Introduction
Ovarian cancer represents the most lethal gynecological malignancy, with an overall 5-year survival rate of approximately 50% [
[1]Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2018, National Cancer Institute. Bethesda, MD, based on November 2020 SEER data submission, posted to the SEER web site, April 202Available from: https://seer.cancer.gov/csr/1975_2018/.
]. This is partially explained by its early and “silent” spread, with more than half cases presenting in an advanced-stage [
[1]Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2018, National Cancer Institute. Bethesda, MD, based on November 2020 SEER data submission, posted to the SEER web site, April 202Available from: https://seer.cancer.gov/csr/1975_2018/.
]. Ovarian cancer frequently presents with peritoneal carcinomatosis, with diaphragmatic involvement observed in about 40% of cases [
[2]Diaphragmatic surgery during cytoreduction for primary or recurrent epithelial ovarian cancer: a review of the literature.
]. The goal of treatment includes complete surgical cytoreduction associated with a platin-taxane-based chemotherapy [
[3]- du Bois A.
- Reuss A.
- Pujade-Lauraine E.
- Harter P.
- Ray-Coquard I.
- Pfisterer J.
Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO).
], and the complete excision of all diaphragmatic lesions appears to be a crucial step that plays a significant role in the overall survival of these patients [
[4]- Rodriguez N.
- Miller A.
- Richard S.D.
- Rungruang B.
- Hamilton C.A.
- Bookman M.A.
- et al.
Upper abdominal procedures in advanced stage ovarian or primary peritoneal carcinoma patients with minimal or no gross residual disease: an analysis of Gynecologic Oncology Group (GOG) 182.
].
Diaphragmatic cytoreduction can be achieved by several approaches, depending on the volume, distribution, and depth of infiltration of the metastatic lesions. Superficial lesions can be treated by electrocoagulation, vaporization (e.g., argon beam vaporization), or peritonectomy (i.e., peritoneal stripping), while diaphragmatic full-thickness resections (DFTRs) are indispensable to treat peritoneal carcinomatosis nodules that deeply infiltrate the diaphragm [
[5]- Halkia E.
- Efstathiou E.
- Spiliotis J.
- Romanidis K.
- Salmas M.
Management of diaphragmatic peritoneal carcinomatosis: surgical anatomy guidelines and results.
]. When DFTRs are performed, diaphragmatic defects are closed with direct sutures or, more rarely, with a prosthetic mesh in case of extensive resections. DFTRs involve opening the pleural cavity and are associated with a high rate of postoperative complications such as pleural effusion and pneumothorax, often requiring a chest tube drainage [
5- Halkia E.
- Efstathiou E.
- Spiliotis J.
- Romanidis K.
- Salmas M.
Management of diaphragmatic peritoneal carcinomatosis: surgical anatomy guidelines and results.
,
6- Shin W.
- Mun J.
- Park S.Y.
- Lim M.C.
Narrative review of liver mobilization, diaphragm peritonectomy, full-thickness diaphragm resection, and reconstruction.
]. Limiting these complications is crucial to improving postoperative recovery and preventing adjuvant treatment delays [
[7]- Lin H.
- Chen W.-H.
- Wu C.-H.
- Ou Y.-C.
- Chen Y.-J.
- Chen Y.-Y.
- et al.
Impact of the time interval between primary debulking surgery and start of adjuvant chemotherapy in advanced epithelial ovarian cancer.
].
In 2018, in order to reduce the morbidity associated with DFTRs, we implemented a novel surgical technique, performing diaphragmatic resections using a vascular stapler [
[8]- Huber D.
- Christodoulou M.
- Fournier I.
- Seidler S.
- Besse V.
- Hurni Y.
How to perform complete resection of peritoneal carcinomatosis nodules infiltrating the diaphragm without opening the pleural cavity in patients with advanced-stage ovarian cancers.
]. DFTRs using this technique require neither opening the pleural cavity nor a prophylactic chest drain. In the present study, we report our initial experience using this novel approach for diaphragmatic resections in patients with advanced-stage ovarian cancer, according to the IDEAL (idea, development, exploration, assessment, long-term study) framework [
[9]- McCulloch P.
