Randomized clinical trials

Herrod PJJ, Kwok AT, Lobo DN.

BJS Open 2022; 6: zrac100.

Eight RCTs including 3203 participants were analyzed. Early optimism about the benefits of antibiotic therapy were tempered in this analysis by reduced treatment efficacy compared with appendicectomy, higher readmission rate, and no advantage in duration of stay at index admission.

Comment: Antibiotic treatment for appendicitis has a place, but not as standard therapy.

Sali L, Ventura L, Mascalchi M, Falchini M, Mallardi M, Carozzi F et al.

Lancet Gastro Hepatol 2022; 7: 1016-1023.

Some 15,000 people were randomized and invited. Attendance was lower for CT colonography (26.7 per cent versus 33.4 per cent who participated in all three faecal testing rounds). Although the detection rate was higher with CT colonography (5.2 versus 3.1 per cent, P=0.0002). Overall detection (referral to work-up) was higher after three rounds of faecal testing (7.5 versus 2.7 per cent, P<0.0001).

Comment. Interesting that compliance with screening may be more important than the accuracy of the test.

Zhang L, Cheng M, Lin Y, Zhang J, Shen B, Chen Y et al.

Br J Surg 2022; 109: 1232–1238.

In this study that included 330 women, the sentinel node identification rate was similar: 94.5 per cent with ultrasound assistance versus 95.8 per cent with dual tracer. Number of sentinel nodes, number of metastatic nodes and duration of surgery were similar between the groups.

Comment: Ultrasound-assisted carbon nanoparticle mapping was non inferior.

Feng Q, Yuan W, Li PT, Tang B, Jia B, Zhou Y et al, for the REAL Study Group.

Some 1240 patients were included in the study, and 1171 included in the analysis. Rates of positive resection margin were: robotic 4 per cent, laparoscopic 7.2 per cent, P=0.023. Complete resection rates were similarly improved: 95.4 versus 91.8 per cent, respectively. Relative postoperative complication rates were 16.2  and 23.1 per cent, P=0.003. Hospital stay was also shorter: 7 versus 8 days, P=0.0001.

Comment: The first real evidence that the robot beats the laparoscope. But what are the long term results, and are the benefits worth the increased costs?

Albers KI, Polat F, Helder L, Panhuizen IF, Snoeck MMJ, Polle S et al, for the RECOVER Study Collaborators.

Ann Surg 2022; 276: e664-e673.

A total of 178 patients were randomized to high or low pressure pneumoperitoneum. Quality of recovery score was significantly improved on day one after low pressure pneumoperitoneum (167 versus 159, P=0.005). Inflammatory markers were also reduced. Pain scores were lower and there were fewer infectious complications.

Comment: But is the view as good?

Abbassi F, Muller SA, Steffen T, Schmied BM, Warschkow R, Beutner U et al.

Br J Surg 2022; 109: 1216–1223.

Sixty patients were randomized to one of two caffeine doses given three times a day, or a control group. There was no measurable effect from caffeine; time to first bowel movement was not improved: 68.2 h after caffeine versus 67.3 h in controls (P=0.887).

Comment; Well there goes the excuse to ask for a coffee after your operation.

Kang B, Ibrahim S, Weil A, Reynolds K, Johnson T, Wilson S et al.

Ann Surg 2022; 276: 975-980.

Patients who had skin surgery with primary wound closure were randomly allocated to one of two different laser therapies for eight weeks or a control group. Fifty-two patients were eligible for analysis. Laser treatment improved wound score after 36 weeks, particularly with regards to scar thickness, stiffness and erythema.

Comment: Whether laser treatment improves wound healing still remains unproven.

Dehghan M, Nauth A, Schemitsch E, Vicente M, Jenkinson R, Kreder H et al, for the Canadian Orthopaedic Trauma Society and the Unstable Chest Wall RCT Study Investigators.

JAMA Surg 2022; 157: 983-990.

The study included 207 patients followed for up to 30 days. Ventilator-free days were higher in the operated group (22.7 versus 20.6; mean difference 2.1 days, P=0.09), and mortality was lower (0 versus 6, P=0.01). The advantage was mainly seen in patients ventilated at time of randomization. Complications rates and length of stay were similar.

Comment: Good study, but relatively modest benefit seen from surgery.

