1st description analysis of MLH1, MSH2 & MSH6 in Algerian families with suspected Lynch syndrome

open access:
First description of mutational analysis of MLH1, MSH2 and MSH6 in Algerian families with suspected Lynch syndrome 

  21 different families from East of Algeria

  This work represents the implementation of a diagnostic algorithm for the identification of Lynch syndrome patients in Algerian families.

Results

We screened 21 unrelated Algerian probands (13 males and 8 females) with suspicion of Lynch syndrome. In fact, 19 patients of 21 were younger than 50 years when diagnosed with confirmed adenocarcinoma of the colon or rectum or of the HNPCC spectrum, and 2 patients were older than 50 years but presenting a family history of Lynch syndrome at the time of diagnosis. The individual age at the moment of the study varied between 25 and 57 with a median age of 41 years. Clinical and tumor related characteristics of patients and their relatives are summarized in Table 2. Genealogical data of the three families fulfilling Amsterdam I/II criteria for HNPCC are presented in Fig. 1.

Conclusion

Definitive conclusions are not possible, given the limited number of samples analyzed. The benefits of universal tumor testing may be limited by the availability and patient acceptance of genetic testing. More attention should be given to increasing the awareness of the Algerian population of hereditary CRC. Initially, we confirmed that MSH2, MLH1, andMSH6 contribute to CRC susceptibility in our families. The exploration of the MMR genes by sequencing and MLPA, in this work, has enabled the implementation of a diagnostic algorithm for the identification of HNPCC. However, it should be interesting to adopt a specific program on cancer genetics to improve the strategies for identifying individuals at high risk of CRC. Therefore, further screening tests in tumors need to be performed like IHC or MSI-analysis of all CRCs. This may be an effective tool for identifying more LS in Algerian families. In terms of prevention, the surveillance of individuals at high risk for CRC prevents the development of advanced CRC, and the clinical management may result in reduced cancer mortality for probands and their families.

(urology) Lynch syndrome in upper tract urothelial carcinoma: significance, screening, and surveillance

abstract

Purpose of review:  

Lynch syndrome is a genetic syndrome that integrates a large spectrum of cancers caused by germline mutations in mismatch repair genes. Its incidence is underestimated due to a lack of systematic screening in the population. Because upper tract urothelial carcinoma is the third-most common cancer associated with the syndrome, urologists should be aware of the diagnostic pathway.

Recent findings: 

Lynch syndrome can be positively diagnosed after the three following distinct steps: meeting the clinical criteria, tissue and genetic testing, and familial genetic counseling. It must be suspected for patients with upper tract urothelial carcinoma before the age of 60 years and in cases of evocative personal/familial medical histories. When a diagnosis is suspected, immunohistochemistry and Polymerase Chain Reaction are the next steps to confirm the diagnosis. After confirmation, the key to management is a good surveillance to prevent disease recurrence using urinary analysis and imaging as well as screening of first-degree relatives.

Summary:  

Despite the lack of high-level studies of upper tract urothelial carcinoma in Lynch syndrome, its prevalence is not negligible. Thus, expert recommendations are required for its management. Individuals and family should be informed of the importance of close screening and surveillance.

Risk factors of epithelial ovarian carcinomas among women with endometriosis: a systematic review

abstract

Introduction

To evaluate the published literature on epidemiologic risk factors for epithelial ovarian cancer (EOC) among women with a diagnosis of endometriosis.

Material and methods

A systematic literature search was conducted in PubMed and Scopus. Studies comparing epidemiologic risk factors of EOC among women with endometriosis were included. A quality assessment was conducted using the Newcastle-Ottawa Scale.

