The GIST of it all: management of gastrointestinal stromal tumors (GIST) from the first steps to tailored therapy. A bibliometric analysis.

PURPOSE: Improvement of patient care is associated with increasing publication numbers in biomedical research. However, such increasing numbers of publications make it challenging for physicians and scientists to screen and process the literature of their respective fields. In this study, we present a comprehensive bibliometric analysis of the evolution of gastrointestinal stromal tumor (GIST) research, analyzing the current state of the field and identifying key open questions going beyond the recent advantages for future studies to assess. METHODS: Using the Web of Science Core Collection, 5040 GIST-associated publications in the years 1984-2022 were identified and analyzed regarding key bibliometric variables using the Bibliometrix R package and VOSviewer software. RESULTS: GIST-associated publication numbers substantially increased over time, accentuated from year 2000 onwards, and being characterized by multinational collaborations. The main topic clusters comprise surgical management, tyrosine kinase inhibitor (TKI) development/treatment, diagnostic workup, and molecular pathophysiology. Within all main topic clusters, a significant progress is reflected by the literature over the years. This progress ranges from conventional open surgical techniques over minimally invasive, including robotic and endoscopic, resection techniques to increasing identification of specific functional genetic aberrations sensitizing for newly developed TKIs being extensively investigated in clinical studies and implemented in GIST treatment guidelines. However, especially in locally advanced, recurrent, and metastatic disease stages, surgery-related questions and certain specific questions concerning (further-line) TKI treatment resistance were infrequently addressed. CONCLUSION: Increasing GIST-related publication numbers reflect a continuous progress in the major topic clusters of the GIST research field. Especially in advanced disease stages, questions related to the interplay between surgical approaches and TKI treatment sensitivity should be addressed in future studies.

A century of retroperitoneal soft-tissue sarcoma research: From single center experience to precision oncology? A bibliometric analysis of past, present, and future perspectives.

BACKGROUND: Increasing publication numbers in the biomedical field led to an improvement of patient care in many aspects but are challenging for scientists when integratively processing data of their fields. Using bibliometric analyses, the present study assesses the productivity and predominant topics in retroperitoneal soft-tissue sarcoma (RPS) research across the past 122 years, thereby identifying crucial questions to address in future RPS research. METHODS: Using the Web of Science Core Collection, 1018 RPS-associated publications from 1900 to 2022 were identified and analyzed regarding key bibliometric variables using the Bibliometrix R package and the VOSviewer software. RESULTS: A continuous increase in RPS-associated publication numbers can be noticed over the time, which is strongly pronounced from 2005 onwards, and is characterized by a multinationally driven collaborative clinical research focus. The research primarily reflects progression regarding surgical techniques, histology-based therapy, radiotherapy regimens, and identification of prognostic clinicopathological factors. This progression is accompanied with improved overall survival of RPS patients. However, a paucity of RPS-specific basic/translational research indicates that such research might be additionally needed to better understand the pathophysiology of RPS and with that to enable the development of personalized therapies and to further improve patient outcome. CONCLUSION: Increasing publication numbers of multinationally driven clinical RPS research are accompanied with improved overall survival of RPS patients, highlighting the importance of international collaborations to facilitate future clinical trials. However, this bibliometric analysis reveals a lack of RPS-specific basic/translational research which is needed to further improve patient outcome in the context of precision oncology.

Standard of Care and Outcomes of Primary Laparotomy Versus Laparotomy in Patients with Prior Open Abdominal Surgery (ReLap Study; DRKS00013001).

