Study design in evidence-based surgery:What is the role of case-control studies?

Randomized controlled trials(RCTs) are the gold standard in terms of study design, however, in the surgical setting conducting RCTs can often be unethical or logistically impossible. Case-control studies should become the major study design used in surgical research when RCTs are unable to be conducted and definitely replacing case series which offer little insight into surgical outcomes and disease processes.

Ampullary cancer of intestinal origin and duodenal cancer-A logical clinical and therapeutic subgroup in periampullary cancer

Periampullary cancers include pancreatic, ampullary, biliary and duodenal cancers. At presentation, the majority of periampullary tumours have grown to involve the pancreas, bile duct, ampulla and duodenum. This can result in difficulty in defining the primary site of origin in all but the smallest tumors due to anatomical proximity and architectural distortion. This has led to variation in the reported proportions of resected periampullary cancers. Pancreatic cancer is the most common cancer resected with a pancreaticoduodenectomy followed by ampullary(16%-50%), bile duct(5%-39%), and duodenal cancer(3%-17%). Patients with resected duodenal and ampullary cancers have a better reported median survival(29-47 mo and 22-54 mo) compared to pancreatic cancer(13-19 mo). The poorer survival with pancreatic cancer relates to differences in tumour characteristics such as a higher incidence of nodal, neural and vascular invasion. While small ampullary cancers can present early with biliary obstruction, pancreatic cancers need to reach a certain size before biliary obstruction ensues. This larger size at presentation contributes to a higher incidence of resection margin involvement in pancreatic cancer. Ampullary cancers can be subdivided into intestinal or pancreatobiliary subtype cancers with histomolecular staining. This avoids relying on histomorphology alone, as even some poorly differentiated cancers preserve the histomolecular profile of their mucosa of origin. Histomolecular profiling is superior to anatomic location in prognosticating survival. Ampullary cancers of intestinal subtype and duodenal cancers are similar in their intestinal origin and form a logical clinical and therapeutic subgroup of periampullary cancers. They respond to 5-FU based chemotherapeutic regimens such as capecitabine-oxaliplatin. Unlike pancreatic cancers, KRAS mutation occurs in only approximately a third of ampullary and duodenal cancers. Future clinical trials should group ampullary cancers of intestinal origin and duodenal cancers together given their similarities and their response to fluoropyrimidine therapy in combination with oxaliplatin. The addition of anti-epidermal growth factor receptor therapy in this group warrants study.

Evidence-based assessment of proton-pump inhibitors in Helicobacter pylori eradication: A systematic review

Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world.Helicobacter pylori(H.pylori)infection associated duodenal ulcers should undergo eradication therapy.There are many regimens offered for H.pylori eradication which include triple,quadruple,or sequential therapy regimens.The central aim of this systematic review is to evaluate the evidence for H.pylori therapy from a meta-analytical outlook.The consequence of the dose,type of proton-pump inhibitor,and the length of the treatment will be debated.The most important risk factor for eradication failure is resistance to clarithromycin and metronidazole.

Multimodality treatment of potentially curative gastric cancer: Geographical variations and future prospects

After much controversy, multimodality therapy is now accepted worldwide as the gold standard for treatment of resectable bulky localized gastric cancer. There is significant regional variation in the style of multimodality treatment with adjuvant chemoradiation the North American standard, neoadjuvant chemotherapy preferred in Europe and Australasia, whilst adjuvant chemotherapy is preferred in Asia. With further standardization of surgery and D1+/D2 resections increasingly accepted world wide, and in particular in the West, as the surgical standard of care for potentially curable disease, it is timely to reassess the multimodality regimes being used. The challenge in the use of multimodality therapy is how current outcomes can be standardized and improved further. Recent studies indicate that mere intensification of the regime in time, dosage or addition of further agents does not improve localized gastric cancer outcomes. More novel strategies including early commencement of adjuvant therapies, intra-peritoneal chemotherapy or assessing neoadjuvant response with positron emission tomography scanning may give improvements in outcomes. The introduction of targeted therapies means that the adjuvant use of biological agents needs to be explored. By proper assessment of the patient’s co-morbidities, full tumour staging, and a better understanding of the tumour’s molecular pathology, multimodality therapy for gastric adenocarcinoma may be individualized to optimize the likelihood of cure.

How to decide on stent insertion or surgery in colorectal obstruction?

