Rectal Exams Still Important – Sorry
Most GPs of a certain vintage would have heard the old adage “if you don’t put your finger in, you put your foot in.”
It refers of course to the digital rectal examination and its importance as part of a thorough physical examination especially when symptoms indicate some potential pathology in that area.
However it would be fair to say that most doctors, let alone patients are not particularly enthusiastic about this particular test. Indeed you could almost hear the collective sigh of relief when the authoritative guidelines suggested regular DRE was not useful as a means of screening for prostate cancer.
The downside of this change in recommendation and general avoidance behaviour is that one can become deskilled in this examination, potentially missing an opportunity to diagnose a variety of conditions from prostate abnormalities to cancer.
In the latest MJA, Dr Christopher Pokorny from the South Western Sydney Medical School at UNSW gives a synopsis of indications for DRE and a run through of the appropriate technique.
“About 25% of colorectal cancers occur in the rectum and up to half can be palpated, but accuracy depends on training, experience, examination technique and the length of the examining finger,” Dr Pokorny writes.
His list of indications for the procedure include the more obvious symptoms such as PR bleeding or mucus, change in bowel habit and prostatic symptoms but also a history of faecal urgency, difficult defaecation, faecal incontinence and anorectal pain (with the caveat that DRE should be avoided if there is an obvious anal fissure).
Placing the patient in the left lateral position for the procedure is recommended with the patient drawing their knees to their chest and assuming that the patient is safe from falling off the examination couch.
Assessment is made of the skin around the anus – looking for fissures, fistulae, skin tags, skin diseases such as warts or psoriasis, abscesses and haemorrhoids. The well-lubricated, gloved finger is then gently inserted, rotated in a clockwise direction into the rectum. Dr Pokorny suggests a systematic examination of the rectal mucosa anteriorly, posteriorly and laterally for masses that should be described as soft, hard, irregular or smooth. Prostatic abnormalities in men and ovarian or uterine abnormalities in women may be noted being careful not to confuse a palpable cervix in a woman with a mass.
Finally, the doctor needs to check for any blood, including malaena on the glove.
Dr Pokorny does concede the value of this examination is limited by the body habitus of the patient, and the length of the examiner’s fingers. Nonetheless, it is unwise to miss this diagnostic opportunity in general practice.
“DRE is an often neglected but important part of the physical examination and should be performed whenever symptoms suggest anorectal or prostatic pathology,” he concludes.
MJA doi:10.5694/mja17.00373
Assessment Of Excision Margins
When assessing skin cancer specimens, the pathologist must address three main questions: what is the lesion; what prognostic information can be inferred; and is the lesion completely excised? In many instances, the assessment of the margins is the most important part of the pathological examination, since most skin cancers can be cured by complete excision.
It is salutary to note that ‘recurrent’ skin cancers are very often the result of recrudescence of a lesion that was incorrectly reported as having been completely excised.
As a general rule, the more thoroughly a skin specimen is sampled, the more likely the margin status will be reported correctly. When a specimen arrives in the laboratory, it is inspected by a scientist. The scientist will selectively sample the specimen, depending on its type and size, the size of any lesion and the clinical history.
Different laboratories have different protocols for sampling lesions and margins. The main techniques for assessing margins in elliptical excisions are illustrated to below.
The ‘bread-loaf’ technique involves producing parallel slices from the specimen at intervals of approximately 3mm. From each 3mm slice, a section or sections are cut. These sections are around 3μm thick and thus, each section is about one thousandth of the thickness of the tissue slices.
In some laboratories, the part of the lesion that is macroscopically obvious is bread-loafed, and the tips sampled separately. A potential problem with this technique is that segments of skin close to the lesion may be inadequately sampled.
The ‘cruciate’ or ‘hot cross bun’ technique enables the pathologist to determine the extent of the lesion in two planes, but leaves a significant proportion of the margin circumference not examined.
The en face technique is used by some laboratories, as, theoretically, it allows examination of the entire margin of the specimen. In practice, this is a poor technique when performed on small fixed specimens, as it is difficult to create a satisfactory section of the ‘true margin’. As a result, there can be false positive (and false negative) reporting of margin status.
