Schrag D, Uno H, Rosovsky R, Rutherford C, Sanfilippo K, Villano JL et al, for the CANVAS Investigators.
JAMA 2023; 329: 1924-1933.
This study included 671 patients with cancer and a new episode of VTE. After six months, the risk of recurrent VTE was not inferior with oral anticoagulation (6.1per cent), compared to those receiving low molecular weight heparin (8.8 per cent). Bleeding complication rates were similar.
Welcome to the July 2023 edition of the @BJSAcademy social media review!
Here, we spotlight captivating and popular posts from the BJS community accounts on X.
Continuing the #AI series on @BJSAcademy, the article “The role of artificial intelligence in diagnostic imaging” authored by Barbara Seeliger, Alexandros Karargyris, and Didier Mutter was shared on July 1st on X. This post garnered 2,204 views by Aug 14th:
On July 2nd, @BJSOpen initiated a poll on X, seeking readers’ opinions on recently published impact factors, given the consistent drop in numbers. Results showed that most respondents (39.7% out of 68 votes) found the outcome as expected. Interestingly, 35.3% opined that the impact factor is overrated. By Aug 14th, the post accumulated 5,589 views:
In part 6 of the @BJSAcademy series, the article “Opportunities, functions and three wise monkeys” by Ameera AlHasan was shared on July 4th on X:
On the same day, @BJSOpen posted an #openaccess article link, reporting results from a retrospective cohort study on the effects of preoperative polypharmacy or hyper-polypharmacy on surgical patient outcomes:
@BJSOpen shared the paper “What’s the influence of #obesity on perioperative outcomes after gastrointestinal #surgery?” on July 11th. Surprisingly, this meta-analysis challenges assumptions about higher postoperative mortality in patients with obesity:
Exploring the theme of efficient resource utilization and environmental sustainability, on July 13th, @BJSOpen shared the #openaccess article titled “Waste not, want not: orthopaedic waste data,” which amassed 1571 views by Aug 14th:
On July 14th, @BJSurgery linked to the #openaccess article “Multisocietal European consensus on the terminology, diagnosis, and management of patients with synchronous colorectal cancer and liver metastases.”:
Finally, on July 30th, @BJOpen posted the most-viewed post of the month on X (22.7K views). The poll questioned when surgeons perform prophylactic mesh augmentation after laparotomy, with 65.3% of 147 votes leaning towards “Never!”:
This article highlights the close relation between the central nervous system and peripheral immune system, forming a neuroimmune axis that has clinical implications we are just beginning to understand. This article from the journal Science and Translational Medicine couples both patient data and a mouse model of intracranial haemorrhage (ICH) to explore the influence of ICH on haematopoietic stem cells (HSC) and the subsequent impact of HSCs on the brain.
In the first experiment, bone marrow cells were harvested from skull flaps of patients requiring decompressive craniotomies for ICH and compared with cells from patients with unruptured aneurysms. In the second, ICH was induced in a mouse model by injection of autologous blood into brain parenchyma and subsequent harvest of femur bone marrow cells. Both the human and mouse data demonstrated increased myeloid progenitor cells and haematopoiesis with ICH. Adrenergic innervation through the β3 receptor on haematopoietic cells promotes production of Ly6Clow , a patrolling non-classical monocyte (NCM), in the bone marrow, which rapidly travels to the brain after ICH. Through transcriptomic analysis of the HSCs after ICH, Cdc42 (cell division cycle 42) was identified as an upregulated gene. Cdc42 was noted to be ablated in β3-adrenergic knockout mice, Adrb3-/-, linking the relationship of Cdc42 and adrenergic innervation. Treatment with a Cdc42 inhibitor led to decreased bone marrow proliferation, reduced Ly6Clow monocytes, and exacerbated brain injury. Given the role of the β3 receptor in proliferation and targeting of haematopoietic cells, mice were treated with a US Food and Drug Administration approved β3 receptor agonist, mirabegron. As expected, mirabegron treatment increased the Cdc42 activity in HSCs and increased Ly6Clow production and concentration in the brain. Most importantly mirabegron treatment reduced functional neurological deficits, perihaematomal oedema, and overall brain oedema after ICH.
This article demonstrates that brain injury leads to a cascade of mechanisms modulated by β3-adrenergic innervation in which an NCM population provides protective effects to the brain. Lastly, the authors tested a potential targeted therapy upregulating the pathway and demonstrated improvement in brain injury outcomes.
Brain injuries have unique mechanisms that differ from peripheral organ injury. In normal conditions, the brain is sheltered within the blood brain barrier (BBB); endothelial cells and the microvasculature tightly regulate the exchange of molecules, ions, and cells from the blood to the brain.2 When the brain is injured, in particular in traumatic brain injury (TBI), there is a combination of mechanical disruption and endothelial dysfunction leading to BBB permeability. Disruption of the BBB leads to the circulation of brain-derived damage associated molecular patterns (DAMPs) in the peripheral circulation.3 At the same time, the injured brain is exposed to the peripheral circulation, due to BBB disruption. The complex interplay and cross-talk between the injured brain and the distant organs is just beginning to be investigated.
