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Stapled diaphragm resection: A new approach to diaphragmatic cytoreductive surgery for advanced-stage ovarian cancer

Open AccessPublished:October 21, 2022DOI:https://doi.org/10.1016/j.ejogrb.2022.10.014

      Abstract

      Objective

      To evaluate a novel technique for diaphragmatic full-thickness resection (DFTR) using a vascular stapler to perform cytoreductive surgeries in patients with advanced ovarian cancer.

      Study Design

      Single-center retrospective analysis of consecutive patients with advanced-stage ovarian cancer undergoing stapled diaphragmatic full-thickness resections (S-DFTRs) as part of cytoreductive surgeries between January 2018 and June 2022, according to the IDEAL recommendations.

      Results

      Fifteen patients underwent cytoreductive surgeries with S-DFTRs. The median operative time was 300 (114–547) minutes. Cytoreduction was considered complete in all cases. All S-DFTRs were performed on the right diaphragm. Concomitant left diaphragmatic peritoneal stripping was performed in 5 cases (33.3%) and was associated with a conventional DFTR in 1 case (6.7%). Prophylactic intraoperative tube thoracostomy was never required. Four patients (26.7%) were admitted to the intensive care unit. Pleural effusion was observed in 9 patients (60.0%), and 4 (26.7%) required a postoperative pigtail catheter thoracostomy. Three patients (20.0%) required catheter placement on the right hemithorax (ipsilaterally to the S-DFTR) and 2 patients (13.3%) required catheters on the left hemithorax (contralaterally to the S-DFTR). Pneumothorax requiring tube thoracostomy was observed in 1 case (6.7%) on the left hemithorax (contralaterally to the S-DFTR). Pulmonary embolism and pneumonia were both observed once (6.7%). The median hospitalization length was 14 (5–36) days. During the follow-up, 6 patients (40.0%) had a recurrence, but none involved the pleura or the diaphragm. According to the IDEAL classification, this study could be ranked as stage 2a (development).

      Conclusions

      This technique appears to be a fast and safe method for performing diaphragmatic cytoreductive surgeries and could reduce postoperative complications.

      Abbreviations:

      DFTR (diaphragmatic full-thickness resection), S-DFTR (stapled diaphragmatic full-thickness resection), SCS (surgical complexity score), PCI (peritoneal carcinomatosis index), ICU (intensive care unit), CD (Clavien-Dindo classification), ASA (American Society of Anesthesiologists)

      Keywords

      Introduction

      Ovarian cancer represents the most lethal gynecological malignancy, with an overall 5-year survival rate of approximately 50% [

      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 [

      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 [
      • Papadia A.
      • Morotti M.
      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 [
      • 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 [
      • 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 [
      • 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 [
      • Halkia E.
      • Efstathiou E.
      • Spiliotis J.
      • Romanidis K.
      • Salmas M.
      Management of diaphragmatic peritoneal carcinomatosis: surgical anatomy guidelines and results.
      ,
      • 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 [
      • 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 [
      • 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 [
      • 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.
      ].

      Material and methods

      Patient selection and Data collection

      We retrospectively reviewed all consecutive patients with advanced-stage ovarian cancer who underwent a stapled diaphragmatic full-thickness resection (S-DFTR) as part of a cytoreductive surgery at our institution between January 2018 and June 2022. We included patients who underwent an S-DFTR for primary or interval cytoreduction or for the treatment of relapses. We excluded patients who exclusively underwent other techniques to perform diaphragmatic cytoreductions. The study design followed the IDEAL framework and was classified as stage 2a (development). The study received approval from the local ethical committee (CER-VD), with registration number 2021–02473.
      All data were retrospectively collected from chart reviews and included patients’ demographic characteristics, perioperative details, histopathological findings, adjuvant therapies, and long-term follow-up data. Operative data, collected from operative reports, focused on intraoperative complications such as iatrogenic organ lesions, complications in performing S-DFTRs, inadvertent opening of the pleural cavity, and the need for tube thoracostomies. The complexity of surgical procedures and tumor distributions were categorized using the surgical complexity score (SCS) and the tumor dissemination subgroups previously described by Aletti et al. [
      • Aletti G.D.
      • Eisenhauer E.L.
      • Santillan A.
      • Axtell A.
      • Aletti G.
      • Holschneider C.
      • et al.
      Identification of patient groups at highest risk from traditional approach to ovarian cancer treatment.
      ]. In addition, the peritoneal carcinomatosis index (PCI) was obtained [
      • Sugarbaker P.H.
      Surgical management of peritoneal carcinosis: diagnosis, prevention and treatment.
      ]. The sizes of diaphragmatic resections were obtained from the histopathological report. Postoperative data focused on respiratory outcomes and included intensive care unit (ICU) admission, length of hospital stay, pleural effusion, pneumothorax, hemothorax, pneumonia, pulmonary embolism, catheter/tube thoracostomies, reintubation, and mechanical ventilation. Postoperative complications were graded using the Clavien-Dindo (CD) classification [
      • Dindo D.
      • Demartines N.
      • Clavien P.A.
      Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey.
      ]. Long-term outcomes were based on patients’ oncological and/or gynecological follow-up reports and focused on long-term respiratory complications, adjuvant oncological treatment, and disease recurrence.

