paywalled: Diathermy-Induced Injury May Affect Detection of Occult Tubal Lesions at Risk-Reducing Salpingo-Oophorectomy

Diathermy: In the natural sciences, the term diathermy means "electrically induced heat" and is commonly used for muscle relaxation. It is also a method of heating tissue electromagnetically or ultrasonically for therapeutic purposes in medicine.

Diathermy-Induced Injury May Affect Detection of Occult Tuba... : International Journal of Gynecological Cancer

Background: Electrosurgery-induced tubal thermal injury obscures cellular detail and hampers histomorphological assessment for occult pathology.

Objective: 

The objectives of this study were to report on diathermy-related thermal injuries to the fallopian tube observed at RRSO and explore its potential impact on the detection of occult tubal epithelial lesions.

Design: 

This study was composed of high-risk women from breast and/or ovarian cancer families attending a tertiary high-risk familial gynecologic cancer clinic. This was a retrospective case-control analysis of high-risk women who underwent RRSO. Cases were all women detected to have occult lesions (tubal atypia/carcinoma in situ/cancer) between January 2005 and December 2010. Control subjects were all women with normal tubal/ovarian histology between August 2006 and December 2007.

Conclusions: This report highlights the potential impact of electrosurgical thermal injury on detection of occult tubal pathology following RRSO. It is important for surgeons to avoid thermal injury to the distal end of the tube.

paywalled: Individuals at high-risk for pancreatic cancer development: Management options and the role of surgery (Lynch Syndrome, breast/ovarian BRCA 2....)

 Blogger's Note: while full access is by subscription only, key words indicate 'high risk' categories not limited to Lynch Syndrome, BRCA 2;  BRCA 2 - blogger's assumption based on genetics in absence of full text acccess)

Individuals at high-risk for pancreatic cancer development: Management options and the role of surgery

Abstract 

Pancreatic cancer (PC) is a highly lethal disease. Despite advances regarding the safety and long-term results of pancreatectomies, early diagnosis remains the only hope for cure. This necessitates the implementation of an intensive screening program (based mainly on modern imaging), which – given the incidence of PC – is not cost effective for the general population. However, this screening program is recommended for individuals at high-risk for PC development.

Indications for screening include the following three clinical settings: hereditary cancer predisposition syndromes associated with PC, hereditary pancreatitis and familial pancreatic cancer syndrome. The aim of this strategy is to identify pre-invasive (precursor) lesions, which are curable. Surgery is recommended in the presence of recognizable lesion on imaging lesions. Partial (anatomic) pancreatectomy – depending on the location of the suspicious lesion – is the most widely accepted type of surgical intervention in this setting; occasionally, however, total pancreatectomy may be required, in carefully selected patients. Despite that experience still remains limited, there is evidence that this aggressive strategy allows early detection of neoplastic lesions, thereby improving the effectiveness of surgery and prognosis.

Keywords: Pancreas, Surgery, Cancer, PanIN, MCN, IPMN, Pancreatectomy, Total pancreatectomy, Screening

Abbreviations: PanIN, pancreatic intraepithelial neoplasia, IPMN, intraductal papillary mucinous neoplasm, MCN, mucinous cystic neoplasm, PJS, Peutz–Jeghers syndrome, FAMMM syndrome, familial atypical multiple mole melanoma syndrome, HNPCC, hereditary non-polyposis colon cancer (Lynch syndrome), HOBC, hereditary ovarian and breast cancer, VHL, von Hippel–Lindau, PD, pancreatoduodenectomy

abstract: Unusual DNA mismatch repair-deficient tumors in Lynch syndrome: a report of new cases and review of the literature.

Unusual DNA mismatch repair-deficient tumors in Lynch syndrome: a report of new cases and review of the literature.

Hum Pathol. 2012 Apr 17;


Abstract

Immunohistochemical detection of DNA mismatch repair proteins and polymerase chain reaction detection of microsatellite instability have enhanced the recognition of mismatch repair-deficient neoplasms in patients with Lynch syndrome and, consequently, led to the identification of tumors that have not been included in the currently known Lynch syndrome tumor spectrum.

