Incomplete Debulking Research Articles

The Influence of Inflammatory and Nutritional Status on the Long-Term Outcomes in Advanced Stage Ovarian Cancer.

Despite improving surgical techniques and achieving more often complete debulking procedures, certain patients with advanced-stage ovarian cancer still have a very poor prognosis. The aim of the current paper is to investigate whether inflammatory and nutritional status can predict the long-term outcomes of ovarian cancer patients. A retrospective analysis of 57 cases diagnosed with advanced-stage ovarian cancer submitted to surgery as first intent therapy was carried out. In all cases, the preoperative status was determined by calculating the CRP/albumin ratio, as well as the Glasgow score, the modified Glasgow score and the prognostic nutritional index. Patients presenting higher values of the CRP/albumin ratio, with a higher Glasgow score, modified Glasgow score and prognostic nutritional index (PNI), were more frequently associated with incomplete debulking surgery, a higher peritoneal carcinomatosis index and poorer overall survival (20 months versus 9 months for the CRP/albumin ratio p = 0.011, 42 versus 27 versus 12 months for the Glasgow score p = 0.042, 50 versus 19 versus 12 months for the modified Glasgow score, p = 0.001, and 54 months versus 21 months, p = 0.011 for the prognostic nutritional index). A strong relationship between the nutritional and inflammatory status in advanced-stage ovarian cancer seems to exist.

Benefit From Fractionated Dose-Dense Chemotherapy in Patients With Poor Prognostic Ovarian Cancer: ICON-8 Trial.

An international meta-analysis identified a group of patients with advanced epithelial ovarian cancer (EOC) with a very poor survival because of two unfavorable features: (1) a poor chemosensitivity defined by an unfavorable modeled CA-125 ELIMination rate constant K (KELIM) score <1.0 with the online calculator CA-125-Biomarker Kinetics, and (2) an incomplete debulking surgery. We assumed that patients belonging to this poor prognostic group would benefit from a fractionated densified chemotherapy regimen. The data set of ICON-8 phase III trial (ClinicalTrials.gov identifier: NCT01654146), where patients with EOC were treated with the standard three-weekly, or the weekly dose-dense, carboplatin-paclitaxel regimens and debulking primary surgery (immediate primary surgery [IPS] or delayed primary [or interval] surgery [DPS]), was investigated. The association between treatment arm efficacy, standardized KELIM (scored as favorable ≥1.0, or unfavorable <1.0), and surgery completeness was assessed by univariate/multivariate analyses in IPS and DPS cohorts. Of 1,566 enrolled patients, KELIM was calculated with the online model in 1,334 with ≥3 CA-125 available values (85%). As previously reported, both KELIM and surgery completeness were complementary prognostic covariates, and could be combined into three prognostic groups with large OS differences: (1) good if favorable KELIM and complete surgery; (2) intermediate if either unfavorable KELIM or incomplete surgery; and (3) poor if unfavorable KELIM and incomplete surgery. Weekly dose-dense chemotherapy was associated with PFS/OS improvement in the poor prognostic group in both the IPS cohort (PFS: hazard ratio [HR], 0.50; 95% CI, 0.31 to 0.79; OS: HR, 0.58; 95% CI, 0.35 to 0.95) and the DPS cohort (PFS: HR, 0.53; 95% CI, 0.37 to 0.76; OS: HR, 0.57; 95% CI, 0.39 to 0.82). Fractionated dose-dense chemotherapy might be beneficial for patients belonging to the poor prognostic group characterized by lower tumor chemosensitivity assessed with the online calculator CA-125-Biomarker Kinetics and incomplete debulking surgery. Further investigation in the future SALVOVAR trial is warranted.

The impact of thrombocytosis on the long term outcomes in relapsed ovarian cancer

The presence of thrombocytosis has been widely associated with poor prognostic in patients diagnosed with ovarian cancer at the time of the initial diagnostic. Once this fact has been widely accepted, attention was focused on studying whether this biological parameter could be also a diagnostic tool for identifying patients with poorer outcomes at the time of secondary cytoreduction. Therefore the most commonly encountered questions are whether patients presenting thrombocytosis at the time of primary cytoreduction are expected to have also thrombocytosis at the time of relapse and if thrombocytosis at the time relapse is corelated with lower disease free intervals, with higher rates of incomplete debulking and with poorer rates of overall survival respectively. This is a literature review of the most relevant studies conducted on this issue.

Comparison of Peritoneal Carcinomatosis Scoring Methods in Predicting Resectability and Prognosis in Gynecologic Malignancies.