- Altman D.G.
- Campbell W.B.
- Flum D.R.
- Glasziou P.
- Marshall J.C.
- et al.
No surgical innovation without evaluation: the IDEAL recommendations.
].
Results
Fifteen patients with advanced-stage ovarian cancer underwent S-DFTRs as part of cytoreductive surgeries at our institution between January 2018 and June 2022.
Table 1 summarizes the patients’ demographic, oncological, and preoperative characteristics. The median age was 67 (26–80) years, and the median body mass index was 22.1 (16.0–31.1) kg/m
2. Patients had peritoneal carcinomatosis attributable to primary ovarian cancer (93.3%) or peritoneal cancer (6.7%). Tumors were high-grade in 86.7% of cases and low-grade in 13.3%. FIGO stages were IIIB (13.3%), IIIC (40.0%), IVA (6.7%), and IVB (40.0%). Patients underwent diaphragmatic resection as part of primary cytoreductive surgery in 7 cases (46.7%), interval surgery in 5 cases (33.3%), and as a treatment for recurrence in 3 cases (20.0%). Patients presenting with recurrence underwent a secondary cytoreductive surgery in 2 cases and a tertiary cytoreductive surgery in 1 case. During previous surgical procedures, none of these patients had had any diaphragmatic interventions.
Table 1Demographic, Oncologic and Preoperative Characteristics.
Data are presented as median (minimum and maximum values) or number (%).
Abbreviations: BMI, body mass index; ASA, American Society of Anesthesiologists.
Regarding tumor distribution at the time of surgery, 5 patients (33.3%) had intermediate tumor dissemination, and 10 (66.6%) had high tumor dissemination. A median PCI of 19 (3–26) was reported. Two patients (13.3%) had a low SCS, 4 (26.7%) had an intermediate SCS, and 9 (60.0%) had a high SCS. In all cases, peritoneal carcinomatosis was observed on the right diaphragm in all cases, with concomitant left diaphragm involvement in 5 patients (33.3%). All S-DFTRs were performed on the right diaphragm (15/15), with a mean resected area of 17.0 (8.0–44.0) cm
2. In addition, concomitant left diaphragm peritoneal stripping was performed in 5 cases (33.3%) and was accompanied with a conventional DFTR in 1 case (6.7%). S-DFTRs were successfully achieved in all cases without converting to other surgical techniques, allowing for complete diaphragmatic cytoreduction. Pleural cavity opening was reported in 2 cases (13.3%). Both cases were observed on the left diaphragm (contralaterally to the S-DFTRs), and were associated with a conventional DFTR in 1 case and with an inadvertent diaphragmatic tearing during peritoneal stripping in another. No intraoperative prophylactic chest tubes were required. Neither inadvertent opening of the pleural cavity nor intraoperative complications were associated with S-DFTRs. The median operative time was 300 (114–547) minutes, and the median estimated blood loss was 425 (100–2000) mL. Cytoreduction was considered complete in all cases. Operative characteristics are detailed in
Table 2.
Table 2Surgical Procedure and Operative Characteristics.
Data are presented as median (minimum and maximum values) or number (%).
Abbreviations: S-DFTR, stapled diaphragmatic full-thickness resection; DFTR, diaphragmatic full-thickness resection.
