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Friday, July 03, 2015

Lynch Syndrome: A Primer for Urologists and Panel Recommendations - The Journal of Urology

open access

" Early descriptions of UTUC in LS were limited by small patient numbers, lack of pathological confirmation, placement in the broad categories of genitourinary malignancy (together with bladder or renal cell carcinomas) or kidney malignancy (without distinguishing renal pelvis or renal cell carcinoma) and no available molecular or genetic testing. Not until the later introduction of the Amsterdam Criteria II20 and the Bethesda Criteria21 did patients with extracolonic malignancies receive full consideration for study inclusion."

 Article Outline


Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is a common genetic disease. The predisposition of patients with Lynch syndrome to urological cancer, particularly upper tract urothelial carcinoma, is underappreciated. Urologists may be involved in several aspects of care involving Lynch syndrome, including identifying undiagnosed patients, surveillance of those with established Lynch syndrome or screening family members, in addition to treating patients with Lynch syndrome in whom upper tract urothelial carcinoma develops. We sought to increase awareness in the urological community about Lynch syndrome and provide some guidance where little currently exists.

Review: Paclitaxel and Its Evolving Role in the Management of Ovarian Cancer

open access

"Dose-dense therapy survival benefits were also not seen in patients with clear cell or mucinous histology type, unlike serous type."

Future Directions

A plateau has been reached regarding the benefits associated with standard 3-weekly intravenous administration of cytotoxic chemotherapy in advanced epithelial ovarian cancer. The ongoing battle for a better treatment regimen to delay relapse, promote remission, and most importantly improve the quality of life of patients with advanced epithelial ovarian cancer need not to go further than the ability to relook at the chemotherapy agents that are already available in a different approach.

Novel compounds to date have not yet shown clinical superiority, and parent compounds such as paclitaxel continue to surprise us with their feasibility, effectiveness, and manageable toxicity profiles. Intraperitoneal paclitaxel will require further evaluation. Better effort in understanding the mechanism of action of drugs including the role of dose scheduling and the effect on the immune system may provide a more cost-effective route to better clinical outcomes.

Exceptional Responders Inspire Change: Lessons for Drug Development From the Bedside to the Bench and Back

open access

 Targeted therapies have changed the landscape of cancer treatment. Unfortunately, the promise of “targeted therapy” still fails too many patients with advanced cancer. Oncologists should ask why and how can we rapidly develop novel strategies. In medicine, exciting and novel occurrences are often first publicized as a case report. This quick yet detailed description of the clinical presentation, diagnosis, treatment, and outcome of an individual patient remains an important part of medical progress. However, although case reports serve as anecdotal clinical evidence that may be shared for educational, scientific, or medical purposes, the amount of information that can be generalized to a wider group of cancer patients is typically limited. Can case reports extend knowledge beyond the single patient experience and offer mechanistic insight or lead to novel therapeutic strategies?.....

Can targeted genetic testing offer useful health information to adoptees?

Nature Publishing Group

Impact of Chemotherapy Dosing on Ovarian Cancer Survival According to BMI + Editorial

Online First

Original Investigation  FREE
Includes: Supplemental Content
Original Investigation  Open Access

Inflammation-regulating factors in ascites as predictive biomarkers of drug resistance/progression-free survival serous epithelial ovarian cancers

 Full text 

Platinum-based combination therapy is the standard first-line treatment for women with advanced serous epithelial ovarian carcinoma (EOC). However, about 20 % will not respond and are considered clinically resistant. The availability of biomarkers to predict responses to the initial therapy would provide a practical approach to identify women who would benefit from a more appropriate first-line treatment. Ascites is an attractive inflammatory fluid for biomarker discovery as it is easy and minimally invasive to obtain. The aim of this study was to evaluate whether six selected inflammation-regulating factors in ascites could serve as diagnostic or drug resistance biomarkers in patients with advanced serous EOC. 


A total of 53 women with stage III/IV serous EOC and 10 women with benign conditions were enrolled in this study. Eleven of the 53 women with serous EOC were considered clinically resistant to treatment with progression-free survival < 6 months. Ascites were collected at the time of the debulking surgery and the levels of cytokines were measured by ELISA. The six selected cytokines were evaluated for their ability to discriminate serous EOC from benign controls, and to discriminate platinum resistant from platinum sensitive patients........

Thursday, July 02, 2015

Lynch syndrome: five unanswered questions - Commentary

open access

"A large proportion of deaths in LS are associated with extra-colonic and extra-endometrial cancers."

Despite the great advances that have occurred in the century following the first description of a Lynch syndrome (LS) family and more especially, in more than 20 years since the discovery of causal mutations in the mismatch repair genes (MMR), long-standing clinical questions remain unanswered. Moreover, as a result of novel technologies, new questions have arisen. With this commentary, we aim to briefly cover some of these aspects of LS. We will focus on current challenges regarding the definition of LS-related tumors, their prevention and early detection, the role of next-generation sequencing (NGS) in the molecular diagnostics of LS and advances in the treatment of LS tumors.

"Although LS was initially thought of as a colorectal cancer (CRC) syndrome, the established spectrum of LS-associated tumors includes endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, and brain (Turcot syndrome) tumors, sebaceous gland adenomas and keratoacanthomas (Muir–Torre syndrome), and carcinoma of the small bowel [1]."

Tumor spectrum of LS: is there a risk for breast cancer?


Can LS-associated cancers be diagnosed early or prevented?


Should all colorectal and endometrial carcinomas be tested for MMR 


Are we ready to properly implement NGS into the diagnostics of LS?


Should treatment of cancer be influenced by MMR status?



Wednesday, July 01, 2015

CA 125 : Get Facts on Testing for Tumor Marker Levels + comments (Medicinenet)

CA 125 : Get Facts (reviewed 4/2015)


ESMO Magnitude of Clinical Benefit Scale ESMO/theLancet Oncology

ESMO (website)

 A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS)

The ESMO-MCBS will be a dynamic tool and its criteria will be revised on a regular basis.

theLancet Oncology

 Several new cancer medicines are of little clinical benefit to patients, suggests a new study by investigators from the European Society for Medical Oncology (ESMO). The investigators devised a “validated and reproducible” method to assess the magnitude of cancer medicines' clinical benefits—called the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS).