BACKGROUND: Patients undergoing relaparotomy are generally underrepresented in trials, despite how common the procedure is in clinical practice. The aim of this trial was to determine standard of care and gain evidence of intra- and postoperative outcomes for patients undergoing relaparotomy compared to primary laparotomy. METHODS: In this single-center controlled clinical trial, adult patients scheduled for elective abdominal surgery via relaparotomy or primary laparotomy were consecutively screened for eligibility. The perioperative course was monitored prospectively in five study visits during hospital stay and one study visit 1 year after surgery. Intraoperative standards, short and long-term outcomes were statistically explored at a level of significance of 5%. RESULTS: A total of 131 patients with relaparotomy and 50 patients with primary laparotomy were analyzed. In the relaparotomy group, the access to the abdomen took longer (23.5 min vs. 8.8 min; p = < 0.001) and the peritoneal adhesion index was higher (10.8 vs. 0.4; p = < 0.001). Inadvertent enterotomies were more frequent in the relaparotomy group (relaparotomy 0.3 versus primary laparotomy: 0.0; p = 0.002). The overall comprehensive complication index and rates of surgical site infection and wound dehiscence with evisceration were not different between the two groups. At long-term follow-up, rates of incisional hernia did not differ (relaparotomy: n = 12/104 (11.5%); primary laparotomy: n = 7/35 (20.0%); p = 0.208). DISCUSSION: In this first prospective comparison of relaparotomy with primary laparotomy, inadvertent enterotomies were more frequent in the relaparotomy group. However, contrary to previous retrospective studies, the risk of complications and incisional hernias was not increased compared to primary laparotomy. TRIAL REGISTRATION: Deutsches Register Klinischer Studien ( www.germanctr.de ): DRKS00013001.

Randomised-controlled feasibility trial on abdominal wall closure techniques in patients undergoing relaparotomy (ReLap study; DRKS00013001).

BACKGROUND: Patients undergoing relaparotomy are generally underrepresented in clinical trials, despite how common the procedure is in clinical practice. Specifically, techniques for re-do abdominal wall closure have never been evaluated in a randomised-controlled trial. The aim of this trial was to identify the optimal abdominal wall closure technique in patients undergoing relaparotomy. METHODS: In this monocentric, randomised feasibility trial, patients scheduled for elective relaparotomy were randomised to abdominal wall closure with either the small stitches technique, using Monomax® 2-0, or the large stitches technique, using PDS II® 1 loop. Patients' postoperative courses were followed for 1 year after the index operation. Effectiveness and safety outcomes were compared at a level of significance of 5% between the two techniques. RESULTS: A total of 100 out of 131 patients (76.3%) were evenly randomised to the small stitches and large stitches groups. The time for abdominal wall closure did not differ between the two techniques (small stitches 27.5 ± 9.5 min versus large stitches 25.3 ± 12.4 min; p = 0.334). The overall comprehensive complication index was 14.4 ± 15.5 in the small stitches group and 19.9 ± 23.4 in the large stitches group (p = 0.168). Specifically, rates of surgical site infection (small stitches 30.0% versus large stitches 36.0%; p = 0.524) and burst abdomen (small stitches 4.0% versus large stitches 0.0%; p = 0.495) did not differ. After 1 year, incisional hernia rate was 7.5% in the small stitches group and 10.0% in the large stitches group (p > 0.999). DISCUSSION: Both abdominal wall closure techniques investigated in this trial were feasible in relaparotomy patients. This exploratory trial revealed no noticeable difference in the effectiveness or safety of the small stitches technique with Monomax® 2-0 versus the large stitches technique with PDS II® 1 loop. Therefore, surgeons should stay with their preferred suture technique in relaparotomy patients. TRIAL REGISTRATION: Deutsches Register Klinischer Studien ( www.germanctr.de ): DRKS00013001.

Urgent surgery in colon cancer has no impact on survival.

BACKGROUND AND OBJECTIVES: Despite advances in early detection of colon cancer, a minority of patients still require urgent surgery. Whether such urgent conditions result in poor outcome remains a topic of debate. METHODS: Using a prospectively maintained database, patients suffering exclusively from colon cancer and receiving either elective or emergent resection between 2001 and 2014 were analyzed with respect to overall, disease-specific, and relative survival using Cox regression and propensity score analyses. RESULTS: From a total of 877 patients analyzed, 2.7% (24) presented with complications requiring urgent surgery. Propensity-scoring identified strongly biased patient characteristics (0.097 ± 0.069 vs 0.028 ± 0.043; P < 0.001). An unadjusted Cox proportional hazards regression analysis revealed urgent surgery as a statistically significant prognostic factor with an approximately 207% increased risk of mortality (hazard ratio [HR] = 3.07; 95% confidence interval [CI]: 1.62-5.81; P = 0.003). After adjusting the data according to the propensity score analysis, urgent surgery was not associated with a decreased overall (HR = 1.67; 95%CI; 0.84-3.36; P = 0.174), disease-specific (HR = 1.62; 95% CI; 0.81-3.24; P = 0.201) or relative survival (HR = 1.86; 95% CI: 0.92-3.79; P = 0.086). CONCLUSIONS: After risk-adjustment, using multivariable Cox regression and propensity score analyses, no significant disadvantage could be noted with regard to overall, disease-specific, or relative survival in patients with exclusively colon cancer who received emergent oncological resection.

