- Open Access
Role of primary surgery in advanced ovarian cancer
© Münstedt and Franke; licensee BioMed Central Ltd. 2004
- Received: 04 July 2004
- Accepted: 02 October 2004
- Published: 02 October 2004
Major issues in surgery for advanced ovarian cancer remain unresolved. Existing treatment guidelines are supported by a few published reports and fewer prospective randomized clinical trials.
We reviewed published reports on primary surgical treatment, surgical expertise, inadequate primary surgery/quality assurance, neoadjuvant chemotherapy, interval debulking, and surgical prognostic factors in advanced ovarian cancer to help resolve outstanding issues.
The aim of primary surgery is a well-planned and complete intervention with optimal staging and surgery. Surgical debulking is worthwhile as there are further effective treatments available to control unresectable residual disease. Patients of gynecologic oncology specialist surgeons have better survival rates. This may reflect a working 'culture' rather than better technical skills. One major problem though, is that despite pleas to restrict surgery to experienced surgeons, specialist centers are often left to cope with the results of inadequate primary surgical resections. Patients with primary chemotherapy or those who have had suboptimal debulking may benefit from interval debulking. A proposal for a better classification of residual tumor is given.
Optimal surgical interventions have definite role to play in advanced ovarian cancers. Improvements in surgical treatment in the general population will probably improve patients' survival when coupled with improvements in current chemotherapeutic approaches.
- Residual Tumor
- Advanced Ovarian Cancer
- Stage IIIc
- Optimal Debulking
- Residual Tumor Size
The Fédération Internationale de Gynécologie et d'Obstétrigue (FIGO) classifies ovarian carcinoma in stage I to IV [1, 2]. Stage I has been defined as growth limited to the ovaries; stage II as growth involving one or both ovaries with pelvic extension; stage III as tumor involving one or both ovaries with peritoneal implants, and outside the pelvis and/or positive retroperitoneal or inguinal nodes and stage IV as having distant metastasis [1, 2].
Tumors in stages I and II are generally considered to represent early disease, while stages III and IV evince late or advanced disease [3, 4]. The strong prognostic value of the FIGO classification system has been proved in number of studies .
Unfortunately, most ovarian carcinomas are detected only when they are advanced. Results of studies evaluating screening by tumor markers (a raised CA125 value) and/or ultrasonography to detect early disease are not clear [6, 7]. Ultrasonography may become an increasingly important tool as it has been associated with higher detection rates in early stage disease and in patients with a genetic predisposition to tumor [8–11]. However, use of proteomics will perhaps identify more ovarian carcinomas at early stages in the future .
Though controversial till 70s, surgery is now recognized an integral part of the treatment armamentarium in advanced ovarian carcinoma. Aure et al.,  presented convincing evidence that extensive tumor removal resulted in better survival even in advanced stage disease and introduced the idea of primary tumor debulking surgery. The value of primary debulking surgery was confirmed and its theoretical background was elucidated by Griffith and Fuller . Subsequent work showed that debulking surgery improves an adverse vegetative function and nutritional problems such as loss of appetite and nausea [15, 16]. It was also suggested that primary debulking surgery removes therapy-resistant tumor cells and increases the number of proliferating tumor cells (the Gompertzian phenomenon), which makes these cells more susceptible to subsequent chemotherapy [17–19]. These early hypotheses have partly been confirmed by the finding of increased postoperative tumor proliferation rates in patients after surgery .
Ongoing discussions about quality assurance and guideline-based therapy had helped to foster the impression that the main issues in treating ovarian cancer have been resolved and that the value of each procedure involved has been supported by high levels of scientific evidence [21–23]. Closer inspection reveals that it is not true. Only a few treatment guidelines are supported by published reports, and even fewer by prospective randomized clinical trials. However, we strongly believe the value of retrospective studies is greatly underestimated. Recent analyses show that the treatment effects assessed by observational studies do not greatly differ in magnitude or quality from those published in randomized, controlled trials [24, 25]. Furthermore, biases created by the selection criteria inherent in prospective randomized trials are frequently ignored.
Thus, in this article we will concentrate on looking more closely at several issues in surgical treatment, their effects and importance in relation to outcome in advance ovarian cancer.
Primary surgical treatment
The utility of primary surgery for advanced ovarian cancer is well established. Its aim should be a well-planned, extensive and complete intervention. Thus, no facility should offer surgery for patients with ovarian cancer if adequate standards of care cannot be met.
The optimal preparation of patients for surgery is very important. Patients must be in a position to give fully informed consent to any additional surgical procedures found necessary during the operation. They should also undergo colonic lavage, which will provide the surgeon with better access to the lymph nodes and reduce risks in cases where intestinal surgery is undertaken. Where cytological evaluation of peritoneal fluid aspired preoperatively, a raised concentration of serum CA125, or ultrasound results indicate advanced malignancy, the patient should be transferred to a specialist surgeon (see below).
Many cases where the staging is not clear, laparoscopy appears to be good tool for obtaining a definitive histological diagnosis in advanced ovarian cancer and helps in planning the best surgical approach. Laparoscopic staging, in particular, can give a clear view of the extent of surgery required and the difficulties that may be expected, and it may be helpful in selecting patients for primary (neoadjuvant) chemotherapy . Video recording can document the findings during laparoscopy and can be used subsequently by the surgeon to plan optimal debulking surgery.
However, laparoscopic surgery of any suspicious adnexal mass is not encouraged unless the risk of capsular rupture and tumor spill is minimized by the use of endobags . No cystic mass which is >10 cm in diameter and/or adherent to the lateral pelvic wall should be removed laparoscopically .
The fear due to some in-vitro and animal studies that showed carbon dioxide pneumoperitoneum has adverse effects on outcomes is probably unfounded, as a recent analysis from second-look laparoscopies showed no influence of pneumoperitoneum on overall survival . Certainly, more data on this issue is required.
Since laparoscopy may increase tumor growth rates, delays between laparoscopy and definitive surgery should be avoided . Although this view has not yet been supported by any other study, we believe that the time between the suspected diagnosis of advanced ovarian cancer and surgery should be kept as short as possible. Delays may result in a higher preoperative tumor mass which has been identified as an adverse prognostic factor .
