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Abstract
Background A Total Retroperitoneal en bloc resection Of Multivisceral-Peritoneal packet (TROMP operation) is a no-touch isolation technique in a retroperitoneal space to resect the parietal peritoneum and the affected organs in advanced ovarian cancer. The study prescribed and analysed the results of this novel technique for primary cytoreductive surgery.
Methods The study included 208 patients operated between January 2015 and December 2017 in Charité, Berlin. The TROMP operation was performed in 58 patients, whereas the other 150 patients were operated with the conventional cytoreductive method.
Results The complete tumor resection rate accounts for 87.9% in TROMP group and 61.3% in the conventional surgery group. (p=0.001). This difference was even stronger in the sub-group of very advanced stages (T3c+T4) (85.1% of TROMP group and in only 53.1% in the conventional surgery group, p=0.001). The duration of the primary cytoreductive surgery was about 33 minutes shorter in TROMP group (median: 335 minutes vs 368 minutes; TROMP vs conventional, respectively) in spite of the fact that the most advanced cytoreductive procedures were performed statically significant more in TROMP operation arm in comparison with the conventional surgery arm. There was no statistically significant difference between the groups regarding the postoperative complication, blood loss or the length of stay in intensive care unit.
Conclusion Total retroperitoneal en bloc resection of multivisceral-peritoneal packet (TROMP operation) is a feasible and very effective technique of surgical therapy in advanced ovarian cancer. This technique increased the complete tumor resection rate to 87.9% without increasing the blood loss, postoperative complications or the duration of surgery. A prospective randomized study is advised to validate these results.
- cystadenocarcinoma, serous
- surgical oncology
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HIGHLIGHTS
The total retroperitoneal en bloc resection of multivisceral-peritoneal packet (TROMP) technique is feasible for primary surgery in advanced ovarian cancer.
The TROMP technique increases the rate of complete tumor resection in advanced ovarian cancer.
There was no statistically significant difference between the two treatment groups (TROMP vs conventional cytoreductive surgery) regarding postoperative complications.
Introduction
In 2010, the Gynecologic Cancer InterGroup defined optimal resection after primary cytoreductive surgery for ovarian cancer as cases with complete removal of all macroscopic lesions to leave no residual disease.1 This new definition is based on accumulated evidence indicating that complete tumor resection at primary cytoreductive surgery for advanced ovarian cancer results in a significantly improved prognosis.2–6 Complete tumor resection will be achieved only by appropriate peritonectomy procedures and en-bloc resection of the viscera where required.7
Peritonectomy plays an essential role, since the peritoneum is one of the most affected organs in advanced ovarian cancer.8–10 The increased utilization of advanced surgical procedures and the implementation of a structured quality management program in surgical treatment could enhance surgical outcomes in primary advanced ovarian cancer, but the complete tumor resection rate even in the best centers is under 70%.9 11 12 To enhance the rate of complete tumor resection in advanced ovarian cancer, The first author developed a novel technique based on a total retroperitoneal approach to remove the parietal peritoneum with a no-touch isolation and resection technique of all infiltrated organs (en bloc) as one surgical packet (Figure 1). We consider that this minimizes the duration of surgery and allows a complete resection of all the parietal peritoneum with less blood loss and fewer complications. This study analyzed the results of this surgical technique in advanced ovarian cancer cases in comparison with conventional procedures in the same institution over the same period.
Specimen following use of the total retroperitoneal en bloc resection of multivisceral-peritoneal packet (TROMP) technique.
Methods
All women with a diagnosis of primary epithelial advanced ovarian cancer, referred to our Department of Gynaecology and Centre for Oncological Surgery, Charité Medical University of Berlin between January 2015 and December 2017, were identified in our database from the tumor bank for ovarian cancer (www.toc-network.de). Exclusion criteria included: patients with non-epithelial ovarian cancer or borderline tumors, patients who underwent interval debulking surgery or only a second look operation or diagnostic procedure, and patients with early stages of epithelial ovarian cancer. The primary aim of this study was to evaluate the results of the Total Retroperitoneal en bloc resection Of Multivisceral-Peritoneal packet (TROMP) technique in terms of rate of complete tumor resection, blood loss, operative time, and complications and mortalities in the first 30 postoperative days, and compare them with the results of conventional primary cytoreductive surgery.