Shi et al1 add to the body of literature evaluating the connection between brain injury and the immune system. Given the relatively broad potential aetiologies of ICH (e.g. trauma, aneurysm rupture, tumour, coagulopathy), this article is widely applicable and should stimulate future questions in understanding brain injury. Severe TBI has been associated with a systemic inflammatory response syndrome with downstream effects that can lead to multi-organ dysfunction (MOD). The systemic response provides notable clinical evidence for the interactions between the brain and periphery. In 2021, Yang et al evaluated the role of the Ly6clow NCM in the mechanisms of pulmonary oedema following TBI.4 Their group demonstrated that there is a significant increase in Ly6clow NCM in the lungs of mice after TBI. Upon depletion of NCMs, there was a decrease in pulmonary oedema suggesting that NCMs contribute to post-TBI lung injury. Taken together, these articles show that NCMs are stimulated in the bone marrow following TBI. Subsequently, their response plays a role in both local brain inflammation, as well as distant organ injury. Interestingly, while the Ly6clow NCM migration appears to improve brain injury,1 the increase of Ly6clow in the lungs was associated with worse outcomes. Given the interconnected nature of the immune system, these findings raise many more questions than answers. Among the many are: what the NCM response is in other organs, what downstream cell type do they effect, and how do the NCMs migrate to the distant organs?
In understanding the mechanisms and pathways driving the brain and peripheral cross-talk, we may begin to not only investigate therapies and diagnostics in brain injury, but also target the associated MOD. Currently, the treatment for brain injury is largely supportive, with no interventions that target the underlying mechanisms. These mechanisms provide promising avenues for future research and the potential for advancing the clinical management of TBI and other brain injuries.
An additional future application may be in the field of transplantation. Solid organ allografts from donation after brain death, the leading source of donor organs, have been noted to have inferior graft survival compared to those from living donors.5 Given the systemic nature of brain injury and brain death, it is likely that the organs similarly undergo immune and inflammatory responses, potentially predisposing the allograft to dysfunction post-transplantation.
Thus, a better understanding of what happens at the cellular and molecular levels following brain injury may have wide-reaching clinical benefits. In addition to the potential to improve outcomes for patients with brain injury, the effects on post-transplantation organ function highlight the central role of basic and translational investigation in the development of novel therapies. This sentiment was probably best captured by the Noble Laureate Francis Crick (1916-2004) when he wrote “Almost all aspects of life are engineered at the molecular level, and without understanding molecules we can only have a very sketchy understanding of life itself.” What Mad Pursuit (1988).
Maemoto R, Noda H, Ichida K, Miyakura Y, Kakizawa N, Machida E et al.
Ann Surg 2023; 277: 727-733.
Lavage with povidone iodine before skin closure for 1 min was compared to saline lavage in this study that included 941 procedures. The rate of surgical site infection was similar: 7.6 per cent with iodine and 5.1 per cent with saline, P=0.154.
Comment: the fact that the wound is flushed may be more important than what with.
Welcome to the @BJSAcademy social media review for June 2023, where we highlight some of the most interesting and relevant posts from BJS community accounts. In fact, we have chosen some tweets with 15 or more likes.
Whether you are a trainee, a consultant, or a researcher, we hope you will find something useful and inspiring in this digest. Please feel free to share your feedback and suggestions with us on Twitter, Facebook, or Instagram. Thank you for your support and engagement!
On June 3rd, @BJSurgery tweeted a retrospective study comparing endoscopic retrograde appendicitis therapy with antibiotics for uncomplicated appendicitis:
On June 11th, @BJSurgery shared an open access paper on diagnosis and treatment for gastro-oesophageal cancer in England and Wales. What’s the most important finding? Little improvements in early diagnosis:
The BJS Society Award Ceremony was held at the Olympic Museum in Lausanne on June 16th. On that same date, @BJSAcademy tweeted “A surgical life by Henrik Kehlet”. We highly recommend you read it if you want to know more about Prof. Kehlet and how surgeons can translate knowledge into impact:
A very much liked @BJSurgery tweet shared an article by @swexner’s group reporting a propensity score-matched outcomes study for robotic and laparoscopic colectomy from a national cancer database on June 27th:
Last but not least, @BJSOpen took advantage of its blue tick and tweeted the abstract of the paper titled “Global cost of postoperative ileus following abdominal surgery: meta-analysis” on June 28th. It has received 33 likes by July 2nd:
One day later, May 2nd, @BjsOpen tweeted: “#RCT from China with n=96 shows that single ivof 1.5mg/kg lignocaine 10min b.f. tourniquet inflation in arthroscopic surgery inhibits tourniquet hypertension by TNF-α release & has beneficial effects on postop pain and recovery!”
On May 9th, @BJSAcacemy announced that the second article in the AI series was available. The authors are @irene_spiridon and @DocSeeliger and the paper is about the optimisation of surgical pathology and the potential role of AI:
On May 18th, @BjsOpen added more fuel to the “volume debate” in colorectalsurgery with these questions: What’s the correlation of surgical specialization and surgeon resection volume on short-term outcome after emergent colon cancer resections? Differences between colorectal, general and acute care surgeons?
A tweet to thank all the speakers and participants who contributed to the @BJSAcademy workshop – “how to referee a paper” was posted on May 27th:
The last tweet of the month was posted on May 30th by @BJSurgery and shared the manuscript titled: “Clinical outcomes following mechanochemical ablation of superficial venous incompetence compared with endothermal ablation”:
The following tweets were posted between April 1st and April 29th, 2023. They contain useful information and insights about various topics related to surgery. You can browse through them and find the ones that are most relevant to your interests and needs.
