Post-hepatectomy liver failure (PHLF) represents the major determinant for death after liver resection. Early recognition is essential. Early postoperative lactate values are powerful, readily available markers for clinically relevant PHLF and associated complications after hepatectomy with potential for guiding postoperative care. This video explains the recent study published in BJS.
Each year 13 000 patients undergo cholecystectomy in Sweden, and routine intraoperative cholangiography (IOC) is recommended to minimize bile duct injuries. IOC plus an intervention to remove CBD stones identified during cholecystectomy was associated with reduced risk for retained stones and unplanned ERCP, even for the smallest asymptomatic CBD stones in this BJS study.
J.V. Groen, Department of Surgery, Leiden University Medical Centre, Leiden, J.V.Groen@lumc.nl
N. Michiels, Department of Surgery, Leiden University Medical Centre, Leiden, N.Michiels@lumc.nl
J.S.D. Mieog, Department of Surgery, Leiden University Medical Centre, Leiden, J.S.D.Mieog@lumc.nl
The use of venous resection (portal or superior mesenteric vein [PV-SMV]) during pancreatoduodenectomy is increasing.1-4 In a recent international survey, we found that most pancreatic surgeons prefer a segmental resection with primary anastomosis over a partial wedge resection, because of a lower perceived risk of complications.5 The impact of the type of venous resection (wedge or segmental) on postoperative morbidity and survival is poorly understood in current literature.
Does type of venous resection during pancreatoduodenectomy for pancreatic cancer impact postoperative morbidity and overall survival?
We performed a nationwide retrospective analysis of 1311 patients who underwent pancreatoduodenectomy for pancreatic cancer within the Dutch Pancreatic Cancer Group (2013-2017). A venous resection was performed in 27% patients (65% wedge resection; 35% segmental resection). Patients with segmental resection had more Clavien-Dindo ≥III complications (adjusted odds ratio 1.90, 95% confidence interval 1.22-2.98) and worse survival (adjusted hazard ratio 1.40, 95% confidence interval 1.10-1.78) compared to no venous resection. Patients with segmental resection had a higher rate of PV-SMV thrombosis (18%) as compared to patients with wedge resection (5%) and without venous resection (1%). Vascular complications (PV-SMV thrombosis or haemorrhage) were the indication for relaparotomy in 18 out of 23 (78%) patients with segmental resection. Tumour invasion in the resected PV-SMV did not differ between patients with segmental (67%) or wedge resection (69%).
In patients treated with neoadjuvant therapy, survival was comparable between types of venous resection, although patients with segmental resection had more Clavien-Dindo ≥III complications (52%) compared to venous wedge (19%) and without venous resection (21%).
In contrast with the found preference for a segmental resection in the international survey, most patients underwent a wedge resection. Little is known what exactly drives the surgeon’s preference regarding choice of type of venous reconstruction.5 The results of this study implicate that an upfront segment resection is associated with both poor postoperative morbidity and poor survival. These findings are in line with a recent large international cohort study6 and contribute to the growing evidence that neoadjuvant chemotherapy should be considered in borderline resectable disease and suspected venous involvement.
This study, and other studies from our group5,7, on venous resection during pancreatoduodenectomy demonstrated that there is much to gain with regards to patient selection (~30% of patients with venous resection do not have tumour invasion in the resected PV-SMV), surgical technique (variation in clamping techniques, heparinization, types of reconstruction and use of grafts and flow measurements), postoperative management (e.g. vascular complications as PV-SMV thrombosis, haemorrhages and portal hypertension) and pathological assessment (lack of internationally accepted grossing techniques of venous resections). We believe this is especially relevant for the future since venous resection will be even more common with the increasing use of neoadjuvant therapy.
Several imaging tools are being investigated which can help selecting the right patients who need a venous resection to achieve a radical resection. Intraoperative ultrasound provides real-time imaging and feedback about the tumour, vascular involvement and resectability in patients with pancreatic cancer.8,9 We are currently analysing the data of our ULTRAPANC study which assesses the added value of intraoperative ultrasound in patients with pancreatic cancer and vascular involvement (https://www.trialregister.nl/trial/7621). A recent study showed the utility of computed tomography coupled with 3-dimensional image reconstruction in the assessment of superior mesenteric artery involvement after neoadjuvant therapy, the authors distinguish a “halo sign” (not involved) from a “string sign” (involved).10 An interesting topic would be if these ‘’halo and string signs’’, are also useful in the assessment of venous involvement with intraoperative ultrasound (or analogous ‘’signs’’, as the venous wall does not have an tunica adventitia).
Recently defined benchmark outcomes for pancreatoduodenectomy with venous resection can be used to assess outcomes and identify areas for improvement on a hospital, regional or national level.11 The PREOPANC-4 trial (protocol in preparation) within the Dutch Pancreatic Cancer Group will investigate the implementation of a best-practice algorithm for patients with locally advanced pancreatic cancer. This study has the potential to improve surgical technique and management of patients undergoing arterial/venous resection during pancreatoduodenectomy in the Netherlands.
In the present study, no data were available on the diagnosis, treatment and outcome of patients with PV-SMV thrombosis. We are currently collecting data for a successive study in which we will provide an overview of the current clinical practice in the Netherlands regarding the prevention, diagnosis, treatment and outcome of PV-SMV thrombosis following venous resection during pancreatoduodenectomy. A group from Japan recently performed an impressive study among 40 centres which showed that venous resection during pancreatoduodenectomy with splenic vein division frequently causes variceal formation, bleeding, and thrombocytopenia.12
Within the Dutch Pancreatic Cancer Group, pathological assessment of venous involvement have recently been standardized. The location of deepest invasion in the resected PV-SMV is assessed and all edges of the resected PV-SMV are assessed for radicality. A prospective study with this standardized pathological assessment is needed in to investigate the true prognostic value of (depth of) tumour invasion in the resected PV-SMV.