      Surgical technique: stapled diaphragmatic full-thickness resection

      All surgical procedures were performed by the same surgical team, including a gynecologic oncology surgeon (DH) and a general/visceral surgeon (IF). A thoracic surgeon was present if needed (MC).
      To undergo S-DFTRs, patients are placed under general anesthesia in a dorsal lithotomy position, and a midline xipho-pubic laparotomy is performed to access the abdominal cavity. The round, falciform, coronary, and triangular ligaments are sectioned for complete liver mobilization. The diaphragmatic peritoneum is stripped until the lesions infiltrating the diaphragm are identified. Peritoneal stripping is performed with care in order to preserve the suprahepatic veins, the phrenic neurovascular pedicles, and the diaphragmatic muscle. The infiltrating lesions are exposed by traction using Kelly forceps, creating a fold of the diaphragm. During a prolonged forced mechanical expiration, the diaphragmatic fold is then excised at its base using a 45- or 60-mm linear Endo GIA black articulating reload stapler (for extra thick tissues) with tri-staple technology (Medtronic, Inc., Dublin, Ireland) (Fig. 1). If needed, the stapled line is subsequently reinforced with an absorbable running suture to reduce the traction on the staples. This technique avoids opening the pleural cavity, and no transthoracic or transdiaphragmatic drains are needed.
      Figure thumbnail gr1
      Fig. 1Main Steps in Stapled Diaphragmatic Full-Thickness Resection (A, B) The peritoneum overlying the diaphragm is stripped, and the liver is mobilized as needed. Gentle hepatic lateral traction is applied, and the infiltrating nodule (black arrowheads) is excised through a full-thickness diaphragm resection performed with a linear stapler. (C, D) Graphic reconstructions showing nodules (black arrowheads) of peritoneal carcinomatosis infiltrate the diaphragm. The nodules are exposed by traction on Kelly forceps, and the diaphragmatic fold formed by this traction is resected at its base using an articulating linear stapler.

      Statistical analysis

      The primary objective was to determine the intraoperative and postoperative surgical complications associated with S-DFTRs. The secondary objective was to assess this surgical technique’s feasibility by evaluating its success rate, the conversion rate to other surgical techniques, and the diaphragmatic cytoreduction completeness. Continuous variables are represented by their medians with minimum and maximum values, and categorical variables are represented as numbers and percentages.

