Excerpt
Wednesday, September 16, 2015
A Historical Argument for Changing the Name of a Major Syndrome (Lynch syndrome)
Abstract
Dr
Aldred Scott Warthin discovered a "cancerous" family in the early 1900s,
mapped its kindred, and studied their diseases to the extent possible
in his day. His seminal article was published in 1913. Dr Henry Lynch
took Warthin's studies and began using more modern techniques to
characterize this so-called "Family G," beginning in the 1960s. Somehow
in this process, Warthin's observations became "Lynch syndrome." We need a better name for this condition, and propose "Warthin-Lynch syndrome" to also honor its primary discoverer.
Papillary thyroid carcinoma (PTC) in Lynch syndrome
Papillary thyroid carcinoma (PTC) in Lynch syndrome: Report of two cases and discussion on Lynch syndrome behaviour and genetics
abstract
We
present here two cases of papillary thyroid carcinoma (PTC) in patients
affected by Lynch syndrome (LS). The first case is a 47-year-old woman
with typical hereditary non-polyposis colorectal cancer (HNPCC)
syndrome, reported with endometrial and ovarian carcinoma at age 43, and
colon cancer at age 45. The patient underwent total thyroidectomy and
central node dissection in 2007, at 47 years old, with a histological
diagnosis of PTC (T1aN1a). Molecular genetics showed a germ-line
mutation of the MLH1 gene, 1858 G>T(E620X), with
substitution of glycine with a stop codon at position 620. This mutation
has pathogenetic significance and was considered responsible for the
various tumours of the HNPCC spectrum. In particular, in the same
kindred, spanning 5 generations, there were 5 members with colorectal
cancer, 4 with endometrial cancer, 3 with gastric and 2 with breast
cancer. The second case is a 34-year-old man with typical HNPCC syndrome
with colonic resection for colon cancer at age 21. The patient
underwent total thyroidectomy with central and lateral node dissection
in 2010, at age 34, with a histological diagnosis of PTC with nodal
metastases (pT4N1b). Molecular genetic analysis showed a germ-line
mutation of the MSH2 gene (thymine insertion at position 907).
This mutation had pathogenetic significance and was considered
responsible for HNPCC development. Two similar cases have been reported:
a 39-year-old woman, and a 44-year-old woman, affected by HNPCC
syndrome, with anaplastic thyroid carcinoma and undifferentiated thyroid
carcinoma, respectively. We reviewed the Lynch syndrome literature on
the history, genetics and expanding tumour spectrum of this condition.
An Analysis of Near Misses Identified by Anesthesia Providers in the Intensive Care Unit
Medscape
Finally, the rate of near misses reported in the ICU and OR was similar. Although this may be due to a bias in the type of reporting system used, it also suggests anesthesiologist involvement in the ICU may result in lower event rates.
..... Existing literature on adverse events and near misses in the ICU is primarily based on incident reports submitted by critical care nurses and intensivists.[4–9] To our knowledge, this is the first study evaluating patient safety in the ICU from the unique perspective of the anesthesiologist. The results of our study differ from the results of previous studies, supporting our hypothesis that anesthesia providers can highlight systems weaknesses and causal mechanisms in the ICU not identified by other personnel. As compared to previous work on critical incidents in the ICU by Donchin, et al., a larger proportion of near misses from our study occurred at night or on the weekend,[14] which could imply that decreased staffing in the ICU on off-hours impacts the ability of critical care providers to recognize, react to, and report near misses and adverse events.....
The Undiagnosed Diseases Network of the NIH (U.S.): A National Extension
JAMA
In 2008, an Undiagnosed Diseases Program (UDP)1,2 was established within the Intramural Research Program of the National Institutes of Health (NIH). This program evaluates patients and families for whom medicine has failed to provide a diagnosis........ The UDN is an ambitious new venture. Although leaders of the member institutions know they will succeed in some measure, despite best efforts, some patients will still not receive a diagnosis. Even then, there is value in moving families from stagnation to hope; the knowledge that a team of physicians and scientists will continue to work in the pursuit of a diagnosis can be very powerful. This reestablishes the bond with patients who live in diagnostic limbo, many of whom share the simple goal of helping others avoid the uncertain fate of the undiagnosed.