Coping with anastomotic leaks, harder when older? Tweeted by @BJSurgery on April 1st:
It may not sound sophisticated, but it is extremely important. On April 10th, @BJSurgery shared the NINJA multicentre randomized clinical trial investigating the effectiveness of nail bed repair in children with or without replacing the fingernail:
On April 17th, @BJSAcademy announced the launch of the AI series on Twitter. These are the topics:
Basic Introduction to AI
Surgical Pathology and AI
Role of AI in clinical surgery
AI in Radiology
An interesting #systematicreview and meta-analysis of machine learning models in kidney TPL found they could improve prediction of graft survival. An overall model including 29 models showed sens & spec of 0.81 and AUC of 0.82. It was tweeted by @BJSOpen:
Patel SP, Othus M, Chen Y, Wright GP, Yost KJ, Hyngstrom JR et al.
N Engl J Med 2023; 388: 813-823.
Some 313 patients with advanced melanoma undergoing surgical resection followed by one year of adjuvant Pembrolizumab, were randomly allocated three additional doses of Pembrolizumab preoperatively. After two years, event-free survival was significantly better with the neoadjuvant treatment: 72 versus 49 per cent, P=0.004.
Comment: This is important evidence for the benefit of neoadjuvant treatment for melanoma.
Kimball AB, Jemec GBE, Alavi A, Reguiai Z, Gottlieb AB, Bechara FG et al.
Lancet 2023; 401: 747-761.
This analysis of two identical trials included over one thousand patients. Secukinumab given fortnightly was more effective in both trials at reducing the signs of symptoms of hidradenitis than placebo (or Secukinumab every four weeks).
Over 5000 patients were included in this multicentre trial. Thirty-day mortality was 0.56 per cent (n = 14) in the control and 0.44 per cent (n = 12) in the intervention group (odds ratio 0.74, 95% Confidence interval 0.34–1.62).
Comment: Would results have been different if the focus had been on high risk patients only?
Almeida I, Gonqalves AC, Corrêa FB, Castro J, Guirro E, Farina JA et al.
Ann Surg 2023; 277: 198-205.
Patients with burn contractures at least one year old were randomized to split skin grafting alone, or with the addition of one of three dermal matrix preparations. Detailed scar assessment showed no improvement over skin grafting alone with any of the dermal matrices.
Comment: Disappointing outcome for the dermal matrices.
On March 1st, the second @BJSAcademy essay writing competition was launched. All medical students and young trainees are invited to send their essays on “Something interesting I learnt in the operating room”:
On the 3rd of March, comments related to the variation in limb amputation rates in Denmark and it’s becoming a national scandal were discussed. In the age of tweets and fast responses, it is sometimes necessary to take a moment to carefully analyse results that can become great reasons for debate:
Gender stereotypes and bias continue to prevail in our culture, and Medicine and Surgery are no exception. On the 5th of March, ‘Gender divergence: scoping the surgical gap’ was published on @BJSurgery:
Early-onset colorectal cancer (#EOCRC, <50y) is increasing worldwide with many underlying reasons not yet elucidated. A thread of @OUPMedicine covering @BJS articles which shed light on this important issue has been published during #ECCAM2023:
Again, studies regarding outcomes based on surgical volume are a matter of debate. In this case, bariatric surgery is s in the spotlight. You can see more on @BJSurgery, and it was tweeted on March 22nd:
Wei Y, Wu J, Yuxin C, Fan K, Yu X, Li X et al, on behalf of the PL-5 Investigators.
Ann Surg 2023; 277: 43-49.
This study examined the use of a new antimicrobial spray compared to silver sulphadiazine in 220 patients with a skin wound infection. Use of the spray at four varying doses all improved healing rates significantly (P<0.05).
Comment: This seems to be working more like an antiseptic.
On February 6th, Jonathan Earnshaw @JJEarnshaw invited the surgical community on Twitter to join the @BJSAcademy:
On February 11th, Prof. Jose Balibrea @BalibreaJose tweeted a comment in Spanish about a @BJSOpen #researchletter on gastroparesis and bezoar formation in patients with GLP-1 antagonists and the potential implications of MBS patients:
How to manage general surgical emergencies in pregnant and breastfeeding woman? @BJSurgery recently published the international guidelines and they were shared by @drnaumanAhmed on Twitter on February 13th:
@BJSOpen tweeted the results of a poll for endocrine surgeons with the following question “What is the most important consideration when choosing your skin closure after thyroid/parathyroid surgery?” on February 26th:
On February 27th, Prof. Russell Petty @RussellPetty19 tweeted a summary of a @BJSurgery paper on the impact of Covid19 on gastroesophageal cancer patients:
For the first time since 1913, @BJSurgery was not printed in January 2023. Now, it will only be published online. The two journals, BJS and BJS Open, together with the BJS Academy, are leading the digital transformation of surgical research dissemination. Many changes will be announced soon, but in the meantime, let’s focus on the excellent articles shared on social media.
The first tweet of the year from @BJSurgery was on pancreatic cancer!