      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/m2. 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.
      VariablePatients (n = 15)
      Age (y)67 (26–80)
      BMI (Kg/m2)22.1 (16.0–31.1)
      ASA class
      • -
        1
      2/15 (13.3)
      • -
        2
      8/15 (53.3)
      • -
        3
      5/15 (33.3)
      • -
        4
      Primary tumor
      • -
        Ovarian
      14/15 (93.3)
      • -
        Peritoneal
      1/15 (6.7)
      Histology
      • -
        Serous
      13/15 (86.7)
      • -
        Endometrioid
      2/15 (13.3)
      Tumor grade
      • -
        Low-grade
      2/15 (13.3)
      • -
        High-grade
      13/15 (86.7)
      FIGO stage
      • -
        IIIB
      2/15 (13.3)
      • -
        IIIC
      6/15 (40.0)
      • -
        IVA
      1/15 (6.7)
      • -
        IVB
      6/15 (40.0)
      Preoperative pleural effusion
      • -
        Right
      • -
        Left
      1/15 (6.7)
      • -
        Bilateral
      1/15 (6.7)
      Preoperative CA-125 (UI/mL)115 (22–990)
      Temporality of surgery
      • -
        Primary
      7/15 (46.7)
      • -
        Interval
      5/15 (33.3)
      • -
        Recurrence
      3/15 (20.0)
      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) cm2. 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.
      VariablePatients (n = 15)
      Tumor dissemination
      • -
        Low
      • -
        Intermediate
      5/15 (33.3)
      • -
        High
      10/15 (66.7)
      Peritoneal carcinomatosis index19 (3–26)
      • -
        ≤ 9
      3/15 (20.0)
      • -
        10–19
      5/15 (33.3)
      • -
        20–29
      7/15 (46.7)
      • -
        ≥ 30
      Surgical complexity score8 (2–11)
      • -
        Low (≤3)
      2/15 (13.3)
      • -
        Intermediate (47)
      4/15 (26.7)
      • -
        High (≥8)
      9/15 (60.0)
      Diaphragmatic involvement
      • -
        Right diaphragm
      15/15 (100)
      • -
        Left diaphragm
      5/15 (33.3)
      Diaphragmatic procedures and complications
      • -
        Right diaphragm
      • o
        Peritoneal stripping
      15/15 (100.0)
      • o
        S-DFTR
      15/15 (100.0)
      • o
        Conventional DFTR
      • o
        Pleural cavity opening
      • o
        Right hemithorax tube thoracostomy
      • -
        Left diaphragm
      • o
        Peritoneal stripping
      5/15 (33.3)
      • o
        S-DFTR
      • o
        Conventional DFTR
      1/15 (6.7)
      • o
        Pleural cavity opening
      2/15 (13.3)
      • o
        Left hemithorax tube thoracostomy
      Cytoreduction
      • -
        Complete
      15/15 (100)
      • -
        Incomplete
      Operative time (min)300 (114–547)
      Estimated blood loss (mL)425 (100–2000)
      Intraoperative blood transfusion1/15 (6.7)
      • -
        Units of blood transfused
      2 (2–2)
      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.
      VariablePatients (n = 15)
      Intensive care unit admission4/15 (26.7)
      • -
        Length of stay (d)
      2 (1–3)
      Hospital length of stay (d)14 (5–36)
      Respiratory complications
      • -
        Pleural effusion
      9/15 (60.0)
      • o
        Right hemithorax
      2/15 (13.3)
      • o
        Left hemithorax
      2/15 (13.3)
      • o
        Bilateral
      5/15 (33.3)
      • -
        Pneumothorax
      1/15 (6.7)
      • o
        Right hemithorax
      • o
        Left hemithorax
      1/15 (6.7)
      • o
        Bilateral
      • -
        Pneumonia
      1/15 (6.7)
      • -
        Pulmonary embolism
      1/15 (6.7)
      • -
        Clavien-Dindo classification*
      • o
        Grade I
      3/15 (20.0)
      • o
        Grade II
      2/15 (13.3)
      • o
        Grade IIIa
      5/15 (33.3)
      • o
        Grade IIIb
      Reintubation
      Postoperative tube thoracostomy1/15 (6.7)
      • -
        Right hemithorax
      • -
        Left hemithorax
      1/15 (6.7)
      • -
        Duration (hours)
      240 (240–240)
      Postoperative pigtail catheter thoracostomy4/15 (26.7)
      • -
        Right hemithorax
      3/15 (20.0)
      • -
        Left hemithorax
      2/15 (13.3)
      • -
        Duration (hours)
      24 (18–72)
      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.
      VariablePatients (n = 15)
      Follow-up (months)13.0 (2.0–45.8)
      Adjuvant chemotherapy14/15 (93.3)
      • -
        Time between surgery and chemotherapy (weeks)
      34 (23–94)
      • o
        46
      13/14 (92.9)
      • o
        > 6
      1/14 (7.1)
      • -
        No adjuvant chemotherapy
      1/15 (6.7)
      Cancer recurrence6/15 (40.0)
      • -
        After primary cytoreductive surgery
      3/7 (42.8)
      • o
        Time after surgery (months)
      30 (16–30)
      • -
        After interval cytoreductive surgery
      3/5 (60.0)
      • o
        Time after surgery (months)
      12 (7–14)
      • -
        After secondary/tertiary cytoreductive surgery
      0/3 (0)
      • o
        Time after surgery (months)
      • -
        Pleural/diaphragmatic recurrence
      Status at last visit
      • -
        DOD
      1/15 (6.7)
      • -
        AWD
      5/15 (33.3)
      • -
        NED
      9/15 (60.0)