Results

Eight of 794 articles met the inclusion criteria; all were case-control studies. A lower risk of EOC was observed in women with documented complete surgical excision of endometriotic tissue and suggested among women with unilateral oophorectomy. The use of oral contraceptives (≥10 years) may be associated with a lower risk of EOC among women with endometriosis, whereas older age at endometriosis diagnosis (≥45 years, pre- or postmenopausal), nulliparity, hyperestrogenism (endogenous or exogenous), pre-menopausal status at endometriosis diagnosis solid compartments as well as larger size of endometrioma (≥9 cm in diameter at endometriosis diagnosis) were all associated with an increased risk of ovarian cancer.

Conclusion

A subgroup of women with endometriosis characterized by endometriosis observed through surgery or imaging after the age of 45 years, nulliparity, post-menopausal status at endometriosis diagnosis, larger size of endometrioma (>9cm) at endometriosis diagnosis, hyperestrogenism (endogenous or exogenous) and/or cysts with solid compartments may have an elevated risk of EOC. However, due to the limited number and size of studies in this area we cannot draw definitive conclusions. Further research into a risk factor profile among women with endometriosis is needed before clear recommendations can be made.

Synchronous and Metachronous Malignancies After Malignant Struma Ovarii in the SEER Database (thyroid/salivary)

abstract

BACKGROUND/AIM:

Second primary tumors (SPTs) often occur, either synchronous or metachronous. Struma ovarii is a rare ovarian tumor represented by thyroid tissue in the ovary. Among other factors, production of thyroid hormones by the tumor or a shared genetic predisposition can further influence the development of SPTs. The occurrence of SPT, either synchronous or metachronous, following a long follow-up, has never been considered extensively.

PATIENTS AND METHODS:

We analyzed the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2011 to follow-up all the cases of malignant struma ovarii in an effort of calculate the occurrence of SPTs in this cohort of patients.

RESULTS:

We identified 21 patients with malignant struma ovarii in the period between January 1973 and December 2011. In a follow-up period of 219.57 person-years, 3 patients had SPT. One patient had synchronous thyroid sclerosing carcinoma, 1 patient had metachronous papillary adenocarcinoma with a latent time of 7 years and 1 patient had synchronous salivary ductal carcinoma.

CONCLUSION:

Up to date, only thyroid synchronous tumors have been reported in the literature. A synchronous and a metachronous thyroid tumor, plus a synchronous salivary gland tumor, were found. A significant association between malignant struma ovarii and thyroid/salivary gland cancer is herein demonstrated.

Genomic alterations in neuroendocrine cancers of the ovary (small cell carcinoma of the ovary)

Journal of Ovarian Research | Full Text

Background

As we have previously reported, small cell carcinoma of the ovary (SCCO) is a rare, aggressive form of ovarian cancer associated with poor outcomes. In an effort to identify new treatment options, we utilized comprehensive genomic profiling to assess the potential for novel therapies in SCCO.

 Conclusion

Neuroendocrine cancers of the ovary are rare malignancies. With no recurrent actionable mutations, treatment remains a challenge. Future clinical trials looking at standard of care chemotherapy using platinum based chemotherapeutics and comparing that to specific chemotherapy regimens based off of IHC mutations may prove to be of significance in treating this rare disease. Our study showed that all SCCO types showed high expression of TOP2A, therefore, trials comparing platinum based therapies to topoisomerase II inhibitors such as doxorubicin or etoposide in patients who have high expression of ERCC1, which is associated with platinum resistance, may lead to a change in our approach to this subset of diseases. Also, there is potential for clinical trials comparing standard chemotherapy to PD1/PDL1 inhibition in SCCO as our subset of SCCO patients showed increased expression of PD1 and PDL1. Novel treatment options can be used on a case-by-case basis depending on the genomic profile. Prospective studies need to be conducted for better results, but given the rarity of this disease, that may prove to be difficult.

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Clinical Actionability of Comprehensive Genomic Profiling for Management of Rare or Refractory Cancers

the Oncologist

Background. The frequency with which targeted tumor sequencing
results will lead to implemented change in care is unclear.
Prospective assessment of the feasibility and limitations
of using genomic sequencing is critically important.