Tumor stage is one of the primary prognostic factors. Appropriate staging is vitally important for effective postoperative therapeutic decision-making. Patients who have been accurately staged as stage I may not require adjuvant chemotherapy [32, 33].
Surgical quality categories for staging of ovarian carcinomas (based on Trimbos et al. 2003)
Category of surgical quality
Staging procedures included
Inspection and palpation of all peritoneal surfaces; biopsies of any suspect lesion for metastasis; peritoneal washings; infra-colic omentectomy; blind biopsies of the right diaphragm and right and left para-colic gutter, pelvic side-walls of the ovarian fossa, of the bladder peritoneum and of the cul-de-sac and sampling of iliac and para-aortic lymph nodes
Everything between optimal and minimal staging
Inspection and palpation of all peritoneal surfaces and the retroperitoneal area; biopsies of any suspect lesions for metastasis; peritoneal washing; infracolic omentectomy
Less than minimal staging but at least careful inspection and palpation of all peritoneal surfaces and the retroperitoneal area; biopsies of any suspect lesion for metastasis
Extent of surgery
In addition to the staging procedures mentioned earlier, optimal surgical treatment for ovarian cancer comprises tumor removal; removal of remaining ovaries, uterus, and fallopian tubes, omentectomy, and radical para aortic and pelvic lymphadenctomy [3, 37]. The German national treatment guidelines recommend a simultaneous appendectomy and removal of the cul de sac over the peritoneum of the small pelvis . Since removal of all grossly visible tumor is considered crucial for long-term survival, surgery should be extended to include hemicolectomy, splenectomy and stripping of the peritoneal reflection of the diaphragm when the tumor masses infiltrate the entire abdominal cavity, the colon, the diaphragm or other structures respectively.
Although the reasoning behind performing these measures seems convincing, only lymphadenectomy has been partly evaluated in a prospective, randomized trial. The previously held belief that mere palpation of lymph nodes is sufficient to gauge nodal status was refuted in this study .
Lymphadenectomy plays a triple role in the treatment of ovarian cancer. First, it is of diagnostic value since tumors of apparently early stage show nodal involvement in about 20% to 40% of the cases , If found positive, the tumor must be classified as stage IIIc. Secondly, lymphadenectomy is of immense prognostic value. Most importantly, lymphadenectomy may also have a therapeutic effect as retrospective studies comparing lymphadenectomy with no lymphadenectomy reported a survival benefits with this procedure [41–43]. The data on lymphadenectomy is however conflicting with one study showing that the patients with stage III disease (tumor residuals >2 cm) that has been debulked suboptimally do not benefit from lymphadenectomy . Other workers report no benefit even if the residual tumor size is smaller (1 cm) . Though not fully published, the only prospective, randomized trial shows that systematic lymphadenectomy did not result in better survival compared to selective lymphadenectomy . Mainly based on the retrospective findings current views on treating stage III disease suggest: systematic lymphadenectomy in cases of residual tumors <1 cm, nodal debulking only where tumors are larger than intra-abdominal residuals, and nodal sampling in stage IV disease with pleural effusions only .
To the best of our knowledge, there has been no study testing the benefit of hysterectomy or omentectomy. However, the concurrent incidence of endometrial carcinoma in 10% to 25 % of patients, or its precursors in about 30% to 50% of all ovarian cancers justifies this procedure [48, 49].
Ovarian cancer is one of the tumors where surgical debulking is considered worthwhile. This is due to availability of further effective treatments that are available to control the unresectable residual disease. As early as 1934, Meigs suggested that maximum cytoreductive surgery was beneficial . Many years later, in 1968, Munnell followed this idea and proposed the idea of 'maximum surgical effort' . He distinguished between definitive surgery, partial removal of the tumor and biopsy only. Since partial removal covers a wide range of interventions that requires varying amount of efforts, optimal debulking was distinguished from suboptimal debulking. Although there is no generally accepted definition, most early studies considered a residual tumor size of <2 cm as optimal . In a more recent survey among gynecological oncologists from United States of America (USA), 12% of the responders defined optimal debulking surgery as no visible tumor residuals, while 14% described it as residual tumor masses less than 0.5 cm. However, 61% chose a 1 cm threshold and 13% considered a tumor of 1.5 cm to 2.0 cm as optimal . Comparative analysis of diameters of various residual diseases has shown that there exists some sort of a threshold at 2 cm, above which no significant differences in survival can be found. In contrast, subset analyses of smaller diameters in residual disease show improved patient prognosis . This variation in the interpretation of thresholds with prognostic impact calls for a commonly accepted definition (see concluding remarks) and more controlled trials, that need to be non-randomized as it will not be ethically possible to leave some tumor behind.
The results of an earlier meta analysis on cytoreductive surgery might have been flawed not only due to absence of clear definitions but also due to the combined effects of subsequent chemotherapy . In this study, the then novel, platinum-containing chemotherapy had a stronger impact on survival than cytoreductive surgery. A recent and otherwise comparable meta analysis however, confirms the greater survival benefit of patients undergoing maximum cytoreduction . Another interesting study stated that optimal cytoreduction means no visible residual tumor . It has been further shown that the volume of the residual tumor and the success of subsequent chemotherapy are interdependent .
Expertise of gynecological oncology surgeons
Based on available evidence it is generally accepted that the experience and technical expertise of a surgeon are important prognostic factors. Comparisons of overall survival in patients treated by gynecological oncology, gynecologists and general surgeons have shown that patients treated by surgeons trained in gynecology (gynecological oncology) have a significantly better prognosis [57, 58]. This finding may not reflect primarily on the technical skills of these surgeons but rather reflection the 'environment' in which they work – where views and thoughts on the biology of advanced tumors are freely shared and patients are often treated by a team rather then individuals. As for surgeons there are only select patients with uncommon neoplasms like gastrinomas, glucagonomas, stomatostatinomas, and VIPomas, who profit from debulking surgery with particular reference to prevent deleterious hormonal side-effects . It is expected that new chemotherapy and immunotherapeutical approaches will probably lead to a re-evaluation of debulking surgery as a complementary approach [60–62]. Till such time where definite evidence is available, it is strongly recommended that all patients should be treated by a gynec-oncologist. There had been constant calls to regionalize specialist surgery, however, no studies have yet shown better survival in patients treated by 'high volume' operators or such specialists [63, 64]. A recent study on quality control from Hesse, Germany, showed striking deficiencies even at central-referral hospitals . Treatment by a multidisciplinary team of specialists, has been shown to increase patients' chances of survival without any disputes [65, 66]. Patients probably benefit most from being treated in centers which promote excellent scientific exchange, and continuous education and self-evaluation among surgeons besides providing multidisciplinary approach to management.
