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Surgical science advances at an extraordinary pace, and all surgeons have a duty to keep up to date to offer their patients treatment based on the latest research.
Surgical science advances at an extraordinary pace, and all surgeons have a duty to keep up to date to offer their patients treatment based on the latest research.
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.
Caffeine and postop ileus after lap colorectal surgery: yes or no? Marcel André Schneider @MA_Schneider shared a @BJSurgery article reporting the results of a RCT:
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!
#BariatricSurgery is still a matter of debate. Long-term effects of BS are discussed in this new paper @BJSurgery. The tweet was published on January 6th:
A highly engaging tweet by @BJSurgery shared the “Updated guideline for closure of abdominal wall incisions from the European and American Hernia Societies” on January 20th.
On January 29th, @BJSAcademy shared Professor Derek Alderson’s post “Life in Surgery”. Prof. Alderson is Vice Chair of the BJS Society Executive Committee:
Did you read this interview with Professor Derek Alderson's "Life in Surgery", BJSS Executive Vice Chair?
A surgeon's path: training, struggling, achieving, teaching, reflecting..beyond surgery
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.
And also on December 1st, @BJSurgery tweeted an #openacces paper published in the December 2022 issue on the impact of tranexamic acid on surgical bleeding during general surgery procedures:
“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”:
@BJSOpen tweeted the following poll: “What outcomes would/should feature in a “textbook” outcomes for #HPB #surgery? Survival was the most voted option:
The Essay Competition “The day I decided surgery was for me” deadline closed on December 31st and @BJSAcademy did not miss the chance of reminding us on Twitter on December 5th:
📢Medical Students and Young Trainees1
Essay Competition deadline 31 December 2022 – last chance to submit: The day I decided surgery was for me.
⭐️Up to 500 words in English (or 5min📽️) ⭐️What it was, or what happened, that made you choose surgery.
In December, a new author video was posted on the BJS YouTube Channel. @BJSurgery tweeted it on Dec 12th: CONFERD-HP: recommendations for reporting COmpeteNcy FramEwoRk Development:
New BJS video: Author video: CONFERD-HP: recommendations for reporting COmpeteNcy FramEwoRk Development https://t.co/hwJJYyvNLK
On December 21st, @BJSurgery announced with a tweet that the journal will be online only starting January 2023. Things have greatly changed since the publication of the first issue in 1913:
As we transition BJS to online-only, this image shows the first-ever inside cover of the Journal in 1913 alongside the final print cover. BJS is a journal that moves with the times.
We wish all our followers a peaceful festive season and all the very best for 2023! pic.twitter.com/FZ2gYygFLd
On December 28th, @BJSurgery tweeted an #openaccess paper titled “ Prognostic role of preoperative circulating systemic inflammatory response markers in primary breast cancer: meta-analysis”:
And the last tweet of 2022 was shared by @BJSurgery on December 30th: Ultrasound-assisted carbon nanoparticle suspension mapping vs dual tracer-guided sentinel lymph node biopsy:
NIHR Global Research Health Unit on Global Surgery.
Lancet 2022; 400: 1767-1776.
In this study that included over 13,000 procedures, this simple change reduced the rate of surgical site infection from 18.9 to 16 per cent, P=0.0032.
Comment: I really like studies that appear simple and generalisable. Hospitals around the world with the highest infection rates stand to see the biggest differences.
Tandon S, Ensor ND, Pacilli M, Laird AJ, Bortagaray JI, Stunden RJ et al.
Br J Surg 2022; 109: 1087-1095.
After six weeks, cosmetic scores were best with sutures and worst with glue (P=0.014), but the differences were no longer apparent in this study that included 295 children (333 surgical wounds).
Comment: No strong conclusion about which method should be used.
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:
📸 MADELINE (1988), in which Madeline undergoes an open appendicectomy (laparoscopy not yet widely used) and shows off her scar pic.twitter.com/KY9gHG6C3S
— Rebecca C Grossman MA MBBS AKC DHMSA MRCS (@rebgross) November 1, 2022
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:
One day after, an open access article on postoperative delirium after elective orthopedic surgery was tweeted by @BJSurgery. 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:
🔥 #BJSABookshelf – War Doctor: Surgery on the Front Line🔥
📚Recommendations from Surgical colleagues 📚Both clinical and non clinical books 📚For your entertainment and education
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:
🔥New Surgical Science Post🔥@gmboland and @dedeilia discuss individualised neoadjuvant immunotherapy for patients with melanoma.