On January 30th, @BJSOpen tweeted: “How does #digital #consent impact informed consent?” A #systematicreview of 40 papers found a generally positive effect on early and delayed comprehension. Few studies cover all aspects of informed consent:
Sali L, Ventura L, Mascalchi M, Falchini M, Mallardi M, Carozzi F et al.
Lancet Gastro Hepatol 2022; 7: 1016-1023.
Some 15,000 people were randomized and invited. Attendance was lower for CT colonography (26.7 per cent versus 33.4 per cent who participated in all three faecal testing rounds). Although the detection rate was higher with CT colonography (5.2 versus 3.1 per cent, P=0.0002). Overall detection (referral to work-up) was higher after three rounds of faecal testing (7.5 versus 2.7 per cent, P<0.0001).
Comment. Interesting that compliance with screening may be more important than the accuracy of the test.
Albers KI, Polat F, Helder L, Panhuizen IF, Snoeck MMJ, Polle S et al, for the RECOVER Study Collaborators.
Ann Surg 2022; 276: e664-e673.
A total of 178 patients were randomized to high or low pressure pneumoperitoneum. Quality of recovery score was significantly improved on day one after low pressure pneumoperitoneum (167 versus 159, P=0.005). Inflammatory markers were also reduced. Pain scores were lower and there were fewer infectious complications.
Abbassi F, Muller SA, Steffen T, Schmied BM, Warschkow R, Beutner U et al.
Br J Surg 2022; 109: 1216–1223.
Sixty patients were randomized to one of two caffeine doses given three times a day, or a control group. There was no measurable effect from caffeine; time to first bowel movement was not improved: 68.2 h after caffeine versus 67.3 h in controls (P=0.887).
Comment; Well there goes the excuse to ask for a coffee after your operation.
Kang B, Ibrahim S, Weil A, Reynolds K, Johnson T, Wilson S et al.
Ann Surg 2022; 276: 975-980.
Patients who had skin surgery with primary wound closure were randomly allocated to one of two different laser therapies for eight weeks or a control group. Fifty-two patients were eligible for analysis. Laser treatment improved wound score after 36 weeks, particularly with regards to scar thickness, stiffness and erythema.
Comment: Whether laser treatment improves wound healing still remains unproven.
With the advent of cellular targets and immunotherapy, cancer treatment has undergone significant improvement over the past several decades. While curative treatment of malignancy often relies on surgical excision, adjuvant modalities such as loco-regional irradiation remain important tools in comprehensive cancer care. Adjuvant radiotherapy (RT) is highly effective in reducing cancer burden, limiting the need for extensive surgery and decreasing the risk of local recurrence.1-3 However, RT brings collateral damage to the healthy surrounding soft tissues. Exposure to ionizing radiation results in a series of tissue changes marked by erythema, ulceration and oedema in the acute phase, followed by chronic inflammation and skin fibrosis, which may persist after treatment 4,5. As cancer survival rates continue to improve, an increasing number of patients are living with chronic morbidity related to RT.
Autologous fat transfer (AFT) has emerged as a possible treatment to the harmful effects of irradiation.6,7 Here, adipose tissue is suctioned from one part of the body, processed and then injected in small aliquots directly into the irradiated tissues.8 The mechanism through which lipoaspirate exerts a reparative effect is poorly understood but thought to be through direct and indirect actions: direct differentiation of transferred adipose-derived stem cells (ASCs) into new adipocytes, and paracrine signalling of cytokines and growth factors (HGF, TGF-ß, FGF-1,2, VEGF) that inhibit profibrotic signalling pathways and contribute to the recruitment of proangiogenic cells 9.
Like a skin graft, the adipose graft in AFT is dependent on the recipient tissue bed for nutrition and engraftment to achieve adequate ‘take.’ One of the challenges of fat grafting, in particular into a poorly perfused, irradiated tissue bed, is its unreliable retention rate, which is cited at between 30%-70%. Repeat procedures are often performed.10,11 As an alternative to AFT, decellularized adipose matrices (DAM) derived from discarded lipoaspirate have been developed. The allografts are processed through physical, chemical, and enzymatic purification techniques to develop decellularized scaffolds that retain the complex macromolecular architecture of the adipose tissue, and potentially its paracrine function via key growth factors retained in the graft. In recent studies, DAMs have been shown to promote adipose tissue regeneration, and have become a promising alternative to traditional fat grafting for soft tissue defects. 12 However, DAMs have not been studied in the context of radiation or a former tumour bed.
In the current study, Adem et al. compared the effectiveness of DAMs with autologous fat grafts in treating radiation injury in both murine and human tissue by analyzing the dermal architecture and vascular density of irradiated skin.13 First, immunocompromised mice were divided into several treatment conditions: radiation only, radiation with AFT, radiation with DAMs, and a control group that received neither radiation nor grafting. In grafted mice, volumetric analysis was conducted using micro-computed tomography (CT) at baseline and every two weeks for a total of eight weeks. Irradiated mice were sacrificed after twelve weeks, at which time the scalp skin and explanted fat were subjected to histological and mechanical analysis. Next, human skin samples (including nonirradiated, irradiated, and irradiated with grafting) were obtained from three women who had undergone grafting with autologous fat or DAM following breast cancer excision with radiation, during subsequent autologous breast reconstruction.
