Perioperative Therapy Research Articles

Neoadjuvant therapy for resectable non-small cell lung cancer

Treatment perspectives for non-small cell lung cancer (NSCLC) have been significantly expanded by the integration of immune checkpoint inhibitors into multimodal therapy concepts. Currently, combined, immune checkpoint-inhibitor-based therapy concepts are also advancing into early, resectable stages of NSCLC. Neoadjuvant and perioperative chemoimmunotherapy opened up a promising new preoperative treatment approach, but also raises some new questions and challenges. With the expanded perioperative treatment options and the perspective on a further improvement in the absence of recurrence after tumor resection, there is push towards comprehensively collecting therapy-relevant findings for imaging, molecular and histopathological diagnostics at an early stage. All patients with lung carcinoma, regardless of the therapy intention, should be presented to an interdisciplinary tumor board with thoracic oncological expertise. This is regularly given in certified lung cancer centers.A standardized procedure contributes to optimized pre-therapeutic diagnostics and facilitates coordination for the best possible multimodal approach in the interdisciplinary tumor board. In the case of centrally located resectable tumors, for example, neoadjuvant treatment increases the chances of a procedure that is as parenchymal sparing as possible. Some questions cannot yet be answered conclusively. Perioperative systemic therapy with molecular-targeted and immune checkpoint inhibitors is the subject of numerous ongoing studies. The considerable dynamics in newly approved therapies and the development of perioperative therapy concepts require continuous adaptation of diagnostic algorithms and standards. Integration into standard pre-surgical routine makes rapid classification of the relevant findings as well as close coordination between the diagnostic and interventional disciplines essential.

Perioperative systemic therapy in high-risk renal cell carcinoma following nephrectomy: a narrative review.

For patients with resectable renal cell carcinoma (RCC), extirpative surgery with curative intent remains the standard of care. Despite surgical resection, most patients with high-risk features experience disease recurrence. The role of perioperative systemic therapy in the management of these patients' disease remains unclear. Several studies have evaluated the efficacy and safety of tyrosine kinase inhibitors (TKIs); however, most trials have yielded negative results. Adjuvant pembrolizumab demonstrated a disease-free survival benefit in the KEYNOTE-564 trial; however, multiple studies of other immune checkpoint inhibitors (ICIs) in a similar patient population did not yield consistent results. This review summarizes the current evidence for perioperative systemic therapy studies in RCC. The PubMed, American Society of Clinical Oncology (ASCO), and clinicaltrials.gov databases were used to retrieve articles published from January 1, 2001 to December 31, 2023 using the following search terms: "adjuvant", "neoadjuvant", "perioperative", "VEGF inhibitors", "immune checkpoint inhibitors", and "renal cell carcinoma". The search was limited to articles published in English. We summarize the major perioperative systemic therapy studies in RCC patients and provide an analysis of study outcomes, comparing differences in trial design and patient selection. We also discuss ongoing trials and the emergence of novel biomarkers designed to improve patient selection. The optimal use of perioperative systemic therapy in high-risk RCC is an area of active investigation. The use of adjuvant TKIs failed to demonstrate a survival benefit and was limited by high rates of toxicity. Several neoadjuvant and adjuvant ICI-based combination studies are being carried out to further improve clinical outcomes. Further studies will be needed to identify effective biomarkers to improve patient selection while avoiding overtreatment.

Life-threatening complications in ophthalmic surgery: a systematic review.

Ophthalmic surgical procedures are widely acknowledged for their safety and efficacy. Undoubtedly, advances in ophthalmic surgery, along with the improvement of anaesthetic techniques, have contributed to the reduction in the occurrence of these events. However, although uncommon, systemic severe and life-threatening adverse events can still occur and it is imperative for an ophthalmologic surgeon to have a comprehensive understanding of them to act in terms of proactive prevention, prompt recognition, and optimal treatment, thus maximizing patients' outcomes. Among life-threatening complication following ophthalmic surgery, cardiovascular events represent the most common ones, including a range of different clinical entities: the oculocardiac reflex, potentially leading to haemodynamic instability and asystole; iatrogenic vascular air embolism, in form of venous air embolism or "pefluorocarbon syndrome", which can lead to obstruction of the pulmonary circulation, respiratory distress and cardiovascular collapse; postoperative venous thromboembolism, in the context of which the management of perioperative antiplatelet and anticoagulant therapy has a crucial role. Furthermore, among infectious complications, that are more commonly limited to the ocular tissues, necrotizing fasciitis represents a potentially lethal infection. This review aims to provide an up-to-date, evidence-based overview of potential life-threatening complications associated with ophthalmic surgery, exploring pathogenesis, risk factors, signs, symptoms, and, briefly, management strategies.