- Kantor O, Talamonti MS, Wang CH, Roggin KK, Bentrem DJ, Winchester DJ, Prinz RA, Baker MS. The extent of vascular resection is associated with perioperative outcome in patients undergoing pancreaticoduodenectomy. HPB (Oxford) 2018;20(2): 140-146.
- Kleive D, Sahakyan MA, Berstad AE, Verbeke CS, Gladhaug IP, Edwin B, Fosby B, Line PD, Labori KJ. Trends in indications, complications and outcomes for venous resection during pancreatoduodenectomy. Br J Surg 2017;104(11): 1558-1567.
- van Roessel S, Mackay TM, Tol J, van Delden OM, van Lienden KP, Nio CY, Phoa S, Fockens P, van Hooft JE, Verheij J, Wilmink JW, van Gulik TM, Gouma DJ, Busch OR, Besselink MG. Impact of expanding indications on surgical and oncological outcome in 1434 consecutive pancreatoduodenectomies. HPB (Oxford) 2019;21(7): 865-875.
- Worni M, Castleberry AW, Clary BM, Gloor B, Carvalho E, Jacobs DO, Pietrobon R, Scarborough JE, White RR. Concomitant vascular reconstruction during pancreatectomy for malignant disease: a propensity score-adjusted, population-based trend analysis involving 10,206 patients. JAMA Surg 2013;148(4): 331-338.
- Groen JV, Stommel MWJ, Sarasqueta AF, Besselink MG, Brosens LAA, van Eijck CHJ, Molenaar IQ, Verheij J, de Vos-Geelen J, Wasser MN, Bonsing BA, Mieog JSD, Dutch Pancreatic Cancer G. Surgical management and pathological assessment of pancreatoduodenectomy with venous resection: an international survey among surgeons and pathologists. HPB (Oxford) 2021;23(1): 80-89.
- Machairas N, Raptis DA, Velázquez PS, Sauvanet A, de Leon AR, Oba A, Koerkamp BG, Lovasik B, Chan C, Yeo C, Bassi C, Ferrone CR, Kooby D, Moskal D, Tamburrino D, Yoon DS, Barroso E, de Santibañes E, Kauffmann EF, Vigia E, Robin F, Casciani F, Burdío F, Belfiori G, Malleo G, Lavu H, Hartog H, Hwang HK, Han HS, Marques HP, Poves I, Rosado ID, Park JS, Lillemoe KD, Roberts K, Sulpice L, Besselink MG, Abuawwad M, Del Chiaro M, de Santibañes M, Falconi M, D’Silva M, Silva M, Hilal MA, Qadan M, Sell NM, Beghdadi N, Napoli N, Busch OR, Mazza O, Muiesan P, Müller PC, Ravikumar R, Schulick R, Powell-Brett S, Abbas SH, Mackay TM, Stoop TF, Gallagher TK, Boggi U, van Eijck C, Clavien PA, Conlon KCP, Fusai GK. The Impact of Neoadjuvant Treatment on Survival in Patients Undergoing Pancreatoduodenectomy with Concomitant Portomesenteric Venous Resection: An International Multicenter Analysis. Ann Surg 2021.
- Groen, Jesse V. MD∗; van Manen, Labrinus MD∗; van Roessel, Stijn MD, PhD†; van Dam, Jacob L. MD‡; Bonsing, Bert A. MD, PhD∗; Doukas, Michael MD, PhD§; van Eijck, Casper H.J. MD, PhD‡; Farina Sarasqueta, Arantza MD, PhD∥; Putter, Hein MD, PhD¶; Vahrmeijer, Alexander L. MD, PhD∗; Verheij, Joanne MD, PhD∥; Besselink, Marc G. MD, PhD†; Groot Koerkamp, Bas MD, PhD‡; Mieog, J. Sven D. MD, PhD∗ Resection of the Portal-Superior Mesenteric Vein in Pancreatic Cancer, Pancreas: September 2021 – Volume 50 – Issue 8 – p 1218-1229 doi: 10.1097/MPA.0000000000001897
- Sibinga Mulder BG, Feshtali S, Farina Sarasqueta A, Vahrmeijer AL, Swijnenburg RJ, Bonsing BA, Mieog JSD. A Prospective Clinical Trial to Determine the Effect of Intraoperative Ultrasound on Surgical Strategy and Resection Outcome in Patients with Pancreatic Cancer. Ultrasound Med Biol 2019;45(8): 2019-2026.
- van Veldhuisen E, Walma MS, van Rijssen LB, Busch OR, Bruijnen RCG, van Delden OM, Mohammad NH, de Hingh IH, Yo LS, van Laarhoven HW, van Leeuwen MS, Nio CY, van Santvoort HC, de Vries J, Wessels FJ, Wilmink JW, Molenaar IQ, Besselink MG, van Lienden KP, Dutch Pancreatic Cancer G. Added value of intra-operative ultrasound to determine the resectability of locally advanced pancreatic cancer following FOLFIRINOX chemotherapy (IMAGE): a prospective multicenter study. HPB (Oxford) 2019.
