Randomized clinical trials

van der Heijden JAG, Kalkdijk-Dijkstra AJ, Pierie JPEN, van Westreenen HL, Broens PMA, Klarenbeek BR, et al on behalf of the FORCE trial group.

Ann Surg 2022; 276: 38-45.

Overall, a course of pelvic floor rehabilitation did not improve continence compared to usual care (Wexner score) in this study that included 128 patients. However, several subgroups were identified that did benefit: those with urgency and moderate incontinence postoperatively.

Comment: This sounds like valuable research for patients with a troublesome problem. More research into the subgroups that may benefit is indicated.

Mohamed AH, Thadani S, Mohamed SH, Sidapra M, Smith G, Chetter I, et al.

Br J Surg 2022; 109: 679-685.

There were 18 studies including 2584 legs. Use of compression for 1 to 2 weeks after intervention was associated with improved comfort and quality of life. Use of compression after 1-2 weeks was not beneficial.

Comment: This is helpful, but not novel. Focus should turn to which is the best form of compression.

Toesca A, Sangalli C, Maisonneuve P, Massari G, Girardi A, Baker L, et al.

Ann Surg 2022; 276: 11-19.

Eighty women were included in this study. Robotic surgery took one hour and 18 minutes longer, but was associated with improved postoperative satisfaction, physical and sexual well-being. Complication rates were similar.

Comment: A cost effectiveness analysis is needed here.

Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S et al, for the DYNAMIC Investigators.

N Engl J Med 2022; 386: 2261-2272.

Patients were randomized to adjuvant chemotherapy depending on the presence of circulating DNA (n=302), or a control group (n=153). Fewer patients in the DNA group had chemotherapy (15 versus 28%), without compromising the rate of recurrence-free survival at a median of 37 months.

Comment: The optimal adjuvant treatment for surgically treated colorectal cancer continues to evolve. This study is another step forwards, and helps limit adjuvant therapy to those who will benefit most.

Milne T, Liu C, O’Grady G, Woodfield J, Bissett I. 

Br J Surg 2022; 109: 704–710.

Return of gut function was not improved by prucalopride, a serotonin agonist, 2 mg given before surgery and 2 mg daily for six days, in this study that included 148 patients.

Comment: Disappointing.

Sanabria A, Betancourt-Agüero C, Sánchez-Delgado J, García-Lozano C.

Ann Surg 2022; 276: 66-73.

There were five RCTs with 763 treated patients. Rates of recurrence were similar: 2.7 per cent after additional node dissection and 2.5 per cent after thyroidectomy alone. Node dissection increased the rate of permanent hypoparathyroidism: risk difference 3 per cent.

Comment; This result seems definitive.

Meima-van Praag LM, van Rijn KL, Wasmann KAT, Snijder H, Stoker J, D’Haens GR et al.

Lancet Gastroenterol Hepatol 2022; 7: 617-626.

Some 95 patients were included in this trial. After 18 months, radiological (MRI) healing was higher after surgery with anti-TNF (32 per cent) than anti-TNF alone (9 per cent); P=0.005. In contrast, clinical closure rates were reported as similar: 68 versus 52 per cent, respectively.

Comment: Shouldn’t there have been a surgery only arm for the perfect trial?

Hosoi T, Abe T, Higaki E, Fujieda H, Nagao T, Ito S, et al.

Ann Surg 2022; 276: 30-37.

In this study of 100 oesophagectomies, the rate of postoperative anastomotic stricture was 42 per cent after stapled and none after the Collard technique. Anastomotic leak rates were similar. Quality of life domains concerning swallowing were also significantly better after three months.

Comment: Should this be the standard of care?

Forsberg A, Westerberg M, Metcalfe C, Steele R, Blom J, Engstrand L et al.

Lancet Gastroenterol Hepatol 2022; 7: 513-521.

This study included 278,280 people. More people accepted the faecal testing than colonoscopy (55.5 versus 35.1 per cent). Similar rates of cancer were detected (0.16 and 0.2 per cent, respectively). More  advanced adenomas were detected by colonoscopy (2.05 versus 1.61 per cent, respectively).

