Longer operative time is associated with increased post-operative complications in patients undergoing minimally-invasive surgery for endometrial cancer.

OBJECTIVE: To examine the impact of operative time on the development of post-operative medical and surgical complications in patients undergoing minimally-invasive surgery for endometrial cancer. METHODS: Patients who underwent laparoscopic surgery for endometrial cancer from 2005 to 2014 were identified from the ACS-NSQIP database. Operative times were initially divided into hour-long intervals and complication rates were determined. Outcomes included development of any complication, medical complication, or surgical complication. Subsequent analysis were based on dividing patients into 2 groups based on operative times <240min and operative times ≥240min. Associations between categorical variables were determined using Chi-Squared and Fisher's exact tests. Differences between means of continuous variables were determined using Student's t-tests. Univariate and multivariate analysis using logistic regression were used to identify predictors of post-operative complications. RESULTS: 9145 patients were included, of which 639 (7%) experienced a complication. As operative time increased, rates of complications also increased. Operative time ≥240min was associated with increased overall complication rate (11.7% vs. 6%, p<0.001), medical complication rate (9.3% vs. 4.2%, p<0.001), and surgical complication rate (3.9% vs. 2.4%, p=0.001). When performing multi-variate logistic regression of factors associated with increased complication rates, increased operative time, COPD, hypertension, diabetes, ASA class ≥3, dependent functional status, and chronic steroid use were found to be independently associated with increased complications. Lymphadenectomy was not associated with increased operative time or increase in complications. CONCLUSION: Increased operative time is independently associated with increased risk of developing complications after laparoscopic surgery for endometrial cancer.

Lynch Syndrome and Endometrial Cancer.

In patients with Lynch syndrome, gynecologic cancer often can be the first presenting malignancy. In this review, we summarize the genetics of Lynch syndrome and review the various modalities of identifying patients at risk for this syndrome. The clinical characteristics of Lynch-associated endometrial cancer and screening and risk-reducing strategies also are described.

Preoperative predictors of delay in initiation of adjuvant chemotherapy in patients undergoing primary debulking surgery for ovarian cancer.

OBJECTIVE: The objective of this study was to identify preoperative characteristics of patients that experience a delay in initiation of adjuvant chemotherapy after primary debulking surgery for ovarian cancer. MATERIALS/METHODS: We performed a retrospective review of patients with Stage II to IV high-grade epithelial ovarian, tubal, and peritoneal carcinoma who underwent primary debulking surgery followed by adjuvant chemotherapy from 2005 to 2013. Patients were divided into 2 groups: Control (those who received their first cycle of chemotherapy within 6weeks of debulking surgery) vs. chemotherapy delay (those who received their first cycle of chemotherapy at an interval >6weeks from primary debulking surgery). Relevant clinical variables and survival outcomes were compared between the 2 groups using standard statistical methods. RESULTS: A total of 221 patients were included in the analyses - 169 (76.5%) were in the control group and 52 (23.5%) were in the chemo delay group. On multi-variate analysis, risk factors that were significantly associated with a delay in initiation in chemotherapy included: age >65, albumin <3.5, and high age-adjusted Charlson Comorbidity Index score. Delay in chemotherapy initiation was associated with a shorter progression-free (p=0.014) but not overall survival (p=0.19). CONCLUSIONS: Delay in initiation of chemotherapy affected 23.5% of patients in our study population. Easily identifiable risk factors for chemotherapy delay exist that can help us pre-operatively identify patients for which neoadjuvant chemotherapy may be a better treatment option. Further study into prospective modeling with these identified risk factors is warranted.

Patterns of First Recurrence in African American Patients with High Grade Epithelial Ovarian Carcinoma.