Objective: Peritoneal carcinomatosis is a disease’s presentation in the advanced stages of many gynecologic tumours. The distribution and volume of the disease are the main factors in achieving complete debulking. Diagnostic laparoscopy is a technique to allow evaluation of the disease. This study’s objective is to compare two laparoscopic scores (Fagotti’s index and Sugarbaker’s peritoneal cancer index (PCI)) and assess the diagnostic accuracy to select patients for neoadjuvant treatment and reduce unnecessary laparotomies. Methods: A non-randomised retrospective cohort study was conducted in patients with peritoneal carcinomatosis (ovarian and endometrial origin) who underwent laparoscopy and subsequent laparotomy. We evaluated the scores’ ability to predict incomplete surgery and whether they were related to the patients’ prognosis. Results: We included 34 patients, of which 23.5% received neoadjuvant chemotherapy. The rate of complete cytoreductive surgery was 79.4% (n = 27 patients). The highest sensitivity was obtained with a PCI value greater than 20. It was the best parameter to determine incomplete debulking. Survival curves were analysed according to the “cut off” established for each score, and statically significant differences were found using PCI with respect to Fagotti’s Index. However, these differences were not found with Fagotti’s score. Conclusion: The best diagnostic method to classify patients with peritoneal cancer is the PCI. It could be adapted to each surgical team because it allows identifying the “cut off point”, which depends on incomplete surgery rate.

Metabolic active peritoneal sites affect tumor debulking in ovarian and peritoneal cancers

Rationale and objectivesTo evaluate the impact of metabolic parameters in the peritoneal cavity on the likelihood of achieving complete tumor debulking in patients with ovarian and peritoneal cancers.Materials and methodsForty-nine patients with ovarian and peritoneal cancers were included, who underwent pre-operative 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT). The immediate surgical outcome was dichotomized into complete and incomplete tumor debulking. 18F-FDG PET/CT was qualitatively and quantitatively assessed by scrutinizing 15 anatomical sites for the presence of peritoneal carcinomatosis (PC). Patient-based and site-based diagnostic characteristics were described. Metabolic parameters (SUVmax, metabolic tumor volume and total lesion glycolysis) and the number of 18F-FDG avid peritoneal sites were evaluated between the two groups. Receiver operating curve (ROC) analysis was performed to determine the optimal cut-off value in predicting incomplete tumor debulking.ResultsTwenty-seven out of the 49 patients had PC and 11 had incomplete debulking. Patient-based and site-based accuracies for detection of PC were 87.8 and 97.6%, respectively. The number of 18F-FDG avid peritoneal sites was significantly different between complete and incomplete debulking groups (0.6 ± 0.8 versus 2.3 ± 1.7 sites respectively, p = 0.001), and the only independent significant risk factor among other metabolic parameters tested (odd ratio = 2.983, 95% CI 1.104–8.062) for incomplete tumor debulking with an optimal cut-off value of ≥4 (AUC = 0.816).ConclusionThe number of 18F-FDG avid peritoneal sites increased the risk of incomplete tumor debulking after surgery and potentially useful in assisting treatment stratification in patients with ovarian and peritoneal cancers.

P1306 A large cardiac mass of left sections in a young man

Abstract Background Heart tumors are very rare lesions. Their prevalence is about 0.001 to 0.03 % in an autopsy series. In most cases, primitive lesions are benign, with atrial myxomas that represent up to 2/3 of cases. Malignant neoplasms have a high mortality; sarcomas are the most frequent typologies. The most aggressive tumors are characterized by greater size, muscle invasion and pericardial effusion. Clinical case A 39-year-old man with recent history of worsening dyspnea went to the emergency room because of an aggravation of the symptoms. An echocardiogram showed a large atrial inhomogeneous mass, adherent to the mitral ring and involving both left atrial and ventricle, causing a severe valvular stenosis, suggestive for malignancy. Thus the patient performed a cardiac-MRI, confirming the neoplasm localization with parietal infiltration, pericardial extension and effusion. A total-body CT scan ruled out metastasis. The patient underwent heart surgery and a partial excision was performed. Macroscopically the tumor had a scirrhous consistency and a diameter of about 5 cm. The histologic examination showed a high-grade sarcoma with fused cells and with condrosarcomatous areas. Discussion The study of heart massesincludes the execution of echocardiographies as first-line examinations, while the in-depth diagnostics (necessary in the anticipation of surgery) require cardiac-MRI or CT. Malignant lesions are characterized by an inomogeneous appearance, with a wide plant base and sizes larger than 5 cm, they are also able to take contrast medium during diagnostic examinations. High grade neoplasms are rapidly evolving with a very severe prognosis. The symptoms are essentially due to the localization and the mass bulk. In our case, its development on the mitral valve caused severe hemodynamic impairment, requiring immediate intervention. The treatment of these lesions is necessarily surgical. The only positive prognostic factor is a complete excision of neoplasm with free resection margins. As the diagnosis is often not early, chemotherapy or radiotherapy are often required after surgery. Conclusion Cardiac masses are rare entities and their evaluation may be a diagnostic challenge. Myxoma represent the most common primary cardiac neoplasm in adults, while about 25% of other primary ones are malignant. Our patient was suffering from a sarcoma, whose incomplete debulking made further therapies necessary. The correct interpretation of instrumental findings together with a possible radical surgery are mandatory for a successful therapeutic strategy. Abstract P1306 Figure.