Coping with inadequate primary surgery
Surgical treatment of advanced ovarian cancer is one of the most demanding procedures in gynecological surgery. Despite repeated requests to restrict surgery to experienced surgeons, considerable numbers of patients are still operated by others. A population based study from Germany showed that omentectomies were performed in about 50% of all cases of ovarian cancer and lymphadenectomy were carried out only in 30% . Another study from USA showed that only about half of the patients receive 'standard' care . In spite of the establishment of gynecological oncology as a specialty in the USA, fewer than half of the patients were originally seen by such a specialist . More over the terminologies like "standard" are not defined well.
The situation with regard to specialism depends strongly on the medical infrastructure, and varies from country to country and region to region. However, the problem of inadequate primary surgery is real, and coping with it is a frequent task in specialist centers even in developed countries. The question is what should be done for the patient concerned? Interestingly, this is something that cannot be found in textbooks [3, 69, 70]. Some of the literature suggest re-laparotomy by experienced surgeons to achieve reductions in all possible tumor mass [71, 72] however, there is no evidence to support this strategy.
In general, one of two situations occurs. First patients present with no evidence of macroscopic tumor residuals but staging procedures and/or operative measures were omitted. Computed tomography (CT) or Magnetic resonance imaging (MRI) to identify enlarged lymph nodes or possible residual tumors in these situations may help to decide on the need for second surgery. The belief that tumor cells in retroperitoneal lymph nodes are better able to survive chemotherapy is supported by low cytotoxic drug concentrations in these . Therefore, it is reasonable to consider enlarged lymph nodes as a decisive factor favoring a direct surgical approach. It is interesting to note that in endometrial carcinomas, a clinically negative omentum was also found to be histologically negative in most cases (sensitivity 89%) .
Patients with residual tumor mass have to be evaluated to determine if it is possible to achieve no residual tumor or microscopic residual tumor by immediate secondary surgery. Although immediate laparotomy seems to be a good idea, the limited capacity for surgery at specialist departments and delays in having the surgery are to be considered. The peritoneum shows inflammation shortly after surgery reaching a high about 7 to 14 days afterwards . Surgery at this time is considered far more complicated and may result in higher blood loss and greater risk of injury to neighboring abdominal organs . However, waiting for the inflammatory processes to resolve will give the tumor further time to proliferate . Therefore, interval debulking surgery after three courses of chemotherapy should be considered as an appropriate alternative.
Disease spread >2 cm to the spleen, diaphragm, liver surface, mesentery, or gallbladder is generally believed to be inoperable. However, even these patients may often undergo effective debulking procedures [26, 77]. As mentioned earlier, laparoscopy can be used to reach decisions on surgery. The only problem with laparoscopy in combination with neoadjuvant chemotherapy is a 30% rate of port site metastasis, which is believed to be a result of the pneumoperitoneum procedure created for laparoscopy . These metastases should be excised at the time of any subsequent surgery .
An analysis of several retrospective studies on neoadjuvant chemotherapy showed that there are no good reasons to assume that this approach is associated with a poorer prognosis . The European Organisation for Research and Treatment of Cancer (EORTC) protocol 55971 comparing upfront tumor debulking surgery with neoadjuvant chemotherapy in patients with stage IIIc or IV disease is accruing and its results will provide better insights on this issue.
Interval tumor debulking
Interval debulking, is another approach to reduce tumor burden between the cycles of chemotherapy. It has been evaluated in two prospective randomized trials [80, 81]. The EORTC study showed a clear survival advantage for interval debulking (still noted in the 2001 update), the Gynecologic Oncology Group (GOG-152) study has, as yet, failed to show any benefit from interval debulking [80, 81]. Patients with residual tumor >1 cm received three courses of cyclophosphamide/cisplatinum in the EORTC study  or three courses of paclitaxel/cisplatinum in the GOG-152 study. In both studies, patients who did not respond to chemotherapy were removed from the study. Those who responded were randomized to either secondary surgery or no surgery. Afterwards, all patients received three more courses of the earlier chemotherapeutic regimen.
Although there seem to be only minor differences in the design of both trials, a closer look shows that in the GOG-152 study, the number of stage IV patients was lower (6%) compared with the EORTC (21%) study, the performance status was better, and there was less residual tumor. This was due to the eligibility criteria for GOG 152 which stated that patients should have had surgery with maximal effort to resect the uterus, tubes, ovaries, omentum, and all gross residual ovarian cancer at the time of primary surgery.
The questions about the benefit of interval debulking surgery remain unresolved. However, it appears that patients who have had neoadjuvant chemotherapy or suboptimal debulking may profit from this treatment, while those who have undergone primary, maximum effort surgery by a gynecological oncologist are less likely to profit from it .
Surgical prognostic factors
Size of the residual tumor, volume of the residual disease and experience of the surgeon are important prognostic factors [56, 77]. Among these, only few can be influenced by human intervention. Except for dose intensity of chemotherapy, recent literature indicates that the hemoglobin concentrations before chemotherapy are of prognostic value [83, 84]. The latter may be influenced by the use of erythropoietin which has shown positive effects on survival in cervical cancer .
As mentioned above, the frequently used definition of <2 cm for optimal debulking is arbitrary since every further reduction in the size of residual tumor improves the prognosis . Thus, each threshold between 0 and 2 cm will have its own prognostic relevance. While the criterion 'diameter of residual tumor' reflects tumor cell hypoxia and reduces the pool of proliferating tumor cells susceptible to chemotherapy, the criterion 'residual tumor volume' alludes to the removal of therapy-resistant tumor cells, which are believed to be responsible for early recurrences. A comparison of both criteria in relation to their prognostic impact has shown that residual tumor volume is of greater importance . As shown in subgroup analyses of the intergroup trial confirming the results of the GOG-111 study, a possibly superior chemotherapeutic regimen containing taxanes cannot compensate for the tumor left behind after primary surgery .
