Tag Archives: guest blog

Increased level of fluorescence intensity of breast cancer and normal mammary gland tissue a Haematoxylin and eosin-stained sections of normal and cancer tissue. The area outlined in green indicates the breast cancer. b Top images are fluorescence intensity images of γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) (green) at each time point overlaid on white light images. The fluorescence increase (FI) was obtained by subtracting the baseline fluorescence from the fluorescence at each time point. FIs are represented by the pseudocolour scale on the right side of the image.

Guest blog: a novel fluorescence technique for detecting breast cancer

Author: Hiroki Ueo, Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Ueo Breast Cancer Hospital, Oita, Japan

Breast cancer is the most common cancer in women, and its incidence continues to increase worldwide. From the patient’s perspective, breast conserving surgery (BCS) with radiation achieves a balance between a satisfactory cosmetic result and a low recurrence rate. Although it has been established as a routine surgery, surgeons need to be careful about positive surgical margins. Remnant cancer cells in the preserved tissue increase the risk of recurrence. Therefore, a positive margin on postoperative pathology warrants additional surgery. In these cases, the additional treatment harbours unexpected outcomes, including physical, mental, cosmetic, and economic burden on the patients. 

To avoid the additional operation, pathological evaluation using an intraoperative frozen section is conducted. It is the most reliable method to prevent misdiagnosis and to achieve clear surgical margins. However, this conventional method is time consuming and costly. Moreover, it is dependent on the skill and experience of the pathologists and personnel, and it requires space for preparation of the frozen sections. Therefore, only a limited number of samples are examined to save time and resources. An alternative, rapid, and reliable technique to detect cancer in surgical margins enables simultaneous testing, leading to a reduced false negative rate of local recurrence incidence. In addition, pathologists can focus on the definitive diagnosis using permanent paraffin sections because it is difficult to make a diagnosis based on intraoperative frozen sections without pathological architecture. Pathologists only need to make an intraoperative diagnosis when the specimen cannot be evaluated via the fluorescence procedure. Thus, it is important to enhance the rapid fluorescent detection of breast cancer during surgery. To address these diagnostic issues, Prof. Urano invented chemical reagents (gamma-glutamyl hydroxymethyl rhodamine green [gGlu-HMRG]) that quickly fluoresce by reacting with an enzyme (gamma-glutamyl transferase [GGT]), overexpressed in cancerous tissues. It exhibits strong fluorescence a few minutes after reacting with GGT in vitro. A gGlu-HMRG solution is applied to the surgical margins to recognize cancer cells as green fluorescence intraoperatively. A previous study in 2015 documented the ability of this reagent to mark cancerous tissues in surgical breast tissues. Furthermore, this reagent did not interfere with the pathological examination, while the frozen section analysis tissues were difficult to reuse as formalin-fixed and paraffin-embedded permanent pathological specimens. 

The clinical utility of this technique was examined. The results were published in the British Journal of Surgery. Since the initial report in 2015, a more feasible and reproducible sample preparation protocol has been developed. Then, a dedicated apparatus, including a built-in camera, software program, and multiple sample wells, was developed. This system automatically measured and analyzed the increase in fluorescence of multiple samples simultaneously. Then, the increase in fluorescence of gGlu-HMRG, applied to breast tissues, was measured in four different institutes. The sample tissues were examined by four pathologists independently. These pathologists diagnosed the samples without knowing the background information of the patients. The clinical utility of the current fluorescent procedure was evaluated by comparing the fluorescence data and the pathological diagnosis. 

A clear threshold to distinguish between cancerous and non-cancerous tissues was not determined due to the heterogeneity of breast cancer tissues. Instead, the negative threshold to achieve a false negative rate <2% and the positive threshold to achieve a false positive rate <2% were established. Samples in which the increase in fluorescence was below the negative threshold value were considered cancer-free margins with a false negative rate <2%. The false negative samples in our study were tissues containing non-invasive cancer. This suggested that the samples below the negative threshold can be considered free of invasive cancer. Samples in which the increase in fluorescence was above the positive threshold value were considered cancerous tissue with a false positive rate <2%.

The disease prevalence determines the performance of a diagnostic tool. The percentage of positive and negative test results among those with or without the disease are the positive and negative predictive values, respectively. These positive and negative predictive values depended on the prevalence. Therefore, to estimate the performance of this technique, the prevalence and margin positive rate in this case should be considered. The margin positive rate was expectedly lower than that of our clinical study. In our protocol, three pieces of tissue were sampled: the central portion, where the breast cancer is located; its periphery, which contains non-invasive cancer; and the distal portion, which ideally contains normal mammary tissue. Cancer was detected in 46% of the samples. Based on the actual margin assessment, the prevalence was lower than that of our study. Assuming a prevalence <30%, the negative predictive value, the ratio of true negative samples among fluorescent negative samples, was larger than 98%. This indicated that this method was useful for detecting negative margins. 

According to this multicenter study, the fluorescent diagnosis was applicable to any breast cancer subtype, regardless of its pathological findings and subtype. Moreover, the similar accuracy among several institutes confirmed that the fluorescent diagnosis was applicable to any institute, following the protocol. Compared to the intraoperative frozen section analysis, the fluorescent diagnosis was a more rapid and accessible method with a low cost. It was not dependent on the skills of pathologists, and it did not require a large amount of space.           

In conclusion, this method can facilitate the rapid assessment of negative surgical margins during BCS while reducing the testing time, cost of diagnosis, and tasks of the pathologists and staff. 