BACKGROUND/AIMS: The aim of this study is to compare the distribution of anatomic sites of first recurrence in African American (AA) patients with ovarian carcinoma compared to Caucasians. METHODS: Patients diagnosed with high-grade epithelial ovarian, fallopian tube or peritoneal carcinoma from 2007 to 2013 were identified. Patterns of recurrence were compared for AA and Caucasian patients. Progression-free survival (PFS) and overall survival (OS) were compared. RESULTS: A total of 238 patients were included - 210 Caucasians and 28 AAs. At a follow-up time of 28 months, AAs were more likely to have multiple anatomic sites of recurrence rather than a single site when compared to Caucasians (63.6 vs. 35.5%, p = 0.01). Time to first recurrence was shorter for AA patients (12 vs. 18 months, p < 0.01). PFS and OS did not differ. AA patients with multiple sites of first recurrence had a significantly shorter OS than Caucasian patients with multiple sites of first recurrence (24 vs. 30 months, p = 0.022). CONCLUSION: Patterns of first recurrence differ between AAs and Caucasians. AAs have shorter times to first recurrence and are more likely to have multiple anatomic sites involved. AA patients with multiple sites of recurrence have a shorter OS than Caucasian patients with multiple sites.

Wandering Spleen. A Case of Spontaneous Hemoperitoneum in an HIV-positive Patient with Recurrent Tuboovarian Abscess.

BACKGROUND: Wandering spleen is a rare and potentially devastating condition that can present in a variety of ways. Here we present a case that led to acute abdomen and hemoperitoneum in a young woman. CASE: A 27-year-old woman with a history of human immunodeficiency virus (HIV), pelvic inflammatory disease, and tuboovarian abscess was readmitted to the hospital for intravenous antibiotic treatment. When her clinical picture did not improve, she underwent placement of a pelvic drain for abscess drainage. Overnight she developed an acute abdomen and hemorrhagic shock. She was taken to the operating room for an exploratory laparotomy, which revealed a ruptured spleen with a single, elongated vascular pedicle. CONCLUSION: Wandering spleen is a rare diagnosis, more common in reproductive-aged women, with potentially fatal complications. It is a necessary component of a differential diagnosis for acute abdomen in reproductive-aged women.

Radiochemotherapy plus 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in advanced-stage cervical and vaginal cancers.

OBJECTIVE: Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy. METHODS: We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, 25 mg/m(2)) co-administered with 1× weekly intravenous cisplatin (40 mg/m(2)) and daily pelvic radiation (45 Gy) in women with stage I(B2)-IV(B) cervical (n=22) or stage II-IV vaginal (n=3) cancers. Brachytherapy followed (40 Gy). Toxicity was monitored by common terminology criteria for adverse events (version 3.0). The primary end point of response was assessed by 3-month posttherapy 2-[(18)F] fluoro-2-deoxy-d-glucose positron emission tomography (PET/CT) and clinical examination. RESULTS: 3-AP radiochemotherapy achieved clinical responses in 24 (96% [95% confidence interval: 80-99%]) of 25 patients (median follow-up 20 months, range 2-35 months). 23 (96% [95% confidence interval: 80-99%]) of 24 patients had 3-month posttherapy PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. The most frequent 3-AP radiochemotherapy-related adverse events included fatigue, nausea, diarrhea, and reversible hematological and electrolyte abnormalities. CONCLUSIONS: The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal cancers. Future randomized phase II and III clinical trials of 3-AP radiochemotherapy are warranted.

Small-Molecule-Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death.

High-grade serous carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP inhibitors (PARPi) have become the mainstay of HGSC-targeted therapy, given that these tumors are driven by a high degree of genomic instability (GI) and homologous recombination (HR) defects. Nonetheless, approximately 30% of patients initially respond to treatment, ultimately relapsing with resistant disease. Thus, despite recent advances in drug development and an increased understanding of genetic alterations driving HGSC progression, mortality has not declined, highlighting the need for novel therapies. Using a small-molecule activator of protein phosphatase 2A (PP2A; SMAP-061), we investigated the mechanism by which PP2A stabilization induces apoptosis in patient-derived HGSC cells and xenograft (PDX) models alone or in combination with PARPi. We uncovered that PP2A genes essential for cellular transformation (B56α, B56γ, and PR72) and basal phosphatase activity (PP2A-A and -C) are heterozygously lost in the majority of HGSC. Moreover, loss of these PP2A genes correlates with worse overall patient survival. We show that SMAP-061-induced stabilization of PP2A inhibits the HR output by targeting RAD51, leading to chronic accumulation of DNA damage and ultimately apoptosis. Furthermore, combination of SMAP-061 and PARPi leads to enhanced apoptosis in both HR-proficient and HR-deficient HGSC cells and PDX models. Our studies identify PP2A as a novel regulator of HR and indicate PP2A modulators as a therapeutic therapy for HGSC. In summary, our findings further emphasize the potential of PP2A modulators to overcome PARPi insensitivity, given that targeting RAD51 presents benefits in overcoming PARPi resistance driven by BRCA1/2 mutation reversions.