Colorectal cancer is one of the most common cancers in western society and malignant obstruction of the colon accounts for 8%-29% of all large bowel obstructions. Conventional treatment of these patients with malignant obstruction requiring urgent surgery is associated with a greater physiological insult on already nutritionally replete patients. Of late the utility of colonic stents has offered an option in the management of these patients in both the palliative and bridge to surgery setting. This has been the subject of many reviews which highlight its efficacy, particulary in reducing ostomy rates, allowing quicker return to oral diet, minimising extended post-operative recovery as well as some quality of life benefits. The uncertainity in managing patients with malignant colonic obstructions has lead to a more cautious use of stenting technology as community equipoise exists. Decision making analysis has demonstrated that surgeons' favored the use of stents in the palliative setting preferentially when compared to the curative setting where surgery was preferred. We aim to review the literature regarding the use of stent or surgery in colorectal obstruction, and then provide a discourse with regards to the approach in synthesising the data and applying it when deciding the appropriate application of stent or surgery in colorectal obstruction.

Methylation of TIMP3 in esophageal squamous cell carcinoma

AIM: To measure the frequency of DNA methylation of the tissue inhibitor of metalloproteinase 3 (TIMP3) promoter and relate this to any change of gene expression in esophageal squamous cell carcinoma in patients from a region of high incidence in China.METHODS: Cancer cell lines were treated with or without the demethylating reagent 5-aza-2’-deoxycytidine. Methylation of the TIMP3 promoter was assessed in three regions by melt curve analysis and its expression was assessed by real-time RT-PCR. Tumors and proximal resection margins were obtained from 64 patients with esophageal squamous cell carcinoma from a region of high incidence in China. Methylation was assessed by melt curve analysis and expression by immunohistochemistry.RESULTS: Methylation in one of the three promoter regions assessed correlated with gene silencing in esophageal cell lines. A degree of methylation of TIMP3 was found in only four esophageal squamous cell carcinomas, and partial loss of TIMP3 protein expression in just one.CONCLUSION: Methylation and loss of expression of TIMP3 occurs infrequently in esophageal squamous cell carcinoma in a region of high incidence in China.

Serum outperforms plasma in small extracellular vesicle microRNA biomarker studies of adenocarcinoma of the esophagus

BACKGROUND Circulating microRNAs(miRNAs)are potential biomarkers for many diseases.However,they can originate from non-disease specific sources,such as blood cells,and compromise the investigations for miRNA biomarkers.While small extracellular vesicles(sEVs)have been suggested to provide a purer source of circulating miRNAs for biomarkers discovery,the most suitable blood sample for sEV miRNA biomarker studies has not been defined.AIM To compare the mi RNA profiles between matched serum and plasma s EV preparations to determine their suitability for biomarker studies.METHODS Matched serum and plasma samples were obtained from 10 healthy controls and10 patients with esophageal adenocarcinoma.s EV isolates were prepared from serum and plasma using Exo Quick TM and quantified using Nano Sight.RNA was extracted from s EV preparations with the mi RNeasy Serum/Plasma kit and profiled using the Taqman Openarray q PCR.The overall mi RNA content and theexpression of specific mi RNAs of reported vesicular and non-vesicular origins were compared between serum and plasma s EV preparations.The diagnostic performance of a previously identified multi-mi RNA biomarker panel for esophageal adenocarcinoma was also compared.RESULTS The overall mi RNA content was higher in plasma s EV preparations(480 mi RNAs)and contained 97.5%of the mi RNAs found in the serum s EV preparations(412 mi RNAs).The expression of commonly expressed mi RNAs was highly correlated(Spearman’s R=0.87,P<0.0001)between the plasma and serum s EV preparations,but was consistently higher in the plasma s EV preparations.Specific blood-cell mi RNAs(hsa-mi R-223-3 p,hsa-mi R-451 a,mi R-19 b-3 p,hsa-mi R-17-5 p,hsa-mi R-30 b-5 p,hsa-mi R-106 a-5 p,hsa-mi R-150-5 p and hsa-mi R-92 a-3 p)were expressed at 2.7 to 9.6 fold higher levels in the plasma s EV preparations compared to serum s EV preparations(P<0.05).In plasma s EV preparations,the percentage of protein-associated mi RNAs expressed at relatively higher levels(Ct 20-25)was greater than serum s EV preparations(50%vs 31%).While the percentage of vesicle-associated mi RNAs expressed at relatively higher levels was greater in the serum s EV preparations than plasma s EV preparations(70%vs 44%).A 5-mi RNA biomarker panel produced a higher cross validated accuracy for discriminating patients with esophageal adenocarcinoma from healthy controls using serum s EV preparations compared with plasma s EV preparations(AUROC 0.80 vs 0.54,P<0.05).CONCLUSION Although plasma s EV preparations contained more mi RNAs than serum s EV preparations,they also contained more mi RNAs from non-vesicle origins.Serum appears to be more suitable than plasma for s EV mi RNAs biomarkers studies.