Roux en Y gastric bypass

Guest blog: Bariatric Surgery – the safe solution to the metabolic pandemic

Authors: A G N Robertson (Twitter: @robertson_a), T Wiggins (@TomWiggins23), F P Robertson, L Huppler (@LucyLucyHuppler), B Doleman, E M Harrison (@ewenharrison), M Hollyman (@misshollyman), R Welbourn

Obesity is the preventable and reversible disease of our lifetime. It is a worldwide health, economic and environmental problem in need of urgent and essential attention, and it has become clear that the world needs more than the traditional recommendations to survive this metabolic pandemic.  The traditional advice has been acknowledged for centuries and even more so since the worldwide prevalence of obesity nearly tripled between 1975 and 20161. These lifestyle recommendations include physical exercise, less high calorific food content, balanced meals, optimising portion size, intermittent fasting and so on; we all know them. However, the human race is still falling short of tackling the major public health concern that this disease threatens to be. 

Bariatric or weight loss surgery is a surgical sub-speciality which has been evolving since the first procedures of this type in the mid 20th century. Its development has led to the most effective method to achieve long-term weight loss, as well as the additional health benefits weight loss offers as a by-product. However, accessibility to this specialist treatment is limited with only 1% of eligible patients going on to receive bariatric surgery.2Reasons for this limited access are multifactorial, however a considerable factor is thought to be concerns regarding the perceived risks of weight-loss surgery from patients across all populations. We should therefore aim to give our patients the most up to date worldwide risk of mortality of these potentially life-saving procedures. 

This month in the BJS, we’ve published the largest meta-analysis asking this question to date – and the findings are pivotal at providing a unanimous international statistic on this discussion. We’ve looked at perioperative mortality rates (inpatient, 30 day and 90 day mortality) of a range of bariatric procedures to include laparoscopic adjustable gastric band (LAGB), sleeve gastrectomy (SG), Laparoscopic Roux-en-Y gastric bypass (LRYGB), one-anastomosis gastric bypass (OAGB), biliopancreatic diversion/duodenal switch (BPD-DS) and other malabsorptive procedures. We’ve included 58 studies in our meta-analysis which has given us information on roughly 3.6 million patients over a 6-year period from worldwide practice. Multiple sources for data were used including administrative datasets, bariatric surgery registries, large scale case series as well as randomised controlled trials (RCTs). 

The paper looks at mortality within each subgroup of operation. There are interesting findings within this showing significant differences in perioperative mortality between procedures (P<0.001) with biliopancreatic diversion/duodenal switch or other malabsorptive procedures having the highest perioperative mortality rates (0.41%) and laparoscopic adjustable gastric band (LAGB) followed by sleeve gastrectomy (SG) being the procedures with the lowest perioperative mortality rates (0.03% and 0.05% respectively). This naturally reflects the trend towards these latter procedures being offered more commonly in international practice. Although this paper looks closely at perioperative mortality it is noteworthy to mention that it doesn’t look at long term morbidity following these procedures or their potential complication rates. 

Without a doubt, our most noteworthy finding has been the discovery that overall perioperative mortality following bariatric surgery is likely much lower than previously thought, with our pooled perioperative mortality rate at 0.08% (95% CI 0.06%-0.10%). It perhaps makes this statistic even more relatable when this is compared to other procedures we consider as ‘low-risk’ in our daily surgical practice. For example, laparoscopic cholecystectomy or fundoplication have comparable perioperative mortality rates reported at 0.1%. This new statistic is also lower than previously quoted in the literature from smaller scale studies. The mortality rate calculated in this meta-analysis puts bariatric surgery as a whole at lower risk of mortality as knee arthroplasty (0.3%)3. With this in mind, we hope that there can be a culture shift from avoidance of bariatric surgery due to risk, to giving patients the correct information to confidently weigh up the true risks and benefits of these procedures when indicated. 

How should these findings shape the future of bariatric surgery in Europe and beyond? Certainly in the UK, the acceptability of bariatric surgery as a viable treatment option for obesity is limited. It is surprising how often we see patients who are eligible for bariatric surgery and who have met the criteria for some time yet to be offered this as a treatment option. There is a distinct barrier to accessing bariatric surgery for the wider population, perhaps due to taboo surrounding broaching the issue of weight in the primary care setting, and although many general practitioners do this very well, there remain limiting factors. Another stand-out factor includes lack of funding or commissioning within the public health service for referral for weight loss specialist services. Therefore, with the addition of this new internationally applicable statistic, our hope is that the most effective treatment option for sustained weight loss can now be available for all that require it. Bariatric surgery is safe. 

  1. https://www.worldobesity.org/about/about-obesity/prevalence-of-obesity
  2. Welbourn R, le Roux CW, Owen-Smith A, Wordsworth S, Blazeby JM. Why the NHS should do more bariatric surgery; how much should we do? Bmj. 2016;353:i1472.
  3. Aminian A, Brethauer SA, Kirwan JP, Kashyap SR, Burguera B, Schauer PR. How safe is metabolic/diabetes surgery? Diabetes, Obes Metab. 2015; 17(2):198-201.

Image source: Eslam ibrahim66 2021 Creative Commons

Visual abstract for COVIDHAREM appendicitis study

Guest blog: Antibiotics – not operations – to treat adult appendicitis?

By Hannah Javanmard-Emamghissi (@hannahjavanmard), NELA Research Fellow and RCSEng Research fellow on behalf of the COVID:HAREM Collaborative 

Keyhole surgery (laparoscopic appendicectomy) has been the mainstay of adult appendicitis treatment in Europe and the United States for the last several decades. In spite of this numerous trials have been ongoing exploring if there is a role for non-operative management of appendicitis with antibiotics. The APPAC and CODA trials both demonstrated that antibiotics were effective at treating simple appendicitis that was not perforated, gangrenous or associated with an abscess in the majority of patients.(1,2) However, it remained an underutilised treatment strategy. 

