Gynaecological oncology
DOI: 10.1111/j.1471-0528.2011.03197.x www.bjog.org
Upper abdominal cytoreduction and thoracoscopy for advanced epithelial ovarian cancer: unanswered questions and the impact on treatment AC Fleury,a CL Kushnir,a RL Giuntoli II,
a
NM Spirtosb
a
Johns Hopkins Medical Institutions, Baltimore, MD, USA b Women’s Cancer Center of Nevada, Las Vegas, NV, USA Correspondence: Dr A Fleury, Johns Hopkins Medical Institutions, 600 N. Wolfe Street, Phipps 281, Baltimore, MD 21287, USA. Email
[email protected] Accepted 18 September 2011. Published Online 15 November 2011.
Gynaecological oncologists, by conducting Phase II and III chemotherapy trials, have sought to improve survival in women with epithelial ovarian cancer. The greatest impact on survival has been the use of intraperitoneal chemotherapy in women who have had all visible disease removed. No change in drug regimen has had an impact on survival equivalent to that associated with complete cytoreduction or the use of intraperitoneal chemotherapy. Interestingly, these two treatment modalities (complete cytoreduction and intraperitoneal chemotherapy) have not been universally adopted. Most often it is the inability to achieve optimal cytoreduction in the upper abdomen that defines the limit of the cytoreductive effort, and ultimately the integration of intraperitoneal chemotherapy. The importance of identifying
disease outside the abdominal cavity, along with achieving complete cytoreduction, is paramount, if the use of intraperitoneal chemotherapy is to be logically integrated in treatment algorithms for women with advanced-stage epithelial ovarian cancer. This report summarises pertinent literature on upper abdominal cytoreduction, discusses surgical techniques and introduces new data on women with epithelial ovarian cancer undergoing thoracoscopy, suggesting consideration of its incorporation into the surgical management of advanced epithelial ovarian cancer. Keywords Cytoreduction, diaphragm, ovarian cancer, splenec-
tomy, thoracocscopy.
Please cite this paper as: Fleury A, Kushnir C, Giuntoli R, Spirtos N. Upper abdominal cytoreduction and thoracoscopy for advanced epithelial ovarian cancer: unanswered questions and the impact on treatment. BJOG 2012;119:202–206.
Introduction Ovarian cancer is the most lethal of all gynaecological cancers.1–5 Survival is related to stage at diagnosis and the amount of residual disease. Over the last two decades the definition of optimal cytoreduction has changed from residual disease of 1 cm) visceral pleural metastases and one was found to have tumour involving the entire parietal pleura. All 75 women underwent aortic and pelvic lymphadenectomy
ª 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2011 RCOG
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Fleury et al.
Table 1. Patient characteristics (n = 75)
n (%) Median (range) age, years GOG Performance Status (0,1) Location of largest disease Diaphragm Omentum Pelvis Lymph nodes Mesentery
Positive thoracoscopy
Negative thoracoscopy
27 (36.0) 60.5 (29–75) 100%
48 (64.0) 63 (39–76) 100%
2/27 7/27 15/27 2/27 2/27
1/48 10/48 37/48 1/48 1/48
(7.4%) (25.9%) (55.6%) (7.4%) (7.4%)
(2.1%) (20.8%) (77.1%) (2.1%) (2.1%)
GOG, Gynecologic Oncology Group.
Table 2. Surgical procedures Procedure performed
Positive thoracoscopy
Negative thoracoscopy
Modified posterior exenteration Aortic and pelvic lymphadenectomy Splenectomy Omentectomy Distal pancreatectomy Cholecystectomy Large bowel resection Small bowel resection Partial gastrectomy Partial cystectomy Nephrectomy Liver resection Diaphragm stripping Full-thickness diaphragm resection Peritoneal resection No residual disease Residual disease 1 cm
19/27 (70.4%)
38/48 (79.2%)
27/27 (100%)
48/48 (100%)
4/27 27/27 1/27 1/27 2/27 5/27 0/27 1/27 0/27 1/27 25/27 12/27
(14.8%) (100%) (3.7%) (3.7%) (7.4%) (18.5%) (0%) (3.7%) (0%) (3.7%) (92.6%) (44.4%)
8/48 48/48 1/48 1/48 6/48 4/48 2/48 1/48 1/48 1/48 43/48 3/48
(16.7%) (100%) (2.1%) (2.1%) (12.5%) (8.3%) (4.2%) (2.1%) (2.1%) (2.1%) (89.6%) (6.3%)
26/27 22/27 3/27 2/27
(96.3%) (81.5%) (11.1%) (7.4%)
45/48 43/48 2/48 3/48
(93.8%) (89.6%) (4.2%) (6.3%)
with resection of the gonadal vessels. Notably, 25 of the 27 (92.6%) women with disease identified in the right thorax had positive retroperitoneal lymph nodes. Overall 55 (73.3%) of the 75 women had metastatic disease identified in the lymph nodes with macroscopic disease identified in lymph nodes above the inferior mesenteric artery in 46 (61.3%) of the women. Given the high percentage of women requiring thoracentesis to drain postoperative pleural effusions (69.3%; 52 of 75), we now routinely place a chest tube at the time of thoracoscopy. Additionally subdi-
