BACKGROUND:The oncological non-inferiority of sentinel lymph node biopsy omission in patients with small, clinically and imaging node-negative (cN0/iN0) breast cancer has been demonstrated for patients undergoing breast-conserving surgery and adjuvant radiotherapy, but not for those undergoing mastectomy. This single-centre, retrospective cohort study compared nodal involvement and adjuvant therapy indications in these patients by use of mastectomy versus breast-conserving surgery. METHODS:Patients with cT1-T2, cN0/iN0, hormone receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer who underwent upfront surgery including sentinel lymph node biopsy between January 2014 and December 2024 were included. Adjuvant therapy indications were estimated using monarchE (abemaciclib), NATALEE (ribociclib), TAILORx and RxPONDER (chemotherapy), and MA.20 and EORTC22922/10925 (nodal irradiation) eligibility criteria. Multivariable logistic regression models identified factors associated with nodal involvement and adjuvant treatment indications. RESULTS:Among 454 patients, 145 (31.9%) underwent mastectomy who more frequently had multifocal tumours (23.5% versus 9.7%), lobular subtype (21.4% versus 11.3%), and grade 2-3 differentiation (73.8% versus 63.8%) compared with those who underwent breast-conserving surgery. Neither nodal involvement (18.6% versus 14.9%; P = 0.149) nor missed indications for adjuvant abemaciclib (7.6% versus 6.1%; P = 0.550), ribociclib (9.7% versus 7.8%; P = 0.586), and nodal irradiation (4.8% versus 4.5%; P = 1.000) differed between patients who underwent mastectomy or breast-conserving surgery. Lymphovascular invasion was independently associated with nodal involvement (odds ratio 6.8, 95% confidence interval 3.7 to 12.8; P < 0.001) and adjuvant treatment indications (CDK4/6 inhibitors: odds ratio 5.1, 2.6 to 10.1; P < 0.001; nodal irradiation: odds ratio 7.1, 3.6 to 14.4; P < 0.001), whereas type of surgery was not. CONCLUSIONS:In patients with cT1-T2, cN0/iN0, hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer, type of breast surgery was not associated with nodal involvement and adjuvant therapy.
INTRODUCTION:Surgical site infection (SSI) after major lower limb amputation (MLLA) significantly affects function, mobility, morbidity, and mortality, alongside broader impacts on healthcare services. Limited data exist on the incidence, prevention, and management of SSI after MLLA. Improving outcomes and wound healing have been identified as research priorities for patients following MLLA. METHODS:Surgical Site Infection in Major Lower Limb Amputation (SIMBA) is an international, prospective, collaborative observational study. Data were collected for consecutive patients undergoing MLLA over 8 months, with 30-day follow-up. Outcomes included the incidence of SSI (defined using Centers for Disease Control and Prevention criteria), wound dehiscence (defined as any partial or complete separation of the incision or flap, with or without infection), further intervention, mortality, adjunct use, and SSI predictors. RESULTS:Validated data for 1314 MLLAs from 46 centres in the UK (34), Europe (9), Australasia (2), and Asia (1) were collected, comprising 643 (48.9%) transfemoral, 41 (3.1%) through-knee, and 628 (47.8%) transtibial amputations. The most common indications were ischaemia (56.6%, 742) and uncontrolled infection (22.3%, 293). The incidences of SSI and wound breakdown were 10.9% (135 of 1238) and 16.7% (204 of 1217), respectively. Low glomerular filtration rate, cardiac disease, dirty/infected wound class, and transtibial amputations were independent predictors of SSI. SSI was associated with increased postoperative morbidity, wound breakdown, further intervention, and delays in fitness for discharge. The 30-day mortality rate was 7.0% (92 of 1314), with no significant association with SSI. CONCLUSION:SSI and wound breakdown are common following MLLA, and are associated with increased morbidity, delayed recovery, and revision surgery. These findings identify patient- and procedure-specific factors associated with elevated SSI risk, and a lack of procedure-specific evidence, revealing critical gaps in SSI prevention strategies. Addressing these are essential to improve patient outcomes, reduce healthcare costs, and guide future research.
