Category Archives: guest blog

Hernias in children

Guest blog in plain English: Hernias in children

Nathalie Auger, Francesca del Giorgio, Annie Le-Nguyen, Marianne Bilodeau-Bertrand, Nelson Piché

University of Montreal Hospital Research Centre, Montreal, Quebec, Canada

Are women who have inguinal hernias more likely to have a child with an inguinal hernia? Have you ever wondered why a child may develop an inguinal hernia? Inguinal hernias affect about 4% of children1,2, but the reasons why are very unclear. An inguinal hernia occurs when intestinal tissues push through a weak spot in the abdominal wall. Most children with inguinal hernias are thought to have developed this disorder while still in their mother’s womb1,3. Yet there has been little attention to the possibility that the characteristics of mothers could predict which children will develop inguinal hernias while growing up.

We studied whether women who were previously diagnosed or treated for an inguinal hernia were more likely to have a child with an inguinal hernia. To test our research question, we analyzed the health status of 795,590 children from the province of Quebec, Canada4. We collected information from their mothers including her age, pregnancy complications, diseases she may have had in the past, and whether she was ever treated for an inguinal hernia. We closely followed her child over time to find out if the child was ever hospitalized for an inguinal hernia between birth and 13 years of age. We used regression methods to determine how characteristics of the mothers were associated with the chance of having an inguinal hernia in the child, and made sure that we controlled for confounders that could lead to incorrect measurements.

Our findings were very enlightening. We confirmed that mothers with a history of inguinal hernia were more likely to have a child who develops an inguinal hernia. But we found that the risk was higher for daughters than sons. Girls whose mothers had an inguinal hernia were 5 times more likely to themselves have an inguinal hernia. Additionally, mothers with connective tissue disorders such as rheumatoid arthritis or lupus were more likely to have sons with inguinal hernias. The figure illustrates just how strong some of the associations were.

These results suggest that the characteristics of a mother may affect a child’s chance of having an inguinal hernia. The likelihood of having an inguinal hernia also depends on if the child is a girl or a boy. Some of this difference may be because the development of inguinal hernias in boys is not the same as in girls. But it is also possible that there is a genetically sex-linked component. Finally, the relationship between maternal connective tissue diseases and the risk of inguinal hernia in boys suggests that connective tissue architecture may be involved as well.

Although more research is needed to confirm these findings, doctors and patients should be aware that children with abdominal symptoms who have a mother with a history of an inguinal hernia or connective tissue disorder may themselves be more likely to have an inguinal hernia. For more information, we invite you to read our study that was recently published in British Journal of Surgery4.

References

1          Azarow K, Cusick R. Pediatric Surgery [Internet]. The Surgical clinics of North America, Vol. 92. 2012. Available from: http://www.sciencedirect.com/science/article/pii/S0039 610912000680 [accessed 11 February 2021]

2          Lao OB, Fitzgibbons RJ, Cusick RA. Pediatric inguinal hernias, hydroceles, and undescended testicles. Surgical Clinics of North America 2012; 92: 487–504.

3          Kapur P, Caty MG, Glick PL. Pediatric hernias and hydroceles. Pediatric Clinics of North America 1998; 45: 773–789.

4          Auger P, Del Giorgio F, Le-Nguyen A, Bilodeau-Bertrand M, Piché N. Pediatric hernias and hydroceles. British Journal of Surgery 2021.

Guest blog: Venous resection during pancreatoduodenectomy – there is still much to gain

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 

IMPORTANCE

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.

QUESTION

Does type of venous resection during pancreatoduodenectomy for pancreatic cancer impact postoperative morbidity and overall survival?

FINDINGS

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%).

MEANING

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. 

FUTURE

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.

REFERENCES

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
Cerebral microbleed

Guest blog: Cerebral microbleeds following thoracic endovascular aortic repair

W. Eilenberg a,b**, M. Bechstein d**, P. Charbonneauc, F. Rohlffs a, A. Eleshra a, G. Panuccio a, J. Bhangu b, J. Fiehler d, R. Greenhalgh e, S. Haulon c, T. Kölbel a*

German Aortic Center, Department of Vascular Medicine, University Heart & Vascular Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany

Department of General Surgery, Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria

Centre de l’Aorte, Hôpital Marie Lannelongue, Groupe hospitalier Paris Saint Joseph, Université Paris Saclay, France

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Vascular Surgical Research Group, Imperial College, London, UK.