Here, we report 4 such unusual tumors. Three of the 4, a peritoneal mesothelioma, a pancreatic acinar cell carcinoma, and a pancreatic well-differentiated neuroendocrine tumor, represented tumor types that, to the best of our knowledge, have not been previously reported in Lynch syndrome. The fourth tumor was an adrenocortical carcinoma, which has rarely been reported previously in Lynch syndrome. Three of our 4 patients carried a pathogenic germ-line mutation in a mismatch repair gene. The unusual tumor in each of the 3 patients showed loss of the mismatch repair protein corresponding to the mutation. The fourth patient did not have mutation information but had a history of colonic and endometrial carcinomas; both lacked MSH2 and MSH6 proteins. Interestingly, none of the 4 unusual tumors revealed microsatellite instability on polymerase chain reaction testing, whereas an appendiceal carcinoma from 1 of the study patients who was tested simultaneously did. The recognition of such tumors expands the repertoire of usable test samples for the workup of high-risk families.

As yet, however, there are no data to support the inclusion of these tumors into general screening guidelines for detecting Lynch syndrome, nor are there data to warrant surveillance for these tumors in patients with Lynch syndrome.

abstract: BRCA genetic testing of individuals from families with low prevalence of cancer: experiences of carriers and implications for population screening : small study 14 Ashkenazi Jewish women

BRCA genetic testing of individuals from families with low prevalence of cancer: experiences of carriers and implications for population screening : Genetics in Medicine : Nature Publishing Group

Purpose:

BRCA genes are associated with hereditary breast and ovarian cancers. Guidelines worldwide currently recommend BRCA genetic testing in asymptomatic individuals only if they belong to “high-risk” families. However, population screening for BRCA1/2 may be the logical next step in populations with a high prevalence of founder mutations, such as Ashkenazi Jews. This study aimed to explore (i) the impact of a positive BRCA genetic test result on individuals who have neither a personal history nor a familial history of cancer and (ii) their attitudes toward the concept of population screening.

Methods:

Semistructured in-depth interviews were carried out with 14 Ashkenazi Jewish women who were asymptomatic BRCA carriers and who belonged to families with low prevalence of cancer.

Results:

Three main findings emerged: (i) having no family history of cancer was a source of optimism but also confusion; (ii) engaging in intensified medical surveillance and undergoing preventive procedures was perceived as health-promoting but also tended to induce a sense of physical and psychological vulnerability; and (iii) there was overall support for BRCA population screening, with some reservations.

Conclusion:

Women belonging to low-cancer-prevalence families within a “high-risk” ethnic community view BRCA genetic testing positively despite the difficulties entailed, because it allows prevention or early detection of cancer. However, implementing a BRCA population screening program should be carried out with proper pre- and post-testing preparation and support for the individuals undergoing testing.

abstract: Presence of key findings in the medical record prior to a documented high-risk diagnosis.

Presence of key findings in the medical record prior to a documented high-risk diagnosis.


Abstract

Background
Failure or delay in diagnosis is a common preventable source of error. The authors sought to determine the frequency with which high-information clinical findings (HIFs) suggestive of a high-risk diagnosis (HRD) appear in the medical record before HRD documentation.
  
Methods
A knowledge base from a diagnostic decision support system was used to identify HIFs for selected HRDs: lumbar disc disease, myocardial infarction, appendicitis, and colon, breast, lung, ovarian and bladder carcinomas. Two physicians reviewed at least 20 patient records retrieved from a research patient data registry for each of these eight HRDs and for age- and gender-compatible controls. Records were searched for HIFs in visit notes that were created before the HRD was established in the electronic record and in general medical visit notes for controls.

Results
25% of records reviewed (61/243) contained HIFs in notes before the HRD was established. The mean duration between HIFs first occurring in the record and time of diagnosis ranged from 19 days for breast cancer to 2 years for bladder cancer. In three of the eight HRDs, HIFs were much less likely in control patients without the HRD.
  
Conclusions
In many records of patients with an HRD, HIFs were present before the HRD was established. Reasons for delay include non-compliance with recommended follow-up, unusual presentation of a disease, and system errors (eg, lack of laboratory follow-up). The presence of HIFs in clinical records suggests a potential role for the integration of diagnostic decision support into the clinical workflow to provide reminder alerts to improve the diagnostic focus.

abstract: Factors Associated With Pain Among Ambulatory Patients With Cancer With Advanced Disease at a Comprehensive Cancer Center (Center for Patient Safety, Dana-Farber Cancer Institute)

Factors Associated With Pain Among Ambulatory Patients With Cancer With Advanced Disease at a Comprehensive Cancer Center

Conclusion:
Younger age, minority race, and recent onset of advanced disease are associated with severe pain among patients with cancer. Recognizing these high-risk groups could inform targeted interventions to address pain care in ambulatory patients with advanced cancer.