BACKGROUND:The contralateral limb is at risk after major lower limb amputation (MLLA) for peripheral arterial disease or diabetes mellitus due to the systemic nature of these diseases, with a subsequent bilateral MLLA required in over 10% of patients. The present study aims to determine the natural history of the contralateral limb after MLLA for peripheral arterial disease or diabetes. METHODS:A single-centre retrospective cohort study of patients undergoing MLLA for peripheral arterial disease or diabetes between January 2013 and July 2023 was performed. The primary outcome was clinically relevant contralateral limb disease (CR-CLD), defined as symptomatic disease of the contralateral limb or asymptomatic disease requiring prophylactic intervention. Statistical analysis used both survival analysis and competing risk modelling techniques. RESULTS:A total of 531 patients were included, with 175 (33%) going on to develop CR-CLD. The leading aetiology was chronic limb-threatening ischaemia, with 79.7% of these patients presenting with tissue loss. A total of 67% of CR-CLD presented by 1 year and 81% by 2 years after index MLLA. A diagnosis of diabetes, chronic peripheral arterial disease, ischaemic heart disease, and previous contralateral vascular intervention were identified as independent risk factors for the development of CR-CLD on multivariable analysis. A total of 72.6% of patients with CR-CLD underwent intervention, 28.6% of these requiring contralateral MLLA. For those not undergoing intervention, 56.3% were turned down due to co-morbidity or frailty. CONCLUSION:CR-CLD after MLLA is common, and presents early after index MLLA but with late-stage clinical disease. High-risk groups are identifiable. Outcomes are poor, with many patients undergoing a contralateral MLLA or being palliated.
BACKGROUND:Although recent guidelines recommend parathyroid autotransplantation for inadvertent excision of ischaemic glands, its benefit for the recovery of parathyroid function after total thyroidectomy remains uncertain. METHODS:This retrospective study analysed patients with normal parathyroid hormone (PTH) concentrations who underwent primary total thyroidectomy at Sun Yat-sen University Cancer Center between September 2013 and November 2024. Postoperative hypoparathyroidism and PTH trajectories were compared across three groups: autotransplantation, inadvertent parathyroid resection, and all glands preserved in situ. Long-term recovery was modelled using generalized additive mixed models (GAMM). RESULTS:Of 7539 eligible patients, 441 (5.8%) underwent autotransplantation and 814 (10.8%) had inadvertent parathyroid resection. Higher proportions of parathyroid autotransplantation or inadvertent resection were observed among patients undergoing central neck dissection, particularly bilateral procedures. Postoperative (POD) 1 hypoparathyroidism (PTH < 15 pg/ml) occurred in 64.9% and 62.4% of patients in the autotransplantation and inadvertent resection groups, respectively, compared with 50.7% of patients with in situ gland preservation. At 1 month, hypoparathyroidism was present in 17.1% and 22.5% of patients in the autotransplantation and inadvertent resection groups, respectively, compared with 11.9% of patients with in situ gland preservation. Among patients with POD1 hypoparathyroidism, the recovery of parathyroid function at 1 month was similar in the autotransplantation and in situ preservation groups (∼72% and ∼74%, respectively), but lower in the group with inadvertent resection (∼62%). GAMMs showed poorest long-term recovery after inadvertent resection, whereas recovery in the autotransplantation group approached in situ preservation without clear superiority. CONCLUSIONS:Parathyroid autotransplantation improved long-term recovery compared with inadvertent resection but did not outperform in situ preservation. These findings support autotransplantation for inadvertently resected parathyroid glands, but not for devascularized glands.
BACKGROUND:Rectal cancer with mesorectal fascia involvement (MRF+) requires neoadjuvant downstaging and/or induction therapy, followed by (beyond) total mesorectal excision and/or multivisceral resection (MVR) depending on response. Decisions on the need for MVR and plane of dissection vary. This nationwide cross-sectional study aimed to evaluate treatment and oncological outcomes in MRF+ primary rectal cancer and the impact of MVR types. METHODS:Using collaborative research, extensive clinical data on all rectal cancer resections in 2016 across 67 Dutch hospitals were retrospectively collected. Patients with cT3-4 MRF+ primary rectal cancer and standardized re-assessment of primary and restaging magnetic resonance imaging were selected. Patients were categorized by radiologically involved structures or organs and by MVR type. The primary outcome measures were microscopically positive margin (R1) resection rate, 4-year cumulative local recurrence, and 4-year overall survival. RESULTS:Of 3178 patients registered, 571 cT3-4 MRF+ were selected resections, 125 of which were MVR. Tumours remained MRF+ on restaging magnetic resonance imaging in 76.4%. The overall R1 rate was 11.8% (9.7% in cT3/4a MRF+ and 17.9% in cT4b tumours). The R1 rate after MVR was 20.8%. Overall, the 4-year local recurrence rate was 15.1% and 4-year overall survival 67.5%. When comparing total mesorectal excision with MVR and/or beyond total mesorectal excision, the local recurrence rate was 12.7% versus 24.2% (P = 0.001), and overall survival 71.3% versus 53.7% (P < 0.001). Patients with radiological anterior involvement seemed to have a higher R1 rate compared with other locations. Anterior resections in both men and women appeared to be associated with relatively low local recurrence and high overall survival, whereas other resections resulted in numerically lower R1 rates, but worse long-term oncological outcomes. However, neither anatomical location of MRF+ and/or ingrowth nor MVR type was significantly associated with the primary outcomes. Pelvic sepsis (hazard ratio 1.533, 95% confidence interval 1.0 to 2.3) and positive margins (hazard ratio 1.837, 1.2 to 2.8) were independent predictors of worse overall survival. CONCLUSION:Oncological outcomes of MRF+ rectal cancer were not significantly influenced by the anatomical location of MRF involvement or MVR type.