Innovation is using knowledge to generate value. Is robotic cholecystectomy an IDEAL surgical innovation? A systematic review was tweeted by @BJSOpen on November 7th. The tweet is here:
#robotic cholecystectomy is a new approach, and should follow @IDEALCollab process for evaluation. But do studies report these?
On November 12th @BJSurgery tweeted the link to an open access article from Sweden: major surgical postoperative complications and survival after breast surgery. The tweet is here:
Shall we continue stenting left-sided obstructed colon cancer? On November 22nd, @BJSurgery shared the link to the paper reporting the results of the CREST randomized trial. The tweet is here:
Nov 28th @BjsOpen: High hospital volume is associated with improved outcomes in locally advanced colon cancer. Should complex procedures be centralized? You can see the tweet 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:
"The end of an era" ☄️
📰 The December 2022 issue of @BJSurgery is the last one that will be available in print!
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.
On October 3rd, the link to the article “Postoperative Packing of Perianal Abscess Cavities (PPAC2): randomized clinical trial” was tweeted by @BJSurgery. The tweet can be seen here:
🩹No pain no gain?
🛑Not when packing perianal abscess cavities in the PPAC2 RCT – packing caused more pain, with no gain!
Postoperative Packing of Perianal Abscess Cavities (PPAC2): randomized clinical trial
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…
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:
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:
Con gran tristeza os comunicamos la pérdida de Kees Dejong, extraordinario cirujano y persona, miembro destacado de @BJSurgery, revista en la que fue líder destacado del equipo editorial. Haremos llegar nuestras condolencias a su familia y amigos #RIP@BjsOpen@BJSAcademypic.twitter.com/6cDVaeAVJU
So sorry to convey the very sad news of the passing of Professor Kees Dejong who died peacefully yesterday after a long illness. He was a great leader in academic and HPB surgery and a wonderful friend to many. Our thoughts and prayers are with his family ❤️ pic.twitter.com/nRXcdMhzq1
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:
Single centre #RCT of surgery for T3/4 N+ #rectalcancer before or after 8 weeks of CRT
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:
Endoluminal vacuum therapy (EVT) is a devloping technology for #anastomoticleak management.
“Be a doctor, as well as a surgeon,” Michael G. Sarr, a world-renowned surgical leader, wrote in his “Surgical Life” post on @BJSAcademy. It was tweeted on Oct 31st. The tweet is here:
"Be a doctor as well as a surgeon – you are not just a surgical technician": a surgical life by Michael G Sarr.
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.
In September 2022, the first @BJSurgery tweet shared the link to the paper reporting the results of the international EUBREAST survey. The tweet can be seen here:
On September 5th, the paper titled “Surgical services during the war in Ukraine” was tweeted by @BJSurgery. This article is free to access. The tweet can be seen here:
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.
📢BJS Society Award: Call for nominations
Nominate an exceptional individual for the inaugural BJS Society Award.
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:
The @NEJM has launched an explanatory video on early fluid resuscitation for acute pancreatitis:
Management guidelines for acute pancreatitis recommend early aggressive fluid resuscitation, yet evidence supporting this approach is limited. New research findings are summarized in a short video. https://t.co/0m9geyWRBHpic.twitter.com/OThLbLRt1E
On September 17th, @BjsOpen shared a very interesting study looking at use of PET-CT in regional lymph node assessment in colorectal cancer. The tweet is here:
#ICYMI Study looking at use of PET-CT in regional lymph node assessment in #colorectalcancer
Short axis diameter of 7mm + SUVMax 1.5 show sens/spec >80%
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:
For those that follow my instrument posts, I may now announce there will be an ongoing series in BJS (British Journal of Surgery) called The Instrumentalist.
The first entry in the series is on scalpel handles and blades. Access is free, and is here:https://t.co/HqsDXUXvDH
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:
#ASurgicalLife: Takeshi Sano MD PhD "I never hesitate to call other people, even my juniors, instead of trying to solve a problem alone." Key life lessons from a world-renowned #gastriccancer surgeon: training, challenges, dilemmas, triumphs: Read more ⬇️https://t.co/L8NxHdCgNT
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:
How do multidisciplinary tumor boards (MDTs) work? They are frequently challenged by administrative and process issues, as reported in a paper published in @BJSOpen. 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.
Paper for discussion: Fachi JL, Felipe JS, Pral LP, Silva BK, Correa RO, Cristiny M et al.Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism. Cell Rep. 2019 Apr 16; 27: 750-761.e7.