Germline BRCA1/2 Mutations: Are They Good Enough to Determine Who Will Respond to Poly(ADP–Ribose) Polymerase Inhibitor Therapy in Advanced Cancer?


..... It remains to be shown what exactly determines the response to PARP inhibitor therapy; Is it germline BRCA1/2 mutations? Is it platinum sensitivity? Is it HRD? Or is it a combination of all? Currently, identification of germline BRCA mutations through a blood test seems to be the only US Food and Drug Administration–approved surrogate marker for HRD. However testing tumor tissue for somatic BRCA mutations as well as for genes associated with HRD may better define the subgroup of patients with cancer who would benefit from a number of PARP inhibitors yet to come into clinical practice. The recent US Food and Drug Administration approval of olaparib for ovarian cancer along with a companion diagnostic blood test of BRACAnalysis CDx (Myriad Genetics Laboratories, Salt Lake City, UT) seems to be just the beginning.


  1. 1.

To BRCA or Not to PALB (Correspondence/Original research paper)

JCO - Letter

 To the Editor:
Kaufman et al1 report interesting data from a nonrandomized phase II multicenter study of an oral poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, monotherapy in a spectrum of germline BRCA1 and BRCA 2 (BRCA 1/2) –mutated cancers (ovarian, breast, pancreatic, and prostate cancer). This article by Kaufman et al adds to the growing body of evidence of the potential for PARP inhibitor inclusion in the therapeutic management of patients with BRCA 1/2 mutations.25....


  1. 1.

To Better Understand Emotions of Bereaved Caregivers Who Took Care of Patients at Home

JCO open access 

1) open access - Letter

....We should be grateful to Kinoshita et al1 for conducting such a challenging study, and we suggest that the authors investigate whether the group of caregivers of patients who died at home had differences in incidence of severe emotional distress compared with caregivers of patients who died in palliative care units and/or hospitals.

2) open access: Authors' Response

3) open access (original paper): To Better Understand Emotions of Bereaved Caregivers Who Took Care of Patients at Home

Potential therapeutic targets in ARID1A-mutated cancers


 The Wistar Institute, Gene Expression and Regulation Program , Room 312, Philadelphia, PA 19104 , USA +1 215 495 6840 ; rzhang@wistar.org.


ARID1A is a subunit of the Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex that regulates gene expression by controlling gene accessibility. ARID1A shows one of the highest mutation rates across different human cancer types. For example, ARID1A is mutated in ∼ 50% of ovarian clear cell carcinoma (OCCC). There is considerable interest in developing cancer therapeutics that correlate with ARID1A mutational status. A recent study demonstrated a synthetic lethality by targeting EZH2 histone methyltransferase activity in ARID1A-mutated OCCC using a clinically applicable small-molecule inhibitor. The observed synthetic lethality correlated with inhibition of PI3K/AKT signaling. In addition, there is evidence indicating that ARID1A-mutated cancer may also be subjected to therapeutic intervention by targeting residual SWI/SNF activity, the PI3K/AKT pathway, the DNA damage response, the tumor immunological microenvironment and stabilizing wild-type p53. In summary, we propose EZH2 inhibitor-based combinatorial strategies for targeting ARID1A-mutated cancers.

Tuesday, June 30, 2015

Perineal Powder Use and Risk of Ovarian Cancer - JNCI


Talc Use and Ovarian Cancer: Epidemiology Between a Rock and a Hard Place

open access JNCI


 International Journal of Gynecological Cancer

Genomic Vision Poised to Expand 'Molecular Combing' Dx Offerings in US, Europe


 NEW YORK (GenomeWeb) – French molecular diagnostics firm Genomic Vision plans to release several new tests based on its molecular combing technology over the next two years, both through an existing licensing agreement with Quest Diagnostics in the US, and through sales of testing kits to European hospitals and clinical centers......

Woman Battling (ovarian) Cancer and Amnesia Relies on Faith, Social Media to Retrace Past

media/FB/Interpol links

Talcum Powder Lawsuit News: Ovarian Cancer Allegations Head to Trial

Press release

PharmaMar Initiates the Phase III Study CORAIL for the Anticancer Agent PM1183 Platinum-resistant Ovarian Cancer

Press release

Psychosocial factors associated with withdrawal from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)....

 Psychosocial factors associated with withdrawal from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) following one episode of repeat screening


Objective: The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) aims to establish the efficacy of two different ovarian cancer screening schedules. The psychosocial sub study examines the psychological factors associated with the screening programme. 
Methods: Women aged 50 to 75 years from 16 UK gynaecological centres randomised to annual multimodal screening (MM), or ultrasound screening (US) groups were followed for seven years. Psychosocial data from women who withdrew from the study following a repeat screen were examined. 
Results: 16% (3499/21733) of women requiring a repeat screening test in addition to annual screen withdrew from the study; 12.9% (1560/12073) from the MM group, and 20.1% (1939/9660) from the US group; an estimated relative risk of withdrawal of 1.46 (95%CI: [1.36, 1.56]; p=<0.001) for the US arm. High anxiety trait and increased psychological morbidity significantly influenced withdrawal even when age, screening centre, and group were taken into account (p<0.001). The risk of withdrawal decreased significantly the longer a woman stayed in UKCTOCS, irrespective of the number of screens and intensity in the preceding year. 
Conclusions: Withdrawal rate was greater in women undergoing US screening and in those who had repeats earlier in UKCTOCS. Having a high predisposition to anxiety, high current state anxiety and above threshold general psychological morbidity all increased the withdrawal rate.


This is the author accepted manuscript. It is currently under an indefinite embargo pending publication of the final version.