Comment: Overall, more cancers were found by the method that was more acceptable to people. Late benefits in disease-specific mortality will be used to decide on the method of choice.

Lastunen KS, Leppäniemi AS, Mentula PJ.

Br J Surg 2022; 109: 588-594.

Some 185 Patients with suspected appendicitis were randomised to imaging with ultrasound followed by CT if needed, or observation. More patients in the imaging group had treatment for appendicitis (72 versus 57 per cent; difference 15, confidence interval 1 to 29 per cent). Rates of complicated appendicitis and negative appendicectomy were similar.

Comment: Some patients with appendicitis do not need surgery; I think we knew that, but this is good science.

Koelemay M, van Reijen NS, van Dieren S, Frans FA, Vermeulen EJG, Buscher HCJL, et al for the SUPER Study Collaborators.

Eur J Vasc Endovasc Surg 2022; 63: 421-429.

The trial was terminated after 240 patients were included and analysed. Compliance with supervised exercise was 50 per cent at six months. After one year, mean maximum walking distance improved similarly in both groups (P=0.69).

Comment: The authors conclude that supervised exercise should be the initial treatment, followed by revascularisation if that is not successful.

Ashrafi M, Ahmad SA, Antoniou SA, Khan T, Antoniou GA.

Eur J Vasc Endovasc Surg 2022; 63: 323-334.

Seven RCTs were examined. Active clot removal strategies resulted in higher patency than anticoagulation alone for proximal (iliofemoral) DVTs. Complication rates were similar. Active treatments have not been shown to reduce post thrombotic syndrome.

Comment: Lots more work to be done here before active clot removal can be recommended routinely.

Takii Y, Mizusawa J, Kanemitsu Y, Komori K, Shiozawa M, Ohue M et al.

Ann Surg 2022; 275: 849-855.

Use of the no touch technique during colon cancer resection failed to improve three year disease-free survival in this multicentre study that included 853 procedures: hazard ratio 1.03, 95 per cent confidence interval 0.8 to 1.3, P=0.59.

Comment: Perhaps other factors are just more important.

Smith S, Ridley S, Gani, J, Carroll, R, Lott, N, Hampton, et al.

Ann Surg 2022; 275: 842-848.

In this study that included 3123 procedures, surgical site infection rates were similar with all skin preparations: povidone iodine with alcohol 10.9 per cent; chlorhexidine with alcohol 11.1 per cent;  aqueous povidone iodine 12.6 per cent. There were no adverse events or differences in secondary outcomes.

Comment: This challenges the perceived benefits of alcoholic skin preparation.

Belramman A, Bootun R, Tang TY, Lane TRA, Davies AH.

JAMA Surg 2022; 157: 395-404.

Pain scores were similar after both of these non tumescent venous ablation methods in this study that included 167 procedures. Both methods improved disease-specific quality of life.

Comment: Late clinical outcomes will be important.

Gao X, Liu Y, Zhang L, Zhou D, Tian F, Gao T et al.

JAMA Surg 2022; 157: 384-393.

The study included 230 patients undergoing major abdominal surgery. Early (three days after surgery) feeding reduced the rate of nosocomial infection from 18.4 to 8.7 per cent (P=0.04) compared with late feeding (eight days after surgery).

Comment: The findings in many studies are consistent: early feeding is beneficial.

Smits FJ, Henry AC, Besselink MG, Busch OR, van Eijck CH, Arntz M et al, for the Dutch Pancreatic Cancer Group.

Lancet 2022; 399: 1867-1875.

This multicentre study included 1748 pancreatic resections. Use of the algorithm reduced the composite risk of complications from 14 to 8 per cent, relative risk 0.48, 95 per cent confidence interval 0.38 to 0.61, P<0.0001.

Comment: There is no substitute for specialist care.

Sessler DI, Pei L, Li K, Cui S, Chan MTV, Huang Y et al, on behalf of the PROTECT Investigators.

Lancet 2022; 399: 1799-1808.