Positron emission tomography (PET) and magnetic resonance imaging (MRI) for assessing tumour resectability in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer.

Ovarian cancer is the leading cause of death from gynaecological cancer in developed countries. Surgery and chemotherapy are considered its mainstay of treatment and the completeness of surgery is a major prognostic factor for survival in these women. Currently, computed tomography (CT) is used to preoperatively assess tumour resectability. If considered feasible, women will be scheduled for primary debulking surgery (i.e. surgical efforts to remove the bulk of tumour with the aim of leaving no visible (macroscopic) tumour). If primary debulking is not considered feasible (i.e. the tumour load is too extensive), women will receive neoadjuvant chemotherapy to reduce tumour load and subsequently undergo (interval) surgery. However, CT is imperfect in assessing tumour resectability, so additional imaging modalities can be considered to optimise treatment selection. To assess the diagnostic accuracy of fluorodeoxyglucose-18 (FDG) PET/CT, conventional and diffusion-weighted (DW) MRI as replacement or add-on to abdominal CT, for assessing tumour resectability at primary debulking surgery in women with stage III to IV epithelial ovarian/fallopian tube/primary peritoneal cancer. We searched MEDLINE and Embase (OVID) for potential eligible studies (1946 to 23 February 2017). Additionally, ClinicalTrials.gov, WHO-ICTRP and the reference list of all relevant studies were searched. Diagnostic accuracy studies addressing the accuracy of preoperative FDG-PET/CT, conventional or DW-MRI on assessing tumour resectability in women with advanced stage (III to IV) epithelial ovarian/fallopian tube/primary peritoneal cancer who are scheduled to undergo primary debulking surgery. Two authors independently screened titles and abstracts for relevance and inclusion, extracted data and performed methodological quality assessment using QUADAS-2. The limited number of studies did not permit meta-analyses. Five studies (544 participants) were included in the analysis. All studies performed the index test as replacement of abdominal CT. Two studies (366 participants) addressed the accuracy of FDG-PET/CT for assessing incomplete debulking with residual disease of any size (> 0 cm) with sensitivities of 1.0 (95% CI 0.54 to 1.0) and 0.66 (95% CI 0.60 to 0.73) and specificities of 1.0 (95% CI 0.80 to 1.0) and 0.88 (95% CI 0.80 to 0.93), respectively (low- and moderate-certainty evidence). Three studies (178 participants) investigated MRI for different target conditions, of which two investigated DW-MRI and one conventional MRI. The first study showed that DW-MRI determines incomplete debulking with residual disease of any size with a sensitivity of 0.94 (95% CI 0.83 to 0.99) and a specificity of 0.98 (95% CI 0.88 to 1.00) (low- and moderate-certainty evidence). For abdominal CT, the sensitivity for assessing incomplete debulking was 0.66 (95% CI 0.52 to 0.78) and the specificity 0.77 (95% CI 0.63 to 0.87) (low- and low-certainty evidence). The second study reported a sensitivity of DW-MRI of 0.75 (95% CI 0.35 to 0.97) and a specificity of 0.96 (95% CI 0.80 to 1.00) (very low-certainty evidence) for assessing incomplete debulking with residual disease > 1 cm. In the last study, the sensitivity for assessing incomplete debulking with residual disease of > 2 cm on conventional MRI was 0.91 (95% CI 0.59 to 1.00) and the specificity 0.97 (95% CI 0.87 to 1.00) (very low-certainty evidence). Overall, the certainty of evidence was very low to moderate (according to GRADE), mainly due to small sample sizes and imprecision. Studies suggested a high specificity and moderate sensitivity for FDG-PET/CT and MRI to assess macroscopic incomplete debulking. However, the certainty of the evidence was insufficient to advise routine addition of FDG-PET/CT or MRI to clinical practice..In a research setting, adding an alternative imaging method could be considered for women identified as suitable for primary debulking by abdominal CT, in an attempt to filter out false-negatives (i.e. debulking, feasible based on abdominal CT, unfeasible at actual surgery).