Quality Initiative Endorsed by Cancer Care Ontario in Partnership with the Program in Evidence

Person-Centred Care Guideline 

The Person-Centred Care (PCC) Guideline outlines a level of service that any person (i.e., patient, family member, carer) using adult oncology services in Ontario should expect to receive, namely PCC. The PCC guideline was endorsed in partnership with the PEBC and the guideline working group. The guidance was approved by an Expert Panel convened by the PCC Program to advise on behaviours and practices of PCC.
The PCC Guideline, approved by the Expert Panel, is available below, which includes reference to the original National Health Services (NHS) Guideline from which the PCC Guideline was adapted for the Ontario context.
The PEBC has a formal and standardized process to ensure the currency of each document (please see the PEBC Assessment & Review Protocol for more information). This process guides clinical experts to assess a document’s current status and relevance. A final status statement is added to the document when this review process is complete. The current status of each guidance document is noted beside the title and link as outlined below:
  • Documents listed as CURRENT are 3 years old or less, up-to-date, and can be used for decision making.
  • Documents listed as IN REVIEW are undergoing assessment for currency and relevance. The DSG/GDG has determined that it is still appropriate for this document to continue to be available while this updating process unfolds.
  • Documents that are listed as “FOR EDUCATION AND INFORMATION PURPOSES” are documents for which no further updates are planned and whose recommendations may no longer be consistent with recent evidence. They may be of educational, historical, clinical, or system interest.
Last modified: Fri, May 08, 2015

Editorial: Dietary Advice for Melanoma: Not Ready for Prime Time (re: grapefruit)


(Canada- CMA) Doctors’ group proposes assisted death protocols in absence of rules from government - media

....MacKay has hinted the government would seek an extension to the court-imposed deadline, something University of Calgary bioethicist and lawyer Juliet Guichon said the justices are highly unlikely to grant.
“The issue isn’t, ‘Does the government need more time?’ ” said Guichon. “For the Supreme Court, the issue is, ‘How long can we prevent citizens from having full access to their rights?’ ”

Comorbidity and survival among women with ovarian cancer: evidence from prospective studies

open access

.... This is the first meta-analysis evaluating the association between comorbidity and survival following EOC diagnosis......

....First, a meta-analysis cannot control for confounders for which there was no adjustment in the primary analysis of individual studies. We excluded the study of Elit et al.26 because they reported the crude risk estimates without adjustment for any potential confounders. In contrast, all included studies had been adjusted for at least two potential confounders in their primary analyses. Furthermore, we cannot exclude the possibility of unmeasured or residual confounding as a potential explanation for the observed associations. Several studies demonstrated that severe comorbidity was associated with older age, higher tumor stage, performance status, and cancer treatment7, 8. Although we found that the associations were robust in analyses stratified by adjustment for these aforementioned confounding factors (Table 2), less than half the studies adjusted for tumor grade and histology and only two studies adjusted for cancer treatment or residual tumor. Therefore, further studies stratified by established or additional prognostic factors are warranted to better rule out potential effects of residual confounding.....

 In conclusion, the results from this meta-analysis, based on prospective studies, suggest that comorbidity has a negative impact on EOC survival. The status and severity of comorbid diseases should be taken into consideration by clinicians when making decisions on EOC management. Further studies need to figure out which individual comorbid diseases may have the greatest impact on survival of EOC patients.

Monday, June 29, 2015

Retraction: Role of Pelvic and Para-aortic Lymph Node Metastases in Optimally Cytoreduced Advanced Ovarian Cancer


The article entitled “Role of Pelvic and Para-aortic Lymph Node Metastases in Optimally Cytoreduced Advanced Ovarian Cancer” by C. Bachmann, R. Bachmann, S.Y. Brucker, A. Staebler, F. Fend, E.-M. Grischke and D. Wallwiener, published in Anticancer Research 35: 6 (June) pp. 3479-3484, 2015, is retracted by the Authors.

Pancreatic Resection as Part of Cytoreductive Surgery in Advanced-stage and Recurrent Epithelial Ovarian Cancer (Romania)

open access
 Patients and Methods

After obtaining the Ethics Committee approval (No. 43/2015) we retrospectively reviewed data of patients submitted to surgery for advanced stage or recurrent ovarian cancer at the Dan Setlacec Center of Gastrointestinal Disease and Liver Transplantation, Fundeni Clinical Institute, Romania, between January 2002 and May 2014 and found six cases eligible for the study: one case who was submitted to pancreatic resection at the moment of primary cytoreduction, four cases submitted to pancreatic surgery as part of secondary cytoreduction and another patient submitted to pancreatic surgery during tertiary cytoreduction......


Pancreatic resections can and should be performed as part of cytoreductive surgery for patients with advanced-stage or relapsed ovarian cancer. Although pancreatic fistula is a common complication after this type of surgery, this fact should not be transformed into a contraindication for pancreatic surgery in the context of advanced gynecological malignancies, a good understanding of this complication being mandatory in order to treat it successfully with minimal impact on the postoperative outcomes. Once the pancreatic fistula is assessed, the patient can be safely submitted to adjuvant chemotherapy to maximize the benefits provided by complete surgical cytoreduction.

Results of Primary Cytoreductive Surgery in Advanced-stage Epithelial Ovarian Cancer - Romania

open access

Patients and Methods

We retrospectively reviewed data of patients with advanced epithelial ovarian cancer referred to the Fundeni Clinical Institute between 1 January 2002 and 1 April 2014.....


Total debulking to achieve no residual tumoral tissue is the best chance of long-term survival for patients with advanced ovarian cancer. Maximal upper abdominal surgery including liver resection will bring survival for this category of patients with more advanced disease closer to that of patients with a lower extent of disease. The effort of complete cytoreduction also seems to be perfectly justified in cases presenting upper abdominal involvement including diaphragmatic disease or bowel involvement, while association of multiple resections at these levels seems to be safely performed, with acceptable postoperative rates of morbidity.

VolitionRx begins first ovarian cancer detection study

open access

Q  Today we are focusing our interview on a new pilot study that VolitionRx is conducting in partnership with the Singapore General Hospital. Can you tell us a little about the study & its main aims/goals? How did the partnership with Singapore General Hospital come about?

Previous sectionNext section
Ovarian cancer is a huge problem in women's health. Known as a ‘silent killer’ because the early stages of the disease rarely exhibit symptoms and growths in the ovary are not palpable as other, for example breast, cancers may be. About 75% of ovarian cancers are not detected until after the disease has spread to the abdomen and more than 50% of patients die within 5 years of diagnosis. The study with Singapore General Hospital will be a pilot study – Singapore General Hospital will provide samples from 40 subjects and we will analyze them to assess the ability of our NuQ tests to detect ovarian cancer. We hope that, given positive results from the pilot study, we will be able to expand into further confirmatory trials in larger numbers of patients.......