Prognostic impact of PD-L1 expression in surgically resected EGFR-mutant lung adenocarcinoma: A real-world database study in Japan (CReGYT-01 EGFR study).

The expression of programmed cell death-ligand 1 (PD-L1) and mutation in epidermal growth factor receptor (EGFR) are biomarkers used for perioperative treatment of lung adenocarcinoma. However, the clinical significance of PD-L1 expression in surgically resected EGFR-mutant lung adenocarcinoma remains unclear. We conducted a real-world database of patients with surgically resected lung adenocarcinoma from 2015 to 2018 was constructed across 21 centers in Japan. The association among PD-L1 expression, EGFR mutations, and prognosis was evaluated. Among 847 patients, PD-L1 expression was negative (tumor proportion score [TPS] < 1%) in 429 (51%), weakly positive (TPS = 1%-49%) in 275 (32%), and strongly positive (TPS ≥50%) in 143 (17%) patients. EGFR mutations were detected in 331 (39%) patients. PD-L1 expression was associated with poor recurrence-free survival (RFS) (p < .001) in both EGFR-mutant and wild-type patients. However, in EGFR-mutant patients, PD-L1 expression was not associated with overall survival (OS) (p = .506). Multivariable analysis confirmed an association between PD-L1 expression and RFS but not OS. Furthermore, in EGFR-mutant patients treated with EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment post-relapse, PD-L1 expression was not associated with overall response rate (p = .714), disease control rate (p = .554), or progression-free survival (p = .660). In conclusion, PD-L1 expression predicted poor RFS-independent EGFR status but did not show any association with OS in EGFR-mutant patients. The efficacy of post-relapse EGFR-TKI treatment was independent of PD-L1 expression. The significance of PD-L1 expression in perioperative EGFR-TKI therapy should be evaluated.

Safety and efficacy of infusional perioperative Tacrolimus therapy in Crohn’s Disease patients undergoing intestinal resection

Introduction: Perioperative optimization of Crohn’s Disease (CD) patients is mandatory in order to ensure favorable outcomes and limit perioperative morbidity such as anastomosis-related complications. The use of perioperative tacrolimus may offer beneficial inflammatory control and improve postoperative outcome. However, it also may exhibit unwanted effects of immunosuppression on infectious complications and wound healing. Methods: This is a single-center, retrospective study of CD patients undergoing intestinal resection between 2009 and 2018. Characteristics of CD patients receiving infusional perioperative Tacrolimus or not were systematically evaluated and exploratively compared. To investigate the impact of Tacrolimus and other predictors on postoperative infectious complications, simple regression with a threshold of p&lt;0.05 was used. Significant predictors of the simple regression analysis, as well as Tacrolimus, were then included into multiple logistic regression. Results: This analysis included 30 patients (34.88%) having received Tacrolimus perioperatively and 56 patients (65.12%) that were not treated with Tacrolimus. In median, 1mg/day of Tacrolimus was given intravenously for 11 days. Adverse events occurred in three patients (10%). The most common adverse events were headache and paresthesia. Tacrolimus showed no significant correlation to postoperative infectious complications. Furthermore, multiple regression analysis found no significant effect of Tacrolimus on postoperative infectious complications when controlling for previously identified confounders. Conclusion: Administration of Tacrolimus showed no negative impact on postoperative infectious complications in the study cohort, indicating safety of perioperative Tacrolimus therapy. By describing in detail our study population of patients receiving perioperative Tacrolimus, we provide data guiding future prospective studies.

Perioperative direct oral anticoagulant management during cardiac implantable electronic device surgery: an updated systematic review and meta-analysis.

Patients undergoing cardiovascular implantable electronic device (CIED) implantation are often on direct oral anticoagulation (DOAC). However, the evidence on whether to continue or temporarily discontinue DOAC therapy during the perioperative period in these patients is unclear. We conducted a comprehensive literature review using PubMed, Embase, and Cochrane databases through July 2024. We included studies comparing uninterrupted versus interrupted perioperative DOAC therapy in patients undergoing CIED procedure- primary implants, pulse generator replacement, and device upgrades. Primary outcomes were clinically significant device-pocket hematoma and thromboembolic events. Secondary outcomes included any device-pocket hematoma, all-cause mortality, major bleeding, and any bleeding. A total of 1,607 patients from 8 studies were included. The mean age was 73.2years, with atrial fibrillation as the indication for DOAC therapy in most patients. The mean CHA2DS2-VASc was 3.4. Among the included studies, 2 were randomized control trials (RCTs), while the others were observational cohort studies, including one that was propensity score matched. Our meta-analysis found both strategies to be similar in terms of clinically significant pocket hematoma (RR 1.70; 95%CI 0.84-3.45; p = 0.14; I2 = 0%), thromboembolic complications (RR 0.35; 95%CI 0.04-3.32; p = 0.36; I2 = 19%), any pocket hematoma, all-cause mortality and any bleeding with a higher risk of major bleeding with uninterrupted anticoagulation. This meta-analysis shows that uninterrupted DOAC therapy is comparable to interrupted therapy for CIED procedures, with a potential increase in major bleeding risk but low overall complication rates. Further research is needed to confirm the best approach of periprocedural anticoagulation in these patients.