Although rare, Clostridium difficile-induced diarrhoea or colitis can complicate what otherwise appeared to be an uneventful elective operation. This rare, but potentially lethal complication results from multiple factors inherent to performing surgery, such as prolonged periods of starvation, antibiotic exposure, major physiological stress, and sleep deprivation1. C. difficile spores can spread easily, can resist multiple methods of decontamination and can remain viable for long periods of time. In many cases, the bacteria can remain hidden within the host’s gut microbiome and transferred to the healthcare setting by the patient themselves, rather than vice versa.
While prevention is the best treatment, C. difficile infections (CDI) often prove resistant to antibiotics, and other modalities may be needed to restore homeostasis to the gut microbiome. Although faecal microbiota transplant has been proposed as a method for both prevention and treatment of CDI, even when severe colitis is present, many believe the most important action of the microbiome is to preserve its ability to produce key multifunctional metabolites 2. For example, the ability of the microbiota to produce the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate has been identified to be an important therapeutic aspect in the prevention and treatment of CDI. SCFAs are absorbed by host intestinal epithelial cells (IECs) and participate in several immunoregulatory roles that influence the host response to inflammation and infection. Past studies have detected reduced SCFA concentrations, particularly butyrate, in patients with CDI3. Elevation of butyrate via dietary modulation or provision of SCFA-producing bacteria has been shown to attenuate CDI severity in animal studies4,5.
In this study, Fachi et al. investigate how butyrate potentially alters the course of CDI in mice6. Oral administration of butyrate protects against CDI, improving both clinical symptoms and colonic histological score, with evidence of reduced ulceration and leukocyte infiltration within two days of the onset of infection. Similar effects were observed both with addition of tributyrin, a pro-drug of butyrate, as well as with inulin, a fibrous substrate for SCFA production, which both increased colonic butyrate levels. Once confirming butyrate’s protective effects against CDI, the investigators examined butyrate’s effect on four key parameters of CDI: the growth of C. difficile itself and the viability of the surrounding gut microbiota, IECs, and various other immune cells adjacent to the intestinal track. Although, butyrate was demonstrated to interfere with C. difficile growth and toxin production in vitro, these findings were not observed in vivo, suggesting that butyrate’s protective effects against CDI may not be a function of its direct action on C. difficile colonization or virulence. Furthermore, while butyrate affected overall gut microbiota community structure, it also maintained its protective effects in germ-free mice, indicating some of its protective effects extended beyond its influence on the gut microbiota. In turn, Fachi et al. then examined the effect of butyrate on immune cells, where they observed that butyrate administration reduced colonic pro-inflammatory cytokines IL-6, IL-1b, and Cxcl-1, as well as increased colonic anti-inflammatory cytokines such as IL-10. Also observed were elevated regulatory T cells, Foxp-3, and IL-10 in the mesenteric lymph nodes, supporting an overall anti-inflammatory influence. Even in Rag1- or IL-10-deficient knockout (KO) mice, butyrate still maintained its protective effect, suggesting that pathways independent of regulatory T cell or IL-10 signaling are involved.
Finally, when examining the interaction of C. difficile and butyrate on IECs in this study, investigators observed that butyrate could attenuate the intestinal permeability defects induced by CDI using FITC-dextran as a permeability probe. C. difficile dissemination from the gut was also decreased, as judged by fewer C. difficile colony-forming units in the liver and spleen in butyrate-treated mice. Gene expression studies and immunostaining revealed that butyrate increased key paracellular junction proteins Claudin-1 and Occludin that maintain the gut barrier. To further understand how permeability might be altered by C. difficile and/or butyrate functionally, investigators measured transepithelial/transendothelial electrical resistance (TEER) across cells, which demonstrated that butyrate partially prevented the increased IEC permeability caused by exposure to C. difficile supernatant. Previous studies had shown butyrate could stabilize the transcription factor HIF-1α, which is involved in regulating IEC permeability. To confirm this, the group showed that oral butyrate increased colonic HIF-1α and downstream gene expression. Using a LysMCre mouse model that selectively knocked out HIF-1α expression in IECs, they showed that butyrate no longer prevented the intestinal permeability defect and also failed to attenuate C. difficile dissemination to the liver and spleen. Furthermore, in the HIF-1α IEC KO mice, butyrate no longer reduced CDI severity. In the aggregate, these studies indicate that the permeability defect induced by CDI requires participation by key regulatory elements in the host cellular response to this pathogen, which can be modulated by gut microbiota-derived metabolites such as butyrate.