Getting started in endoscopic ear surgery

Endoscopic ear surgery(EES) is an exciting, rapidly developing and innovative field of otologic surgery.Technically and conceptually, EES is a significant departure from traditional microscopic transcanal approaches to the middle ear and canal that has shown very positive results with respect to patient outcomes. This review serves as a primer for the otologist and otology resident embarking on EES and discusses the theory surrounding the learning process, the optical chain for endoscopic surgery as well as other important underlying principles.

An unusual case of right-sided colon cancer with isolated lateral pelvic side wall lymph node metastases

Lymphatic drainage is typically in the direction of arterial supply,and lymphatic drainage for right-sided colon cancers typically travels to ileocolic lymph nodes.It is rare for right-sided colon cancers to metastasize to the lateral pelvic side wall lymph nodes in the absence of local invasion or other distant metastases.In this report,we present an unusual case of a young female with pT4a right-sided ascending colon cancer with isolated metastases to the pelvic iliac lymph nodes.The patient underwent minimally invasive laparoscopic right hemicolectomy and pelvic lymph node dissection with curative intent.She recovered well with no intraoperative complications and was referred for urgent adjuvant chemotherapy and radiotherapy.

Prevalence of recent immunisation in children with febrile convulsions

AIM:To determine the prevalence of recent immunisation amongst children under 7 years of age presenting for febrile convulsions.METHODS:This is a retrospective study of all children under the age of seven presenting with febrile convulsions to a tertiary referral hospital in Sydney.A total of 78 cases occurred in the period January 2011 to July 2012 and were included in the study.Data was extracted from medical records to provide a retrospective review of the convulsions.RESULTS:Of the 78 total cases,there were five medical records which contained information on whether or not immunisation had been administered in the preceding 48 h to presentation to the emergency department.Of these five patients only one patient(1.28%of the study population) was confirmed to have received a vaccination with Infanrix,Prevnar and Rotavirus.The majority of cases reported a current infection as a likely precipitant to the febrile convulsion.CONCLUSION:This study found a very low prevalence of recent immunisation amongst children with febrile convulsions presenting to an emergency department at a tertiary referral hospital in Sydney.This finding,however,may have been distorted by underreporting of vaccination history.

A systematic review of dedicated models of care for emergency urological patients

Objective:To systematically evaluate the spectrum of models providing dedicated resources for emergency urological patients(EUPs).Methods:A search of Cochrane,Embase,Medline and grey literature from January 1,2000 to March 26,2019 was performed using methods pre-published on PROSPERO.Reporting followed Preferred Reporting Items for Systematic Review and meta-analysis guidelines.Eligible studies were articles or abstracts published in English describing dedicated models of care for EUPs,which reported at least one secondary outcome.Studies were excluded if they examined pathways dedicated only to single presentations,such as torsion,or outpatient solutions,such as rapid access clinics.The primary outcome was the spectrum of models.Secondary outcomes were time-to-theatre,length of stay,complications and cost.Results:Seven studies were identified,totalling 487 patients.Six studies were conference abstracts,while one study was of full-text length but published in grey literature.Four distinct models were described.These included consultant urologists allocated solely to the care of EUPs(“Acute Urological Unit”)or dedicated registrars or operating theatres(“Hybrid structures”).In some services,EUPs bypassed emergency department assessment and were referred directly to urology(“Urological Assessment Unit”)or were managed by other dedicated means.Allocating services to EUPs was associated with reduced time-to-theatre,length of stay and hospital cost,and improved supervision of junior medical staff.Conclusion:Multiple dedicated models of care exist for EUPs.Low-level evidence suggests these may improve outcomes for patients,staff and hospitals.Higher quality studies are required to explore patient outcomes and minimum requirements to establish these models.