All patients were extubated in the operating room, and none required a reintubation. Four patients (26.7%) were admitted to the ICU. Postoperative pleural effusion was observed in 9 patients (60.0%), and 4 (26.7%) required a postoperative 8.5-Fr pigtail catheter drainage. Three patients (20.0%) required catheter placement on the right hemithorax (ipsilaterally to the S-DFTRs) and 2 patients (13.3%) required catheters on the left hemithorax (contralaterally to the S-DFTRs). Pneumothorax requiring a tube thoracostomy was observed in 1 case (6.7%) on the left hemithorax (contralaterally to S-DFTR). No cases of hemothorax were observed. Pulmonary embolism and pneumonia were both observed once (6.7%). The median hospitalization length was 14 (5–36) days. Fourteen patients (93.3%) received adjuvant chemotherapy, while in one case, the patient refused adjuvant treatment, and disease progression was observed 7 months after surgery. The median time between surgery and adjuvant therapy was 34 (23–94) days, and 13 patients (92.9%) started chemotherapy between 4 and 6 weeks after surgery, as planned. The remaining patient started adjuvant chemotherapy on postoperative day 94 because of infectious postoperative complications such as pneumonia and pyelonephritis. The median follow-up period was 13.0 (2.0–45.8) months. Six patients (40.0%) had recurrence, but none involved the pleura or the diaphragm. We observed no long-term respiratory complications associated with S-DFTRs. Postoperative and long-term outcomes are detailed in
Table 3 and
Table 4.
Table 3Postoperative Outcomes.
Data are presented as median (minimum and maximum values) or number (%).
* ln the case of multiple complications, the highest grade is reported.
Abbreviations: DOD, dead of disease; AWD, alive with disease; NED, no evidence of disease.
Table 4Long-term Follow-Up.
Data are presented as median (minimum and maximum values) or number (%).
Abbreviations: DOD, dead of disease; AWD, alive with disease; NED, no evidence of disease.
Regarding the IDEAL evaluation, this study was classified as stage 2a (development).
Discussion
In this retrospective study, we have reported our initial experience with an innovative surgical approach to performing DFTRs in the context of advanced ovarian cancer. As in other techniques used in surgical interventions for benign and malignant diaphragmatic procedures [
13- Lao V.V.
- Lao O.B.
- Abdessalam S.F.
Laparoscopic transperitoneal repair of pediatric diaphragm eventration using an endostapler device.
,
14- Moon S.W.
- Wang Y.P.
- Kim Y.W.
- Shim S.B.
- Jin W.
Thoracoscopic plication of diaphragmatic eventration using endostaplers.
,
15- Juretzka M.M.
- Horton F.R.
- Abu-Rustum N.R.
- Sonoda Y.
- Jarnagin W.R.
- Flores R.M.
- et al.
Full-thickness diaphragmatic resection for stage IV ovarian carcinoma using the EndoGIA stapling device followed by diaphragmatic reconstruction using a Gore-tex graft: a case report and review of the literature.
,
16- Kazaryan A.M.
- Aghayan D.L.
- Fretland Å.A.
- Semikov V.I.
- Shulutko A.M.
- Edwin B.
Laparoscopic liver resection with simultaneous diaphragm resection.
,
17- Karoui M.
- Tayar C.
- Laurent A.
- Cherqui D.
En bloc stapled diaphragmatic resection for local invasion during hepatectomy: a simple technique without opening the pleural cavity.
], we employed a stapler device to perform diaphragmatic resections in ovarian cancer cytoreductive procedures. Although Hanna et al. recently reported using a very similar technique to perform DFTRs in patients undergoing cytoreductive surgeries with hyperthermic intraperitoneal chemotherapy for colorectal and appendiceal cancer [
[18]- Hanna D.N.
- Schlegel C.
- Ghani M.O.
- Hermina A.
- S Mina A.
- McKay K.
- et al.
Stapled Full-thickness diaphragm resection: A novel approach to diaphragmatic resection in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.
], this is the first study describing S-DFTRs in patients with ovarian cancer.
Compared to conventional techniques, S-DFTR does not require opening the pleural cavity and seems easier and faster to perform. The potential advantages of this method include reduced operating time, no need for intraoperative prophylactic tube thoracostomies, reduced risk of significant postoperative respiratory complications, and limited risk of cancer cell contamination of the pleural cavity. The main limitation of this technique is in the case of very large or multiple confluent nodules, not allowing for stapled resections because of inadequate lesion exposure due to tissue rigidity or because of extensive needed resections that would result in excessive diaphragmatic tension. Conventional DFTR with prosthetic mesh repair could be more suitable in these rare cases. Hanna et al. demonstrated that, compared to conventional DFTR, S-DFTR decreased the length of ICU stay, the need for postoperative tube thoracostomy, postoperative pneumonia, reintubation, and mechanical ventilation longer than 48 h [
[18]- Hanna D.N.