It is difficult to assess the future role of surgery in advanced ovarian cancer. Neoadjuvant chemotherapy may become more important. However, as the tumor debulking surgery works, except in stage IV patients with solid distant metastasis, it may be worth trying combined ultrasound-guided laser interstitial thermotherapy for non-resectable liver metastasis with conventional debulking surgery . Apart from technical innovations, quality control, quality assurance and documentation of patient outcomes after surgery will probably play major parts in treatment improvements.
Numerous studies have analyzed the effects of various kind of chemotherapy in ovarian cancer. In contrast, only a few prospective randomized studies have focused on surgical issues in this type of tumor [46, 80, 81]. This lack of surgical trials has probably contributed to inhomogenous definitions regarding the terminology of surgical interventions and surgical stages (early compared with late) and the classification of operative success in general.
In future, we must aim to ensure that all patients are treated along the generally accepted guidelines and receive optimal debulking surgery which leaves only microscopically detectable residual tumor as shown in number of studies; it is certainly unethical at present to evaluate this procedure in randomized clinical trials (see Introduction). Other then this, there are many other relevant issues which need to be resolved or clarified with special reference to neoadjuvant chemotherapy, interval debulking, the surgeon's training, and inadequate primary treatment. It would certainly be very helpful to demonstrate clearly the consequences of what is supposed to be an inadequate treatment.
The simple dichotomization of FIGO stages to early or late does not correspond to any diagnostic, biological or therapeutic advantage. We believe that it is far more reasonable to consider stage I alone as early disease (perhaps even only stage Ia and b), stages II and III (perhaps even stage IV with pleural effusions) as intermediate disease, and stage IV with organ metastasis as advanced disease. Such a classification would follow current views on treatment, since early ovarian carcinomas are treated primarily by surgery (eventually fertility-sparing) and adjuvant chemotherapy in cases of increased risk, intermediate ones by surgery and routine chemotherapy, and advanced disease by chemotherapy only. Thus far, results of studies on stage IV patients with organ metastases are inconsistent regarding the benefit of surgery. This is another issue to be resolved . In this respect, FIGO may find subdividing stage IV into stage IVa (pleural effusions) and IVb (organ metastasis) worthwhile.
Disappointingly, the Tumor-Nodes-Metastasis (TNM) classification follows the FIGO system and violates its own principles by not accepting distant peritoneal metastasis as a natural indicator of primary tumor size but also by summarizing a nodal-positive disease stage as T3c (corresponding to FIGO IIIC) regardless of intra-abdominal findings. This inconsistency has already created curious confusions in current research. Nodal involvement has been shown to impair prognosis, however, smaller intra-abdominal tumors with nodal involvement (presented as stage I to IIIb disease but, by definition, all stage IIIC) show a significantly better prognosis than extensive intra-abdominal tumor masses (again stage IIIC) .
Surgical documentation of residual tumor after debulking of ovarian carcinomas
Residual tumor status*
Maximum diameter of residual tumor
Maximum total volume of residual tumor
No visible tumor
< 1 cm
≤ 10 cm3
1 – 2 cm
> 10 cm3 but ≤ 100 cm3
> 2 cm
> 100 cm3
In summary, more attention need be paid to surgery for advanced ovarian cancer. These include necessary improvements in treatment in the general population, uniform definitions and terminology, and increasing number of surgical clinical trials. Extrapolating from the results of truly optimal ovarian cancer surgery, we believe that improvements in surgery will lead to better patient survival than improvements in current chemotherapeutic approaches [55, 90, 91].
The author takes the opportunity to thank Professor Dr. Wolfgang Künzel, FRCOG, for his helpful comments on the manuscript.
- Benedet JL, Bender H, Jones H, Ngan HY, Pecorelli S: FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet. 2000, 70: 209-262. 10.1016/S0020-7292(00)90001-8.View ArticlePubMedGoogle Scholar
- Wittekind C, Meyer HJ, Bootz F: TNM-Klassifikation maligner Tumoren. Heidelberg, Springer. 2003Google Scholar
- Ozols RF, Rubin SC, Thomas G, Robboy S: Epithelial ovarian cancer. In: Principles and practice of gynecologic oncology. Edited by: Hoskins WJ, Perez CA, Young RC. 1997, Philadelphia: Lippincott-Raven Publishers, 919-986.Google Scholar
- Winter-Roach B, Hooper L, Kitchener H: Systematic review of adjuvant therapy for early stage (epithelial) ovarian cancer. Int J Gynecol Cancer. 2003, 13: 395-404. 10.1046/j.1525-1438.2003.13316.x.View ArticlePubMedGoogle Scholar
- Brinkhuis M, Meijer GA, Baak JPA: An evaluation of prognostic factors in advanced ovarian cancer. Eur J Obstet Gynecol Reprod Biol. 1995, 63: 115-124. 10.1016/0301-2115(95)02211-2.View ArticlePubMedGoogle Scholar