BACKGROUND:Enhanced recovery after surgery (ERAS) pathways improve postoperative outcomes across surgical specialties, but the impact of ERAS compliance on outcomes after liver resection remains unclear. A retrospective cohort study of consecutive patients undergoing liver resection in an ERAS-certified centre was conducted to examine the association between overall and item-specific ERAS compliance and postoperative morbidity and length of hospital stay (LOS). METHODS:This retrospective cohort included elective liver resections performed between 2020 and 2024 at an ERAS-certified centre of excellence. ERAS compliance was prospectively recorded and categorized as high (≥ 70%) versus low/moderate (< 70%). Primary outcomes were any postoperative complication, major morbidity (Clavien-Dindo grade ≥ IIIa), and LOS; these were assessed by univariable and multivariable analyses, including a sensitivity analysis using an early compliance score excluding postoperative items. RESULTS:Data from 637 consecutive liver resections were analysed. Mean (standard deviation) overall ERAS compliance was 64.0 (10.2%) and remained stable over time. High compliance was associated with fewer complications (51% (104) versus 69.8% (303); odds ratio (OR) 0.45; 95% confidence interval (c.i.) 0.30 to 0.67; P < 0.001), lower major morbidity (7.25% (15) versus 12.8% (55); OR 0.25, 95% c.i. 0.10 to 0.64; P = 0.001), and shorter LOS (7.42 versus 10.62 days; mean difference -3.21 days; P < 0.001). In multivariable analyses, high overall compliance was associated with major morbidity (OR 0.16; 95% c.i. 0.04 to 0.56; P = 0.005). Minimally invasive surgery independently decreased overall complications (OR 0.41; 95% c.i. 0.21 to 0.75; P = 0.005), major morbidity (OR 0.13; 95% c.i. 0.01 to 0.66; P = 0.050), and LOS (β = -2.31 days; P = 0.020). In sensitivity analyses, high compliance remained associated with fewer complications (OR 0.62; 95% c.i. 0.40 to 0.96; P = 0.035). Higher intraoperative intravenous fluid volume independently predicted morbidity and prolonged LOS (P < 0.001). CONCLUSION:Higher ERAS compliance after liver resection is associated with lower severe morbidity and shorter LOS. Prioritizing potentially high-impact items may maximize recovery benefits.
BACKGROUND:Evidence-based medicine (EBM) was conceived to support decisions for individual patients by integrating the best available evidence, clinical expertise, and patient values. However, the application of EBM in many fields has become associated with rigid algorithms and guideline pathways, sometimes interpreted as prescriptive rather than as aids to decision-making. Hepatocellular carcinoma (HCC) offers an informative case study of this dichotomy. This paper traces the evolution of personalized decision-making in HCC over two decades and its implications for the future of EBM. METHODS:This is a narrative, conceptual review. Rather than a systematic synthesis, it draws selectively on landmark staging frameworks, guidelines, and methodological literature to construct a schematic account of how clinical reasoning in HCC has evolved. RESULTS:HCC decision-making has evolved through a sequence of schematic frames: from stage-centred algorithms (the Ptolemaic frame), to recognition of differential treatment effects (the Copernican shift), to multiparametric expert deliberation (the Newtonian perspective), and finally to dynamic, time-dependent, bidirectional strategies (the Einsteinian perspective). The expansion of systemic immunotherapy options has reinforced this bidirectional logic while complicating stage reassessment. This trajectory culminates in a Heisenberg moment, in which uncertainty is acknowledged as intrinsic to individual decisions. The multiparametric therapeutic hierarchy, developed within multidisciplinary HCC practice, reflects this maturation towards a personalized, transparent, context-sensitive approach. CONCLUSION:HCC is a paradigmatic example of personalized decision-making in complex, multidisciplinary care. The future of EBM lies not in choosing between algorithms and personalization, but rather in transparent approaches that apply evidence rigorously while acknowledging uncertainty and respecting patient values and local context.
