Surgical Cytoreduction Research Articles

Assessment of a novel mucolytic solution for dissolving mucus in pseudomyxoma peritonei: an ex vivo and in vitro study.

Pseudomyxoma peritonei (PMP) is difficult to treat. Intraperitoneal delivery of mucolytic solutions might potentially improve therapy, in addition to surgical cytoreduction and hyperthermic intraperitoneal chemotherapy. Comparison of mucolytic effect of two formulations (control: bromelain 300 µg/mL+N-Acetylcystein 250 mM; test: bromelain 200 µg/mL+200 mM cysteamine) in vitro on a mucin producing cell lines (HT29) and ex vivo on mucus obtained from 18 PMP patients. Mucin plugs were classified according to their density into three categories: hard, semi hard and soft. Simulation of peritoneal washing ex vivo using a closed heated circulating pump. Solubilisation was faster with the test vs. the control formulation (90 vs. 180 min) for dissolving the soft mucin plugs (p < 0.05). The test solution was also more effective in dissolving the hard mucus plugs compared to control (82.5±2.74 % vs. 36.33±3.27 %). All mucin types disintegrated in simulated peritoneal washing. Cytotoxicity of the test solution on HT29 cell line was time-dependent. The test formulation is more effective and faster than the control formulation in dissolving mucus plugs of various densities. Mucus plugs were all solubilised after 40 min in simulated peritoneal washing. This novel mucolytic formulation might pave the way for an effective and less invasive therapy of PMP in the future.

Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives.

Carcinosarcomas (CS) in gynecology are very infrequent and represent only 2–5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50–80%). Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms “uterine carcinosarcoma”, “uterine Malignant Mixed Müllerian Tumors”, “target therapies”, “angiogenesis therapy”, “cancer stem cell therapy”, “prognostic biomarker”, and “novel antibody-drug”. Based on our results, the differential expression and accessibility of epithelial cell adhesion molecule-1 on metastatic/chemotherapy-resistant CS cells in comparison to normal tissues and Human Epidermal Growth Factor Receptor 2 (HER2) open up new possibilities in the field of target therapy. Nevertheless, future investigations are needed to clarify the impact of these new therapies on survival rate and medium-/long-term outcomes.

Clinical trial in progress: A phase 3 study of maintenance bi-shRNA-furin/GM-CSF-expressing autologous tumor cell vaccine in women with stage IIIb-IV high-grade epithelial ovarian cancer.

TPS5604 Background: Vigil is an immuno-stimulatory autologous cellular therapy, which uses patient tumor cells transfected with a plasmid encoding genes for GM-CSF and furin (to down regulate TGFβ 1&amp;2). In Phase I, systemic immune activation was demonstrated in the majority of patients using an IFNƔ ELISPOT assay. A randomized Phase 2 assessment of Vigil maintenance therapy vs. observation in ovarian cancer demonstrated prolonged relapse free survival (RFS) (Oh J, Barve M, et al. Gynecologic Oncology, 2016; 143: 504–510.). Based on these observations, a Phase 3 study of maintenance Vigil therapy in patients with advanced ovarian cancer was initiated (NCT02346747). Methods: This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study of maintenance Vigil in women with Stage IIIb,c or IV high-grade papillary serous/clear cell/ endometrioid ovarian, fallopian tube or primary peritoneal cancer. Patients will have a minimum of 4 and a maximum of 12 Vigil doses manufactured from tumor obtained at primary debulking surgery. Patients must achieve a complete clinical remission following primary surgery and chemotherapy before being randomized 1:1 to receive either monthly intradermal Vigil or placebo. Randomization is stratified by extent of surgical cytoreduction (complete/microscopic vs. macroscopic residual disease) and neoadjuvant vs. adjuvant chemotherapy. The primary objective is to compare RFS of subjects randomized to Vigil vs. placebo, and the key secondary objective is overall survival (OS). The sample size calculation of 222 patients assumes 24 months for accrual and 36 months of follow-up with a median RFS of 19 months from randomization, in the control group. This provides 90% power to detect a hazard ratio (HR) of 0.6 favoring Vigil at the 0.05 level of significance. To date, 61 patients have been randomized and an additional 55 patients are receiving chemotherapy in anticipation of randomization. Tumor tissue is being obtained from approximately 20 patients per month at multiple sites across the U.S. At their last meeting in January, 2017 the independent DSMB recommended that the study continue without change. Clinical trial information: NCT02346747.

