Professor
Brian Andrews NEJM Recommendations for Medical Students and Tutors
Week
of 13th October 2016 (#64)
University
of Notre Dame Australia (Fremantle Campus)
Occasional Editorial Comment
In this week’s Journal there is a series of articles
which will lead to further discussion on the treatment of malignancies which
are detected in an early phase because of advances in technology. They also
explore the inability to predict, at this stage of our medical ignorance, which
of these tumours will possibly kill the patient before they die from other
comorbidities.
This has been a problem with asymptomatic patients with
prostate cancer diagnosed by an elevated PSA and a subsequent confirmatory
biopsy. An attempt to answer the question of treatment options has been
addressed in a serious of articles in the current issue of the Journal.
Also this issue of the Journal has an article describing the overdiagnosis of breast
cancer and how this form of cancer might be managed in the future.
Screening for lung cancer using low-dose CT to monitor
those who “continue to smoke” is also mentioned, but I digress.
In a previous issue of the blog (#56) a similar issue
was raised for thyroid cancer (http://www.nejm.org/doi/full/10.1056/NEJMp1604412 ).
Must Read Articles
Perspective
Hard
Time or Hospital Treatment? Mental Illness and the Criminal Justice System
When
a mentally ill person comes into contact with the criminal justice system, the
decision about whether that person belongs in jail or in the hospital is rarely
a clinical one. But it may shape the course of the person's life for many years
to come.
This Perspective
describes the totally different outcomes when a psychotic individual arrested
by police is taken to either a jail or to a hospital (in Providence RI). This
study give us all pause to reflect on how this applies to Australia,
particularly within the Aboriginal community.
MEDICINE AND SOCIETY
Liberty
versus Need — Our Struggle to Care for People with Serious Mental Illness
Of
9.8 million U.S. adults with serious mental illness, an estimated 40% receive
no treatment in any given year, often with dire consequences. But the
structural impediments to care can’t be addressed without reconciling the
conflicting ideals underlying them.
This is a must read, compassionate, and evidence-based
article which addresses serious mental illness in the US, though equally transferable
to Australia. The article outlines the ethical issues involved in treating
patients who deny they have a treatable mental illness and reject treatment. This
situation is particularly difficult when their future deterioration if
untreated is predictable. There is also a section on medical illness and the
adverse effects of anti-psychotic drugs in patients with serious mental
illness.
I particularly enjoyed reading the final section
entitled, “Good and Compassionate Care,” which argues that there should be a
middle ground between coercion and persuasion.
I quote: a University of Southern California law
professor who was in high school when she had her first episode of
schizophrenia-induced psychosis, offers nuanced analyses of coercion, judgment
impairment, and ethical, legal, and medical considerations. Although she is generally
protective of autonomy, she advocates a one-time autonomy violation for forced
treatment “the first time a person comes to the attention of treaters in a
psychotic state.” She also supports a controversial approach called
Ulysses grants, whereby people sign agreements when they’re relatively well to
receive psychiatric treatment when they have a psychotic episode, overriding
any future refusal of care. The latter is really an advanced directive for
future psychiatric care.
The article is provocative yet balanced and offers an excellent
vehicle to discuss these ethical issues.
Perspective
Hearing
without Listening
Computers
put patient data at our fingertips, but medical teams hypnotized by their
screens may not have the true intellectual interchange that lets them wrap
their minds around patients' problems. Yet there are ways to turn computers
from our masters into our servants.
My wife correctly points out that I hear without
listening. Thus I cannot but wonder how
much of this process applies to the swarms of medical care professionals with
or without their WOWs (workshops on wheels) flying from patient to patient on hospital
ward rounds.
Articles Recommended for Medical Students
ORIGINAL ARTICLE
10-Year
Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate
Cancer
In
the ProtecT trial, over 1600 men with PSA-detected localized prostate cancer
were assigned to active monitoring, prostatectomy, or radiotherapy. Although
more patients assigned to active monitoring had disease progression, overall
survival was similar in the three groups.
ORIGINAL ARTICLE
Patient-Reported
Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer
The
choice of treatment for PSA-detected, localized prostate cancer is influenced
by effects of the interventions on quality of life. In the ProtecT trial,
patterns of side-effect severity, improvement, and decline in urinary, sexual,
and bowel function differed among the treatments.
EDITORIAL
Treatment
or Monitoring for Early Prostate Cancer
These two articles and the Editorial provide the most current information on managing prostate
cancer patients found to have an elevated PSA on screening with biopsy proven
cancer (Gleason score of 6-7 in 98% of patients). 1643 patients from the UK were randomized
equally into groups for active monitoring, radical prostatectomy (robotic
prostatectomy was not performed), or radiotherapy with or without 3-6 months of
androgen-suppressive therapy.
A summary of the
results and reasonable recommendations (similar to current Australian
recommendations) are presented in the Editorial:
1.
For
today, we can conclude on the basis of level 1 evidence that PSA
monitoring, as compared with treatment of early prostate cancer, leads to
increased metastasis.
2.
If
a man wishes to avoid metastatic prostate cancer and the side effects of its
treatment, monitoring should be considered only if he has life-shortening
coexisting disease such that his life expectancy is less than the 10-year
median follow-up of the current study.
3.