This all changed during February and March of 2020, when the Sars-COV-2 virus (COVID-29) swept across much of the globe. Healthcare providers were forced to make contingency plans for hospitals that faced being overwhelmed by patients infected with COVID-19. Much of the anaesthetic workforce had been redeployed to intensive cares and there was uncertainty of the safety of general anaesthesia for patients with peri-operative COVID-19 and of the safety of the theatre teams exposed to virus aerosols during laparoscopy.(3,4) Non-operative management strategies were implemented recommended by surgical professional bodies across many surgical disciplines as a way of mitigating for these uncertainties.(5)

Our collaborative’s report, just published in BJS, represents the first time non-operative management of appendicitis has been implemented on a wide scale in the United Kingdom. We collected data on patients over the age of 18 presenting during the first wave of the COVID-19 pandemic presented with signs and symptoms suggestive of acute appendicitis, whether they were managed operatively and non-operatively. These patients were followed up for 90 days for length of hospital stay, complications, representation to hospital and appendicitis recurrence. Patients managed non-operatively were matched with similar patients managed operatively using propensity score matching, and their outcomes were compared.

Patients from 97 hospitals across the United Kingdom and Republic of Ireland were included in our study. Three thousand four hundred and twenty patients were included, of which 41% had initially been treated with antibiotics. When they were matched using propensity score matching with similar patients who had non-operative management, the group treated with antibiotics spent less time in hospital and had fewer complications than those who had an operative management. Non-operative management was successful in 80% of the patients managed in this way, with 20% going on to have an appendicectomy in the 90 days after their first attendance. 

We also teamed up with a health economics team from the London School of Tropical Medicine to calculate the costs associated with each treatment method. We found that, even when accounting for the 20% of patients that had surgery within the 3 months of being treated with antibiotics, non-operative management was associated with a cost reduction of €1034 per patient compared to operative management. 

This study proves that antibiotics are an effective management strategy for appendicitis and can be utilised on a large scale beyond trials for the first time ever. Patients may be keen to avoid surgery for a number of reasons and going forward surgeons should incorporate a discussion about the risks, benefits and uncertainties of non-operative management into conversations they have with patients about appendicitis management options. Our results have shown how reducing the number of operations we do for appendicitis can have benefits for the patient in terms of complications and days in the hospital away from work and home, but it may have wider benefits to the hospital and world. Not only is non-operative management cheaper for the hospital, but reducing the number of appendicectomies performed can free up theatre time so the most urgent surgical emergencies have less delay accessing theatre. All operations are associated with a significant amount of carbon emissions and single use plastic waste, but despite our best efforts to reduce the harm that surgery can cause to the environment the most effective strategy remains reducing the amount of unnecessary surgery performed.(6)

That is not to say that the study of non-operative management of appendicitis is over, there is still debate about the long-term efficacy of antibiotic management and concern that some cancers of the appendix may be missed by not removing the appendix at the first presentation, as well as questions about how acceptable patients find non-operative management. Our collaborative hopes to answer these questions and more in a one year follow up study and ongoing patient and public involvement work. 

Conflicts of Interest 

None to declare 

Funding

No funding was received for this blog article 

References

1.        Salminen P, Tuominen R, Paajanen H, Rautio T, Nordström P, Aarnio M, et al. Five-year follow-up of antibiotic therapy for uncomplicated acute appendicitis in the APPAC randomized clinical trial. JAMA. 2018 Sep 25;320(12):1259–1265. 

2.        CODA Collaborative, Flum DR, Davidson GH, Monsell SE, Shapiro NL, Odom SR, et al. A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis. N Engl J Med. 2020 Nov 12;383(20):1907-1919.

3.        Nepogodiev D, Bhangu A, Glasbey JC, Li E, Omar OM, Simoes JF, et al. Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study. Lancet [Internet]. 2020 Jul 4 [cited 2020 Nov 5];396(10243):27–38. Available from: https://doi.org/10.1016/

4.        SH E. Should we continue using laparoscopy amid the COVID-19 pandemic? Br J Surg [Internet]. 2020 Jul 1 [cited 2021 Sep 5];107(8):e240–1. Available from: https://pubmed.ncbi.nlm.nih.gov/32432344/

5.        Hettiaratchy S, Deakin D. Guidance for surgeons working during the COVID-19 pandemic from the Surgical Royal Colleges of the United Kingdom and Ireland. Intercollegaite Royal Colleges of Surgery. London; 2020. 

6.        MacNeill AJ, Lillywhite R, Brown CJ. The impact of surgery on global climate: a carbon footprinting study of operating theatres in three health systems. Lancet Planetary Health [Internet]. 2017 Dec 1 [cited 2021 Sep 5];1(9):e381–8. Available from: http://www.thelancet.com/article/S2542519617301626/fulltext

External aspect of the operative field: DaVinci™ robotic system docked to the patient

Guest blog: What advantage does robot-assisted and transanal TME have over laparoscopy?

Authors: Jeroen C. Hol, Colin Sietses

Contact: j.c.hol@amsterdamumc.nl

Correspondence to: “Comparison of laparoscopic versus robot-assisted versus TaTME surgery for rectal cancer: a retrospective propensity score matched cohort study of short-term outcomes

Image source: Robinson Poffo et. al. Robotic surgery in Cardiology: a safe and effective procedure. https://creativecommons.org/licenses/by/4.0/ under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The emergence of minimally invasive surgery has led to the development of three new surgical techniques for oncological rectal resections: laparoscopic, robot-assisted and transanal TME (TaTME). When we compared the three techniques executed in expert centres, we expected to find an advantage for one of the three techniques in terms of reduced complication rates. But contrary to our expectations, no difference was seen. There was one striking difference however, when comparing these techniques, though it might be something different than you might have thought. We shine a light on all three techniques to explain their advantages. 

Laparoscopy: minimally invasive surgery

In the 1980’s, Heald introduced the total mesorectal excision (TME) principle, which comprises excision of the rectum and its surrounding fatty envelop with preservation of the autonomic nerves [1]. TME has become the golden standard for surgical resection for rectal cancer and helped dropping local recurrence rates drastically. The past decades laparoscopy has been introduced and gradually replaced open surgery. Laparoscopy offers short term benefits of minimally invasive surgery, such as faster recovery and reduced complication rates [2, 3]. It offers similar long-term outcome as open surgery [4]. But laparoscopy is technically demanding because it is difficult to work with rigid instruments in the narrow and confined area of the pelvis. Therefore, conversion rates to open surgery of more than 10% were seen [5]. Conversion is linked to increased morbidity and worse oncological outcome [6]. In order to overcome those technical limitations of laparoscopic TME, new techniques have been introduced; robot-assisted TME and TaTME. 