Clinicopathologic and survival analyses of synchronous primary endometrial and epithelial ovarian cancers (Turkey)
abstract
AIM:
The aim of the study was to describe clinicopathologic characteristics, survival outcomes and the factors associated with recurrence in patients diagnosed with synchronous primary endometrial and epithelial ovarian cancers.MATERIAL AND METHODS:
In this retrospective study, 50 patients who were diagnosed with synchronous primary endometrial and epithelial ovarian cancers and underwent surgery between 1998 and 2010 were reviewed.RESULTS:
In our study, the median age at the time of diagnosis was 53 years (range 28-79). The most common presenting symptom was abnormal uterine bleeding with a ratio of 36%. Fifty-four percent of the patients had endometrioid type endometrial cancer and endometrioid type ovarian cancer. All patients were surgically staged and the majority of the patients were in stage I for both endometrial cancer (58%) and ovarian cancer (60%). Nearly one-third (32%) of the patients had a recurrence during the follow-up period and by Cox regression analysis the level of cancer antigen 125 (P = 0.023) (CA125) at diagnosis, serous or clear-cell histopathologic type ovarian cancer (P = 0.029) and stage of endometrial cancer above I (P = 0.048) were found to be independent risk factors associated with development of recurrence. Patients with endometrioid type endometrium histology and endometrioid type ovarian histology had favorable prognosis with 120.00 months mean disease-free survival and 92% disease-free survival rate at 36 months.CONCLUSION:
In our cohort, we found that endometrioid/endometrioid type synchronous primary endometrial and ovarian cancer had different clinical histopathologic characteristics and favorable prognosis compared to the other histologic types of these cancers. Histopathologic type of the ovarian cancer component, stage of endometrial cancer and level of cancer antigen 125 at diagnosis were observed to have a great influence on the development of recurrence and survival of synchronous primary carcinomas of the endometrium and ovary.Tuesday, September 15, 2015
What Is Our Goal? | Prevent Ovarian Cancer (Ontario, Canada) call for participants (BRCA not Lynch)
Go to preventovariancancer.ca or call 1-866-330-0180 to find out about the program. Because the program is just getting started, there is currently only funding for 500 women.
You can participate in the POCP from home. This means you will not have to come to the Princess Margret Cancer Centre in Toronto to be part of this program. If you need additional support or information during the program, we will connect you to resources in your community.
Through this program, genetic counselling and genetic testing will be available to 500 women living in Ontario who have a first-degree relative (mother, sister, daughter) with a confirmed diagnosis of a specific type of ovarian cancer called high-grade serous ovarian cancer (or “HGSC” for short), but that do not currently qualify for genetic testing through the Ontario Ministry of Health.
Participation in this program is a multi-step process that is outlined in Do I Qualify? and What is the Process? Your participation will help determine if you have an increased risk for ovarian cancer, and if so, provide you with options for reducing that risk. This life saving information may prevent you, or someone you love, from developing ovarian cancer in the future.
Ovarian cancer is the deadliest female cancer
HGSC (high grade serous carcinoma) is the most common type of ovarian cancer and is almost always diagnosed at an advanced stage. Only 30% of women diagnosed with HGSC live more than five years and 90% eventually die from the disease. Unfortunately, it is currently not possible to screen for HGSC or to detect it at an early stage.....
Do I Qualify?
You may qualify to participate in the Prevent Ovarian Cancer Program if you meet all the following criteria:- Are an Ontario resident
- Are a female at least 18 years of age
- Have a deceased first-degree relative (mother, sister or daughter) previously diagnosed with ovarian cancer
You will not qualify if:
- You do not meet all 3 criteria listed above
- Someone in your family was previously tested and identified as having a BRCA1 or BRCA2 mutation
- You were previously tested and identified as having a BRCA1 or BRCA2 mutation yourself
If you think that you qualify based on these criteria, click What is the Process? to learn more.