Outcomes of Pringle maneuver in patients undergoing hepatic resection for colorectal liver metastases

To the Editor:The Pringle maneuver(PM)was initially described more than a century ago to control bleeding associated with hepatic trauma and it remains the most common method to block hepatic inflow and minimize blood loss during hepatic resections[1].

Transanal minimally invasive surgery to rescue anastomosis following leak after low anterior resection: A case report

Restorative low anterior resection(LAR)for rectal cancer carries a significant risk of anastomotic leak:One of the most feared complications in colorectal surgery.Operative management may include takedown of the anastomosis and end colostomy which,in some cases,is permanent.Other contemporary operative measures include over the scope clips and Endosponge.Recently,there have been case reports and a Society of American Endoscopic and Gastrointestinal Surgeons video on the novel use of transanal minimally invasive surgery(TAMIS)in the management of anastomotic leak.We present a 59-year-old female who underwent LAR after declining radiotherapy for a bulky 9 cm rectal tumour 9-10 cm from the anal verge.Following clinical deterioration,computed tomography demonstrated an anastomotic leak communicating with a 5-cm pelvic collection containing gas.At laparoscopy,pus and faeculent material were washed from the pelvic cavity and drains were placed.Intra-operative endoscopy demonstrated a 7-8 mm dehiscence at the anastomosis.The defect(approximately 7 cm from the anal verge)was successfully closed using TAMIS and a running V-lock suture.The patient recovered well and was discharged home on post-operative day 20.In this case,a low colorectal anastomotic leak was successfully rescued with TAMIS.This novel technique may be useful in the armamentarium of colorectal surgeons experienced in TAMIS.

国际糖尿病足工作组:指南的制定和方法学(2023)——《国际糖尿病足工作组:糖尿病相关的足病预防与管理指南(2023)》的一部分

糖尿病相关的足病是造成糖尿病患者经济负担和增加社会成本的主要原因之一。本指南以主要目标为导向,以循证医学为依据,且在全球得到合理实施。践行国际糖尿病相关的足病指南对于减轻患者经济负担和社会成本有着重要影响。国际糖尿病足工作组(IWGDF)从1999年起开始发布并随后更新国际指南。2023年更新版指南相关推荐均基于推荐、评估、发展和评价分级(GRADE)系统,包括制定相关临床问题和重要结局,完成系统的文献系统综述和荟萃分析,完成评判表汇总,并且给予具体、明确、操作性强的推荐以及理论依据。本文阐述了《国际糖尿病足工作组:糖尿病相关的足病预防和管理指南(2023版)》(以下简称为指南)的制定过程。指南由7个部分组成,包括预防、糖尿病相关的足溃疡分类、减压、周围动脉病变、感染、创面愈合干预以及活动性夏科神经骨关节病,分别由7个独立的国际专家工作组编写。IWGDF编辑委员会对7个章节进行了整合和简化,形成IWGDF实践指南。指南中的每条推荐均经过IWGDF编辑委员会成员和相关领域的独立的国际专家审阅通过。本文是IWGDF指南的制定和方法学。我们相信,医务人员、公共卫生机构和政策制定者采用和实施2023年IWGDF指南,将会改善糖尿病相关的足病的预防和管理水平,从而减少全球该疾病患者和减轻该疾病引起的全球社会负担。

Techniques for colorectal anastomosis

Colorectal anastomotic leak remains one of the most feared post-operative complications, particularly after anterior resection of the rectum with, the shift from abdomino-peritoneal resections to total mesorectal excision and primary anastomosis. The literature fails to demonstrate superiority of stapled over hand-sewn techniques in colorectal anastomosis, regardless of the level of anastomosis, although a high stricture rate was noted in the former technique. Thus, improvements in safety aspects of anastomosis and alternatives to handsewn and stapled techniques are being sought. Here, we review alternative anastomotic techniques used to fashion bowel anastomosis. Compression anastomosis using compression anastomotic clips, endoluminal compression anastomotic rings, AKA-2, biofragmental anastomotic rings, or Magnamosis all involve the concept of creating a sutureless end-to-end anastomosis by compressing two bowel ends together, leading to a simultaneous necrosis and healing process that joins the two lumens. Staple line reinforcement is a new approach that reduce the drawbacks of staplers used in colorectal practice, i.e. leakage, bleeding, misfi ring, and inadequate tissue approximation. Various nonabsorbable, semi or fully absorbable materials are now available. Two other techniques can provide alternative anastomotic support to the suture line: a colorectal drain and a polyester stent, which can be utilized in ultra-low rectal excision and can negate the formation of a defunctioning stoma. Doxycycline coated sutures have been used to overcome the post-operative weakness in anastomosis secondary to rapid matrix degradation mediated by matrix metalloproteinase. Another novel technique, the electric welding system, showed promising results in construction of a safe, neat, smooth sutureless bowel anastomosis. Various anastomotic techniques have been shown to be comparable to the standard techniques of suturing and stapling. However, most of these alternatives need to be accepted and optimized for future use.