Determinants of suicidal ideation in gynecological cancer patients - Psycho-Oncology


Gynecological cancer survivors are at increased risk of psychological problems including suicide risk. Suicidal ideation (eg. thoughts/ideas), which was thought to be precursor to suicide attempts, has not been well studied. This study aimed to investigate the prevalence, and determinants of suicidal ideation for women with gynecological cancer, and then to assess the effect of coping style and social support on suicidal ideation.


Patients with cervical, ovarian and endometrial cancers seen at Hunan Provincial Tumor Hospital from September 2012 to June 2013 were consecutively recruited and were asked to complete the Zung Self-Rating Depression Scale, Suicidal Ideation of Self-rating Scale, Medical Coping Modes Questionnaire and Social Support Rating Scale. Path analysis was used to examine the relationship among coping style, social support, depression symptoms and suicidal ideation.


A total of 579 (579/623, 93.0%) gynecological cancer patients were enrolled in this study and completed all investigations between September 2012 and June 2013. Among them, 105 (18.1%) patients reported suicidal ideation, with the highest rate in patients with ovarian cancer (30.16%). Suicidal ideation was associated with depression symptoms, care providers, chemotherapy history and acceptance-resignation. Path analysis showed that the acceptance-resignation affected suicidal ideation directly as well as mediated by social support and depression symptoms, while confrontation and avoidance affected suicidal ideation entirely through social support and depression symptoms.


Suicidal ideation is high among patients with gynecological cancer, especially among ovarian cancer patients. Coping strategies such as confrontation and avoidance, and social support may be helpful for preventing suicidal ideation among them.

...patient self-administered cancer family history questionnaire in identification of gyn cancer pts suspected of Lynch syndrome (Japan)

Usefulness of the patient self-administered cancer family history questionnaire in identification of gynecological cancer patients suspected of Lynch syndrome: KCOG-G1302 study
Background: Detailed family history collection is necessary to detect gynecological cancer patients suspected of Lynch syndrome (LS). However, clinicians have little time for family history interviews. In addition, there is a lack of genetic counselors in Japan. Therefore, information from medical records on the first visit (MR) is insufficient to determine if a patient may be at risk of LS. We showed that using the self-administered cancer family history questionnaire (SACFHQ) improves identification of patients suspected of LS.  

Methods: We recruited endometrial or ovarian cancer patients already diagnosed or newly diagnosed from research participating institutions. After consent was obtained, participants completed the questionnaire. By referring to the cancer family history obtained from MR and SACFHQ, we referred to cases that met the Amsterdam criteria II(AMSII), the SGO20-25% criteria (SGO20-25%), ACOG’s clinical bulletin 2014 criteria (ACOG2014).  

Results: There was a total of 493 participants. 38 patients were excluded by exclusion criteria. Finally, 455 were eligible. Median age at diagnosis was 56 (range21-84). 243 participants were endometrial cancer patients, and 213 were ovarian cancer, including peritoneal and tubal cancer. 12 cases had either synchronous/metachronous endometrial and colorectal cancer. 4 cases had either synchronous/metachronous ovarian and colorectal cancer. Among these 16 cases, endometrial or ovarian cancer was sentinel in 8 cases. By using MR, 0/455 (0%), 4/455 (0.9%), and 170/455 (37%) cases met AMSII, SGO20-25%, ACOG2014 criteria, respectively. By using SACFHQ, 6/455 (1.3%), 9/455 (2.0%), and 217/455 (48%) cases met AMSII, SGO20-25%, ACOG2014 criteria, respectively. All 6 cases that met AMSII were endometrial cancer patients. 8 of 9 patients who met SGO20-25% were endometrial cancer patients, and one patient was ovarian cancer.  

Conclusions: Family cancer history obtained from MR was shown to be insufficient to identify individuals at risk of LS. SACFHQ (self-administered cancer family history questionnaire) improves identification of gynecological cancer patients suspected of LS. Clinical trial information: 000013192.

The Ovarian Cancer Consortium for Long-Term Survival - seeking OC patient participation

Massachusetts General Hospital, Boston, MA

 The Consortium for Long-Term Survival, led by the Mass General Cancer Center and funded by the Department of Defense, is a research group seeking long-term survivors of ovarian cancer. If you are a 8 year or more stage III or stage IV ovarian cancer survivor, your participation can help to improve the treatment, survival, and survivorship of all women.
We now have the technological tools to try to unlock the reasons why some women do much better than others who face advanced ovarian cancer. We hope to find the key to long-term survival.
With your help, we want to better define five aspects of ovarian cancer in long-term survivors of the condition:
  1. The ability of their tumor cells to grow and survive, even after surgery
  2. Just how capable these tumors are to grow their own blood supply channels
  3. How these cancers interact and invade surrounding structures
  4. How women coped with their cancer in the past and in the present
  5. What their quality of life is like now, compared to how it was in various times in their cancer journey
It may be that differences in these five factors have an influence on a woman’s ability to survive and thrive after diagnosis. Our hope is to identify a biologic, molecular, and psychosocial pattern that can predict long-term survival in hopes that their lessons can be learned by all women with ovarian cancer.

 If you would like more information about this research program, click here to contact Giulia Fulci, Project Co-Ordinator

The Value of Intraoperative Near-Infrared Fluorescence Imaging Based on Enhanced Permeability and Retention of Indocyanine Green: Feasibility and False-Positives in Ovarian Cancer

open access

In ovarian cancer, two of the most important prognostic factors for survival are completeness of staging and completeness of cytoreductive surgery. Therefore, intra-operative visualization of tumor lesions is of great importance. Preclinical data already demonstrated tumor visualization in a mouse-model using near-infrared (NIR) fluorescence imaging and indocyanine green (ICG) as a result of enhanced permeability and retention (EPR). The aim of this study was to determine feasibility of intraoperative ovarian cancer metastases imaging using NIR fluorescence imaging and ICG in a clinical setting.


