Lynch Syndrome: A Primer for Urologists and Panel Recommendations

abstract

 Purpose

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.

Materials and Methods

Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement we reviewed the available published literature and guidelines from 1998 to 2014 on Lynch syndrome and its association with upper tract urothelial carcinoma. Recommendations based on the literature and the consensus of expert opinion are provided.

Results

No randomized or prospective study has been done to evaluate Lynch syndrome in the setting of urological cancer. All data were based on retrospective studies. Lynch syndrome is an autosomal dominant genetic disease caused by germline mutations in 4 mismatch repair genes, leading to the accumulation of DNA errors in microsatellite regions. Upper tract urothelial carcinoma develops in up to 28% of patients with known Lynch syndrome. The diagnosis of Lynch syndrome is established by clinical criteria, tumor tissue testing and genetic evaluation. Urologists should suspect Lynch syndrome when a patient with upper tract urothelial carcinoma presents before age 60 years or meets the 3-2-1 rule. Screening patients with Lynch syndrome for upper tract urothelial carcinoma presents a particular challenge. While no ideal screening test exists, at a minimum routine urinalysis is recommended using the AUA guideline of 3 or more red blood cells per high power field as a trigger for further assessment. Upper tract urothelial carcinoma associated with Lynch syndrome presents at a younger age than sporadic upper tract urothelial carcinoma. It shows a higher proportion of ureteral cancer with a female preponderance and a possible predisposition to bilaterality.

Conclusions

Lynch syndrome is a common genetic disease that is an underappreciated cause of upper tract urothelial carcinoma and possibly other urological cancers. Optimal screening for upper tract urothelial carcinoma in this population is unclear. Further study is needed to identify the best screening test and interval of testing. Urologists should consider routine tissue testing of de novo upper tract urothelial carcinoma tissue in individuals at risk.

Key Words:

kidney neoplasms, ureteral neoplasms, colorectal neoplasms, hereditary nonpolyposis, carcinoma, transitional cell, DNA mismatch repair

High-Dose Intravenous Vitamin C Combined with Cytotoxic Chemotherapy in Patients with Advanced Cancer: A Phase I-II Clinical Trial

open access

 Conclusions

A chief interest of this early-phase cancer trial for general readers is the paradoxical nature of IVC therapy. Despite its biological and clinical plausibility, with only rare exceptions [11] it is ignored by conventional cancer investigators and funding agencies even as integrative and complementary cancer therapists prescribe it widely, without reporting the kind of clinical data that is normally gathered in conventional cancer drug development [27].
The present state of cancer chemotherapy is unsatisfactory. New cancer drugs continue to be developed and approved on the basis of marginal improvements in survival at an unsustainably high financial cost [59]. It would seem more rational for cancer investigators to attempt to improve the effectiveness of well known, inexpensive generic cancer chemotherapies by studying their clinical interactions with antioxidants, especially vitamin C [32]. However, the lack of financial reward and tainted association with alternative medicine could dissuade conventional investigators and funding agencies from seriously considering this approach. At present, the few cancer clinical trials of IVC being carried out are, like this one, small and supported by limited funding from integrative cancer foundations. Even if serious interest in funding and carrying out large, formal clinical trials were to develop, data are lacking as to which cancers and chemotherapy regimens to focus on.
The present study neither proves nor disproves IVC’s value in cancer therapy. The present data indicate it would be premature to attempt unfocused phase III clinical trials of this therapy at the present time. This study does provide useful information, and suggests a feasible, individual-case oriented strategy for evaluating plausible but poorly understood and unproven metabolic therapies in a mainstream academic environment that is uninterested in them [60]. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, IVC and chemotherapy regimen in which unexpectedly beneficial outcomes or exceptional responses occur frequently enough to justify focused clinical trials.

BRCA2 variant aerodigestive cancer risk

The Lancet Oncology - abstract

 A rare BRCA2 genetic variant, known as rs11571833 (K3326X), is strongly associated with squamous-cell cancers of the upper aerodigestive tract (UADT), a new study reports. BRCA2 is involved in DNA repair, and previous evidence has suggested significant associations of this variant with cancers of the lung, oesophagus, and pancreas, and to a lesser degree, with breast cancer. This new study adds UADT cancers to the list of diseases affected by rs11571833.

Pazopanib + weekly paclitaxel vs weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer phase 2 trial

Lancet Oncology: abstract

 Background

Inhibition of angiogenesis is a valuable treatment strategy for ovarian cancer. Pazopanib is an anti-angiogenic drug active in ovarian cancer. We assessed the effect of adding pazopanib to paclitaxel for patients with platinum-resistant or platinum-refractory advanced ovarian cancer.

Interpretation

Our findings suggest that a phase 3 study of the combination of weekly paclitaxel plus pazopanib for patients with platinum-resistant or platinum-refractory advanced ovarian cancer is warranted.

Tissue invasion and metastasis: Molecular, biological and clinical perspectives

abstract

Cancer is a key health issue across the world, causing substantial patient morbidity and mortality. Patient prognosis is tightly linked with metastatic dissemination of the disease to distant sites, with metastatic diseases accounting for a vast percentage of cancer patient mortality. While advances in this area have been made, the process of cancer metastasis and the factors governing cancer spread and establishment at secondary locations is still poorly understood. The current article summarizes recent progress in this area of research, both in the understanding of the underlying biological processes and in the therapeutic strategies for the management of metastasis. This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), β-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming growth factor beta (TGF-β), together with inactivation of activator protein-1 (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key targets and the use of phytochemicals, or natural products, such as those from Agaricus blazei, Albatrellus confluens, Cordyceps militaris, Ganoderma lucidum, Poria cocos and Silybum marianum, together with diet derived fatty acids gamma linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as useful approaches to target tissue invasion and metastasis as well as other hallmark areas of cancer. Together, these strategies could represent new, inexpensive, low toxicity strategies to aid in the management of cancer metastasis as well as having holistic effects against other cancer hallmarks.

The Association between Type 2 Diabetes Mellitus and Women Cancer: The Epidemiological Evidences and Putative Mechanisms

Tabstract

 Type 2 diabetes mellitus (T2DM), a chronic disease increasing rapidly worldwide, is well established as an important risk factor for various types of cancer. Although many factors impact the development of T2DM and cancer including sex, age, ethnicity, obesity, diet, physical activity levels, and environmental exposure, many epidemiological and experimental studies are gradually contributing to knowledge regarding the interrelationship between DM and cancer. The insulin resistance, hyperinsulinemia, and chronic inflammation associated with diabetes mellitus are all associated strongly with cancer. The changes in bioavailable ovarian steroid hormone that occur in diabetes mellitus (the increasing levels of estrogen and androgen and the decreasing level of progesterone) are also considered potentially carcinogenic conditions for the breast, endometrium, and ovaries in women. In addition, the interaction among insulin, insulin-like growth factors (IGFs), and ovarian steroid hormones, such as estrogen and progesterone, could act synergistically during cancer development. Here, we review the cancer-related mechanisms in T2DM, the epidemiological evidence linking T2DM and cancers in women, and the role of antidiabetic medication in these cancers.