BACKGROUND:The study evaluated the associations of individual and combined lifestyle-related risk factors with long-term recurrence after primary and incisional ventral hernia repair compared with patients without lifestyle-related risk factors. METHODS:This nationwide study used registry and survey data from Danish patients who underwent ventral hernia repair between 2014 and 2024. Patients were identified in the Danish National Patient Register, after which digital surveys were distributed. Survey data on recurrence and lifestyle factors were linked with data from the Danish Ventral Hernia Database and Danish National Patient Register. The outcome was hernia recurrence (reoperation or self-reported). Average treatment effects were estimated using adjusted logistic regression and standardization (G-computation). RESULTS:In total, 18 959 patients were included in the study, comprising 15 186 patients undergoing primary ventral repair and 3773 undergoing incisional hernia repair (response rate 78%). More than half the patients reported one or more lifestyle-related risk factors. For primary ventral hernia repair, the adjusted population-averaged recurrence prevalence was 14% without lifestyle-related risk factors. Smoking, obesity, and their combination were associated with a higher recurrence prevalence, with absolute differences of 3% (95% confidence interval (c.i.) 0% to 5%), 3% (95% c.i. 2% to 5%), and 6% (95% c.i. 2% to 10%), respectively. Other lifestyle combinations showed similar trends but were less consistently significant across analyses. For incisional hernia repair, the adjusted population-averaged recurrence prevalence was 25% without lifestyle-related risk factors. Smoking and obesity were associated with absolute increases in recurrence prevalence of 6% (95% c.i. 0% to 11%) and 5% (95% c.i. 1% to 9%), respectively. CONCLUSIONS:Smoking and obesity were associated with a higher recurrence prevalence after primary ventral and incisional hernia repair. Associations for combined lifestyle factors were less consistent overall. Given the number of analyses performed, the findings should be interpreted with caution.
BACKGROUND:Axillary lymph node dissection (ALND) in breast cancer causes substantial arm morbidity and long-term functional impairment. Less extensive axillary surgery, such as targeted axillary dissection (TAD), significantly reduces this risk. Although omission of ALND is standard in clinically node-negative disease with limited sentinel node involvement, this is not the case for patients with clinically node-positive disease undergoing upfront surgery. The aim of the SENOMAC-ULTRA trial is to evaluate whether TAD can safely replace ALND in patients with clinically node-positive breast cancer receiving upfront surgery. METHODS:SENOMAC-ULTRA is a prospective, international, multicentre, randomized non-inferiority trial. Adults with stage II-III invasive breast cancer and axillary metastases detectable by ultrasound and confirmed by fine needle aspiration or core biopsy are eligible for inclusion. Participants are randomized 1 : 1 to TAD (removal of marked metastatic nodes plus sentinel lymph node biopsy) or standard ALND. The primary endpoint is recurrence-free survival, assessed for non-inferiority using a Cox proportional hazards model. Secondary endpoints include overall survival, locoregional recurrence, regional nodal recurrence, distant relapse-free survival, invasive breast cancer-free survival, patient-reported arm morbidity, and health-related quality of life, as well as performance measures of axillary ultrasound and marking techniques. A sample size of 1380 patients has been calculated to provide 81% power to exclude a hazard ratio > 1.47 for recurrence-free survival at 5 years, adopting a non-inferiority margin of 4.5%. Follow-up is planned for 10 years. The trial protocol has been approved by the Swedish Ethical Review Authority (Dnr 2025-07730-01); each participating country will obtain local ethics approval. CONCLUSION:It is anticipated that the SENOMAC-ULTRA trial will fill an important knowledge gap guiding the surgical management of patients with clinically node-negative breast cancer. Registration number: NCT06869629 (https://clinicaltrials.gov).