Minimal access surgery compared to laparotomy for secondary surgical cytoreduction in patients with recurrent ovarian carcinoma: Perioperative and oncologic outcomes

ObjectivesTo assess the perioperative outcomes of minimal access surgery (MAS) in secondary surgical cytoreduction (SSCR) for recurrent epithelial ovarian cancer (ROC); to compare oncologic outcomes with laparotomy (LAP). MethodsUsing an institutional database, we identified all patients with ROC undergoing SSCR from 1/5/09–6/14/14. Selection for MAS or LAP was based on surgeon preference. To minimize selection bias, preoperative imaging was reviewed for all LAP cases. In this manner, we identified potential MAS candidates, who were used in the comparison. Intent-to-treat analyses were undertaken using statistical testing. Results170 cases were identified (131 LAP, 8 LSC, 31 RBT). 68/131 (52%) LAP cases were deemed potential candidates for MAS. Feasibility analyses included 68 LAP and 39 MAS cases. Six (15%) MAS cases were converted to LAP. Median age, BMI, operative time did not differ significantly between the groups. Complete gross resection was achieved in 37/39 (95%) MAS, 63/68 (93%) LAP (P=1.0). Median estimated blood loss was 50cm3 (range, 5–500) MAS, 150cm3 (range, 0–1500) LAP (P=0.001). Median length of stay was 1day (range, 0–23) MAS, 5days (range, 1–21) LAP (P<0.001). Complications occurred in 3/39 (8%) MAS, 15/68 (22%) LAP (P=0.06). The 2-year progression-free survival was 56.1% (SE 9%) MAS, 63.5% (SE 6%) LAP (P=1.0). The 2-year overall survival was 92.2% (SE 5.4%) MAS, 81.4% (SE 5.5%) LAP (P=0.7). ConclusionsMAS for SSCR is feasible in properly selected cases. MAS is associated with favorable perioperative outcomes and similar oncologic outcomes, compared to LAP.

Abstract IA13: A practical approach to reducing the burden of ovarian cancers

Abstract Ovarian cancer has seen a modest improvement in five-year survival over the past three decades. It is well known that the lack of further success is solely due to the advanced stage at diagnosis for most women with ovarian cancers. To reduce the burden of ovarian cancer, we must decrease the incidence (primary prevention), improve early detection (secondary prevention), or develop more effective treatments for newly diagnosed disease (tertiary prevention). Large scale screening trials using traditional methods of imaging and tumor markers have not led to meaningfully stage migration, reduction in mortality, or widespread clinical adoption. In fact, the FDA recently issued a safety alert about the risks associated with the use of tests being marketed as ovarian cancer screening tests. The FDA was specifically concerned about ovarian cancer screening tests being used in lieu of established risk-reduction approaches. This presentation will review practical approaches to reducing the burden of ovarian cancer through primary, secondary, and tertiary prevention. Genetic testing of probands for BRCA1 and BRCA2 germline mutations alone and cascade testing of relatives are currently available approaches to reduce the incidence of ovarian cancer by more than 10%. This tactic is consistent with professional guidelines and has the added advantage of identifying therapeutic options for ovarian cancer patients that could contribute to tertiary prevention efforts today and in the future. Lower penetrant genes also have the potential to lead to primary prevention through risk reduction strategies, but further data is required to firmly establish appropriate age-based recommendations. The identification of the distal fallopian tube as a likely site of origin for most ovarian cancers has opened a new domain for ovarian cancer primary prevention. Some governmental organizations suggest population-based bilateral salpingectomy at the time of any pelvic or abdominal surgery for primary prevention of ovarian cancers considering that one-third of US women will have a hysterectomy by age 70. The reasons for success and failure of this approach will be discussed. The fallopian tube as the site of origin for ovarian cancers has led to new approaches for early detection. The anatomy of the fallopian tube and its proximity to the lower genital tract has led to the development of creative strategies for sampling derivatives of precursor lesions and early invasive disease. Collection of uterine fluid for proteomic analyses and DNA sequencing holds promise for enrichment of cancer-specific biomolecules. Cervical pap smears and the collection of vaginal secretions offer a less invasive approach to early detection through similar theoretical avenues. Through the study of long-term survivors of advanced stage high-grade serous ovarian cancer, we have learned that primary surgical cytoreduction reduces the risk of cancer recurrence and serves as a useful approach to tertiary prevention. Citation Format: Douglas A. A practical approach to reducing the burden of ovarian cancers. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr IA13.