** both authors contributed equally

E-mail: wolf.eilenberg@meduniwien.ac.at

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article. 

Stroke and cerebral damage are frequent findings after thoracic endovascular aortic repair (TEVAR) with a postoperative clinical stroke rate of 3-4% and silent brain infarcts (SBI) in about 80%.(1-4) However, the mechanism of stroke and subclinical cerebral damage in TEVAR is under-investigated. Current clinical research-efforts such as the STEP-registry (strokes from thoracic endovascular procedures) aim to better understand incidence of, and risk factors for stroke and cerebral damage after TEVAR, and to develop strategies for prevention.(5, 6) More than 60% of patients undergoing arch-TEVAR were reported to have SBIs on diffusion weighted magnetic resonance imaging (DW-MRI) despite protective efforts such as carbon dioxide (CO2) flushing of the endografts.(5, 6) The aim of the current study is to examine the occurrence of CMBs in patients after TEVAR within the STEP-registry and to evaluate their association with patient- and procedural factors.

Ninety-one patients treated with TEVAR in proximal landing zone (PLZ) 0-3 from September 2018 to January 2020 at the German Aortic Center (Hamburg, Germany) and Marie Lannelongue Hospital (Paris, France) were included in the study.(5) The location and number of CMBs were identified and analyzed with regards to procedural aspects, clinical outcome and Fazekas-score as indicator of preexisting vascular leukoencephalopathy.

Indication for TEVAR was type B dissection, degenerative aneurysm or other aortic disease in 44/91 (48.4%), 34/91 (37.3%) and 13/91 (14.3%) patients, respectively. Anatomical details have been described in detail previously.(5)

PLZ were 0, 1, 2 and 3 in 23/91 (25.3%), 10/91 (11.0%), 47/91 (51.6%) and 11/91 (12.1%) patients, respectively. Seventy-one/91 (78.0%) patients were treated in an elective setting. 23 (25%) patients received branched-TEVAR (B-TEVAR), 15 (17%) patients fenestrated-TEVAR (F-TEVAR) of which 4 (4%) patients had in-situ laser fenestrations. Fifty-three/91 (58%) patients received tubular endografts. The median proximal diameter of the aortic endoprosthesis was 38 (34-46) mm and 37/91 (40.7%) patients received a proximal bare stent. Technical success was reported in all cases. Intraoperative complications, such as prolonged hypotension, iatrogenic dissection of the left subclavian artery, aortic rupture during deployment of a stent-graft and proximal common iliac rupture, were reported in 4/91 (4.4%) patients. No periprocedural ischemic stroke or death occurred within 30 postoperative days (POD). 

On MRI performed within 7 POD (Median 4 (2-7)), a total of 1531 CMBs were detected in 58 (63.7%) patients by two neuroradiological experts; bilateral CMBs were identified in 46/58 (79.3%) patients (P=0.078). CMBs were present unilaterally in the right or left hemisphere in 9/58 (15.5%) and 3/58 (5.2%) patients (P=0.0001) respectively. 

More CMBs were found in the middle cerebral territory vs. the posterior territory and the anterior territory ((3.35 (5.56 SD) vs. 2.26 (4.05 SD) vs. 0.966 CMBs (2.87 SD) (P=0.045)),  Procedural factors associated with the presence of CMBs were deployment in zone 0/1 vs. 2/3 (P=0.001), placement of a branched or fenestrated endograft (P=0.025) and longer procedure time (≥120 min) (P=0.019). Proximal diameter of the endoprosthesis ≥40mm (P=0.016), reoperations linked to primary operation (P=0.017) and atheroma grade 4 and 5 (P=0.048) were significantly associated with CMB in a multivariate logistic binary regression model, whereas compliant balloon (P=0.053) use showed only a tendency.  

Multiple linear regression with Firth regression showed more CMBs in TEVAR with proximal diameter ≥40mm OR 6.8 (95% CI 1.65-41.59; P=0.007) and higher DWM Fazekas-score in postoperative MRI OR 2.6 (95% CI 1.06-7.92; P=0.037, indicator of pre-existing vascular leukoencephalopathy). There was no significant correlation between CMBs and SBIs (P=0.376). 