Methods. A prospective clinical study was conducted on 100
patients with diverse-histology, rare, or poor-prognosis cancers
to evaluate the clinical actionability of a Clinical Laboratory
Improvement Amendments (CLIA)-certified, comprehensive
genomic profiling assay (FoundationOne), using formalin-fixed,
paraffin-embedded tumors. The primary objectives were to
assess utility, feasibility, and limitations of genomic sequencing
for genomically guided therapy or other clinical purpose in the
setting of a multidisciplinary molecular tumor board.....

                         RESULTS
Genomic Spectrum Reflects Both Intertumoral and Tumor Type–Specific Commonalities

Four pediatric and 96 adult patients with rare histology or refractory
cancers underwent tumor genomic profiling for a varied spectrum
of epithelial and mesenchymal origin tumors (supplemental online
Figs. 1, 2; supplemental online Table 1). At enrollment, 91% of
patients were stage IV and had received a mean of 2.5 prior
therapies.....

Understanding “PrecisionMedicine” (eg. importance of case reports...)

the Oncologist

Dr. Robert Coleman on BRCA Testing in Ovarian Cancer (video 1:34 min)

Dr. Robert Coleman (onclive) 
Aug 26, 2016

Robert Coleman, MD, professor in the department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, discusses BRCA testing for ovarian cancer.

The current recommendations for BRCA testing say that high-grade serous patients should get it at the diagnosis. However, recent data has shown that other histology types have enough of a frequency that it's worth testing there as well, says Coleman. Outside mucinous tumors, germline testing has been done across the board, says Coleman.  

Germline and somatic BRCA alterations look similar, says Coleman. There isn’t much data on other non-BRCA germline mutations that might be associated with familial or genetic risk, and what their likelihood is, but that field is expanding, says Coleman.

SEE ALL VIDEOS FROM: Robert Coleman, MD

Spotlight on ASCO’s Geriatric Oncology Webpage - The ASCO Post

The ASCO Post

 
ASCO’s Web-Based Resource
Through a recent grant sponsored by the Association of Specialty Professors, ASCO, in conjunction with the Geriatric Oncology Special Interest Group, has been able to develop the first Web-based resource for many aspects pertaining to geriatric oncology, ranging from patient care to training (https://www.asco.org/practice-guidelines/cancer-care-initiatives/geriatric-oncology/geriatric-oncology-resources).
Currently, the geriatric oncology resource Webpage is divided into six main sections:....

Dear Health Minister Eric Hoskins – Concerned Ontario Doctors letter to healthcare minister

Dear Health Minister Eric Hoskins – letter

Concerned Ontario Doctors

Dear Health Minister Eric Hoskins

Thank you for your letter on August 25, 2016.

A motivated profession is a productive profession. We stand united in our belief that you are wrong.

Doctors want binding arbitration as it is our right. It was granted once to us, and legislated away. So we have a challenge before the courts to get it back. We’ll likely win, but it will take years. Until then, we will continue to serve our patients.....

 

Aug 25th letter - legal opinion re: Ontario Doctors (OMA/Ontario Government)

legal opinion/history of events (pdf)

plus Twitter:

Your Ontario Doctors ‏@OnCall4ON

Legal Report Reveals Damning Details of OMA Negotiations with Ministry of Health http://goo.gl/UKgTyY  #onpoli

Editorial: (Lynch et al) Rare diseases of the digestive system (case studies/publication)

Editorial: Rare diseases of the digestive system
 


... It appears clear to the editors that rare diseases involving the digestive system may have significant impact on the individual patients, public health, medical education and scientific advancement. There are currently 7,000 rare diseases identified [5, 17]. CD and Lynch syndrome are just two examples where case reports eventually led to critical scientific and clinical research findings, and benefited numerous patients. Many rare diseases, however, are poorly studied. Their etiopathogenesis, clinical presentation, diagnosis, management and prognosis are poorly defined. We therefore believe that there is an under-recognized need for more reports and studies on rare or uncommon diseases. A decision of accepting case reports in American Journal of Digestive Disease is thus made to meet such a need. While many journals have started eliminating the category of case report, we hope that this journal will offer a platform for publication of rare, yet interesting, cases with exceptional educational values. We are particularly interested in publishing cases with unique clinical, pathological and molecular features, ideally exceedingly rare yet clinically important. It is our hope that the publications will increase the awareness of rare diseases and thus strengthen the world-wide efforts in combating these diseases [5, 18].