Increased human epididymis protein 4 in benign gynecological diseases complicated with chronic renal insufficiency patients

abstract

We examined the serum concentration of human epididymis protein (HE4) in patients with benign gynecological diseases complicated with chronic renal deficiency and its significance in the differential diagnosis of benign and malignant gynecological diseases. Serum HE4 and cancer antigen 125 concentrations were detected by chemiluminescence. Clinically or pathologically confirmed gynecological diseases were grouped and retrospectively analyzed, including 50 cases of gynecological benign diseases, 35 cases of non-mucinous epithelial ovarian carcinoma, 36 cases of endometrial adenocarcinoma, 15 cases of gynecological benign diseases patients complicated with chronic renal deficiency, 15 cases of gynecological diseases without chronic renal deficiency, and 30 normal controls. Serum HE4 values in the ovarian cancer group, endometrial cancer group, gynecological benign diseases with chronic renal deficiency group, and chronic renal deficiency group were significantly increased compared with the benign gynecological diseases and normal control groups, showing a significant difference (P < 0.001). A comparison of 4 groups with high HE4 showed that the HE4 level in the 2 groups with renal deficiency were higher than those in the ovarian cancer and endometrial cancer groups, but the difference was not significant (P > 0.05); there was no significant difference between 2 groups with renal deficiency (P > 0.05). Serum concentration of HE4 was high in patients with chronic renal deficiency, which should be distinguished during differential diagnosis of gynecological benign and malignant tumors in patients with chronic renal deficiency to avoid misdiagnosis.

Family Health History: The Case for Better Tools

JAMA Network 

OC Patient to Gyn Onc: "I am going to Canada for lunch!" - pic Ovarian Cancer Get Together (Whitby)

Missing:    Yi, Cora, Cathy, Monique, Dianna, Janet, Pam, Sandi

Are urothelial carcinomas of the upper urinary tract a distinct entity from urothelial carcinomas of the urinary bladder?

Note references to Lynch syndrome

Full text 

The corporate reputation of the medical-device industry, 2014-15: a patient perspective Survey

Survey

Study on the corporate reputation of the medical-device industry in 2014/2015—the perspective of patient groups

-------------------------- Dear health campaigner, For the 4th time, PatientView is asking health campaigners worldwide to help compile the annual CORPORATE REPUTATION INDEX OF THE MEDICAL-DEVICE INDUSTRY.  • The Index is taken seriously by industry as part of its efforts to become more patient-friendly. • The results of this 2015 survey will show you how your colleagues rate the world’s various MEDICAL-DEVICE companies in 2014-2015 (whether good or bad). To thank you for your participation in this study ... ... all respondents to any PatientView study get a final copy of the resulting report (if they wish). About the questionnaire The survey is open to any health-advocacy organisation. Please circulate this email to any other patient groups that you think might also be interested. The survey has only 10 very simple questions, and will probably take no more than 10-15 minutes of your time to complete. The survey is anonymous, unless you prefer to specify otherwise. If you wish to participate in this study, you need to get your responses in by Monday, 1st June 2015. To enter the survey, please click on the following live link: Study on the corporate reputation of the medical-device industry in 2014-2015 [http://www.surveymonkey.com/s/Medical-Device-Companies-Corporate-Reputation-2014-2015] If you have any questions, please contact: Dr Alex Wyke, CEO, PatientView, UK email: alexwyke@patient-view.com A brief statement of clarification This study intends to determine how patient groups around the world perceive the medical-device industry, with the aim of improving standards throughout the industry to levels that are satisfactory to patients. The study is paid for solely by PatientView, a UK-based research and publishing group that specialises in studying trends in the patient-advocacy movement, and which passes valuable information back to patient groups. All NGOs participating in the study are sent a free copy of the report on the survey results (if they wish to receive it). PatientView is then able to fund the exercise by selling the report to any companies that wish to read it. Further information about PatientView can be found at our website: www.patient-view.com

Surgeons Say 'We Can Fix It,' Patients May Misunderstand Risks

medscape

 ....Another flaw (we can fix it) is the assumption that surgery will return patients back to how they normally were before they got sick or hurt. "For many patients, especially patients with lots of medical problems who need big operations, they are not normal after surgery."
Schwarze and colleagues analyzed 48 recordings of surgeons explaining high-risk operations to patients treated at three different academic hospitals in Madison, Boston and Toronto and found that variations on the "fix-it" theme regularly cropped up in these conversations.
Researchers reviewed transcripts of the discussions to see how surgeons deployed "fix-it" analogies to describe operations, which included various heart and brain surgeries as well as complex tumor-removal procedures.......Patients need to understand their condition, and know that sometimes the surgery can ease symptoms but can't solve the underlying problem, he said. Symptom relief can also be an open question......


 

 http://ovariancancerandus.blogspot.com/feeds/posts/default

Early Ovarian Cancer (childhood and adolescence) Increases Risk of Other Malignancies

medscape

....Corresponding author Dr. Sisti told Reuters Health in an e-mail that surveillance can be strengthened by screening for certain types of second primary malignancies, such as endocrine tumors and lymphoma. "These are usually overlooked because previous studies did not find their occurrence," he said.....


 

Initial incomplete surgery modifies prognosis in advanced ovarian cancer regardless of subsequent management

abstract

BACKGROUND:

Prognosis in ovarian cancer is determined by completeness of cytoreduction and proper management by specialized oncological gynecologists. Incomplete initial debulking surgery in non-specialized Centers is, however, a reality and there is ongoing discussion about the best subsequent management of such patients.

PATIENTS AND METHODS:

Patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics - FIGO FIGO stages IIIC-IV) who had biopsy by laparotomy or incomplete cytoreduction followed or not by chemotherapy further referred to our Institution between January 2002 and May 2014 were included. The two groups of incomplete cytoreduction [followed by upfront surgery or followed by chemotherapy and interval debulking surgery (IDS)] were compared and also compared against a cohort of 197 patients with similar characteristics who underwent upfront maximal surgery according to the standard at our Iinstitution during the same period.

RESULTS:

A total of 99 eligible patients were identified. Sixty-seven of them underwent biopsies by laparotomy and 32 underwent incomplete cytoreduction in other institutions. Twenty-eight patients underwent direct re-operation while 71 patients underwent neoadjuvant chemotherapy followed by IDS. The mean overall survival duration for patients with upfront reoperation was 31 months and 54 months for patients with neoadjuvant chemotherapy and IDS, considerably lower than the 72 months obtained for the group of 197 patients with maximal up-front complete cytoreduction at our Institution.

CONCLUSION:

Primary biopsy or incomplete cytoreduction reduces survival regardless of the subsequent approach. However, if incomplete cytoreduction has occurred, neoadjuvant chemotherapy followed by IDS is preferable to up-front reoperation.

Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

EPCAM - epithelial cell adhesion molecule - Genetics Home Reference

 Genetics Home Reference

Molecular characterization of 7 new established cell lines from high grade serous ovarian cancer

abstract

 Cancer cell lines are good in vitro models to study molecular mechanisms underlying chemoresistance and cancer recurrence. Recent works have demonstrated that most of the available ovarian cancer cell lines are most unlikely high grade serous (HGSOC), the major type of epithelial ovarian cancer. We aimed at establishing well characterized HGSOC cell lines, which can be used as optimal models for ovarian cancer research. We successfully established seven cell lines from HGSOC and provided the major genomic alterations and the transcriptomic landscapes of them. They exhibited different gene expression patterns in the key pathways involved in cancer resistance. Each cell line harbored a unique TP53 mutation as their corresponding tumors and expresses cytokeratins 8/18/19 and EpCAM. Two matched lines were established from the same patient, one at diagnosis and being sensitive to carboplatin and the other during chemotherapy and being resistant. Two cell lines presented respective BRCA1 and BRCA2 mutations. To conclude, we have established seven cell lines and well characterized them at genomic and transcriptomic levels. They are optimal models to investigate the molecular mechanisms underlying the progression, chemo resistance and recurrence of HGSOC.

Multi-institutional analysis of renal function outcomes following radical nephroureterectomy & partial ureterectomy for UTUC

 Note: of interest to Lynch Syndrome patients

abstract

 Purpose

To compare renal function outcomes in patients undergoing radical nephroureterectomy (RNU) or partial (distal) ureterectomy (PU) for upper tract urothelial carcinoma (UTUC).

Methods

Clinicopathologic data of patients undergoing RNU or PU for UTUC from 1998 to 2012 were compiled. Glomerular filtration rate was calculated preoperatively and postoperatively using the Modification of Diet in Renal Disease equation. We defined “event” as new-onset stage III chronic kidney disease (CKD) or worsening of CKD stage with preexisting CKD. Event-free survival was assessed with Kaplan-Meier methods. Cox regression analyses were performed to identify predictors of events.

Results

In total, 193 patients underwent RNU (n = 143) or PU (n = 50) over a median follow-up of 25.9 months. Overall, 15% of patients died of UTUC. High tumor grade (85.9% vs. 66.0%, P = 0.003) and locally advanced stage (>pT2, 37.8% vs. 18.0%, P = 0.014) were significantly more frequent in the RNU cohort. Stage III or higher CKD was present in 61% of RNU patients vs. 48% of PU patients (P = 0.135) at baseline. Although total event rate was higher in the PU cohort (66% vs. 43.4%, P = 0.008), event rates within the first 3 months of surgery were similar between the groups (P = 0.572). Adjuvant chemotherapy was the only predictor of events on Cox regression.

Conclusions

Rates of new-onset CKD or worsening of CKD stage were similar in patients treated with RNU and PU. Adjuvant chemotherapy may have a more significant effect on renal outcomes than surgical approach, warranting further investigation. Consideration should be given to preoperative chemotherapy, as adjuvant chemotherapy is limited by decreased renal function following surgery.

Keywords

• Upper tract urothelial carcinoma;
• Partial ureterectomy;
• Radical nephroureterectomy;
• Renal function

Plasma immune analytes in patients with epithelial ovarian cancer (comparisons with CA125)

abstract
 

OBJECTIVES:

Inflammation is a common feature of epithelial ovarian cancer (EOC), and measurement of plasma markers of inflammation might identify candidate markers for use in screening or presurgical evaluation of patients with adnexal masses.


METHODS:

Plasma specimens from cohorts of 100 patients with advanced EOC (AJCC Stage III and IV), 50 patients with early stage EOC (Stage I and II), and 50 patients with benign surgical conditions were assayed for concentrations of multiple cytokines, toll-like receptor agonists, and vascular growth factors via ELISA and electrochemiluminescence. Immune proteins were then analyzed for association with EOC. Differences in plasma protein levels between benign, early, and advanced EOC patient groups were assessed with and without adjustment for plasma cancer antigen 125 (CA-125) levels.


RESULTS:

Out of 23 proteins tested, six-including interferon gamma (IFNγ), interleukin 6 (IL-6), IL-8, IL-10, tumor necrosis factor alpha (TNFα), and placental growth factor (PlGF)-were univariately associated with EOC (all p<0.005), and one-IL-6-was associated with early stage EOC (p<0.0001). Heat shock protein 90kDa beta member 1 (HSP90B1, gp96) was associated with EOC and early stage EOC with borderline statistical significance (p=0.039 and p=0.026, respectively). However, when adjusted for (CA-125), only HSP90B1 independently predicted EOC (p=0.008), as well as early stage EOC (p=0.014).


CONCLUSIONS:

Multiple plasma cytokines, including IFNγ, IL-6, IL-8, IL-10, TNFα, PlGF, and HSP90B1 are associated with EOC. Of these, HSP90B1 is associated with EOC independent from the biomarker CA-125.

Peritoneal Carcinomatosis in Primary Ovarian Cancer Staging: Comparison Between MDCT, MRI, and 18F-FDG PET/CT

abstract

        PURPOSE:

The aim of this study was to compare multidetector CT (MDCT), MRI, and FDG PET/CT imaging for the detection of peritoneal carcinomatosis (PC) in ovarian cancer.

PATIENTS AND METHODS:
Fifteen women with ovarian cancer and suspected PC underwent MDCT, MRI, and FDG PET/CT, shortly before surgery. Nine abdominopelvic regions were defined according to the peritoneal cancer index. We applied lesion size scores on MDCT and MR and measured FDG PET/CT standard uptake. We blindly read MDCT, MR, and PET/CT before joint review and comparison with histopathology. Receiver operating characteristics analysis was performed.

RESULTS:
Ten women had PC (67%). Altogether, 135 abdominopelvic sites were compared. Multidetector CT, MRI, and FDG PET/CT had a sensitivity of 96%, 98%, and 95%, and specificity was 92%, 84%, and 96%, respectively. Corresponding receiver operating characteristics area was 0.94, 0.90, and 0.96, respectively, without any significant differences between them (P = 0.12). FDG PET/CT detected supradiaphragmatic disease in 3 women (20%) not seen by MDCT or MRI.

CONCLUSIONS:
Although MRI had the highest sensitivity and FDG PET/CT had the highest specificity, no significant differences were found between the 3 techniques. Thus, MDCT, as the fastest, most economical, and most widely available modality, is the examination of choice, if a stand-alone technique is required. If inconclusive, PET/CT or MRI may offer additional insights. Whole-body FDG PET/CT may be more accurate for supradiaphragmatic metastatic extension.

Comparison of MRI and CT for Predicting the Peritoneal Cancer Index (PCI) Preoperatively in Patients Being Considered for Cytoreductive Surgical Procedures

abstract

PURPOSE:

To compare the accuracy of MRI and CT for predicting the Peritoneal Cancer Index (PCI) preoperatively compared with the PCI tabulated at surgery.


METHODS:

Twenty-two patients underwent preoperative MRI and CT scanning followed by cytoreductive surgery for appendiceal (n = 17) and ovarian (n = 5) cancer. MR and CT examinations were retrospectively reviewed to determine the PCI. The results of these scores were compared with PCI tabulated at surgery. Patients were categorized as small volume tumor (PCI 0-9), moderate volume (PCI 10-20), and large volume (PCI > 20). Respective anatomic site scores for MRI and CT were compared with surgical findings.