Robot-assisted TME: the same, but different

Robot-assisted TME comprises the same approach as laparoscopy, but with the use of a surgical robot. The surgical robot provides a stable platform with supreme vision and supreme instrument handling. Surgeons thought this technique might improve results in terms of reduced complication rates and reduced conversion rates. However, the largest randomized trial so far comparing robot-assisted and laparoscopic TME failed to show any difference in these outcomes [7]. This might have been the result of a methodological flaw, because the robotic surgeons in that trial were not as experienced as their laparoscopic colleagues [8]. In our study, we tried to eliminate this by only selecting experienced centres that were beyond their learning curve. However, we did not see reduced complication rates or reduced conversion rates after robot-assisted TME compared to laparoscopy.

Transanal TME: a different approach

TaTME comprises a different approach to address the most difficult part of the dissection. In TaTME the most distal and difficult part of the rectum is dissected from below using a transanal insufflator port. However, this is a technically demanding technique and has a long learning curve [9]. Some initial series showed high loco regional recurrence rates, which even led to a halt of TaTME in Norway [10, 11]. The potential learning curve effect is now part of an ongoing debate about the oncological safety of this technique. Most initial results however looked promising and showed consistently good quality specimen and lower conversion rates [12, 13]. In our study, conversion rates, number of complete specimen and morbidity rates did not differ from the other laparoscopy and robot-assisted TME. 

Technological advantage 

The results of our study showed similar and acceptable short-term results for all three techniques in expert centres. The most striking difference was that in centres with robot-assisted or TaTME, more primary anastomoses were made. The technological advantage of the two new techniques could have contributed to higher restorative rates. Both robot-assisted and TaTME provide better access and visibility to the distal rectum, enabling surgeons to complete the TME dissection safely and create an anastomosis. Robot-assisted TME could overcome technical limitations of laparoscopy in the narrow pelvis thanks to the use of 3D vision, lack of tremor, and superior instrument handling, thereby facilitating safe creation of an anastomosis [7, 14]. TaTME does not need multiple staple firing to transect the distal rectum and without requiring conversion to open surgery [13]. In fact, TaTME does not need cross-stapling at all, preventing the creation of dog-ears which are prone to ischemia [15]. 

Patient’s perspective

In conclusion, the technological advantage of robot-assisted TME and TaTME manifests itself in higher restorative rates. Each technique seems to be equally beneficial in terms of oncological outcomes and morbidity. However, anastomosis creation, quality of life and functional outcome are becoming of great importance to patients. It seems to be that an increasing proportion of patients is now in pursue of an anastomosis. The overall anastomosis rate of more than 84% for robot-assisted and TaTME in our study was higher than the anastomosis rate of 50% in a previous national study [16]. A note of caution should be added, as an anastomosis might not be always better in terms of functional outcome and quality of life. Patients with a low anastomosis are at risk of developing severe low anterior resection syndrome (LARS) symptoms. Severe LARS symptoms can have a detrimental effect on quality of life [17].  Further research should be undertaken to investigate whether a higher anastomosis rate is beneficial in terms of quality of life and functional outcome and whether this higher anastomosis rate actually leads to increased patient satisfaction. 

References

1.         Heald, R.J., E.M. Husband, and R.D. Ryall, The mesorectum in rectal cancer surgery–the clue to pelvic recurrence? Br J Surg, 1982. 69(10): p. 613-6.

2.         Stevenson, A.R., et al., Effect of Laparoscopic-Assisted Resection vs Open Resection on Pathological Outcomes in Rectal Cancer: The ALaCaRT Randomized Clinical Trial. JAMA, 2015. 314(13): p. 1356-63.

3.         van der Pas, M.H., et al., Laparoscopic versus open surgery for rectal cancer (COLOR II): short-term outcomes of a randomised, phase 3 trial. Lancet Oncol, 2013. 14(3): p. 210-8.

4.         Bonjer, H.J., et al., A Randomized Trial of Laparoscopic versus Open Surgery for Rectal Cancer. N Engl J Med, 2015. 373(2): p. 194.

5.         Chen, K., et al., Laparoscopic versus open surgery for rectal cancer: A meta-analysis of classic randomized controlled trials and high-quality Nonrandomized Studies in the last 5 years. Int J Surg, 2017. 39: p. 1-10.

6.         Allaix, M.E., et al., Conversion of laparoscopic colorectal resection for cancer: What is the impact on short-term outcomes and survival? World J Gastroenterol, 2016. 22(37): p. 8304-8313.

7.         Jayne, D., et al., Effect of Robotic-Assisted vs Conventional Laparoscopic Surgery on Risk of Conversion to Open Laparotomy Among Patients Undergoing Resection for Rectal Cancer: The ROLARR Randomized Clinical Trial. JAMA, 2017. 318(16): p. 1569-1580.

8.         Corrigan, N., et al., Exploring and adjusting for potential learning effects in ROLARR: a randomised controlled trial comparing robotic-assisted vs. standard laparoscopic surgery for rectal cancer resection. Trials, 2018. 19(1): p. 339.

9.         Koedam, T.W.A., et al., Transanal total mesorectal excision for rectal cancer: evaluation of the learning curve.Tech Coloproctol, 2018. 22(4): p. 279-287.

10.       Larsen, S.G., et al., Norwegian moratorium on transanal total mesorectal excision. Br J Surg, 2019. 106(9): p. 1120-1121.

11.       van Oostendorp, S.E., et al., Locoregional recurrences after transanal total mesorectal excision of rectal cancer during implementation. Br J Surg, 2020.