BACKGROUND:KRAS mutations are common in colorectal cancer, but the impact of KRAS mutation subtypes on treatment response remains poorly understood. This research aimed to investigate whether different KRAS mutations influence pathological complete response (pCR) rates after neoadjuvant chemoradiotherapy in locally advanced rectal cancer (LARC). METHODS:A systematic review and meta-analysis of studies describing genetic determinants of response to neoadjuvant chemoradiotherapy in LARC was conducted, searching for manuscripts published up to March 2026. The primary outcome of interest was the odds ratio for KRAS mutations and pCR. A random-effects model estimated the pooled effect size of KRAS mutations within and outside exon 2 on pCR. Genomic data sets were analysed to investigate the molecular characteristics of KRAS exon 2 and non-exon 2 mutant rectal cancers and their impact on overall and disease-free survival. Finally, a transcriptomic data set was analysed to elucidate the underlying response mechanisms. RESULTS:Out of 11 537 manuscripts identified, 15 studies (3354 patients) were included in the meta-analysis. The odds ratio for any KRAS mutation and pCR was 0.48 (95% confidence interval 0.32 to 0.70), indicating reduced odds of pCR in KRAS-mutant LARC. Subgroup analysis revealed that KRAS mutations in exon 2 accounted for this effect, whereas variants outside exon 2 had no influence (odds ratio 0.96, 95% confidence interval 0.11 to 8.49). Analysis confirmed poorer disease-free survival in patients with exon 2 alterations (P = 0.019) as well as poorer overall survival (P = 0.047). Transcriptomic analysis revealed that non-exon 2 KRAS-mutant tumours were enriched for inflammatory signalling pathways, suggesting that these tumours represent a subgroup with high immune infiltration. CONCLUSION:The presence of KRAS mutations adversely affects pCR odds after neoadjuvant chemoradiotherapy in LARC, but this effect is specific to exon 2 mutations.
BACKGROUND:Quality of life (QoL) and bowel function are key outcomes in mid- and low rectal cancer. The comparative impact of laparoscopic total mesorectal excision (LaTME) versus transanal total mesorectal excision (TaTME) on patient-reported outcomes and long-term oncological results in randomized trials remains unclear. METHODS:This prospective multicentre randomized trial enrolled patients with resectable mid-low rectal adenocarcinoma. QoL was assessed using the 30- and 29-item European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaires EORTC QLQ-C30 and QLQ-CR29, respectively) and bowel dysfunction was assessed using the Low Anterior Resection Syndrome (LARS) score before surgery and at the long-term follow-up (≥ 12 months after index surgery). The sample size calculation was based on the primary endpoint from the original randomized clinical trial (composite conversion outcome), for which 116 patients were required. The minimum oncological follow-up was 5 years. Modified intention-to-treat (mITT) and per-protocol analyses were prespecified. RESULTS:In all, 116 patients were randomized (LaTME, 57; TaTME, 59); 105 patients were included in the mITT analysis. Sixty-seven valid QoL questionnaires were obtained (63.8%). Postoperative global health status (EORTC QLQ-C30) was high in both groups (median score 83.3) with no significant differences between them, and functional scales remained near maximum, with improved emotional functioning after LaTME only. Using the EORTC QLQ-CR29 score, TaTME showed higher postoperative stool frequency, flatulence, and faecal incontinence, with similar body image and sexual function. LARS scores (assessed only in patients without a permanent stoma) were comparable between LaTME and TaTME (median 24 versus 27, respectively), with major LARS (score 30-42) in 30 and 44% of LaTME and TaTME patients respectively. There were no significant differences between LaTME and TaTME in local recurrence (6.4% versus 3.7%, respectively), distant recurrence (14.9% versus 18.5%, respectively), disease-free survival, and overall survival. CONCLUSION:Overall QoL and bowel function remained high, with no detectable between-group differences. TaTME was associated with a higher burden of specific evacuatory symptoms on the EORTC QLQ-CR29. Long-term oncological outcomes did not differ significantly between techniques. Registration number: NCT02550769 (http://www.clinicaltrials.gov).