Ten patients suspected of ovarian cancer scheduled for staging or cytoreductive surgery were included. Patients received 20 mg ICG intravenously after opening the abdominal cavity. The mini-FLARE NIR fluorescence imaging system was used to detect NIR fluorescent lesions.


6 out of 10 patients had malignant disease of the ovary or fallopian tube, of which 2 had metastatic disease outside the pelvis. Eight metastatic lesions were detected in these 2 patients, which were all NIR fluorescent. However, 13 non-malignant lesions were also NIR fluorescent, resulting in a false-positive rate of 62%. There was no significant difference in tumor-to-background ratio between malignant and benign lesions (2.0 vs 2.0; P=0.99).


This is the first clinical trial demonstrating intraoperative detection of ovarian cancer metastases using NIR fluorescence imaging and ICG. Despite detection of all malignant lesions, a high false-positive rate was observed. Therefore, NIR fluorescence imaging using ICG based on the EPR effect is not satisfactory for the detection of ovarian cancer metastases. The need for tumor-specific intraoperative agents remains.

Trial Registration

ISRCTN Registry ISRCTN16945066

 .....Clinical feasibility trials using this effect with ICG in breast cancer patients in a pre-operative diagnostic setting and in gastric cancer patients during endoscopic surgery showed that it was possible to distinguish tumor from surrounding tissue [1823]. In addition, Kosaka et al.[24] detected small ovarian (1–2 mm in size) cancer implants using NIR fluorescent imaging after intravenous (IV) administration of ICG in a mouse model. Pathophysiological heterogeneity of solid tumors, for examples in size, presence of necrosis, or presence of vascular mediators may influence accumulation of macromolecules in tumor tissue [25,26]. It is therefore not clear if all preclinical results can be translated to the clinic.

Postoperative Complications After Distal Pancreatectomy Performed During Cytoreductive Surgery for Gynecologic Malignancies


 Objectives: To investigate the incidence of pancreatic leak and other postoperative complications after distal pancreatectomy performed during debulking surgery for gynecologic malignancies.

Methods: All patients who underwent distal pancreatectomy during their debulking surgery from 2010 to 2014 were identified. Postoperative complications within 30 days and pancreatic leak within 120 days after surgery were included.

Results: Eighteen patients met the inclusion criteria. The median age was 62 years (36–78 years). Four patients (22%) were admitted to the intensive care unit, and the average length of hospital stay was 10 days. Nine patients developed postoperative complications within 30 days after surgery (50%) with no perioperative mortality up to 90 days after surgery. No patients required reexploration.

Impact of Age on 30-Day Mortality and Morbidity in Patients Undergoing Surgery for Ovarian Cancer



To examine the effect of age on postoperative 30-day morbidity and
mortality after surgery for ovarian cancer.


The American College of Surgeons National Surgical Quality
 Improvement Program files were used to identify patients with ovarian
 cancer who underwent surgery in 2005 to 2011. Women were divided
 into 4 age groups: <60, 60 to 69, 70 to 79, and ≥80 years. Multivariable
 logistic regression models were performed.


Of 2087 patients included, 47% were younger than 60 years, 28% were
 60 to 69 years old, 18% were 70 to 79 years old, and 7% were 80 years
 or older. Overall 30-day mortality and morbidity rates were 2% and 30%.
Elderly patients 80 years or older were more likely to die within 30 days
  compared with patients younger than 60 years, 60 to 69 years old, and
 70 to 79 years old (9.2% vs. 0.6% vs .2.8% vs 2.5%, P < 0.001). Elderly
 patient aged 80 years or older were more likely to develop pulmonary
  (9% vs 2% vs 5% vs 3%, P < 0.001) and septic (9% vs 3% vs 5% vs
 4%, P = 0.01) complications compared with patients younger than
 60 years, 60 to 69 years old, and 70 to 79 years old, respectively.

Make New Friends But Keep the Old: Minimally Invasive Surgery Training in Gynecologic Oncology Fellowship Programs


 Objectives: To evaluate the role of minimally invasive surgery (MIS) in gynecologic oncology fellowship training and fellows’ predictions of their use of MIS in their future practice.

Methods: All fellows-in-training in American Board of Obstetrics and Gynecology–approved training programs were surveyed in 2012 through an online or mailed-paper survey. Data were analyzed and compared to results of a similar 2007 survey.

Results: Of 172 fellows, 69 (40%) responded. Ninety-nine percent of respondents (n = 68) indicated that MIS was either very important or important in gynecologic oncology, a proportion essentially unchanged from 2007 (100%). Compared to 2007, greater proportions of fellows considered laparoscopic radical hysterectomy and node dissection for cervical cancer (87% vs 54%; P < 0.0001) and trachelectomy and staging for cervical cancer (83% vs 32%; P < 0.0001) appropriate for MIS. Of the respondents, 92% believed that maximum or some emphasis should be placed on robotic-assisted surgery and 89% on traditional laparoscopy during fellowship training. Ten percent rated their fellowship training in laparoendoscopic single-site surgery as very poor; 44% said that the question was not applicable.

Role of Minimally Invasive Surgery in Gynecologic Oncology - update SGO


Objectives: To evaluate the current patterns of use of minimally invasive surgical procedures, including traditional, robotic-assisted, and single-port laparoscopy, by Society of Gynecologic Oncology (SGO) members and to compare the results to those of our 2004 and 2007 surveys.

Methods: The Society of Gynecologic Oncology members were surveyed through an online or mailed-paper survey. Data were analyzed and compared with results of our prior surveys.

Results: Four hundred six (32%) of 1279 SGO members responded. Eighty-three percent of respondents (n = 337) performed traditional laparoscopic surgery (compared with 84% in 2004 and 91% in 2007). Ninety-seven percent of respondents performed robotic surgery (compared with 27% in 2007). When respondents were asked to indicate procedures that they performed with the robot but not with traditional laparoscopy, 75% indicated radical hysterectomy and pelvic lymphadenectomy for cervical cancer. Overall, 70% of respondents indicated that hysterectomy and staging for uterine cancer was the procedure they most commonly performed with a minimally invasive approach. Only 17% of respondents who performed minimally invasive surgery performed single-port laparoscopy, and only 5% of respondents indicated that single-port laparoscopy has an important or very important role in the field.