- Jacobs IJ, Skates SJ, MacDonald N, Menon U, Rosenthal AN, Davies AP, Woolas R, Jeyarajah AR, Sibley K, Lowe DG, Oram DH: Screening for ovarian cancer: a pilot randomised controlled trial. Lancet. 1999, 353: 1207-1210. 10.1016/S0140-6736(98)10261-1.View ArticlePubMedGoogle Scholar
- Bell R, Petticrew M, Sheldon T: The performance of screening tests for ovarian cancer: results of a systematic review. Br J Obstet Gynaecol. 1998, 105: 1136-1147.View ArticlePubMedGoogle Scholar
- Bourne TH, Campbell S, Reynolds KM, Whitehead MI, Hampson J, Royston P, Crayford TJ, Collins WP: Screening for early familial ovarian cancer with transvaginal ultrasonography and color blood flow imaging. BMJ. 1993, 306: 1025-1029.PubMed CentralView ArticlePubMedGoogle Scholar
- van Nagell JR, DePriest PD, Reedy MB, Gallion HH, Ueland FR, Pavlik EJ, Kryscio RJ: The efficacy of transvaginal sonographic screening in asymptomatic women at risk for ovarian cancer. Gynecol Oncol. 2000, 77: 350-356. 10.1006/gyno.2000.5816.View ArticlePubMedGoogle Scholar
- DePriest PD, Gallion HH, Pavlik EJ, Kryscio RJ, van Nagell JR: Transvaginal sonography as a screening method for the detection of early ovarian cancer. Gynecol Oncol. 1997, 65: 408-414. 10.1006/gyno.1997.4705.View ArticlePubMedGoogle Scholar
- Tailor A, Bourne TH, Campbell S, Okokon E, Dew T, Collins WP: Results from an ultrasound-based familial ovarian cancer screening clinic: a 10-year observational study. Ultrasound Obstet Gynecol. 2003, 21: 378-385. 10.1002/uog.65.View ArticlePubMedGoogle Scholar
- Petricoin EF, Ardekani AM, Hitt BA, Levine BA, Fusaro VA, Steinberg SM, Mills GB, Simone C, Fishman DA, Kohn EC, Liotta LA: Use of proteomic patterns in serum to identify ovarian cancer. Lancet. 2002, 359: 572-577. 10.1016/S0140-6736(02)07746-2.View ArticlePubMedGoogle Scholar
- Aure JC, Hoeg K, Kolstad P: Clinical and histologic studies of ovarian carcinoma. Long-term follow-up of 990 cases. Obstet Gynecol. 1971, 37: 1-9.PubMedGoogle Scholar
- Griffith CT, Fuller AF: Intensive surgical and chemotherapeutic management of advanced ovarian cancer. Surg Clin North Am. 1978, 58: 131-142.Google Scholar
- Michel G, De Iaco P, Castaigne D, el-Hassan MJ, Lobreglio R, Lhomme C, Rey A, Duvillard P: Extensive cytoreductive surgery in advanced ovarian carcinoma. Eur J Gynaecol Oncol. 1997, 18: 9-15.PubMedGoogle Scholar
- Griffiths CT: Surgery at the time of diagnosis of ovarian cancer. In: Management of ovarian cancer. Edited by: Blackledge G, Chan KK. 1986, London: Butterworth, 60-Google Scholar
- Goldie JH, Coldman AJ: A mathematical model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep. 1979, 63: 1727-1733.PubMedGoogle Scholar
- McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, Clarke-Pearson DL, Davidson M: Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996, 334: 1-6. 10.1056/NEJM199601043340101.View ArticlePubMedGoogle Scholar
- Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E, Stuart G, Kaye S, Vegote I, Blom R, Grimshaw R, Atkinson RJ, Swenerton KD, Tropé C, Nardi M, Kaern J, Tumolo S, Timmers P, Roy JA, Lhoas F, Lindwall B, Bacon M, Birt A, Anderson JE, Zee B, Paul J, Baron B, Pecorelli S: Randomized intergroup trial of ciplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst. 2000, 92: 699-708. 10.1093/jnci/92.9.699.View ArticlePubMedGoogle Scholar
- Kehoe ST, Luesley DM, Ward K, Chan KK: In vivo evidence of increased malignant cell proliferation following surgery in ovarian cancer. Int J Gynecol Cancer. 1995, 5: 121-127. 10.1046/j.1525-1438.1995.05020121.x.View ArticlePubMedGoogle Scholar
- Shaw M, Wolfe C, Raju KS, Papadopoulos A: National guidance on gynecological cancer management: an audit of gynecological cancer services and management in the South East of England. Eur J Gynaecol Oncol. 2003, 24: 246-250.PubMedGoogle Scholar
- Münstedt K, von Georgi R, Zygmunt M, Misselwitz B, Stillger B, Künzel W: Shortcomings and deficits in surgical treatment of gynecological cancers: a German problem only?. Gynecol Oncol. 2002, 86: 337-343. 10.1006/gyno.2002.6767.View ArticlePubMedGoogle Scholar
- Münstedt K, von Georgi R, Misselwitz B, Zygmunt M, Stillger R, Künzel W: Centralizing surgery for gynecologic oncology – a strategy assuring better quality treatment?. Gynecol Oncol. 2003, 89: 4-8. 10.1016/S0090-8258(03)00071-4.View ArticlePubMedGoogle Scholar
- Benson K, Hartz AJ: A comparison of observational studies and randomized, controlled trials. N Engl J Med. 2000, 342: 1878-86. 10.1056/NEJM200006223422506.View ArticlePubMedGoogle Scholar
- Concato J, Shah N, Horwitz RI: Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med. 2000, 342: 1887-1892. 10.1056/NEJM200006223422507.PubMed CentralView ArticlePubMedGoogle Scholar
- Vergote I: Controversies in surgery in ovarian cancer – what is its real role?. Eur J Cancer. 2003, 39 (Suppl 1): 115-125.View ArticleGoogle Scholar
- Arzouman DA, Caccavale RJ, Sisler GE, Lewis RJ: Endobag. Ann Thorac Surg. 1993, 55: 1266-1267.View ArticlePubMedGoogle Scholar