- Schlegel C.
- Ghani M.O.
- Hermina A.
- S Mina A.
- McKay K.
- et al.
Stapled Full-thickness diaphragm resection: A novel approach to diaphragmatic resection in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.
]. In our cohort, all S-DFTRs were performed successfully without any intraoperative complications, and complete cytoreduction was achieved in all cases. Compared to Hanna et al., we reported similar intra- and postoperative outcomes but with a lower ICU admission rate (27% vs 53%) [
[18]- Hanna D.N.
- Schlegel C.
- Ghani M.O.
- Hermina A.
- S Mina A.
- McKay K.
- et al.
Stapled Full-thickness diaphragm resection: A novel approach to diaphragmatic resection in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.
], probably due to the higher risk of complications associated with hyperthermic intraperitoneal chemotherapy [
19- Mehta S.S.
- Gelli M.
- Agarwal D.
- Goéré D.
Complications of cytoreductive surgery and HIPEC in the treatment of peritoneal metastases.
,
20- Chua T.C.
- Yan T.D.
- Saxena A.
- Morris D.L.
Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure?: a systematic review of morbidity and mortality.
]. However, respiratory outcomes were similar, suggesting that, compared to conventional DFTR, stapled techniques could reduce the rate of respiratory complications even in patients with advanced ovarian cancer.
Respiratory complications are frequently observed after diaphragmatic surgery in patients with ovarian cancer, including pleural effusion, pneumothorax, pulmonary embolism, and respiratory tract infections [
2Diaphragmatic surgery during cytoreduction for primary or recurrent epithelial ovarian cancer: a review of the literature.
,
6- Shin W.
- Mun J.
- Park S.Y.
- Lim M.C.
Narrative review of liver mobilization, diaphragm peritonectomy, full-thickness diaphragm resection, and reconstruction.
,
21- Chéreau E.
- Ballester M.
- Lesieur B.
- Selle F.
- Coutant C.
- Rouzier R.
- et al.
Complications of radical surgery for advanced ovarian cancer.
]. Although pleural effusion may also occur as a result of postoperative volume overload, these respiratory complications seem correlated mainly with the inflammatory response associated with extensive diaphragm manipulation, pleural cavity effraction, and the size of the diaphragmatic resection [
22- Zapardiel I.
- Peiretti M.
- Zanagnolo V.
- Biffi R.
- Bocciolone L.
- Landoni F.
- et al.
Diaphragmatic surgery during primary cytoreduction for advanced ovarian cancer: peritoneal stripping versus diaphragmatic resection.
,
23- Chéreau E.
- Rouzier R.
- Gouy S.
- Ferron G.
- Narducci F.
- Bergzoll C.
- et al.
Morbidity of diaphragmatic surgery for advanced ovarian cancer: retrospective study of 148 cases.
,
24- Fanfani F.
- Fagotti A.
- Gallotta V.
- Ercoli A.
- Pacelli F.
- Costantini B.
- et al.
Upper abdominal surgery in advanced and recurrent ovarian cancer: role of diaphragmatic surgery.
]. Symptomatic pleural effusions and pneumothoraces seem observed more often in the case of DFTRs than in peritoneal stripping or coagulation [
2Diaphragmatic surgery during cytoreduction for primary or recurrent epithelial ovarian cancer: a review of the literature.
,
22- Zapardiel I.
- Peiretti M.
- Zanagnolo V.
- Biffi R.
- Bocciolone L.
- Landoni F.
- et al.
Diaphragmatic surgery during primary cytoreduction for advanced ovarian cancer: peritoneal stripping versus diaphragmatic resection.