Conclusions: Since our prior surveys, we found a significant increase in the overall use and indications for robotic surgery. Radical hysterectomy or trachelectomy and pelvic lymphadenectomy for cervical cancer and total hysterectomy and staging for endometrial cancer were procedures found to be significantly more appropriate for the robotic platform in comparison to traditional laparoscopy. The indications for laparoscopy have expanded beyond endometrial cancer staging to include surgical management of early-stage cervical and ovarian cancers, but the use of single-port laparoscopy remains limited.

Thrombocytosis is Predictive of Postoperative Pulmonary Embolism in Patients With Gynecologic Cancer


Objectives: The prompt diagnosis of postoperative pulmonary embolism (PE) in gynecologic oncology patients is imperative, but the clinical presentation is nonspecific in this high-risk group. We sought to determine risk factors and clinical findings that may assist clinicians in diagnosing PE in the inpatient setting.

Methods: Radiology data were queried to identify patients with gynecologic cancer who had a postoperative PE evaluation with computed tomography pulmonary angiography (CT-PA). Patient clinical findings at the time of the PE evaluation were abstracted, and univariate and multivariate regression analyses were performed to identify predictors of PE.

Results: For 6 years, there were 2498 major gynecologic oncology surgical procedures performed at our institution. Within 14 days of surgery, 107 CT-PA studies were obtained with a positive study rate of 24.3%. In patients with and without PE, there was no significant difference noted for age, oxygen saturations, body mass index and heart rate. After controlling for stage, history of venous thromboembolism (VTE), heart rate, and oxygen saturation, platelet count and history of VTE (odds ratio, were identified as independent predictors of PE in the multivariate model.

Conclusions: Although clinicians often use tachycardia and low oxygen saturation as triggers to order PE imaging studies, these signs have a very low specificity. Given the findings of our study, accounting for high platelet count and history of VTE increases the pretest probability of CT-PA study.

Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer:

open access

 Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer: Results of a Retrospective, Single-Institution Study

.... It should be noted that because there were no responses in patients
with platinum-refractory or clear cell disease, logistic regression results for these parameters were nonestimable....Although the regression models
suggest that platinum-refractory status is a stronger predictor
of poor outcomes than clear cell histology, examination of a
larger data set is needed to increase confidence in this conclusion.....

Objective: Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome “resistance” in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting.

Sunday, June 28, 2015

Does one size fit all? The updated ovarian cancer staging: Still a work in progress

Editorial - abstract

 The International Federation of Gynecology and Obstetrics (FIGO) has recognized serous tubal intraepithelial carcinoma as a precursor lesion for high-grade serous epithelial ovarian cancer. Future staging systems should consider reclassifying stage based on tumor biologic behavior.

Abridged republication of FIGO's staging classification for cancer of the ovary, fallopian tube, and peritoneum


 Ovarian, fallopian tube, and peritoneal cancers have a similar clinical presentation and are treated similarly, and current evidence supports staging all 3 cancers in a single system. The primary site (i.e. ovary, fallopian tube, or peritoneum) should be designated where possible. The histologic type should be recorded. Intraoperative rupture (“surgical spill”) is IC1; capsule ruptured before surgery or tumor on ovarian or fallopian tube surface is IC2; and positive peritoneal cytology with or without rupture is IC3. The new staging includes a revision of stage III patients; assignment to stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination. Extension of tumor from omentum to spleen or liver (stage IIIC) should be differentiated from isolated parenchymal metastases (stage IVB).

Rheumatoid Arthritis as a Therapeutic Challenge in a Patient with Lynch Syndrome

open access

  American Journal of Case Reports
Rheumatoid Arthritis as a Therapeutic Challenge in a Patient with Lynch Syndrome
Hossam Abdalla, Arindam Bagchi, Sabiha Bandagi
Am J Case Rep 2015; 16:390-392
DOI: 10.12659/AJCR.892906

..... With relation to RA treatment options, effectively decreasing systemic inflammation may in fact reduce the risk for cancer, but treatment of RA using the newer biologic agents like infliximab or adalimumab has been associated with increasedrisk of malignancy, specifically lymphoma [16,20,21].....

BACKGROUND: Lynch syndrome (LS) is an inherited colorectal cancer (CRC) syndrome accounting for about 3–5% of all cases and involves significantly higher risk of subsequent malignancies, colonic as well as extra-colonic. Increased risk of malignancies, especially lymphoid malignancies, have been described in patients with autoimmune diseases like rheumatoid arthritis (RA), systemic lupus erythematosus, and Sjögren’s syndrome. Epidemiological studies demonstrated that hematopoietic, lung, skin, and prostate cancers are increased in RA, while breast and colon cancers are decreased, with an overall slight increase in all cancers.

CASE REPORT: Our case demonstrates the development of CRC, endometrial cancer, and breast cancer as a presentation of LS in a patient with RA and presents a therapeutic challenge for RA treatment.

CONCLUSIONS: We describe a patient with LS and RA presenting a therapeutic challenge because biologic agents commonly used to treat severe RA need to be used cautiously in patients with history of malignancy.

Keywords: Arthritis, Rheumatoid, Biological Therapy, Lynch Syndrome II

Investigating the performance/cost-effectiveness of the simple ultrasound-based rules compared to the risk of malignancy index in the diagnosis of ovarian cancer

BMC Cancer  - open access

Investigating the performance and cost-effectiveness of the simple ultrasound-based rules compared to the risk of malignancy index in the diagnosis of ovarian cancer (SUBSONiC-study): protocol of a prospective multicenter cohort study in the Netherlands http://ovariancancerandus.blogspot.com/feeds/posts/default

Background Estimating the risk of malignancy is essential in the management of adnexal masses. An accurate differential diagnosis between benign and malignant masses will reduce morbidity and costs due to unnecessary operations, and will improve referral to a gynecologic oncologist for specialized cancer care, which improves outcome and overall survival. The Risk of Malignancy Index is currently the most commonly used method in clinical practice, but has a relatively low diagnostic accuracy (sensitivity 75–80 % and specificity 85–90 %). Recent reports show that other methods, such as simple ultrasound-based rules, subjective assessment and (Diffusion Weighted) Magnetic Resonance Imaging might be superior to the RMI in the pre-operative differentiation of adnexal masses. 