Since there is no pre-operative MRI data to compare to, a causal association between CMBs and TEVAR cannot be proven by the study design. Nevertheless, the observed rate of CMBs after TEVAR (63,7%) was increased compared to rates reported in the literature among a general population of similar mean age (28%).(7) Although the rate among elderly patients with preexisting cardiovascular diseases may generally be higher, a causal linkage between TEVAR and CMBs can therefore also not be ruled by our findings. With the multi-territorial pattern, an embolic and secondary hemorrhagic origin caused by TEVAR may be hypothesized. The middle cerebral artery territory was most frequently affected due to its higher volume and share of blood.(8), (9) CMBs may be of various origin. As SW-MRI is sensitive to para-, dia- and ferromagnetic compounds, the susceptible MRI lesions referred to as “CMBs” may in this postoperative state also result from embolic micromaterial originating from endovascular devices or dispersed microcalcifications from the aortic arch.

We could not identify a significant correlation between SBI and CMBs (P=0.376). In contrast to SBI, which were found predominantly in the left hemisphere, CMBs were detected bilaterally in the vast majority of patients (79.3 %) and unilateral occurrence was more frequent in the right hemisphere (P=0.0001). While cerebral microbleeds are known to occur predominantly in deep or infratentorial regions in the presence of cardiovascular risk factors, and in the temporal lobe in patients with cerebral amyloid angiopathy, a spatial predilection for the right hemisphere in case of unilateral occurrence has so far not been described.(10, 11)

We found an association of CMBs with the PLZ and atheroma grade of the aortic arch matching previously described associations of stroke, SBI and high-intensity transient signals on transcranial doppler with atheroma grade and PLZ. (12, 13)

Although the occurrence of CMBs after TEVAR did not lead to clinically apparent stroke, a potential long-term effect on cognitive function cannot be ruled out. 

The limitations of this study include its retrospective nature and the non-consecutive patient cohort. Pre-operative MRI weren´t available to safely differentiate between procedure-related and preexisting CMBs.  Multivariable and subgroup analysis are limited by low patient numbers and third error in multivariable analysis. Results should be interpreted with caution and only be used to generate hypotheses for future studies. 

CMBs are present bi-hemispherical in the majority of patients after endovascular arch TEVAR and associated with morphological and procedural factors. The clinical importance of this finding needs to be further examined.

References

1.         Kahlert P, Eggebrecht H, Jánosi RA, Hildebrandt HA, Plicht B, Tsagakis K, et al. Silent cerebral ischemia after thoracic endovascular aortic repair: a neuroimaging study.  Ann Thorac Surg. 98. Netherlands: © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc; 2014. p. 53-8.

2.         Perera AH, Rudarakanchana N, Monzon L, Bicknell CD, Modarai B, Kirmi O, et al. Cerebral embolization, silent cerebral infarction and neurocognitive decline after thoracic endovascular aortic repair. Br J Surg. 2018;105(4):366-78.

3.         Ullery BW, McGarvey M, Cheung AT, Fairman RM, Jackson BM, Woo EY, et al. Vascular distribution of stroke and its relationship to perioperative mortality and neurologic outcome after thoracic endovascular aortic repair.  J Vasc Surg. 56. United States: © 2012 Society for Vascular Surgery. Published by Mosby, Inc; 2012. p. 1510-7.

4.         Varkevisser RRB, Swerdlow NJ, de Guerre L, Dansey K, Li C, Liang P, et al. Thoracic Endovascular Aortic Repair With Left Subclavian Artery Coverage Is Associated With a High 30-Day Stroke Incidence With or Without Concomitant Revascularization. J Endovasc Ther. 2020;27(5):769-76.

5.         Charbonneau P, Kölbel T, Rohlffs F, Eilenberg W, Planche O, Bechstein M, et al. Silent Brain Infarction After Endovascular Arch Procedures: Preliminary Results from the STEP Registry.  Eur J Vasc Endovasc Surg. England: © 2020 European Society for Vascular Surgery. Published by Elsevier B.V; 2020.

6.         Rohlffs F, Haulon S, Kolbel T, Greenhalgh R, Collaborators S. Stroke From Thoracic Endovascular Procedures (STEP) Collaboration. Eur J Vasc Endovasc Surg. 2020;60(1):5-6.