- Habib JR, Kinny-Köster B, van Oosten F, Javed AA, Cameron JL, Lafaro KJ, Burkhart RA, Burns WR, He J, Thompson ED, Fishman EK, Wolfgang CL. Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: Surgical planning with the “halo sign” and “string sign”. Surgery 2020.
- Raptis DA, Sánchez-Velázquez P, Machairas N, Sauvanet A, Rueda de Leon A, Oba A, Groot Koerkamp B, Lovasik B, Chan C, Yeo CJ, Bassi C, Ferrone CR, Kooby D, Moskal D, Tamburrino D, Yoon DS, Barroso E, de Santibañes E, Kauffmann EF, Vigia E, Robin F, Casciani F, Burdío F, Belfiori G, Malleo G, Lavu H, Hartog H, Hwang HK, Han HS, Poves I, Rosado ID, Park JS, Lillemoe KD, Roberts KJ, Sulpice L, Besselink MG, Abuawwad M, Del Chiaro M, de Santibañes M, Falconi M, D’Silva M, Silva M, Abu Hilal M, Qadan M, Sell NM, Beghdadi N, Napoli N, Busch ORC, Mazza O, Muiesan P, Müller PC, Ravikumar R, Schulick R, Powell-Brett S, Abbas SH, Mackay TM, Stoop TF, Gallagher TK, Boggi U, van Eijck C, Clavien PA, Conlon KCP, Fusai GK. Defining Benchmark Outcomes for Pancreatoduodenectomy With Portomesenteric Venous Resection. Ann Surg 2020;272(5): 731-737.
- Mizuno S, Kato H, Yamaue H, Fujii T, Satoi S, Saiura A, Murakami Y, Sho M, Yamamoto M, Isaji S. Left-sided Portal Hypertension After Pancreaticoduodenectomy With Resection of the Portal Vein/Superior Mesenteric Vein Confluence in Patients With Pancreatic Cancer: A Project Study by the Japanese Society of Hepato-Biliary-Pancreatic Surgery. Ann Surg 2021;274(1): e36-e44.
U Narbe, P -O Bendahl, M Fernö, C Ingvar, L Dihge, L Rydén
Invasive lobular breast cancer is the second most common histological subtype and constitutes around 10-15% of all breast cancer. It is recognized by a peculiar diffuse growth pattern and disseminated spread of cancer cells contributing to diagnostic delay and difficulties in detecting the primary tumors by mammography and nodal metastasis by axillary ultrasound. Consequently, although invasive lobular breast cancer mainly displays a favorable luminal A molecular subtype, it is often diagnosed at a higher stage than invasive cancer of no special type. Despite these characteristics, histopathological subtype is not accounted for in Clinical Guidelines, in contrast to the molecular subtypes. In the BJS publication “The St. Gallen 2019 Guidelines understage the Axilla in Lobular Breast Cancer: a Population-Based Study” by Ulrik Narbe and co-authors, we have elaborated on the consequences for patients with invasive lobular cancers if completion axillary clearance would be omitted in patients with 1-2 nodal metastases.
For the breast surgeon, lobular cancer poses a challenge to surgery of the breast and to the axilla. Large tumor size and diffuse infiltrating margins are associated with an increased risk of positive margins after breast conserving surgery and in breast centers where MRI is available, complementary imaging is recommended ahead of primary surgery. Still a larger proportion of patients (66%) with lobular cancer undergo a mastectomy compared to other histological subtypes (43%) according to our registry study, supporting previous publications. So the dogma of de-escalating breast surgery from mastectomy to partial mastectomy in lobular cancer is challenging, keeping in mind that positive resection margins is a mandatory quality criteria in most centers pushing the choice of initial surgery towards upfront mastectomy.
Axillary surgery is moving towards de-escalation of surgical interventions for patients with 1-2 sentinel node metastases after the results of the Z0011 trial have been implemented worldwide and clearly supports that omission of completion axillary dissection is non-inferior provided the inclusion criteria for the trial is fulfilled. The Z0011 criteria for omission of completion axillary dissection is restricted to patients undergoing breast-conserving surgery, and is thus not applicable for lobular cancers operated by mastectomy. The St. Gallen 2019 guidelines extended the indication for abstaining completion axillary dissection to all patients of any tumor size irrespective of type of breast surgery. In addition, the guidelines recommended that the decision on adjuvant chemotherapy for luminal A-like tumors should include nodal staging and patients with 4 or more nodal metastasis (nodal stage II) were recommended adjuvant chemotherapy. For these patients there is hitherto no data on the role of genomic tests for risk stratification until the results of OPTIMA trial are presented. In this paper, we present data from the National Swedish Quality Registry with prospectively collected data retrieved from the period when a completion axillary clearance for patients with sentinel node metastases was recommended. We found a strong association between invasive lobular breast cancer and nodal stage II disease independent of other determinants such as tumour size.
Moreover, we validated the predominance of luminal A-like subtype in lobular cancer and among those the risk of nodal stage II disease was higher than for the corresponding group of invasive cancers of no specific type (19% compared with 3%). Importantly, patients with lobular cancer retained a predominance (60%) for luminal A-like subtype in the nodal stage II subgroup. In contrast, patients with nodal stage II disease and non-lobular cancers had a lower fraction of luminal A-like tumors (23%) compared with patients with a lower nodal status implicating that for most patients with nodal stage II and non-lobular cancers, the molecular subtype would guide adjuvant treatment decisions rather than nodal stage.