Irinotecan therapy and molecular targets in colorectal cancer: A systemic review

Irinotecan is the second line chemotherapy for advanced stage colorectal cancer (CRC) after failure of first line chemotherapy with oxaliplatin and 5-fluorouracil. The aim of this review is to analyse the data on irinotecan as second line chemotherapy for advanced CRC and the potential roles of the molecular markers, p53 and vascular endothelial growth factor (VEGF) in the management of advanced CRC. Thus, the English literature from 1980 to 2008 concerning irinotecan, p53, VEGF and CRC was reviewed. On review, Phase and clinical trials showed thatirinotecan improves pain-free survival, quality of life, 1-year survival, progression-free survival and overall survival in advanced CRC. p53 and VEGF were expressed in CRC and had a predictive power of aggressive clinical behaviour in CRC. Irinotecan sensitizes p53 wild type, mutant and null cells to Fasmediated cell apoptosis in CRC cells. Wild type p53 cells were more sensitive to irinotecan than mutated p53. Irinotecan has an anti-VEGF effect inhibiting endothelial cell proliferation, increasing apoptosis and reducing microvascular density which is onlylimited by irinotecan toxicity levels. To conclude, irinotecan improves the patient's quality of life and the survival rates of patients with advanced CRC. p53 and VEGF status of the patients' tumour is likely to affect the responsiveness of CRC to irinotecan. It is recommended that studies of the expression of these molecular markers in relation to chemoresponsiveness ofirinotecan should be carried out for better management of patients with advanced CRC.

Indications and surgical options for small bowel, large bowel and perianal Crohn's disease

Despite advancements in medical therapy of Crohn's disease(CD), majority of patients with CD will eventually require surgical intervention, with at least a third of patients requiring multiple surgeries. It is important to understand the role and timing of surgery, with the goals of therapy to reduce the need for surgery without increasing the odds of emergency surgery and its associated morbidity, as well as to limit surgical recurrence and avoid intestinal failure. The profile of CD patients requiring surgical intervention has changed over the decades with improvements in medical therapy with immunomodulators and biological agents. The most common indication for surgery is obstruction from stricturing disease, followed by abscesses and fistulae. The risk of gastrointestinal bleeding in CD is high but the likelihood of needing surgery for bleeding is low. Most major gastrointestinal bleeding episodes resolve spontaneously, albeit the risk of re-bleeding is high. The risk of colorectal cancer associated with CD is low. While current surgical guidelines recommend a total proctocolectomy for colorectal cancer associated with CD, subtotal colectomy or segmental colectomy with endoscopic surveillance may be a reasonable option. Approximately 20%-40% of CD patients will need perianal surgery during their lifetime. This review assesses the practice parameters and guidelines in the surgical management of CD, with a focus on the indications for surgery in CD(and when not to operate), and a critical evaluation of the timing and surgical options available to improve outcomes and reduce recurrence rates.

Hypothesized summative anal physiology score correlates but poorly predicts incontinence severity