7.         Poels MM, Ikram MA, van der Lugt A, Hofman A, Krestin GP, Breteler MM, et al. Incidence of cerebral microbleeds in the general population: the Rotterdam Scan Study. Stroke. 2011;42(3):656-61.

8.         Naylor AR. Translating Evidence into Practice: Surveillance after Carotid Interventions. Eur J Vasc Endovasc Surg. 2018;56(2):298-9.

9.         Kim DE, Park JH, Schellingerhout D, Ryu WS, Lee SK, Jang MU, et al. Mapping the Supratentorial Cerebral Arterial Territories Using 1160 Large Artery Infarcts. JAMA Neurol. 2019;76(1):72-80.

10.       Mesker DJ, Poels MM, Ikram MA, Vernooij MW, Hofman A, Vrooman HA, et al. Lobar distribution of cerebral microbleeds: the Rotterdam Scan Study.  Arch Neurol. 68. United States2011. p. 656-9.

11.       Vernooij MW, van der Lugt A, Ikram MA, Wielopolski PA, Niessen WJ, Hofman A, et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study.  Neurology. 70. United States2008. p. 1208-14.

12.       Feezor RJ, Martin TD, Hess PJ, Klodell CT, Beaver TM, Huber TS, et al. Risk factors for perioperative stroke during thoracic endovascular aortic repairs (TEVAR). J Endovasc Ther. 2007;14(4):568-73.

13.       Morita Y, Kato T, Okano M, Suu K, Kimura M, Minamino-Muta E, et al. Incidence and Predictors of Catheterization-Related Cerebral Infarction on Diffusion-Weighted Magnetic Resonance Imaging. Biomed Res Int. 2016;2016:6052125.

St Gallen

Guest blog: Invasive lobular cancer of the breast remains a surgical challenge

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.

Calculator

Guest blog: “Are you a gambler or an accountant?”

Permanent stoma rates after anterior resection for rectal cancer

Authors: E Back, J Häggström, K Holmgren, M M Haapamäki, P Matthiessen, J Rutegård, M Rutegård

Anterior resection for rectal cancer is a beautiful operation. Whether with hand-held electrocautery or robotic scissors, uncovering the mesorectal package in embryological planes is a most satisfying moment, especially when followed up by a nice, tension-free and well-perfused anastomosis; when all goes well, of course. Unfortunately, anastomotic breakdown is a far too common and dangerous event, tripling the risk of early death1. Quite often, such an event also leads to reoperation and a permanent stoma2. No wonder then that, after decades of research on the merits of defunctioning stomas preventing anastomotic leakage3, there’s a near ubiquitous use in low anterior resection4 (though recent reports challenge this dogma5). The caveat, it seems, is that even temporary stomas cause problems6 and might never be reversed7, questioning the sphincter-saving procedure itself. Moreover, the spectre of severe low anterior resection syndrome rears its ugly head even when a textbook outcome is accomplished8; on the other hand, quality of life might be worse for patients with a permanent stoma9, and this was reported even in the stoma-friendly Scandinavian environment.

The problem is insurmountable, it seems. Do you choose bowel dysfunction and the risk of a leak, or do you opt for a permanent stoma at the get go? Would you dare omit the defunctioning stoma? In short, are you a gambler or an accountant?

In any case, information on an individual patient level is sorely needed for such an important discussion. We’ve recently published a prediction study using pre-operative variables collected from the Swedish Colorectal Cancer Registry, where an attempt has been made at forecasting the risk of a permanent stoma at two years after anterior resection for rectal cancer. While close to five thousand patients contributed data in the analysis, using the ensemble method SuperLearner to develop and validate a moderately accurate prediction model, the real thrust from this study lies in the on-line calculator. The input is shown in Figure 1, where the key predictors can be varied to reflect the patient at hand.

Figure 1. Variables included in the logistic forward-backward selection model can be varied, reflecting the individual patient.

There are certainly more variables of importance out there, and the experienced surgeon will surely add some data to a mental recalculation; smoking, on-going inflammation, continuous immunosuppressive medication, as well as a weak sphincter might decrease the chances of a stoma-free outcome even more. The output can be seen in Figure 2, where the risk of a permanent stoma is depicted in a cross-tabulation of defunctioning stoma use and laparoscopy use; those factors are the only ones that can be altered at a preoperative consultation. Importantly, the output is a predicted risk with measures of uncertainty, providing lower and upper bounds of the permanent stoma risk. Consistently, there is a higher risk of a permanent stoma with the use of a defunctioning stoma, which recently was shown using mediation analysis4.