      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 [
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      ,
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      • Edwin B.
      Laparoscopic liver resection with simultaneous diaphragm resection.
      ,
      • Karoui M.
      • Tayar C.
      • Laurent A.
      • Cherqui D.
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      ], 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 [
      • 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 [
      • 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%) [
      • 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 [
      • Mehta S.S.
      • Gelli M.
      • Agarwal D.
      • Goéré D.
      Complications of cytoreductive surgery and HIPEC in the treatment of peritoneal metastases.
      ,
      • Chua T.C.
      • Yan T.D.
      • Saxena A.
      • Morris D.L.
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      ]. 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 [
      • Papadia A.
      • Morotti M.
      Diaphragmatic surgery during cytoreduction for primary or recurrent epithelial ovarian cancer: a review of the literature.
      ,
      • Shin W.
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      Narrative review of liver mobilization, diaphragm peritonectomy, full-thickness diaphragm resection, and reconstruction.
      ,
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      • Lesieur B.
      • Selle F.
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      ]. 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 [
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      • 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 [
      • Papadia A.
      • Morotti M.
      Diaphragmatic surgery during cytoreduction for primary or recurrent epithelial ovarian cancer: a review of the literature.
      ,
      • 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% [
      • Papadia A.
      • Morotti M.
      Diaphragmatic surgery during cytoreduction for primary or recurrent epithelial ovarian cancer: a review of the literature.
      ,
      • 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.
      ,
      • Chéreau E.
      • Ballester M.
      • Lesieur B.
      • Selle F.
      • Coutant C.
      • Rouzier R.
      • et al.
      Complications of radical surgery for advanced ovarian cancer.
      ,
      • 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.
      ,
      • 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 [
      • 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) [
      • 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 [
      • 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 [
      • Chéreau E.
      • Ballester M.
      • Lesieur B.
      • Selle F.
      • Coutant C.
      • Rouzier R.
      • et al.
      Complications of radical surgery for advanced ovarian cancer.
      ,
      • 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 [
      • 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.
      ,
      • 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 [
      • 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.
      ,
      • Winter-Roach B.A.
      • Kitchener H.C.
      • Lawrie T.A.
      Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer.
      ,
      • 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 [
      • 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 [
      • 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 [
      • 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.

      Conclusions

      We conclude that S-DFTR appears to be a fast and simple method for diaphragmatic resections. This approach allowed for complete diaphragmatic cytoreduction, and compared to conventional DFTR; it could theoretically reduce respiratory surgical morbidity and the risk of postoperative complications in patients with advanced ovarian cancer.
      According to the IDEAL guidelines, our study has shown the safety and feasibility of our surgical technique and can be classified as stage 2a. Complemented by similar results reported by Hanna et al. [
      • 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 study allows moving to the next stages of research in the IDEAL framework. These include evaluations focusing on defining the intervention, its indications, and the standards quality via prospective cohort studies, followed by randomized controlled trials to evaluate this technique's short- and long-term impact on mortality, morbidity, and oncological outcomes compared with the conventional surgical treatment.

      Funding

      This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
      Statement of Prior presentation: This study has never been presented or published.
      Local Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki. Informed consent was obtained from the patients involved in the study. This study was approved by the local review board: project-ID 2021-02473 (24/03/2022, CER-VD, Lausanne, Switzerland).

      Data Availability Statement:

      Data are available on request from the authors.

      Declaration of Competing Interest

      The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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