RESULTS:

Compared with surgical PCI, MRI correctly categorized tumor volume in 20 (0.91) of 22 patients, including 3 of 4 patients with small volume tumor, 2 of 2 patients with moderate volume tumor, and 15 of 16 patients with large volume tumor. CT correctly categorized tumor volume in 11 of 22 (0.50) patients, including 2 of 4 patients with small-volume tumor, 2 of 2 patients with moderate volume tumor, and 7 of 16 patients with large-volume tumor. In 19 of 22 patients, CT underestimated the volume of tumor found at surgery. For all patients, the median PCI score at surgery was 33 compared with 36 for MRI and 15 for CT. Surgery confirmed 222 sites of tumor. MRI demonstrated per site sensitivity of 0.95, specificity 0.70, and accuracy 0.88. CT showed a corresponding per site sensitivity 0.55, specificity 0.86, and accuracy 0.63.


CONCLUSIONS:

MRI more accurately predicts PCI preoperatively in patients undergoing evaluation for cytoreductive surgery.

open access (2014) Pathophysiology of Cisplatin-Induced Acute Kidney Injury

open access

Abstract

Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. A known complication of cisplatin administration is acute kidney injury (AKI). The nephrotoxic effect of cisplatin is cumulative and dose-dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI may result in chronic kidney disease. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, oxidative stress, inflammation, and vascular injury in the kidney. There is predominantly acute tubular necrosis and also apoptosis in the proximal tubules. There is activation of multiple proinflammatory cytokines and infiltration of inflammatory cells in the kidney. Inhibition of the proinflammatory cytokines TNF-α or IL-33 or depletion of CD4+ T cells or mast cells protects against cisplatin-induced AKI. Cisplatin also causes endothelial cell injury. An understanding of the pathogenesis of cisplatin-induced AKI is important for the development of adjunctive therapies to prevent AKI, to lessen the need for dose decrease or drug withdrawal, and to lessen patient morbidity and mortality.

1. Introduction

Acute kidney injury (AKI) is defined as a clinical syndrome characterized by a rapid decrease in renal (kidney) function together with the accumulation of waste products such as urea [1]. The incidence of non-dialysis-requiring AKI is about 5000 cases per million people per year and incidence of dialysis requiring AKI is 295 cases per million people per year [2]. AKI complicates 1–7% of all hospital admissions and 1–25% of intensive care unit admissions [3, 4]. Furthermore, AKI is known as an independent risk factor for mortality. AKI increases the risk of death by 10- to 15-fold and results in a mortality rate of 50% [5, 6]......

Dose-Dense Approaches to Ovarian Cancer Treatment

abstract

OPINION STATEMENT:

Currently, paclitaxel and carboplatin are administered every 3 weeks as the standard agents for the first-line treatment of advanced ovarian cancer. The concept of "dose-dense therapy" is based on the Norton-Simon hypothesis that a shorter interval between the doses of cytotoxic agents is more effective in reducing tumor burden than dose escalation. The results of phase III clinical trials demonstrating the superiority of weekly paclitaxel administration, compared with a 3-week schedule in breast cancer in both the metastatic and adjuvant settings support the hypothesis. The Japanese Gynecologic Oncology Group reported the results from a phase III study comparing the conventional paclitaxel and carboplatin every 3-week administration vs dose-dense weekly administration of paclitaxel combined with the every 3-week administration of carboplatin in advanced epithelial ovarian cancer, Fallopian tube, or primary peritoneal cancer. The median progression-free survival (PFS), the primary endpoint of this study, was substantially improved in the dose-dense treatment group (28 vs 17.2 months, hazard ratio [HR]: 0.71, 95 % CI: 0.58-0.88, P = 0.0015), and the overall survival (OS) at 3 years was also higher in the dose-dense treatment group (72 · 1 %) than in the conventional treatment group (65.1 %; HR 0.75, 0.57-0.98; P = 0 · 03). The long-term outcomes at a median follow-up period of 76.8 months were reported. The median PFS was significantly longer in the dose-dense regimen than in the conventional regimen (28.2 vs 17.5 months; hazard ratio [HR], 0.76; 95 % CI, 0.62-0.91; P = 0.0037), and the median OS was 100.5 months (95 % CI 65.2-∞) in the dose-dense regimen and 62.2 months (52.1-82.6) in the conventional regimen (HR, 0.79; 95 % CI, 0.63-0.99; P = 0.039; log-rank test). Dose-dense treatment offers a potential new standard of care for first-line chemotherapy for patients with advanced epithelial ovarian cancer. Ongoing studies will clarify the best dose, schedule, and route of administration.

Role of Minimally Invasive Surgery in Gynecologic Oncology: An Updated Survey of Members of the SGO

Rabstract

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.

PMS2 monoallelic mutation carriers: the known unknown (Lynch Syndrome)

abstract

 Germ-line mutations in MLH1, MSH2, MSH6, and PMS2 have been shown to cause Lynch syndrome. The penetrance of the cancer and tumor spectrum has been repeatedly studied, and multiple professional societies have proposed clinical management guidelines for affected individuals. Several studies have demonstrated a reduced penetrance for monoallelic carriers of PMS2 mutations compared with the other mismatch repair (MMR) genes, but clinical management guidelines have largely proposed the same screening recommendations for all MMR gene carriers. The authors considered whether enough evidence existed to propose new screening guidelines specific to PMS2 mutation carriers with regard to age at onset and frequency of colonic screening. Published reports of PMS2 germ-line mutations were combined with unpublished cases from the authors' research registries and clinical practices, and a discussion of potential modification of cancer screening guidelines was pursued. A total of 234 monoallelic PMS2 mutation carriers from 170 families were included. Approximately 8% of those with colorectal cancer (CRC) were diagnosed before age 30, and each of these tumors presented on the left side of the colon. As it is currently unknown what causes the early onset of CRC in some families with monoallelic PMS2 germline mutations, the authors recommend against reducing cancer surveillance guidelines in families found having monoallelic PMS2 mutations in spite of the reduced penetrance.

Evidence for a dualistic model of high-grade serous carcinoma: BRCA mutation status, histology, and tubal intraepithelial carcinoma

abstract

Most early adnexal carcinomas detected in asymptomatic women with germline BRCA mutations (BRCA) present as serous tubal intraepithelial carcinomas (STIC). However, STICs are found in only ∼40% of symptomatic high-grade serous carcinomas (HGSCs) and less frequently in pseudoendometrioid variants of HGSC. Consecutive cases of untreated HGSC from BRCA and BRCA women with detailed fallopian tube examination (SEE-FIM protocol) were compared. STIC status (+/-) was determined, and tumors were classified morphologically as SET ("SET", >50% solid, pseudoendometrioid, or transitional) or classic predominate ("Classic"). SET tumors trended toward a higher frequency in BRCA versus BRCA women (50% vs. 28%, P=0.11), had a significantly younger mean age than those with classic HGSC in BRCA women (mean 56.2 vs. 64.8 y, P=0.04), and displayed a better clinical outcome in both groups combined (P=0.024). STIC was significantly more frequent in tumors from the BRCA cohort (66% vs. 31%, P=0.017) and specifically the BRCA tumors with classic morphology (83%) versus those with SET morphology (22%, P=0.003). Overall, several covariables-histology, BRCA status, age, coexisting STIC, and response to therapy-define 2 categories of HGSC with differences in precursor (STIC) frequency, morphology, and outcome. We introduce a dualistic HGSC model that could shed light on the differences in frequency of STIC between symptomatic and asymptomatic women with HGSC. This model emphasizes the need for further study of HGSC precursors to determine their relevance to the prevention of this lethal malignancy.