Bevacizumab and paclitaxel–carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial

Platinum-based chemotherapy doublets are a standard of care for women with ovarian cancer recurring 6 months after completion of initial therapy. In this study, we aimed to explore the roles of secondary surgical cytoreduction and bevacizumab in this population, and report the results of the bevacizumab component here. The multicentre, open-label, randomised phase 3 GOG-0213 trial was done in 67 predominantly academic centres in the USA (65 centres), Japan (one centre), and South Korea (one centre). Eligible patients were adult women (aged ≥18 years) with recurrent measurable or evaluable epithelial ovarian, primary peritoneal, or fallopian tube cancer, and a clinical complete response to primary platinum-based chemotherapy, who had been disease-free for at least 6 months following last infused cycle of platinum. Patients were randomly assigned (1:1) to standard chemotherapy (six 3-weekly cycles of paclitaxel [175 mg/m2 of body surface area] and carboplatin [area under the curve 5]) or the same chemotherapy regimen plus bevacizumab (15 mg/kg of bodyweight) every 3 weeks and continued as maintenance every 3 weeks until disease progression or unacceptable toxicity. Individuals who participated in both the bevacizumab objective and surgical objective (which is ongoing) were randomly assigned (1:1:1:1) to receive either of these two chemotherapy regimens with or without prior secondary cytoreductive surgery. Randomisation for the bevacizumab objective was stratified by treatment-free interval and participation in the surgical objective. The primary endpoint was overall survival, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00565851. Between Dec 10, 2007, and Aug 26, 2011, 674 women were enrolled and randomly assigned to standard chemotherapy (n=337) or chemotherapy plus bevacizumab (n=377). Median follow-up at the end of the trial on Nov 5, 2014, was 49·6 months in each treatment group (IQR 41·5-62·2 for chemotherapy plus bevacizumab; IQR 40·8-59·3 for chemotherapy), at which point 415 patients had died (214 in the chemotherapy group and 201 in the chemotherapy plus bevacizumab group). Based on pretreatment stratification data, median overall survival in the chemotherapy plus bevacizumab group was 42·2 months (95% CI 37·7-46·2) versus 37·3 months (32·6-39·7) in the chemotherapy group (hazard ratio [HR] 0·829; 95% CI 0·683-1·005; p=0·056). We identified incorrect treatment-free interval stratification data for 45 (7%) patients (equally balanced between treatment groups); a sensitivity analysis of overall survival based on the audited treatment-free interval stratification data gave an adjusted HR of 0·823 (95% CI 0·680-0·996; p=0·0447). In the safety population (all patients who initiated treatment), 317 (96%) of 325 patients in the chemotherapy plus bevacizumab group had at least one grade 3 or worse adverse event compared with 282 (86%) of 332 in the chemotherapy group; the most frequently reported of these in the chemotherapy plus bevacizumab group compared with the chemotherapy group were hypertension (39 [12%] vs two [1%]), fatigue (27 [8%] vs eight [2%]), and proteinuria (27 [8%] vs none). Two (1%) treatment-related deaths occurred in the chemotherapy group (infection [n=1] and myelodysplastic syndrome [n=1]) compared with nine (3%) in the chemotherapy plus bevacizumab group (infection [n=1], febrile neutropenia [n=1], myelodysplastic syndrome [n=1], secondary malignancy [n=1]; deaths not classified with CTCAE terms: disease progression [n=3], sudden death [n=1], and not specified [n=1]). The addition of bevacizumab to standard chemotherapy, followed by maintenance therapy until progression, improved the median overall survival in patients with platinum-sensitive recurrent ovarian cancer. Although the intention-to-treat analysis for overall survival was not significant, our sensitivity analysis based on corrected treatment-free interval stratification indicates that this strategy might be an important addition to the therapeutic armamentarium in these patients. National Cancer Institute and Genentech.

