treatment option in patients with diffuse peritoneal metastases. Initial results show that it is feasible and safe. However, well designed and (ideally) randomized controlled trials are urgently needed to determine the additional value of PIPAC in this setting. Until then, PIPAC should preferably be performed in the setting of clinical trials

Primary and metastatic peritoneal surface malignancies.

Peritoneal surface malignancies comprise a heterogeneous group of primary tumours, including peritoneal mesothelioma, and peritoneal metastases of other tumours, including ovarian, gastric, colorectal, appendicular or pancreatic cancers. The pathophysiology of peritoneal malignancy is complex and not fully understood. The two main hypotheses are the transformation of mesothelial cells (peritoneal primary tumour) and shedding of cells from a primary tumour with implantation of cells in the peritoneal cavity (peritoneal metastasis). Diagnosis is challenging and often requires modern imaging and interventional techniques, including surgical exploration. In the past decade, new treatments and multimodal strategies helped to improve patient survival and quality of life and the premise that peritoneal malignancies are fatal diseases has been dismissed as management strategies, including complete cytoreductive surgery embedded in perioperative systemic chemotherapy, can provide cure in selected patients. Furthermore, intraperitoneal chemotherapy has become an important part of combination treatments. Improving locoregional treatment delivery to enhance penetration to tumour nodules and reduce systemic uptake is one of the most active research areas. The current main challenges involve not only offering the best treatment option and developing intraperitoneal therapies that are equivalent to current systemic therapies but also defining the optimal treatment sequence according to primary tumour, disease extent and patient preferences. New imaging modalities, less invasive surgery, nanomedicines and targeted therapies are the basis for a new era of intraperitoneal therapy and are beginning to show encouraging outcomes