Nomograms Predicting Survival, Recurrence and Beneficiary Identification of Adjuvant Chemotherapy in Treatment-naïve Patients with Rectal Cancer who Underwent Upfront Curative Resection: A multi-institutional study

Objective: To create and validate nomograms predicting overall survival and recurrence in treatment-naïve rectal cancer (RC) patients who underwent upfront surgery. Background: Although multidisciplinary treatment is standard for locally advanced RC, understanding surgical efficacy is important for determining indications for perioperative adjuvant therapy. Methods: RC patients who underwent upfront surgery at the Japanese Society for Cancer of the Colon and Rectum institutions were analyzed. A training cohort (n = 1925) of treatment-naïve patients who underwent surgery between 2007 and 2008 was analyzed to construct prognostic models predicting postoperative survival and recurrence. Discrimination and calibration were performed using an external validation cohort (n = 2957; Japanese colorectal cancer registry, procedures in 2005–2006). Effects of adjuvant chemotherapy on survival were evaluated based on nomogram prediction and Surveillance, Epidemiology, and End Results (SEER) data (n = 10,482; upfront surgery for RC in 2010–2015). Results: In the training cohort, age predicted survival, venous invasion predicted recurrence, and sex, tumor location, histological type, preoperative carcinoembryonic antigen, invasion depth, lymphatic invasion, positive radial margin, and numbers of metastatic nodes and examined nodes predicted both. Internal and external validated Harrell’s C-index values were respectively 0.77 and 0.75 for survival and 0.75 and 0.74 for recurrence. RC patients who underwent upfront surgery in the SEER database were stratified into 3 risk levels by nomogram score. Adjuvant chemotherapy did not improve 5-year survival in low-risk patients, but did so for middle-risk (62.4% vs 76.8%) and high-risk (39.4% vs 63.5%) patients. Conclusion: These nomograms could predict survival and recurrence after upfront curative resection of RC and identify cases expected to benefit more from adjuvant chemotherapy.

OGC SO37 - Pyloric drainage interventions for delayed gastric conduit emptying after oesophagectomy: A single centre analysis

Abstract Background Oesophagectomy in combination with perioperative multimodal therapy is the cornerstone of modern curative treatment for resectable oesophageal cancer. Delayed gastric emptying (DGE) is a common postoperative complication that results from the anatomical and physiological changes in the gastric conduit after an oesophageal resection. It is associated with an increased risk of pneumonia, anastomotic leak and prolonged hospital stay. Although several prophylactic pyloric drainage interventions have been postulated to mitigate the risk of DGE, the optimal modality remains debatable. This study aimed to define the incidence, evaluate prognostic factors, and characterise the management of DGE following oesophagectomy. Method Consecutive patients who underwent an oesophagectomy for oesophageal cancer between January 2022 and March 2024 were retrospectively identified from a hospital database. Pyloric drainage procedures consisted of expectant management, endoscopic/open pyloric Botox and pyloroplasty. Univariable and multivariable analyses were performed to define the incidence of DGE after each pyloric drainage modality, evaluate prognostic factors for DGE, and characterise the need for subsequent intervention in the management of DGE. Results The study cohort comprised 137 patients – mean age 66 years, male 78%. The incidence of DGE was 31%. Pyloroplasty had the lowest incidence of DGE (16%) followed by endoscopic botox (21%). Intra-operative pyloric drainage reduced the risk of DGE (p=0.03). The modality of prophylactic pyloric drainage used significantly influenced the risk of developing DGE (p=0.028). No significant differences were identified between patient demographics, operative approach, and oncological variables in the development of DGE. On multivariable analysis, pyloroplasty was associated with a reduced risk of DGE (OR 0.27, 95% CI 0.09 – 0.71). DGE did not influence overall survival. Conclusion DGE is a common postoperative complication which affects up to 39% of patients undergoing oesophagectomy. Patients who did not undergo a prophylactic pyloric drainage procedure during the index oesophagectomy were at an increased risk of developing DGE. Most patients with DGE (71%) require further intervention via endoscopy and botox injection. Pyloroplasty as a prophylactic drainage modality significantly reduced the risk of developing DGE compared to endoscopic botox. Further prospective randomised controlled trials are required to validate these findings.