- Childers JM, Nasseri A, Survit EA: Laparoscopic management of suspicious adnexal masses. Am J Obstet Gynecol. 1996, 175: 1451-1459.View ArticlePubMedGoogle Scholar
- Abu-Rustum NR, Sonoda Y, Chi DS, Teoman H, Dizon DS, Venkatraman E, Barakat RR: The effects of CO2 pneumoperitoneum on the survival of women with persistent metastatic ovarian cancer. Gynecol Oncol. 2003, 90: 431-434. 10.1016/S0090-8258(03)00330-5.View ArticlePubMedGoogle Scholar
- Volz J, Koster S, Scaeff B: Laparoscopic management of gynaecologic malignancies, time to hesitate. Gynecol Endosc. 1997, 84: 358-361.Google Scholar
- Eisenkop SM, Spirtos , Friedman RL, Lin W-CM, Pisani AL, Perticucci S: Relative influences of tumor volume before surgery and the cytoreductive outcome on survival for patients with advanced ovarian cancer: a prospective study. Gynecol Oncol. 2003, 90: 390-396. 10.1016/S0090-8258(03)00278-6.View ArticlePubMedGoogle Scholar
- Zanetta G, Rota S, Chiari S, Bonazzi C, Bratina G, Torri V, Mangioni C: The accuracy of staging: an important prognostic determinator in stage I ovarian carcinoma. A multivariate analysis. Ann Oncol. 1998, 9: 1097-1101. 10.1023/A:1008424527668.View ArticlePubMedGoogle Scholar
- Trimbos JB, Vergote I, Bolis G, Vermorken JB, Mangioni C, Madronal C, Franchi M, Tateo S, Zanetta G, Scarfone G, Giurgea L, Timmers P, Coens C, Pecorelli S: Impact of adjuvant chemotherapy and surgical staging in early-stage ovarian carcinoma: European Organisation for Research and Treatment of Cancer – Adjuvant Chemotherapy in Ovarian Neoplasm Trial. J Natl Cancer Inst. 2003, 95: 113-125. 10.1093/jnci/95.2.113.View ArticlePubMedGoogle Scholar
- Simojoki M, Santala M, Vuopala S, Kauppila A: The prognostic value of peritoneal cytology in ovarian cancer. Eur J Gynaecol Oncol. 1999, 20: 357-360.PubMedGoogle Scholar
- Young RC, Decker DG, Wharton JT, Piver MS, Sindelair WF, Edwards BK, Smith JP: Staging laparotomy in early ovarian cancer. JAMA. 1983, 250: 3072-3061. 10.1001/jama.250.22.3072.View ArticlePubMedGoogle Scholar
- Soper JT, Johnson P, Johnson V, Berchuck A, Clarke-Pearson DL: Comprehensive restaging laparotomy in women with apparent early ovarian carcinoma. Obstet Gynecol. 1992, 80: 949-953.PubMedGoogle Scholar
- Moore DH: Primary surgical management of early epithelial ovarian carcinoma. In: Rubin SC, Sutton GP. Ovarian cancer. Edited by: Rubin SC, Sutton GP. 2001, Philadelphia: Lippincott Williams & Wilkins, 201-218.Google Scholar
- Arbeitsgemeinschaft für Gynäkologische Onkologie: Leitlinien Maligne Ovarialtumoren. Frauenarzt. 2000, 41: 909-915.Google Scholar
- Eisenkop SM, Spirtos NM: The clinical significance of occult macroscopically positive retroperitoneal nodes in patients with epithelial ovarian cancer. Gynecol Oncol. 2001, 82: 143-149. 10.1006/gyno.2001.6232.View ArticlePubMedGoogle Scholar
- Morice P, Joulie F, Camatte S, Atallah D, Rouzier R, Pautier P, Pomel C, Lhomme C, Duvillard P, Castaigne D: Lymph node involvement in epithelial ovarian cancer: analysis of 276 pelvic and paraaortic lymphadenectomies and surgical implications. J Am Coll Surg. 2003, 197: 198-205. 10.1016/S1072-7515(03)00234-5.View ArticlePubMedGoogle Scholar
- Allen DG, Coulter J: Survival of patients with epithelial ovarian cancer and the effect of lymphadenectomy in those with stage 3 disease. Aust N Z J Obstet Gynaecol. 1999, 39: 420-424.View ArticlePubMedGoogle Scholar
- Kikkawa F, Ishikawa H, Tamakoshi K, Suganuma N, Mizuno K, Kawai M, Arii Y, Tamakoshi A, Kuzuya K, Tomoda Y: Prognostic evaluation of lymphadenectomy for epithelial ovarian cancer. J Surg Oncol. 1995, 60: 227-231.View ArticlePubMedGoogle Scholar
- Yokoyama Y, Sakamoto T, Sato S, Saizo Y: Evaluation of cytoreductive surgery with pelvic and paraaortic lymphadenectomy and intermittent cisplatin-based combination chemotherapy for improvement of long-term survival in ovarian cancer. Eur J Gynaecol Oncol. 1999, 20: 361-366.PubMedGoogle Scholar
- Saygili U, Guclu S, Uslu T, Erten O, Ture S, Demir N: Does systematic lymphadenectomy have a benefit on survival of suboptimally debulked patients with stage III ovarian carcinoma? A DEGOG* Study. J Surg Oncol. 2002, 81: 132-137. 10.1002/jso.10124.View ArticlePubMedGoogle Scholar
- Parazzini F, Valsecchi G, Bolis G, Guarnerio P, Reina S, Polverino G, Silvestri D: Pelvic and paraortic lymph node status in advanced ovarian cancer and survival. Gyncol Oncol. 1999, 74: 7-11. 10.1006/gyno.1999.5397.View ArticleGoogle Scholar
- Favalli G, Odicino F, Torri V, Pecorelli S: Early stage ovarian cancer: the Italian contribution to clinical research. An update. Int J Gynecol Cancer. 2001, 11 (Suppl 1): 12-19. 10.1046/j.1525-1438.2001.11(suppl.1)sup1012.x.View ArticlePubMedGoogle Scholar
- di Re F, Baiocchi G, Fontanelli R, Grosso G, Cobellis L, Raspagliesi F, di Re E: Systematic and paraaortic lymphadenectomy for advanced ovarian cancer: prognostic significance of node metastasis. Gynecol Oncol. 1996, 62: 360-365. 10.1006/gyno.1996.0249.View ArticlePubMedGoogle Scholar
- Wheeler JE: Pathology of malignant ovarian epithelial tumors and miscellaneous and rare ovarian and paraovarian neoplasms. In: Ovarian cancer. Edited by: Rubin SC, Sutton GP. 2001, Philadelphia: Lippincott Williams & Wilkins, 99-134.Google Scholar