BACKGROUND:The multicentre ALaCaRT and ACOSOG Z6051 randomized trials were unable to demonstrate non-inferiority of laparoscopic versus open surgery for rectal cancer with respect to a composite pathology metric indicating successful resection. Neither trial was individually powered to detect differences in long-term recurrence or survival. This planned meta-analysis determined long-term oncological outcomes of laparoscopic versus open proctectomy for rectal adenocarcinoma. METHODS:This prospective meta-analysis included individual patient data from patients with cT1-3 N0-2 M0 rectal adenocarcinoma enrolled in the ALaCaRT and ACOSOG Z6051 trials. Pathologically successful resection was defined as complete or near-complete total mesorectal excision, a clear circumferential resection margin (CRM; > 1 mm), and a clear distal resection margin (> 1 mm). The non-inferiority margin for disease-free survival (DFS) was an absolute difference of 5% at least 3 years after surgery. RESULTS:The combined data set included 935 patients (65.6% men, mean age 60.7 years, mean body mass index 26.7 kg/m2) randomized to open (457 patients) or laparoscopic (478 patients) proctectomy. Pathologically successful resection was lower in the laparoscopic than open group (85.1% versus 89.9%, respectively; pooled estimate 4.6% difference; 95% confidence interval (c.i.) -8.6% to -0.5%). The median follow-up was 60.2 (interquartile range 49.9-61.1) months. Three-year DFS was 75.2% (95% c.i. 71.1% to 79.2%) and 76.5% (95% c.i. 72.5% to 80.6%) for the laparoscopic and open groups, respectively (pooled estimate difference -1.5%; 95% c.i. -7.2% to 4.2%). Non-inferiority of laparoscopic surgery was not demonstrated because the lower one-sided 95% c.i. (-6.3% to 100%) crossed -5%. Three-year locoregional recurrence was higher in laparoscopic than open group (5.4% (95% c.i. 3.3% to 7.5%) versus 2.0% (95% c.i. 0.7% to 3.4%), respectively; pooled estimate 3.1% difference (95% c.i. 0.6% to 5.6%)). A clear CRM was the most significant and only pathological predictor of both DFS (P < 0.0001) and overall survival (P < 0.0001). CONCLUSION:Laparoscopic proctectomy led to a lower rate of pathologically successful resection and a higher rate of locoregional recurrence at 3 years. The possibility of subsequent poorer DFS or overall survival rate requires further evaluation, because this analysis was not specifically powered for these endpoints.
BACKGROUND:There are disparities in the prevalence of peripheral arterial disease (PAD). This study examined socioeconomic, ethnic, and geographical variations in population-based revascularization rates for PAD and the associations between these rates and PAD-related major lower limb amputation. METHODS:Hospital admissions in England (April 2008-March 2018) for revascularization for moderate and severe PAD, and for major lower limb amputation, were examined using a population-based study design and Poisson and logistic regression. RESULTS:In the 10-year time span, there were 309 839 revascularization admissions (44% severe PAD, 56% moderate PAD; > 90% White ethnicity) and 38 601 major lower limb amputations from a population aged ≥ 25 years of 36 million. Overall, 39.9% of patients with amputation had previously had revascularization. Revascularization rates for moderate and severe PAD and amputation rates increased with increasing socioeconomic deprivation. The ratio of amputations to revascularizations also increased with increasing deprivation, and patients admitted for revascularization from more deprived areas had more severe PAD. Revascularization rates for patients of Black ethnicity were generally substantially lower than those for patients of White ethnicity, the only exception being for severe PAD in patients aged ≥ 65 years. The amputation rate was also lower but the ratio of amputations to revascularizations, and the percentage of revascularization admissions with severe PAD, were higher for patients of Black relative to White ethnicity. Revascularization and amputation rates were substantially lower, and the ratio of amputations to revascularizations was also lower, for patients of Asian relative to White ethnicity, but patients of Asian ethnicity admitted for revascularization had a marginally higher percentage of severe PAD. There was substantial variation in revascularization and amputation rates across Integrated Care Board areas, with high rates in the North and in parts of the Midlands and South West. There was also wide variation in the ratio of amputations to revascularizations. CONCLUSION:There were substantial socioeconomic, geographical and ethnic disparities in revascularization rates in England.
