Long-term Survival and Propensity Score Matched Outcomes of Bilateral vs. Unilateral Diaphragm Interventions in Cytoreductive Surgery plus Intra-peritoneal Chemotherapy

Discussion

Diaphragmatic interventions are performed in nearly 50% of all CRS/IPC patients. With such a large cohort undergoing diaphragmatic CRS/IPC, factors that may pertain to a higher morbidity need to be identified. Many authors have examined the feasibility and safety of diaphragmatic interventions in CRS/IPC. However, there is a paucity of data available on the perioperative outcomes and long-term survival of bilateral diaphragm interventions.

In the literature, studies on diaphragmatic interventions are limited to ovarian pathology and attempts to compare the perioperative morbidity of diaphragm CRS/IPC to non-diaphragmatic CRS. Muallem and colleagues (10) found significant postoperative complications, infections and pleural effusions. Zapardiel and colleagues (14) attempted to quantify the effect of diaphragm resection and compared it to stripping in ovarian malignancies. In their postoperative univariate analysis, the resection group had more complete cytoreduction and significantly increased incidence of pleural effusions. Other authors such as Pounds and colleagues (15) performed a similar analysis.

The only other study that merits citation is by Franssen (9) and colleagues. They examined the short-term perioperative morbidity of diaphragmatic interventions in LAMNs. They discovered that intra-operative diaphragm interventions were associated with increased PRBC and 30-day mortality rate. Prolonged ICU-stay and length of hospital stay were also observed. Importantly, they are the only authors to mention bilateral diaphragm interventions. In their diaphragmatic cohort, 28 (31.4%) of their 89 patients had bilateral diaphragm interventions. No subgroup analysis examining the effect of bilateral diaphragm interventions on perioperative mortality was performed.

After understanding the literature, our study attempted to identify whether bilateral diaphragm interventions are a risk factor for higher morbidity and mortality in CRS/IPC. Firstly, univariate analysis was conducted to quantify preoperative heterogeneity. This built the basis of our propensity matching method. Secondly, the matched data set was then utilized to measure intraoperative, postoperative and respiratory outcomes. Thirdly, an OS analysis based on tumor type was conducted. In essence, by comparing the long-term survival we were able to evaluate whether the short-term perioperative morbidity justifies the interventions.

The preoperative markers that determined heterogeneity between the diaphragm and non-diaphragm groups were carefully selected. These included ASA, sex, diagnosis, PSS, age and PCI. Categories such as intraoperative time and number of organs were deliberately not included because it was felt that they would be derivatives of the categories above. This would make the data of our study too specific and possibly not applicable to other populations.

In our analysis, significant heterogeneity was found in regard to diagnosis, PSS and PCI. LAMNs were more likely to undergo bilateral intervention, whereas colorectal cancers were unlikely to. This is a reflection of the strict PCI criterion of 10 or less for CRS + HIPEC in this diagnosis. Conversely, LAMNs patients had a significantly increased rate of bilateral intervention, reflecting the relaxed PCI bias in patient selection. Significantly increased numbers of patients with PSS 0 underwent bilateral intervention, whereas patients with PSS 1 were less likely to. This is likely the result of extensive dissection and preoperative PCI bias or technical difficulties in a redo versus a virgin abdomen or abdomen with limited resections. Unsurprisingly, the mean PCI was considerably higher in the bilateral diaphragmatic group. The data were propensity matched for diagnosis, PSS and PCI and yielded 165 matched pairs.

Univariate analysis was then conducted on these matched data. Our analysis identified significantly increased operative hours. Postoperatively, there were significantly increased incidences of RBC transfusion and grade III and IV complications. In terms of respiratory specific complications, a significantly increased incidence of pneumothorax was noted. Interestingly, OS was decreased in bilateral diaphragm interventions in LAMNs. We believe that the diaphragmatic disease in patients with LAMNs requiring bilateral diaphragm interventions, represents advanced infiltrative disease, which is contributing to the difference in OS.

Our study has several limitations. It is a retrospective, observational study with limitations inherent to this design. Firstly, unidentified confounding factors could influence results. Secondly, our data did not contain extubation times, which would be an important end-point to measure in terms of respiratory failure related to diaphragmatic instrumentation. Thirdly, our sample size may be too low to detect complications, which have low event rates. Lastly, this is a single institution study and the results may not be applicable to all institutions.

Despite the increase in short-term morbidity, bilateral diaphragm interventions allow for complete cyto-reduction and result in similar long-term survival to unilateral interventions.