Correlation between CA125 levels after sixth cycle of chemotherapy and clinical outcome in advanced ovarian carcinoma

abstract

       AIM:

To correlate CA125 levels after platinum- and paclitaxel-based chemotherapy with progression-free survival (PFS) and overall survival (OS) in advanced ovarian carcinoma following primary cytoreduction.

MATERIALS AND METHODS:
The study was conducted on 247 patients.

RESULTS:
By log-rank test, PFS and OS were related to performance status (PS), residual disease, ascites and post-chemotherapy CA125 using 10.8 U/ml as cut-off . PFS was related to post-chemotherapy CA125 assay (cut-off values of 7.1 U/ml, 18.5 U/ml and 35.0 U/ml. OS was related to FIGO stage (p=0.02). On multivariate analysis, residual disease, ascites and post-chemotherapy CA125 with any selected cut-off were independent prognostic variables for PFS, whereas residual disease, PS and post-chemotherapy CA125 (10.8 U/ml as cut-off) were independent prognostic variables for OS.

CONCLUSION:
Post-operative CA125 using 10.8 U/ml as cut-off was an independent prognostic variable for both PFS and OS.

Inflammatory markers and risk of epithelial ovarian cancer by tumor subtypes

abstract

BACKGROUND:

Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse.

METHODS:

We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), interleukin-6 (IL-6), and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n=1,497) were matched per case. We used multivariable conditional logistic regression to assess associations.

RESULTS:

CRP and IL-6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 vs. CRP ≤1 mg/L was associated with higher overall EOC risk (OR=1.67 [1.03 - 2.70]). We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference: (e.g., IL-6: waist <80: ORlog2=0.97 [0.81 - 1.16]; waist >88: ORlog2=1.78 [1.28 - 2.48], pheterogeneity ≤0.01).

CONCLUSIONS:

Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL-6 and CRP may be associated with EOC risk among women with higher adiposity.

IMPACT:

Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu.

Effectiveness of the Risk of Malignancy Index and the Risk of Ovarian Malignancy Algorithm in a Cohort of Women With Ovarian Cancer: Does Histotype and Stage Matter?

abstract
 
       OBJECTIVE:

To examine the performance of the Risk of Malignancy Index (RMI) and Risk of Ovarian Malignancy Algorithm (ROMA) by histologic subtype and stage of disease in a cohort of women with ovarian cancer.

METHODS:
All patients with confirmed ovarian cancer at the Princess Margaret Hospital between February 2011 and January 2013 were eligible for study inclusion. Preoperative cancer antigen 125, human epididymis protein 4, and ultrasound findings were reviewed, and the sensitivity and false-negative rates of the RMI and ROMA were determined by stage of disease and tumor histology.

RESULTS:
A total of 131 patients with ovarian cancer were identified. High-grade serous (HGS) histology was most frequently associated with stage III/IV disease (n = 46 [72% of stage III/IV]) vs stage I (n = 5 [11% of stage I]; P < 0.0001). Clear cell (CC) and endometrioid (EC) histology presented most commonly with stage I disease (n = 9 [20%] and n = 13 [29% of stage I cases], respectively). Median cancer antigen 125 and human epididymis protein 4 values were significantly higher for HGS than for EC or CC histology. Risk of Malignancy Index II demonstrated the highest sensitivity of the 3 RMI algorithms. All RMIs and ROMA were significantly more sensitive in predicting malignancy in patients with HGS than EC or CC histology. Risk of Malignancy Index II (n = 38) and ROMA (n = 35) exhibited sensitivities of 68% and 54% and false-negative rates of 32% and 46%, respectively, for patients with stage I disease vs sensitivities of 94% and 93% and false-negative rates of 6% and 7% for patients with stage III/IV disease.

CONCLUSION:
Both RMI and ROMA performed well for the detection of advanced ovarian cancer and HGS histology. These triaging algorithms do not perform well in patients with stage I disease where EC and CC histologies predominate. Clinicians should be cautious using RMI or ROMA scoring tools to triage isolated adnexal masses because many patients with stage I malignancies would be missed.

U.S. FDA Grants Breakthrough Therapy Designation to Rucaparib in Advanced Ovarian Cancer With BRCA Mutations

The ASCO Post

Prevalence of Germline Mutations in Cancer Predisposition Genes in Patients With Pancreatic Cancer

open access

 Background & Aims

We investigated the prevalence of germline mutations in APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, and TP53 in patients with pancreatic cancer.

 Article Outline

1. Materials and Methods
   1. Patients
   2. Patient Sampling Procedure
   3. Next-Generation Sequencing and Bioinformatics
   4. Variant Characterization
   5. Statistical Analysis
2. Results
   1. Patient Selection and Clinical Characteristics
   2. Variant Detection and Characterization
   3. Pathogenic Mutation Carriers
   4. Clinical Characteristics and Mutation Carrier Status
3. Discussion
4. Supplementary Material

Conclusions

A small but clinically important proportion of pancreatic cancer is associated with mutations in known predisposition genes. The heterogeneity of mutations identified in this study shows the value of using a multiple-gene panel in pancreatic cancer.

FAQ: Are Compounded Bioidentical Hormones Safe for HRT?

FAQ: Medscape

DREMECELS | DNA Repair Mechanisms Database

DREMECELS  (MSH2 as an example (see main page for further information)

 

Variation in Lynch Syndrome : Correspondence

open access: Diseases of the Colon & Rectum

To the Editor—

In the latest version of “For Debate,” 2 articles are presented that discuss the variation in the clinical presentation of Lynch syndrome. The first, by Ponti et al,¹ deals with genetic anticipation by which affected members of a family with an hereditary syndrome develop disease at earlier ages in succeeding generations. The second, by Nancy You,² focuses more on variability in expression due to different genotypes and other, yet to be identified, genetic modifiers. There is really no debate here, with exception, perhaps, of the unresolved controversy over the existence of anticipation in hereditary colorectal cancer. As with other hereditary syndromes of colorectal cancer predisposition, different Lynch syndrome families, with different mutations, sometimes in different genes, have different clinical pictures. This is expected. It is more surprising that affected family members, carrying the same mutation, may also have different clinical presentations. This is clinically relevant given the suggestion that surveillance in Lynch syndromes families be designed around the family pattern of disease......

...... We can always relax surveillance when the safety of the relaxation becomes better established, but missing an early cancer because of a conservative approach from the start goes against the grain.