Evidence-based recommendations for blinding in surgical trials.

RATIONALE: Blinding reduces performance and detection bias in randomized controlled trials (RCT). There is evidence that lack of blinding leads to overestimation of treatment effects in pharmacological trials. Since surgical trials use interventions with a physical component, blinding is often complicated. The aim of this study was to analyze, in general and abdominal surgery RCT, the status of blinding, the potential for blinding, and the influence of blinding on outcomes. METHODS: A systematic search of the literature in CENTRAL, MEDLINE, and Web of Science was conducted to identify RCT with a surgical intervention, starting in 1996, the year when the first CONSORT statement was published. Information on general study characteristics and blinding methods was extracted. The presence or absence of blinding of the study contributors-patients, surgeons, data collectors, outcome assessors, and data analysts-was analyzed. The association of blinding with the trial outcome was investigated for every study contributor. RESULTS: Out of 29,119 articles, 378 RCT were included in the analysis. These investigated a total of 62,522 patients, of whom 15,025 were blinded (24.0%). Contributors could have been blinded in far more trials, as the potential for blinding measures ranged from 69% for outcome assessors to 98% for data analysts. If blinding of surgeons would have been possible but had not been performed, this was associated with more significant trial outcomes (OR 13.670; 95% CI 1.308 to 142.840; p = 0.0289). DISCUSSION: The potential of blinding, an important quality measure in surgical RCT, has not been exhausted. This study summarizes the existing evidence on blinding in surgical trials and gives evidence-based recommendations for the use of blinding in future surgical trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2015:CRD42015026837.

Prospective mixed-methods study of patients undergoing relaparotomy (ReLap study; DRKS00013001).

BACKGROUND: Patients undergoing relaparotomies are underrepresented in clinical trials. Standard of care, relative outcomes compared to primary laparotomy, and the ideal fascial closure technique are unknown. OBJECTIVE: The ReLap study has three objectives: First, to determine standard of care and gain evidence of intra-/postoperative outcomes for patients undergoing relaparotomy compared to patients undergoing primary laparotomy. Second, to gain evidence of an association between biomarkers and adhesion grade in a clinical-translational approach in patients undergoing relaparotomy or primary laparotomy. Third, to gain evidence of the feasibility and comparative effectiveness of fascial closure after relaparotomy using the small stitches technique with Monomax 2-0 versus the large stitches technique with PDS 1 loop. METHODS: The ReLap study is a monocentric, prospective, mixed-methods, exploratory study with three steps: health care research, translational research, and randomized controlled trial. All patients scheduled for elective laparotomies or relaparotomies at the University of Heidelberg will be screened for eligibility. There will be five study visits during the hospital stay and one study visit one year after surgery. The clinical course will be followed and outcomes necessary to answer the study objectives will be captured prospectively. Relaparotomy patients eligible for closure with the small and large stitches technique will be randomized intraoperatively to one technique. DISCUSSION: The ReLap study will bridge a significant knowledge gap regarding patients undergoing relaparotomy. Differences in the standard of care between relaparotomies and primary laparotomies will be determined. The relation between biomarkers and manifestation of adhesions will be explored and evidence for the comparative effectiveness of fascial closure after relaparotomy will be gained.

Antibiotics Versus Surgical Therapy for Uncomplicated Appendicitis: Systematic Review and Meta-analysis of Controlled Trials (PROSPERO 2015: CRD42015016882).