Abstract 4138635: The Association of Perioperative Statins and Cardiac Surgery Associated Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Grafting

Backgrounds: Cardiac surgery associated acute kidney injury (CSA-AKI) is a prevalent and detrimental complication following cardiac surgery, with significant effects on both in-hospital and long-term morbidity and mortality. The renal protective effect of statins for patients undergoing cardiac surgery remains unclear. Purpose: This study aims to evaluate the association between perioperative statin therapy and the risk of CSA-AKI following coronary artery bypass grafting (CABG). Methods: This retrospective cohort study included consecutive patients undergoing CABG between 2013 and 2022, with one year follow-up after hospital discharge. Any usage of statin initiated from admission to 72 hours after surgery was defined as perioperative statin therapy. The primary outcome was in-hospital postoperative AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The secondary outcomes were composite measures including all-cause mortality and dialysis at 30 days and one year. Multivariate Cox proportional hazards regression models were constructed to assess the association between perioperative statin and pre-defined outcomes. Results: Among the included 36288 patients, 22272 (61.3%) patients received perioperative statin therapy, with a total of 19683 (54.2%) patients developing CSA-AKI. For the primary outcome, perioperative statin was associated with a significantly decreased risk of CSA-AKI (52.8% vs. 56.5%; adjusted Odds Ratio [OR], 0.865 [95% CI, 0.829-0.904]; p &lt; 0.001). Additionally, the occurrence of a composite measure including all-cause mortality and dialysis was statistically lower in patients who underwent perioperative statin therapy at 30 days (0.7% vs. 1.6%; OR, 0.485 [95% CI, 0.394-0.597]; p &lt; 0.001), as well as at one year (adjusted Hazard Ratio [HR], 0.632 [95% CI, 0.543-0.737], p &lt; 0.001). For the subgroup analysis, the association between perioperative statin and reduced CSA-AKI risk was greater among patients with chronic heart failure and undergoing on-pump CABG. Conclusions: Perioperative statin therapy was associated with significantly lower risks of CSA-AKI following CABG, and a composite measure including all-cause mortality and dialysis at both 30 days and one year. The preventive effect of perioperative statin was more pronounced in patients with chronic heart failure and undergoing on-pump CABG.

Abstract 4116340: The Effect of Periprocedural Statin Therapy on Mortality and Cardiovascular Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis

Background: Transcatheter aortic valve replacement (TAVR) stands as a notable alternative to surgery for severe aortic stenosis (AS). Despite the established benefits of statins in cardiovascular pathologies, their specific impact in patients with severe AS undergoing TAVR remains uncertain. Our study aims to assess whether perioperative statin use improves survival and outcomes post-TAVR. Methods: A search was conducted across various databases to retrieve studies comparing perioperative statin use versus no statin use in patients undergoing TAVR. The primary outcome of interest was all-cause mortality (ACM). Secondary outcomes included stroke, acute kidney injury (AKI), 30-day mortality, myocardial infarction (MI), cardiovascular complications, and in-hospital mortality. Comprehensive Meta-Analysis Software (v. 3) was used to pool odds ratio (OR) under a random-effects model, with statistical significance set at p &lt; 0.05. Results: Our analysis encompassing 20663 patients from 15 observational studies found that perioperative statin use was associated with a significant reduction in ACM (OR= 0.71, 95% CI: 0.61-0.83, I 2 = 50.3%, p&lt;0.001). Although not statistically significant, perioperative statin use demonstrated a trend towards a decreased risk of stroke (OR= 0.90, 95% CI: 0.68-1.19, I 2 = 0%, p= 0.455), AKI (OR= 0.99, 95% CI: 0.75-1.31, I 2 = 49%, p= 0.968), and 30-day mortality (OR= 0.71, 95% CI: 0.46-1.10, I 2 = 0%, p= 0.126), and no difference was seen in the risk of MI (OR= 1.72, 95% CI: 0.73-4.04, I 2 = 0%, p= 0.214), cardiovascular complications (OR= 1.12, 95% CI: 0.91-1.37, I 2 = 0%, p= 0.297), and in-hospital mortality (OR= 0.42, 95% CI: 0.13-1.38, I 2 = 65.8%, p= 0.151) (Figure 1 and 2). Conclusion: Perioperative statin therapy reduces all-cause mortality in TAVR patients but shows limited impact on other outcomes. Further large-scale prospective studies and trials are necessary to corroborate our findings.