The biological mechanism behind the prevalence of a higher nodal burden in lobular cancer is today speculative. Hormone responsive tumors (ER positive) of all histological subtypes are characterized by a slightly increased risk of nodal metastasis, probably linked to a lower immunologic reaction in the primary tumor facilitating lymphatic spread. Moreover, the cornerstone of lobular cancers – loss of E-cadherin – facilitates detachment of cancer cells which might be of importance for metastatic spread. In the present study, we clearly present data on the independent association of lobular cancer with nodal spread underscoring that this association is not solely explained by a hormone responsive phenotype or a larger tumor size.
This study highlights that lobular cancer is associated with a higher nodal burden than non-lobular cancer and omission of completion axillary clearance in sentinel node positive patients could thus understage the axilla. The consequence of this is that some 19% of all patients with invasive lobular cancer and luminal A-like subtype would be dismissed from recommendation of adjuvant chemotherapy. Today, the updated St. Gallen 2021 guidelines states that completion axillary clearance is recommended for patients where staging is necessary for adjuvant treatment recommendations and would largely correspond to lobular cancers with a luminal A-like molecular subtype. The challenge of de-escalating axillary surgery in lobular cancer is thus unresolved.
The consequence of understaging of the axilla in lobular cancer in terms of clinical outcome is, however, unclear while the responsiveness of chemotherapy in lobular cancer is considered poorer than the corresponding effect in non-lobular cancer. Despite the findings from neoadjuvant trials, lobular cancer is included in general recommendations on adjuvant chemo-endocrine therapy due to the lack of data specific for lobular cancer. The ongoing randomized trial SENOMAC holds some promise to shed light on the outcome for lobular cancers in the experimental arm in which adjuvant recommendations are not based on complete axillary staging. A strong recommendation for the future is to always include data on histological subtype in clinical trials to be able to stratify the cohort in future analysis. The small but aggressive molecular subtypes, triple-negative and HER2-positive, represent subgroups as small as the lobular histological subtype and today clin.trials.gov is overloaded by adjuvant and neoadjuvant treatment protocols specific for these molecular subtypes. So isn´t it time to reconsider protocols on invasive lobular breast cancer with luminal A-like subtypes? The phenotype indicates cancers at low-risk of distant spread which is balanced by a higher stage at diagnosis associated with a substantial risk of recurrence and death after long-term follow-up. The role of neoadjuvant endocrine therapy in this subgroup is far from settled and might open up for de-escalating surgery of the breast and axilla and shed light on the fascinating biology of lobular breast cancer.
Morihiro Katsura, Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan and Department of Surgery, Okinawa Chubu Hospital, Okinawa, Japan
Yasushi Tsujimoto, Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan and Scientific Research Works Peer Support Group (SRWS-PSG), Osaka, Japan
Shingo Fukuma, Associate Professor – Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan
Toshi A Furukawa, Professor – Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan
As systematic review papers on the same topic continue to be published, a massive amount of information pours down on the readers, a trend that gradually amplifies like a tsunami every year1. This phenomenon is still not well unknown in our field for surgeons. A meta-epidemiological study conducted by our research team showed that considerable variability in results and methodological quality can be found among multiple systematic reviews and meta-analyses (SRs/MAs) on the same topic. Additionally, high methodological quality in the systematic review evaluation is independently associated with increased citation counts in the subsequent five years after adjusting for journal impact factors and other covariates. These results highlight the current situation wherein surgeons seeking high-quality “evidence-based surgery“ do not know which review results to believe in the clinical setting, even though SRs/MAs are central to “evidence-based medicine“. To reduce the burden on busy surgeons in finding the most relevant evidence, this study suggests that quality evaluations should play a complementary role, and researchers and journal editors should concentrate their efforts on reviews of more limited quantity but higher quality.
“These results highlight the current situation wherein surgeons seeking high-quality “evidence-based surgery“ do not know which review results to believe in the clinical setting“
Many clinicians and researchers have felt the wastefulness of the recent explosion of similar review articles1,2. Several descriptive studies regarding duplicate review articles on pharmacological intervention have been reported3,4 but particularly in surgery, this is rarely discussed. Therefore, we hypothesized that there are many redundant overlapping SR/MA publications with conflicting results and variable qualities, even in the field of surgery5. We first identified all SRs/MAs focusing on surgical interventions published in 2015 via PubMed. We then searched for SRs/MAs of similar RCTs published within the preceding five years (between 2011 and 2015). As the research progressed, an interesting idea arose among our research team to examine the number of citations as a measure of scientific impact after publication; therefore, we decided to investigate factors associated with the number of five-year citations through 2020 (Figure 1). This research was conducted in collaboration with the Research Group on Meta-epidemiology at Kyoto University School of Public Health.The results of this study were published online in the British Journal of Surgery on 17th November 2021.
Omission and commission phenomenon
Ideally, all randomized controlled trials (RCTs) included in previous SRs/MAs should also be included in subsequently published SRs/MAs. In the real world, however, some of them have been omitted (Figure 2). We attempted to visualize this omission and commission phenomenon and compared the coverage probabilities of all RCTs that were published until the publication year of each SR/MA (one example is shown in Table 2). As a result, we found that there was considerable variability in coverage probability for relevant RCTs, and this was observed on almost every topic except the Cochrane update review.
Discrepant results among overlapping systematic reviews
We found discrepancies among overlapping SRs/MAs on the same topic, such as different effect sizes, different statistical precisions, and even different directions of effect for many topics. Of course, although this is only the result of a sample within a wide surgical field, we believe that it is highly representative.