Both AFT and DAM grafts were found to have significant reparative effects on irradiated skin compared to controls in both murine and human tissue. However, AFT was superior to DAM in all metrics investigated. Tissue from mice injected with autologous fat had greater adipocyte integrity, greater vascularity, less inflammation, and less fibrosis compared to those grafted with DAMs. Both fat grafted and DAM grafted skin showed a decrease in dermal thickness, collagen density, and stiffness when compared to irradiated, non-grafted skin, though AFT showed significantly superior results to DAM. The authors observed high levels of factors known to regulate adipogenesis and increase angiogenesis such as FGF2, EGF2, and PDGF compared to the controls. Longitudinal CT analysis of graft retention in irradiated sites found a decrease in both AFT- and DAM-graft volume, though retention in DAM-injected mice was significantly lower. Analysis of human skin had similar findings. AFT and DAM significantly reduced dermal thickness and collagen density, with increasing tissue vascularity, when compared to irradiated, non-grafted skin.
The similar findings between the murine model and proof-of-concept human tissue lays a promising groundwork for necessary randomized control clinical trials. It remains unclear whether the decellularized matrix serves merely as an extracellular scaffold that becomes repopulated with native adipocytes, or whether the growth factors and cytokines embedded in the graft contribute to remodelling and angiogenesis observed. Previous studies suggest that it may be a combination of the two processes.14 As such, it will be critical to ascertain the oncogenic properties, if any, of the DAMs when delivered to a former tumour bed. Furthermore, given that chronic radiation effects can develop over the course of months to years after initial injury, a longer duration of study is required to substantiate the effects of DAM. Despite these drawbacks, this study provides encouraging evidence that DAM use in irradiated skin can improve and reverse several of the negative effects seen with RT, and provides a good translational model for future work in the field.
The study by Adem and colleagues has important implications for the use of DAM in clinical practice. Though it was found to be inferior to AFT, DAM showed a significant improvement in fibrosis, dermal thickness, and vascularity compared to non-grafted controls without the additional donor site or soft tissue requirement. This would have particular value in patients who may not have excess fat stores following oncological treatment. While there is much work to be done, this study provides encouraging evidence to support to the use of DAM in soft tissue reconstruction and offers a suitable translational model.
“Textbook outcomes” is a hot topic and both @BJSurgery and @BJSOpen tweeted about it on December 4th. @BJSurgery shared an #openaccess paper titled “A call for patient-centred textbook outcomes for emergency surgery and trauma”:
Two hundred patients had their pilonidal sinus curetted and then treated with either plasma gel or phenol crystals. Healing was more likely after a single application of plasma – 96 versus 53 per cent; it was also quicker (6 versus 10 days, P<0.001) and recurrence after one year was lower (4 versus 12 per cent).
Comment: Extraordinary result that needs confirmation to ensure it is generalisable.
November 2022 was a special month for the BJS community.
The BJS Society Council winter meeting was again held in London on November 1t6th. It was a fantastic opportunity to meet the new Council members and to learn how the editorial teams are reimagining the future of surgical publishing. In addition, the BJS Society International Award nomination deadline was November 30th.
On social media, we would like to highlight the following tweets and post:
On November 1st, Rebecca Grossman @rebgross tweeted a short report published in @BJSurgery: “Paediatric #appendicitis: international study of management in the #COVID-19 pandemic”. The tweet is here:
Almost simultaneously, @BJSAcademy announced that the final part of “How to write a clinical paper” titled “Completion and submission” by @des_winter, @BJSurgery Editor-in-Chief, is available as a free video. The tweet can be seen here:
On the same day, Irene Bello @Dra_Belloirene commented a @BJSurgery tweet sharing a leading article on frailty and surgery. Dr. Bello stated that “Frailty shouldn’t be a contraindication for cancer surgery, it should be an indication to increase ERAS protocol”. The tweet can be seen here:
An educational platform needs a bookshelf, and the @BJSAcademy has got a big one. @GianlucaPellino reviewed “War doctor. Surgery on the front line” and it was tweeted on November 3rd. The tweet can be seen here:
In addition to a bookshelf, @BJSAcademy proudly runs a Surgical Science blog. On November 7th, the link to a post by @gmboland and @dedeilia on personalized neoadjuvant immunotherapy for stage III malignant melanoma was tweeted. The tweet is here:
On Nov 30th @BJSOpen tweeted a systematic review that answers a relevant question for HPB surgeons: How to maximise functional liver remnant ahead of #hepatectomy – Portal vein or dual vein embolisation? The tweet can be seen here:
On the same day, a short video reporting the results of a meta-analysis clinical and oncological outcomes after laparoscopic vs open colectomy for locally advanced T4 colonic cancer was posted on the BJS YouTube channel. You can see the video here:
On the last day of November 2022 we were reminded by Giovanni Marchegiani @Gio_Marchegiani that an era is coming to an end. No more paper copies of @BJSurgery. The tweet and the results of the Twitter poll can be seen here:
Moncrieff MD, Bastiaannet E, Underwood B, Francken AB, Garioch J, Damude S et al.
Ann Surg 2022; 276: e208-e216.
Some 388 patients were enrolled into a study comparing standard follow-up with a reduced frequency schedule. There was no difference in recurrence rates between the groups. Three quarters of patients in both groups found their recurrence by self-examination.
Comment: Routine follow-up may not help patients with melanoma; perhaps an approach teaching them self-examination would be better.