Other sampling techniques are sometimes used, but in all methods, there is a compromise in balancing the minimisation of false negative and false positive reports, the cost, and the obtaining of adequate tissue for assessment of the lesion. Some of these techniques, for example, Mohs surgery, result in very low recurrence rates, but cost and availability limit their widespread application.
Whatever technique is utilised, the reader of the pathology report should be able to assess the extent and method of sampling.
The sampling of sections from shave excisions and punch biopsy excisions does not allow accurate assessment of margins, and there is a high rate of false negative reports in both types of specimens.
When a pathologist assesses the margins of an excisional specimen with a skin cancer, he or she seeks the presence or absence of malignant cells at the margin, and will report the margins as being involved or uninvolved. In some instances, the distance of the tumour from the margin may be reported.
A negative margin means that no tumour cells are identified at the margin in the specific sections examined by the pathologist. In some cases, the boundaries of a tumour are very obvious, but in others, where the tumour is poorly circumscribed, the pathologist must exercise skill and judgement to render an accurate report of margin status.
It should be clear from the discussion above, that the number of samples taken by a laboratory will also influence the accuracy of the reported margin status. The pathologist can never be absolutely certain that the margins are clear, because of the limited sampling.
A positive margin means that tumour cells are present at the edge of the specimen, but it does not follow that tumour cells extend into adjacent tissues. Furthermore, even if tumour cells remain, they may not survive to cause recrudescence (‘recurrence’). In basal cell carcinoma, for example, regrowth occurs in less than 30% of cases where the margins are involved and no additional treatment is performed. The rate of regrowth depends on the subtype of the tumour, with nodular basal cell recurring in less than 25% of cases of incomplete excision.
The reporting of the proximity of the tumour to the margins often creates confusion, and interpretation of measurements requires considerable clinical insight. Little empirical data is available to guide the skin surgeon in the use of microscopic measurements. These difficulties arise because there is no standardisation in the sampling of skin lesions and skin specimens, or the sectioning of the processed tissue. The more sections and tissue slices that are taken, the closer a measurement will reflect the true proximity of the tumour to the margin.
Additional difficulties arise when a tumour is poorly circumscribed, as both the skin surgeon and the pathologist may fail to identify the extent of the lesion accurately. Thus, a margin of less than 0.5mm might be quite adequate to ensure a nodular basal cell carcinoma is completely removed, but an identical margin in an aggressive basal cell carcinoma might be accompanied by margin involvement nearby.
Another factor which renders margin measurements unsatisfactory is the variable shrinkage of the skin specimen after excision. This shrinkage was formerly attributed to fixation in formalin, but it is now recognised that the shrinkage reflects the intrinsic contractile properties of skin. That is to say, skin, once excised, will contract ex vivo. Unfortunately, the extent of contraction is not predictable. Sun-damaged skin contracts less than juvenile skin, neoplastic tissue shrinks less than the surrounding dermis, and the epidermis shrinks less than the dermis. Because of this unpredictable contraction, measurements in vitro bear little relationship to the situation in vivo.
Finally, there are a number of practical issues which limit the utility of margin measurements. Some neoplasms, for example, squamous cell carcinomas, may exhibit a spectrum of changes, from normal, through changes resembling solar keratosis, to invasive carcinoma. There is no agreement amongst pathologists as to what constitutes the edge of such tumours and, as a consequence, measurements in this situation are poorly repeatable. In melanoma, individual abnormal melanocytes may extend a considerable distance from the main tumour and, again, measurements may be poorly reproducible.
General Practice Pathology is a new fortnightly column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs.
The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.
Poo Transplants Beat Antibiotics
Faecal transplantation has been gaining momentum as a mainstream treatment over recent years, but now a systematic review published in the MJA puts it ahead of antibiotics in effectiveness against Clostridium difficile-associated diarrhoea.
The literature search examined all the randomised controlled trials on the topic up until February this year, including some recently published studies, and concluded there was moderate quality evidence that faecal microbiota transplantation is more effective in patients with Clostridium difficile-associated diarrhoea than either vancomycin or placebo.
The review also found that samples that had been frozen and then thawed prior to transplantation were as effective as fresh samples.