OBJECTIVE: The aim was to investigate available evidence regarding effectiveness and safety of surgical versus conservative treatment of acute appendicitis. SUMMARY OF BACKGROUND DATA: There is ongoing debate on the merits of surgical and conservative treatment for acute appendicitis. METHODS: A systematic literature search (Cochrane Library, Medline, Embase) and hand search of retrieved reference lists up to January 2016 was conducted to identify randomized and nonrandomized studies. After critical appraisal, data were analyzed using a random-effects model in a Mantel-Haenszel test or inverse variance to calculate risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). RESULTS: Four trials and four cohort studies (2551 patients) were included. We found that 26.5% of patients in the conservative group needed appendectomy within 1 year, resulting in treatment effectiveness of 72.6%, significantly lower than the 99.4% in the surgical group, (RR 0.75; 95% CI 0.7-0.79; P = 0.00001; I = 62%). Overall postoperative complications were comparable (RR 0.95; 95% CI 0.35-2.58; P = 0.91; I = 0%), whereas the rate of adverse events (RR 3.18; 95% CI 1.63-6.21; P = 0.0007; I = 1%) and the incidence of complicated appendicitis (RR 2.52; 95% CI 1.17-5.43; P = 0.02; I = 0%) were significantly higher in the antibiotic treatment group. Randomized trials showed significantly longer hospital stay in the antibiotic treatment group (RR 0.3 days; 95% CI 0.07-0.53; P = 0.009; I = 49%). CONCLUSIONS: Although antibiotics may prevent some patients from appendectomies, surgery represents the definitive, one-time only treatment with a well-known risk profile, whereas the long-term impact of antibiotic treatment on patient quality of life and health care costs is unknown. This systematic review and meta-analysis helps physicians and patients in choosing between treatment options depending on whether they are risk averse or risk takers.

Placebo-Controlled Trials in Surgery: A Systematic Review and Meta-Analysis.

This systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized placebo-controlled surgical trials.Central, MEDLINE, and EMBASE were systematically searched to identify randomized controlled trials comparing a surgical procedure to a placebo. "Surgical procedure" was defined as a medical procedure involving an incision with instruments. Placebo was defined as a blinded sham operation involving no change to the structural anatomy and without an expectable physiological response in the target body compartment.Ten randomized placebo-controlled controlled surgical trials were included, all of them published in high-ranking medical journals (mean impact factor: 20.1). Eight of 10 failed to show statistical superiority of the experimental intervention. Serious adverse events did not differ between the groups (rate ratio [RR] 1.38, 95% confidence interval [CI]: 0.92-2.06, P = 0.46). None of the trials had a high risk of bias in any domain. The ethical justification for the use of a placebo control remained unclear in 2 trials.Placebo-controlled surgical trials are feasible and provide high-quality data on efficacy of surgical treatments. The surgical placebo entails a considerable risk for study participants. Consequently, a placebo should be used only if justified by the clinical question and by methodological necessity. Based on the current evidence, a pragmatic proposal for the use of placebo controls in future randomized controlled surgical trials is made.

Portal annular pancreas: a systematic review of a clinical challenge.

Portal annular pancreas (PAP) is an asymptomatic congenital pancreas anomaly, in which portal and/or mesenteric veins are encased by pancreas tissue. The aim of the study was to determine the role of PAP in pancreatic surgery as well as its management and potential complication, specifically, postoperative pancreatic fistula (POPF).On the basis of a case report, the MEDLINE and ISI Web of Science databases were systematically reviewed up to September 2012. All articles describing a case of PAP were considered.In summary, 21 studies with 59 cases were included. The overall prevalence of PAP was 2.4% and the patients' mean (SD) age was 55.9 (16.2) years. The POPF rate in patients with PAP (12 pancreaticoduodenectomies and 3 distal pancreatectomies) was 46.7% (in accordance with the definition of the International Study Group of Pancreatic Surgery).Portal annular pancreas is a quite unattended pancreatic variant with high prevalence and therefore still remains a clinical challenge to avoid postoperative complications. To decrease the risk for POPF, attentive preoperative diagnostics should also focus on PAP. In pancreaticoduodenectomy, a shift of the resection plane to the pancreas tail should be considered; in extensive pancreatectomy, coverage of the pancreatic remnant by the falciform ligament could be a treatment option.