Some 175 patients were randomized into one of three treatment arms. After a median of 49.2 months, recurrence-free survival was 64.2 per cent after the combination of nivolumab and ipilimumab, 31.4 per cent after nivolumab alone and 15 per cent after placebo; P<0.0001. Combination treatment also improved overall survival.
Comment; Combination treatment should be standard in this group.
Some interesting debate followed the new #SurgicalPoll tweeted by Rebecca Grossman @rebgross on October 3rd: To pack or not to pack abscess cavities? That was the question after the publication of the PPAC2 randomized clinical trial in @BJSurgery. And the winner was…
On October 12th, the nomination window for the BJS Society Award opened:
It has been considered the biggest prize in the modern history of surgery. Whom would you nominate? The nomination window closes on November 30th!
On Oct 16th, @BJOpen posted a poll on Twitter: Do you listen to music when operating? We would like to hear your opinion. The tweed and the results can be seen here:
On October 21st, New ASMBS/IFSO Guidelines – 2022 were published, expanding patient eligibility for weight-loss surgery.
The BJS Society and its strategic partners shared the sad news of the passing of Kees Dejong on Oct 21st. The tweet by the Sociedad Española de Investigaciones Quirúrgicas be seen here:
@ProfW_edinsurg tweet can be seen here:
Are eight weeks enough? On Oct 24th @BJSOpen shared the link to an open-access paper reporting a single-center randomized clinical trial of surgery for T3/4 N+ #rectalcancer before or after eight weeks of chemoradiotherapy. Are you interested in the results? The tweet can be seen here:
Why and when did you decide surgery was for you? @JJEarnshaw tweeted about the new @BJSAcademy “Medical Student and Young Trainee essay writing competition” and the outstanding piece by @Dami_Jesuyajolu on Oct 27th The tweet can be seen here:
Managing colorectal anastomotic leaks is quite a challenge. The link to an expert consensus paper on endoluminal vacuum therapy for colorectal anastomotic leaks was shared by @BJSOpen on Oct 27th. The tweet can be seen here:
While significant changes have occurred in the management of microscopic stage III disease due to the data from MSLT-21, the current standard of care for macroscopic stage III nodal malignant melanoma consists of initial surgical treatment with therapeutic lymph node dissection (TLND), followed by consideration for adjuvant therapy consisting of either anti-PD-1 monotherapy2 or BRAF/MEK inhibitors3. This results in improved relapse-free survival, but recurrence is still observed in almost half of the patients within 3-5 years4-6. Preclinical trials7-9 and emerging clinical data10 suggest that neoadjuvant immune checkpoint inhibition may have clinical benefit over adjuvant approaches. Given increasing enthusiasm for adjuvant and neoadjuvant approaches, the OpACIN (NCT02437279, phase I) and OpACIN-neo (NCT02977052, phase II) studies were established to investigate the safety and efficacy of neoadjuvant treatment with immune checkpoint inhibitors (ICI) combination, and to establish optimal dosing regimens to maximize clinical benefit while minimizing toxicity in patients with stage III melanoma.
The OpACIN and OpACIN-neo trials
The OpACIN study, a two-arm phase Ib trial, evaluated the efficacy of the combination of ipilimumab (anti-cytotoxic T-cell lymphocyte antibody – anti-CTLA) and nivolumab (anti-programmed cell death protein 1 – anti-PD-1) in an adjuvant or split neoadjuvant-adjuvant fashion for a limited number of patients (10 patients in each arm). Primary data from that study in 201811 demonstrated the remarkable efficacy of the neoadjuvant-adjuvant combinations, with a pathological response rate (pRR) of 78% after neoadjuvant therapy. However, toxicity was a significant concern, as grade 3 and 4 adverse events related to the immunotherapy affected 90% of the participants. For comparison, the pRR and adverse events (AE) in the adjuvant arm of the study were 60% and 70%, respectively. These results are comparable with the results of other trials12.
The subsequent phase II OpACIN-neo trial further investigated the safety and efficacy of neoadjuvant combinations of ipilimumab and nivolumab for stage III melanoma at varying doses. The randomized multicenter study comprised three arms with different neoadjuvant combination doses (Arm A: 2 courses of ipilimumab 3mg/kg and nivolumab of 1mg/kg; Arm B: 2 courses of ipilimumab 1mg/kg and nivolumab 3mg/kg; Arm C: 2 courses of ipilimumab 3mg/kg followed by 2 courses of nivolumab 3mg/kg). The 86 patients enrolled in the study were randomized in a 1:1:1 fashion, with almost 30 patients per arm (A:30, B:29, C:24). At a follow-up of 24 months, the AE related to the immunotherapy course and pRR were: Arm A: 40% irAE and 80% pRR, Arm B: 20% irAE and 77% pRR, and Arm C: 50% irAE and 65% pRR. Based on this the Arm B, often termed flip-dose Ipi/Nivo (IPI 1mg/kg, NIVO 3mg/kg), was identified as the optimal dosing regimen since it demonstrated the lowest toxicity (20%) with an equivalent pathological response rate (77%).