Lynch Syndrome: Don't Miss It (Transcript including slides))

Blogger's Opinion/Note:
guidelines indicate varying ages of screening depending on organ assuming there are screening mechanisms (eg. ovarian cancer has no screening for the general population however increased surveillance is possible for those at high risk,  albeit, ineffective; generally 25 yrs +;  'averages' are not helpful and therefore the urging of family history taking by primary/family care physicians, see NCCN guidelines for Lynch Syndrome which includes gene-specific details (eg. MLH1, MSH2/6, PMS2.....)

Lynch Syndrome: Don't Miss It (Transcript)

Clinical Implications

"Lynch syndrome is a genetic defect that has significant implications on the clinical side. A patient whose genetic testing is positive for Lynch syndrome has a likelihood of developing colon cancer that approaches 70% over his or her lifetime. The risk for uterine cancer is similar or a bit higher, and the risk for ovarian cancer is13%-15%. Almost certainly, these patients will have some type of cancer during their lifetime.

Metachronous cancers occur in 7%-10% of patients with Lynch syndrome. These patients present with one cancer, and typically in the course of a short period of time, another cancer develops. In patients with Lynch syndrome who have colon cancer, if you don't perform a subtotal colectomy because you didn't recognize that it was Lynch syndrome, the likelihood that the patient will develop a repeat colon cancer over 30 years (even in patients who are being screened) approaches 65%. This is not uncommon. A lot of these diagnoses are missed, and a secondary cancer develops."

"You need to start thinking about syndromic cancers because the relative risk is quite high. You need to be thinking about this in patients with early cancers -- not just colon cancer, but in uterine cancer and ovarian cancer as well." (Blogger's Note: and others including pancreatic, stomach, ureter, renal, bilary tract, gallbladder.....see slides)

" If you look at colon cancer in Lynch syndrome, the average age of onset is earlier (45 years) and some patients may be in their 20s. For sporadic uterine cancer, the average age is approximately 60 years, but in Lynch syndrome, it is shifted by a decade, to 50 years. When you see these cancers in a younger patient, the bell should go off and you should start thinking about Lynch syndrome and doing the appropriate testing."

"It is important to think about extracolonic cancers in these patients and to start to put the dots together because we are missing the boat on a lot of these syndromic cancers. It's not a zebra; it's 2%-3% of the patients who are presenting with cancer. We need to think outside the box. Even if you are not a gastroenterologist, include the colon when you see syndromic related cancers of the uterus, ovary, small bowel, or stomach."

A Risk-Adapted Strategy of Adjuvant Paclitaxel/Carboplatin in Early-Stage Ovarian Cancer: Time-Dependent Effect of 4 versus 6 Cycles on Outcome.

Abstract

Objective:
We investigated the efficacy of risk-adapted adjuvant paclitaxel/carboplatin chemotherapy in early-stage ovarian carcinoma.

Methods: Fifty-three patients were treated according to the risk of relapse: patients with stages IA or IB or with grade 1 (low risk) received 4 cycles of paclitaxel and carboplatin; patients with IC/IIA and grade 2 or 3 (high risk) received 6 cycles of chemotherapy. The outcome was compared with that of 95 patients who were all treated with 4 cycles.

Results: Median follow-up was 88, 113 and 42 months for the whole cohort, non-risk-adapted and risk-adapted treatment, respectively.

Five-year relapse-free and disease-specific survival was 86 and 93% for the whole population, 96 and 97% for low-risk and 81 and 91% for high-risk patients.

Risk classification was the only significant prognostic factor for relapse-free (p = 0.011) and disease-specific survival (p = 0.039). Among high-risk patients, the administration of 6 cycles was associated with a significantly lower relapse rate after censoring events, which occurred beyond 2 years (3 vs. 18%; p = 0.013), but this difference was diminished at 5 years (23 vs. 25%; p = 0.797).

Conclusions: Six cycles of chemotherapy reduced the risk of relapse within 2 years, but the benefit from two additional cycles beyond this time is questionable.

Reported referral for genetic counseling or BRCA 1/2 testing among United States physicians: a vignette-based study.

 Blogger's Note: in the absence of the full paper ($$$) conclusions should be viewed with caution (eg. detailed reasons, albeit summarized in the abstract...) because....the conclusion do not make sense. 