Practice of skin protection and skin care among German surgeons and influence on the efficacy of surgical hand disinfection and surgical glove perforation.

BACKGROUND: Surgical hand rub and healthy skin are basic requirements to prevent surgical site infections. Nevertheless, there is little knowledge about the current practice of skin protection and/or skin care products (SP/SC) using among surgeons as well as a lack of data pertaining to the influence of SP/SC on the antimicrobial efficacy of surgical hand rub. METHODS: A 10 weeks-survey among German surgeons as well as an experimental crossover study involving 26 participants were conducted. The immediate and sustainable efficacy (IE/SE) of surgical hand rub and participants' hand moisture were measured after an 8-day usage of SP/SC, as well as the influence on micro-perforations on surgical gloves. RESULTS: The questionnaire was available to 16,000 German surgeons. Thereof, 1,771 surgeons accessed the questionnaire, representing a total participation rate of 11%. As 19% (n = 338) of questionnaires were incomplete, a total of 1,433 completed questionnaires were available for further analysis. More than 75% of the participants stated not to use any SP/SC, yet, almost 50% suffered from skin irritation or discomfort. Only 5% used SP/SC at the beginning of their shift. 10% refused to use SP/SC because of concerns that SP/SC may reduce the antimicrobial efficacy of surgical hand rub.After usage of SP/SC over 8-days, skin moisture was significantly higher (P < 0.001), whereas no significant influence on the antimicrobial efficacy of surgical hand rub was observed (IE: P = 0.135; SP: P = 0.681). Micro-perforations were detected in 8/52 surgical gloves (15%), with no statistical significant difference between SP/SC users (n = 2/26; 8%) and non-users (n = 6/26; 23%; P = 0.249). CONCLUSIONS: Following the results of this largest questionnaire base survey among German surgeons on skin care, there is a need to educate and inform surgeons on the correct application and the concept of SP/SC strategies. In the present study, the combination of selected SP/SC products and one alcohol-based hand rub formulation did not show a negative interaction with surgical hand rub or surgical glove perforation. However, it is advisable to ascertain the compatibility of SP/SC products with the used hand disinfectant prior to purchase.

Use and results of consensus definitions in pancreatic surgery: a systematic review.

BACKGROUND: Because of the lack of standardized definitions of complications in gastrointestinal operations, consensus definitions have been developed in recent years. The aim of the current study was to systematically review the available consensus definitions and to report their use, acceptance, and results. METHODS: A systematic search of the literature was conducted of the Medline, Cochrane, and ISI Web of Science databases. All articles published until August 2011 and that applied the identified consensus definitions were considered. Inclusion criteria for quantitative analysis were studies with correct usage of the definition and 100 or more patients who were treated after the year 2000. RESULTS: Seven consensus definitions were identified: postoperative pancreatic fistula, postpancreatectomy hemorrhage, delayed gastric emptying, posthepatectomy liver failure, bile leakage after hepatobiliary and pancreatic surgery, posthepatectomy hemorrhage, and anastomotic leakage after anterior resection of the rectum. Of 1,637 articles retrieved from the literature search, 59 articles that correctly applied the definitions met the inclusion criteria. Subanalyses were feasible for definitions after pancreatic surgery. According to the consensus definitions, the median complication rates of retrospective studies were 21.9% (postoperative pancreatic fistula, n = 11,244 patients), 5.9% (postpancreatectomy hemorrhage, n = 3,311 patients), and 22.8% (delayed gastric emptying, n = 4,553 patients) after pancreatic resections. The incidences were not substantially different in prospective trials. Validation was performed for all three definitions, demonstrating that the severity grades significantly correlated with the clinical course of the patients. CONCLUSION: The available consensus definitions were increasingly cited and facilitate scientific comparability and transparency if appropriately applied. The present data update the incidences of major pancreatic complications.