Pasireotide: A potential therapeutic alternative for resistant prolactinoma

ContextAbout 10% of prolactinomas are resistant to dopamine-agonists (DAs). The only alternatives for tumor and prolactin control are surgery or radiotherapy. While studies on first generation somatostatin analogs have shown no efficacy against prolactinomas, no study has been conducted on the new multireceptor-targeted somatostatin receptor ligand pasireotide, which presents high affinity for 5, 3, 2 and 1 receptor subtypes. Case descriptionA 41 year-old woman presented with a macroprolactinoma showing resistance to all available DAs. She was first diagnosed at 17 years old after which she had undergone two incomplete debulking surgeries. Under pasireotide long-acting release (LAR) treatment, plasma prolactin levels normalized and symptoms disappeared within one month after initiation. The clinical benefits of the monotherapy (specifically, prolactin levels within normal range and stable tumor volume) were maintained for seven years. Glucose tolerance was satisfactory. Pathological analysis of the tumor revealed high SSTR5 and low SSTR2 expression (25 and 5% of cells respectively). ConclusionThis is a promising first report of a patient with a DA-resistant macroprolactinoma who achieved long-term control, in terms of prolactin normalization and tumor volume, under pasireotide treatment alone. Pasireotide could thus be an alternative in prolactinomas resistant to DA. SSTR expression analysis on pathology could guide patient selection.

Prognostic factors influencing survival in small bowel neuroendocrine tumors with liver metastasis.

e15688 Background: Management of liver metastasis in patients with small bowel neuroendocrine tumors (SBNET) remains unclear. Complete surgical resection improves long term survival however factors that influence overall prognosis are not clear. Methods: Database review identified 301 patients diagnosed with SBNET from 1990 to 2013. Only patients with known liver metastasis who underwent resection of the primary tumor were included. Outcomes among patients who underwent complete surgical resection, incomplete debulking of liver metastasis, and resection of the primary tumor alone were compared. The Kaplan-Meier method was used for survival estimates and Cox regression was used to identify predictors of death. Results: 111 patients met study criteria. Median age was 59 years (range 16-80); 49% were male. The terminal ileum (47/111, 42%) was the most common primary tumor location. The median number of liver lesions was 8.5 (range 1-31) and median lesions resected was 1 (range 0-31). In addition to resection of the primary tumor, 36 patients (32%) had no liver resection (NR), 41 (36.9%) had complete resection of liver disease (R0) and 34 (30%) had incomplete resection of liver metastasis (R1). 58 patients (36%) had one or more wedge resections, 12 (10.8%) underwent segmentectomy and 5 (4.5%) had a lobectomy. 33 (29.7%) patients underwent post-operative chemoembolization, 25 (22.5%) had radioembolization and 23 (20.7%) had radiofrequency ablation. The R1 group differed from the R0 group in median size of primary tumor (2.5 cm R1 vs 1.6 cm R0, p = 0.05) and median number of positive lymph nodes (5.0 R1 vs 3.0 R0, p = 0.05). The 5-year OS was 80.9%, 81.1% and 100% for NR, R1 and R0 groups respectively (p = 0.01). 10-year OS did not differ between groups (72.8% NR vs 81.1% R1vs 82.5% NR, p = 0.31). Cox regression showed post-operative administration of chemotherapy (HR = 3.68, p &lt; 0.01) and higher tumor grade (HR = 18.4, p = 0.02) increased risk of death. Conclusions: In patients with SBNET with liver metastasis, higher tumor grade and post-operative chemotherapy increased risk of death. However, resection of the primary tumor along with liver metastasis improves the 5-year OS with complete cytoreduction providing the most benefit.

Recurrent female adnexal tumor of probable Wolffian origin treated with debulking surgery, imatinib and paclitaxel/carboplatin combination chemotherapy: A case report.

In view of the small number of recurrent and metastatic cases of female adnexal tumors of probable Wolffian origin (FATWO), there is a distinct lack of evidence to support recommendations regarding treatment. In the present study, a 37-year-old female was diagnosed with a left adnexal tumor and underwent a left salpingo-oophorectomy (SO). The tumor was found to arise from the left tubal fimbria and extend to the posterior leaf of the broad ligament. Pathological examination identified a number of solid, tubular and cystic architectures, with areas of hyalinization, hemorrhage and necrosis. Immunohistochemistry detected that the tumor cells were positive for cytokeratin (CK)7, vimentin, inhibin and calretinin, and negative for CK20, epithelial membrane antigen, and the estrogen and progesterone receptors. Thus, the patient was diagnosed with FATWO. Following 15 months, the patient developed recurrent tumors and subsequently underwent a total abdominal hysterectomy, a right SO and extirpation of the disseminated tumors, but with incomplete debulking. The tumor cells were immunoreactive for KIT. As there are a limited number of treatment options and few reported cases, limiting the therapy recommendations, imatinib mesylate was administered for 6 months and the tumors were temporarily stabilized for 4 months until the disease progressed. The patient underwent a further debulking surgery that did not achieve complete debulking and was subsequently administered a combination chemotherapy of paclitaxel and carboplatin. This regimen resulted in an almost complete response after 10 cycles. The tumors continued to decrease in size, and the tumors in the left side of the Douglas pouch and the right para-colic gutter were no longer detectable. To the best of our knowledge, the current study is the first to report carboplatin and paclitaxel combination therapy demonstrating a response of this degree to recurrent FATWO following the failure of imatinib treatment. However, surgical debulking remains the most effective treatment for FATWO when is it is possible. The precise role of chemotherapy, radiotherapy and molecular-targeting therapy in the treatment of recurrent or metastatic FATWO remains to be elucidated, and therefore, novel strategies to overcome this disease must be prioritized.