We show some examples of the discrepancies of pooled effect estimates among overlapping SRs/MAs in Table 2. For the topic ‘Appendectomy vs. Antibiotic treatment for acute appendicitis’, while the largest odds ratio (OR) was 8.13, the smallest was 0.54, a difference by a factor of 15.06 (Table 2), which was the largest difference among the 29 surgical topics which we reviewed in this study. We hypothesize that the major reasons why the pooled effect estimates are so different among overlapping SRs/Mas are related to differences in coverage probability for relevant RCTs (Table 1) and differences among the study subjects. Of course, there could be many other reasons, so we expect further research to shed light on some of them. Interestingly, overlapping publications have continued to increase since 2015, according to an updated PubMed search, particularly for topics with a large discrepancy in the study results.
How do you select a systematic review paper for citation?
When we write a scientific paper, what important factors are considered when picking systematic review articles to cite for our research? Many researchers may answer that it is the journal’s name recognition or impact factor. We used a mixed-effects regression model with a random intercept for surgical topics, which has been used as an analytical method in previous meta-epidemiological studies6, to investigate factors associated with the five-year citation counts of each SR/MA. As expected, a high journal impact factor (5.50 counts more per 1-point increment; 95% CI, 3.97 to 7.03; P <.001) was associated with a greater 5-year citation count. In addition, after adjusting for journal impact factors and other covariates, a high quality score (AMSTAR score 8-11) was independently associated with greater 5-year citation counts with a low quality score (AMSTAR score of 0-3) used as a reference (33.36 counts more; 95% CI, 16.20 to 50.51; P <.001). It is natural for researchers to evaluate the quality of the papers they would cite.
Implication for research and practice
Surgical SRs/MAs rarely include RCTs but instead focus on many nonrandomized trial designs. In this study, we evaluated SRs/MAs with only RCTs, which means that most SRs/MAs were excluded, and therefore, the situation is expected to be more serious in the real world. Surgical SRs/MAs may also be conducted predominantly by surgeons, lacking the involvement of methodologists or evidence synthesis experts, which could limit the quality of the research. There may be a significant risk of accepted wisdom concerning the hierarchy of evidence levels if numerous SRs/MAs on the same topic show high variability in the results and methodological quality. To prevent unnecessary duplication, the international Prospective Register for Systematic Reviews (PROSPERO) was launched in 2011; today, however, it may rarely work properly in practice and may only be considered as a courtesy7. Another novel approach, the “Living systematic review“, has been proposed: SRs are continually updated, incorporating relevant new evidence as it becomes available. It may be time to seek such new and more efficient methods8. Prior to initiating a project in surgical SRs/MAs, adequate communication and team building between surgeons and methodologists are critical in preventing duplication of research efforts and ensuring methodological rigor and currency. While further study is needed to discuss the problems of overlapping publications in surgical SRs/MAs, findings from our study may help guide clinicians, researchers and journal editors.
“Researchers and journal editors should concentrate their efforts on reviews of more limited quantity but higher quality.“
- Ioannidis JP. The mass production of redundant, misleading, and conflicted systematic reviews and meta-analyses. Milbank Q 2016;94:485-514.
- Créquit P, Trinquart L, Yavchitz A, Ravaud P. Wasted research when systematic reviews fail to provide a complete and up-to-date evidence synthesis: the example of lung cancer. BMC Med 2016;14:8.
- Siontis KC, Hernandez-Boussard T, Ioannidis JP. Overlapping meta-analyses on the same topic: survey of published studies. BMJ 2013;347:f4501.
- Hacke C, Nunan D. Discrepancies in meta-analyses answering the same clinical question were hard to explain: a meta-epidemiological study. J Clin Epidemiol 2020;119:47-56
- Katsura M, Kuriyama A, Tada M, Yamamoto K, Furukawa TA. Redundant systematic reviews on the same topic in surgery: a study protocol for a meta-epidemiological investigation. BMJ Open 2017;7(8):e017411.
- Tsujimoto Y, Fujii T, Onishi A, Omae K, Luo Y, Imai H, et al. No consistent evidence of data availability bias existed in recent individual participant data meta-analyses: a meta-epidemiological study. J Clin Epidemiol 2020;118:107-114.
- Moher D, Booth A, Stewart L. How to reduce unnecessary duplication: use PROSPERO. BJOG 2014;121:784-786.
- Hilton J, Tovey D, Shemilt I, Thomas J; Living Systematic Review Network. Living systematic review: 1. Introduction-the why, what, when, and how. J Clin Epidemiol 2017;91:23-30.
The illustration was created by the Tsuchimochi design office. Image source: hand drawing/Shutterstock.com under license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Eight surgeons came together to review the available evidence on the management of rectus diastasis and produce evidence-based guidelines. Sadly the evidence quality ranged from very low to moderate. Despite this, the team were able to provide nine recommendations, with the strength of the recommendation ranging from weak to strong.
The nine key questions were:
KQ1 What is the definition of RD?
KQ2 Which modalities are most suitable for diagnosis and assessment of RD?
KQ3 What are the classification systems for RD?
KQ4 What symptoms are associated with RD?
KQ5 Which outcome measures should be used to evaluate treatment for RD?
KQ6 Are there non-operative treatment options for RD?
KQ7 What are the surgical treatment options in patients without concomitant hernias?
KQ8 What is the optimal treatment of rectus diastasis with concomitant umbilical or epigastric hernias?
KQ9 Is there a role for specific postoperative management of RD repair?
This is clearly an area of surgery where higher-quality research is needed; until that is achieved, these guidelines, together with detailed, honest, and open discussions with patients, offer the best pathway towards shared, evidence-based, decision making.