The MeMaLoc substudy
Within the OpACIN-neo study, 12 patients were enrolled in the MeMaLoc pilot trial (Magnetic Seed Localization for Melanoma, NL58293.031.16), a substudy examining whether the pathological response of the index lymph node (ILN) to treatment could accurately predict the response of the total lymph node basin. A magnetic seed was placed in the ILN in a similar fashion to breast surgery13, and the data demonstrated 100% concordance between the magnetically marked and resected ILN with the entire basin after neoadjuvant therapy (12/12 cases)14. This proved that the localization and resection of the index node is safe, feasible, and reliable, thus paving the way for patients with a complete response potentially to avoid a TLND in the future.
The PRADO extension cohort of OpACIN-neo
The extension cohort of the OpACIN-neo trial called PRADO constitutes a multicenter cohort study that assessed the effect of personalized surgical and adjuvant treatment based on the response of patients with stage III melanoma to the neoadjuvant therapy after 2 cycles of “flip-dose Ipi/Nivo”, i.e. ipilimumab 1mg/kg and nivolumab 3mg/kg (the most successful arm of the OpACIN-neo trial). The response to the neoadjuvant immune checkpoint inhibitor (ICI) combination was measured through ILN assessment with the use of a magnetic seed (52%) (in the fashion of the MeMaLoc study), a nitinol marker (34%), a radioactive I125 seed (9%), or a hydrogel marker (4%).
If the ILN had a major pathological response (MPR), i.e. a complete response (CR) or near CR (nCR), with <10% viable tumour cells remaining, TLDN was omitted along with any further adjuvant immunotherapy or radiotherapy. If the ILN showed a pathological partial response (PR), with 10-50% of viable tumour cells left, then TLDN followed the neoadjuvant therapy, but no further adjuvant immune or radiotherapy was offered. Lastly, in the case of non-response (NR, >50% viable tumour cells left in the ILN), TLDN took place, followed by standard-of-care adjuvant therapy consisting of either nivolumab (for BRAF wild-type tumours) or the BRAF/MEK inhibitors dabrafenib and trametinib (for BRAFV600E/K-mutated tumours), along with the possible addition of local radiotherapy.
A total of 99 patients who met the RECIST 1.115 criteria were enrolled. After 6 weeks of neoadjuvant therapy, 62% achieved MPR (49% CR, 12% nCR) and thus avoided TLND, 11% achieved PR and thus underwent only TLND, and 21% had NR and underwent TLND. Of the 21 patients with NR who underwent TLDN, only 17 followed with adjuvant therapy ( 7 of them with nivolumab and 10 with a combination of the BRAF/MEK inhibitors). Furthermore, 8 out of 17 patients received additional local radiotherapy.
The first outcome of the study was the evaluation of the morbidity of TLND. Avoiding TLDN resulted in a significant reduction of morbidity as there was a significantly lower rate of surgery-related adverse events (based on the CTCAE v4 criteria) in patients who underwent ILN resection alone compared to those with ILN and TLND (46% versus 84%, p<0.001). There was the same trend shown with the Clavien-Dindo classification (52% vs 93%, p<0.001). Similarly, the HRQoL rates were significantly increased in the group that omitted the TLND.
The next outcomes of the study were the overall survival (OS), relapse-free survival (RFS), and distant-metastasis-free survival (DMFS) rates of the participants. At a 24-month endpoint, the combined OS for patients was 95%, with RFS rates for the patients with MPR being 93%, PR of 64%, and NR of 71% respectively, with similar DMFS rates observed (MPR: 98%, PR: 64%, and NR: 64%). It was unexpected that the RFS rates for those with a PR was similar to that with neoaduvant pathological NR. However the PR patients had a TLND, but did not (per study protocol) receive adjuvant therapy.
In conclusion, the PRADO study, based on the promising outcomes of the OpACIN and OpACIN-neo, and using the pioneering tools from the MeMaLoc study, made some interesting observations, which can be summarized as follows:
It supported the efficacy and safety of the OpACIN-neo trial’s most favourable neoadjuvant treatment arm (ipilimumab 1mg/kg and nivolumab 3mg/kg).
The study validated the data supporting that the ILN response can be an accurate representation of the entire tumour basin.
The study made a significant step towards precision medicine of stage III melanoma, as it showed that de-escalation is possible in patients with MPR, whereas in patients with PR or NR, escalation might improve their outcome.
While the encouraging outcomes of those with a major pathological response with focused nodal surgery support consideration for less invasive approaches to surgery after neoadjuvant therapy, the integration of surgery and neoadjuvant/adjuvant choices should be considered thoughtfully. The disappointing outcomes of the PR group who received TLND but did not have additional adjuvant therapy suggests that de-escalation of surgery without adjuvant therapy may be a less optimal approach, since their outcomes paralleled that of the pathological NR group. Future efforts at patient-specific therapy decisions should consider adjuvant therapy for both PR and NR groups. However, this does not dampen the importance of this study in validating the importance of a major pathological response as an opportunity to de-escalate surgery.
Overall, neoadjuvant therapy, ILN assessment and consequent response-directed treatment are significant added tools that could potentially be added to the oncological treatment of stage III melanoma and achieve even better outcomes. Further clinical trials are needed to examine this in more detail, expanding and further illuminating this thought-provoking and noteworthy topic.
Krige A, Brearley SG, Mateus C, Carlson GL, Lane S.
BJS Open 2022; 6: zrac055.