- Breitenecker G, Bartl W, Schreiber V: Die prognostische Bedeutung morphologischer Parameter bei malignen Ovarialtumoren. Pathologe. 1983, 4: 29-40.PubMedGoogle Scholar
- Meigs JV: Tumors of the female pelvic organs. New York, McMillan. 1934Google Scholar
- Munnell E: The changing prognosis and treatment in cancer of the ovary. A report of 235 patients with primary ovarian carcinoma 1952–1961. Am J Obstet Gynecol. 1968, 100: 790-805.PubMedGoogle Scholar
- Hunter RW, Alexander ND, Soutter WP: Meta-analysis of surgery in advanced ovarian carcinoma: is maximum cytoreductive surgery an independent determinant of prognosis?. Am J Obstet Gynecol. 1992, 166: 504-511.View ArticlePubMedGoogle Scholar
- Eisenkop SM, Spirtos NM: What are the current surgical objectives, strategies, and technical capabilities of gynecologic oncologists treating advanced epithelial ovarian cancer?. Gynecol Oncol. 2001, 82: 489-497. 10.1006/gyno.2001.6312.View ArticlePubMedGoogle Scholar
- Hoskins WJ, McGuire WP, Brady MF, Homesley HD, Creasman WT, Berman M, Ball H, Berek JS: The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial epithelial ovarian carcinoma: a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1994, 170: 974-980.View ArticlePubMedGoogle Scholar
- Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ: Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol. 2002, 20: 1248-1259. 10.1200/JCO.20.5.1248.View ArticlePubMedGoogle Scholar
- von Georgi R, Franke FE, Münstedt K: The influence of tumorbiology, surgery, and postoperative therapy on patient prognosis in advanced ovarian carcinomas. Eur J Obstet Gynecol Reprod Biol. 2003, 111: 189-196. 10.1016/S0301-2115(03)00239-2.View ArticlePubMedGoogle Scholar
- Kehoe S, Powell J, Wilson S, Woodman C: The influence of the operating surgeons's specialisation on patient survival in ovarian carcinoma. Br J Cancer. 1994, 70: 1014-1017.PubMed CentralView ArticlePubMedGoogle Scholar
- Nguyen HN, Averette HE, Hoskins W, Penalver M, Sevin BU, Steren A: National survey of ovarian carcinoma. Part V. The impact of physician's specialty on patients' survival. Cancer. 1993, 72: 3663-3670.View ArticlePubMedGoogle Scholar
- Zollinger RM, Ellison EC, Fabri PJ Johnson J, Sparks J, Carey LC: Primary peptide ulceration of the jejunum associated with islet cell tumors. Twenty-five year appraisal. Ann Surg. 1980, 120: 422-430.View ArticleGoogle Scholar
- Merlo A, Müller-Brand J, Mäcke HR: Comparing monoclonal antibodies and small peptidic hormones for local targeting of malignant gliomas. Acta Neurochir Suppl. 2003, 88: 83-91.PubMedGoogle Scholar
- Sarmiento JM, Heywood G, Rubin J, Ilstrup DM, Nagorney DM, Que FG: Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg. 2003, 197: 29-37. 10.1016/S1072-7515(03)00230-8.View ArticlePubMedGoogle Scholar
- Kondo K, Monden Y: Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg. 2003, 76: 878-884. 10.1016/S0003-4975(03)00555-1.View ArticlePubMedGoogle Scholar
- Woodman C, Baghdady A, Collins S, Clyma JA: What changes in the organization of cancer services will improve the outcome for women with ovarian cancer?. Br J Obstet Gynaecol. 1997, 104: 135-139.View ArticlePubMedGoogle Scholar
- Grilli R, Minozzi S, Tinazzi A, Labianca R, Sheldon TA, Liberati A: Do specialists do it better? The impact of specialization on the processes and outcomes of care for cancer patients. Ann Oncol. 1998, 9: 365-374. 10.1023/A:1008201331167.View ArticlePubMedGoogle Scholar
- Junor EJ, Hole DJ, Gillis CR: Management of ovarian cancer: referral to a multidisciplinary team matters. Br J Cancer. 1994, 70: 363-370.PubMed CentralView ArticlePubMedGoogle Scholar
- Junor EJ, Hole DJ, McNulty L, Mason M, Young J: Specialist gynaecologists and survival outcome in ovarian cancer: a Scottish national study of 1866 patients. Br J Obstet Gynaecol. 1999, 106: 1130-1136.View ArticlePubMedGoogle Scholar
- Harlan LC, Clegg LX, Trimble EL: Trends in surgery and chemotherapy for women diagnosed with ovarian cancer in the United States. J Clin Oncol. 2003, 21: 3488-3494. 10.1200/JCO.2003.01.061.View ArticlePubMedGoogle Scholar
- Carney ME, Lancaster JM, Ford C, Tsodikov A, Wiggins CL: A population-based study of patterns of care for ovarian cancer: who is seen by a gynecologic oncologist and who is not?. Gynecol Oncol. 2002, 84: 36-42. 10.1006/gyno.2001.6460.View ArticlePubMedGoogle Scholar
- Gershenson DM, McGuire WP: Ovarian cancer: controversies in management. New York: Churchill Livingstone. 1998Google Scholar
- Rubin SC, Sutton GP: Ovarian cancer. Philadelphia: Lippincott Williams & Wilkins. 2001Google Scholar
- Hirsch HA, Käser O, Iklé FA: Atlas der gynäkologischen Operationen. Stuttgart, New York: Thieme. 1999, 349-351.Google Scholar
- Kuhn W, Hamann U, Kimmig R, Rehbock J, Schmalfeldt B, Schwoerer M: Operative Therapie. In: Tumorzentrum München (Kuhn W). Maligne Ovarialtumoren – Empfehlungen zur Diagnostik, Therapie und Nachsorge. München, Bern, Wien, New York: Zuckschwerdt. 2001, 4-31.Google Scholar
