Complete Surgical Cytoreduction Research Articles

Die intraoperative hypertherme intraperitoneale Chemotherapie als Therapieoption beim Ovarialkarzinom - Entwicklungen der letzten Jahre

Der peritoneale Befall ist eine der größten therapeutischen Herausforderungen beim Ovarialkarzinom. Die komplette chirurgische Resektion der Tumorreste spielt dabei eine entscheidende Rolle für die Prognose der Patientinnen. Der chirurgische Teil des Konzeptes beinhaltet die parietale und viszerale Peritonektomie, oft in Form einer multiviszeralen Resektion. Die Kombination der Chirurgie mit der hyperthermen intraperitonealen Chemotherapie (HIPEC) hat bei gastrointestinalen Malignomen mit Peritonealkarzinose für ausgewählte Patienten die Prognose erheblich verbessert. Analog dazu wurden beim Ovarialkarzinom mit Peritonealkarzinose Daten von über 300 Patientinnen, die multimodal behandelt wurden, über die letzten vier Jahre publiziert. Die Kollektive sind relativ klein und inhomogen, die Patientinnen zum Teil unterschiedlich behandelt worden. Es konnte jedoch die technische Durchführbarkeit mit einer niedrigen Letalität und vertretbaren Morbidität in Zentren nachgewiesen werden. Die intraoperative HIPEC ergänzt das therapeutische Konzept für ausgewählte Patientinnen, jedoch ersetzt sie nicht die adjuvante systemische Chemotherapie. Prospektiv randomisierte Phase-III-Studien sollen klären, welchen Stellenwert die HIPEC in dem vorgestellten Konzept einnimmt. Ein gemeinsames Studienprotokoll der Deutschen Gesellschaft für Viszeralchirurgie/Arbeitsgruppe Chirurgische Onkologie zusammen mit der Arbeitsgruppe Gynäkologische Onkologie/Ovar wäre daher hilfreich.

Surgical Management of Mesenteric Lymph Node Metastasis in Patients Undergoing Rectosigmoid Colectomy for Locally Advanced Ovarian Carcinoma

We sought to determine the incidence of mesenteric lymph node metastases in patients undergoing rectosigmoid resection for epithelial ovarian carcinoma and to evaluate the potential contribution of sigmoid mesocolectomy toward achieving complete surgical cytoreduction. Pathology results for patients undergoing rectosigmoid colectomy for epithelial ovarian carcinoma from August 1998 through September 2005 were retrospectively reviewed. Fifty-three patients with pathological documentation of mesenteric lymph nodes were selected for further review. A focused analysis was performed on cases with an adequate surgical sampling of mesenteric lymph nodes (more than one positive or five total mesenteric lymph nodes) to determine the overall incidence of nodal metastases. Chi2 analysis was used to identify clinicopathologic factors associated with mesenteric lymphatic spread. A total of 39 (73.6%) of 53 patients had an adequate mesenteric resection suitable for nodal analysis. In this subgroup, 32 (82.1%) of 39 patients had one or more mesenteric lymph nodes containing metastatic ovarian carcinoma. Invasion beyond the serosa of the rectosigmoid colon was present in 31 (79.5%) of 39 of cases; however, increasing depth of invasion was not associated with risk of mesenteric nodal disease. In addition to bowel wall involvement, the only clinical factor that correlated with mesenteric lymph node involvement was concurrent tumor spread to retroperitoneal lymph nodes (P = .025). Locally advanced ovarian carcinoma involving the rectosigmoid colon is associated with a high incidence of mesenteric nodal metastasis. Standard surgical technique should include a sigmoid mesocolectomy with resection of the associated lymphatic tributaries at the time of rectosigmoid colectomy if the surgical objective is complete cytoreduction of occult nodal disease.