Figure 2. Output from the prediction model with corresponding measures of uncertainty.

We urge all fellow surgeons to play around with the calculator – it’s actually quite addictive. Perhaps it can be informative in a patient-centred approach to anterior resection, as it seems that, stoma avoidance has the same priority as cure of cancer in some patient populations10. While at it, we can also recommend the internationally validated prediction model for low anterior resection syndrome, POLARS11. While all these prediction models can be improved, it is certainly worthwhile for both surgeon and patient to have some idea of the expected results after anterior resection. 

References

1 Boström P, Haapamäki MM, Rutegård J, Matthiessen P, Rutegård M. Population-based cohort study of the impact on postoperative mortality of anastomotic leakage after anterior resection for rectal cancer. BJS Open. 2019 Feb; 3: 106–111. 

2 Holmgren K, Kverneng Hultberg D, Haapamäki MM, Matthiessen P, Rutegård J, Rutegård M. High stoma prevalence and stoma reversal complications following anterior resection for rectal cancer: a population-based multicentre study. Colorectal Dis. 2017 Dec; 19: 1067–1075. 

3 Matthiessen P, Hallböök O, Rutegård J, Simert G, Sjödahl R. Defunctioning stoma reduces symptomatic anastomotic leakage after low anterior resection of the rectum for cancer: a randomized multicenter trial. Ann Surg. 2007 Aug; 246: 207–214. 

4 Holmgren K, Häggström J, Haapamäki MM, Matthiessen P, Rutegård J, Rutegård M. Defunctioning stomas may reduce chances of a stoma-free outcome after anterior resection for rectal cancer. Colorectal Dis. 2021 Jul 26; 

5 Talboom K, Vogel I, Blok RD, Roodbeen SX, Ponsioen CY, Bemelman WA, et al. Highly selective diversion with proactive leakage management after low anterior resection for rectal cancer. Br J Surg. 2021 Jun 22; 108: 609–612.

6 Gessler B, Haglind E, Angenete E. A temporary loop ileostomy affects renal function. Int J Colorectal Dis. 2014 Sep; 29: 1131–1135. 

7 Jørgensen JB, Erichsen R, Pedersen BG, Laurberg S, Iversen LH. Stoma reversal after intended restorative rectal cancer resection in Denmark: nationwide population-based study. BJS Open. 2020 Dec 2; 4: 1162–1171. 

8 Emmertsen KJ, Laurberg S, Rectal Cancer Function Study Group. Impact of bowel dysfunction on quality of life after sphincter-preserving resection for rectal cancer. Br J Surg. 2013 Sep; 100: 1377–1387. 

9 Näsvall P, Dahlstrand U, Löwenmark T, Rutegård J, Gunnarsson U, Strigård K. Quality of life in patients with a permanent stoma after rectal cancer surgery. Qual Life Res. 2017 Jan; 26: 55–64. 

10        Wrenn SM, Cepeda-Benito A, Ramos-Valadez DI, Cataldo PA. Patient Perceptions and Quality of Life After Colon and Rectal Surgery: What Do Patients Really Want? Dis Colon Rectum. 2018 Aug; 61: 971–978. 

11        Battersby NJ, Bouliotis G, Emmertsen KJ, Juul T, Glynne-Jones R, Branagan G, et al. Development and external validation of a nomogram and online tool to predict bowel dysfunction following restorative rectal cancer resection: the POLARS score. Gut. 2018 Apr; 67: 688–696. 

Guest blog: Keyhole versus open surgery for oesophageal cancer

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. 

Guest blog: Emergency surgery in patients with COVID-19

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.  

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

Guest blog: a novel fluorescence technique for detecting breast cancer

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

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

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

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

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

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

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

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

Roux en Y gastric bypass

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

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

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

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

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

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

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

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

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

Image source: Eslam ibrahim66 2021 Creative Commons

Visual abstract for COVIDHAREM appendicitis study

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

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

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

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

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

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

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

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

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

Conflicts of Interest 

None to declare 

Funding

No funding was received for this blog article 

References

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

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

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

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

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

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