Authors: B. P. Müller-Stich, P. Probst, H. Nienhüser, S. Fazeli, J. Senft, E. Kalkum, P. Heger, R. Warschkow, F. Nickel, A.T. Billeter, P. P. Grimminger, C. Gutschow, T. S. Dabakuyo-Yonli, G. Piessen, M. Paireder, S. F. Schoppmann, D. L. van der Peet, M. A. Cuesta, P. van der Sluis, R. van Hillegersberg, A. H. Hölscher, M. K. Diener, T. Schmidt
Minimally invasive resection of esophageal cancer might be less traumatic than open resection and has the potential to reduce complications and even improve survival. In contrast, oncological radicality might be negatively affected by the minimal-invasive approach. The aim of this BJS study was to generate 1A level of evidence on the question whether a minimally invasive approach for oncological esophagectomy is advantageous. A systematic literature search was performed and exclusively randomized-controlled trials (RCTs) comparing minimally invasive to open oncological esophagectomy were included in a meta-analysis.
Among 3219 articles six RCTs (four trials from Europe, two from Asia) were found including 822 patients. Survival data and short-term postoperative outcome data was analyzed. From the four European trials (Biere et al. Lancet 2012; Paireder et al. Eur Surg 2018; van der Sluis et al. Ann Surg 2019; Mariette et al. NEJM 2019) individual patient data was retrieved to analyze survival according to the different surgical approaches. Overall survival (56% minimally invasive) vs. (52% open) and disease-free survival (54% vs. 50%) after three years were comparable. Strikingly, the risk of postoperative complications was significantly reduced to one third in the minimal invasive group mainly due to the reduction of pulmonary complications and, in particular, pneumonia. Other parameters, especially those indicating oncological quality of the resection as number of harvested lymph nodes, did not differ between the two groups while the operation time was shorter in the open group. There was no significant difference in the rate of anastomotic leakage, length of stay in the intensive care unit or in the hospital and in the perioperative mortality while total blood loss was lower in the minimal invasive group.
As this meta-analysis included only high-quality randomized controlled trials, it generates high level evidence for the perioperative advantages of minimal invasive esophagectomy. The minimally invasive approach significantly reduces the risk of complications compared to open surgery and does not impair long-term oncological outcome. It should therefore be the preferred approach for cancer-related oesophagectomy.
J Osorio, Z Madrazo, S Videla, B Sainz, A Rodríguez-González, A Campos, M Santamaría, A Pelegrina, C González-Serrano, A Aldeano, A Sarriugarte, C J Gómez-Díaz, D Ruiz-Luna, A García-Ruiz-de-Gordejuela, C Gómez-Gavara, M Gil-Barrionuevo, M Vila, A Clavell, B Campillo, L Millán, C Olona, S Sánchez-Cordero, R Medrano, C A López-Arévalo, N Pérez-Romero, E Artigau, M Calle, V Echenagusia, A Otero, C Tebe, N Pallares, S Biondo, COVID-CIR Collaborative Group Members of the COVID-CIR Collaborative Group
Emergency surgeons may find ourselves attending patients who are potential candidates for emergency surgery and have a COVID-19 infection, with or without evident symptoms. What should we do with these patients?
The purely descriptive studies published to date show that these patients have a much higher than usual postoperative mortality. Considering these results, avoidance or postponement of surgery has been advised in COVID-positive patients.
However, postponing an emergency surgery may also have its risks. In each individual case, the risk of operating must be weighed against the risk of a non-surgical treatment. Therefore, it is very important to fully understand how and to what extent COVID-19 infection increases postoperative mortality.
Or in other words, is the high mortality observed in COVID-positive patients undergoing surgery entirely due to COVID-19 infection?
If we look closely at these descriptive non comparative studies, most of the COVID-positive patients were older than usual, with many underlying pathologies, and in poor general condition at the time of surgery. Could these factors, rather than the COVID-19 infection itself, explain their bad postoperative outcomes?
Additionally: During the lockdown, patients might have had fear or difficulty of going to the hospital and might therefore be diagnosed in a more advanced stage of their surgical pathologies. Moreover, the collapse of the pandemic could also cause hospitals to have difficulties in rescuing patients with postoperative complications.
If we can measure the true impact of these 3 factors involved (the patient’s context, the lockdown effect and the effect of hospital collapse) we will be able to assess how COVID-19 infection increases the mortality of patients undergoing emergency surgery. And that will allow us to make decisions based on evidence about whether, in each specific case, it is more reasonable to operate or to try not to do so.
The COVIDCIR project was born with the objective of answering that question. From the Bellvitge University Hospital, in Barcelona, we led a registry with 25 participating Spanish hospitals including all emergency general and gastrointestinal surgeries performed during the first wave of the pandemic (from March to June 2020) and during the same period of 2019 . More than 5,000 patients were included.
To assess the impact of COVID infection, we compared COVID-positive patients with COVID-negative patients operated on during the pandemic. This comparison was made using a statistical method called propensity-score matching, which consists of matching COVID-positive patients with COVID-negative controls of similar age, underlying pathologies and general condition at the time of surgery, thus achieving two comparable groups.
We observed that the mortality of these two matched comparable groups was not statistically different. Or, put another way, that the high mortality observed in COVID-infected patients undergoing surgery is more due to their age, underlying pathology and preoperative condition than to a hypothetical COVID risk-multiplier effect.
Thus, the fact that a patient is COVID-positive should not be seen as an absolute impediment to perform an emergency surgery. In each individual patient, the assessment of the risk of performing or postponing surgery should be based, as has always been done, on her or his individual anesthetic risk and its state at the time of diagnosis.