Secondary cytoreductive surgery for localized, recurrent epithelial ovarian cancer

The objective of this study was to evaluate the role of secondary cytoreductive surgery in the outcome of patients who had recurrent epithelial ovarian carcinoma that was limited to <or=5 recurrence sites within the abdomen or pelvis on preoperative imaging studies and attempt to define selection criteria associated with improved survival, with specific attention to the number of lesions suspicious for recurrent disease. : Patients who underwent secondary surgical cytoreduction for recurrent epithelial ovarian cancer between September 1997 and March 2005 were identified retrospectively from tumor registry databases. Study inclusion criteria required a complete clinical response to primary therapy, >or=12 months between initial diagnosis and recurrence, and <or=5 recurrence sites on preoperative imaging studies. Univariate and multivariate logistic regression analyses were used to evaluate the effect of clinicopathologic variables on overall postrecurrence survival. Fifty-five patients met the study inclusion criteria. The median patient age at recurrence was 57.7 years, and the median diagnosis-to-recurrence interval was 32 months (range, 12-164 months). Complete cytoreduction was achieved in 41 patients (74.5%). On multivariate analysis, the statistically significant and independent predictors of overall survival were a diagnosis-to-recurrence interval >or=18 months (median survival, 49 months vs 3 months; P < .01), the number of radiographic recurrence sites (median survival, 50 months for patients with 1 or 2 sites vs 12 months for patients with 3 to 5 sites; P < .03), and residual disease (median survival, 50 months for patients with no macroscopic residual disease vs 7.2 months for patients with macroscopic residual disease; P < .01). Age, tumor grade, histology, CA-125 level, ascites, and tumor size were not associated significantly with survival. : The current data supported the definition of localized recurrent ovarian cancer as patients with 1 or 2 radiographic recurrence sites. In this select population, a diagnosis-to-recurrence interval >or=18 months and complete secondary surgical cytoreduction, which was achievable in the majority of patients, were associated with a median postrecurrence survival of approximately 50 months.

Cytoreductive Surgery Combined with Intraperitoneal Chemohyperthermia for the Treatment of Advanced Colon Cancer

Chemohyperthermic peritoneal perfusion (CHPP) after extensive cytoreductive surgery is a possible choice as a regional treatment for peritoneal carcinomatosis (PC). The multicentric France EVOCAPE 1 study demonstrated that the median overall survival of patients with colon peritoneal carcinomatosis subjected to conventional surgical and/or chemotherapeutic treatment was 5.2 months. Historically, mitomycin C is the drug of choice in the treatment of intraperitoneal carcinomatosis from colon cancer. Twenty-five patients affected by stage IV colon cancer with only peritoneal involvement and a prior completion of at least a partial first cycle of systemic chemotherapeutic and/or surgical treatment (24 patients) were enrolled. Immediately following extensive cytoreductive surgery, early postoperative closed abdomen CHPP was performed. Complete surgical cytoreduction (CC0-CC1) was obtained in 22 patients. Postoperative mortality was 1 out of 25 (4%). Major postoperative morbidity was 6 out of 25 (24%). Median overall survival estimated by Kaplan-Meier curve was 30.3 months. Locoregional progression-free survival was 17.3 months. Of all the patients 64% and 40% were alive after 1 and 2 years respectively. In referral centers CHPP after optimal surgical debulking is a safe procedure for peritoneal carcinomatosis from colonic cancer. Locoregional control was obtained in the majority of the pretreated patients and 1-year survival was statistically improved. A closed abdomen CHPP procedure lasting 1 hour and standard mitomycin C at a dosage of 15 mg/m(2) is probably as efficacious as other hyperthermic procedures, using higher mitomycin C dosages, with a comparable or lower number of cases of side effects. These results, as in other published phase II studies, justify future randomized trials to assess definitively the role of CHPP in the treatment of locally advanced colon neoplasms in western countries.

Secondary cytoreductive surgery for localized recurrent epithelial ovarian cancer: Analysis of prognostic factors and survival outcome