Influence of Simultaneous Liver and Peritoneal Resection on Postoperative Morbi-Mortality and Survival in Patients With Colon Cancer Treated With Surgical Cytoreduction and Intraperitoneal Hyperthermic Chemotherapy

IntroductionCytoreductive surgery plus intraperitoneal hyperthermic chemotherapy (HIPEC) has recently been established as the treatment of choice for selected patients with peritoneal carcinomatosis of colonic origin. Until recently, the simultaneous presence of peritoneal and hepatic dissemination has been considered a contraindication for surgery. The aim of this paper is to analyze the morbidity, mortality and survival of patients with simultaneous peritoneal and hepatic resection with HIPEC for peritoneal carcinomatosis secondary to colon cancer. MethodsBetween January 2010 and January 2015, 61 patients were operated on, 16 had simultaneous peritoneal and hepatic dissemination (group RH+), and 45 presented only peritoneal dissemination (group RH−). ResultsThere were no differences between the groups in terms of demographic data, length of surgery and extension of peritoneal disease. Postoperative grade III–V complications were significantly higher in the RH+ group (56.3 vs 26.6%; P=0.032). For the whole group, mortality rate was 3.2% (two patients in group RH−, and none in group RH+). Patients with liver resection had a longer postoperative stay (14.4 vs 23.1 days) (P=.027). Median overall survival was 33 months for RH−, and 36 for RH+ group. Median disease-free survival was 16 months for RH−, and 24 months for RH+ group. ConclusionsSimultaneous peritoneal cytoreduction and hepatic resection resulted in a significantly higher Clavien grade III–V morbidity and a longer hospital stay, although the results are similar to other major abdominal interventions. The application of multimodal oncological and surgical treatment may obtain similar long-term survival results in both groups.

Intra-Thoracic Chemo-Hyperthermia for pleural recurrence of thymoma

BackgroundPleural recurrences are a hallmark of thymomas, and represent a challenge for multidisciplinary management. The purpose of this study was to assess the feasibility and the results in terms of morbidity, mortality and survival rates, of Intra-Thoracic Chemo-Hyperthermia (ITCH) for the treatment of pleural recurrences of thymomas. MethodsRetrospective analysis of 19 consecutives patients between 1997 and 2015 treated by surgical cytoreduction (pleurectomy) followed by ITCH with 25mg/m2 of mitomycin, and 50mg/m2 of Cisplatin. ResultsThere were 8 men and 11 women with a median age of 44 years. ITCH was combined with pleurectomy alone in 4 (22%) patients, pleurectomy and wedge resections in 14 (74%) patients; 1 (5%) patient had a pleuropneumonectomy. There were no perioperative deaths, and 5 patients (26%) presented with postoperative complication, including 3 (16%) cases related to chemotherapy (one case of reversible grade 2 bone marrow aplasia, and 2 cases of reversible, acute kidney failure). The median length of stay in intensive care unit and hospital were 1day and 10days, respectively. After a median follow-up period of 39 months (range 10–127 months), median disease-free survival was 42 months. Five patients (26%) died during follow-up. ConclusionsOur data indicate that ITCH is a feasible option for selected patients with pleural recurrence of thymomas. ITCH clearly provides long local control, without major safety issues, and prolonged survival may be achieved in selected patients. This therapeutic option should be discussed at a multidisciplinary tumor board.

Aggressive Surgical Approach to the Management of Neuroendocrine Tumors: A Report of 1,000 Surgical Cytoreductions by a Single Institution

Neuroendocrine tumors (NETs) are rare neoplasms. Our group has treated more than 2,000 NET patients and has performed more than 1,000 surgical cytoreductive procedures. Records of 834 NET patients who underwent surgical cytoreduction at our institution were reviewed. Demographic information, intraoperative findings, extent of disease, complications, and survival rates were calculated. Eight hundred patients underwent 1,001 cytoreductive operations. Sixty-five percent had small bowel primaries. One hundred and thirty-eight patients presented with an unknown primary site, which was localized intraoperatively in 89% of these cases. The intraoperative complication rate was 9%. The incidence of intraoperative carcinoid crisis was 1%. Mean ± SD operative time was 368 ± 146 minutes. Mean ± SD hospital stay was 9 ± 10 days. Minor postoperative complications occurred after 43% of procedures and major postoperative complications were noted after 19% of procedures. The 30-day postoperative mortality rate was 2%. Median overall survival (OS) for patients with pancreatic NETs was 124 months. The 5-, 10-, and 20-year OS rates for patients with pancreatic NETs were 67%, 51%, and 36%, respectively. The life expectancy difference (between OS and actuarial survival) after surgical cytoreduction for patients with pancreatic NETs was 16.6 years. Median OS for patients with small bowel NETs was 161 months. The 5-, 10-, and 20-year OS rates for patients with small bowel NETs were 84%, 67% and 31%, respectively. The life expectancy difference after surgical cytoreduction for patients with small bowel NETs was 11.7 years. Surgical cytoreduction in NET patients has low morbidity and mortality rates and results in prolonged survival. We believe that surgical cytoreduction should play a major role in the care of patients with NETs.