We hope our decision of publishing case reports will contribute to the effort

The Dualistic Model of Ovarian Carcinogenesis - Revisited, Revised, and Expanded

abstract 
full text (pdf)

Robert J. Kurman

Ie-Ming Shih

Departments of Pathology, Gynecology and Obstetrics and Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland

Since our proposal of a dualistic model of epithelial ovarian carcinogenesis more than a decade ago, a large number of molecular and histopathologic studies were published that have provided important insights into the origin and molecular pathogenesis of this disease. This has required that the original model be revised and expanded to incorporate these findings. The new model divides type I tumors into three groups: i) endometriosis-related tumors that include endometrioid, clear cell, and seromucinous carcinomas; ii) low-grade serous carcinomas; and iii) mucinous carcinomas and malignant Brenner tumors. As in the previous model, type II tumors are composed, for the most part, of high-grade serous carcinomas that can be further subdivided into morphologic and molecular subtypes. Type I tumors develop from benign extraovarian lesions that implant on the ovary and which can subsequently undergo malignant transformation, whereas many type II carcinomas develop from intraepithelial carcinomas in the fallopian tube and, as a result, disseminate as carcinomas that involve the ovary and extraovarian sites, which probably accounts for their clinically aggressive behavior. The new molecular genetic data, especially those derived from next-generation sequencing, further underline the heterogeneity of ovarian cancer and identify actionable mutations. The dualistic model highlights these differences between type I and type II tumors which, it can be argued, describe entirely different groups of diseases.

Supported by the US Department of Defense grant OCRP-OC-100517, the Richard W. TeLinde Research Program, Johns Hopkins University, and the Roseman Ovarian Cancer Foundation (R.J.K. and I.M.S.); and NIH grant CA165807 (I.M.S.).

Epithelial ovarian cancer and type of peritoneal insult: a case–control study

abstract:
Epithelial ovarian cancer and type of peritoneal insult: a case–control study - European Journal of Obstetrics and Gynecology and Reproductive Biology
 

Objective

To evaluate the association between different types of peritoneal insults and the development of sporadic epithelial ovarian cancer (EOC) subtypes in the general population.

Study design

Hospital based case control study comparing sporadic cases of EOC with age matched control group between 2003 and 2008. Medical, surgical, and gynecological histories were compared between 208 women with histological diagnosis of EOC and 224 women in the control group matched for age at presentation for well woman examination.

Risk estimates for Lynch syndrome (interactive chart) - with/without prior cancer

Prospective Lynch Syndrome Database

• Carrier without previous cancer 
• Carrier with previous cancer 
• About

Recent news

[ Dec-08-2015 ]     LScarisk.org launched
[ Jun-03-2016 ]     Risk estimates for subsequent cancers have been added

 About LScarisk.org
This website is based on the following publications:

Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut. 2015 Dec 9.
Møller P, Seppälä T, Bernstein I, Holinski-Feder E, Sala P, Evans DG, Lindblom A, Macrae F, Blanco I, Sijmons R, Jeffries J, Vasen H, Burn J, Nakken S, Hovig E, Rødland EA, Tharmaratnam K, de Vos Tot Nederveen Cappel WH, Hill J, Wijnen J, Jenkins M, Green K, Lalloo F, Sunde L, Mints M, Bertario L, Pineda M, Navarro M, Morak M, Renkonen-Sinisalo L, Frayling IM, Plazzer JP, Pylvanainen K, Genuardi M, Mecklin JP, Möslein G, Sampson JR, Capella G; Mallorca Group (http://mallorca-group.org).(2016)

Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database. Gut. 2016 Jun 3
Note that the number of PMS2 carriers included are insufficient for realiable conclusions. Risk estimates for PMS2 carriers should therefore be interpreted with caution.
The information contained in this website is for general information purposes only. We make no representations or warranties of any kind, expressed or implied, about the completeness, accuracy, reliability, suitability or availability with respect to the website or the information, products, services, for interpretation or use in clinical practice, or otherwise contained on the website for any purpose.
Any reliance you place on such information is therefore strictly at your own risk. In no event will we be liable for any loss or damage including without limitation, indirect or consequential loss or damage, or any loss or damage whatsoever arising from loss of data or profits arising out of, or in connection with, the use of this website.
Editors: Sigve Nakken, Eivind Hovig, & Pål Møller

MRI for discriminating metastatic ovarian tumors from primary epithelial ovarian cancers

Full Text 
(small study/references to related research)

Published: 28 August 2015 

Study subjects

This retrospective study was approved by the institutional review boards of Shanghai First People’s Hospital, Shanghai, China. The informed consent requirement was waived. We searched for data of patients with ovarian tumors from January 2012 to December 2014 on a hospital information system—a picture archiving and communication system (PACS). We encountered 11 consecutive cases (median age, 42 years; range, 21–58 years) of metastatic ovarian tumors confirmed by pathology. Six gastric cancers, two colon cancers, one cervical cancer, one breast cancer and one thyroid cancer were found among the patients. It is obvious that the most common site of primary origin of metastatic ovarian cancers was stomach. Meanwhile, we detected 26 consecutive cases (median age, 56 years; range, 17–82 years) with pathologically confirmed primary epithelial ovarian cancers. None of these cases witnessed the history of malignant tumors except the present cancers. All the primary epithelial ovarian cancers had undergone surgery. Then the cancers were confirmed by histopathological pathologists in Shanghai First People’s Hospital. Consequently, ten serous cystadenocarcinoma, six clear cell cancers, five borderline malignancy, three mucinouscystadenocarcinoma and two endometrioid adenocarcinomas were found (Table 1). (see below)

Conclusions

In conclusion, metastatic ovarian tumors seem to be smaller in size, more bilateral, more uniform in locules and more moderate enhancement in solid portions than those of primary ovarian cancers. Metastatic ovarian tumors were with less elevated levels of CA125 and HE4 in contrast with primary ovarian cancers. (note: see Table 3)  Although the sensitivity, specificity, and accuracy of any features are not sufficient for diagnoses, the combination of three key features (patients’ age, small size, and bilaterality) tends to have a high sensitivity, specificity, and accuracy for identifying metastatic ovarian tumors. The radiologist must depend on a combination of the imaging features as well as the clinical examinations in order to diagnose metastatic ovarian tumors.

Table 1

Summary of the cases

Tumor type		Total cases	Histopathologically confirmed cases
Metastatic ovarian tumors	Gastric cancer	6	6
	Colon cancer	2	2
	Thyroid cancer	1	1
	Uterine cervical cancer	1	1
	Breast cancer	1	1
	Subtotal	11	11
Primary ovarian tumors	Serous cystadenocarcinoma	10	10
	Clear cell carcinoma	6	6
	Borderline malignancy	5	5
	Mucinous cystadenocarcinoma	3	3
	Endometrioid adenocarcinoma	2	2
	Subtotal	26	26
Total		37	37

Potential implications on female fertility and reproductive lifespan in BRCA germline mutation women

open access
First Online: 25 August 2016
 
Conclusions

BRCAm women should not delay pregnancy, especially if they are BRCA1, older than 35 years or with previous gonadotoxic treatments. Future prospective studies on infertility outcomes in this population are needed.