Farber A, Menard MT, Conte MS, Kaufman JA, Powell RJ, Choudhry NK et al, for the BEST-CLI Investigators.

N Engl J Med 2022; 387: 2305-2316.

This international trial enrolled 1830 patients, and the endpoint was a composite of amputation, major reintervention or death. In the group with adequate saphenous vein, after a median of 2.7 years of follow-up, the endpoint was reached by 42.6 per cent of the surgery group compared to 57.4 per cent of the endovascular first group P<0.001). Outcomes were equivalent in those without an adequate vein.

Comment: Great study that confirms what many vascular surgeons have thought for a long time: endovascular treatment is great, but if you are fit enough and have vein for a bypass it will probably last you longer.

Stallard S, Savioli F, McConnachie A, Norrie J, Dudman K, Morrow ES et al.

Br J Surg 2022; 109: 1224–1231.

In this study that included 871 procedures, a single dose of Amoxicillin-clavulanic acid did not reduce the risk of wound infection up to 30 days: 16.2 per cent versus 19.2 per cent in controls, P=0.25.

Comment: not beneficial even in higher risk subgroups – obese or Staph aureus carriers.

NIHR Global Research Health Unit on Global Surgery.

Lancet 2022; 400: 1767-1776.

In this study that included over 13,000 procedures, this simple change reduced the rate of surgical site infection from 18.9 to 16 per cent, P=0.0032.

Comment: I really like studies that appear simple and generalisable. Hospitals around the world with the highest infection rates stand to see the biggest differences.

Tandon S, Ensor ND, Pacilli M, Laird AJ, Bortagaray JI, Stunden RJ et al.

Br J Surg 2022; 109: 1087-1095.

After six weeks, cosmetic scores were best with sutures and worst with glue (P=0.014), but the differences were no longer apparent in this study that included 295 children (333 surgical wounds).

Comment: No strong conclusion about which method should be used.

Son S, Hur H, Hyung WJ, Park Y-K, Lee H-J, Aj JY et al.

JAMA Surg 2022; 157: 879-886.

Some 1050 patients were originally included. After five years, overall survival was similar: open 88.7 per cent versus laparoscopic 88.9 per cent. Late intestinal obstruction was more common after open surgery: 5 versus 2.6 per cent.

Comment: Confirms published three year results that the laparoscopic approach can be recommended.

Asnong A, D’Hoore A, Van Kampen M, Wolthuis A, Van Molhem Y, Van Geluwe B et al.

Ann Surg 2022; 276: 761-768.

Training for one month after stoma closure improved symptoms after six months (low anterior resection symptom category): 47.8 versus 21.3 per cent, P=0.0091, in this study that included 104 patients. This improvement was lost after one year.

Comment: Improves short term recovery, but questionable efficacy in the longer term.

Merdrignac A, Garnier J, Dokmak S, Regenet N, Lesurtel M, Mabrut JY, et al.

Ann Surg 2022; 276: 769-775.

Use of the reinforced stapler actually increased the overall rate of pancreatic fistula compared to the standard device: 83 versus 67.7 per cent (P=0.021), in this study that included 199 procedures. The rates of clinically relevant fistula and other complications was similar.

Comment: Disappointing results.

Ruiz-Tovar J, Llavero C.

Dis Colon Rectum 2022; 65: 406-412.

Use of tocopherol ointment improved pain scores after eight weeks (P=0.018) in this study that included 160 patients. It also reduced recurrence rates after 16 weeks: 2.9 versus 13.2 per cent, P=0.031.

Comment: Worth more trials?

Jin JZ, Bhat S, Park B, Hardy M-H, UnasaH, Mauiliu-Wallis M et al.

Surgery 2022; 172: 41-52.

Sixty-nine RCTs were included. Botulinum toxin was shown to be similarly effective to other medical treatments for initial care. Surgical lateral sphincterotomy had the highest healing rate and was considered definitive after failed medical treatment.

Comment; Clear evidence-based advice.

Sevinç B, Damburaci N, Karahan O.

Dis Colon Rectum 2022; 65:735-741.

Two hundred patients had their pilonidal sinus curetted and then treated with either plasma gel or phenol crystals. Healing was more likely after a single application of plasma – 96 versus 53 per cent; it was also quicker (6 versus 10 days, P<0.001) and recurrence after one year was lower (4 versus 12 per cent).