Several conclusions can be made that may be relevant to the surgical patient. First, it may be important to know a patient’s colonic (faecal) butyrate level before surgery. This should not only be able to be easily measured as a point-of-care assay, but should also be easily modifiable via dietary prehabilitation. This may involve dietary consultation, attention to when antibiotics have been most recently prescribed, changes in life-style (smoking cessation, reducing alcohol consumption) and removal of unnecessary medication until which time it can be determined that a patient’s microbiome is “ready” for a major operative intervention7. Second, over the course of surgery when butyrate and other relevant microbiome metabolites may become deficient, it may be possible to develop a protocol of microbiome maintenance that involves orally administered butyrate with specific release patterns packaged in microparticles. Studies such as the one highlighted above demonstrate that defining microbiome “readiness” for surgery, identifying the metabolites that activate immune function, and validating their role in CDI and other infection-related complications after surgery is now within our reach. This approach is not only exciting as a countermeasure to the fact that we are often operating on sicker, older patients with advanced disease, but also as a potential solution to many of the most dreaded infection-related complications that can occur when we perform what otherwise is expected to be an uneventful surgical procedure.
The first @BJSurgery tweet for July 2022: Appendicitis and DIAMONDs. Appendicitis is always in fashion for general surgeons.
An open access @BJSurgery paper reports the results of a randomized clinical trial comparing CT imaging with observation in early equivocal appendicitis. And the results are…
It had 10 retweets and 13 likes by August 7th 2022.
On July 1st the European Hernia Society @eurohernias announced that they offered a EHS member a place in ‘Writing in Surgery’ course, organised by @BJSurgery.
— European Hernia Society (@eurohernias) July 1, 2022
with 8 retweets, 1 quote and 13 likes by August 7th 2022.
A new systematic review regarding the use of social media as a tool for general surgery education was tweeted on July 3rd by Surgical Endoscopy @SurgEndosc. Disseminating high-quality content on social media must be a priority for content creators and institutions.
@BJSOpen celebrated its new impact factor (IF) with a tweet on July 5th. The journal IF raised to 3.875 and it becomes a Q1 #openaccess journal. This is a fantastic achievement and the authors, the BJS Open editorial team and its readers must be congratulated.
The tweet is here:
Pleased to see our IF 🔼 to 3.875, making @BjsOpen a Q1 surgical journal (one of two #openaccess titles in this quartile!)
The tweet had 17 retweets and 28 likes by August 7th.
On the same day, Rebecca Grossman @rebgross launched a poll on Twitter on July 5th. The drain debate never goes out of fashion, and she was interested in knowing more about her followers’ position after the publication of a @EuroSurg collaborative paper in @BJSurgery. The poll received 302 votes and you can see the results here:
🗳️ DRAINS!
Are you pro-drain or anti-drain in elective colorectal surgery?
Does this matched prospective cohort study in @BJSurgery change your mind?
On July 7th, @BJSurgery tweeted the link to the @reacctcollab paper titled “Impact of microsatellite status in early-onset colonic cancer”, which highlights the increased incidence of early-onset colonic cancer worldwide.
The tweet had 11 retweets, 1 quote tweet and 15 likes and is here:
On July 10th, @BJSOpen launched a poll on Twitter about the expected recurrent laryngeal nerve injury rate after a minimally invasive hemithyrodectomy via the axilla. The most voted response was 1.5% (33.3% of 36 votes).
On July 11th, @BJSOpen tweeted a paper on variation in the treatment of varicose veins in England. Unwarranted variation in access, quality and outcomes of surgical treatment is one of the key problems of modern healthcare systems. A population-based study published in @BJSOpen showed that geographic variation in the provision of treatment of varicose veins exists in England, and it is not due to demographic differences.
The tweet is here:
Variation in treatment of #varicoseveins in England: -regional variation in procedure rates -Non-white patients assoc w 🔽 procedure rates -Younger patients less likely to have procedures.
On July 13th, @BJSurgery editor, Des Winter (@deswinter) tweeted some questions about the Gloves Off section and the debate around collaborative research.