BACKGROUND:Gallbladder cancer (GBC) is a rare but aggressive disease, and surgical resection remains the only potential curative treatment. Although tumour-related effects on prognosis are well established, the impact of age is less understood. This study aimed to evaluate the influence of age on overall survival (OS), recurrence-free survival (RFS), and perioperative complications in GBC. METHODS:Data from patients undergoing curative resection for GBC at 133 centres across 41 countries between 2010 and 2020 were analysed to determine the prognostic association of age ≥ 75 years with OS, RFS, and morbidity. Propensity score matching was used to address confounders between the two age groups. RESULTS:In all, 4138 patients underwent surgery for GBC. Patients with macroscopic tumour remaining after surgery, metastatic disease, only high-grade dysplasia were excluded leaving 3676 patients for analyses. Full data on all relevant parameters was available for 2072 patients aged < 75 years and 633 patients aged ≥ 75 years. Patients aged ≥ 75 years had more co-morbidities, underwent less extensive surgery or lymphadenectomy, and received adjuvant chemotherapy less frequently than younger (< 75 years) patients. Age ≥ 75 years was associated with poorer OS in both the unmatched (hazard ratio (HR) 1.34; 95% confidence interval (c.i.) 1.14 to 1.56; P < 0.001) and matched cohorts (HR 1.31; 95% c.i. 1.12 to 1.54; P < 0.001) cohorts, but was not associated with RFS or 1-year survival. Tumour extent and nodal stage had the greatest association with OS and RFS. Age was not associated with increased complications in either the unmatched (odds ratio (OR) 1.11; 95% c.i. 0.85 to 1.45; P = 0.400) or matched (OR 0.90; 95% c.i. 0.72 to 1.12; P = 0.353) cohorts. CONCLUSIONS:Older adults received less extensive surgery and infrequent adjuvant chemotherapy. Age ≥ 75 years was associated with poorer OS following GBC resection but comparable complication rates to younger adults. Older adults of sufficient fitness should not be denied curative treatment based on age, and oncological benefit should be balanced against perioperative risk to personalize treatment and optimize surgical outcomes.
BACKGROUND:Postoperative hypoparathyroidism is the most common complication after total thyroidectomy, and is associated with impaired quality of life and increased long-term healthcare use. Indocyanine green fluorescence imaging enables real-time intraoperative assessment of parathyroid perfusion, potentially improving gland preservation. However, its cost-effectiveness in routine surgical practice has not been formally evaluated. METHODS:A model-based cost-effectiveness analysis was conducted comparing angiography-guided thyroidectomy with conventional thyroidectomy from the perspective of the Spanish National Health System. A state-transition Markov model simulated long-term outcomes for adults undergoing thyroidectomy, incorporating the incidence of transient and permanent hypoparathyroidism, health-related quality-adjusted life-years, and direct medical costs. The model used contemporary surgical data, included a 35-year time horizon, and discounted costs and effects at 3.5% annually. Probabilistic and deterministic sensitivity analyses were used to assess parameter and structural uncertainty. Cost-effectiveness was judged at a willingness-to-pay threshold of €30 000 per quality-adjusted life-year. RESULTS:Angiography-guided thyroidectomy was associated with lower lifetime healthcare costs (€563.7 million versus €613.2 million) and greater health benefits (310 997 versus 299 107 quality-adjusted life-years), yielding a gain of 11 889 quality-adjusted life-years and €49.5 million in cost savings. Angiography-guided thyroidectomy dominated conventional thyroidectomy in all sensitivity analyses, with an incremental net monetary benefit of €406.2 million (95% uncertainty interval €381.7 million to €431.5 million). Scenario and joint probabilistic analyses confirmed robustness under alternative utility values and surgical outcomes. CONCLUSION:Angiography-guided thyroidectomy may be a cost-saving innovation within publicly funded healthcare systems by reducing the incidence and chronic burden of postoperative hypoparathyroidism. These findings support broader adoption of fluorescence-guided surgery and underscore the need for real-world implementation studies to validate cost-effectiveness, and inform training and procurement strategies.
BACKGROUND:The definition of liver perfusion failure (LPF) following pancreatic surgery and its perioperative risk factors remain unclear. This study aimed to define clinically significant LPF among patients undergoing partial pancreatoduodenectomy (PD) or total pancreatoduodenectomy (TP) and to identify perioperative risk factors associated with its incidence. METHOD:Patients undergoing partial PD/TP between 2014 and 2017 were identified from a prospectively maintained database. Various criteria for identifying LPF over time (that is, on postoperative days 1-4) were evaluated for clinical significance based on their association with liver-specific complications. Univariable and multivariable analyses were performed to determine the association of LPF with relevant outcome parameters and perioperative risk factors. RESULTS:In the analysis of 815 patients, the optimal LPF model was identified as an increase in liver enzymes (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) ≥ 200 U/l for two consecutive days (LPF_2d). LPF severity was categorized as no LPF (AST/ALT < 200 U/l), mild (AST/ALT ≥ 200-< 500 U/l), moderate (AST/ALT ≥ 500-< 1000 U/l), and severe (AST/ALT ≥ 1000 U/l). In all, 81 patients were identified with LPF: 29 (3.6%), 29, and 23 with mild, moderate, and severe LPF, respectively. The occurrence of LPF was significantly associated with postoperative outcomes, including liver-specific complications, liver failure, need for radiological interventions, length of intensive care unit stay, and 90-day mortality. Multivariable analysis identified coeliac axis stenosis, arterial resection, and duration of the operation as independent risk factors for LPF. CONCLUSION:LPF is an underrated and serious postoperative complication in patients undergoing partial PD or TP. Based on the proposed definition (LPF_2d), LPF occurs in 9% of patients, is clinically relevant, and is associated with postoperative complications.