A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study.

PURPOSE: This multi-institutional phase II trial assessed the activity and tolerability of the anti-metastatic A6 peptide that binds CD44 in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC/FTC/PPC). PATIENTS AND METHODS: Women with persistent or recurrent EOC/FTC/PPC were eligible for participation if they had measurable disease defined by RECIST criteria, good performance status, and good overall organ function. Patients must have received one prior platinum-based chemotherapeutic regimen and were allowed to have received one additional cytotoxic regimen for the management of recurrent or persistent disease. Women received a 150 mg twice daily subcutaneous dose of A6 and continued on treatment until disease progression or unacceptable toxicity. Primary measures of clinical efficacy were objective tumor response and progression-free survival (PFS) at 6 months. The association of CD44 in archival tissue specimens with clinical outcome was investigated. RESULTS: Thirty-one eligible patients were evaluated. No responses were observed. Two patients (6.5%) were progression free for at least 6 months. The median PFS was 2.0 months, and median overall survival has not yet been reached. One patient died of hemorrhage which was possibly study related. There were no grade 4 toxicities. The most common grade 3 toxicities were constitutional (2/31; 6.5%). Archival specimens were available for 27 patients, and 5 (18.5%) were CD44 positive by immunohistochemistry. CD44 expression was not associated with the 6-month PFS (p=0.342). CONCLUSION: A6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/FTC/PPC.

Mismatch repair status and outcomes after adjuvant therapy in patients with surgically staged endometrial cancer.

OBJECTIVES: To determine whether DNA mismatch repair (MMR) modifies the response to chemotherapy or radiotherapy in patients with endometrial cancer. METHODS: Immunohistochemistry (IHC) for the DNA MMR proteins MLH1, MSH2, MSH6, and PMS2 was performed on a tissue microarray of specimens of primary endometrial cancer. MMR deficiency was defined as lack of expression of one or more proteins. Expression of all proteins classified a tumor as having an intact MMR system. Recurrence rates were calculated for women treated with platinum-based chemotherapy or pelvic external beam radiation. Comparisons were made using the log-rank test. Multiple comparisons were controlled for by utilizing the Bonferroni correction method. RESULTS: Four hundred seventy-seven cases of endometrial cancer were evaluated on a tissue microarray (TMA). One hundred fifty-eight patients (41%) received chemotherapy. Sixty-six patients (17%) received pelvic teletherapy. Overall and progression-free survival were not different between patients whose tumors had intact MMR and those with defective MMR when stratified by adjuvant treatment with radiation or chemotherapy. Subgroup analyses stratified by histology (non-endometrioid versus endometrioid) and stage did show significant survival differences. There was a significant increase in overall (p=0.003) and progression-free (p=0.004) survival in those with MMR-deficient, non-endometrioid tumors treated with teletherapy compared to those with an intact MMR system. Improved progression-free survival was noted in patients with intact MMR with stage III/IV disease treated with adjuvant chemotherapy (p=0.031). CONCLUSIONS: Subgroups of patients with non-endometrioid endometrial cancer and defective MMR may have improved survival after adjuvant radiotherapy. Patients with advanced stage endometrial cancer and defects in mismatch repair may receive less benefit from adjuvant chemotherapy.

Comprehensive miRNA profiling of surgically staged endometrial cancer.

OBJECTIVE: We sought to determine a microRNA (miRNA) profile of surgically staged endometrial cancers. STUDY DESIGN: RNA was extracted from archival primary endometrial cancers, and an miRNA profile was established using a microarray and confirmed with real-time polymerase chain reaction. Targets of differentially expressed miRNAs were explored using real-time polymerase chain reaction and Western blot in endometrial cell lines. RESULTS: Endometrial cancer has an miRNA profile distinct from normal endometrium, even in patients with stage IA grade 1 tumors. This miRNA cancer profile was able to correctly assign a specimen as a malignancy with a sensitivity of 92%. Overexpressed miRNAs were predicted to target PTEN, and transfection of cell lines with these miRNAs led to down-regulation of PTEN expression. In advanced disease, an miRNA pattern distinct from early-stage disease was seen, and overexpression of mir-199c predicted improved cancer survival in this population. CONCLUSION: Endometrial cancer has a distinct miRNA profile, and miRNAs can be used as a predictive biomarker.