Early Data Of Patients With Pseudomyxoma Peritonei From Appendiceal Origin Treated By A Strategy Of Cytoreductive Surgery And Hyperthermic Intraperitoneal Chemotherapy

Background. Appendiceal peritoneal pseudomyxoma (PMP) is very rare disease and its longterm prognosis is poor. The aim of this study was to evaluate the results of an aggressive treatment approach used in our institution for the last 4 years. Methods. We selected all patients with PMP from appendiceal origin who were treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) at the Klaipeda University Hospital between January 2012 and January 2016. Data from all patients with PMP arising from the appendix were retrospectively collected and analyzed. Treatment consisted of complete surgical cytoreduction , followed by hyperthermic intraperitoneal chemotherapy with mitomycin at 42°C over 90 minutes. Ronnett’s hystologic classification was used for tumor grading. Results. A total of 6 patients underwent cytoreduction and peritonectomy plus HIPEC. Median age at diagnosis was 57 years (range, 39-67). All our patients were female. The previous surgery score at the moment of admission was PSS-2 for three patients, PSS-3 for 3 patients. Four patients were diagnosed as diffuse peritoneal adenomucinosis (DRAM) and two as peritoneal mucinous carcinomatosis( PMCA). In all of the patients, optimal cytoreduction CC-0 (5 patients) and CC-1 (one patient) was achieved. The median peritoneal cancer index (PCI) was 17 (range, 14-25) as an indicator of disease extension.The median number of visceral resections performed per patient was 3 (range, 1-5). The median duration of CRS/HIPEC was 8 hours and 10 minutes (range, 7 hours and10 min. to 9 hours 20 min). Mean postoperative stay was 13 days (range, 8-18). The 30 days postoperative and in-hospital mortality were zero . One patient experienced temporary haemorhagic cystitis. The mean follow-up period was 28 months ( range, 8-45). At the time of analysis all patients are alive and without recurrence. Conclusions PMP from appendiceal origin can be treated with curative intent in a large percentage of cases by cytoreductive surgery associated with HIPEC. This new approach could be performed safely with acceptable morbidity and mortality in selected patients treated in specialized centers.

Beyond the Beyond: First Case of 9 Cytoreductive Surgeries in a Long-Surviving Ovarian Cancer Patient: Case Report

The role of surgery in recurrent ovarian cancer (ROC) is debated. Multiple prospective and retrospective series reported improved survival with optimal secondary surgical cytoreduction, but definitive results from randomized trials are needed. Up to the fourth cytoreductive surgery for recurrent disease in an attempt to improve patients' prognosis has been reported. We report the first case of multiple ROC in an Italian woman, 50 years old at diagnosis, who underwent 9 cytoreductive surgeries during her 17 years of disease with no serious postoperative complications. Multiple surgeries should not be considered as the standard treatment for ROC. In carefully selected patients, optimal cytoreductive surgery performed by highly specialized gynecologic oncologists might represent a useful tool in adjunction to chemotherapy for the management of ROC.

Treatment of peritoneal carcinomatosis from ovarian cancer by surgical cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Ovarian cancer is an “intraperitoneal disease” by itself. When first standard treatment fails, usually, the disease is characterized by poor prognosis. Encouraging results have been reported by the treatment of peritoneal carcinomatosis (PC) from epithelial ovarian cancer (EOC) by complete surgical cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC). The purpose of this study is to evaluate survival benefit and morbidity of patients with recurrent EOC treated by cytoreductive surgery and HIPEC.

Surgical cytoreduction and hyperthermic intraperitoneal chemotherapy in patients affected by recurrent or persistent peritoneal carcinomatosis form epithelial ovarian cancer with high peritoneal cancer index values: Our single center experience

Surgical cytoreduction and hyperthermic intraperitoneal chemotherapy in patients affected by recurrent or persistent peritoneal carcinomatosis form epithelial ovarian cancer with high peritoneal cancer index values: Our single center experience

The optimal time for surgery in women with serous ovarian cancer.