12.       Detering, R., et al., Three-Year Nationwide Experience with Transanal Total Mesorectal Excision for Rectal Cancer in the Netherlands: A Propensity Score-Matched Comparison with Conventional Laparoscopic Total Mesorectal Excision. J Am Coll Surg, 2019. 228(3): p. 235-244 e1.

13.       Grass, J.K., et al., Systematic review analysis of robotic and transanal approaches in TME surgery- A systematic review of the current literature in regard to challenges in rectal cancer surgery. Eur J Surg Oncol, 2019. 45(4): p. 498-509.

14.       Kim, M.J., et al., Robot-assisted Versus Laparoscopic Surgery for Rectal Cancer: A Phase II Open Label Prospective Randomized Controlled Trial. Ann Surg, 2018. 267(2): p. 243-251.

15.       Penna, M., et al., Four anastomotic techniques following transanal total mesorectal excision (TaTME). Tech Coloproctol, 2016. 20(3): p. 185-91.

16.       Borstlap, W.A.A., et al., Anastomotic Leakage and Chronic Presacral Sinus Formation After Low Anterior Resection: Results From a Large Cross-sectional Study. Ann Surg, 2017. 266(5): p. 870-877.

17.       Emmertsen, K.J. and S. Laurberg, Low anterior resection syndrome score: development and validation of a symptom-based scoring system for bowel dysfunction after low anterior resection for rectal cancer. Ann Surg, 2012. 255(5): p. 922-8.

Schematic of process for classifier design

Guest blog: 21st century surgery is digital

Ronan Cahill, Digital Surgery Unit, Mater Misericordiae University Hospital, Dublin, Ireland and UCD Centre for Precision Surgery, Dublin, Ireland.

Niall Hardy, UCD Centre for Precision Surgery, Dublin, Ireland.

Pol MacAonghusa, IBM Research, Dublin, Ireland.

Twitter @matersurgery Email: ronan.cahill@ucd.ie

Cancerous tissue behaves differently from non-cancerous tissue. Every academic oncology paper ever written tells us this. The appearances of any cancer primary (or indeed secondary lesion) result from biological and molecular processes that are the hallmarks of malignancy including dysregulated cell function and composition, host-cancer stromal and inflammatory response and angiogenesis. However, we surgeons haven’t really yet been able to exploit this knowledge during surgery in a way that helps us make a better operation. Instead, our learning and research about oncological cellular processes has predominantly advanced through basic science geared more towards perioperative prognostication and/or adjuvant therapy stratification. Wouldn’t it be great if realisation of cancer microprocesses could usefully inform decision-making intraoperatively?

We’ve just published an initial report in the BJS showing this very thing – that it is indeed possible to ‘see’ cancer by its behaviour in real-time intraoperatively. We’ve used Artificial Intelligence (AI) methods in combination with near-infrared fluorescence laparoendoscopy to judge and classify neoplastic tissue nature through the observation of differential dye diffusion through the region of interest in comparison with that happening in normal tissue being viewed alongside it. Through our understanding of biophysics (flow parameters and light/dye interaction properties), a lot of information can be drawn out over short periods of times via advanced computer vision methodology. With surgical video recording in the region of 30 frames per second, big data generates over the time frame of a few minutes.  While the gross signal shifts are discernible even without AI, smart machine learning capabilities certainly mean their interrogation becomes really usable in the provision of classification data within moments. What’s more, while we’ve focused initially on colorectal cancer, the processes we are exploiting seem common across other solid cancers and using other camera-based imaging systems. By combining with the considerable amount of knowledge we already have accrued regarding tissue biology, chemistry, physics as relate and indeed surgery, our AI methods are giving explainable and more importantly interpretable recommendations with confidence using a smaller dataset than that demanded by deep learning methodologies.

This though is just an early exemplar of what’s becoming possible through ‘Digital Surgery’, a concept that seems far more likely to transform contemporary surgical practice than our current general surgery “robotic” systems, hulking electromechanical tools entirely dependent on the user – a rather 20th century concept! Indeed, there is sophisticated technology everywhere in today’s operating theatres – surgeons sure don’t lack technical capability. Yet often despite vaulting costs, advance of real, value-based outcomes has been disappointingly marginal in comparison over the last two decades. The key bit for evolved surgery is instead going to be assisting surgeons to make the best decision possible for each individual patient by providing useful, discerning information regarding the surgery happening right now, and somehow plugging this case circumstances directly into the broad knowledge bank of expertise we have accrued as a profession (and not just be dependent on any single surgeon’s own experience).

To do this we need to realise the importance of visualisation in surgical procedures versus manual dexterity.  All surgery is performed through the visual interpretation of tissue appearances and proceeds via the perception-action cycle (‘sense, predict, act, adjust’). This is most evident during minimally invasive operations where a camera is used to display internal images on a screen but applies of course to open procedures as well. As all intraoperative decisions are made by the surgeon, the entire purpose of surgical imaging has been to present the best (‘most visually appealing’) picture to the surgeon for this purpose. Experiential surgical training is for the purpose of developing the ‘surgical eye’, that is learning how to make qualitative intraoperative judgments reliably to a reasonable standard. We haven’t however gotten the most out of the computer attached to the camera beyond image processing where we have concerned ourselves with display resolutions and widths. 

Imagine instead if some useful added interpretations of images could be made without adding extra cognitive burden to the surgeon, perhaps with straightforward on-screen prompts to better personalise decisions? This would be particularly exciting if these data were not otherwise easily realisable by human cognition alone and could be immediately and directly relevant to the person undergoing the operation. Every operation is in effect a unique undertaking, informed by probabilities accruing through individual and collected prior experience for sure but a new thing in and of itself for which the outcome at the time of its performance is unknown. How this individual patient differs from others and most especially how might an adverse outcome be avoided is a crucial thing to flag before any irreversible surgical step that commits an inevitable future. 