The tweet is here:
What do you think of this new section of @BJSurgery? Debate. Is collaborative research worthwhile? Team building or gratuitous inclusion? Are you in or out? Is there a middle ground? @young_bjs@BJSAcademyhttps://t.co/0RkN9hN1Bo
On July 19th, a YouTube video was posted by @BJSurgery. It shows how to make running sutures easy by using a simple technical gesture: the Cambridge Twist. The video is here:
A new strategy to improve outcomes after rectal cancer surgery attracted attention a lot of attention with a tweet on July 22nd (24 retweets, 1 quote tweet and 52 likes by August 7th 2022). @BJSurgery tweeted a link to the paper “Inferior mesenteric artery embolization ahead of rectal cancer surgery: AMIREMBOL pilot study”
Abuse and harassment in surgery cannot be tolerated. Profound changes in culture and behavior are needed and @BJSurgery tweeted Rebecca Grossman @rebgross paper on July 23rd.
The high impact tweet (21 retweets, 1 quote tweet and 30 likes by August 7th 2022) is here:
The announcement of the #monkeypox outbreak becoming a public health emergency of international concern was tweeted by @WHO on July 23rd 2022. @DrTedros, Director-General of the World Health Organization @WHO, declared #monkeypox outbreak a public health emergency of international concern.
The tweet is here:
🚨 BREAKING: "For all of these reasons, I have decided that the global #monkeypox outbreak represents a public health emergency of international concern."-@DrTedrospic.twitter.com/qvmYX1ZBAL
— World Health Organization (WHO) (@WHO) July 23, 2022
Last but not least, a systematic review of compression after superficial venous insufficiency (SVÏ) treatment. On July 31st, @BJSurgery tweeted a link to a systematic review showing that although postprocedural compression after SVI treatment is beneficial, the optimal pressure and type of compression remain unclear.
The tweet (8 retweets and 13 retweets by August 7th) is here:
Smith S, Ridley S, Gani, J, Carroll, R, Lott, N, Hampton, et al.
Ann Surg 2022; 275: 842-848.
In this study that included 3123 procedures, surgical site infection rates were similar with all skin preparations: povidone iodine with alcohol 10.9 per cent; chlorhexidine with alcohol 11.1 per cent; aqueous povidone iodine 12.6 per cent. There were no adverse events or differences in secondary outcomes.
Comment: This challenges the perceived benefits of alcoholic skin preparation.
Gao X, Liu Y, Zhang L, Zhou D, Tian F, Gao T et al.
JAMA Surg 2022; 157: 384-393.
The study included 230 patients undergoing major abdominal surgery. Early (three days after surgery) feeding reduced the rate of nosocomial infection from 18.4 to 8.7 per cent (P=0.04) compared with late feeding (eight days after surgery).
Comment: The findings in many studies are consistent: early feeding is beneficial.
Sessler DI, Pei L, Li K, Cui S, Chan MTV, Huang Y et al, on behalf of the PROTECT Investigators.
Lancet 2022; 399: 1799-1808.
Of the 5013 patients studied, those who had warming had a higher core temperature at the end of the surgery (37.1 versus 35.6 degrees C). Warming did not reduce the rate of complications: 9.9 versus 9.6 per cent, respectively, P=0.69.
Comment: This does not confirm previous studies of benefits from heating, maybe because the unheated patients did not get too cold.
Devereaux PJ, Marucci M, Painter TW, Conen D, Lomivorotov V, Sessler DI et al, for the POISE-3 Investigators.
N Engl J Med 2022; 386: 1986-1997.
A total of 9535 procedures were studied. Tranexamic acid reduced bleeding complications (11.7 versus 9.1 per cent, P<0.001), but slightly increased the risk of cardiovascular complications (14.2 versus 13.9 per cent, P=0.04).
Comment: Is the trade-off worth it, except for specific procedures with high blood loss?
June 2022 has been an important month for colorectal research in @BJSurgery, attested by high social media activity on this topic.
It all started with a tweet about a paper on the response to neoadjuvant immunotherapy in patients with mismatch repair-deficient/microsatellite instability colorectal cancer. The tweet had 21 likes and 16 retweets by July 7th, and it can be seen here:
On the same day, the @BJSOpen published a systematic review on specimen extraction after colorectal resections. Access the article here. This is the tweet:
Postoperative complications after colorectal cancer surgery have also attracted significant social media attention.
On June 6th, @martin_rutegard tweeted a paper published in @BJSOpen, which found that two chemokines (CXCL6 and CCL11) might predict leakage in rectal cancer. The paper is open access and can be read here. This is the tweet:
Glad to see this paper on preoperative inflammation and anastomotic leak out in @BjsOpen. We found that two chemokines (CXCL6 and CCL11) might predict leakage in rectal cancer, though validation is required. @MalinASund@UmeaUniversityhttps://t.co/XGoFG6nyS7
The day after, @BJSurgery posted a tweet about the core outcome set for clinical studies of postoperative ileus after intestinal surgery. This is a frequent postoperative complication that still puzzles us. You can read about it here.