Centralisation of epithelial ovarian cancer surgery: results on survival from a peripheral teaching hospital

ObjectiveThe objective of this retrospective descriptive study was to assess overall survival and disease free survival of patients treated for epithelial ovarian cancer by a gynaecologic-oncologist in a single Dutch peripheral teaching hospital and to identify independent prognostic factors. Study designA retrospective series of 242 patients treated for epithelial ovarian cancer between 1999 and 2011 at Meander Medical Centre was reviewed. Data on patient, tumour and treatment characteristics were collected. Outcomes were overall survival and progression free survival. Data were analysed using the Kaplan–Meier method, log-rank test and Cox regression analysis. ResultsMedian follow-up was 35 months (range 1–203). Staging procedures were performed in 81 patients of which 63% were complete. 61% of patients had advanced stage disease. In 46%, debulking surgery was complete. Five-year overall survival and progression free survival for all patients was 52% and 47%, respectively. Multivariate analysis identified performance status [HR=1.89 and 1.92 for performance status 2, HR=7.01 and 2.69 for performance status 3], FIGO stage [HR=3.59 for stage II, HR=5.43 and 5.64 for stage III, HR=12.17 and 10.21 for stage IV] and residual disease after debulking surgery [HR=2.01 and 1.72 for incomplete debulking] as independent prognostic factors for overall survival and progression free survival respectively. ConclusionSurvival after surgery for epithelial ovarian cancer in this cohort is comparable to survival in centralised clinics presented in literature. Partial concentration of cancer care by recruitment of specialised gynaecologic-oncologists in teaching hospitals might be an alternative to complete centralisation of epithelial ovarian cancer treatment in larger cancer centres.

The efficacy of tumor debulking surgery is improved by adjuvant immunotherapy using imiquimod and anti-CD40.

BackgroundTumor debulking surgery followed by adjuvant chemotherapy or radiotherapy is a standard treatment for many solid malignancies. Although this approach can be effective, it often has limited success against recurrent or metastatic cancers and new multimodality approaches are needed. Adjuvant immunotherapy is another potentially effective approach. We therefore tested the efficacy of the TLR7 agonist imiquimod (IMQ) combined with agonistic anti-CD40 in an incomplete debulking model of malignant mesothelioma.MethodsEstablished subcutaneous murine ABA-HA mesothelioma tumors in BALB/c mice were surgically debulked by 75% and treated with either: i) saline; ii) intratumoral IMQ; iii) systemic anti-CD40 antibody, or using a combination of IMQ and anti-CD40. Tumour growth and survival were monitored, and the role of anti-tumor CD4 and CD8 T cells in therapeutic responses was determined.ResultsThe combination therapy of partial debulking surgery, IMQ and anti-CD40 significantly delayed tumor growth in a CD8 T cell dependent manner, and promoted tumor regression in 25% of animals with establishment of immunological memory. This response was associated with an increase in ICOS+ CD8 T cells and tumor-specific CTL activity in tumor draining lymph nodes along with an increase in ICOS+ CD8 T cells in responding tumours.ConclusionsWe show that the post-surgical environment can be significantly altered by the co-administration of adjuvant IMQ and anti-CD40, resulting in strong, systemic anti-tumor activity. Both adjuvants are available for clinical use/trial, hence this treatment regimen has clear translational potential.