Lynch syndrome screening strategies among newly diagnosed endometrial cancer patients.

OBJECTIVE: To estimate the cost-effectiveness of screening strategies for Lynch syndrome among newly diagnosed endometrial cancer patients. METHODS: A decision analysis compared four strategies to screen women with newly diagnosed endometrial cancer for Lynch syndrome: 1) Amsterdam criteria strategy, where full gene sequencing was performed for women who meet Amsterdam criteria; 2) Sequence-all strategy, where full gene sequencing was performed for all women with endometrial cancer; 3) Sequence aged younger than 60 years strategy, where full gene sequencing was performed for women aged younger than 60 years with endometrial cancer; and 4) immunohistochemistry/single gene strategy, where immunohistochemistry was performed for the DNA mismatch repair genes for all women after single gene sequencing for specific women lacking protein expression. Prevalence rates, probabilities of immunohistochemistry staining loss, and gene mutation rates were calculated from published data. Costs were estimated from Medicare reimbursement rates. Cost-effectiveness ratios and incremental cost-effectiveness ratios were estimated for each strategy. RESULTS: For the estimated 40,000 women diagnosed annually with endometrial cancer, the sequence-all strategy detects 920 patients with Lynch syndrome at a cost of $105 million. The Amsterdam criteria give the least-expensive strategy ($7 million), but detect the fewest patients (n=83) with Lynch syndrome. The immunohistochemistry/single gene sequencing strategy detects 858 patients at a cost of $17 million; this strategy has an incremental cost-effectiveness ratio of $13,812. The sequence aged younger than 60 years strategy was less effective and more costly than other strategies. CONCLUSION: Of the strategies studied, immunohistochemical evaluation of tumor specimens for mismatch repair protein expression after single gene sequencing for patients with endometrial cancer is a cost-effective strategy for detecting Lynch syndrome. LEVEL OF EVIDENCE: : III.

Current and emerging trends in Lynch syndrome identification in women with endometrial cancer.

OBJECTIVE: Lynch syndrome is a heritable, cancer susceptibility syndrome. This study aims to review current and emerging trends in the identification of Lynch syndrome in the endometrial cancer patient population. METHODS: We performed a comprehensive review of past and present screening algorithms for Lynch syndrome, including a review of the utility of both the Amsterdam criteria and Bethesda guidelines. Because non-colon cancers have historically not been the focus of Lynch syndrome research, current literature is ripe with questions regarding screening among this patient population. Low BMI, age less than 50, positive family history and pathologic features have all been identified as risk factors in endometrial cancer patients who might benefit from Lynch screening. Additionally, based on experience at our own institution we offer a feasible screening algorithm for these patients. RESULTS: A comprehensive review of the data demonstrated that immunohistochemistry is becoming an efficient, inexpensive way to screen tumors at risk for mismatch repair deficiency. The sensitivity and specificity of immunohistochemistry for predicting Lynch syndrome approaches 100%. Ideally, prospective screening of all endometrial cancer patients with IHC is a feasible, cost-efficient way to detect Lynch in this patient population given the limitations of using personal/family history of malignancy as well as pathologic risk factors. CONCLUSION: It is imperative that clinicians be mindful of the risk of Lynch syndrome in women with endometrial cancer. Given the opportunity for colon cancer screening and prevention strategies to be initiated, the identification of probands with endometrial cancer as a result of Lynch syndrome will lead to a reduction in morbidity and mortality for these patients and their families.

The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform.