BACKGROUND:Patients undergoing metabolic bariatric surgery are at risk of both venous thromboembolism (VTE) and bleeding complications, but the optimal thromboprophylaxis strategy remains uncertain. Therefore, this retrospective cohort study evaluated perioperative outcomes depending on the perioperative thromboprophylaxis strategy. METHODS:This study used data from the validated nationwide Scandinavian Obesity Surgery Registry, including all primary bariatric procedures in Sweden between 2008 and 2023. Exposures were timing of initiation (preoperative, postoperative, other) and the duration of thromboprophylaxis (< 7, 7-10, 11-14, or > 14 days). The primary outcome was VTE; secondary outcomes were intraoperative and postoperative bleeding. Outcomes were analysed using logistic regression models, adjusting for demographic, clinical, and surgical covariates. RESULTS:Among 83 801 patients (76.9% female, mean age 40.9 years, mean body mass index 41.8 kg/m2), the incidences of VTE, intraoperative bleeding, and postoperative bleeding were 0.1% (76 patients), 0.7% (577), and 1.6% (1373), respectively. No statistically significant associations were observed between the timing of thromboprophylaxis and VTE, or between thromboprophylaxis duration and either VTE or postoperative bleeding. Initiation of prophylaxis after surgery was associated with a lower risk of intraoperative bleeding than preoperative initiation (odds ratio 0.52; 95% confidence interval 0.37 to 0.74). Risk factors for VTE included previous VTE, intraoperative bleeding, and longer operating time, whereas risk factors for postoperative bleeding included higher age, male sex, cardiovascular co-morbidity, and antidepressant use. CONCLUSION:The overall incidence of thrombotic complications after metabolic bariatric surgery was low, whereas bleeding events were more common. Compared with preoperative thromboprophylaxis initiation, postoperative initiation was associated with reduced intraoperative bleeding, whereas no increase in VTE was detected.
BACKGROUND:The Lancet Oncology Commission on Global Cancer Surgery recommended that access to and the quality of surgical care be improved. This study aimed to understand differences in surgical quality between emergency and elective resection among patients with potentially curative colorectal cancer. METHODS:This preplanned secondary analysis included patients undergoing only curative-intent surgery for colorectal cancer from three contemporary global prospective cohort studies (GlobalSurg-3, 5506 patients; CovidSurg-Cancer, 6719 patients; APOLLO, 876 patients) registered from 2018 to 2023. Hierarchical multilevel logistic regression models quantified associations between the urgency of surgery (elective versus emergency) and surgical quality, measured by margin-positive resection, adjusting for patient, disease, and health system factors. Bootstrap multivariable simulations evaluated effect modification by country income level, cancer stage, and location. RESULTS:Of the 45 699 patients registered, 13 101 across 95 countries were included in this analysis. Overall, 678 patients (5.4%) had margin-positive resections, with higher rates in the emergency than elective surgery group (13.7 versus 4.5%; P < 0.0001). In adjusted multilevel models, emergency surgery was associated with increased odds of margin-positive resections (adjusted odds ratio 2.45, 95% confidence interval (c.i.) 1.86 to 3.22), consistent across all country income groups and robust to alternative health system indicators. Bootstrap-derived absolute risk differences revealed the greatest disparities in patients with stage III-IV rectal cancers, with absolute differences of 12.6% (95% c.i. 10.2 to 15.7) in high-income countries, 19.0% (95% c.i. 13.6 to 23.9) in upper middle-income countries, and 14.1% (95% c.i. 10.9 to 16.5) in lower middle- and low-income countries. Variance decomposition demonstrated that hospital- and country-level factors accounted for 76% of the explained variation in surgical quality. CONCLUSION:Emergency surgery was associated with a two- to threefold increase in the risk of margin-positive resections globally, independent of resource availability, highlighting a neglected area of global surgical practice. These findings challenge the assumption that poorer outcomes after emergency surgery are due to advanced disease stage. For patients presenting as an emergency with potentially curative resection, enhanced decision-making around resectability, ensuring specialist surgeon availability, and developing bridge-to-surgery pathways represent immediate, low-cost strategies to improve global cancer outcomes.