The tweet had had 16 retweets and 23 likes by July 7th:
Anything related to intraperitoneal drains always attracts lots of attention. On June the 9th, @BJSOpen shared another paper with predictor factors of anastomotic leakage, but now found in the abdominal drain on postoperative day 3. The article can be accessed here. This is the tweet:
However, drains seem to not be associated with earlier detection of postoperative collections, as shown in an open access paper tweeted by @BJSurgery. You can read more here. This was a very popular tweet. It had 25 likes and 17 retweets by July 7th:
June was also a memorable month for the BJS community because after two previous cancellations in June 2020 and June 2021, Madrid received the BJS Society Council meeting and General Assembly amidst a heat wave. And social media echoed the joy.
Rebecca Grossman @rebgross and Laura Lorenzon @LauraLorenzonMD kept us updated:
We were also very happy because the @BJSAcademy reached 1000 followers by June 21st:
Thank you to our 1000 followers!
Recently launched in May 2022, #BJSAcademy is committed to leading lifelong surgical learning through ⭐️Cutting-edge reviews ⭐️Educational modules ⭐️Tutorials, blogs & digests ⭐️#MyNightOnCall ⭐️Videos & more
One more achievement for @BJSAcademy: @jcalverdy opens the Surgical Science section with a post on microbiome and surgery:
*⃣ NEW POST *⃣ #Microbiome & surgery: breakthrough or hype? Drs @JCAlverdy & Benjamin Shogan discuss: "The data output of a typical microbiome analysis can be vast, and determining what is signal versus noise has become problematic." READ full article ⬇️https://t.co/ipVvEwtZn9
Last, but not least, the Journal of Citation Reports announced the 2-year impact factors of scientific journals in late June 2022. The good news brought joy to both @BJSurgery and @BJSOpen editorial boards.
On Instagram, @BJSurgery proudly announced that, for the first time, its impact factor had gone well over 10 to an amazing 11.112. This is a spectacular achievement.
In addition, the @BJSOpen impact factor went up to 3.875 and led the journal into the first quartile of surgical journals. BJSOpen editor @LauraLorenzonMD tweeted about it. Her tweet had had 45 likes and 16 retweets by July 7th, 2022:
What a day for @BjsOpen! IF increased to 3.875, now officially ranking a Q1 journal. Thks to all the authors who trusted us with their research! Ad majora semper! And guess what happened to @BJSurgery…..?@BJSAcademypic.twitter.com/aDxJoxBgFg
John C. Alverdy MD FACS FSIS and Benjamin Shogan MD
In 1980, the number of studies including the word “microbiome” was around eleven, today using microbiome as a search word in pubmed yields over 100,000 entries. For surgeons, the relevance of the gut microbiome lies in its promise to explain disease pathogenesis (i.e cancer, appendicitis, diverticulitis, surgical site infections) and treatment effects (antibiotic prophylaxis, bowel preparation, etc). Yet because the data output of a typical microbiome analysis can be vast, determining what is signal versus noise has become problematic. Similar to the early days when human gene chips became available, displays of massive datasets indicating that a patient in group A is “different” from patients in group B leaves readers skeptical. For example, when the human gene chip became available, the transcriptome (mRNA expression of nearly 20,000 protein coding genes) of human samples could be compared between patient samples. Yet these initial screens only described “differences” between groups of patients and failed to identify actionable items. The descriptive nature of these studies has forced some, for example, to completely question the genetic basis of cancer. Are we falling into the same trap with microbiome studies?
Why microbiome studies are different. Claims that sequencing of the human genome was going to lead to major cures of complex diseases such as cancer have indeed been disappointing. First we were told that cancer is a genetic disease; once “junk” DNA turned out not to be junk, and once it became clear that gene-environment interactions (via histone modification?) played an important regulatory role in gene expression, the role of “lifestyle” became the new hype1. So where does that leave the microbiome in all of this? Issues such as how indoor and outdoor air quality, smoking, alcohol consumption, dietary choices, etc., influence one’s microbiome and then how in turn, its metabolites change host genetics is now under investigation.