], with a typical rate of intra- and postoperative thoracic drainage between 22.7% and 100% [
2Diaphragmatic surgery during cytoreduction for primary or recurrent epithelial ovarian cancer: a review of the literature.
,
18- Hanna D.N.
- Schlegel C.
- Ghani M.O.
- Hermina A.
- S Mina A.
- McKay K.
- et al.
Stapled Full-thickness diaphragm resection: A novel approach to diaphragmatic resection in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.
,
21- Chéreau E.
- Ballester M.
- Lesieur B.
- Selle F.
- Coutant C.
- Rouzier R.
- et al.
Complications of radical surgery for advanced ovarian cancer.
,
25- Ye S.
- He T.
- Liang S.
- Chen X.
- Wu X.
- Yang H.
- et al.
Diaphragmatic Surgery and Related Complications In Primary Cytoreduction for Advanced Ovarian, Tubal, and Peritoneal Carcinoma.
,
26- Cianci S.
- Fedele C.
- Vizzielli G.
- Pasciuto T.
- Gueli Alletti S.
- Cosentino F.
- et al.
Surgical outcomes of diaphragmatic resection during cytoreductive surgery for advanced gynecological ovarian neoplasia: A randomized single center clinical trial - DRAGON.
]. In our cohort, we report a total intra- and postoperative thoracic drainage rate of 33.3%. This rate appears even lower when focusing on hemithoraces treated with S-DFTRs, where intraoperative thoracic drainages were never required, postoperative pigtail catheter thoracostomies were needed in 20.0% of cases, and conventional tube thoracostomies were never used.
These results suggest that our stapled technique could be a simple, fast, and safe alternative to performing conventional DFTRs, allowing for simultaneous diaphragmatic resection and repair with minimal muscular manipulations and no opening of the pleural cavity. These features could limit the pleural inflammatory response, potentially reducing the development of significant pleural effusions or pneumothoraces, limiting the use of thoracic drainages, and generally decreasing the risk of respiratory complications. Although some authors have suggested the systematic use of chest tubes for diaphragmatic resections [
[26]- Cianci S.
- Fedele C.
- Vizzielli G.
- Pasciuto T.
- Gueli Alletti S.
- Cosentino F.
- et al.
Surgical outcomes of diaphragmatic resection during cytoreductive surgery for advanced gynecological ovarian neoplasia: A randomized single center clinical trial - DRAGON.
] and even for large diaphragmatic peritonectomies (without pleural cavity opening) [
[27]- Sandadi S.
- Long K.
- Andikyan V.
- Vernon J.
- Zivanovic O.
- Eisenhauer E.L.
- et al.
Postoperative outcomes among patients undergoing thoracostomy tube placement at time of diaphragm peritonectomy or resection during primary cytoreductive surgery for ovarian cancer.
], we propose avoiding their systematic use when performing an S-DFTR. In the ERAS (Enhanced Recovery After Surgery) era, restricting the use of chest drains appears essential, allowing for improved postoperative respiratory functions, decreased postoperative pain, and easier patient mobilization, thus enhancing postoperative recovery [
[28]- Nelson G.
- Bakkum-Gamez J.
- Kalogera E.
- Glaser G.
- Altman A.
- Meyer L.A.
- et al.
Guidelines for perioperative care in gynecologic/oncology: Enhanced Recovery After Surgery (ERAS) Society recommendations-2019 update.
].
Limiting surgical morbidity is essential, especially in the context of advanced-stage ovarian cancer, where the frequently encountered combination of fragile patients and complex surgical procedures involves a high risk of postoperative complications [
21- Chéreau E.
- Ballester M.
- Lesieur B.
- Selle F.
- Coutant C.
- Rouzier R.
- et al.
Complications of radical surgery for advanced ovarian cancer.
,
23- Chéreau E.
- Rouzier R.
- Gouy S.
- Ferron G.
- Narducci F.
- Bergzoll C.
- et al.
Morbidity of diaphragmatic surgery for advanced ovarian cancer: retrospective study of 148 cases.