The Effects of Perioperative Gender-affirming Hormone Therapy on Facial Feminization Surgery Adverse Events, Facial Features Addressed, and Esthetic Satisfaction: A Multimodal Analysis.

Facial feminization surgery (FFS) treats gender dysphoria in transfeminine patients by addressing the facial bony and soft tissue components. Individuals seeking FFS may be taking gender-affirming hormone replacement therapy [gender-affirming hormone therapy (GAHT)]. This study aims to better characterize the GAHT's impact on venous thromboembolism (VTE) risk, surgical planning, and outcomes. A systematic review and meta-analysis of the literature were carried out to assess the effect of perioperative GAHT continuation on VTE. Cochrane Q and I2 statistics measured study heterogeneity with the following meta-regression exploring these results. Simultaneously, a retrospective review of the senior author's FFS cohort was conducted to investigate GAHT duration's impact on FFS revision rate, complication incidence, and facial structures operated on. Eleven articles were included: 602 patients stopped GAHT, of whom 3 VTEs were recorded (0.49%). This is compared with one episode among the 925 who continued GAHT perioperatively (0.11%). Study heterogeneity was low (0%), but limited VTE sample size precluded meta-analytic conclusions. Gender-affirming hormone therapy duration does not impact the incidence of all-cause complications (P = 0.478), wound infection (P = 0.283), hematoma (P = 0.283), or VTE (P = 1). The only procedures significantly less associated with higher GAHT were tracheal shaving (P = 0.002) and mandibuloplasty (P = 0.003). Finally, the FFS revision rate was not associated with GAHT duration (P = 0.06). There is a paucity of data to assess the safety or harm of continuing GAHT in the FFS perioperative period. Thus, a shared provider-patient decision-making process examining the risks and benefits of GAHT perioperative continuation is warranted. As patients seeking gender-affirming care are diverse, a "one-protocol-fits-all" is not appropriate.

Antithrombotic therapy and the risk of pocket hematoma after subcutaneous implantable cardioverter-defibrillator implantation

Abstract Introduction The PRAETORIAN trial, which randomized S-ICD versus TV-ICD in patients with a class I or IIa indication for ICD therapy, showed that clinically significant pocket hematomas were more frequent following S-ICD implantation. Many ICD recipients have comorbidities requiring anticoagulant (AC) and/or antiplatelet (AP) therapy, which increase the risk for hematoma formation post implantation. In contrast to TV-ICD implantation, little data exists regarding the optimal AC and AP strategy during S-ICD implantation to prevent pocket hematomas. Methods All patients who underwent de novo S-ICD implantations between February 2009 and January 2023 at our tertiary center were included. Data was collected retrospectively from electronic patient records. Clinically significant pocket hematomas were defined as an accumulation of blood at the pocket site within 30 days after S-ICD implantation, necessitating actions including applying a pressure bandage, surgical evacuation, drain insertion, a change in medication or an extended hospital stay or blood transfusion. Results A total of 348 patients were included of which 224 (64.4%) patients used antithrombotic therapy pre-implantation. Median age at implantation was 50 years (IQR: 36-61 years), 33.4% of the patients were female and the vast majority of implants were intermuscular (90.2%). Eighteen (5.2%) patients developed a clinically significant pocket hematoma. A total of 94 (27%) patients used AC therapy prior to the implantation of which 73 (21%) patients used a vitamin K antagonist (VKA). A total of 130 (37.4%) patients used AP therapy at baseline of which 49 (14.1%) patients were on dual AP therapy (DAPT). Continuation of VKA and continuation of DAPT with ticagrelor were independent predictors for pocket hematoma formation (p&amp;lt;0.001, and p&amp;lt;0.001 respectively). There were significantly more pocket hematomas in patients with continued VKA compared to patients with interrupted VKA (27.3 % (6/22) vs. 4.3% (2/47), respectively, p=0.011). Moreover, continuation of DAPT with ticagrelor was associated with significantly more pocket hematomas post implantation compared to continuation of DAPT with clopidogrel (4/12 vs 1/28, respectively, p=0.022). Conclusion This study showed that continuation of VKA during S-ICD implantation was associated with an increased risk of pocket hematoma formation compared to interruption of VKA. The continuation of DAPT with ticagrelor was an independent predictor of pocket hematoma formation and showed significantly more pocket hematomas compared to continuation of DAPT with clopidogrel. These findings support the need for specific peri-operative thrombotic therapy guidelines for S-ICD implantations to reduce the risk of pocket hematomas.