Methods/Design A prospective multicenter cohort study will be performed in the south of The Netherlands. A total of 270 women diagnosed with at least one pelvic mass that is suspected to be of ovarian origin who will undergo surgery, will be enrolled. We will apply the Risk of Malignancy Index with a cut-off value of 200 and a two-step triage test consisting of simple ultrasound-based rules supplemented -if necessary- with either subjective assessment by an expert sonographer or Magnetic Resonance Imaging with diffusion weighted sequences, to characterize the adnexal masses. The histological diagnosis will be the reference standard. Diagnostic performances will be expressed as sensitivity, specificity, positive and negative predictive values and likelihood ratios. 

Discussion We hypothesize that this two-step triage test, including the simple ultrasound-based rules, will have better diagnostic accuracy than the Risk of Malignancy Index and therefore will improve the management of women with adnexal masses. Furthermore, we expect this two-step test to be more cost-effective. If the hypothesis is confirmed, the results of this study could have major effects on current guidelines and implementation of the triage test in daily clinical practice could be a possibility. Trial registration ClinicalTrials.gov: registration number NCT02218502

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Cancer risk among parous women following assisted reproductive technology

open access

STUDY QUESTION Do women who give birth after assisted reproductive technology (ART) have an increased risk of cancer compared with women who give birth without ART?
SUMMARY ANSWER Without correction, the results indicate an increase in overall cancer risk, as well as a 50% increase in risk of CNS cancer for women giving birth after ART, however the results were not significant after correcting for multiple analyses.
WHAT IS KNOWN ALREADY Studies regarding the effects of hormonal treatments involved with ART on subsequent cancer risk have provided inconsistent results, and it has also been suggested that infertility itself could be a contributory factor......

How Do You Triage Abdominal Pain in a Patient With Ovarian Cancer?

open access


B.V. is a 53-year-old nulliparous woman who was initially diagnosed with recurrent stage 3C epithelial ovarian carcinoma in 2011. She underwent a hysterectomy, bilateral salpingo-oophorectomy, and optimal tumor debulking. Adjuvant therapy consisted of a clinical trial (Gynecologic Oncology Group [GOG] 262) protocol of 6 cycles of IV carboplatin, paclitaxel, and bevacizumab (Avastin) followed by bevacizumab every 3 weeks.
In 2013, B.V. was diagnosed with invasive ductal breast cancer, which necessitated discontinuation of bevacizumab after 12 months of maintenance therapy. She underwent lumpectomy and adjuvant radiation therapy, which was completed in January 2014. Her breast tumor was estrogen-/progesterone-receptor (ER/PR) positive. She was started on tamoxifen.
In February 2014, B.V. had a recurrence of her ovarian cancer......


Diagnosis of Constitutional Mismatch Repair-deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents


Background & Aims

Patients with bi-allelic germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) develop a rare but severe variant of Lynch syndrome called constitutional MMR deficiency (CMMRD). This syndrome is characterized by early-onset colorectal cancers, lymphomas or leukemias, and brain tumors. There is no satisfactory method for diagnosis of CMMRD because screens for mutations in MMR genes are non-informative for 30% of patients. MMR-deficient cancer cells are resistant to genotoxic agents and have microsatellite instability (MSI), due to accumulation of errors in repetitive DNA sequences. We investigated whether these features could be used to identify patients with CMMRD.

Screening for Occult Cancer in Unprovoked Venous Thromboembolism — SOME trial

open access + Commentary

Venous thromboembolism, which comprises deep-vein thrombosis and pulmonary embolism, is the third most common cardiovascular disorder.1-3 It is classified as provoked when it is associated with a transient risk factor (e.g., trauma, surgery, prolonged immobility, or pregnancy or the puerperium) and as unprovoked when it is associated with neither a strong transient risk factor nor overt cancer.
Unprovoked venous thromboembolism may be the earliest sign of cancer4,5; up to 10% of patients with unprovoked venous thromboembolism receive a diagnosis of cancer in the year after their diagnosis of venous thromboembolism.6 More than 60% of occult cancers are diagnosed shortly after the diagnosis of unprovoked venous thromboembolism.6 Thereafter, the incidence rate of cancer diagnosis gradually declines and returns to the rate in the general population after 1 year.5-7
Faced with these troubling statistics, clinicians, patients, and policymakers struggle with how aggressive to be in screening for occult cancers in patients who present with unprovoked venous thromboembolism.

Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): phase 3l

open access

 Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial

Published online June 24, 2015

The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial.

 Bevacizumab, added to platinum-based chemotherapy, did not increase overall survival in the study population as a whole. However, an overall survival benefit was recorded in poor-prognosis patients, which is concordant with the progression-free survival results from ICON7 and GOG-218, and provides further evidence  towards the optimum use of bevacizumab in the treatment of ovarian cancer.

.....Although the results of ICON7 offer the tantalising possibility that a patient subgroup might derive an overall survival benefit from first-line bevacizumab, caution should be exercised when interpreting subset analyses, and additional questions remain unanswered regarding the use of bevacizumab in newly diagnosed ovarian cancer. Only a small proportion of patients in ICON7 received bevacizumab after disease recurrence, and therefore whether or not bevacizumab use in the recurrent setting could off set the overall survival benefits recorded in this high-risk population remains unknown. Additional studies to understand the effect of subsequent bevacizumab treatment on survival and to further identify and validate molecular markers of anti- angiogenic response will be important to better define our understanding of the role of bevacizumab therapy inovarian cancer.

SNP of the EpCAM-coding gene TACSTD1 in patients with ovarian cancer and their potential translational aspects (catumaxomab)

abstract - Single nucleotide polymorphisms of the EpCAM-coding gene TACSTD1 in patients with ovarian cancer and their potential translational aspects


EpCAM is overexpressed in many neoplasms including ovarian cancer. We screened the EpCAM-coding gene TACSTD1 for single nucleotide polymorphisms (SNPs), which could alter ovarian cancer risk, impact upon disease progression, or alter binding of the therapeutic EpCAM-binding antibody, catumaxomab.