OBJECTIVE: To determine the utility of serum miRNAs as biomarkers for epithelial ovarian cancer. METHODS: Twenty-eight patients with histologically confirmed epithelial ovarian cancer were identified from a tissue and serum bank. Serum was collected prior to definitive therapy. Fifteen unmatched, healthy controls were used for comparison. Serum was obtained from all patients. RNA was extracted using a derivation of the single step Trizol method. The RNA from 9 cancer specimens was compared to 4 normal specimens with real-time PCR using the TaqMan Array Human MicroRNA panel. Twenty-one miRNAs were differentially expressed between normal and patient serum. Real-time PCR for the 21 individual miRNAs was performed on the remaining 19 cancer specimens and 11 normal specimens. RESULTS: Eight miRNAs of the original twenty-one were identified that were significantly differentially expressed between cancer and normal specimens using the comparative C(t) method. MiRNAs-21, 92, 93, 126 and 29a were significantly over-expressed in the serum from cancer patients compared to controls (p<.01). MiRNAs-155, 127 and 99b were significantly under-expressed (p<.01). Additionally, miRs-21, 92 and 93 were over-expressed in 3 patients with normal pre-operative CA-125. CONCLUSION: We demonstrate that the extraction of RNA and subsequent identification of miRNAs from the serum of individuals diagnosed with ovarian cancer is feasible. Real-time PCR-based microarray is a novel and practical means to performing high-throughput investigation of serum RNA samples. miRNAs-21, 92 and 93 are known oncogenes with therapeutic and biomarker potential.

Passive Monitoring of Mental Health Status in the Criminal Forensic Population.

Current approaches to monitoring patients' mental status rely heavily on self-reported symptomatology, clinician observation, and self-rated symptom scales. The limitations inherent in these methodologies have implications for the accuracy of diagnosis, treatment planning, and prognosis. Certain populations are particularly affected by these limitations because of their unique situations, including criminal forensic patients, who have a history of both criminal behavior and mental disorder, and experience increased stigma and restrictions in their access to mental health care. This population may benefit particularly from recent developments in technology and the growing use of mobile devices and sensors to collect behavioral information via passive monitoring. These technologies offer objective parameters that correlate with mental health status and create an opportunity to use Big Data and machine learning to refine diagnosis and predict behavior in a way that represents a marked shift from current practices. This article reviews the approaches to and limitations of psychiatric assessment and contrasts this with the promise of these new technologies. It then discusses the ethics concerns associated with these technologies and explores their potential relevance to criminal forensic psychiatry and the broader implications they carry for health and criminal justice policy.

The Highly Recurrent PP2A Aα-Subunit Mutation P179R Alters Protein Structure and Impairs PP2A Enzyme Function to Promote Endometrial Tumorigenesis.

Somatic mutation of the protein phosphatase 2A (PP2A) Aα-subunit gene PPP2R1A is highly prevalent in high-grade endometrial carcinoma. The structural, molecular, and biological basis by which the most recurrent endometrial carcinoma-specific mutation site P179 facilitates features of endometrial carcinoma malignancy has yet to be fully determined. Here, we used a series of structural, biochemical, and biological approaches to investigate the impact of the P179R missense mutation on PP2A function. Enhanced sampling molecular dynamics simulations showed that arginine-to-proline substitution at the P179 residue changes the protein's stable conformation profile. A crystal structure of the tumor-derived PP2A mutant revealed marked changes in A-subunit conformation. Binding to the PP2A catalytic subunit was significantly impaired, disrupting holoenzyme formation and enzymatic activity. Cancer cells were dependent on PP2A disruption for sustained tumorigenic potential, and restoration of wild-type Aα in a patient-derived P179R-mutant cell line restored enzyme function and significantly attenuated tumorigenesis and metastasis in vivo. Furthermore, small molecule-mediated therapeutic reactivation of PP2A significantly inhibited tumorigenicity in vivo. These outcomes implicate PP2A functional inactivation as a critical component of high-grade endometrial carcinoma disease pathogenesis. Moreover, they highlight PP2A reactivation as a potential therapeutic strategy for patients who harbor P179R PPP2R1A mutations. SIGNIFICANCE: This study characterizes a highly recurrent, disease-specific PP2A PPP2R1A mutation as a driver of endometrial carcinoma and a target for novel therapeutic development.See related commentary by Haines and Huang, p. 4009.

Robotic trocar site small bowel evisceration after gynecologic cancer surgery.

BACKGROUND: Trocar site hernia is a known, rare complication after laparoscopic surgery. We describe a case of bowel herniation, evisceration, and bowel obstruction through an 8-mm robotic port site. CASE: A 67-year-old patient with endometrial cancer underwent an uncomplicated robotic hysterectomy, bilateral salpingo-oophorectomy, and pelvic and aortic lymphadenectomy. Four days later, she presented with symptoms of a small bowel obstruction and was found to have evisceration through a laterally placed 8-mm robotic port site. The bowel was reduced locally and the fascial defect repaired without midline laparotomy or bowel resection. CONCLUSION: Bowel herniation can occur through the fascial defect after placement of an 8-mm robotic port. Continued reporting is needed to accurately gauge the occurrence of this complication.