Chemotherapy reduces PARP1 in cancers of the ovary: implications for future clinical trials involving PARP inhibitors
open access
Conclusion
Our
data suggest that patients should be screened for PARP1 expression
prior to therapy with PARP inhibitors. Further, the observed reduction
of intratumoral PARP1 post-chemotherapy suggests that treating
chemo-naïve patients with PARP inhibitors prior to the administration of
chemotherapy, or concurrently, might increase the responsiveness to
PARP1 inhibition. Thus, a change in the timing of PARP inhibitor
administration may be warranted for future clinical trials.
Red Blood Cell Transfusion: Precision vs Imprecision Medicine
JAMA
....Current transfusion guidelines, though well-intentioned are admittedly deficient.3
..... Using hemoglobin concentration to determine the need for red blood cell transfusion is a time-honored and well-reasoned concept, but the original recommendations from 1942 have regularly been misunderstood and misused. The oft-cited “10/30 rule” (hemoglobin/hematocrit) was less a rule than a proposal to include hemoglobin as one of several perioperative measures to improve care for poor-risk surgical patients. That guidance was prudent for the intended patients and the era, but was never meant to be generalized as the sole determinant of transfusion....
Using Human Factors and Systems Engineering to Evaluate Readmission after Complex Surgery
abstract
Background
Our objective was
to use a human factors and systems engineering approach to understand
contributors to surgical readmissions from a patient and provider
perspective. Previous studies on readmission have neglected the patient
perspective. To address this gap and to better inform intervention
design, we evaluated how transitions of care relate to and influence
readmission from the patient and clinician perspective using the Systems
Engineering Initiative for Patient Safety (SEIPS) model.....
BRCA1/2 testing in newly diagnosed breast and ovarian cancer patients without prior genetic counselling: the DNA-BONus study
open access:
Germline BRCA1/2
testing of breast and ovarian cancer patients is growing rapidly as the
result affects both treatment and cancer prevention in patients and
relatives. Through the DNA-BONus study we offered BRCA1/2 testing and familial risk assessment to all new patients with breast (N=893) or ovarian (N=122)
cancer diagnosed between September 2012 and April 2015, irrespective of
family history or age, and without prior face-to-face genetic
counselling. BRCA1/2 testing was accepted by 405 (45.4%) and 83 (68.0%) of the patients with breast or ovarian cancer, respectively. A pathogenic BRCA1/2 variant was found in 7 (1.7%) of the breast cancer patients and 19 (22.3%) of the ovarian cancer patients. In retrospect, all BRCA1/2 mutation carriers appeared to fulfill current criteria for BRCA1/2
testing. Hospital Anxiety and Depression Scale (HADS) scores showed
that the mean levels of anxiety and depression were comparable to those
reported for breast and gynecological cancer patients in general, with a
significant drop in anxiety symptoms during a 6-month follow-up period,
during which the test result was forwarded to the patients. These
results show that BRCA1/2 testing is well
accepted in newly diagnosed breast and ovarian cancer patients. Current
test criteria based on age and family history are sufficient to
identify most BRCA1/2 mutation carriers among breast cancer patients. We recommend germline BRCA1/2 testing in all patients with epithelial ovarian cancer because of the high prevalence of pathogenic BRCA1/2 variants.