- Tokuhashi Y, Kikkawa F, Ishikawa H, Tamakoshi K, Hattori S, Matsuzawa K, Inoue T, Suganuma N, Tomoda Y: Distribution of platinum in human gynecologic tissues and pelvic lymph nodes after administration of cisplatin. Gynecol Obstet Invest. 1997, 44: 270-274.View ArticlePubMedGoogle Scholar
- Gehrig PA, Van Le L, Fowler WC: The role of omentectomy during the surgical staging of uterine serous carcinoma. Int J Gynecol Cancer. 2003, 13: 212-215. 10.1111/j.1525-1438.2003.13355.x.View ArticlePubMedGoogle Scholar
- Sendt W, Amberg R, Schoffel U, Hassan A, von Specht BU, Farthmann EH: Local inflammatory peritoneal response to operative trauma: studies on cell activity, cytokine expression, and adhesion molecules. Eur J Surg. 1999, 165: 1024-1030. 10.1080/110241599750007838.View ArticlePubMedGoogle Scholar
- Salzer H, Denison U, Breitenecker G, Lax G, Kapp K: Ovarialkarzinom. [accessed October 11th, 2003], http://www.aco.at/manual/ovar/kap_12.html
- Eisenkop SM, Friedman RL, Wang HJ: Complete cytoreductive surgery is feasable and maximizes survival in patients with advanced ovarian cancer: a prospective study. Gynecol Oncol. 1998, 69: 103-108. 10.1006/gyno.1998.4955.View ArticlePubMedGoogle Scholar
- Cavina E, Goletti O, Molea N, Buccianti P, Chiarugi M, Boni G, Lazzeri E, Bianchi R: Trocar site tumor recurrences. May pneumoperitoneum be responsible?. Surg Endosc. 1998, 12: 1294-1299. 10.1007/s004649900843.View ArticlePubMedGoogle Scholar
- Gryspeerdt S, Clabout L, Van Hoe L, Berteloot P, Vergote IB: Intraperitoneal contrast material combined with CT for detection of peritoneal metastases in ovarian cancer. Eur J Gynaecol Oncol. 1998, 19: 434-437.PubMedGoogle Scholar
- van der Burg ME, van Lent M, Buyse M, Kobierska A, Colombo N, Favalli G, Lacave AJ, Nardi M, Renard J, Pecorelli S: The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. N Engl J Med. 1995, 332: 629-634. 10.1056/NEJM199503093321002.View ArticlePubMedGoogle Scholar
- Rose PG, Nerenstone S, Brady M, Clarke-Pearson D, Olt G, Rubin SC, Moore DH: A phase III randomized study of interval secondary cytoreduction in patients with advanced stage ovarian carcinoma with suboptimal residual disease: a Gynecologic Oncology Group study. Proc Am Soc Clin Oncol. 2002, 21: 201a-[Abstract 802]Google Scholar
- van der Burg MEL, Vergote I: The role of interval debulking surgery in ovarian cancer. Curr Oncol Rep. 2003, 5: 473-481.View ArticlePubMedGoogle Scholar
- Münstedt K, Hering Kv, Prittwitz J, Zygmunt M, Franke FE, Vahrson H: Verletzungen des therapieplans und des chemotherapieprotokolls beim ovarialkarzinom – Gründe und Konsequenzen. Zentralbl Gynäkol. 1998, 120: 534-539.PubMedGoogle Scholar
- Münstedt K, Kovacic M, Zygmunt M, von Georgi R: Impact of hemoglobin levels before and during chemotherapy on survival of patients with ovarian cancer. Int J Oncol. 2003, 23: 837-843.PubMedGoogle Scholar
- Gaducci A, Cosio S, Fanucchi A, Manganelli L, Conte PF, Cristofani R, Genazzani AR: Is pretreatment hemoglobin level a predictor of complete response to salvage chemotherapy for recurrent platinum-pretreated ovarian carcinoma?. Eur J Gynaecol Oncol. 2003, 24: 405-410.Google Scholar
- Blohmer U, Wurschmidt F, Petry U, Weise G, Sehouli J, Kimmig R, Dressler , Kentenich , Kohls A, Lichtenegger W, for the NOGGO-AGO-Intergroup: 6th interim analysis of a prospective, randomized, open and controlled AGO- and NOGGO-intergroup study: Sequential adjuvant chemo-radiotherapy with vs without epoetin alfa for patients with high-risk cervical cancer. Proc Am Soc Clin Oncol. 2003, 22: 447-[Abstract 1798]Google Scholar
- Wietzke-Braun P, Ritzel U, Nolte W, Leonhardt U, Armbrust T, Koc M, Funke M, Grabbe E, Ramadori G: Ultrasound-guided laser interstitial thermo therapy for treatment of non-resectable primary and secondary liver tumours – a feasibility study. Ultrasound Med. 2003, 24: 107-112. 10.1055/s-2003-38664.Google Scholar
- Berek JS, Bertelsen K, du Bois A, Leonhardt U, Armbrust T, Koc M, Funke M, Grabbe F, Ramadori G: Advanced epithelial ovarian cancer: 1998 consensus statements. Ann Oncol. 1999, 10 (Suppl 1): 87-92. 10.1023/A:1008323922057.View ArticlePubMedGoogle Scholar
- Konazawa K, Suzuki T, Tokashiki M: The validity and significance of substage IIIC by node involvement in epithelial ovarian cancer: impact of nodal metastasis on patient survival. Gynecol Oncol. 1999, 73: 237-241. 10.1006/gyno.1999.5349.View ArticleGoogle Scholar
- Lück HJ, du Bois A, Weber B, Pfisterer J, Goupil A, Kuhn W, Barats JC, Blohmer J, Mousseau M, Schröder W, Meier W, Möbus V, Richter B, for the AGO-GINECO Intergroup: The integration of anthracyclines in the treatment of advanced ovarian cancer. Int J Gynecol Cancer. 2001, 11 (Suppl 1): 34-38.View ArticlePubMedGoogle Scholar
- Pfisterer J, Lortholary A, Kimmig R, Weber B, Du Bois A, Bourgeois H, Wagner U, Coudert B, Meier W, Costa S, for the AGO and GINECO Study Groups: Paclitaxel/carboplatin (TC) vs. paclitaxel/carboplatin followed by topotecan (TC-TOP) in first-line treatment of ovarian cancer FIGO stages IIB – IV. Interim results of a Gynecologic Cancer Intergroup phase III trial of the AGO Ovarian Cancer Study Group and GINECO. Proc Am Soc Clin Oncol. 2003, 22: 446-[Abstract 1793]View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.