Surgical resection of extra-abdominal metastases of low-grade serous ovarian cancer.Thomas GAILLARD, MD (1,4)Alessio MARIOLO, MD (2)Judicael HOTTON, MD, PhD (3,6)Enora LAAS, MD, PhD (1,5)Fabrice LECURU, MD, PhD (1,4,5)Institut Curie. Gynecologic Oncology department. 26 rue d’Ulm. 75005. Paris. France.Institut Medico-chirurgical Monsouris. Department of Thoracic Surgery, Curie-Montsouris Thoracic Institute. Paris. France.Institut Godinot, Gynecologic Oncology, Reims, FranceUniversité Paris Cité. Faculté de médecine. Paris. France.Institut Curie, Institut Hospitalo-Universitaire Cancers des Femmes (ANR-23-IAHU-0006), Paris, France.CReSTIC (Centre de Recherche en Sciences et Technologies de l’Information et de la Communication), UR 3804, Université de Reims Champagne-Ardenne, Reims, FRANCEKey clinical message.Removal of extra-abdominal spread of low-grade serous ovarian cancer is feasible. It seems having no deleterious impact on global management. Real impact on survival remains unclear.Introduction.Low-grade serous ovarian cancer (LGSC) has been individualized by Malpica 20 years ago (1). Few literature is available for the surgical aspects of this disease. The main recommendation is to perform a complete abdominal cytoreduction at primary surgery (2). However, these patients can present with extra-abdominal lesions. To our best knowledge, there is no specific guideline concerning this issue.We report three cases of patients with LGSC, having extra-abdominal disease which has been resected during initial treatment.Cases history/examination.Mrs B, 39-year-old is referred for bilateral suspicious ovarian masses. She has been previously treated for ectopic pregnancy, peritoneal endometriosis and she delivered two times after assisted medical procreation. Her familial history includes an endometrial cancer in her mother.Pelvic MRI showed bilateral complex masses, classified as ORADS 5. Thoraco-abdomino-pelvic CT-scan showed bilateral pelvic masses, moderate carcinosis, ascites and a right pleural effusion. PET-CT showed similar findings and revealed subcutaneous thoracic fixation and parasternal and mediastinal suspicious nodes. CA125 was elevated (697 UI/L). CA199 and ACE were normal.A diagnostic laparoscopy confirmed a carcinosis considered as resectable (PCI 25/39). However, the clinical examination showed two sub-cutaneous thoracic masses of 2cm in maximal diameter and a left breast mass. The omental biopsy confirmed the diagnosis of low-grade serous carcinoma (PAX8+, CK7+, WT1+, EMA+, CK20-, ER+ (100%), PR-, Ki67 15%, pMMR, without p53 or BRCA mutation). Biopsy of one sub-cutaneous lesion and of the breast mass confirmed metastases of the LGSC.Over follow-up, the thoracic and breast masses showed a progressive increase in size. The tumor board proposed a neo-adjuvant chemotherapy with paclitaxel (175mg/m2) and carboplatine (AUC 5). The patient thus received six cycles of treatment which were well tolerated. The CT-scan and the 18-F-FDG PET-CT showed a regression of the ascites and pleural effusion, but only mild regression of the carcinosis and thoracic masses. CA125 was at 78UI/L.A laparotomy with resection of the peritoneum of the right diaphragm and Morison space (+opening of the right diaphragm + resection of a part of the Glisson capsule), resection of the peritoneum of the left diaphragm, radical omentectomy and splenectomy, resection of the peritoneum of the two flanks, of the iliac fossae and mesentery, coagulation with argon beam of small bowel implants, total hysterectomy and bilateral salpingo-oophorectomy, resection of the pouch of Douglas, appendectomy, cholecystectomy and partial left mastectomy was performed. Sub-cutaneous thoracic masses had disappeared. Resection was considered macroscopically complete (CC0). A reoperation for biliary effusion was necessary on postoperative day 7 and was then uneventful.She was referred to the thoracic department one month later for evaluation of bilateral pleural effusion. The right-side effusion was recurrent and required placement of a permanent pleural drain for repeated evacuations.CT-scan demonstrated nodular infiltration of the right parietal pleura with diffuse hypermetabolism on preoperative 18F-FDG PET-scan, without pulmonary or lymph node involvement. Multidisciplinary tumor board decided for surgical exploration of the right pleural cavity and debulking of pleural metastases. The permanent drain was removed