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aphragmatic and pelvic drains are also placed (Figure 1 and see Supplementary material, Figures S1–S4). Undertaking surgical resection to this extent carries with it associated morbidity and mortality requiring careful patient selection and counselling. For a more detailed discussion on operative technique and sites of special concern, please see the appendix (see Supplementary material, Appendix S1). The anaesthesiologist and critical-care specialists are important and necessary parts of the team effort required to undertake such procedures. It is our practice to begin transfusion of both red blood cells and fresh frozen plasma as soon as coeliotomy is performed and widespread resectable disease is identified. Since beginning this practice we have essentially eliminated the development of significant intraoperative disseminated intravascular coagulopathy. If epidural anaesthesia is to be considered then the associated venous dilatation requires a significant effort to maintain intravascular volume and the issue of the perioperative use of low-molecular-weight heparin must be addressed. The associated sympathetic block results in constriction of the bowel, which may make the use of stapling devices more challenging. For these reasons it is our preference to avoid epidural or spinal anaesthesia as an adjunct to general anaesthesia and prefer no nitrous oxide be used because its accumulation in the gastrointestinal tract can make exposure problematic and closure of the abdominal wall difficult after a long surgical procedure. In an attempt to minimise postoperative complications, all women undergoing modified posterior exenteration and low rectal anastomosis had either a diverting ileostomy or colostomy. Despite taking these preventative measures, three enteric fistulae developed. Two were associated with breakdown of staple lines and one woman developed a duodenal leak following a Billroth II procedure. The majority of the hospital re-admissions were associated with the development of intra-abdominal abscesses, partial small bowel obstruction or dehydration secondary to copious output from an ileostomy (Table 3). Median operative time was 252 minutes (180–320 minutes). Median hospital stay was 11 days (5–62 days). It was impossible to accurately estimate blood loss because of the amount of ascites present and the use of large amounts of saline and water for hydrodissection during surgery. The median number of units of packed red blood cells and fresh frozen plasma transfused was 7 units (range 1–16 units) and 6 units fresh frozen plasma (1–14 units). The median amount of fluid resuscitation was 9500 ml crystalloid and blood products (range 4000–14 500 ml). Postoperative deaths resulted from sepsis, as the result of an anastomotic leak; a pulmonary embolism; and a perforated trachea associated with the replacement of an endotracheal tube in anticipation of performing a bronchoscopy (Table 3).
ª 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2011 RCOG
Upper abdominal cytoreduction in epithelial ovarian cancer
Conclusions
Table 3. Morbidity and mortality Complication
Positive thoracoscopy
Negative thoracoscopy
Pneumonia Gastrointestinal fistula Pancreatic leak Chylous ascites Urinary tract fistula Pulmonary embolism Pleural effusion requiring drainage Abscess Re-admission Postoperative death
1/27 1/27 0/27 0/27 0/27 1/27 19/27 3/27 3/27 1/27
1/48 2/48 1/48 1/48 1/48 1/48 33/48 4/48 5/48 2/48
(3.7%) (3.7%) (0%) (0%) (0%) (3.7%) (70.4%) (11.1%) (11.1%) (3.7%)
(2.1%) (4.2%) (2.1%) (2.1%) (2.1%) (2.1%) (68.8%) (8.3%) (10.4%) (4.2%)
Evaluation of the thoracic cavity can be accomplished either transdiaphragmatically or transthoracically with video assistance, neither of which is technically challenging but may require the assistance of a cardiovascular surgical team for surgeons unfamiliar with these techniques. Multiple authors have reported on the use of these techniques in women with pleural effusions and when suboptimal disease is identified instead of undertaking a primary cytoreductive effort, neoadjuvant chemotherapy can be initiated with the intent of performing an interval debulking procedure in those women responding to chemotherapy.16–19 Many of the same authors have reported success undertaking primary cytoreduction of thoracic disease before undertaking laparotomy with the intent to resect all visible disease.16–20 Although controversial and not fully understood, the role of intrathoracic evaluation and cytoreductive surgery does provide one more method to ensure that unnecessary intra-abdominal cytoreductive surgery is not undertaken in women who otherwise would remain with suboptimal residual disease. This apparently can be performed with minimal morbidity and may have a positive effect on survival.
Epithelial ovarian cancer is most commonly diagnosed in advanced stages. The prognostic value of complete cytoreduction has been reported and confirmed in several publications.6,21,22 Similarly intraperitoneal chemotherapy is associated with improved overall survival in women with small-volume residual disease (