Renal Autotransplantation in Lynch Syndrome: A Viable Option in a Patient With Contralateral Metachronous Ureteral Cancer

abstract

The success of human kidney allotransplantation was realized over six decades ago. First described 50 years ago, renal (kidney) autotransplantation has been utilized sparingly as a salvage procedure for patients at risk of losing renal function, either from a benign or malignant condition. While classically associated with colorectal malignancies, Lynch syndrome also carries a small yet significant risk for the development of ureteral carcinoma. For these patients who develop chronic kidney disease, allotransplantation may not be an option due to the lifelong risk of several malignancies. We report the first known case of renal autotransplantation in a patient with metachronous ureteral cancer due to Lynch syndrome.

Perspectives on Progress: Using Genomics to Guide Clinical Therapy

selected abstracts

Abstract 1 – Lessons From the Cancer Genome Atlas

D. Neil Hayes, University of North Carolina (UNC) School of Medicine, UNC Lineberger, Chapel Hill, North Carolina, USA

The past 5 years have seen an explosion of data from cancer genome sequencing projects. The single largest endeavor is the Cancer Genome Atlas (TCGA). As of the beginning of 2015, TCGA had deposited more than 11,000 patient genome profiles into the public record, covering more than 30 tumor types. The experience gained by TCGA offers insights into future translational research in the era of genomics. Lessons learned from the analysis of these 11,000 patients will direct researchers and clinicians alike. The goal of this talk is to summarize the TCGA experience and to look forward to next steps in genomics research, clinical trials, and clinical care.

 Abstract 3 – Functional Genomics and Proteomics of Ovarian Cancer Elucidate Novel Targets and Therapies

 Gordon B. Mills, The University of Texas MD Anderson Cancer Center, Houston, Texas USA

Ovarian cancer is a disease of copy number change, with few recurrent genomic mutations other than almost universal changes in TP53 and abnormalities in BRCA1/2 in the pathways regulated by BRCA1/2. A number of drugs are emerging that can normalize the function of a subset of TP53 mutations, and additional drugs, such as WEE1 inhibitors, may exert greater activity in TP53-mutant tumors. The most exciting opportunity in ovarian cancer therapy is the emergence of poly(ADP ribose) polymerase (PARP) inhibitors as synthetic lethal drugs with abnormalities in BRCA1/2 defects. Furthermore, it is critically important to identify markers of benefits and rational drug combinations for patients receiving PARP inhibitors. Finally, it is unlikely that monotherapy will have major impact on patients with ovarian cancer because of its complex genomic nature. Thus, it will be critical to identify rational drug combinations. Approaches to each of these opportunities and challenges will be presented.

Shared Decision Making in Cancer Care: Does One Size Fit All?

JAMA Network

Patient Demands and Requests for Cancer Tests and Treatments

open access

The Myth of the Demanding Patient

JAMA Oncology 

Losing “Losing the Battle With Cancer”

Blogger's Note: although the webpage indicates there is opportunity to Comment this section is available to subscribers only

JAMA Network

....As physicians who treat oncology patients, and as advocates, we believe that this quote is unsuitable and even demeaning to the patient, his or her family, and friends.....

CDC - Breast Cancer in Young Women - deadline May 15th

Share Your Story

Share Your Story

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Share Your Story. Empower and Educate Young Women.
About 11% of new breast cancer cases in the United States affect women under the age of 45, but many young women may not realize they are at risk for this disease.
The Centers for Disease Control and Prevention (CDC) is looking for women to share their stories about hereditary breast cancer, breast cancer risk, exploring their family history of cancer, and breast health for their new campaign, Bring Your Brave.
Please respond no later than May 15, 2015, if you are interested in being considered for the campaign and fit the following criteria.
We are looking for stories from women ages 18 through 44 who—

• Found a lump or abnormal change in their breast that turned out not to be breast cancer.
• Have a mother, sister, or first cousin who had breast cancer before the age of 50 and has a BRCA gene mutation.
• Have undergone genetic counseling and testing, and fit at least one of the following criteria—
  • Have had breast cancer and have a BRCA gene mutation.
  • Have a family history of breast or ovarian cancer and have a BRCA gene mutation.
  • Have a personal or family history of breast cancer, have a BRCA gene mutation, and are of Ashkenazi Jewish heritage.

We are also looking for stories from women of any age who—

• Have been diagnosed with breast cancer before age 50, have a BRCA gene mutation, and have a daughter age 18 through 40. Both women must be willing to share their story about hereditary cancer, learning about family history, and having a BRCA gene mutation.

To be considered for this project, women must—

• Not smoke or use illegal drugs.
• Have completed their cancer treatment (if applicable) at least one year ago.

Prospective cast members must be willing to—

• Share their story publicly as part of a national campaign.
• Have their doctor complete a form about their medical history.
• Submit to a background check.
• Participate in a video and/or photo shoot.

Help young women learn about their risk for breast cancer by sharing your story by May 15, 2015.
For more information or to participate, send e-mail to BYBRecruitment@cdc.gov or call (202) 729-4099.

• Page last reviewed: April 2, 2015
• Page last updated: April 2, 2015
• Content source:
  • Division of Cancer Prevention and Control,
  •  Centers for Disease Control and Prevention

Paper/Letter/Author's Response: 2 Types of Ovarian Cortical Inclusion Cysts: Proposed Origin and Possible Role in Ovarian Serous Carcinogenesis

open access - Letter:
 

The above publication is very interesting and deals with an important topic, that is, the source of high-grade serous ovarian carcinomas. The authors propose that all of these highly malignant tumors originate from oviductal fimbriae, or from ovarian cortical inclusion cysts (CICs) that are derived from fimbriae, rather than from CICs derived from ovarian surface epithelium (OSE). Several points in the publication require clarification before this conclusion can be accepted:......

Author's Response: (open access)   To the Editor: We appreciate Dr Auersperg's letter regarding our paper as it gives us the opportunity to address and clarify issues which she raises. As we understand from her letter, Dr Auersperg primarily takes issue with the view that all high-grade ovarian serous carcinomas are derived from fallopian tube-type epithelium. Although we do subscribe to this view, this was not the primary aim of our study. The specific aim was to try to characterize the nature and presumed origin of ovarian cortical inclusion cysts (CICs) because they have been proposed to be the source of these ovarian carcinomas..... Original Article: Two Types of Ovarian Cortical Inclusion Cysts: Proposed Origin and Possible Role in Ovarian Serous Carcinogenesis Banet, Natalie; Kurman, Robert J.   International Journal of Gynecological Pathology

Ovarian Strumal Carcinoid Containing Appendiceal-Type Mucinous Tumor Patterns Presenting as Pseudomyxoma Peritonei

abstract

We report for the first time a case of ovarian strumal carcinoid containing both trabecular carcinoid and mucinous glands lined by both goblet and neuroendocrine cells and a low-grade mucinous neoplasm that presented clinically as pseudomyxoma peritonei in the absence of appendiceal lesion in a 58-yr-old woman. Histologically, there were both a tall columnar cell epithelial component lacking neuroendocrine cells, showing the scalloped contours and subepithelial clefts of low-grade appendiceal-type neoplasms and a mixed goblet cell neuroendocrine element. Characteristically, both reproduced appendiceal neoplastic phenotypes in a teratoid fashion. In addition, we present previously unreported oncocytic and mucinous changes in the thyroideal components of strumal carcinoid. This case represents a rare instance of pseudomyxoma peritonei of primary ovarian origin and is an example of multiple somatic teratoid endodermal differentiations of the different sections of the embryonal gut: foregut represented by thyroid, midgut by both mucinous appendiceal components, and hindgut by trabecular carcinoid.