Second, to understand the effect of lockdown, to see if patients were diagnosed too late due to fear or difficulty in accessing, we compared surgical pathologies of COVID-negative patients operated on during the pandemic with those operated during the previous year. We saw that in the pandemic, patients did not present with more advanced peritonitis and that the inflammatory parameters of their laboratory tests were not higher. Thus, the increased mortality observed during the pandemic cannot be attributed to the effect of lockdown.
And finally, to understand the consequences of hospital collapse, we assessed what is called Failure to Rescue of patients: that is, what percentage of patients who present postoperative complications could not be rescued and died as a consequence of the complication. We compared Failure-to-Rescue of COVID-negative patients operated during the pandemic with those operated before the pandemic. Also on this occasion we carried out the propensity-score matching comparison, matching patients from both groups from the same hospital and of similar age, underlying pathologies and severity of surgical pathology.
We found that COVID-negative patients operated on during the COVID-19-pandemic had the same risk of postoperative complications, but a greater Failure-to-Rescue than before. This fact was evident in the 25 participating hospitals and is probably explained by the hospital collapse in the pandemic context.
Author: Hiroki Ueo, Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Ueo Breast Cancer Hospital, Oita, Japan
Breast cancer is the most common cancer in women, and its incidence continues to increase worldwide. From the patient’s perspective, breast conserving surgery (BCS) with radiation achieves a balance between a satisfactory cosmetic result and a low recurrence rate. Although it has been established as a routine surgery, surgeons need to be careful about positive surgical margins. Remnant cancer cells in the preserved tissue increase the risk of recurrence. Therefore, a positive margin on postoperative pathology warrants additional surgery. In these cases, the additional treatment harbours unexpected outcomes, including physical, mental, cosmetic, and economic burden on the patients.
To avoid the additional operation, pathological evaluation using an intraoperative frozen section is conducted. It is the most reliable method to prevent misdiagnosis and to achieve clear surgical margins. However, this conventional method is time consuming and costly. Moreover, it is dependent on the skill and experience of the pathologists and personnel, and it requires space for preparation of the frozen sections. Therefore, only a limited number of samples are examined to save time and resources. An alternative, rapid, and reliable technique to detect cancer in surgical margins enables simultaneous testing, leading to a reduced false negative rate of local recurrence incidence. In addition, pathologists can focus on the definitive diagnosis using permanent paraffin sections because it is difficult to make a diagnosis based on intraoperative frozen sections without pathological architecture. Pathologists only need to make an intraoperative diagnosis when the specimen cannot be evaluated via the fluorescence procedure. Thus, it is important to enhance the rapid fluorescent detection of breast cancer during surgery. To address these diagnostic issues, Prof. Urano invented chemical reagents (gamma-glutamyl hydroxymethyl rhodamine green [gGlu-HMRG]) that quickly fluoresce by reacting with an enzyme (gamma-glutamyl transferase [GGT]), overexpressed in cancerous tissues. It exhibits strong fluorescence a few minutes after reacting with GGT in vitro. A gGlu-HMRG solution is applied to the surgical margins to recognize cancer cells as green fluorescence intraoperatively. A previous study in 2015 documented the ability of this reagent to mark cancerous tissues in surgical breast tissues. Furthermore, this reagent did not interfere with the pathological examination, while the frozen section analysis tissues were difficult to reuse as formalin-fixed and paraffin-embedded permanent pathological specimens.
The clinical utility of this technique was examined. The results were published in the British Journal of Surgery. Since the initial report in 2015, a more feasible and reproducible sample preparation protocol has been developed. Then, a dedicated apparatus, including a built-in camera, software program, and multiple sample wells, was developed. This system automatically measured and analyzed the increase in fluorescence of multiple samples simultaneously. Then, the increase in fluorescence of gGlu-HMRG, applied to breast tissues, was measured in four different institutes. The sample tissues were examined by four pathologists independently. These pathologists diagnosed the samples without knowing the background information of the patients. The clinical utility of the current fluorescent procedure was evaluated by comparing the fluorescence data and the pathological diagnosis.
A clear threshold to distinguish between cancerous and non-cancerous tissues was not determined due to the heterogeneity of breast cancer tissues. Instead, the negative threshold to achieve a false negative rate <2% and the positive threshold to achieve a false positive rate <2% were established. Samples in which the increase in fluorescence was below the negative threshold value were considered cancer-free margins with a false negative rate <2%. The false negative samples in our study were tissues containing non-invasive cancer. This suggested that the samples below the negative threshold can be considered free of invasive cancer. Samples in which the increase in fluorescence was above the positive threshold value were considered cancerous tissue with a false positive rate <2%.
The disease prevalence determines the performance of a diagnostic tool. The percentage of positive and negative test results among those with or without the disease are the positive and negative predictive values, respectively. These positive and negative predictive values depended on the prevalence. Therefore, to estimate the performance of this technique, the prevalence and margin positive rate in this case should be considered. The margin positive rate was expectedly lower than that of our clinical study. In our protocol, three pieces of tissue were sampled: the central portion, where the breast cancer is located; its periphery, which contains non-invasive cancer; and the distal portion, which ideally contains normal mammary tissue. Cancer was detected in 46% of the samples. Based on the actual margin assessment, the prevalence was lower than that of our study. Assuming a prevalence <30%, the negative predictive value, the ratio of true negative samples among fluorescent negative samples, was larger than 98%. This indicated that this method was useful for detecting negative margins.