“Our systematic review also highlights the fact that frozen/thawed transplants – a more convenient approach that reduces the burden on a donor to supply a sample on the day it is needed – is as effective as fresh [faecal microbiota transplant],” the authors said.
However, there was less clarity about the optimal method of administering the transplanted microbiota.
“Our analysis indicates that naso-duodenal and colonoscopic application may be more effective than retention enemas, but this conclusion relies on indirect comparisons of subgroups,” they concluded suggesting that further research was needed to determine the best route of administration.
There also needs to be more evidence into the most appropriate donor – whether they should be related, unrelated or anonymous, or whether ‘pooling stool from several donors’ would be the best way to go.
“Over the past 20 years the worldwide incidence of [Clostridium difficile-associated diarrhoea] has more than doubled, and outbreaks have been associated with greater morbidity and mortality, although to a lesser extent in Australia,” the study authors said.
Even though recent guidelines from Europe and North America now recommend these transplants to treat antibiotic-resistant Clostridium difficile-associated diarrhoea, the international authors of the review said these recommendations were based on relatively poor evidence.
It is expected this systematic review that includes more scientifically robust clinical trials will inform future guidelines on the topic, particularly in Australia and New Zealand whose guidelines on treating Clostridium difficile-associated diarrhoea currently need updating.
Ref: doi: 10.5694/mja17.00295
Man flu is real, but women get more autoimmune diseases and allergies
Men and women respond differently to diseases and treatments for biological, social and psychological reasons. In this series on Gender Medicine, experts explore these differences and the importance of approaching treatment and diagnosis through a gender lens.
We know that sex hormones drive characteristic male and female traits such as breast enlargement and hip widening in women, or increased muscle mass and growth of facial hair in men. But now we also recognise they have a major impact on the immune system – our body’s inbuilt mechanism that helps fight and protect us against disease.
Research suggests this has an evolutionary basis: survival of the species may mean men are harder hit by viruses, but a woman’s reactive immune system leaves her more susceptible to autoimmune diseases and allergies.
Viruses see men as weaker
Men die significantly more often from infectious diseases than women. For instance, men are 1.5 times more likely to die from tuberculosis, and twice as likely to develop Hodgkin’s lymphoma following Epstein–Barr virus (EBV) infection. Men are also five times more likely to develop cancer after infection with human papillomavirus (HPV), than women.
This is because women’s immune systems mount a stronger response against foreign invaders, particularly viruses. While the male hormone testosterone tends to dampen immune responses, the female hormone oestrogen increases the number of immune cells and the intensity of their response. So women are able to recover more quickly from an infection.
All this may reflect a sneaky evolutionary trick used by viruses to enable their survival. Women have developed multiple mechanisms to transmit infections; mainly through passing bugs from mother to child during gestation or birth, or through breastfeeding. So women are better vessels for viruses.
Meanwhile, viruses have singled men out as the weaker sex. While popular culture has come up with the term “man flu”, suggesting men are over-dramatising flu symptoms, evidence suggests they may in reality be suffering more due to this dampening down of their immune responses.
Read more – Health Check: is man flu real?
However, this increased susceptibility of men to infection may not be an advantage for the long-term (over tens of thousands of years) survival of a disease-causing organism (pathogen), if it induces such severe disease that it results in the death of the host.
Pathogens modify themselves so they can be transmitted by women during pregnancy, birth or breast feeding. Because of this, many have adapted to be less aggressive in women allowing wider infection, generally across a population.
However, this feature alone is not likely to be sufficient to ensure the ongoing survival of a virus. The fitness of both sexes is necessary to reproduce long-term and thus provide new hosts for invading pathogens. Thus, the hit to the male sex must somehow be balanced by other advantages to their immune system.
Autoimmune diseases
Autoimmune diseases occur when the immune system turns on and attacks the body’s own cells or tissues, initiating a chronic cycle that results in damage or destruction of specific organs. These diseases include type 1 diabetes, lupus, rheumatoid arthritis, multiple sclerosis, and up to 80 different diseases that affect systems such as the intestine, bones, joints and nervous systems.The most striking sex differences in the immune system are seen in autoimmune diseases. Autoimmune disease affects about 8% of the population, but 78% of those affected are women. Women are three times more likely than men to develop these types of disease.