Right now, we are in a golden age of imaging. This is intricately linked to advances in computer processing and sharing power along with AI methods. This means we can harvest great additional information from the natural world around us across the spectrum of enormous (radio waves spanning the universe) to tiny (high resolution atomic imaging) distances and apply methods to help crystalise what this means to the observer. While a lot of AI is being directed at the easier and safer areas of standard patient cohort datasets, increasingly it’s possible to apply computer intelligence to the data rich surgical video feeds being generated routinely during operations to present insights to the surgeon. While early first steps at the moment relate to rather bread and butter applications such as instrument or lesion recognition and tracking as well as digital subtraction of smoke or anonymization protocols to prevent inadvertent capture of operating rooms teams when the camera is outside the patient, soon the capability to parse, segment and foretell likely best next operative steps will be possible at scale.

At present, the biggest limitation is that surgery lacks large warehoused archives of annotated imagery because operative video is a more complex dataset to scrutinise than the narrower image datasets available in specialities such as radiology, pathology and ophthalmology. Thanks to advances in computing, this is changing. Surgical video aggregation to enable building of representative cohorts is increasingly possible and, by combining with metadata and surgical insights, its full value can begin to be realised. GDPR frameworks provide structure and surgeons are increasingly understanding of the value of collaborating in research, education and practice development. However, while certain siloed sites focused around specific industry projects are already manifesting, the key area for greatest general advance lies within the surgical community combining broadly to construct appropriately developed and secured, curated video banks of procedures that can then be made accessible to entities from regulators and standard bodies, academia and indeed corporations capable of advancing surgery. This gives by far the greatest chance of the best of surgical traditions carrying through the 21st century while our weak spots are fortified for better surgery in the public interest.

Further reading: 
Artificial intelligence indocyanine green (ICG) perfusion for colorectal cancer intra-operative tissue classification.
 Cahill RA, O’Shea DF, Khan MF, Khokhar HA, Epperlein JP, Mac Aonghusa PG, Nair R, Zhuk SM.Br J Surg. 2021 Jan 27;108(1):5-9. https://doi.org/10.1093/bjs/znaa004 PMID: 33640921 

The age of surgical operative video big data – My bicycle or our park? Cahill RA, MacAonghusa P, Mortensen N. The Surgeon 2021 Epub ahead of press https://doi.org/10.1016/j.surge.2021.03.006

Ways of seeing – it’s all in the image. Cahill RA. Colorectal Dis. 2018 Jun;20(6):467-468. https://doi.org/10.1111/codi.14265 PMID: 29864253

The Anatomy Lesson of Dr. Nicolaes Tulp by Rembrandt

Guest post: Why should you care about the history of surgery?

Dr. Tyler Rouse is an anatomical pathologist at the Huron Perth Healthcare Alliance in Stratford, Canada, and an adjunct professor in the Department of Pathology at the Schulich School of Medicine and Dentistry, Western University. He is the creator and host of the history of surgery podcast ‘Legends of Surgery’.

Why should you care about the history of surgery?

To begin with, it is unquestionably fascinating and fun. The history of surgery is filled with heroes and villains, triumphs and tragedies, progress and setbacks, but continuously moves towards the easing of suffering and the protection and prolonging of life. Yet there is something deeper and more meaningful that can be gained from the study of history. It grounds us, gives us a richer understanding of the world in which we live, and tells us how we arrived at this point in history, and provides a sense of identity and belonging in the world. 

The knowledge we now possess finds its origins in the writings of Hippocrates and Galen and the classical world of ancient Greece and Rome, which is reflected in the Latin and Greek roots of the words of the ‘lingua franca’ of medicine that we use every day. This was preserved and advanced during the Dark Ages by the physicians and surgeons of the Islamic Golden Age, and then “rediscovered” in the Renaissance, until the scientific revolution of the Age of Enlightenment shook us from the bonds of classical dogma and led to an explosion of medical and surgical knowledge through experimentation. The Industrial Age created added significant technological advances, arguably the most important of which was the ability to inhibit pain and avoid infection, allowing surgeons to delve ever deeper into the mysteries of the human body. This opened the window to the contributions from surgeons from across the globe that have brought us to this moment in time. This accumulated knowledge has been passed down from master to apprentice, teacher to learner, staff to student, in an unbroken chain that directly links us with the surgeons of the past.

Their influence is all around us when we step into the operating theatre, from hand washing (Semmelweiss), to the asepsis of the operative field (Lister), to the wearing of surgical gloves (Halsted) to the countless eponymously named instruments, procedures, and anatomical structures, that are part of every operating theatre around the world. Just about every part of an operation links us to the past, and to the people that came before us who discovered this hard-won knowledge. 

File:Use of the Lister carbolic spray, Antiseptic surgery, 1882. Wellcome M0003436.jpg
Use of the Lister carbolic spray. Credit: Antiseptic surgery : its principles, practice, history and results / by W. Watson Cheyne. Public Domain Mark. From Wellcome Images.

Studying these individual surgeons can both inspire us, and serve as a warning by demonstrating how good intentions can lead us astray. In addition to their contributions to surgical practice, many surgeons were basic scientists, Nobel Prize winners, public health advocates, artists, musicians, writers, and influential public figures that captured the imagination of society, both with their innovative breakthroughs and sometimes, their larger than life personalities. The English surgeon Percival Potts discovered the link between chimney sweeping and scrotal cancer in 1775, considered the first identification of an environmental carcinogen. American neurosurgeon Harvey Cushing won a Pulitzer Prize for his biography on Sir William Osler. South African surgeon Christiaan Barnard, who performed the world’s first successful heart transplant, was also an outspoken opponent of apartheid. And there are countless other examples.