Comment: Extraordinary result that needs confirmation to ensure it is generalisable.

Akgun E, Caliskan C, Bozbiyik O, Yoldas T, Doganavasargil B, Ozkok S et al.

BJS Open 2022; 6: zrac107.

Although locoregional recurrence was higher at five years (10.1 per cent if over 8 weeks after chemotherapy versus 6.9 per cent if less than 8 weeks, P=0.14), disease-free and overall survival were similar in this study that included 350 patients.

Comment: Remains controversial, but no clear evidence here that waiting for surgery is detrimental.

Ben-Arye E, Hausner D, Samuels N, Gamus D, Lavie O, Tadmor T et al.

Cancer 2022; 128: 3641-3652.

In this study that included 168 patients, acupuncture, with or without other complementary therapies improved the symptoms of neuropathy, particularly hand numbness and discomfort (P=0.007) after six weeks, and improved emotional wellbeing (P=0.04).

Comment: Neuropathy is one of the most unpleasant side effects of chemotherapy, so this study gives optimism that it may at least be minimised by intervention.

Massimimiliano G, Maccauro M, Mariani L, Listorti C, Sigari C, De Vivo A et al.

Cancer 2022; 128: 4185-4193.

Reverse axillary mapping with selective axillary dissection reduced the rate of lymphoedema by 21 per cent (confidence intervals 3-37 per cent, P=0.03) in this study that included 130 patients. Self-reported rates of lymphoedema were not different between the groups.

Comment; Disappointing that the women did not notice a difference.

Fahim M, Couwenberg A, Verweij ME, Dijksman LM, Verkooijen HM, Smits AB.

Br J Surg 2022; 109: 1081-1086.

Some 163 patients were included in the study. Using the sponge to avoid the Trendelenburg (head down) position did not affect postoperative complications or hospital stay. There were no adverse events from the sponge.

Comment: Not worth the investment, unless perhaps it is expected the procedure will be prolonged.

Dohrn N, Yikilmaz H, Laursen M, Khesrawi F, Clausen FB, Sørensen F et al.

Ann Surg 2022; 276: e294-e301.

There was no difference in any of the outcome parameters in this study that included 89 procedures, except that intracorporeal anastomosis took longer to perform 17 vs 13 min, P=0.003.

Comment: Why make the procedure more difficult?

CReST Collaborative Group.

Br J Surg 2022; 109: 1073-1080.

Stenting relieved the obstruction in 82 per cent in this study that included 245 patients. Thirty day outcomes were similar, but stented patients were less likely to need a stoma: 47 versus 68 per cent, P=0.003.

Comment: This is a good study, and an important result, given the difficulties of managing even a temporary stoma.

Stachs A, Bollmann J, Martin A, Stubert J, Reimer T, Gerber B et al.

BJS Open 2022; 6: zrac091.

The new radiology technique did not reduce the risk of positive resection margins (31.7 versus 26.3 per cent, P=0.127) in this study that included 122 procedures.

Comment: No benefit.

Dewulf M, Muysoms F, Vierendeels T, Huyghe M, Miserez M, Ruppert M et al.

Ann Surg 2022; 276: e217-e222.

After five years, 67 patients were available for analysis by clinical examination. The rate of incisional hernias was 49.2% in the no mesh group versus none in the mesh group. Some 5/23 in the no mesh group required reoperation.

Comment: Prophylactic mesh remains controversial, but the evidence of benefit is increasing, and incisional hernia can be very debilitating in this patient group who tend to be elderly.

Stubenrouch FE, Peters LJ, de Mik SML, Klemm PL, Peppelenbosch AG, Schreurs SC et al, on behalf of the OVIDIUS study group.

Eur J Vasc Endovasc Surg 2022; 64: 73-81.

The study included 342 patients with various vascular conditions. Those seen by clinicians trained in how to apply shared decision making (SDM) had improved OPTION-5 scores (an objective tool to assess the level of SDM): 28.7 to 37.8 per cent, P=0.025.

Comment: More support for shared decision making.

Eid MA, Barry MJ, Tang GL, Henke PK, Johanning JM, Tzeng E et al, for the Preferences for Open Versus Endovascular Repair of Abdominal Aortic Aneurysm (PROVE-AAA) Study Team.