 

 Consequences of the germline mutation on cancer risk are widely known, but not the non-oncological implications [2]. Controversy exists about the impact of BRCA1/2 germline mutations (BRCA1/2m) on female fertility [3]. There is a current interest in identifying the possible association between BRCA germline mutation (BRCAm) and reproductive performance [1]. Recent research articles suggest that BRCAm, especially BRCA1, decreases ovarian reserve [4], increases fertility-related problems [1] and determines early menopause (also known as premature or occult primary ovarian failure) [5] (Fig. 1).....

Prognostic factors in young ovarian cancer patients: An analysis of four prospective phase III intergroup trials

abstract: 
Prognostic factors in young ovarian cancer patients: An analysis of four prospective phase III intergroup trials of the AGO Study Group, GINECO and NSGO

Highlights

• •To detect the effect of young age on survival in ovarian cancer patients.
• •A meta-database analysis of 5055 ovarian cancer patients.
• •Potential confounding and effect measure modification are considered.
• •Prognostic factors of survival are similar in patients under and over 40 years of age.
• •Young age at diagnosis of ovarian cancer improves survival.

Abstract

Objectives

We evaluated in a large study meta-database of prospectively randomised phase III trials the prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients < and >40 years of age with advanced epithelial ovarian cancer.

Methods

A total of 5055 patients of the AGO, GINECO, NSGO intergroup studies AGO-OVAR 3, 5, 7 and 9 were merged to identify 294 patients <40 years and 4761 patients ≥40 years. We conducted survival analyses and Cox proportional hazard regression models and additionally analysed a very homogeneous subcohort of 405 patients with serous epithelial ovarian cancer, excellent performance status, who had received complete macroscopic upfront cytoreduction and ≥5 chemotherapy cycles.

Results

For patients <40 years, the median PFS was 28.9 months and the median OS was 75.3 months, while the median PFS for patients ≥40 years was 18.1 months and the median OS was 45.7 months. Independent prognostic factors were similar in both age groups. In a multivariate analysis including prognostic factors potentially leading to confounding, young age appeared to improve PFS and OS. The observed effect was even stronger in the subcohort of optimally treated patients with SEOC: PFS and OS.

Discussion

Prognostic factors were similar in both age groups. Young age appeared a strong independent protective prognostic factor for PFS and OS in the subcohort.

The dual role of complement in cancer and its implication in anti-tumor therapy

open access- Annals of Translational Medicine

 (technical)

Review Article July 2016

The dual role of complement in cancer and its implication in anti-tumor therapy
 

Ioannis Kourtzelis¹, Stavros Rafail²

¹Department of Clinical Pathobiochemistry, Technische Universität Dresden, 01307 Dresden, Germany; ²Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA 19104-6160, USA

Contributions: (I) Conception and design: All authors; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: None; (V) Data analysis and interpretation: None; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Stavros Rafail. Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA 19104-6160, USA. Email: srafail@upenn.edu; Ioannis Kourtzelis. Department of Clinical Pathobiochemistry, Technische Universität Dresden, 01307 Dresden, Germany

 

Abstract: Chronic inflammation has been linked to the initiation of carcinogenesis, as well as the advancement of established tumors. The polarization of the tumor inflammatory microenvironment can contribute to either the control, or the progression of the disease. The emerging participation of members of the complement cascade in several hallmarks of cancer, renders it a potential target for anti-tumor treatment. Moreover, the presence of complement regulatory proteins (CRPs) in most types of tumor cells is known to impede anti-tumor therapies. This review focuses on our current knowledge of complement’s potential involvement in shaping the inflammatory tumor microenvironment and its role on the regulation of angiogenesis and hypoxia. Furthermore, we discuss approaches using complement-based therapies as an adjuvant in tumor immunotherapy.

Keywords: Anaphylatoxins; antibody therapy; cancer immunotherapy; complement dependent cytotoxicity

 

 

 

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Cochrane
 

Gene testing in rare tumor type could uncover 'cancer families (sarcoma/BRCA...)