The TROMP technique was developed in 2013 in our institution by the first author of this article. The learning curve extended from 2013 to 2015. The detailed description of the surgical steps is provided in online supplementary 1. All patients provided their written informed consent for the surgery before clinical data were collected. Approval from Charité local ethics Committee was provided for this retrospective study (EK207/2003 Amendment 15/2012). All patients included in the study had International Federation of Gynecology and Obstetrics (FIGO) stages III or IV.
Supplemental material
Perioperative morbidity and mortality were defined as any adverse event occurring within 30 days of surgery. The postoperative complications in this study were graded according to the Calvien-Dindo classification.13 All grades of complications were included in the assessment of postoperative complications.
The statistical analysis was performed at the Charité Medical University Berlin. All analyses were performed by International Business Machines Statistical Package for the Social Sciences (IBM SPSS) Statistics 21.0 (SPSS, Chicago, IL). Data were analyzed by descriptive statistics. Frequency counts and percentages were used to describe categorical variables, and continuous variables were used to summarize the median and range. Statistical significance was defined by p<0.05 and two-sided tests were applied.
Results
A total of 208 consecutive patients who had undergone surgery were included in the analysis: 58 patients in the TROMP group and 150 patients in conventional cytoreductive surgery group. Patient characteristics of the entire cohort are summarized in Table 1. There were no statistically significant differences between both groups regarding patient age, preoperative CA125, histology, grading, and volume of intraoperative ascites. A total of 75.7% of all patients had intraoperative evaluated FIGO III, whereas 20.7% of all patients had FIGO IV according to the intraoperative surgical evaluation (25.9% in the TROMP group vs 18.7% in the conventional surgery group, p=0.34). The TNM classification revealed a significant difference between the groups for advanced stages (T3c+T4); 81% in the TROMP group versus 64% in the conventional surgery group (p=0.03). Infiltration of the upper abdomen was found in 82.8% of the TROMP group and in 64.7% of the conventional surgery cases (p=0.02). The nerve-sparing lymph node dissection (Figure 2) was performed in 89.7% of the TROMP group (LION trial data14 were not published at that time) and in 73.3% of the conventional surgery patients (p=0.02). Optimal cytoreductive surgery to no visible disease was performed in 68.8% of all patients; a complete tumor resection rate was performed in 87.9% of the patients in the TROMP group and 61.3% of the patients in the conventional surgery group (p=0.001). This difference was more significant in the sub-group of very advanced stages (T3c+T4). The resection to no visible disease was achieved in 85.1% of the patients in the TROMP group and in only 53.1% of the patients in the conventional surgery group (p=0.001). Surgery to <10 mm residual tumor was achieved in 100% of the patients in the TROMP group and in 90.7% of the patients in the conventional surgery group (p<0.05).
Anatomical explanation of para-aortic nerve-sparing lymph node dissection following utilization of the TROMP technique. TROMP, total retroperitoneal en bloc resection of multivisceral-peritoneal packet.
Patient characteristics
The duration of the primary cytoreductive surgery was approximately 33 min shorter in the TROMP group (median 335 min vs 368 min for TROMP vs conventional surgery, respectively) (p=0.113, Mann-Whitney U Test). Details on the cytoreductive procedures are shown in Table 2.
Surgery characteristics
There was a higher rate of complex procedures in the TROMP group compared with the conventional surgery group: omentectomy (98.3% vs 88%, p=0.04), pelvic lymph node dissection (77.6% vs 58%, p=0.01), para-aortic lymph node dissection (82.8% vs 59.3%, p=0.003), appendectomy (43.1% vs 27.3%, p=0.04), small bowel resection (32.8% vs 15.3%, p=0.009), large bowel resection (82.8% vs 58.7%, p=0.002), partial liver resection (17.2% vs 5.3%, p=0.014), and splenectomy (43.1% vs 8%, p<0.001).
To achieve more comparable results, both sub-groups of patients with more advanced stages (T3c and T4) were studied in detail. Table 3 shows the surgical results and complications of very advanced ovarian cancer cases.
Surgical results and complications of advanced ovarian cancer (T3c and T4)
The postoperative complication rate in patients with advanced stages was 54.5%. There was no statistically significant difference between the groups regarding postoperative complications (TROMP group 59.6% vs conventional group 52%, p=0.5). There were no mortalities in the first 30 postoperative days in either group. Postoperative infections were diagnosed in 23.4% of patients in the TROMP group and 10.4% of patients in the conventional surgery group (p=0.07). The incidence of postoperative anastomotic leaks was 8.5% in the TROMP group compared with 3.1% in the conventional surgery group (p=0.32). Although the rate of pneumonia was higher in the TROMP group compared with the conventional surgery group (10.6% vs 2%), this difference was not significant (p=0.07).