at patient’s request as it significantly impaired her quality of life. A three-port right thoracoscopy was performed. Pleural cavity presented multiples nodules involving the parietal, diaphragmatic and visceral pleura, as well as the pericardium (Figure 1 a, b, c). An extensive pleurectomy of parietal and diaphragmatic pleura was conducted. Considering the extension of the disease affecting the pericardium and the pulmonary hilum, pericardium was preserved to prevent any potential vascular injury. After confirming adequate lung re-expansion via pulmonary recruitment test, chemical pleurodesis was realized by instilling six grams of sterile medical talc into the pleural cavity. Due to the presence of a left pleural effusion, a left drain was also positioned at the end of surgery. In the immediate postoperative period, the patient developed isolated anemia without evidence of hemothorax, requiring blood transfusion. The left pleural drain was removed in postoperative day three: cytologic analysis of the pleural effusion confirmed malignancy. The right pleural drain was removed in postoperative day four and patient was discharged in postoperative day five.At one month of follow-up surgery the patient is in good general condition with a restored breathing on ambient air. Chest radiography showed a small bilateral residual pleural effusion that did not require further evacuation.She finally received 2 additional cycles of paclitaxel (175mg/m2) and carboplatine (AUC 5), followed by bevacizumab + exemestane. The patient is progression-free, five months after initial surgery.Mrs P aged 41 years was referred for an abdomino-pelvic mass discovered during a pelvic pain work-up. She had no hereditary or personal medical history. She was nullipara. The MRI showed a complex ovarian mass measuring 22cm in largest diameter (ORADS 5), without carcinosis. The CT-scan revealed mild ascites, several calcified pelvic and paraaortic nodes and no carcinosis. CA125 was elevated (1200 UI/L). The PET-CT showed similar findings plus thoracic and left axillary calcified nodes.She underwent a right salpingo-oophorectomy by laparotomy. Carcinosis was attested as minimal (PCI 7/39). Pathology showed at least a serous borderline tumor. An infracolic omentectomy was performed at the same time.Definitive pathology showed a low-grade serous ovarian carcinoma. Molecular biology showed no p53 mutation but a mutation of BRAF. The patient underwent a second operation with an infra-gastric omentectomy, paraaortic and pelvic lymphadenectomy, total hysterectomy and left salpingo-oophorectomy, bilateral inguinal lymphadenectomy and left axillary dissection. Resection was macroscopically complete (CC0). Postoperative course was uneventful, and the patient went back home on day 8.She was then referred to the thoracic surgery department. Chest CT-scan showed bilateral pathological mediastinal lymph-nodes, the largest measuring 18 mm in the subcarinal region. Lymph nodes presented a pathognomonic calcification highly suspected for secondary localization (Fig 2 a-b). The 18-F-FDG TEP-scan confirmed the absence of extranodal hypermetabolic activity in the chest. After a multidisciplinary discussion, bilateral radical lymph node resection with curative intent was recommended, and patient was scheduled for sequential surgery (day 21 after the laparotomy). A muscle sparing right lateral thoracotomy was first performed through the 5th intercostal space. The thoracic duct was identified and dissected behind the esophagus and azygos vein and was clipped s to prevent potential postoperative chylothorax. A radical mediastinal lymphadenectomy was performed including stations 9, 8, 7, 2, and 4. Dissection of subcarinal lymph node was technically demanding due to the size of the lesion and its compression of the carina and right main bronchus as well as the presence of the calcification and hypervascularization that made the specimen hardly manipulating and hemorrhagic during exposition (Figure 3). Postoperative course was uneventful with no chylothorax, recurrent laryngeal nerve palsy or other common complications related to extended lymph node dissection. Pleural drain was removed in postoperative day two and patient discharged the day after.One month later, a follow-up chest CT-scan confirmed the stability of the left-side lymph-node metastases without any other extra-thoracic disease. Given her good clinical condition, the