DNA fragments of 10 healthy volunteers were analyzed to identify SNPs. Subsequently, DNA of ovarian cancer patients (n = 117) and age-matched healthy controls (n = 115) was genotyped by restriction fragment length polymorphism and pyrosequencing. TACSTD1 genotypes 4461T>C were cloned into a gene expression vector; Hek293 cells were subsequently used for stable transfection. FACS analysis of the transfected Hek293 cells was conducted with HO-3-the EpCAM binding site of catumaxomab-to determine antibody binding.

Development of a Risk Stratification System to Guide Treatment for Female Germ Cell Tumors



Due to their rarity, little is known about prognostic factors in female germ cell tumors (GCTs) or outcomes following systemic therapy. Management is largely based on studies of male GCT and epithelial ovarian cancer.


Chart review was performed for all females with GCT seen at Memorial Sloan Kettering Cancer Center (MSKCC) from 1990 to 2012. Patients receiving chemotherapy were stratified using a modification of the male IGCCCG risk system, and the classifier was correlated with outcome.

Glucocorticoid Receptor Activation Inhibits Chemotherapy-induced Cell Death in High-grade Serous Ovarian Carcinoma



  • GR activation promotes cell survival in GR-positive high-grade serous ovarian carcinoma (HGS-OvCa) cell lines treated with chemotherapy.
  • GR antagonism increases chemotherapy-induced cell death in a GR-positive HGS-OvCa xenograft model.
  • GR is expressed in the majority of primary HGS-OvCas examined.


To test the hypothesis that glucocorticoid receptor (GR) activation increases resistance to chemotherapy in high-grade serous ovarian cancer (HGS-OvCa) and that treatment with a GR antagonist will improve sensitivity to chemotherapy.

ASCO 51st Annual Meeting 2015: An overview and summary of selected abstracts


On May 29 to June 2, 2015, the American Society of Clinical Oncology (ASCO) held its annual meeting in Chicago, IL, USA. The theme of the meeting this year was “Illumination and Innovation” and the data presented held up to this high aspiration. The main plenary session focused on novel immunotherapy in melanoma, pediatric cancer survivorship, and the cost of new cancer therapy. There were 11 gynecologic oncology abstracts selected for poster discussion and 14 abstracts in gynecologic oncology presented as oral presentations in three different sessions.

Hormone Receptors as a Marker of Poor Survival in Epithelial Ovarian Cancer



Androgen receptor (AR), estrogen receptor α and β (ERα, ERβ), and progesterone receptor (PR) are potential therapeutic targets in epithelial ovarian cancer. In this study we evaluate the prognostic value of these hormone receptors in ovarian cancer patients.


In a prospective multicenter randomized controlled phase II trial 196 ovarian cancer patients were randomized to carboplatin/docetaxel±celecoxib. Of 121 patients sufficient tumor tissue was available for hormone receptor analysis. Tissue micro-arrays were stained for AR, ERα, ERβ, and PR. Cluster analysis was performed to identify subgroups based on hormone receptor expression profile. Receptor expression was correlated to progression-free survival (PFS) and overall survival (OS) in uni- and multivariate analysis.


AR, ERα, ERβ, and PR were expressed in respectively 10%, 31%, 73%, and 19%. In patients with synchronous metastasis tissue available (n=69 patients), discordant receptor expression was observed in 9-32%. ERβ-expression was associated with poor PFS and OS (hazard ratios 1.88 and 1.92). Clustering analysis revealed a subgroup with hormone receptor negative disease that had a favorable PFS and OS.


Hormone receptors are expressed in the majority of ovarian cancer tumors and may serve as therapeutic targets. Clustering analysis can reveal subgroups with different outcome, which may prove valuable in selecting patients for endocrine therapy.

Immuno-PET of epithelial ovarian cancer: harnessing the potential of CA125 for non-invasive imaging

abstract - in research (preclinical)


Epithelial ovarian cancer (EOC) is characterized by the overexpression of cancer antigen 125 (CA125), a mucinous glycoprotein that serves as a tumor biomarker. Early diagnosis of EOC is plagued by its asymptomatic nature of progression and the limitations of currently used immunoassay techniques that detect CA125 as a shed antigen in serum samples. Presently, there is no technique available for the in vivo evaluation of CA125 expression in malignant tissues. Moreover, there could be an unexplored pathophysiological time window for the detection of CA125 in EOC, during which it is expressed on tumor cells prior to being shed into the bloodstream. A method for the in vivo evaluation of CA125 expression on ovarian neoplasms earlier along disease progression and/or recurrence can potentially contribute to better disease management. To this end, the present work utilizes an anti-CA125 monoclonal antibody (MAb) and a single-chain variable fragment (scFv) labeled with the positron-emitting radionuclide (64)Cu for preclinical molecular imaging of CA125 expression in vivo.


Anti-CA125 MAb and scFv were prepared and functionally characterized for target binding prior to being tested as radiotracers in a preclinical setting.

Ovarian Sertoli-Leydig Cell Tumor with Predominant Heterologous Mucinous Differentiation and Foci of Hepatocytic Differentiation

abstract: Ovarian Sertoli-Leydig Cell Tumor with Predominant Heterologous Mucinous Differentiation and Foci of Hepatocytic Differentiation: Case Report and Review of the Literature

Sertoli-Leydig cell tumor is a rare ovarian neoplasm and belongs to the group of sex cord stromal tumors. We present a case of a 15-year old girl diagnosed with Sertoli-Leydig cell tumor with heterologous elements consisting predominantly of mucinous epithelium and a sparse Sertoli-Leydig cell component, mimicking mucinous neoplasm. Furthermore, foci of hepatocytic differentiation were also identified. Immunohistochemical stains showed the component of Sertoli cell differentiation was positive for cytokeratin 18 and inhibin. The component of Leydig cell differentiation was strongly positive for inhibin. The component of hepatocytic differentiation was positive for low molecular weight keratin, HepPar1, alpha-fetoprotein and weakly positive for inhibin. Thus, this was a very rare case which created a challenge for pathologists, especially on frozen sections.