5029 Background: To evaluate prognostic factors and survival outcome of patients undergoing secondary cytoreductive surgery for recurrent epithelial ovarian cancer with ≤ 5 sites of recurrence on pre-operative imaging studies. Methods: Patients undergoing secondary cytoreduction for recurrent epithelial ovarian carcinoma between 9/1997–3/2005 were retrospectively identified from tumor registry databases. Inclusion required: complete clinical response to primary therapy, ≥12 months between initial diagnosis and recurrence, and ≤5 recurrence sites on pre-operative imaging studies. Univariate and multivariate logistic regression analyses were used to evaluate the effect of clinico-pathologic variables on overall post-recurrence survival. Results: Fifty-five patients met study inclusion criteria. The median age at recurrence was 57.7 years and the median diagnosis-to-recurrence interval was 32 months (range 12 to 164 months). Complete cytoreduction was achieved in 41 patients (74.5%). On multivariate analysis, the statistically significant and independent predictors of overall survival were diagnosis-to-recurrence interval ≥18 months (median survival=49 months vs 3 months, p = 0.001), the number of radiographic recurrence sites (median survival: 1–2 sites=50.0 months vs 3–5 sites=12.0 months, p &lt; 0.03) and residual disease (median survival: no gross residual=50 months vs macroscopic residual=7.2 months, p &lt; 0.01). Age, tumor grade, histology, CA-125 level, ascites, and tumor size were not significantly associated with survival. Conclusions: These data support the definition of localized recurrent ovarian cancer as patients with 1–2 radiographic recurrence sites. In this select population, a diagnosis-recurrence interval ≥18 months and complete secondary surgical cytoreduction, which was achievable in the majority of cases, were associated with a median post-recurrence survival time of approximately 50 months. No significant financial relationships to disclose.

The role of secondary cytoreductive surgery for recurrent ovarian cancer

Objective The aim of this study was to assess the survival benefit of salvage surgical cytoreduction in patients with recurrent ovarian cancer and compare the surgical outcome with salvage chemotherapy alone. Methods Seventy-five patients with recurrent ovarian cancer were reviewed for possible benefits of salvage therapy. Forty-four had salvage surgery and 31 patients had salvage chemotherapy alone for the treatment of gross recurrent disease. All patients had been clinically free of disease more than 6 months from the completion of primary treatment. Results A macroscopically complete surgical cytoreduction was obtained in 34 (77%) patients. Survival was significantly longer in patients who had salvage surgery compared to those who had salvage chemotherapy alone ( P = 0.03). Moreover, survival was significantly longer in patients who were completely cytoreduced compared to those who were not completely cytoreduced and those who were not operated ( P = 0.007 and P = 0.005, respectively). Conclusions Macroscopically complete surgical cytoreduction significantly improves further survival of recurrent ovarian cancer patients. However, we remain in need to evaluate the debulkability of tumor before surgery to maximize the survival benefit and minimize the number of ineffective surgeries.

Relevance of chemotherapy dose and schedule to outcomes in ovarian cancer

The current standard of care in ovarian cancer is complete surgical cytoreduction followed by adjuvant (postoperative) platinum-based chemotherapy. Taxanes are frequently combined with platinum compounds in the adjuvant chemotherapy setting and, whether they are given in combination or sequentially, they produce greater progression-free and overall survival than historical combination regimens. Because the treatment of ovarian cancer relies on chemotherapy, this article reviews the evidence for a correlation between chemotherapy delivered at full dose on schedule (FDOS) and patient outcomes. Meta-analyses have suggested that the dose intensities of cisplatin and carboplatin correlate with survival. However, the findings in these hypothesis-generating analyses have not been confirmed in prospective trials. In addition, increasing the dose of cisplatin above a certain threshold is not recommended in ovarian cancer because of the greater toxicity with higher doses of platinum compounds. The delivered dose intensities of taxanes used as single agents have not been shown to correlate with patient outcomes, but adding a taxane to platinum compounds appears both to attenuate the toxicity of the platinum compounds and to facilitate the delivery of FDOS chemotherapy. In the literature on ovarian cancer there is no clear consensus on the benefit of maintaining FDOS chemotherapy. Clinical studies, especially a proposed trial of a dose-dense carboplatin and paclitaxel combination, may provide stronger evidence for the effect of FDOS chemotherapy in ovarian cancer.

Cytoreductive Surgery and Intraperitoneal Chemohyperthermia for Recurrent Peritoneal Carcinomatosis from Ovarian Cancer