Positron Emission Tomography/Computed Tomography Predictors of Overall Survival in Stage IIIC/IV Ovarian Cancer

To evaluate the role of 2-deoxy-2-(F)fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) for selecting patients with extensive ovarian cancer (OC) for neoadjuvant chemotherapy by evaluating predictors of overall survival in patients with stage IIIC/IV OC. From September 1, 2004, to November 20, 2011, 514 consecutive patients with a pelvic tumor underwent preoperative PET/CT; 179 patients had stage IIIC/IV OC. Patients' characteristics were collected from 153 patients with stage IIIC/IV OC who underwent primary surgery. In 152 patients with stage IIIC/IV OC, clinical predictors and PET/CT predictors of survival were evaluated. Median age was 64 years (range, 38-88 years); 87% (113) of the 153 patients had a performance status of less than 2; 55% (84) of the 153 patients had PET/CT stage III, and 45% (69) of the 153 patients had PET/CT stage IV. Using univariate analysis, incomplete debulking (P = 0.0001), pleural exudates (P = 0.001), postmenopausal state (P = 0.01), WHO performance status greater than 2 (P = 0.01), PET/CT stage IV (P = 0.01), and large bowel mesentery implants (P = 0.02) were statistically significant prognostic variables. Using multivariate Cox regression analysis, incomplete debulking was the only statistically significant independent prognostic variable (P = 0.0001). Median overall survival was significantly longer in the 53 patients with no residual tumor than in the 99 patients with residual tumor (33.3 vs 25.5 months; P = 0.0001) Suggested PET/CT criteria for referral of patients with advanced OC to neoadjuvant chemotherapy are PET/CT stage IV, pleural exudates, and PET-positive large bowel mesentery implants. Evaluation of selection criteria for neoadjuvant chemotherapy should be promoted in prospective clinical trials, with survival as the primary end point.

Rapid progression of synchronous ovarian and endometrial cancers with massive omental carcinomatosis

We present a rare case of a 41-year-old woman with synchronous primary cancers of the endometrium and ovary, both in advanced stages. Palliative surgery with incomplete tumor debulking followed by the first trial of chemotherapy provided no treatment benefit to her prognosis and she died shortly thereafter. A 41-year-old woman, para 1, was referred to our department for prolonged and profuse menstrual bleeding, poor appetite and marked abdominal distension. Abdominal ultrasound and computed tomography showed a large left adnexal tumor accompanied by massive ascites and carcinomatosis (Fig. 1). The levels of tumormarkers, including cancer antigen (CA) 125, CA 19-9, and carcinoembryonic antigen (CEA), were 1588 U/ mL, 21 U/mL, and 1.4 ng/mL, respectively. During her operation, we noted a huge omental cake of about 35 cm (Fig. 2), a left ovarian tumorwith rectal serosa invasion, diffuse intraperitoneal (including bowels) tumor implantation, and massive ascites totaling about 6600 mL. The uterus, the contralateral ovary and tube, and the liver surface were not involved. Suboptimal debulking surgery was done (residual tumor size > 1 cm), and the estimated blood loss was 2000 mL. The microscopic findings included two synchronous tumors of the left ovary and endometrium. The histological types were mixed clear cell (moderately differentiated), endometrioid (well-differentiated) carcinoma of the left ovary (90% clear and 10% endometrioid), and mucinous (moderately differentiated) carcinoma of the endometrium, respectively. The contralateral ovary revealed a microscopic tumor implant. The final histopathological findings were synchronous ovarian clear celleendometrioid carcinoma and endometrial mucinous carcinoma, with massive omental carcinomatosis, without lymph nodes metastasis, FIGO IIIC (pT3cN1) (Figs. 3 and 4). She received adjuvant chemotherapy with carboplatin and taxol immediately after the operation. The levels of tumor

Highly sulfated chondroitin sulfates, a novel class of prognostic biomarkers in ovarian cancer tissue

ObjectiveClinical decision making in ovarian cancer needs new (prognostic) biomarkers. Although the search for biomarkers has traditionally focused on tumor cells, their surrounding contains important information as well. Glycosaminoglycans, heterogeneous polysaccharides which are abundantly present in the stromal compartment, are indicated in several pathological processes including cancer. In this study we investigated a specific glycosaminoglycan motif (4,6-disulfated chondroitin sulfate) for its potential as a prognostic biomarker in ovarian cancer. Methods4,6-Disulfated chondroitin sulfate presence was studied immunohistochemically using the single chain antibody GD3G7 on 148 ovarian tumors including benign and malignant tumors, and tumors with low malignant potential. For comparative purposes p53 and Ki-67 were evaluated. X2 tests, univariate and multivariate Cox proportional hazards analyses were applied for statistical analysis. ResultsThe stroma of malignant tumors showed significantly increased expression of 4,6-disulfated chondroitin sulfate (GD3G7 epitope) compared with benign tumors and tumors with LMP (p-values<0.000 and 0.002, respectively). Expression of GD3G7 in malignant tumors was significantly correlated with serous subtype, high tumor grade, advanced FIGO-stage and high CA-125 levels. In patients with advanced FIGO stage GD3G7 expression was significantly correlated with incomplete debulking and good response to platinum-based chemotherapy. GD3G7 surpassed both p53 and Ki-67 in statistical analysis. Multivariate survival analysis revealed GD3G7 expression as an independent predictor for progression free survival. ConclusionGlycosaminoglycan motifs may form a new class of biomarkers for (ovarian) cancer, as indicated here for the GD3G7 epitope. Expression of GD3G7 may contribute in therapeutic decision making and constitutes a potential biomarker for poor prognosis.