Science news

....They found that over half of 1,162 patients with sarcoma tested were born with mutations in at least one gene already known to increase cancer risk.
Some of the most common inherited mutations occurred in genes known to drive the development of multiple tumour types -- p53, APC, BRCA1 and BRCA2 -- putting these patients at increased risk of other cancers such as breast, ovarian or bowel cancer. When such mutations are found, families can be offered genetic counselling and screening, where appropriate....

 A fifth of the patients had mutations in more than one of the genes tested and, importantly, people with genetic errors in multiple cancer genes were found to be more likely to get cancer at a younger age than those with a single genetic mutation. This is the first evidence that multiple genetic mutations interacting could be causing sarcomas in some patients, rather than a single gene driving their disease.

 abstract

Unfurling the Genetic Map of Sarcomas

Abstract

An international team of researchers has uncovered multiple new germline mutations that may influence the development of sarcomas. Notably, they found that variants in several DNA damage sensing and repair genes contribute greatly to sarcoma risk, including BRCA2, ATM, ATR, and ERCC2.

• ©2016 American Association for Cancer Research.

Individualised benefit–harm balance of aspirin as primary prevention measure – a good proof-of-concept, but could have been better… | BMC Medicine | Full Text

open access

Commentary

BMC Medicine201614:101

Published: 6 July 2016

Open Peer Review reports

Abstract

Guidelines from different organisations regarding the use of aspirin for primary prevention vary despite being based on similar evidence. Translating these in practice presents a further major challenge. The benefit–harm balance tool developed by Puhan et al. (BMC Med 13:250, 2015) for aspirin can overcome some of these difficulties and is therefore an important step towards personalised medicine. Although a good proof-of-concept, this tool has some important limitations that presently preclude its use in practice or for further research. One of the major benefits of aspirin that has become apparent in the last decade or so is its effect in preventing cancer and cancer-related deaths. However, this benefit is clear and consistent in randomised as well as observational evidence only for specific cancers. Additionally, it has long lag-time and carry-over periods. These nuances of aspirin’s effects demand a specific and a more sophisticated model such as a time-varying model. Further refinement of this tool with respect to these aspects is merited to make it ready for evaluation in qualitative and quantitative studies with the goal of clinical utility.

Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-015-0493-2

....After a thorough review of the evidence [8], we concluded that a clear and large benefit exists for colorectal, oesophageal and stomach cancer, and the benefit for lung, breast and prostate cancer is smaller and less clear. Many aspirin experts agree with a beneficial effect on only three gastrointestinal (GI) tract cancers due to the biological and pharmacological plausibility of such an effect [19], as well as due to some uncertainty regarding aspirin’s effects on lung, breast and prostate cancer. Therefore, we provided sensitivity analyses with aspirin’s beneficial effect being limited to three GI cancers as well as colorectal cancer alone [8]. Recent analyses by the U.S. Preventive Services Task Force also take into account only the beneficial effect on colorectal cancer [20]. Therefore, assuming aspirin’s effect on cancers other than colorectal, oesophageal, stomach, lung, breast and prostate cancers is not correct, even when simulations and repetitions consider the statistical uncertainty of effect on other cancers.....

We should reward peer reviewers. But how?

science news

Vitamin cocktails: An ethical dilemma of supply and demand

medical news

Stem cell propagation fuels cancer risk in different organs

Medical News (research)

The results appear online today in the journal Cell.
 Article: Multi-organ Mapping of Cancer Risk, Liqin Zhu, et al., Cell, doi: 10.1016/j.cell.2016.07.045, published 25 August 2016.