Advanced high-grade serous ovarian carcinoma (HGSC) is commonly treated with surgery and chemotherapy. We investigated the survival of patients treated with primary or interval surgery at different times following neoadjuvant chemotherapy. Their survival was compared with that of patients treated with primary cytoreductive surgery and adjuvant chemotherapy. Patients with stage III or IV HGSC were included in this retrospective cohort study. Clinical data were obtained from patient records. Patients were divided into 2 groups based on treatment with neoadjuvant chemotherapy and interval cytoreductive surgery (NAC) or with primary cytoreductive surgery and adjuvant chemotherapy (PCS). Study groups were stratified by several clinical variables. We included 334 patients in our study: 156 in the NAC and 178 in the PCS groups. Survival of patients in the NAC group was independent of when they underwent interval cytoreductive surgery following initiation of neoadjuvant chemotherapy (p < 0.001). Optimal surgical cytoreduction had no impact on overall survival in the NAC group (p < 0.001). Optimal cytoreduction (p < 0.001) and platinum sensitivity (p < 0.001) were independent predictors of improved survival in the PCS but not in the NAC group. Patients in the NAC group had significantly worse overall survival than those in the PCS group (31.6 v. 61.3 mo, p < 0.001). Women with advanced HGSC who underwent PCS had better survival than those who underwent interval NAC, regardless of the number of cycles of neoadjuvant therapy. Optimal cytoreduction did not provide a survival advantage in the NAC group.

Abstract 1089: Cardiac glycosides affect miRNA expression profiles in renal cell carcinoma cell lines

Abstract Background: Renal Cell Carcinoma (RCC) is the ninth most common cancer worldwide, with about 338,000 new cases diagnosed in 2012. Especially metastatic renal cell carcinoma has still despite surgical cytoreduction, VEGF-tyrosine kinase inhibitors, mTOR inhibitors and first promising results of immunotherapies a very poor prognosis what implies an urgent need for additional therapies. Cardiac glycosides have come into the focus as potential cancer treatment option. They can have anti-proliferative and apoptotic characteristics in several cancer cell lines but affect only in a much lesser extent normal cell lines. MicroRNAs are small non-coding RNAs of 17-25 nucleotides length that widely exist and they play an important regulating role in many normal and pathophysiological cellular processes, as cell proliferation, differentiation, induction of apoptosis, tumorigenesis and tumor progression. Material and Methods: Four renal cell carcinoma cell lines were treated with three different cardiac glycosides in the IC50 concentrations during 72h. For the investigation of miRNA expression miRNA microarray expression analyses were performed. In silico target gene and pathway enrichment analyses were performed. Results: An overlap between all treatments and all cell lines could be detected for two mature miRNAs and two premature miRNAs. Pathway enrichment analysis identified MAPK and axon guidance pathways. Moreover, we looked for genes predicted to be regulated by the deregulated miRNAs in all cell lines at all treatments in the MAPK and the axon guidance pathways. Conclusion: The identification and characterization of deregulated miRNAs after cardiac glycoside treatment could give insight in their gene regulation and thus help to clarify the molecular basis of their anti-proliferative and apoptotic effects. Citation Format: Elke Nolte, Sven Wach, Izabella T. da Silva, Arif Ekici, Frieder Müller-Uri, Wolfgang Kreis, Julio Vera-Gonzales, Bernd Wullich, Helge Taubert, Xin Lai. Cardiac glycosides affect miRNA expression profiles in renal cell carcinoma cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1089.

High levels of pretreatment CA125 are associated to improved survival in high grade serous ovarian carcinoma.