Prognostic factors and treatment-related outcomes in patients with uterine serous cancer (USC).

5099 Background: USC an uncommon (10%) but aggressive form of uterine cancer, causes 50% of uterine cancer deaths. The purpose of this study is to report a large single-institution experience with USC investigating the effects of clinicopathological parameters and treatment on overall (OS) and disease-free survival (DFS). Methods: Records from our institution were reviewed from 1987-2009. All 334 USC patients (pts) identified were surgically staged. Postoperative treatments used were: (1) observation (OBS, n=33); (2) platinum-based chemotherapy (PCH, n=78); (3) whole pelvis radiation therapy (WPRT, n=16); (4) PCH and vaginal apex brachytherapy (PCHR, n=165); (5) vaginal apex brachytherapy (VAB, n=35). The cancer stages were 121 pts IA (36.2%), 36 IB (10.8%), 27 II (8.1%), 39 IIIA (11.7%), 2 IIIB (0.6%), 32 IIIC1 (9.6%), 9 IIIC2 (2.7%), 28 IVA (8.4%) and 40 IVB (12%). Results: The 5-year OS for stage IA/IB, II, IIIA/IIIB, IIIC1/IIIC2, IVA/IVB were 82%, 70%, 64%, 36%, and 9%, respectively. The 5-year DFS for stage IA/IB, II, IIIA/IIIB, IIIC1/IIIC2, IVA/IVB were 82%, 68%, 56%, 24%, 6%, respectively. Advanced stage was associated with significantly shorter OS and DFS (p &lt;0.01). The 5-year OS for stage IA/IB disease was 94% for pts who received PCHR, 90% for OBS, 75% for PCH, 65% for VAB and 0% for WPRT. The 5-year DFS for PCHR, OBS, PCH, VAB and WPRT for Stage IA/IB were 89%, 82%, 86%, 72% and 0% respectively. For stage II-IVB pts, the 5-year OS was 51% for PCHR, 0% for OBS, 23% for PCH and 20% for WPRT. The 5-year DFS for stage II-IVB with PCHR, OBS, PCH and WPRT were 42%, 0%, 17% and 13% respectively. Older age pts had worse survival, (p&lt;0.01). Race and BMI did not impact survival. Incomplete surgical debulking (p&lt;0.01), depth of myometrial invasion &gt;50% (p&lt;0.01) and lymph node metastasis (p&lt;0.01) were all associated with worse prognosis. Conclusions: PCHR overall exhibited better OS and DFS regardless of disease stage. Age, incomplete surgical debulking, depth of myometrial invasion and lymph node involvement were independent prognostic factors in USC patients in this study.

The influence of tumor cell entrapment phenomenon on the natural history of Pseudomyxoma peritonei syndrome.

Pseudomyxoma peritonei syndrome (PMP) may be associated with slow "benign" or malignant process. However, the natural history of this disease is slow progression to death. Its treatment is variable and controversial. In this current study we have compared the patients with Pseudomyxoma peritonei syndrome with recurrences due to the cell entrapment hypothesis. Data were derived from a database of patients with PMP treated at our hospitals from 2004 to 2009. All patients had undergone various surgical operations prior to referral to our institutions for definitive treatment. All patients had recurrences in special sites due to entrapment of malignant cells. There are 6 patients, four men and two women. The initial clinical presentation of the disease was hernia in one, appendicitis in three and ovarian mass in one. The mean time from the initial operation to be definitive management was 23.5 months with an average of 1.83 operations per patient. After cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) the mean survival was 31 months with minimal recurrences and only 0.3 operations per patient. Our data suggest that the patients should be referred to a center with a peritoneal surface malignancy program after the PMP diagnosis as soon as possible. Incomplete debulking procedures and minimal invasive operations promote uncontrollable intraabdominal tumor growth due to tumor cell entrapment and the tendency of PMP to grow at wound sites.