Perioperative systemic therapy, current paradigm and ongoing clinical trials in upper tract urothelial cancer.

To provide of comprehensive overview of existing and future paradigms for perioperative systemic therapy in the treatment of upper tract urothelial carcinoma. Contemporary treatment paradigms for the management of upper tract urothelial carcinoma focus on use of neoadjuvant cisplatin based chemotherapy for high grade disease primarily based on two small single arm phase II clinical trials. More robust evidence from a phase III randomized clinical trial exists for the use of adjuvant platinum based chemotherapy for invasive disease after radical nephroureterectomy, but there are significant concerns about renal function and platinum eligibility after nephroureterectomy. There are currently ongoing clinical trials for nonplatinum based perioperative systemic therapies including checkpoint inhibitors/immunotherapy as well as antibody-drug conjugates, but currently no recommendation can be made for these approaches. Current evidence supports neoadjuvant cisplatin chemotherapy in the setting of high grade disease or concern for significant renal dysfunction after radical nephroureterectomy or platinum based adjuvant chemotherapy in eligible patients with advanced disease after surgery. While there is no established role for nonplatinum based therapies yet, multiple ongoing trials exploring use of immunotherapies and antibody-drug conjugates as monotherapy or combination may provide new therapeutic options in this population.

Perioperative adjuvant therapy with short course of dupilumab with ESS for recurrent CRSwNP.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a high rate of disease recurrence following endoscopic sinus surgery (ESS). Type 2 disease is associated with a higher incidence of recurrence and is believed to impact disease resolution via interference with epithelial healing and pathogen immunity. We wished to verify if perioperative control of Type 2 inflammation with an anti-IL4/IL13 targeting monoclonal antibody and during the resolution period following surgery leads to better control of the disease long term. In this prospective, placebo-controlled, double-blinded trial. Thirty adult subjects with recurrent CRSwNP underwent ESS plus or minus 14 weeks of perioperative dupilumab, initiated 4 weeks (two injections) pre-ESS. Subjective and objective parameters of nasal patency, olfaction, quality of life (QoL), and adverse events were monitored up to 52 weeks post-ESS. Microbiological culture was performed to characterize pathogens colonization under both conditions. ESS safely improved subjective and objective measures of nasal patency, olfaction, and QoL in both groups. Olfaction was conserved longer in the dupilumab-treated group, with 33.3% of subjects presenting anosmia at 12 months after ESS in the dupilumab group compared to 50.0% with placebo. This was associated with persistent decreases in serum IgE, which were not seen with placebo treatment. No unusual safety signals were observed. Short-course adjuvant perioperative treatment with dupilumab is associated with improved long-term olfactory outcomes and persistent lowering of serum IgE.

Strategies for Perioperative Anticoagulant Reversal in Orthopedic Surgery: A Review.

The administration of anticoagulation therapy during major orthopedic surgeries is a clinical challenge due to the risk of thrombotic events and bleeding complications. This review aims to evaluate the current strategies and emerging developments in perioperative anticoagulation reversal. We conducted a literature review on the management of perioperative anticoagulant therapy, which included the current status of anticoagulant reversal agents, as well as personalized medicine, pharmacogenomics, artificial intelligence (AI), and novel drug delivery systems. The review indicates that reversal agents such as idarucizumab and andexanet alfa are crucial in managing bleeding associated with direct oral anticoagulants (DOACs). Personalized medicine, guided by pharmacogenomics, allows for tailored anticoagulation regimens. AI and machine learning (ML) algorithms can enhance the predictive capabilities for bleeding and thrombotic risks. Additionally, nanotechnology and biomarkers offer innovative approaches to drug delivery and personalized treatment. Integrating evidence-based guidelines with innovative reversal agents, personalized medicine, AI and nanotechnology opens a new era in perioperative anticoagulation management. These advancements can ensure patient safety, minimize bleeding risks, and improve surgical outcomes. Future research should focus on the clinical validation of these strategies to ensure their effectiveness across diverse patient populations.