Read more – Explainer: what are autoimmune diseases?
In the case of lupus, the immune system mistakenly attacks the person’s own DNA (the structure that carries a person’s genetic code) causing damage to multiple organs that will lead to weight loss, anemia and eventually heart and kidney failure. Nine out of ten patients with lupus are women and clinical observations suggest that, again, hormones are the culprits.
These differences of susceptibility between males and females tend to appear after puberty, and flare-ups increase during pregnancy. On the contrary, menopause is associated with a lower disease severity.
Studies have linked oestrogen levels with the exacerbation of lupus. Oestrogens directly act on a particular immune cell (called the plasmacytoid dendritic cell) to promote their capacity to secrete inflammatory signals, which exacerbate lupus symptoms. Although these dendritic cells are generally important for fighting viral infections, in the context of lupus and multiple sclerosis, they cause significant harm.
Hormones and allergies
One in nine Australians (more than 2.5 million in total) suffer from asthma – a disease that causes swelling and narrowing of the airways. This makes it difficult to breathe when we encounter environmental allergens such as pollen.
Twice as many women develop asthma compared to men. Interestingly, males are more susceptible to asthma before to the onset of puberty but, after puberty, females are more affected and develop more severe asthma than men. Until now, the reasons for this were not obvious, but hormones were speculated to play a role.
In a recent study, we showed that high levels of testosterone in males protect them against the development of allergic asthma. During puberty, the level of testosterone increases.
Testosterone acts as a potent inhibitor of a recently discovered immune cell called an innate lymphoid cell (ILC2), which accumulates in the lungs and initiates asthma. ILC2 cells release inflammatory signals that drive the swelling and airway narrowing characteristic of asthma when people are exposed to pollen, dust mites, grass or other common allergens. Testosterone reduces the numbers of ILC2 in the lungs of males, while female hormones provide no protective effect.
Read more: Do kids grow out of childhood asthma?
Immunity and sex are far more intricately linked than we had previously appreciated. More research needs to be done to better understand the triggers involved in the different responses of males and females. But the recent discoveries open the door for tactics to potentially target hormonal pathways or receptors that are preferentially expressed on male or female immune cells.
Read the first article in our Gender Medicine series – Medicine’s gender revolution: how women stopped being treated as ‘small men’
Gabrielle Belz, Professor, Molecular Immunology, Walter and Eliza Hall Institute and Cyril Seillet, Senior research scientist, Walter and Eliza Hall Institute
This article was originally published on The Conversation. Read the original article.
Do Not Order These Tests On Pregnant Women
Hot on the heels of the Choosing Wisely campaign of “do nots” for GPs, the Royal Australasian College of Physicians has released a new list of tests doctors should avoid ordering on pregnant women.
The recommendations come from the Society of Obstetric Medicine in Australia and New Zealand (SOMANZ), and include the advice that the D-dimer test should not be used to diagnose venous thromboembolism in pregnant women as it is unreliable.
Even though women are five times more likely to develop venous thromboembolism in pregnancy, other investigative tests should be used if a clot is suspected as D-dimer concentrations normally rise in pregnancy regardless of whether thrombosis has occurred, making abnormal results ‘incredibly unreliable’.
Another recommendation included in the RACP’s top five low value practices and interventions is to not test for inherited thrombophilia in women who have a history of placenta-mediated complications of pregnancy such as stillbirth, recurrent miscarriages or placental abruption.
The rationale behind the recommendation is that while some older, retrospective studies had suggested there might be an association with an inherited clotting disorder and these complications, more recent and more robust evidence has shown there is no link and what’s more, taking low molecular weight heparin is not useful as a preventive measure.
The experts also advise not to do repeat tests for proteinuria in women with established pre-eclampsia. Even though proteinuria is an important diagnostic marker for pre-eclampsia it is has no prognostic value. The level of the proteinuria does not correlate with the severity of the maternal complications, so repeated testing does not help management.
MTHFR testing has become popular in certain, mainly allied health circles and is controversial. SOMANZ has made a strong recommendation to not undertake MTHFR polymorphism tests as part of a routine evaluation for thrombophilia in pregnancy.