]. Severe postoperative complications can affect recovery time and lengthen time intervals for adjuvant therapies. Delayed adjuvant treatment can have a negative impact on a patient's survival [
7- Lin H.
- Chen W.-H.
- Wu C.-H.
- Ou Y.-C.
- Chen Y.-J.
- Chen Y.-Y.
- et al.
Impact of the time interval between primary debulking surgery and start of adjuvant chemotherapy in advanced epithelial ovarian cancer.
,
29- Seagle B.L.
- Butler S.K.
- Strohl A.E.
- Nieves-Neira W.
- Shahabi S.
Chemotherapy delay after primary debulking surgery for ovarian cancer.
], thus highlighting the importance of enhancing rapid postoperative recovery. Although the debate regarding the optimal timing to start adjuvant chemotherapy is still open, the ideal time seems to be around 4–6 weeks after surgery [
7- Lin H.
- Chen W.-H.
- Wu C.-H.
- Ou Y.-C.
- Chen Y.-J.
- Chen Y.-Y.
- et al.
Impact of the time interval between primary debulking surgery and start of adjuvant chemotherapy in advanced epithelial ovarian cancer.
,
30- Winter-Roach B.A.
- Kitchener H.C.
- Lawrie T.A.
Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer.
,
31- Chan J.K.
- Java J.J.
- Fuh K.
- Monk B.J.
- Kapp D.S.
- Herzog T.
- et al.
The association between timing of initiation of adjuvant therapy and the survival of early stage ovarian cancer patients - An analysis of NRG Oncology/Gynecologic Oncology Group trials.
]. In our cohort, 92.9% of patients were able to start adjuvant therapies between 4 and 6 weeks after surgery, despite one-third of patients being classified as American Society of Anesthesiologists (ASA) class 3 and 60% presenting a high SCS.
The least aggressive approach permitting complete tumor resection should be favored when performing diaphragmatic resections for patients with advanced ovarian cancer. Our S-DFTR technique could be a promising alternative to the standard procedure. In addition to its benefit for patients, the potential surgical morbidity reduction associated with our technique could reduce hospitalization costs and delays of adjuvant chemotherapy.
To the best of our knowledge, this is the first study reporting the use of S-DFTR for cytoreductive surgery in patients with advanced ovarian cancer. We adopted the IDEAL framework to report our data [
[9]- McCulloch P.
- Altman D.G.
- Campbell W.B.
- Flum D.R.
- Glasziou P.
- Marshall J.C.
- et al.
No surgical innovation without evaluation: the IDEAL recommendations.
]. We firstly described our technique in stage 1 (idea) report [
[8]- Huber D.
- Christodoulou M.
- Fournier I.
- Seidler S.
- Besse V.
- Hurni Y.
How to perform complete resection of peritoneal carcinomatosis nodules infiltrating the diaphragm without opening the pleural cavity in patients with advanced-stage ovarian cancers.
], followed by the current stage 2a (development) study. Despite the retrospective nature of the study, it fulfilled the criteria of stage 2a in terms of the number of patients and data concerning the safety and efficacy of this newly developed surgical technique. The remaining IDEAL stages have not yet been met by the available evidence (which is limited to only one other study [
[18]- Hanna D.N.
- Schlegel C.
- Ghani M.O.
- Hermina A.
- S Mina A.
- McKay K.
- et al.
Stapled Full-thickness diaphragm resection: A novel approach to diaphragmatic resection in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.
]), and randomized controlled trials are needed to proceed to further phases.
There are several limitations to this study. First, it was a single-institution, single-surgical team, retrospective case series, resulting in various biases. Second, the retrospective character was not a desirable research format for the IDEAL classification stage 2a. Third, some patients were followed up for a limited time after surgery, limiting the long-term evidence for safety of this surgical technique. Additional studies are therefore needed to confirm our preliminary results.
Article info
Publication history
Published online: October 21, 2022
Accepted:
October 13,
2022
Received in revised form:
October 7,
2022
Received:
August 16,
2022
Copyright
© 2023 The Authors. Published by Elsevier B.V.