Perhaps one of the most striking examples of the power of microbiome analyses is a study examining the gut microbiome of 34 monozygotic twins discordant for multiple sclerosis; one twin suffered from the disease while the other did not2. Deep analysis of faecal samples from the discordant twins demonstrated clear differences; yet when samples were transferred into germ-free mice, only samples from the affected twin produced an encephalomyelitis-like picture whereas unaffected twin samples did not. The neurotoxic metabolites from the gut microbiome that play a role in this effect are now coming to light3. The fact that monozyotic twins are born with different fingerprints and the genomic identity in their microbiomes is highly variable should diminish our enthusiasm for interrogating host genes only4. Animals are holobionts, consisting of both host and microbial genes, each interacting with one another and with the environment. At the individual patient level, this presents major challenges to understand disease pathogenesis and its treatment.
What is now emerging as centrally important to human health is diet, and the gut microbiome is centre stage in this regard. Relevant to surgical sciences and outcome studies is the role of obesity, smoking, diet and medication use on surgical outcome. As many of such factors are modifiable, surgeons are particularly interested in how such factors can be manipulated to decrease complications. While antibiotic exposures, smoking, and substance abuse are clearly areas that can be preoperatively addressed, both the quality and quantity of an individual’s diet is emerging as most relevant and certainly the most modifiable. For example, mice that consume a western diet are not only more susceptible to anastomotic leak, they can also develop surgical site infections from gut microbiota via the Trojan Horse Hypothesis5. Conversely, patients who consume a diet rich in fibre following curative colon cancer surgery are less likely to develop a recurrence6,7. Taken together, nutritional assessment beyond conventional markers such as serum visceral protein status (i.e., albumin, pre-albumin) and muscle mass (sacropenia, frailty) may involve a comprehensive dietary history, the use of food logs and dietary prehabilitation prior to surgery.
Surgeon beware. Surgeons tend to make changes in their practice when the proposed intervention has a strong scientific premise behind it and in some way just seems to “make sense.” Most clinical studies that simply compare one intervention group (i.e bowel prep, symbiotics, probiotics) to another fall short in convincing experts in the field to make a major change in clinical practice. One reason for this is the failure to adequately measure reliable “readouts” that can explain the variance within the group of treated individuals. Comparing mean values only “between treatment groups” without reconciling the differences in outcome “within groups” remains a problem8. Just as it is not helpful to demonstrate that older, sicker patient with more advanced cancer, on average (i.e., mean values comparing between groups) have worse survival compared to younger, healthier patients with less invasive cancer, it is not helpful to present massive datasets from a microbiome study that demonstrate that the microbiomes among those patients with complications are different compared to the microbiomes of patients without complications. Causal inference at the molecular level is needed and within-group variability must be explained.
In summary, microbiome sciences are indeed the next big thing as they are able to explain phenomena at the individual patient level, especially when samples can transferred to mice that phenocopy the disease of interest. How our environment, our life history and the disease process itself affect all genes, be they microbial or host derived, is what matters most. Surgeons recognize that they perturb multiple systems when they operate on patients. As a result, they remain eager to understand, at the individual patient level, how to disentangle the molecular mechanisms that explain why one patient recovers uneventfully while another does not.
May 2022 was a special month for the BJS Community. On May 3rd, the BJS Academy was launched and it was announced with a tweet that attracted a lot of attention, with 57 likes and 44 retweets.
The @BJSAcademy “is an online education resource that supports the professional development of current and future surgeons worldwide by championing research and collaboration”. The website has free content and it is accessible at the link https://www.bjsacademy.com.
BJS Academy leverages social media to disseminate knowledge worldwide. Self-promotion is not always bad, and we tweeted about the @BJSAcademy social media section on May 3rd.
#SoMe is important for surgical education and @BJSAcademy knows it.
One day later, the BJS European Hernia Society Prize was announced. The EHS 2022 Congress will be held in Manchester, with 2 prizes €3500 and €1500 for the winners. It can be seen here.
— European Hernia Society (@eurohernias) May 4, 2022
@Eurohernias is a strategic partner of BJS Society.
On the same day, the BJS Open presented the outcomes of 263 mucinous rectal cancer from our Sweden colleagues, showing a high percentage of downstaging and pCR. It can be read here:
Colleagues from 🇸🇪 present data on 263 mucinous #rectalcancer -53% stage III/28% stage IV -5 yr OS 55% -pCR achieved in 13%, downstaging also commonly achieved with neoadj CRT.
The tweet had 10 likes and 5 retweets by May 31st.
The @Schoolofsurg also announced on May 4th the winner of the BJS Prize session at the ASGBI conference, which took place in Liverpool. An interesting study aiming to improve muscle function after colorectal surgery.