BackgroundSerum levels of CA125 measured before any treatment have been evaluated in epithelial ovarian cancer (EOC) as a predictor of patient survival; however, results in survival index are controversial, as CA125 levels are influenced by several variables. Taking this into consideration, the present study evaluated the association of pretreatment levels of CA125 serum with the clinical stage, histology and differentiation grade of the tumor and the survival rate in a group of patients from an oncology referral center in Mexico, all of them diagnosed with ovarian carcinoma.This retrospective study consisted of 1009 patients with EOC, diagnosed between 2006 and 2013 at the National Cancerology Institute (Instituto Nacional de Cancerología-INCan), considering only those with CA125 measurements before any chemotherapy or surgical cytoreduction. Patients with three years of medical follow-up having pretreatment CA125 value and simultaneous diagnoses of histological subtype, clinical stage and differentiation grade of the tumor (n = 656) were studied in order to determine their survival rate.ResultsThe abnormal level (>35 U/mL) of CA125 was observed in 99 % of serous carcinoma cases rated I to IV in the FIGO stages. Abnormal CA125 proportions were 89 % in endometrioid subtype and 69 % in mucinous tumors, with the highest absolute value of CA125 observed in serous carcinoma surpassing any other histological subtype. Clinical stages III and IV displayed increased CA125 values compared to stages I and II. Undifferentiated carcinomas show the highest level of this indicator compared with those of low and moderate differentiated grade. Survival evaluation by Kaplan-Meier analysis including only high grade serous carcinoma at FIGO stage III (n = 57) demonstrated 57.1 % chances of survival in patients with CA125 pretreatment levels higher than 500 U/mL. Survival was 26.7 % in patients with CA125 lower than 500 U/mL and the hazard ratio for CA125 ≤ 500 U/mL was 2.28, 95 % CI 1.08–4.84, P = 0.032.ConclusionsClinical stage associated with pretreatment absolute values of CA125 should be considered as prognostic factor in EOC patients. Values of CA125 higher than 500 U/mL in high grade serous carcinoma with FIGO stage III resulted in an enhanced survival rate of the patients.

Editorial Comment

Surgical cytoreduction has been an integral component of multimodal therapy for metastatic renal cell carcinoma (mRCC) since the seminal reports supporting cytoreductive nephrectomy (CN) were published. 1 Mickisch G.H. Garin A. van Poppel H. et al. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomized trial. Lancet. 2001; 358: 966-970 Abstract Full Text Full Text PDF PubMed Scopus (1183) Google Scholar , 2 Flanigan R.C. Salmon S.E. Blumenstein B.A. et al. Nephrectomy followed by interferon Alfa-2b compared to interferon Alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001; 345: 1655-1659 Crossref PubMed Scopus (1415) Google Scholar With the introduction and adoption of targeted therapies and increasing enthusiasm for checkpoint inhibition, the role and sequential timing of CN are now the source of considerable debate. Given the emerging data associating CN with significant perioperative morbidity, critical consideration of optimal patient selection remains paramount.

Prediction of 5-year survival in advanced-stage ovarian cancer patients based on computed tomography peritoneal carcinomatosis index.

To evaluate whether the quantification of peritoneal metastases in advanced-stage ovarian cancer patients using the peritoneal carcinomatosis index, detected by CT (CT-PCI), correlates with the serum levels of tumor marker CA-125 and 5-year survival. The CT-PCI was determined in 82 patients with stage III or stage IV ovarian cancer using the Sugarbaker classification prior to cytoreductive surgery. Linear regression analysis was used to correlate CT-PCI and CA-125 levels. Correlation of presurgical CT-PCI, optimal surgical cytoreduction, and 5-year survival was established using binary logistic regression analysis. A score for prediction of 5-year survival probability was established using multivariate backwards binary logistic regression. Presurgical CT-PCI correlates significantly with presurgical CA-125 serum levels (r=0.487, P<0.001). Multivariate binary logistic regression suggested significantly improved 5-year survival with lower CT-PCI and lower ECOG performance scores. CT-PCI allows quantification of peritoneal disease in advanced-stage ovarian cancer patients, similar to CA-125. CT-PCI in combination with ECOG performance has the potential to help evaluate the 5-year survival probability.

Digestive resections in advanced-stage ovarian cancer

The standard frontline treatment for advanced-stage ovarian cancer (ASOC) consists of maximal cytoreduction surgery associated with platinum/paclitaxel-based chemotherapy. Several studies have proven that patients with no gross residual disease (RD) have better survival rates than those with optimal but visible RD (RD ≤1 cm). In order to achieve this, more radical cytoreductive procedures such as radical pelvic resection and extensive upper abdominal procedures are performed. However, some investigators have suggested that, although effective, radical surgery cannot fully compensate tumor biology, which is a major determinant in survival and in turn influences the likelihood of surgical cytoreduction. The aim of this review was to present the procedures defining ultra-radical (extensive) surgery and to evaluate its feasibility and morbidity in the management of ASOC.

Optimal according to whom? Interobserver variability in surgical cytoreduction for advanced ovarian carcinoma

Optimal according to whom? Interobserver variability in surgical cytoreduction for advanced ovarian carcinoma