Aggressive surgical cytoreduction has been shown to have a positive impact on survival of patients with ovarian cancer. After first-line chemotherapy, 47% of patients relapse within 5 years, and median survival after second line chemotherapy is 10-15 months. Adding intraperitoneal chemohyperthermia (IPCH) to surgical cytoreduction could further control ceolomic spread of disease. The aim of this study was to determine morbidity and mortality, regional relapse-free survival and, preliminarily, overall survival after combining cytoreductive surgery with IPCH for the treatment of peritoneal carcinomatosis from ovarian epithelial cancer relapsed after prior chemotherapy. Thirty women affected with such a relapse were included. Patients underwent extensive cytoreductive surgery including tumor resections and peritonectomy, followed by intraoperative IPCH with cisplatin. Complete surgical cytoreduction down to nodules less than 2.5 mm (CC0-CC1) was obtained in 23 patients (77%). One patient died postoperatively from a pulmonary embolism. Major postoperative morbidity was 5/30 (16.7%). We registered one case of anastomotic leakage, a spontaneous ileum perforation, a postoperative cholecystitis, a hydrothorax, and one patient with bone marrow toxicity. Kaplan-Meier estimates of median locoregional relapse-free survival and median overall survival were 17.1 months and 28.1 months, respectively. Patients with CC0-CC1 had locoregional relapse-free and overall survival rates of 24.4 and 37.8 months, whereas the remainder had survival rates of 4.1 and 11.0 months. We concluded that cytoreductive surgery combined with IPCH is feasible with acceptable morbidity and mortality and seems to promise good results in selected patients affected with peritoneal carcinomatosis from ovarian cancer.

The influence of splenic metastases on survival in FIGO stage IIIC epithelial ovarian cancer.

The purposes of this study were to compare the survival of ovarian cancer patients with splenic metastasis to patients without it and to evaluate the complications of the procedure. A retrospective study was performed on 34 patients with ovarian cancer who underwent splenectomy for initial cytoreduction at gynecologic oncology unit of Hacettepe University Hospitals between 1989 and 2001. All patients had FIGO stage IIIC disease and were left with <1 cm residual tumor after surgery. Eighteen patients (52.9%) had splenic metastasis. Patients with splenic metastasis tended poorer survival. Median survivals were 28.9 and 41.3 months for patients with splenic disease and for patients without it, respectively (P > 0.05). Univariate analysis revealed that performance status and histologic type influenced survival. Histologic type and performance status were identified as independent risk factors by multivariate analysis. Postoperative complications were developed in ten (29.4%) patients and three of these (8.8%) died in 1 month after operation. None of the complications was attributed directly to the splenectomy procedure. Complete surgical cytoreduction confers a survival benefit whether the parenchyma was involved or not. The splenectomy should be considered with its acceptable morbidity in selected patients who have a chance to achieve optimal debulking.

Clinically occult recurrent ovarian cancer: patient selection for secondary cytoreductive surgery using combined PET/CT

Objective The aim of this study was to evaluate the utility of combined positron emission tomography/computed tomography (PET/CT) for identifying ovarian cancer tumor masses ≥1 cm in patients with clinically occult recurrent disease by conventional CT imaging. Methods Twenty-two patients with epithelial ovarian cancer, rising serum CA125 levels, and negative or equivocal conventional CT imaging ≥6 months after primary therapy underwent combined PET/CT imaging followed by surgical reassessment. Fisher's exact test was used to measure the ability of PET/CT to predict macroscopic disease ≥1 cm. Results The median patient age was 55 years, and 91% of patients had FIGO Stage IIIC/IV disease. The median increase in serum CA125 was 24 U/ml (range 10 to 330 U/ml). Conventional CT was reported as negative ( n = 15) or equivocal ( n = 7) in all cases. Eighteen patients were ultimately found to harbor recurrent ovarian cancer measuring ≥1 cm at the time of surgery, with a median maximal tumor diameter of 2.3 cm (range 1.5 to 3.2 cm). The overall patient-based accuracy of PET/CT in detecting recurrent disease ≥1 cm was 81.8%, with a sensitivity of 83.3% and positive predictive value of 93.8% ( P = 0.046). Of patients with recurrent ovarian cancer ≥1 cm, complete cytoreduction to no gross residual tumor was accomplished in 72.2%. Conclusion PET/CT imaging demonstrates high sensitivity and positive predictive value in identifying potentially resectable, macroscopic recurrent ovarian cancer among patients with biochemical evidence of recurrence and negative or equivocal conventional CT findings. In appropriately selected patients, early identification of macroscopic recurrent disease may facilitate complete surgical cytoreduction.