“Patients with the thermolabile variant of the methylenetetrahydrofolate reductase (MTHFR) polymorphism are at higher risk of hyperhomocysteinaemia which has been associated with venous thrombosis. However, these associations appear to hold only in countries lacking grain products nutritionally fortified as a public health measure.”
They also say testing may lead to many anxiety-provoking false positives, as up to 15% of the population have homozygous variants, which in most instances appear to have no deleterious effects.
The final test on the list is the erythrocyte sedimentation rate. The experts advise do not measure ESR in pregnancy as the levels can vary widely depending on factors such as gestational age and haemoglobin concentrations and therefore the test cannot reliably distinguish between healthy and unhealthy women in pregnancy.
The list is the latest publication put out as part of the physician-led Evolve initiative run by the RACP. The aim of the initiative is to help ensure high quality patient care by identifying those practices and interventions that represent poor value to patients in terms of improving their clinical outcome and may even cause harm. According to the media release there are now 17 Evolve lists that have been published across a range of medical specialties, and there are another 15 in development.
Ref: https://evolve.edu.au/published-lists/society-of-obstetric-medicine-of-australia-and-new-zealand
Increasing The Accuracy Of Melanoma Diagnosis
The diagnosis of pigmented skin lesions is amongst the most challenging and potentially dangerous areas of skin cancer medicine and dermatopathology. In this article, we discuss the limitations of histopathological diagnosis, and point to ways that the clinician may be able to assist the pathologist to minimise adverse outcomes.
Reliability of pathological diagnosis
To a large extent, the pathological diagnosis of melanocytic lesions is subjective. Most lesions can be readily and reliably diagnosed by an experienced pathologist, but some lesions may possess morphological features that are not stereotypical. In such cases, different observers may render different diagnoses and, in a small number of cases, the diagnoses may range between benignity, on the one hand, and malignancy on the other.
The extent of agreement between observers (or for a single observer making a number of observations) can be measured using a statistical tool called a kappa coefficient, where κ = 1 is perfect agreement, κ = −1 is perfect disagreement and κ = 0 is chance agreement.
A number of studies have examined the reliability of pathologists in reporting pigmented skin lesions. Although almost all of these studies tend to be distorted because of case selection (with most papers studying ‘difficult cases’), the results are worth noting.
In distinguishing melanoma from benign lesions, kappa coefficients around 0.5 (‘moderate agreement’) are reported. In one study, where cases were not selected, a kappa coefficient of 0.6 was achieved and, in more concrete terms, this meant that in 25% of cases, at least one of the four dermatopathologists in the study disagreed with the diagnosis of the remainder.
Other studies have a narrower focus. In dividing naevi into dysplastic, banal or intermediate categories, κ = 0.34 (‘fair agreement’), and in grading dysplasia, κ = 0.2–0.4 (‘slight to fair agreement’). These disappointing results mean that, in practice, expert dermatopathologists agree on the degree of dysplasia in less than 50% of cases.
Difficulties also arise in the diagnosis of ‘Spitzoid’ lesions. This rubric encompasses Spitz naevi, so-called ‘atypical Spitz naevi’ and melanomas with morphological features similar to those seen in Spitz naevi.
In one study, world expert dermatopathologists were unable to agree on cases of Spitz naevi, except in one case. Unfortunately, this case ultimately proved to be a fatal melanoma.
Other areas of poor diagnostic concordance relate to the diagnosis of melanoma in childhood, and in the diagnosis of cellular blue naevus.
The clinician’s role in assisting the pathologist
The problems which might arise from the inability of even expert pathologists to render reliable diagnoses in a subset of cases can be ameliorated by an insightful and prudent clinician. The surgeon must provide adequate clinical information and an adequate specimen. The importance of clinical information cannot be overstated.
Professor Peter Soyer, from the University of Queensland, and colleagues, showed that incremental increases in submitted clinical information improved the concordance of diagnoses rendered by a group of expert dermatopathologists. Moreover, the pathologists reported a substantial increase in the level of confidence in the diagnosis. Unfortunately, it remains the case that, in Australia and New Zealand, useful clinical information is not provided in around one third of specimen submissions.