Outcome of immediate re-operation or interval debulking after chemotherapy at a gynecologic oncology center after initially incomplete cytoreduction of advanced ovarian cancer

BackgroundPrognosis in advanced ovarian cancer is largely determined by completeness of tumor resection achieved during primary surgery. Incomplete initial debulking occurs frequently in non-specialized centers and there is an ongoing discussion about the best time for re-surgery after referral to tertiary centers. MethodsPatients with advanced epithelial ovarian cancer (FIGO IIIB–IV) admitted between 1999 and 2007 who had primary incomplete surgery including those with initiated chemotherapy at an outside institution were included. Surgical results, morbidity and prognosis were evaluated in patients with immediate re-operation before chemotherapy and those with interval debulking. Results48 eligible patients were identified in our tumor registry. Self-referral by patient was the most frequent mode of admission (n=21, 43.8%). 22 patients (45.8%) underwent immediate re-surgery and 26 patients (54.2%) had an interval debulking after chemotherapy. In 12 patients (54.5%), macroscopically complete tumor removal could be achieved by immediate re-operation and in 17 patients (65.4%) after chemotherapy. Major complications were observed more frequently in patients with interval debulking (26.9 vs. 9.1%, p=0.324). Median overall survival time was 53 and 34months (p=0.110) after immediate and delayed re-operation, respectively. ConclusionsUpfront re-operation before start of chemotherapy is feasible and successful in an expertise referral center in more than half of patients with incomplete primary surgery elsewhere. Complete resection even after initial incomplete debulking could improve outcome. Therefore, referral to expertise centers in those patients should be considered. Progression-free survival and overall survival showed a non-significant trend and complication rate is a remarkable advantage in favor of upfront re-operation.

The Impact of Peritoneal Metastases in Epithelial Ovarian Cancer With Positive Nodes

The objective of the study was to evaluate the impact of the extent of intraperitoneal disease, presurgical and postsurgical debulking, in patients with epithelial ovarian cancer (EOC) stages IIIC and IV with nodal metastases. This was a retrospective chart review of 101 patients with EOC treated at the Mayo Clinic between 1996 and 2000. All patients had positive retroperitoneal lymph nodes (stages IIIC and IV). Patients were divided into complete or incomplete debulking, according to no visible or visible residual disease after debulking. Patients with incomplete debulking were subclassifed into residual disease less than 0.5, 0.6 to 1, 1.1 to 1.5, 1.6 to 2, and more than 2 cm. All patients received adjuvant chemotherapy with platinum-based regimen. The mean patient's age was 61.8 years. The mean length of follow-up was 3.5 years. The 5-year overall survival rates were 52.9% and 38.7% for International Federation of Gynecology and Obstetrics stages IIIC and IV, respectively. Significant prognostic factors were the presence of peritoneal metastases before debulking (P = 0.01), the presence of visible residual tumor after debulking, (P = 0.007), and International Federation of Gynecology and Obstetrics stage (P = 0.049). The extent of peritoneal metastases before debulking is a significant factor for survival in patients with node-positive EOC.

Abstract 4723: Soluble L1-CAM in the ascites is a prognostic marker in ovarian cancer

Abstract L1-cell adhesion molecule (L1-CAM) is a 200-220 kDa transmembrane protein that belongs to the immunoglobulin superfamily. It was initially found to be expressed on neuronal cells and is involved in axon outgrowth and guidance during central nervous system development. L1-CAM overexpression has been reported for various tumor entities, where it correlates with advanced stage disease, metastasis and chemoresistance. In mouse models, L1-CAM promotes tumor growth and facilitates experimental tumor metastasis. The extracellular part of the full length L1-CAM is subject to membrane proximal cleavage, which generates a soluble form of about 200kDa (sL1-CAM). L1-CAM cleavage and release of the soluble molecule has been shown to promote migration, adhesion and protection from apoptosis of ovarian cancer cells in vitro. The soluble L1-CAM can be detected in body fluids like saliva, serum or ascites. In a multi-centric retrospective study with 270 ovarian cancer patients, we analysed tumor samples to quantify membrane bound full length L1-CAM as well as ascites for sL1-CAM to study the value of L1-CAM as a prognostic marker. We found that L1-CAM expression on the tumor correlated with sL1-CAM in the ascites (rho=0.41). Increased L1-CAM levels on the tumor and in the ascites correlated significantly with a reduced overall survival (univariate p=0.028; 0.022). Elevated ascitic L1-CAM levels were also associated with poor progression free survival (p&amp;lt;0.0001) and remained an independent prognostic marker in multivariate analysis (p=0.0003). Furthermore, increased L1-CAM levels in the ascites correlated with an increased ascites volume (p=0.003). Patients with elevated L1-CAM levels in the tumor were at high risk for incomplete primary debulking (univariate p=0.01, multivariate p=0.04) and had an increased risk for lymph node metastases (p=0.004). Given the in vitro role of L1-CAM in metastasis and invasion in addition to the findings of our study, we conclude that L1-CAM high expressing tumors show a more invasive phenotype which translates into a higher rate of incomplete debulking during upfront surgery. High levels of sL1-CAM in the ascites could serve as a reliable marker for prediction of early relapse and residual tumor burden in women suffering from ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4723. doi:10.1158/1538-7445.AM2011-4723