Complete Surgical Cytoreduction of Advanced Ovarian Carcinoma Using the Argon Beam Coagulator

Objective.The aim of this study was to evaluate the utility of the argon beam coagulator (ABC) in achieving optimal (≤1 cm) disease status and facilitating the conversion of optimal but visible disease (0.1–1.0 cm) to microscopic residual disease (complete cytoreduction) among patients with advanced ovarian carcinoma.Methods. All patients undergoing their primary attempt at surgical cytoreduction for Stage IIIB–IV epithelial ovarian carcinoma between October 1, 1997 and June 30, 2000 were identified from the tumor registry database. Data were abstracted retrospectively and included: the size/location of precytoreduction disease, surgical procedures performed, the anatomic regions in which the ABC was used for cytoreduction, the size/location of residual tumor, and the date of last follow-up and disease status. Survival curves were generated using the Kaplan–Meier method, and statistical comparisons were performed using the χ2 test, Fisher's exact test, log rank test, and multivariate logistic regression.Results. Forty-five patients were identified (FIGO Stage IIIB = 8, Stage IIIC = 29, Stage IV = 8). Overall, optimal cytoreduction was achieved in 84.4% of patients; 60.0% had only microscopic residual and 24.4% had residual disease 0.1–1.0 cm. The ABC was used to facilitate cytoreduction in 31 patients. Optimal disease status was achieved in 93.6% of cases in which the ABC was used compared with 64.3% for non-ABC cases (P < 0.023). ABC use was also associated with a higher rate of complete cytoreduction (74.2%) compared with non-ABC cases (28.6%, P < 0.004). Among patients left with optimal disease (≤1 cm), conversion to only microscopic residual was achieved in 79.3% of cases using the ABC and 44.4% of cases without ABC use (P < 0.044). The ABC was associated with a statistically significantly higher rate of complete cytoreduction for disease located in the lesser sac/gastrocolic ligament (90.9% vs 14.3%), abdominal peritoneum (95.5% vs 50.0%), bowel mesentery (80.0% vs 0), and pelvis (89.3% vs 50.0%). Multivariate analysis revealed that use of the ABC (P = 0.006) and disease in three or fewer anatomic regions (P = 0.014) were independent predictors of a microscopic residual surgical outcome. Complete cytoreduction was associated with a significant advantage in median progression-free survival (22.2 months) compared with patients with optimal but visible (0.1–1.0 cm) residual disease (12.3 months) and those with suboptimal (>1.0 cm) residual disease (6.3 months, P < 0.001). Among ABC cases, the mean estimated blood loss was 527 ml, and major postoperative complications occurred in 9.7% of patients.Conclusions. The ABC is a useful adjunct to conventional tumor reductive techniques and appears to significantly increase the feasibility of achieving both optimal disease status and complete cytoreduction of all visible tumor in patients with macroscopic metastatic ovarian carcinoma.

Complete Cytoreduction: Is Epithelial Ovarian Cancer Confined to the Pelvis Biologically Different From Bulky Abdominal Disease?

Abstract Objectives. The aim of this study was to determine whether site and size of tumor masses prior to complete surgical cytoreduction affect outcome survival. Methods. A retrospective review was performed of 53 women with stage II and III epithelial ovarian cancer following complete surgical cytoreduction. Results. Fifteen cases (28%) were classified as stage II and the remaining 38 cases (72%) as stage III. The overall median survival was 58 months with overall 2- and 5-year survivals of 76 and 42%, respectively. On univariate analysis, women with well differentiated tumors did significantly better than those with moderately or poorly differentiated tumours ( P = 0.0009). FIGO stage did not reach statistical significance ( P = 0.066). On multivariate analysis, comparing patient's age, previous history of pelvic surgery, previous history of malignancy, performance of lymphadenectomy for visibly/palpably enlarged nodes, performance of bowel resection, presence of concomitant tumors, positive pelvic and/or para-aortic lymph nodes, histological type, histological grade, and FIGO stage, only histological grade remained an independent variable affecting outcome survival ( P = 0.0004; FIGO stage, P = 0.22) (hazard ratio=6.5: well versus poor differentiation, 95% confidence interval, 1.7–25.5). Conclusion. When surgical cytoreduction to no visible disease has been achieved in women with stage II and III epithelial ovarian cancer, FIGO stage, i.e., site and size of tumor masses prior to surgical cytoreduction, does not appear to influence outcome survival. The aggressiveness of the remaining microscopic disease would seem to be determined largely by histological grade. Bearing in mind the retrospective nature of this study and the relatively small cohort of patients, the results would appear to suggest that it is unlikely that there are any other significant parameters (hidden factors) affecting tumor biology which are independent of tumor grade in these patients. A possible implication of this result is that complete surgical cytoreduction confers a survival benefit by producing a biologically more homogenous tumor.