In addition to the site and demographic details, the most pertinent information includes the clinical history, the size of the lesion and the clinical index of suspicion. Increasingly, more experienced clinicians provide dermatoscopic descriptions and photographs, and this additional information can be invaluable.
Biopsy technique has a major impact in the reliability of dermatopathological diagnoses. As a general rule, any lesion suspected of being a melanoma, and where the major differential diagnosis is a naevus, should be excised. This is the case because the features which permit clinical diagnosis of melanoma have microscopic correlates which the pathologist uses to establish the diagnosis. In particular, the symmetry of the lesion, the circumscription of its borders and the regularity in which the melanocytes are disposed, all require substantial breadth in a specimen for assessment.
Pathologists recognise that, on occasion, excisional biopsy is not feasible, but clinicians must be mindful that in parte biopsy specimens are associated with a very substantial increase in false negative and false positive diagnoses, and that interpretation of the pathology report should be tempered with this knowledge.
In a recent study from Melbourne, shave biopsies were associated with a 2.5 times risk of misdiagnosis, compared with excisional biopsies, and punch biopsies, 17 times.
False negative diagnoses with an adverse outcome were 20 times more likely with (partial) punch biopsies. It follows that the use of partial punch biopsies for diagnosis of melanocytic lesions is potentially dangerous, and this technique is inappropriate in most instances. Examples where their use might be appropriate are the biopsy of a papule to distinguish a dermal naevus from a small nodular basal cell carcinoma, and the biopsy of an irregular pigmented macule on the face, where the diagnosis is either a solar lentigo or melanoma. In both of these examples, the diagnosis can be made by identifying the cellular constituents of the lesion, that is, there is no requirement accurately to assess the architecture.
The expert clinician cannot be a passive recipient of a pathology report. Often, reports will have diagnoses couched in terms like ‘suggestive of’, ‘features favouring’ or similar phrases, which reflect the pathologist’s lack of certainty in the diagnosis. In such circumstances, there is an obligation on the clinician either to clarify the diagnosis with the pathologist, or to ensure that an equivocating diagnosis will not adversely affect the patient.
In some circumstances, this might require that an ambiguous lesion is completely excised, to ensure that it is extirpated. Where the pathological diagnosis is discordant with the clinical diagnosis, the clinician may wish to reconcile the diagnoses by asking the pathologist to review the slides, to examine additional tissue or to seek a further opinion.
In Australia, pathology laboratories are obliged to retain pathology slides, tissue and reports for a minimum of seven years, and review of archival material is useful in select cases. This lesion was diagnosed as dysplastic naevus by four pathologists and melanoma by three pathologists. Benign and malignant melanocytic lesions may have features which overlap.
Conclusion
In summary, the diagnosis of naevi and melanomas presents considerable difficulties for the pathologist. In the majority of cases, the diagnosis is straightforward, but in a significant minority of cases, pathological diagnosis is unreliable. Part of the unreliability is an inevitable consequence of the subjective nature of histopathological diagnosis, where different morphological features are given different weights by different observers.
However, at least in some circumstances, and using current dermatopathological techniques, morphology is not a perfect predictor of biology. Consequently, the clinician must assess every pathology report in concert with the other clinical information about the patient and about the lesion.
General Practice Pathology is a new fortnightly column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs.
The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.
Iron Deficiency: Translating New Evidence into Practice
This article discusses the importance, particularly in high risk groups, of the identification and correct management of iron deficiency.
Vaginal Atrophy and Sexual Function
This article discusses management options for vaginal atrophy and the importance of considering these in women for optimal sexual function.
Non-opioid Analgesics and Non-traditional Opioids in General Practice
This article discusses the use of non-opioid analgesics and non-traditional opioids in the management of pain in General Practice
Micronised Progesterone and Its Relevance to the Management of the Menopause
This article discusses why some of the Women’s Health Initiative (WHI) Randomised Clinical Trial conclusions are now considered to be exaggerated.
Body-identical Hormone Replacement Therapy
This article discusses the novel body-identical progesterone compared to other hormone replacement therapies and its place in the treatment of menopause.
Overcoming Barriers to Menopausal Hormone Therapy
This article examines the role of various MHT preparations on the management of menopause.