The tweet can be seen here:
Strong start to @BJSurgery Prize session @asgbi from Ed Hardy. Huge improvement of function and decrease in muscle loss with electrical muscle stimulation after colorectal surgery #ASGBI2022pic.twitter.com/KoAqQg07zQ
@SEIQuirurgica is a Spanish scientific organization devoted to promoting surgical research and innovation. It is one of the BJS Society’s strategic partners. Their website can be accessed here: https://www.investigacionesquirurgicas.com
On May 8th, @juliomayol announced on Twitter that the 26th #SEIQ2022 conference will be held in Gijón, Spain, in September 2022. The best oral communications will compete for the BJS Prize. Abstracts can be submitted here: http://www.congresoseiq.com
The tweet had 15 likes and 14 retweets by May 31st.
On May 14th, Prof. @SWexner cited a @BJSurgery publication from 2012, on the benefits of cutting diathermy for skin incisions.
The tweet had received 29 retweets, 89 likes and on 12 quote tweets by May 31st. It can be seen here
Great point from @BJSurgery “Skin incisions made by cutting diathermy are quicker and associated with less blood loss than those made by scalpel, and there are no differences in the rate of wound complications or postoperative pain.” https://t.co/dR2ZDY8BQf
The tweet led to an interesting debate – click the link to read it:
Great point from @BJSurgery “Skin incisions made by cutting diathermy are quicker and associated with less blood loss than those made by scalpel, and there are no differences in the rate of wound complications or postoperative pain.” https://t.co/dR2ZDY8BQf
On May 17th, the @BjsOpen wondered how does distance and rurality affect outcomes in #emergency #surgery. The tweet had 11 likes and 10 retweets. See their explicative video here:
The tweet had received 4 retweets and 7 likes by May 31st.
More than 25 years of #FastTrackSurgery, published at @BJSAcademy by the @ErasSociety, tweeted on May 27th.
Since 2005 @ErasSociety / #FastTrackSurgery protocols (multimodal approach to recovery) point to huge reductions in hospital stays after major surgery = ✔️Real opportunities! but ✔️Implementation issues
Luke JL, Rutkowski P, Queirolo P, Del Vecchio M, Mackiewicz J, Chiarion-Sileni V et al on behalf of the KEYNOTE-716 Investigators.
Lancet 2022; 399: 1718-1729.
Adjuvant treatment with pembrolizumab every three weeks for up to 17 cycles was examined in the study that included 976 patients with median follow-up of 20.9 months. Treatment improved recurrence-free survival: 85 versus 76%, hazard ratio 0.61, 95 per cent confidence interval 0.45 to 0.82.
Comment: This difference is valuable, but again, it remains to be seen how late outcomes are affected.
Lenet T, Baker L, Park L, Vered M, Zahrai A, Shorr R et al.
Ann Surg 2022; 275: 456-466.
Fourteen trials including 8641 procedures were studied. A restrictive blood transfusion policy did reduce the volume of blood transfused without increasing postoperative morbidity. Two of the trials did show adverse composite outcomes for restrictive transfusion.
Comment: The result isn’t definitive, but further evidence that restrictive transfusion is generally not harmful.
Hemmingson O, Binnermark F, Odensten C, Rutegard M, Franklin KA, Haapamaki MM.
BJS Open 2022; zrac007.
The study was terminated at planned interim analysis when 116 patients were included. Healing was significantly better after Karydakis flap (14 versus 49 days, P<001). Recurrence rates were similar.
Comment: This study has a clear result, but there remain a number of alternatives to the Karydakis flap.
Seidel D, Lefering R. Ann Surg 2022; 275: e290-e298.
This study included 539 patients with an abdominal wound. Negative pressure dressings reduced hospital stay (11.8 versus 13.9 days P=0.047), but duration of actual treatment within 42 days longer: 22.8 versus 30.6h, P<0.001.
Comment: Not as good as a formal cost effectiveness analysis, which is sorely missing for this technology.
Deeken F, Sanchez A, Rapp MA, Denkinger M, Brefka S, Spank J et al, for the PAWEL Study Group. JAMA Surg 2022; 157: e216370.
A total of 1470 patents were randomly allocated to a prevention programme or standard care. Overall, the programme reduced the rate of postoperative delirium: 5.3 per cent versus 6.9 per cent in controls, P=0.047. It was ineffective after cardiac surgery.
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Since its inception in 1913, the readership of BJS has continued to grow across the globe, paving the way for complementary open access journal, BJS Open, in 2017.