Perioperative medication therapy for Muslim patients in Germany undergoing oncological surgery: a retrospective study

PurposeEngagement of healthcare professionals with patients from diverse cultural and religious backgrounds is crucial in our multicultural society, where miscommunication and errors in medical history taking can lead to incorrect treatment. In particular, Muslim patients may present unique considerations due to their specific cultural and religious beliefs, which can significantly impact treatment outcomes. This study focuses on perioperative medication therapy for patients undergoing upper and lower gastrointestinal tract and pancreatic tumor surgery, specifically examining whether Islamic beliefs were duly considered in medication selection compared to a matching patient cohort.Materials and methodsData from January 2004 to July 2023 were analyzed. Muslim patients were identified using the onomastic method and matched with non-Muslim patients at a 1:3 ratio based on age, gender, and procedure. Analysis included examination of subcutaneous, oral, and intravenous medications, with attention to ingredients and compatibility with Islamic principles.ResultsAmong 5272 patients, only 5 met the study’s inclusion criteria as Muslim patients, undergoing procedures such as anterior rectum resection, gastrectomy, and pancreatic head resection. Their religious affiliations were not documented in the admission records. According to the matched-pair analysis, consistent treatment was performed regardless of religious beliefs. All patients received subcutaneous medication, primarily enoxaparin, instead of fondaparinux, an Islam-compliant alternative. Intravenous heparin was used once for short period. Contrary to Islamic dietary restrictions and the availability of alternatives, capsules containing animal-derived gelatin and other non-compliant medications were administered orally.ConclusionThis study underscores the importance of acknowledging Muslim patients’ cultural and religious backgrounds in the perioperative setting, as failure to do so may lead healthcare professionals to overlook their potential alternative medication needs, which are essential for providing tailored medical care in modern societies. Integration of diversity-related topics into medical curricula is essential for better preparing physicians for clinical practice and ensuring patient-centered care.

Vascular Resection for Pancreas Cancer - 10-year Experience from a Single High Volume-center.

Combined pancreatic and vascular resections are increasingly performed for pancreatic ductal adenocarcinoma (PDAC). We evaluated the outcomes after pancreatectomy with non-vascular resection (NVR), venous resection (VR), and arterial resection (AR). Retrospective review (2011-2023) of 715 PDAC patients treated with curative-intent surgery. Associations among clinicopathological data, perioperative therapy, time to recurrence (TTR), and overall survival (OS) were evaluated. Initial staging revealed 533 resectable, 98 borderline, and 84 locally advanced PDAC cases. Pancreaticoduodenectomy was the most common procedure (n=467). NVR was performed in 351 (58.2%) patients, VR in 181 (30.0%), and AR in 70 (11.8%). The median TTR and OS did not significantly differ according to the initial staging or type of pancreas resection. Median TTR and OS were significantly shorter for VR (14.5 and 22.7mo) compared to NVR (18.6 and 30.5mo, P<0.001) and AR (20.6 and 30.9mo, P=0.004 and P=0.017). Chemotherapy or chemoradiation significantly prolonged TTR (20.1 vs. 10.2mo, P<0.001 and 25.3 vs. 16.4mo, P<0.001) and OS (31.5 vs. 17.2mo, P<0.001 and 35.5 vs. 27.5mo, P=0.030). AR was associated with higher 90-day mortality rates. In the multivariable analysis, vascular resection was not associated with OS. Perioperative therapy, pathological N0 status, and absence of perineural invasion were the key predictors of longer TTR and OS. Pancreatectomy with AR was not associated with worse oncological outcomes when controlling for perioperative therapy. However, AR was associated with higher 90-day mortality rates. Patient selection is crucial when performing AR in patients with PDAC.

Predictors for prolonged and escalated perioperative antibiotic therapy after microvascular head and neck reconstruction: a comprehensive analysis of 446 cases

Literature suggests that intravenous prophylaxis exceeding 48 h offers no additional benefit in preventing surgical site infections (SSI) in patients with microvascular head and neck reconstruction. However, protocols for antibiotic therapy duration post-reconstruction are not standardized. This study identifies factors predicting prolonged intravenous antibiotic use and antibiotic escalation in patients receiving free flap head neck reconstruction. A retrospective analysis of 446 patients receiving free flap reconstruction was conducted, examining predictors for antibiotic therapy > 10 days and postoperative escalation. 111 patients (24.8%) experienced escalation, while 159 patients (35.6%) received prolonged therapy. Multivariate regression analysis revealed predictors for escalation: microvascular bone reconstruction (p = 0.008, OR = 2.0), clinically suspected SSI (p < 0.001, OR = 5.4), culture-positive SSI (p = 0.03, OR = 2.9), extended ICU stay (p = 0.01, OR = 1.1) and hospital-acquired pneumonia (p = 0.01, OR = 5.9). Prolonged therapy was associated with bone reconstruction (p = 0.06, OR = 2.0), preoperative irradiation (p = 0.001, OR = 1.9) and culture-positive SSI (p < 0.001, OR = 3.5). The study concludes that SSIs are a primary factor driving the escalation of perioperative antibiotic use. Clinical suspicion of infection often necessitates escalation, even in the absence of confirmed microbiological evidence. Microvascular bone reconstruction was a significant predictor for both the escalation and extension of antibiotic therapy beyond 10 days. Furthermore, preoperative radiation therapy, hospital-acquired pneumonia, and prolonged ICU stay were associated with an increased likelihood of escalation, resulting in significantly extended antibiotic administration during hospitalization. Antibiotic stewardship programmes must be implemented to reduce postoperative antibiotic administration time.Trial registration The study was registered approved by the local Ethics Committee (Nr: 18-1131-104).