Top of pageIntroduction
Breast cancer is by far the most common cancer in women worldwide, with more than 1.6 million new cases diagnosed each year. Ovarian cancer is substantially less common, with ~240 000 new cases each year, but with higher mortality.1 .....Discussing the Implications of Genetic Testing With Patients
JCO
To the Editor:
On March 20, 2015, the American Society of
Clinical Oncology submitted a letter to the US Food and Drug
Administration, Division
of Dockets Management, to note that next-generation
sequencing (NGS) is increasingly used to identify patients at high risk
for developing cancer. Recently, in Journal of Clinical Oncology, Jagsi et al1 repeatedly stressed the critical need for physicians to discuss with patients the potential results of genetic testing before
it is ordered so that patients can make informed decisions regarding genetic testing.
Although NGS testing is typically
explained to patients as a tool that might identify actionable molecular
abnormalities,
which suggests the potential benefit of a targeted
therapy, NGS also might suggest that the patient harbors a germline
mutation
characteristic of an inherited syndrome.
Furthermore, a mutation first suggested in this context might have a far
different
or unknown penetrance than one identified when the
patient is tested because clinical criteria for the inherited syndrome
is met.
I agree with both the American Society of Clinical Oncology statement that strongly supports additional exploration of NGS
and that of Jagsi et al1
to remind clinicians that, before we order genetic testing with such
profound implications, a thorough discussion is essential.
Before NGS is ordered, the clinician should also
discuss the possibility that the test might imply a germline mutation of
uncertain significance, even if the test is ordered
primarily to identify somatic mutations that might direct therapy.
REFERENCE
- 1.↵
Heart failure years after cancer treatment (selected articles)
Future Medicine
Special Report
Heart failure years after cancer treatment
Progress
in cancer treatment has significantly improved survival of patients
with cancer. However, the incidence of cardiovascular diseases such as
left ventricular dysfunction (LVD) and chronic heart failure (HF) is
increasing due to the long-term toxic effects of chemotherapy and
radiotherapy. Cardio-oncology teams are necessary to ensure the
implementation of primary prevention strategies and screening protocols
for early recognition of LVD. Moreover, early administration of advanced
treatment for HF is crucial to achieve left ventricular recovery. In
this article we will focus on the prevalence of chronic HF among cancer
survivors, the main risk factors of LVD and chronic HF, the prevention
strategies and management based on the current evidence and, finally,
the future perspectives in this field.
Cited by
Ellen Clarke, Daniel Lenihan. (2015) Cardio-oncology: a new discipline in medicine to lead us into truly integrative care. Future Cardiology 11:4, 359-361.
Online publication date: 1-Jul-201513-Aug-2015. Citation | Full Text | PDF (1950 KB) | PDF Plus (1964 KB) | Reprints & Permissions Users who read this article also read:
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Assessing the risk of ovarian malignancy algorithm for the conservative management of women with a pelvic mass
Abstract
OBJECTIVE:
To evaluate the use of as an aid in the identification of women who can safely undergo conservative, non-surgical management.METHODS:
All patients referred to the Program in Women's Oncology for surgery with a pelvic mass are evaluated at a prospective multidisciplinary tumor board (TB) where ROMA and imaging are used for management recommendations. This study evaluated women presented to TB with a pelvic mass between 2009 and 2013 who had either surgical or conservative management.RESULTS:
Of the 498 patients assessed, 392 (79%) had benign disease, 22 (4%) had LMP tumors, 28 (6%) had stage I-II epithelial ovarian cancer (EOC), 36 (7%) had stage III-IV EOC and 20 (4%) had non-EOC. Using clinical assessment in conjunction with ROMA, the TB recommended observation in 188 (37.8%) women. All patients diagnosed with an invasive malignancy were recommended for surgery by the TB. In the 315 patients managed surgically, 212 were found to have benign disease and 84 women were diagnosed with an invasive malignancy. The sensitivity for the initial TB recommendations using ROMA in conjunction with clinical judgment for detecting malignancy was 100% with a specificity of 47.7% and a NPV of 100%. When including low malignant potential tumors the sensitivity was 99.1%. For stage I-IV EOC ROMA alone had a sensitivity of 95.3%.CONCLUSIONS:
ROMA in conjunction with clinical assessment can safely identify women for conservative management.
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