Of the 5013 patients studied, those who had warming had a higher core temperature at the end of the surgery (37.1 versus 35.6 degrees C). Warming did not reduce the rate of complications: 9.9 versus 9.6 per cent, respectively, P=0.69.

Comment: This does not confirm previous studies of benefits from heating, maybe because the unheated patients did not get too cold.

Devereaux PJ, Marucci M, Painter TW,  Conen D, Lomivorotov V, Sessler DI et al, for the POISE-3 Investigators.

N Engl J Med 2022; 386: 1986-1997.

A total of 9535 procedures were studied. Tranexamic acid reduced bleeding complications (11.7 versus 9.1 per cent, P<0.001), but slightly increased the risk of cardiovascular complications (14.2 versus 13.9 per cent, P=0.04).

Comment: Is the trade-off worth it, except for specific procedures with high blood loss?

Goodwin PJ, Chen BE, Gelmon KA, Whelan TJ, Ennis M, Lemieux J et al.

JAMA 2022; 327: 1963-1973.

This study included 3643 non diabetic women, who were followed for a median of 96.2 months. Metformin did not have any advantage for women with ER positive (hazard ratio for invasive disease-free survival 1.01, 95 per cent confidence interval 0.84 to 1.21, P=0.93) or ER negative breast cancer (1.01, 0.79 to 1.3, P=0.92).

Comment: Science is the destruction of a beautiful idea by an ugly fact.

Salminen P, Sippola S, Haijanen J, Nordström P, Rantanen T, Rautio T et al. 

Br J Surg 2022: 109: 503-509.

Seventy-two patients with CT confirmed uncomplicated appendicitis for non operative treatment were included.  The ten day successful treatment rate was 87 per cent with placebo and 97 per cent with antibiotics, (P=n.s)

Comment: So how would a surgeon  today choose to be treated if they had uncomplicated appendicitis?

Hu H, Wang J, Wu Z, Liu Y, Ma Y, Zhao J et al.

Eur J Vasc Endovasc Surg 2022; 63: 103-111.

There were seven RCTs including 1146 procedures. Wearing a compression stocking reduced early postoperative pain (P<0.001), but had no effect on complications, quality of life, vein occlusion rates, or time to return to work.

Comment: Post intervention compression is not necessary.

Katsanos K, Spiliopoulos S, Teichgraber U, Kitrou P, Del Giudice C, Bjorkman P et al.

Eur J Vasc Endovasc Surg 2022; 63: 60-71.

This analysis included 21 RCTs with 3760 treated legs. Amputation was increased in the paclitaxel group: 4 versus 2.7%, hazard ratio 1.66, 95 per cent confidence interval 1.14 to 2.42, P=0.008.

Comment: a previous review suggested an increased death rate; this study suggests amputations are increased too with paclitaxel balloons.

Ahn J-H, Kwak JH, Yoon SG, Yi JW, Yu HW, Kwon H et al.

Surgery 2022; 171: 182-189.

Central lymph node dissection improved the yield of positive nodes in this study of 101 procedures, without affecting complication rates. No patient had a recurrence up to four years after surgery.

Comment: This study is too small to provide answers in the long term.

Leboulleux S, Bournaud C, Chougnet CN, Zerdoud S, Al Ghuzlan, Catargi B et al.

N Engl J Med 2022; 386:923-932.

In this study that included 730 patients, there was no difference in structural or functional outcomes up to three years.

Comment: Too early to conclude much, but a good sized group for longer follow-up.

Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).

Lancet Oncol 2022; 23: 382-392.

Aromatase inhibitors were compared with tamoxifen in premenopausal women with ovarian suppression in a study that included 7030 patients followed for a median of eight years. Aromatase inhibitors reduce recurrence, especially in years 1 to 4 (13.2 per cent absolute risk reduction). Recurrence rates were similar in years 5 to 9. Mortality rates were also similar.

Comment: Initial treatment with aromatase inhibitors in this group seems optimal.

Luke JL, Rutkowski P, Queirolo P, Del Vecchio M, Mackiewicz J, Chiarion-Sileni V et al on behalf of the KEYNOTE-716 Investigators.

Lancet 2022; 399: 1718-1729.