There were no differences between the two groups in regard to rates of blood transfusions (median=1 unit in the TROMP group vs 2 units in the conventional surgery group, p=0.58) and fresh frozen plasma concentrates (median=10 units in the TROMP group vs 12 units in the conventional surgery group, p=0.45). There was no difference in the median length of stay in the intensive care unit between the two groups (median=2 days in both groups, p=0.20).
Discussion
The en-bloc pelvic resection of pelvic tumor during primary cytoreductive surgery is now a well established technique and many studies have confirmed its effectiveness in achieving maximal cytoreduction15–17 with acceptable morbidity and mortality.18–21 The advantages of the TROMP technique may be summarized by finding dissection planes within healthy tissue beyond the tumor growth (retroperitoneal) to avoid the distorted anatomy and the aberrant tumor vascularization, and to reduce the blood loss and complications—thus avoiding any direct manipulation of the tumor and the cutting through cancer.22
Hypothetically, adding the no-touch isolation technique for this en bloc resection may even reduce the circulating tumor cell dissemination and the risk of metastasis into the draining vein during tumor mobilization.23 24
The TROMP technique enables the surgeon to perform an en-bloc retroperitoneal resection of all the peritoneal tumor (not only the pelvic tumor) combined with the no-touch technique by retroperitoneal resection of the affected organs. We consider that this makes the TROMP technique an effective tool to enhance visibility and exposure by shifting the dissection plane from intraperitoneal to retroperitoneal space, to minimize blood loss, and to limit the duration of the procedure. In the TROMP technique group, we achieved a more complete tumor resection in the very advanced ovarian cancer patients in a shorter median operation time, despite the significantly increased rate of surgical procedures (omentectomy, pelvic lymph node dissection, para-aortic lymph node dissection, appendectomy, small bowel resection, large bowel resection, partial resection of liver tissue, and splenectomy). This increase in surgical procedures was not associated with increased blood loss, the median admission time to the intensive care unit, or the rate of postoperative complications. The effect of this significant increase in complete tumor resection on progression-free and overall survival is the subject of a future study. Sugarbaker describes five surgical procedures to achieve a complete peritonectomy.25 The TROMP technique differs from his technique by dealing with the peritoneum as one specimen and by developing the isolation of the resected tissue completely retroperitoneally, adding the advantages of the no-touch isolation technique. This led to a complete tumor resection rate of 87.9% in advanced cases of ovarian cancer.
The rates of postoperative infections, pneumonia, anastomotic leaks, and wound dehiscence were higher in the TROMP technique group, but not statistically significantly. The increased rate of infections could be attributed to the higher rate of splenectomy and/or lymph node dissection14 in the TROMP group. A limitation of our study is the retrospective nature of the analysis, which might explain heterogeneity between the groups and may justify some reported differences. In addition, the small number of patients in the TROMP group might have limited our ability to detect true differences in events.
In conclusion, the TROMP technique is feasible and effective in the surgical management of patients with advanced ovarian cancer. This technique increased the complete tumor resection rate to 87.9%, and in the very advanced cases to 85%, without increasing blood loss, postoperative complications or duration of surgery. A prospective randomized study to validate these results is under consideration.
References
Footnotes
Contributors M-ZM wrote the paper, designed the study and contributed to the preparation of the data. JS reviewed the text and contributed to the design of the study. AM and JM collected the data and prepared them. RR performed the statistical studies and helped to write the methods section of the article.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests M-ZM is an adviser for Stryker. In the last 2 years he has received honoraria from Olympus, Ethicon (Johnson & Johnson), Roche and AstraZeneca. JS has received honoraria from AstraZeneca, Eisai, Clovis, Olympus, Johnson & Johnson, PharmaMar, Pfizer, TEVA, TESARO, and MSD, and performs advisory roles for AstraZeneca, Clovis, Lilly, PharmaMar, Pfizer, Roche, TESARO, and MSD. He has received research funding (not for this study) from AstraZeneca, Clovis, Merck, Bayer, PharmaMar, Pfizer, TESARO, and MSD. He has disclosed travel, accommodation, and other expenses paid or reimbursed by AstraZeneca, Clovis, PharmaMar, Roche, Pfizer, TESARO, and MSD, and were part of his scientific activities in the last 2 years. AM, RR and JM have no conflicts of interest.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. All data are to be identified in our database from the tumour bank ovarian cancer (www.toc-network.de).