Please post a message IF this paper is available elsewhere in open text publishing format.

 BACKGROUND:

Genetic counseling and testing is recommended for women at high but not average risk of ovarian cancer. National estimates of physician adherence to genetic counseling and testing recommendations are lacking.

METHODS:

Using a vignette-based study, we surveyed 3200 United States family physicians, general internists, and obstetrician/gynecologists and received 1878 (62%) responses. The questionnaire included an annual examination vignette asking about genetic counseling and testing. The vignette varied patient age, race, insurance status, and ovarian cancer risk. Estimates of physician adherence to genetic counseling and testing recommendations were weighted to the United States primary care physician population.

 CONCLUSION:

Physicians reported that they would refer many average-risk women and would not refer many high-risk women for genetic counseling/testing. Intervention efforts, including promotion of accurate risk assessment, are needed.

open access: Australasian - Adequacy of risk-reducing gynaecologic surgery in BRCA1 or BRCA2 mutation carriers and other women at high risk of pelvic serous cancer

Blogger's Note: see Table 2 for the types of surgery and professional designation of who performed the surgery

"All women who had a hysterectomy had adequate surgery"

"Australasian BRCA1 and BRCA2 mutation carriers and women at high familial risk of “ovarian” cancer who elect RRSO must receive high quality care that will reduce their risk of gynaecological cancer. This study highlights the need for standardised surgical techniques and tissue processing protocols for RRSO. Clinicians who discuss RRSO with these women should consider referring them to specialist gynaecologic oncologists for their surgery, or at least should discuss the specifics of optimal surgery and pathology with the woman’s existing gynaecologist or general surgeon if he/she is planning to undertake the surgery. High risk women themselves should be educated about the likely pathogenesis of pelvic serous cancers from the fallopian tubes rather than the ovaries and hence the type of surgery that is optimal. Using the term “ovarian cancer” to describe this disease is misleading and arguably should be abandoned to reflect the emerging evidence regarding the  pathogenesis of this disease."

The predicted truncation from a (ovarian) cancer-associated variant of the MSH2 initiation codon alters activity of the MSH2-MSH6 mismatch repair complex

Abstract

Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes. MMR recognizes and repairs DNA mismatches and small insertion/deletion loops. Carriers of MMR gene variants have a high risk of developing colorectal, endometrial, ovarian, and other extracolonic carcinomas. We report on an ovarian cancer patient who carries a germline MSH2 c.1A>C variant which alters the translation initiation codon. Mutations affecting the MSH2 start codon have been described previously for LS-related malignancies. However, the patients often lack a clear family history indicative of LS and their tumors often fail to display microsatellite instability, a hallmark feature of LS...."(technical)

Landmark ovarian cancer discovery as scientists unveil high risk gene (RAD51D) : Cancer Research UK

Sunday 7 August 2011

Cancer Research UK Press Release

Cancer Research UK-funded scientists have discovered that women who carry a faulty copy of a gene called RAD51D have almost a one in 11 chance of developing ovarian cancer, the most significant ovarian cancer gene discovery for more than a decade, reveals a study in Nature Genetics1 today (Sunday).

Gynecologic Oncology: Highlights From Asco 2011

The Canadian Press: More testing coming for Ontario women at risk of contracting breast cancer

Perspective: (U.S.) High-Risk Pools — Merely a Stopgap Reform | Health Policy and Reform

abstract: Satisfaction with ovarian carcinoma risk-reduction strategies among women at high risk for breast and ovarian carcinoma

M.R.I.’s Help Women at High Risk for Breast Cancer - NYTimes.com

High detection rate of adenomas in familial colorectal cancer - Gut

Conclusion
The yield of colonoscopic surveillance in familial CRC is substantially higher than the yield of screening reported for the general population."

abstract: PET in women with high risk for breast or ovarian cancer : The Lancet Oncology

Editorial: The Elusive Goal of Maintaining Population (Breast) Cancer Screening: It Is Time for a New Paradigm JNCI

"The promise of breast cancer screening has fallen short of its goals because of its imprecision, failure to screen those at highest risk, lack of compliance with screening continuance over recommended periods of time, and gaps in access to or quality of diagnostic follow-up and treatment (20). It is no longer enough to simply conduct more interventions to understand which work best in motivating individuals to undergo repeat cancer screening. New paradigms, guided by evidence from modeling, novel trials, and new scientific discovery, will be needed to realize the promise of eliminating the burden of cancer."