Concurrent Primary Peritoneal Low-Grade Serous Carcinoma and Endometrial High-Grade Serous Carcinoma

open access

 .....We believe this is the first reported case of synchronous primary peritoneal low-grade serous carcinoma and a (high-grade) serous carcinoma of endometrium. Although this may be an incidental finding, it may also indicate a common histogenetic pathway for these tumors. Additional cases and further studies are required for the evaluation of this hypothesis.

Optimal Sampling of Grossly Normal Omentum in Staging of Gynecologic Malignancies

abstract

 The pathologic detection of microscopic omental metastases is important for the staging and treatment of ovarian and endometrial cancer. The question of how to sample grossly negative omentectomy specimens has not been adequately answered. We reviewed our institutional experience by retrieving a series of gynecologic cancer cases from 1998 to 2013 in which the omentum was grossly negative, but microscopically positive. There were 21 patients with ovarian carcinoma, 7 with ovarian borderline tumors, and 16 with endometrial carcinoma (44 patients in total). Cases in which the omentum was grossly abnormal or suspicious were excluded. A mean of 5.2 blocks were submitted per case (range, 4–15), of which a mean of 2.7 were positive for metastatic disease (range, 1–5). The distribution of cases by percentage of blocks positive was bimodal: some cases showed only 1 or 2 foci of disease in the entire sampled omentum, whereas in other cases nearly every block was positive. Only 3 cases had been sampled with >5 blocks. We used a series of simulated cases, bootstrapped on the retrospective series, to determine the additional sensitivity conferred by submitting >5 blocks. This model indicated that 5 blocks will, in fact, be insufficient to capture microscopic metastases in some cases. Examination of 5 blocks has an estimated sensitivity of 82%, whereas submission of 10 blocks raises the sensitivity to 95%. These results suggest that submission of 10 blocks should be considered for grossly negative omentectomy specimens when other staging is negative.

Simultaneous Carcinomas of the Breast and Ovary: Utility of Pax-8, WT-1, and GATA3 for Distinguishing Independent Primary Tumors from Metastases

abstract

 Breast carcinomas rarely metastasize to the ovary and are even more rarely present clinically as primary ovarian tumors. However, patients with breast cancer not infrequently develop independent primary ovarian carcinomas. In these cases, distinction between independent primaries and metastatic tumors is crucial. Several comparative immunohistochemical studies have been reported, but few included significant clinicopathologic data and none investigated cases of ovarian and breast carcinomas from the same patients. In this study, we compared 18 cases of patients with bona fide independent breast and ovarian carcinomas (15 high-grade serous and 3 clear cell carcinomas), with 9 cases of patients with known mammary carcinomas (7 lobular and 2 ductal carcinomas) metastatic to the ovary. Immunohistochemical stains for Pax-8, WT-1, and GATA3 were carried out on tissue microarrays (TMA). Most primary ovarian carcinomas were larger than the metastatic tumors (P=0.001) and were diagnosed at an advanced stage. All primary ovarian tumors showed marked nuclear pleomorphism, whereas only 2 metastatic breast carcinomas had Grade 3 nuclei (P=0.000). The vast majority of ovarian metastases (7/9) showed the typical pattern of lobular breast carcinoma. Pax-8 and WT-1 expression were found in 16 of 18 (88%) and 13 of 18 (72%) primary ovarian carcinomas, respectively. In contrast, all primary ovarian carcinomas were negative for GATA3. The 2 Pax-8-negative ovarian carcinomas were also negative for WT-1. With the exception of 3 triple-negative carcinomas, all primary breast carcinomas were positive for GATA3. All metastatic breast carcinomas were positive for GATA3 and negative for Pax-8. WT-1 expression was seen in only 1 of 9 metastatic breast carcinomas (11%). Patients with ovarian metastases had worse prognosis than patients with independent breast and ovarian carcinomas (P=0.000). Pax-8, WT-1, and GATA3 immunoreactions are useful in the distinction between independent primaries and metastatic mammary carcinomas to the ovary in the light of clinicopathologic findings.

Morbidity of the Abdominal Wall Resection and Reconstruction After Cytoreductive Surgery and HIPEC

abstract

BACKGROUND: 

CRS/HIPEC has evolved as a therapeutic option for selected patients with peritoneal surface malignancies. To achieve complete cytoreduction (CC), some patients require extensive abdominal-wall resection (AWR) and subsequent complex reconstructions, which may be associated with wound complications (WC) and delay of postoperative cancer therapy.

METHODS:

Review of a prospective database of 350 patients revealed 213 patients with peritoneal carcinomatosis who underwent AWR due to suspected or proven wound/port site metastases during CRS/HIPEC. Tumor origin included: appendix, colon, ovarian, peritoneal mesothelioma, primary peritoneal, and others. WC were related to peritoneal carcinomatosis index (PCI), CC score, length of surgery, type of AWR and closure, blood transfusion, and albumin levels using binary logistic regression (odds ratios (OR) and 95 % CIs) analysis.

RESULTS:

PCI ≥ 20 was found in 151 (71 %), CC was achieved in 178 (84 %). Mean length of surgery was 613 min. Postoperative WC were detected in 49 of 213 (23 %) patients, 13 (6 %) had Grade III (according to Clavien-Dindo's classification) WC, and led to delay of postoperative chemotherapy. WC occurred in 21 of 64 (32.8 %) patients with excision of port sites (odds ratio [OR] = 2.11, confidence interval [CI] = 1.09-4.10, p = 0.026). Primary fascial closure was performed in 191 of 213 (89.7 %) patients, 40 (21 %) of whom had WC. Mesh-assisted abdominal wall reconstruction was required in 22 of 213 (10.3 %) patients, of whom 9 (40.9 %) had WC (OR = 2.61, CI = 1.04-6.55, p = 0.035).

CONCLUSIONS:

Port-site excision and mesh-assisted abdominal wall reconstruction were associated with higher incidence of postoperative WC following CRS/HIPEC. The implications of these preliminary findings may need to be considered during surgical planning for these patients.

Fosbretabulin and Avastin Combo Delays Progression, But Doubles Hypertension in Ovarian Cancer

Cure Today

Bradley J. Monk, presented findings during at the 2015 Society of Gynecologic Oncology’s (SGO) Annual Meeting on Women’s Cancer.
“Based on the progression-free survival and tolerability of these two anti-vascular therapies, further evaluation is warranted for this chemotherapy-free regimen, with the understanding that fosbretabulin may increase the frequency of hypertension,” said Monk, professor of gynecologic oncology at the University of Arizona Cancer Center. “Overall survival data are currently too early in the timeline to warrant any conclusions....