Adjuvant treatment with pembrolizumab every three weeks for up to 17 cycles was examined in the study that included 976 patients with median follow-up of 20.9 months. Treatment improved recurrence-free survival: 85 versus 76%, hazard ratio 0.61, 95 per cent confidence interval 0.45 to 0.82.

Comment: This difference is valuable, but again, it remains to be seen how late outcomes are affected.

Yang Y, Li B, Yi J, Hua R, Chen H, Tan L et al.

Ann Surg 2022; 275: 646-653.

Early results of this study suggest the robotic approach was quicker: 203.8 versus 244.9 minutes, P<0.001. Lymph node dissection was improved but all other clinical comparators and complication rates were similar.

Comment: modest improvement in dissection and duration of surgery, but the key is longer term outcomes.

Onerup A, Andersson J, Angenete E, Bock D, Börjesson M, Ehrencrona C et al.

Ann Surg 2022; 275: 448-455.

The intervention was physical activity for two weeks before and four weeks after surgery. After four weeks there was no demonstrable improvement in recovery in this study that included 761 randomized patients.

Comment: this model of prehabilitation was not effective in this patient group.

Lenet T, Baker L, Park L, Vered M, Zahrai A, Shorr R et al.

Ann Surg 2022; 275: 456-466.

Fourteen trials including 8641 procedures were studied. A restrictive blood transfusion policy did reduce the volume of blood transfused without increasing postoperative morbidity. Two of the trials did show adverse composite outcomes for restrictive transfusion.

Comment: The result isn’t definitive, but further evidence that restrictive transfusion is generally not harmful.

Ruban A, Miras AD, Glaysher M, Goldstone AP, Prechtl CG, Johnson N et al.

Ann Surg 2022; 275: 440-447.

The liner was used for 12 months in this study that included 170 adults with diabetes. Use of the liner reduced glycated haemoglobin by >20 per cent in 54.6 per cent compared to 55.2 per cent in controls (P=0.85).

Comment: Although the liner did have some positive benefits, it failed to improve glycaemic control.

Rosen MJ, Krpata DM, Petro CC, Carbonell A, Warren J, Poulose BK et al.

JAMA Surg 2022; 157: 293-301.

Synthetic mesh significantly reduced the risk of hernia recurrence after two years compared to biological mesh (5.6 versus 20.5 per cent, P=0.01), as well as being cheaper, in this study of 253 procedures.

Comment: No need for biological mesh in this situation; does it have a role at all?

Markmann JF, Aboulijoud MS, Ghobrial RM, Bhati CS, Pelletier SJ, Lu AD et al.

JAMA Surg 2022; 157: 189-198.

Of 293 patients included, machine perfusion reduced the rate of early graft dysfunction (18 versus 31 per cent, P=0.01), and improved use of the liver from donors after cardiac death (51 versus 26 per cent, P=0.007).

Comment: Increasing evidence of the value of this technology.

Bearne M, Volkmer B, Sekhon M, Fisher G, Galea Homes MN, Douiri A, et al for the MOSAIC Trial Collaboration.

JAMA 2022; 327: 1344-1355.

The study included 190 participants randomly allocated to a walking exercise behaviour change intervention by physiotherapists. After three months, those who had received the intervention had an improved 6-minute walking test by around 30m (P=0.009).

Comment: The questions remain whether this improvement is meaningful and durable.

Hemmingson O, Binnermark F, Odensten C, Rutegard M, Franklin KA, Haapamaki MM.

BJS Open 2022; zrac007.

The study was terminated at planned interim analysis when 116 patients were included. Healing was significantly better after Karydakis flap (14 versus 49 days, P<001). Recurrence rates were similar.

Comment: This study has a clear result, but there remain a number of alternatives to the Karydakis flap.

Smedberg J, Graf W, Pekkari K, Hjern F.

BJS Open 2022; zrab140.

A total of 122 patients were available for analysis. All the different procedures improved quality of life, with similar rates of complications. Recurrence rates were higher than expected for all procedures.

Comment: Probably too few patients to make fair comparison, but worrying recurrence rates.