Harvey Williams Cushing. Photograph by W.(?)W.B.
Harvey Williams Cushing. Credit: Harvey Williams Cushing. Photograph by W.(?)W.B. Credit: Wellcome CollectionAttribution 4.0 International (CC BY 4.0)

Surgeons have also experimented on the unwilling; for example, J. Marion Sims (of Sims retractor fame) did much of his ground-breaking work on obstetrical fistulas on African-American enslaved women in the mid-1800s. A number of surgeons were associated with the Nazi party, including Nobel Prize winner and French surgeon-scientist Alexis Carrel and the pioneering German thoracic surgeon Ferdinand Sauerbruch. And surgeons have taken part in the eugenics movement and forced sterilization, among other failings. Studying these examples shows us how surgery is not practiced in isolation, but rather affects and is effected by the world, society, and history. Surgeons have the potential to accomplish great things, but are also human, with all the flaws that come with it, and are not immune to the ills that plague society at large. It is important to recognize the bad with the good, and to ensure that history does not repeat itself.

Finally, one of the greatest challenges in medicine and surgery today is the epidemic of burnout, the causes of which are multifactorial, but includes a loss of finding meaning and purpose in work, and a feeling of disconnection. I believe that knowledge of our shared history, and studying those that came before us, can give a sense of identity and meaning to the practice of surgery. In an era of increasingly burdensome administrative tasks, it is easy to feel a sense of detachment and futility. But by studying the history of surgery, a greater sense of being rooted in community and purpose can be nurtured, and inspiration can be found to further the development of surgery towards better treatments and innovations, and to advocate for the patients that, too, have been a part of this shared history. 

Holding hands by the beach

Guest post: Oncological endpoints and human relationships

By Deep Chakrabarti, MD, Senior Resident, Department of Radiotherapy, King George’s Medical University, Lucknow, India


I reach the radiotherapy outpatient department on a Monday morning geared up and ready for the week ahead. With thoughts of a busy day and a busy week lying ahead of me, little do I appreciate then that my experiences over the week will continually repeat in cycles, much like the entire human existence and offer me reflections on life. The pandemic has made many of us re-evaluate ourselves and our relationships, many of which have been strained.

I believe that oncology endpoints can be assumed to mimic human relationships. A 70-year-old frail gentleman has a metastatic oral cavity cancer and is planned for palliative therapy with oral methotrexate. While his overall survival will most likely be a few months, we offer him oral metronomic chemotherapy and supportive care aiming for a decent quality of life. Most chemotherapeutic agents offer a similar overall survival of around six to nine months in the context of advanced or metastatic head and neck cancers. Similarly, in life, some relationships come with an expiry date, no matter what.

A 50-year-old gentleman presents with a recurrence of his locally advanced rectal cancer nine months after completing adjuvant treatment. Our surgical colleagues have seen him, and his disease has been deemed unresectable. He has been started on chemotherapy with oxaliplatin and capecitabine and has tolerated the first two cycles.  I know well it is a matter of time that the drugs will delay progression. Progression-free survival (PFS) is a popular endpoint in oncology research that loosely means the time it takes for a disease to get worse.1 Interpersonal relationships are often subject to intense emotional and mental stress, that require continual repairing. However, situations arise when it may not be possible to start on a clean slate entirely, and one is left with no choice but to accept whatever has happened and move on. In other words, one has to take the inevitable that the relationship cannot be “cured”, but further worsening can be avoided. For some tumours like advanced ovarian or colorectal cancers, PFS may even be a loose surrogate for overall survival and may often be nearly equal to overall survival. Likewise, some relationships may not worsen again after one episode when both parties make conscious efforts to put things behind them and move on.

On Tuesday, I see a 40-year-old lady with visceral dissemination of hormone receptor-positive breast cancer receiving systemic chemotherapy. While she and her family have been counselled about their predicament, they may still have some time with their loved one to fulfil their wishes. Like the overall tenure of each human relationship, overall survival parameters vary grossly from one cancer to another. For example, a metastatic gall bladder cancer is likely to be fatal in a matter of mere months, even with the best available chemotherapy. On the contrary, a man with metastatic prostate cancer can be expected to survive a few years with the current standards of care. 

Overall survival is the gold standard when it comes to measuring the worth of any cancer-directed intervention.2However, in patients or in relationships where one knows that the writing is on the wall, quality of life, or quality of the time left in the relationship is a premium. Quality of life is a crucial metric that seeks to quantify the actual well-being of an individual.3 While one may explore multiple therapeutic options to prolong life, one has to make a conscious decision as to how the prolongation will impact on its quality. Merely prolonging life while impairing its quality is detrimental. Similarly, when one knows that a relationship is irreparable, it is best to consider its quality than to keep trying to prolong it endlessly.

On Wednesday, I get an urgent consultation request for a lady with non-small cell lung cancer admitted in the neurosurgical ward who has presented with acute onset lower limb weakness with bladder and bowel involvement and has been diagnosed to have metastatic spinal cord compression. She is 70 years old with a WHO performance score of 2. The surgeons have already determined she is not a candidate for decompression. She is taken for urgent palliation with a single fraction of radiotherapy, with adequate steroid cover. Similar to the previous example, while her fate is probably already decided, but the urgent intervention offers to improve her quality of life, even if minimally.

On Friday, I get a call for radiotherapy planning for a patient who has cervical cancer with brain metastases and had received primary chemoradiotherapy three years ago. She is 74 years old, with a WHO performance score of 3 and requires continuous oxygen support. A decision is taken not to treat her with radiotherapy to the brain but offer her supportive care. Her three-year disease-free interval reminds me that a repaired relationship may suffer a relapse at any time. And sometimes a relapse can be so devastating that it does not offer much in terms of salvage.

On Saturdays, I see my radiotherapy patients on their weekly follow-up. We have a preponderance of head and neck cancer patients who will often present with grade II or III acute skin and mucosal toxicities as they move into the last weeks of therapy. Acute radiation reactions are defined as those occurring within 90 days of treatment and usually heal entirely with adequate care. However, late reactions or those occurring beyond 90 days persist and never completely heal. Some acute reactions may persist as late reactions, the so-called “consequential late reactions” (for example, chronic xerostomia is a consequential late reaction to acute xerostomia). For human relations, an acute bad episode may be amenable to rationalization and understanding, that may completely disappear like the resolution of acute radiation mucositis. But they may even persist, and then never go away completely. Therefore, the role of supportive care cannot be overemphasized, both in cancer care and in human relations.

