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

Podocalyxin-like protein expression in primary colorectal cancer and synchronous lymph node metastases

Aims: Previous studies have shown that membranous expression of podocalyxin-like protein (PODXL) is associated with poor prognosis in colorectal cancer (CRC). In this study, we compared PODXL expression in primary CRC and synchronous lymph node metastases. We further analyzed whether its expression changed in rectal tumours after neoadjuvant radiation therapy. Methods and results: The studied cohort consists of 73 consecutive patients from the South-Swedish Colorectal Cancer Biobank. Immunohistochemical PODXL expression was examined on full-face sections from all primary tumours and all 140 available lymph node metastases from 31 cases. Membranous PODXL expression was denoted in 18/73 (24,7%) primary tumours, with a high concordance between primary and metastatic lesions. While all negative primary tumours had negative metastases, some PODXL positive primaries had a varying proportion of positive and negative metastatic lymph nodes. PODXL expression was also found to be mainly unaltered in pre- and post-irradiation surgically resected tumour specimens in rectal cancer patients (n=16). Conclusions: The findings in this study suggest that analysis of PODXL expression in the primary tumour is sufficient for its use as a prognostic and treatment predictive biomarker in CRC, also in patients with metastatic disease

Abdominal Closure With Reinforcing Suture Decreases Incisional Hernia Incidence After CRS/HIPEC

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) entails several risk factors for incisional hernia (IH). A few reports available showing incidences between 7% and 17%. At our institution fascia closure has been performed in a 4:1 suture to wound length manner, with a continuous 2-0 polydiaxanone suture (PDS-group) or with a 2-0 polypropylene suture preceded by a reinforced tension line (RTL) suture (RTL-group). Our hypothesis was that these patients might benefit from reinforcing the suture line with a lower IH incidence in this group. The aim was to evaluate the 1-year IH-incidence of the two different closures.Methods: Patients eligible for inclusion were treated with CRS/HIPEC between 2004 and 2019. IH was diagnosed by scrutinizing CT-scans 1 year ±3 months after surgery. Additional data was retrieved from clinical records and a prospective CRS/HIPEC-database.Results: Of 193 patients, 129 were included, 82 in the PDS- and 47 in the RTL-group. RTL-patients were 5 years younger, had less blood loss and more frequent postoperative neutropenia. No difference regarding sex, BMI, recent midline incisions, excision of midline scars, peritoneal cancer index score, complications (≥Clavien-Dindo 3b), or chemotherapy. Ten IH (7.8%) were found, 9 (11%) in the PDS- and 1 (2.1%) in the RTL-group (p = 0.071).Conclusion: An IH incidence of 7.8% in patients undergoing CRS/HIPEC is not higher than after laparotomies in general. The IH incidence in the PDS-group was 11% compared to 2% in the RTL-group. Even though significance was not reached, the difference is clinically relevant, suggesting an advantage with RTL suture

High resection rates of colorectal liver metastases after standardized follow-up and multimodal management:an outcome study within the COLOFOL trial

Background: Outcome after colorectal liver metastases (CRLM) resection has improved over time, despite increased resection rates. Hence, it's crucial to identify all patients possible to treat with curative intent. The objectives of this study were to map recurrence pattern, treatment strategy and survival depending on treatment and follow-up strategy. Methods: In the COLOFOL-trial, patients with radically resected stage II-III colorectal cancer were randomized to high-frequency (6, 12, 18, 24 and 36 months; HF) or low-frequency (12 and 36 months; LF) follow-up. In this study, all CRLM within 5 years were identified and medical files scrutinized. Overall survival (OS) was analysed in uni- and multivariable analyses. Primary endpoint was 5-year OS. Results: Of 2442 patients, 235 (9.6%) developed metachronous CRLM of which 123 (52.3%) underwent treatment with curative intent, resulting in 5-year OS of 58%. Five-year OS for patients with CRLM was 43% after HF versus 24% after LF. The survival benefit was confirmed for HF 8 years from resection of the primary tumour, HR 0.63 (CI 0.46–0.85). Conclusion: A high proportion of metachronous CRLM was possible to treat with curative intent, yielding high survival rates. More intense follow-up after colorectal cancer resection might be of value in high-risk patients

Systemic and Local Inflammatory Mediator Response to Major Surgery

Cell-signalling via cytokines modulates the local response to surgical trauma, directs the immunologic response and initiates the healing process. Surgical trauma induces a systemic cytokine response and a down-regulation of the antigen presentation capacity of monocytes (HLA-DR expression), which is associated with a poor prognosis if pronounced. The aims with the studies in this thesis were to identify factors that modulate the cytokine and the immune-cell responses to major surgery and to evaluate the role of collagenases in colonic healing. Major surgery evoked a cytokine response in the systemic circulation, which was enhanced by the presence of a cancer, in colorectal resections. The IL-6 response in colorectal surgery originated from the bowel and enhanced concentrations of IL-6 in tissue of colorectal cancers, emanating from an IL-6 expression in the malignant epithelium, might be the source. Open surgery for abdominal aortic aneurysm (AAA) repair induced higher IL-6 responses than transfemorally placement of endoluminal grafts (TPEG), lower peri-operative sigmoidal pH but equal down-regulation of the HLA-DR expression on monocytes. These findings suggest that tissue destruction influences the systemic IL-6 response in trauma, but not the down-regulation HLA-DR expression on monocytes. Experimental colonic obstruction in rats implied a local inflammatory response and an increased break-down of collagen by matrix metalloproteinases in the colonic wall, leading to a decrease in collagen concentration, assessed as hydroxyproline concentration. Inhibition of MMPs in the early phase of anastomotic healing in the colon, resulted in increased breaking strength of the anastomoses in inhibitor-treated animals compared to controls, confirming a negative role of MMPs in this phase of colonic healing. The knowledge on cytokine response to surgical trauma and interactions with the healing process needs to be expanded by studies on local events in tissue. The information on collagenase up-regulation in the local inflammatory response in the colon and the results of MMP-inhibition in anastomotic healing are promising in the efforts to improve healing in colorectal surgery