Complete Salvage Surgical Cytoreduction Improves Further Survival of Patients with Late Recurrent Ovarian Cancer

Objective. The aim of this study was to assess the clinical benefit of salvage surgical cytoreduction in patients with late recurrent ovarian cancer.Methods. Thirty patients with recurrent ovarian cancer who underwent salvage surgical cytoreduction were retrospectively reviewed. All had been initially treated by primary surgery and platinum-based chemotherapy and had a period of clinical remission of at least 6 months. Median time to recurrence was 17.5 months (range, 6–76 months).Results. A macroscopically complete salvage cytoreduction was obtained in 17 (56.7%) patients, whereas 8 patients were left with macroscopic residual disease <2 cm and 5 patients with a larger residuum. Logistic regression showed that the probability of achieving a complete cytoreduction was significantly related to the residual disease after initial surgery (<2 cm versus >2 cm, P = 0.0027, odds ratio = 36.000, 95% confidence interval = 3.473–373.176), but not to FIGO stage, tumor grade, histologic type, patient age at recurrence, and time to recurrence. In the whole series median survival following salvage surgery was 21 months. Survival was significantly longer in patients who were completely cytoreduced compared to those who were not (median: 37 months versus 19 months, P = 0.04). Moreover, survival was significantly related to time to recurrence (>17.5 months versus <17.5 months, median: 25 months versus 15 months, P = 0.039), number of recurrence sites (single versus multiple, median: 40 months versus 19 months, P = 0.009), and residual disease after initial surgery (<2 cm versus >2 cm, median: 37 months versus 19 months, P = 0.01), but not to patient age, recurrence site with the largest size, FIGO stage, tumor grade, and histologic type.Conclusions. The present data seem to show that complete salvage surgical cytoreduction significantly improves further survival of ovarian cancer patients who recur at least 6 months after the completion of primary therapy.

Complete Cytoreduction: Is Epithelial Ovarian Cancer Confined to the Pelvis Biologically Different from Bulky Abdominal Disease?

Objectives. The aim of this study was to determine whether site and size of tumor masses prior to complete surgical cytoreduction affect outcome survival.Methods. A retrospective review was performed of 53 women with stage II and III epithelial ovarian cancer following complete surgical cytoreduction.Results. Fifteen cases (28%) were classified as stage II and the remaining 38 cases (72%) as stage III. The overall median survival was 58 months with overall 2- and 5-year survivals of 76 and 42%, respectively. On univariate analysis, women with well differentiated tumors did significantly better than those with moderately or poorly differentiated tumours (P = 0.0009). FIGO stage did not reach statistical significance (P = 0.066). On multivariate analysis, comparing patient's age, previous history of pelvic surgery, previous history of malignancy, performance of lymphadenectomy for visibly/palpably enlarged nodes, performance of bowel resection, presence of concomitant tumors, positive pelvic and/or para-aortic lymph nodes, histological type, histological grade, and FIGO stage, only histological grade remained an independent variable affecting outcome survival (P = 0.0004; FIGO stage, P = 0.22) (hazard ratio = 6.5: well versus poor differentiation, 95% confidence interval, 1.7–25.5).Conclusion. When surgical cytoreduction to no visible disease has been achieved in women with stage II and III epithelial ovarian cancer, FIGO stage, i.e., site and size of tumor masses prior to surgical cytoreduction, does not appear to influence outcome survival. The aggressiveness of the remaining microscopic disease would seem to be determined largely by histological grade. Bearing in mind the retrospective nature of this study and the relatively small cohort of patients, the results would appear to suggest that it is unlikely that there are any other significant parameters (hidden factors) affecting tumor biology which are independent of tumor grade in these patients. A possible implication of this result is that complete surgical cytoreduction confers a survival benefit by producing a biologically more homogenous tumor.