According to this multicenter study, the fluorescent diagnosis was applicable to any breast cancer subtype, regardless of its pathological findings and subtype. Moreover, the similar accuracy among several institutes confirmed that the fluorescent diagnosis was applicable to any institute, following the protocol. Compared to the intraoperative frozen section analysis, the fluorescent diagnosis was a more rapid and accessible method with a low cost. It was not dependent on the skills of pathologists, and it did not require a large amount of space.
In conclusion, this method can facilitate the rapid assessment of negative surgical margins during BCS while reducing the testing time, cost of diagnosis, and tasks of the pathologists and staff.
Authors: A G N Robertson (Twitter: @robertson_a), T Wiggins (@TomWiggins23), F P Robertson, L Huppler (@LucyLucyHuppler), B Doleman, E M Harrison (@ewenharrison), M Hollyman (@misshollyman), R Welbourn
Obesity is the preventable and reversible disease of our lifetime. It is a worldwide health, economic and environmental problem in need of urgent and essential attention, and it has become clear that the world needs more than the traditional recommendations to survive this metabolic pandemic. The traditional advice has been acknowledged for centuries and even more so since the worldwide prevalence of obesity nearly tripled between 1975 and 20161. These lifestyle recommendations include physical exercise, less high calorific food content, balanced meals, optimising portion size, intermittent fasting and so on; we all know them. However, the human race is still falling short of tackling the major public health concern that this disease threatens to be.
Bariatric or weight loss surgery is a surgical sub-speciality which has been evolving since the first procedures of this type in the mid 20th century. Its development has led to the most effective method to achieve long-term weight loss, as well as the additional health benefits weight loss offers as a by-product. However, accessibility to this specialist treatment is limited with only 1% of eligible patients going on to receive bariatric surgery.2Reasons for this limited access are multifactorial, however a considerable factor is thought to be concerns regarding the perceived risks of weight-loss surgery from patients across all populations. We should therefore aim to give our patients the most up to date worldwide risk of mortality of these potentially life-saving procedures.
This month in the BJS, we’ve published the largest meta-analysis asking this question to date – and the findings are pivotal at providing a unanimous international statistic on this discussion. We’ve looked at perioperative mortality rates (inpatient, 30 day and 90 day mortality) of a range of bariatric procedures to include laparoscopic adjustable gastric band (LAGB), sleeve gastrectomy (SG), Laparoscopic Roux-en-Y gastric bypass (LRYGB), one-anastomosis gastric bypass (OAGB), biliopancreatic diversion/duodenal switch (BPD-DS) and other malabsorptive procedures. We’ve included 58 studies in our meta-analysis which has given us information on roughly 3.6 million patients over a 6-year period from worldwide practice. Multiple sources for data were used including administrative datasets, bariatric surgery registries, large scale case series as well as randomised controlled trials (RCTs).
The paper looks at mortality within each subgroup of operation. There are interesting findings within this showing significant differences in perioperative mortality between procedures (P<0.001) with biliopancreatic diversion/duodenal switch or other malabsorptive procedures having the highest perioperative mortality rates (0.41%) and laparoscopic adjustable gastric band (LAGB) followed by sleeve gastrectomy (SG) being the procedures with the lowest perioperative mortality rates (0.03% and 0.05% respectively). This naturally reflects the trend towards these latter procedures being offered more commonly in international practice. Although this paper looks closely at perioperative mortality it is noteworthy to mention that it doesn’t look at long term morbidity following these procedures or their potential complication rates.
Without a doubt, our most noteworthy finding has been the discovery that overall perioperative mortality following bariatric surgery is likely much lower than previously thought, with our pooled perioperative mortality rate at 0.08% (95% CI 0.06%-0.10%). It perhaps makes this statistic even more relatable when this is compared to other procedures we consider as ‘low-risk’ in our daily surgical practice. For example, laparoscopic cholecystectomy or fundoplication have comparable perioperative mortality rates reported at 0.1%. This new statistic is also lower than previously quoted in the literature from smaller scale studies. The mortality rate calculated in this meta-analysis puts bariatric surgery as a whole at lower risk of mortality as knee arthroplasty (0.3%)3. With this in mind, we hope that there can be a culture shift from avoidance of bariatric surgery due to risk, to giving patients the correct information to confidently weigh up the true risks and benefits of these procedures when indicated.
How should these findings shape the future of bariatric surgery in Europe and beyond? Certainly in the UK, the acceptability of bariatric surgery as a viable treatment option for obesity is limited. It is surprising how often we see patients who are eligible for bariatric surgery and who have met the criteria for some time yet to be offered this as a treatment option. There is a distinct barrier to accessing bariatric surgery for the wider population, perhaps due to taboo surrounding broaching the issue of weight in the primary care setting, and although many general practitioners do this very well, there remain limiting factors. Another stand-out factor includes lack of funding or commissioning within the public health service for referral for weight loss specialist services. Therefore, with the addition of this new internationally applicable statistic, our hope is that the most effective treatment option for sustained weight loss can now be available for all that require it. Bariatric surgery is safe.
- Welbourn R, le Roux CW, Owen-Smith A, Wordsworth S, Blazeby JM. Why the NHS should do more bariatric surgery; how much should we do? Bmj. 2016;353:i1472.
- Aminian A, Brethauer SA, Kirwan JP, Kashyap SR, Burguera B, Schauer PR. How safe is metabolic/diabetes surgery? Diabetes, Obes Metab. 2015; 17(2):198-201.
Image source: Eslam ibrahim66 2021 Creative Commons