Pain scores were improved after epidural analgesia for the first 24h (pain score 33 versus 50.5; P=0.018) in this study that included 131 procedures. After 72h, pain control was better with a rectus sheath catheter (4.5 versus 12.5; P=0.019), which was also more cost effective.
Comment: Perhaps the compromise is opiate analgesia to supplement the rectus sheath catheter.
Fortelny RH, Adrade D, Schirren M, Baumann P, Riedl S, Reisensohn C et al.
Br J Surg 2022; 109: 839–845.
This study included 425 patients who had a midline laparotomy. After one year, the rate of ultrasound-detected incisional hernia was lower after short stitch (5 to 8mm bites every 5mm) than long stitch repair (10mm bites every 10mm): 3.3 versus 6.4 per cent, P=0.173.
Comment: The risk of incisional hernia was low with both methods.
On September 12th a new meta-analysis on non-operative management of appendicitis was tweeted by @BJSOpen. This was a very popular tweet, which had had 32 likes and 18 retweets by October 9th. You can see the tweet and a video-abstract here:
On September 15th, the BJS Society announced the BJS Society Award for an exceptional surgeon who has made contributions that have changed surgical practice. This international award may very well become the new Surgical Nobel Prize. Nominations will open on October 12th.
Surgeons look for more tailored treatments in their daily clinical practice. On September 16th, @BJSurgery tweeted an article on tailored treatment for gallstone disease. You can see the tweet here:
A few days later, on September 24th, the never-ending discussion about lymph nodes continued with @BJSurgery tweeting the article “Lateral local recurrence after total mesorectal excision for mid/low rectal cancer.” The tweet is here:
It is always a hot topic: stoma or not stoma after rectal resections? @BJSurgery shared an interesting study titled “Transanal tube versus defunctioning stoma after low anterior resection for rectal cancer: network meta-analysis of RCTs” The tweet can be seen here:
The Spanish Society of Surgical Research @SEIQuirurgica, strategic partner of the BJS Society, held its 26th Congress in Gijon in late September. It began with an interesting session on Research and Surgery:
The @BJSurgery lecture of the 26th Congress of Sociedad Española de Investigaciones Quirúrgicas was introduced by @ProfDemartines and given by doctor Marja Boermeester @safesurg as part of the @BJSurgery session in Gijón on September 30th:
The first @BJSurgery tweet of the month (August 1st) was about a paper on pain in people with intermittent claudication. A network meta-analysis showed that “There is strong evidence in support of use of structured high-pain exercise, and some evidence in support of structured low-pain exercise, to improve walking ability in people with IC compared with usual-care control”. The tweet is here:
On August 2nd, @BJSurgery tweeted the link to a very interesting narrative review on organ preservation in rectal cancer management. This is a hot topic, as shown by 39 likes, 21 retweets and 2 quote tweets by Sept 6th. The tweet is here:
Ron Barbosa @rbarbosa91 announced the @BJSurgery series “The instrumentalist” on Twitter on August 6th. His first entry was “Scalpel handles and blades”. Surgeons are deeply fond of surgical instruments, and Ron’s tweet has been highly engaging with 832 likes,13 quote tweets, and 152 by Sept 6th 2022. The tweet is here:
On August 11th, @BJSAcademy tweeted about the free videos available on its website, and particularly about Martyn Evan’s @evanscolorectal “How to write a clinical paper” The tweet has had 40 retweets, 5 quote tweets and 60 likes by Aug 7th, and it is here:
Understanding how competent surgeons get their skills is not easy. On August 13th @BJSOpen tweeted the link to a paper by Kjetil Soreide and Benedicte Skjold-Ødegaard, who used an innovative approach to analyze surgical trainees’ skill acquisition during real-life lap appendectomies. The tweet can be seen here:
The availability of kidney grafts for transplantation is limited. Living kidney donation is an excellent option, but it is not risk-free for donors who are otherwise healthy. On August 22nd, @BJSurgery shared a meta-analysis carried out to identify risk factors for living kidney donors. The study found that obesity and male sex are associated with poorer outcomes. The tweet is here:
It is not unusual to come across a difficult situation in the operating theater while performing a surgical procedure. Should I fix it by myself or ask for help? On August 24th, @BJSAcademy tweeted a new chapter of #ASurgicalLife by Takeshi Sano MD PhD, who reminds us “to never hesitate to call other people and ask for help instead of trying to solve a problem alone”. The tweet is here:
Timing matters in surgery. What’s the optimal time to do an appendectomy after hospital admission? On August 28th, @SurgJournal shared a study on the association between time from admission to appendectomy on perioperative outcomes to determine the optimal time-to-surgery window. The tweet is here:
There is no monthly surgical #some review without a paper on drains. This time it was about the HPB surgeons’ dilemma”. On the last day of the month, @BJSurgery tweeted a propensity score-matched study showing that if a pancreatic resection is complex (multivisceral resections and those that took longer), surgeons are reluctant to omit drainage. The tweet is here:
Some 185 Patients with suspected appendicitis were randomised to imaging with ultrasound followed by CT if needed, or observation. More patients in the imaging group had treatment for appendicitis (72 versus 57 per cent; difference 15, confidence interval 1 to 29 per cent). Rates of complicated appendicitis and negative appendicectomy were similar.
Comment: Some patients with appendicitis do not need surgery; I think we knew that, but this is good science.