The previous year has been a revelation for all of us. While it has subjected us to intense mental, emotional, and physical stress4, we have gained a thorough idea of what is vital in our lives. It is imperative that human relationships are valued on par with professional commitments, and the ongoing global crisis should teach us to prioritize personal contentment over professional gains. A morbidity audit from the CDC in August 2020 depicted that nearly one in four healthcare professionals had considered suicide in the immediately preceding one month for their troubles.5 While this is an alarmingly high number, it depicts the frailties ingrained in each of us and reiterates that before clinicians, we are humans. Even when our human forms are damaged and broken, sometimes beyond repair, empathy and patience for ourselves and our fellow beings might hold the key in this perennial struggle. May the progression-free survival of our relationships always closely mimic their overall survival.6 After all, as said by Rabindranath Tagore, “faith is the bird that feels the light and sings when the dawn is still dark.”

Conflicts of interest: There are no conflicts of interest to declare.

Funding: There is no funding to declare.

References

1         Korn RL, Crowley JJ. Overview: Progression-Free Survival as an Endpoint in Clinical Trials with Solid Tumors. Clin Cancer Res 2013; 19: 2607–12.

2         Driscoll JJ, Rixe O. Overall Survival: Still the Gold Standard. Cancer J 2009; 15: 401–5.

3         Selby P. The value of quality of life scores in clinical cancer research. Eur J Cancer 1993; 29A: 1656–7.

4.        Vallée M, Kutchukian  S , Pradère  B et al. Prospective and observational study of COVID-19’s impact on mental health and training of young surgeons in France. Br J Surg. 2020 Oct;107(11):e486-e488.  doi: 10.1002/bjs.11947.

5         Czeisler MÉ, Lane RI, Petrosky E, et al. Mental Health, Substance Use, and Suicidal Ideation During the COVID-19 Pandemic — United States, June 24–30, 2020. MMWR Morb Mortal Wkly Rep 2020; 69: 1049–57.

6         Lebwohl D, Kay A, Berg W, Baladi JF, Zheng J. Progression-Free Survival. Cancer J 2009; 15: 386–94.

Prioritising Surgical Treatment in Coronavirus Pandemic “Salford Score”

Prof Gordon Carlson CBE FRCS

Background

In light of the need to assess priorities of surgical treatment in a resource-limited environment, NHS England have set out clinical priorities for cancer surgery. However, these priorities do not take into account the vulnerability of the patient to excess morbidity and mortality in the event of Covid-19 infection. It seems evident that, particularly when undertaking elective surgery, the vulnerability of a patient to Covid-19 related morbidity and mortality might be equally important to considerations of the timing of surgery as the underlying disease for which surgery is proposed.

The resource allocation system currently in use at Salford Royal NHS Foundation Trust (which has since been adopted throughout other hospitals at Northern care Alliance) takes both of these factors into account, by producing a score based upon the need to prioritise treatment on purely disease related grounds and also the vulnerability of the patient to Covid-19. The aim is to generate a score which can be used to determine the overall surgical treatment priority of a group of patients, possibly from different surgical subspecialties, when surgical resources have become limited as a result of the Covid-19 pandemic. The score allows different groups of surgeons and hospital management to objectively determine how temporarily limited resources might be allocated. It is meant to help guide collective discussions, not to be a rigid indicator of those patients for whom surgical treatment should be deferred, and it should be used to support, not to replace MDT discussions.

Cancer Surgery Priority

The NHS England Suggested Priority for Cancer surgery is summarised in table 1 below.

PriorityDescription
Priority level 1a• Emergency: operation needed within 24 hours to save life
Priority level 1b• Urgent:operation needed with 72 hours
Based on: urgent/emergency surgery for life threatening conditions such as obstruction, bleeding and regional and/or localised infection permanent injury/clinical harm from progression of conditions such as spinal cord compression
Priority level 2Elective surgery with the expectation of cure, prioritised according to:
• Surgery within 4 weeks to save life/progression of disease beyond operability.
Based on:urgency of symptoms, complications such as local compressive symptoms, biological priority (expected growth rate) of individual cancers

NB. Local complications may be temporarily controlled, for example with stents if surgery is deferred and /or interventional radiology.
Priority level 3Elective surgery can be delayed for 10-12weeks with no predicted negative outcome.
Table 1: NHS England Suggested Priority for Cancer surgery

However we could make resource allocation easier if we devised a simple, objective and consistent way of summarising the two variables which influence decision making – clinical treatment priority and risk of COVID-related adverse outcome, into one numerical score;

The “Salford Score” simplifies this to:

  • Priority 1a = score (P)1
  • Priority 1b = score (P)2
  • Priority 2 = score (P)3
  • Priority 3 = score (P)4

Vulnerability

A second component of this relates to vulnerability of the patient in case of a COVID infection (see table 2).

Vulnerability scoreOutcome in case of COVID infection
Vulnerability level 1• Unlikely to have excess mortality (compared to a completely fit individual < 70 years old) in the event of Covid infection
Vulnerability level 2• Likely to have significant excess mortality compared to a completely fit individual < 70 years old in the event of Covid-19 infection, but would ordinarily receive invasive ventilation in that eventuality
Vulnerability level 3• Extremely likely to succumb to Covid-19 infection and would not ordinarily receive invasive ventilation in that eventuality
Table 2: Vulnerability score

Salford Score

A resource allocation score of PxV, is then calculated so that a fit patient at high risk of imminent death of underlying disease (P1or 2) and unlikely to have excess Covid mortality (V1) would score 1 or 2 (and get urgent surgical treatment), whereas a patient with a non-immediately life threatening condition (P4) for which surgical treatment could be safely be delayed for 12 weeks and who would not, as a result of severe pre-existing medical comorbidity, be intubated etc. should they develop Covid and respiratory failure (V3) would score 12 and we would not proceed to offer surgery until the current resource position changes.