Given
no significant difference in death due to prostate cancer with surgery versus
radiation and short-course androgen-deprivation therapy, men with low-risk or
intermediate-risk prostate cancer should feel free to select a treatment
approach using the data on health-related quality of life and without fear
of possibly selecting a less effective cancer therapy.
After considering the data from the study and the
adverse effects of each procedure, my personal selection at this stage would be
radiotherapy. However as robotic radical prostatectomy was not employed in this
study, I predict in the future that, with fewer long-term adverse results by
experienced operators, robotic prostatectomy may well become a clear first
choice.
IMAGES IN CLINICAL MEDICINE
Congenital
Rubella
An
8-month-old child was brought to the clinic by his parents, who reported that
he had had white opacities and “shaky” eyes since 4 months of age. On
examination, the child had wandering eye movements with bilateral central,
dense, white, nuclear congenital cataracts.
Bilateral cataract surgery in this 8 months old child
led to significant functional improvement.
IMAGES IN CLINICAL MEDICINE
Reversible
Acute Mesenteric Ischemia
A
60-year-old man presented with abdominal pain and hypotension. He had recently
had thrombosis of the superior mesenteric artery; CT showed jejunal dilatation
and thinning of the bowel wall. Videos show mucosal gangrene, hemorrhage, and
healing.
This is an example of successful conservative medical
management of a patient with mucosal necrosis and GI bleeding from acute
mesenteric ischaemia in a situation where no further surgical or radiological
intervention was possible.
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL
Case
31-2016 — A 53-Year-Old Man with Diplopia, Polydipsia, and Polyuria
A
53-year-old man was seen in outpatient clinics of this hospital because of a
1-year history of diplopia, polydipsia, and polyuria. Imaging studies showed
mucosal thickening of the sphenoid sinus and enlargement of the pituitary
gland. A diagnostic procedure was performed.
IgG4-related disease is an uncommon cause of
hypophysitis.
An excellent discussion
of the causes of sellar and suprasellar masses is presented.
ORIGINAL ARTICLE
Breast-Cancer
Tumor Size, Overdiagnosis, and Mammography Screening Effectiveness
This
study showed that after implementation of mammography screening, the increase
in the incidence of small lesions exceeded the decline in the incidence of
large lesions, which implied that many of the small tumors were unlikely to
become large lesions had they not been detected.
EDITORIAL
Solving
the Problem of Overdiagnosis
As indicated
above in the Occasional Editorial Comment,
the question will be what to do with small (? overdiagnosed) breast cancers
.
I cannot imagine
a situation currently in which a woman with a small breast cancer (definite
histological diagnosis) would elect for watchful waiting rather than, at a
minimum, lumpectomy with clear margins considering the low morbidity and
adverse effects associated with the procedure (significantly less than radical
prostatectomy or thyroidectomy).
The Editorial
should be read as it discusses screening and the factors involved in
overdiagnosis.
Recommended
learning: Review screening as a public health method for
prevention of malignant and non-malignant (e.g. lipids and bone density)
conditions based on current Australian guidelines.
Important Articles Related to Mechanisms of Disease and
Translational Research
CLINICAL IMPLICATIONS OF BASIC RESEARCH
Modulating Immunity to Treat Autoimmune Disease
A
recent study involving a mouse model showed that a genetically tweaked T cell
can specifically target the effector B cell that causes pemphigus vulgaris.
Rather than remove all CD20+ B cells with an anti-CD20
monoclonal antibody (Rituximab), which is effective in patients with pemphigus vulgaris
associated with autoantibodies directed against desmoglein 3 (Dsg3), the author
describes the work of Ellebrecht et al (Science 2016) which describes the use
of an engineered T cell in mice capable of selectively removing only the
pathogenic autoreactive B cells. This T
cell expresses a chimeric autoantibody receptor whose extracellular domain has
been swapped with desmoglein 3. This Dsg3 bearing T cell recognises
Dsg3-specific B cells through binding to the B-cell receptor destroying the
cell with perforins and cytotoxins.
Other Articles which should interest medical students
ORIGINAL ARTICLE
A
Randomized, Controlled Trial of ZMapp for Ebola Virus Infection
Ebola
virus causes a devastating clinical illness that is associated with high
mortality. In this trial conducted primarily in West Africa during an outbreak,
ZMapp (a cocktail of three monoclonal antibodies against Ebola) showed some
clinical activity.
Seventy one patients with Ebola infection were randomly
assigned into two treatment groups. One
received the current standard of care alone. The other received current
standard of care together with a triple monoclonal antibody cocktail against
Ebola virus (ZMapp). The mortality rate at 28 days for the group receiving
ZMapp was 22%, while for the other was 37%. Although it was apparent that the
group receiving ZMapp had a lower mortality rate, the result did not meet the
prespecified statistical threshold for efficacy.
New Pharmacological Therapies
None
Other articles which may be of interest to certain students
REVIEW ARTICLE
Cardiovascular
Toxic Effects of Targeted Cancer Therapies
Agents
targeting signaling pathways in cancer cells are less specific than advertised.
A number of these agents induce cardiovascular toxic effects ranging from
decreased ejection fraction to atrial arrhythmias.
This review article describes the basis for the new
medical subspecialty of cardio-oncology (see Figures 1, 2. Table 1 indicates
that virtually all current cancer therapy has the potential for
cardiotoxicity).