...."The chance accrual of random mistakes in cell DNA likely plays an important role in generating cancer; but whether this has to happen in specific cell types, such as stem cells, and precisely how other factors such as environmental carcinogens contribute to cancer is unclear," said the study's senior author, Richard Gilbertson, M.D., Ph.D., director of the Cancer Research UK Cancer Center at Cambridge University, England, and former St. Jude scientific and Comprehensive Cancer Center director. "Indeed, an argument has raged across the scientific community for some years now. Some say cancer is 'bad luck' because mutations arise by chance in stem cells, while others argue environmental carcinogens are more important. This disagreement has arisen largely from the use of different mathematical models to look at existing human cancer and stem cell data, from which it is extremely difficult to tease out the impact of individual factors. Therefore, we tested these opinions in actual experimental models that looked at the individual components that might drive cancer."......

 The scientists also showed that stem cells in newborn animals are far less likely to undergo malignant transformation than adult stem cells. This finding suggests that stem cells in the newborn are intrinsically resistant to the formation of tumors. "If this biology were to hold true in humans, then it may explain why cancer rates are many-fold lower in children than adults, despite the fact that childhood cancers accrue significant numbers of mutations that alter proteins, and that the growth rates of organs peak in childhood," said Zhu....

Port site metastatic disease in ovarian carcinoma (2015 small study)

abstract
 

Introduction

Port-site metastases are a recognised complication of laparoscopy in the presence of malignancy. With the increased use of minimally invasive technology to surgically manage gynaecological malignancy, their incidence is likely to increase. We describe three cases where patients underwent laparoscopy prior to referral for definitive surgery.

Materials and methods

Patient one attended a secondary centre complaining of urinary incontinence and abdominal pain. Pre-operative imaging identified omental thickening and ascites. Laparoscopy was performed and malignancy of the omentum and peritoneum was identified in addition to a suspicious appearing ovary. The second case concerned a 65 year-old patient presented with abdominal pain and underwent emergent laparoscopy in which adenocarcinoma of the ovary was diagnosed. After biopsies were obtained, the patient was referred for definitive surgical management. Patient three underwent laparoscopy due to abdominal pain. Pre-operative imaging identified ascites and a pelvic mass. Biopsies were taken at laparoscopy which confirmed ovarian malignancy.

Results

All three patients developed histologically proven port-site metastatic disease prior to undergoing definitive surgical management.

Conclusion

In all cases, port-site metastatic disease developed rapidly and was clinically suspected at the time of definitive surgery. We recommend that consideration be given towards removing port sites when performing cytoreductive surgery for gynaecological malignancy.

Identification of therapeutic targets applicable to clinical strategies in ovarian cancer

open access (technical)
August 24, 2016

Table of Contents

• Abstract
• Background
• Methods
• Results
• Discussion
• Conclusions
• Declarations
• References

Conclusions

Loss-of-function screen followed by in vitro target validation using chemical inhibitors identified clinically relevant targets. This approach has the potential to systematically refine therapeutic strategies in OC. These molecular target-driven strategies may provide additional therapeutic options for women whose tumors have become refractory to standard chemotherapy.

Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening

open access 
Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening

 The 32 cancer cases comprised 16 women with International Federation of Gynecology and Obstetrics (FIGO) stage I and II HGSOC (‘early cancer’), and 16 women with FIGO stages III and IV HGSOC (‘advanced cancer’). The control group included women with benign gynecologic disease undergoing surgery (n = 24), or germline BRCA1 and BRCA2 mutation carriers without evidence of malignancy who were undergoing risk-reduction surgery (n = 8).

 Discussion

In this proof of concept study, low coverage plasma DNA sequencing and analysis for chromosomal CNVs ≥ 15 Mb detected 40 % of HGSOC. Surprisingly, we detected similar proportions of early and advanced stage HGSOC cancers with this approach. This finding was unexpected because one would assume a higher detection rate in the advanced stage cases, given the lower tumor bulk of early disease. This suggests that the detection of ovarian tumor CNVs in plasma is not directly related to cancer stage; other biological factors such as fractional concentration of tumor DNA in plasma, tumor genetic heterogeneity, vascularity, and cell turnover may also be important influences on detection rates.....