JAMA Surg 2022; 157: e222935.

The study included 235 patients with a large AAA suitable for both open and endovascular repair. Patients seen in clinics where a decision aid was used were more likely to receive their preferred type of repair: 95 versus 86 per cent, P=0.03.

Comment: More support for the use of a decision aid.

McDermott M, Bazzano L, Peterson CA, Sufit R, Ferrucci L, Domanchuk K et al.

JAMA 2022; 328: 1315-1325.

After six months, Telmisartan, an angiotensin receptor blocker, did not improve six-minute walking distance compared with placebo in this study that included 114 patients (P=0.08).

Comment: Still no good medicines for claudication.

Bretthauer M, Loberg M, Wieszcy P, Kalager M, Emilsson L, Garborg K et al, for the NordICC Study Group.

N Engl J Med 2022; 387: 1547-1556.

This study included over 84,000 people aged 55 to 64. A single colonoscopy reduced the risk of colorectal cancer by 18% after 10 years (number needed to screen to prevent one colorectal cancer = 455). The risk of death from colorectal cancer and the overall risk of death was not significantly reduced by screening.

Comment: As is so often the case with screening programmes, they can be shown to reduce the rate of the specific condition, but not mortality.

Lindholt JS, Sogaard R, Rasmussen LM, Mejldal A, Lambrechtsen J, Steffensen FH et al.

N Engl J Med 2022; 387: 1385-1394.

Some 46,611 men were randomized. After five years, intention to treat analyses showed no difference in overall mortality rate compared to controls: hazard ratio 0.95, 95 per cent confidence interval 0.9 to 1.0, P=0.06. There was no significant reduction in the rates of stroke, myocardial infarction or aortic aneurysm rupture.

Comment; This is a very disappointing result after the same authors’ previous study showed a significant mortality reduction. It’s back to the drawing board for cardiovascular screening.

Newton K, Dumville J, Briggs M, Law J, Martin J, Pearce L et al, for the PPAC2 Collaborators.

Br J Surg 2022; 109: 951–957.

Packing increased postoperative pain scores (P<0.0001) in this study that included 433 procedures, without increasing the risk of recurrent abscess: 6 versus 3 per cent, P=0.2.

Comment: Simple study with an important message.

Goeteyn J, Pesser N, Houterman S, van Sambeek MR, van Nuenen BFL, Teijink JAW.

Eur J Vasc Endovasc Surg 2022; 64: 119-127.

This study included 50 patients. After three months mean Disability of the Arm, Shoulder and Hand (DASH) score was significantly better in the surgery group: 45.1 versus 64.9, P<0.001. All patients in the conservative group applied for surgery after three months.

Comment: Although small, this is the first study to justify TOS surgery in this group.

de-Madaria E, Buxbaum JL, Maisonneuve P, de Paredes AGG, Zapater P, Guilabert et al for the ERICA Consortium.

N Engl J Med 2022; 387: 989-1000.

This trial was stopped early after interim analysis of 249 patients. Aggressive fluid resuscitation resulted in a higher rate of fluid overload (20.5 versus 6.3 per cent, P=0.004), with no improvement in clinical outcomes.

Comment: Too much fluid.

Moncrieff MD, Bastiaannet E, Underwood B, Francken AB, Garioch J, Damude S et al.

Ann Surg 2022; 276: e208-e216.

Some 388 patients were enrolled into a study comparing standard follow-up with a reduced frequency schedule. There was no difference in recurrence rates between the groups. Three quarters of patients in both groups found their recurrence by self-examination.

Comment: Routine follow-up may not help patients with melanoma; perhaps an approach teaching them self-examination would be better.

Livingstone E, Zimmer L, Hassel JC, Fluck M, Eigentler TK, Loquai C et al, on behalf of the Dermatologic Cooperative Oncology Group.

Lancet 2022; 10358: 1117-1129.

Some 175 patients were randomized into one of three treatment arms. After a median of 49.2 months, recurrence-free survival was 64.2 per cent after the combination of nivolumab and ipilimumab, 31.4 per cent after nivolumab alone and 15 per cent after placebo; P<0.0001. Combination treatment also improved overall survival.

Comment; Combination treatment should be standard in this group.