patient underwent left-side metastasectomy via a muscle-sparing thoracotomy in the fifth intercostal space. Lymph node stations 9, 5 and 6 were dissected. Exploration of subcarinal region confirmed the absence of residual disease. No postoperative complications occurred. Pleural drain was removed in postoperative day one and patient discharged in postoperative day two.She finally received a platinum based chemotherapy followed by aromatase inhibitors, four months after the initial diagnosis. She is free of disease 10 months after the laparotomy.Mrs B is a 31-year-old woman, without personal medical history. Her familial history integrates a cousin with a BRCA2 mutation.A pelvic pain work-up revealed ovarian masses with carcinosis. A biopsy diagnosed a low-grade serous ovarian carcinoma. She was then referred to our department. The clinical examination showed a good general status woman with bilateral pelvic masses without ascites. The thoraco-abdomino-pelvic CT scan showed a diffuse carcinosis with involvement of the spleen, liver scalloping, several peritoneal nodules and several pelvic and paraaortic nodes. There was also a thickening of the pleura and implants in the right scissure. The PET-CT showed similar abdominal findings and revealed right sub-clavicular and axillary calcified nodes, mediastinal and paratracheal nodes associated with a thickening of the right scissure. CA125 was at 794 UI/L. Other markers were normal. A diagnostic laparoscopy showed an involvement of the omentum and both diaphragmatic doms. The abdomen and pelvis were not assessable due to the presence of a large tumoral mass associated with bowel adhesions. Biopsies confirmed the diagnosis of low-grade serous ovarian tumor (PAX8+, WT1+, P53wt, RE+, RP+. Molecular biology found no mutation of p53 and BRCA genes. The laparotomy allowed a complete macroscopic resection (CC0)(Hudson intervention associated with resection of part of the bladder dom, resection of implants on the mesentery and colonic mesos, resection of the peritoneum of the right diaphragmatic dome with opening and resection of pleural implants, resection of the peritoneum of the left diaphragmatic dome, radical omentectomy associated with a splenectomy, resection of an implant in front of the left adrenal gland, as well as implants of the lesser sac, ileo-colectomy, pelvic and paraaortic lymphadenectomy). She had an uneventful postoperative course (6 days in intensive care unit and 5 days in gynecology).She was referred to the thoracic surgery department.The thoracic CT-scan revealed nodular infiltration along the oblique right lung fissure, as well as the presence of suspected nodular thickening of the right parietal pleura and diaphragm (Fig 4 a b c ). An 18- F- FDG TEP scan confirmed the isolated hypermetabolic activity of the thoracic lesions. Following a multidisciplinary tumor board discussion, patient was deemed eligible for surgical resection. One month after the laparotomy, she underwent under general anesthesia, a right muscle-sparing lateral thoracotomy in the fifth intercostal space. Pleural cavity exploration revealed multiple small round lesions of the diaphragmatic pleural, a solitary exophytic lesion of the parietal pleura (Fig 5a) and a confluent nodular infiltration of the pulmonary fissure overlying the pulmonary artery, extending into the upper, middle and lower lung lobes (Fig 5b). The parietal lesion was easily excised including the surrounding pleura and a partial diaphragmatic pleurectomy was performed to remove all visible nodules on the diaphragm. A pneumotomy was then performed using an ultrasonic energy device to achieve en-bloc resection all the pulmonary nodules within the fissure preserving the pulmonary artery (Fig 5 c). Meticulous lung reconstruction was carried out using continuous sutures to ensure hemostasis and prevent air-leakage. Postoperative curse was uneventful.Pleural drain was removed on postoperative day one and patient was discharged on postoperative day 4. At three- months follow-up, she remained in good clinical condition with no evidence of thoracic recurrences.She then received chemotherapy (paclitaxel 175mg/m2 + carboplatine AUC5) followed by bevacizumab and aromatase inhibitor, three months after the initial diagnosis. She was managed by the psychological department. She has no constitutional deleterious mutation of the BRCA2 gene.She is free of disease after a 16 months follow-up.