Perioperative use of enteral nutrition with ω-3 polyunsaturated fatty acid in patients with gastric cancer: a meta-analysis.

To systematically evaluate the efficacy and safety of enteral nutrition with ω-3 polyunsaturated fatty acid preparations or standard enteral nutrition preparations used in patients with gastric cancer during perioperative period, and to provide reference for clinical rational drug use. Pubmed, EMbase, The Cochrane Library, CNKI and Wanfang Medical databases were searched by computer to collect relevant literature. The search period was from the establishment of the database to August 1, 2024. Meta-analysis was performed using Revman5.4 software after two researchers independently screened literature, extracted data, and evaluated the risk of bias in included studies. A total of 20 randomized controlled studies were included. The Meta results showed that there was no statistical difference in mortality between the enteral nutrition with ω-3 polyunsaturated fatty acid group and the control group (RR = 0.46, P = 0.17). However, the IEN group demonstrated superior advantages in reducing infection complications (RR = 0.81, P = 0.05) and wound infection (RR = 0.61, P = 0.04) among gastric cancer patients, as well as improving immune-related indicators (including IgG, IgA, IgM, CD4, and CD4/CD8), inflammation-related markers (including CRP, IL-1β, and IL-6), and nutritional indicators (including Total protein, Albumin, and Transferrin). enteral nutrition with ω-3 polyunsaturated fatty acid preparation has advantages in the efficacy and safety of perioperative nutritional therapy in patients with gastric cancer, and can be used as a clinical choice. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

The New Era of Total Neoadjuvant FLOT Therapy for Locally Advanced, Resectable Gastric Cancer: A Propensity-Matched Comparison With Standard Perioperative Therapy.

The FLOT 4-AIO trial established the docetaxel-based regimen's superiority over epirubicin-based triplet therapy in terms of survival rates and acceptable toxicity for locally advanced resectable gastric (LARGC). Yet, fewer than half of the patients achieved completion of eight prescribed FLOT cycles. We proposed that administering all FLOT cycles in the form of total neoadjuvant therapy may improve completion rates and downstaging. This study contrasted total neoadjuvant therapy (FLOT x8) with standard neoadjuvant therapy (FLOT 4+4) for patients LARGC adenocarcinoma who underwent curative resection with routine D2 lymphadenectomy, focusing on histopathological outcomes, toxicity, and survival outcomes. We reviewed patients with histologically confirmed advanced clinical stage cT2 or higher, nodal positive stage (cN+), or both, with resectable gastric tumors and no distant metastases (January 2017 to July 2023). We divided patients into two groups, FLOT 4+4 and FLOT x8; FLOT 4+4 patients underwent four preoperative and four postoperative bi-weekly cycles of docetaxel, oxaliplatin, leucovorin, and fluorouracil, while FLOT x8 patients received all eight cycles preoperatively after a gradual practice change starting from January 2020. Propensity score matching adjusted for age, clinical stage, tumor location, and histology. Of the 77 patients in the FLOT x8 group, 37 were propensity-matched to an equal number in the FLOT 4+4 group. Demographics, duration of surgery, and hospital stay showed no significant differences between the groups. The FLOT x8 group exhibited a significantly higher all-cycle completion rate at 89.1% compared to FLOT 4+4's 67.6% (p < 0.01). Both groups demonstrated comparable hematological and non-hematological toxicity rates, Clavien-Dindo ≥ 3 complications, and CAP tumor regression grades. The mean number of harvested lymph nodes was 42.5 and 41.2 in the FLOT 4+4 and FLOT x8 groups, respectively. Similar rates of disease-free survival and overall survival were noted in both groups, despite a trend toward a higher pathological complete response rate, albeit not statistically significant (8.1% vs. 18.9%, p = 0.29), in the FLOT x8 group at a median follow-up of 36 months. Total neoadjuvant therapy with the FLOT x8 protocol corresponds to higher treatment completion rates, a safety profile similar to standard perioperative therapy, and a twofold increase in complete pathological response. Further research on long-term oncological outcomes is needed to confirm the effectiveness of total neoadjuvant therapy.