Preoperative frailty is a risk factor for non-home discharge in patients undergoing surgery for endometrial cancer.

OBJECTIVE: Our objective was to examine the association of the modified frailty index (mFI) and non-home discharge in patients undergoing surgery for endometrial cancer (EMCA). METHODS: Patients who underwent surgery for EMCA from 2011 to 2012 were identified from the American College of Surgeons - Nastional Surigical Quality Improvement Project (ACS-NSQIP) database. Current Procedural Terminology (CPT) codes were used to identify surgical characteristics. We excluded patients who were already living in a non-home facility. To determine frailty, we used the NSQIP frailty index. For analysis purposes, patients with an mFI score ≥0.18 were defined as frail. Patients were divided into groups based on discharge destination. Logistic regression were used to identify predictors of post-operative non-home discharge. RESULTS: 1216 patients were identified. 26 (2.1%) were discharged to a non-home facility. On multivariate analysis, patients who were discharged to a non-home facility were older (OR 1.09, 95% CI 1.04-1.14, p < 0.001), had a higher Body Mass Index (BMI) (OR 1.08, 95% CI 1.04-1.12, p < 0.001), were more likely to have disseminated cancer (OR 10.02, 95% CI 2.28-44.1, p = 0.002), and were frail (OR 1.95, 95% CI 1.91-5.01, p = 0.008). Undergoing minimally-invasive surgery was independently associated with discharge to home (OR 0.165, 95% CI 0.059-0.458, p = 0.001). CONCLUSION: Frailty is associated with increased risk of non-home discharge in patients undergoing surgery for EMCA. The mFI can be easily calculated using patient characteristics that are readily available pre-operatively. This information can be used for pre-op counseling and to facilitate appropriate and timely discharge planning.

The Prognostic Value of Baseline Lymphocyte, Neutrophil, and Monocyte Counts in Locally Advanced Cervical Carcinoma Treated with Radiation.

Background. To determine the prognostic significance of pretreatment levels of circulating lymphocyte (CLC), neutrophil (CNC), and monocyte (CMC) counts in patients with locally advanced cervical carcinoma (CC) treated with definitive radiation. Methods. A retrospective, dual-institution review of patients with Stage IB2-IVA CC from 2005 to 2015. Progression-free (PFS) and Overall Survival (OS) were determined for high and low CLC, CNC, and CMC groups. Multivariate analysis was used to confirm prognostic value of baseline leukocyte counts. Results. 181 patients were included. Median follow-up time was 26 (3-89) months. CNC had no effect on PFS or OS. PFS was similar between CMC groups; however, OS was significantly improved for patients with low CMC (62.5 versus 45.3 months, p = 0.016). High CLC was associated with improved PFS (48.5 versus 27.8 months, p = 0.048) and OS (58.4 versus 34.9 months, p = 0.048). On multivariate analysis, high CNC was associated with increased relapse risk (HR 1.12, p = 0.006) and low CLC was associated with increased mortality risk (HR 0.67, p = 0.027). Conclusion. This study demonstrates that leukocyte values can provide prognostic information in CC. These hypothesis-generating findings warrant further prospective investigations.

High-dose chemotherapy and stem-cell rescue for salvage therapy for relapsed malignant mixed ovarian germ cell tumor: A case report.

BACKGROUND: Malignant ovarian germ cell tumors are rare, and often treatable with surgery and chemotherapy. Few data are available for treatment of platinum-resistant tumors. CASE: A 31 year old gravida 0 with a 20 cm pelvic mass was found to have a malignant ovarian germ cell tumor after she underwent debulking surgery. She initially responded to chemotherapy; however her AFP began to rise before all cycles were completed. She underwent additional debulking surgery that was again suboptimal. She was then referred for salvage therapy with high-dose chemotherapy with stem cell transplant, which was successful and she has had no evidence of disease for over two years. CONCLUSION: High-dose chemotherapy with stem cell transplant is a viable salvage therapy for patients with platinum-resistant germ cell tumors.