Bradley J. Monk, presented findings during at the 2015 Society of Gynecologic Oncology’s (SGO) Annual Meeting on Women’s Cancer.

“Based on the progression-free survival and tolerability of these two anti-vascular therapies, further evaluation is warranted for this chemotherapy-free regimen, with the understanding that fosbretabulin may increase the frequency of hypertension,” said Monk, professor of gynecologic oncology at the University of Arizona Cancer Center. “Overall survival data are currently too early in the timeline to warrant any conclusions, because this was a hypothesis-generating trial. But, in general, we now know that vascular disruption is highly significant.” - See more at: http://www.curetoday.com/articles/Fosbretabulin-and-Avastin-Combo-Delays-Progression-But-Doubles-Hypertension-in-Ovarian-Cancer?utm_source=Informz&utm_medium=Cure+Today&utm_campaign=CURExtra%2Demail%2D4%2D8%2D15#sthash.J5MYHZ4C.dpuf

Crossing Tumor Types: BRCA Experience Points Way to New Diagnostic Paradigm (eg. Olaparib)

article

 ....Consider, for example, the recent FDA approval of olaparib (Lynparza) in the second-line treatment of patients with platinum-resistant ovarian cancer. This agent, a PARP (poly [ADP-ribose] polymerase) inhibitor, has been shown in both single-agent efficacy trials and a randomized phase 2 study to have impressive activity in BRCA-mutation positive disease. (Note: The approved indication for this agent in the management of ovarian cancer is very limited, which is surprising and highly questionable in light of existing peer-reviewed data that strongly support the effectiveness of the agent in additional settings in this malignancy.)
The specific point of this commentary is not to highlight the widely recognized favorable biological and clinical activity of olaparib in ovarian cancer, but rather to acknowledge a potential role for the drug in other malignancies. In a highly provocative report, investigators described the effectiveness of this agent in a heterogeneous group of patients with advanced cancers who also possessed a documented BRCA1 or BRCA2 germline mutation. The overall objective response rate in this trial was 26 percent......

Olaparib May Prove Versatile

Consider, for example, the recent FDA approval of olaparib (Lynparza) in the second-line treatment of patients with platinum-resistant ovarian cancer. This agent, a PARP (poly [ADP-ribose] polymerase) inhibitor, has been shown in both single-agent efficacy trials and a randomized phase 2 study to have impressive activity in BRCA-mutation positive disease. (Note: The approved indication for this agent in the management of ovarian cancer is very limited, which is surprising and highly questionable in light of existing peer-reviewed data that strongly support the effectiveness of the agent in additional settings in this malignancy.)

The specific point of this commentary is not to highlight the widely recognized favorable biological and clinical activity of olaparib in ovarian cancer, but rather to acknowledge a potential role for the drug in other malignancies. In a highly provocative report, investigators described the effectiveness of this agent in a heterogeneous group of patients with advanced cancers who also possessed a documented BRCA1 or BRCA2 germline mutation. The overall objective response rate in this trial was 26 percent.

As previously established, olaparib was shown to produce objective tumor regressions in patients with ovarian cancer (31 percent; 60 of 193 patients). - See more at: http://www.curetoday.com/articles/Crossing-Tumor-Types-BRCA-Experience-Points-Way-to-New-Diagnostic-Paradigm?utm_source=Informz&utm_medium=Cure+Today&utm_campaign=CURExtra%2Demail%2D4%2D8%2D15#sthash.q7xsHDLA.dpuf

Enhanced GAB2 expression is associated with improved survival in high-grade serous ovarian cancer and sensitivity to PI3K inhibition.

abstract

Identification of genomic alterations defining ovarian carcinoma subtypes may aid the stratification of patients to receive targeted therapies. We characterised high-grade serous ovarian carcinoma (HGSC) for the association of amplified and overexpressed genes with clinical outcome using gene expression data from 499 HGSC patients in the Ovarian Tumor Tissue Analysis cohort for 11 copy number amplified genes: ATP13A4, BMP8B, CACNA1C, CCNE1, DYRK1B, GAB2, PAK4, RAD21, TPX2, ZFP36 and URI. The Australian Ovarian Cancer Study and The Cancer Genome Atlas data sets were also used to assess the correlation between gene expression, patient survival and tumour classification. In a multivariate analysis, high GAB2 expression was associated with improved overall and progression-free survival (P=0.03 and 0.02), while high BMP8B and ATP13A4 were associated with improved progression-free survival (P=0.004 and P=0.02). GAB2 over expression and copy number gain were enriched in the AOCS C4 subgroup. High GAB2 expression correlated with enhanced sensitivity in vitro to the dual phosphoinositide-3-kinase (PI3K)/mTOR inhibitor, PF-04691502, and could be used as a genomic marker for identifying patients that will respond to treatments inhibiting PI3K signalling.

Patient Education vs. Patient Experiences of Self-advocacy: Changing the Discourse to Support (ovarian) Cancer Survivors

abstract

A growing emphasis on patient self-advocacy has emerged in the public discourse on cancer survivorship. This discourse shapes patients' conceptualizations about self-advocacy and in turn influences their health care attitudes and behaviors. The purpose of this discourse analysis is to explore the language of self-advocacy by comparing a published self-advocacy guide with the lived experiences of women with ovarian cancer. Data sources include (1) a self-advocacy patient education guide published by the National Coalition for Cancer Survivorship and (2) transcripts of focus groups conducted with ovarian cancer survivors. Discourse analysis techniques were used to take a close look at the language used by both to uncover the meaning each group ascribed to self-advocacy. Challenges and inconsistencies were noted between the patient education guide and transcripts including viewing self-advocacy as a skill set to assert one's needs as opposed to a means by which to preserve a positive attitude and maintain a trusting relationship with health care providers, respectively. Some women saw themselves as self-advocates yet struggled to locate relevant health information and hesitated to upset their relationship with their health care providers. This analysis highlights tensions between the discourses and points to ways in which patient education materials can be adjusted to support cancer survivors in advocating for their needs according to their unique situations and preferences.

Time for a Level Playing Field: Inequalities in Regulatory/Approval Processes—The Example of Bevacizumab in Epithelial Ovarian Cancer

open access

..... In summary, the decision to not approve bevacizumab in certain jurisdictions for ovarian cancer runs contrary to the evidence......Finally, harmful drugs, such as those with excessive and unmanageable adverse effects, should not be approved. However, this judgment needs to be made with the input of experts in the field: patients, their families, and practicing oncologists.

Retraction Note: Gene-gene interaction network analysis of ovarian cancer using TCGA data

Journal of Ovarian Research

 Retraction

The Publisher and Editor regretfully retract this article [1] because the peer-review process was inappropriately influenced and compromised. As a result, the scientific integrity of the article cannot be guaranteed. A systematic and detailed investigation suggests that a third party was involved in supplying fabricated details of potential peer reviewers for a large number of manuscripts submitted to different journals. In accordance with recommendations from COPE we have retracted all affected published articles, including this one. It was not possible to determine beyond doubt that the authors of this particular article were aware of any third party attempts to manipulate peer review of their manuscript.