To explore the relationship between such a construct and an existing continence score. METHODSA retrospective study of incontinent patients who underwent anal physiology (AP) was performed. AP results and Cleveland Clinic Continence Scores (CCCS) were extracted. An anal physiology score (APS) was developed using maximum resting pressures (MRP), anal canal length (ACL), internal and external sphincter defects and pudendal terminal motor latency. Univariate associations between each variable, APS and CCCS were assessed. Multiple regression analyses were performed. RESULTSOf 508 (419 women) patients, 311 had both APS and CCCS measured. Average MRP was 51 mmHg (SD 23.2 mmHg) for men and 39 mmHg (19.2 mmHg) for women. Functional ACL was 1.7 cm for men and 0.7 cm for women. Univariate analyses demonstrated significant associations between CCCS and MRP (P = 0.0002), ACL (P = 0.0006) and pudendal neuropathy (P < 0.0001). The association between APS and CCCS was significant (P < 0.0001) but accounted for only 9.2% of the variability in CCCS. Multiple regression showed that the variables most useful in predicting CCCS were external sphincter defect, pudendal neuropathy and previous pelvic surgery, but only improving the scores predictive ability to 12.5%. CONCLUSIONThis study shows that the ability of AP tests to predict continence scores improves when considered collectively, but that a constructed summation model before and after multiple regression is poor at predicting the variability in continence scores.

Colorectal surgeon consensus with diverticulitis clinical practice guidelines

AIM To determine the application of clinical practice guidelines for the current management of diverticulitis and colorectal surgeon specialist consensus in Australia and New Zealand.METHODS A survey was distributed to 205 colorectal surgeons in Australia and New Zealand, using 22 hypothetical clinical scenarios.RESULTS The response rate was 102(50%). For 19 guidelinebased scenarios, only 11(58%) reached consensus(defined as > 70% majority opinion) and agreed with guidelines; while 3(16%) reached consensus and did not agree with guidelines. The remaining 5(26%) scenarios showed community equipoise(defined as less than/equal to 70% majority opinion). These included diagnostic imaging where CT scan was contraindicated, management options in the failureof conservative therapy for complicated diverticulitis, surgical management of Hinchey grade 3, proximal extent of resection in sigmoid diverticulitis and use of oral mechanical bowel preparation and antibiotics for an elective colectomy. The consensus areas not agreeing with guidelines were management of simple diverticulitis, management following the failure of conservative therapy in uncomplicated diverticulitis and follow-up after an episode of complicated diverticulitis. Fifty-percent of rural/regional based surgeons would perform an urgent sigmoid colectomy in failed conservative therapy of diverticulitis compared to only 8% of surgeons city-based(Fisher's exact test P = 0.016). In right-sided complicated diverticulitis, a greater number of those in practice for more than ten years would perform an ileocecal resection and ileocolic anastomosis(79% vs 41%, P < 0.0001).CONCLUSION While there are areas of consensus in diverticulitis management, there are areas of community equipoise for future research, potentially in the form of RCTs.

Clinical outcomes for men with positive surgical margins after radical prostatectomy—results from the South Australian Prostate Cancer Clinical Outcomes Collaborative community-based registry

Objective Positive surgical margins(PSMs)after radical prostatectomy(RP)indicate failure of surgery to completely clear cancer.PSMs confer an increased risk of biochemical recurrence(BCR),but how more robust outcomes are affected is unclear.This study investigated factors associated with PSMs following RP and determined their impact on clinical outcomes(BCR,second treatment[radiotherapy and/or androgen deprivation therapy],and prostate cancer-specific mortality[PCSM]).Methods The study cohort included men diagnosed with prostate cancer(pT2-3b/N0/M0)between January 1998 and June 2016 who underwent RP from the South Australian Prostate Cancer Clinical Outcomes Collaborative database.Factors associated with risk of PSMs were identified using Poisson regression.The impact of PSMs on clinical outcomes(BCR,second treatment,and PCSM)was assessed using competing risk regression.Results Of the 2827 eligible participants,28%had PSMs—10%apical,6%bladder neck,17%posterolateral,and 5%at multiple locations.Median follow-up was 9.6 years with 81 deaths from prostate cancer recorded.Likelihood of PSM increased with higher pathological grade and pathological tumor stage,and greater tumour volume,but decreased with increasing surgeon volume(odds ratio[OR]:0.93;95%confidence interval[CI]:0.88-0.98,per 100 previous prostatectomies).PSMs were associated with increased risk of BCR(adjusted sub-distribution hazard ratio[sHR]2.5;95%CI 2.1-3.1)and second treatment(sHR 2.9;95%CI 2.4-3.5).Risk of BCR was increased similarly for each PSM location,but was higher for multiple margin sites.We found no association between PSMs and PCSM.Conclusion Our findings support previous research suggesting that PSMs are not independently associated with PCSM despite strong association with BCR.Reducing PSM rates remains an important objective,given the higher likelihood of secondary treatment with associated comorbidities.