Understanding futility in pancreaticoduodenectomy: Insights from a national cohort.

BACKGROUND AND OBJECTIVES: Pancreaticoduodenectomy (PD), the only surgical option for right-sided pancreatic ductal adenocarcinoma (PDAC), carries significant morbidity. Not all patients may be deriving a survival benefit from this operation. We sought to identify the rate of futile PD and its associated factors in a large national cohort. METHODS: We performed a retrospective analysis using the National Cancer Database (2004-2020), including all patients who underwent PD for non-metastatic PDAC. The primary outcome was operative futility, which was defined as death within 12 months of diagnosis despite PD. Multivariable regression was used to identify factors associated with futility. We performed a subgroup analysis on patients who received neoadjuvant systemic therapy. RESULTS: Data from 66 326 patients were analyzed, and 16 772 (25.3%) underwent PD that met criteria for futility. Macroscopically positive margins (odds ratio [OR]: 2.87; 95% confidence interval [CI]: 2.36-3.48), poor tumor differentiation (OR: 2.44; 95% CI: 2.25-2.65), and N2 nodal stage (OR: 2.09; 95% CI: 1.98-2.20) were associated with the greatest odds of futility. Meanwhile, receipt of any systemic therapy (OR: 0.33; 95% CI: 0.31-0.34), receipt of any radiation (OR: 0.60; 95% CI: 0.57-0.63), and receipt of neoadjuvant systemic therapy (OR: 0.62; 95% CI: 0.57-0.66) were associated with the lowest odds of futility. In the neoadjuvant subgroup, a longer diagnosis-to-surgery interval was associated with lower odds of futility. CONCLUSION: PD was futile in about one quarter of patients. Futility was associated with higher age and worse tumor biology. Receipt of neoadjuvant therapy resulted in fewer futile operations.

Implementation of a perioperative registry in Ethiopia to enhance surgical quality improvement.

BACKGROUND: Despite a glaring need and proven efficacy, prospective surgical registries are lacking in low- and middle-income countries. The objective of this study was to design and implement a comprehensive prospective perioperative registry in a low-income country. METHODS: This study was conducted at Hawassa University Comprehensive Specialized Hospital in Hawassa, Ethiopia. Design of the registry occurred from June 2021 to May 2022 and pilot implementation from May 2022 to May 2023. All patients undergoing elective or emergent general surgery were included. Following one year, operability and fidelity of the registry were analyzed by assessing capture rate, incidence of missing data, and accuracy. RESULTS: A total of 67 variables were included in the registry including demographics, preoperative, operative, post-operative, and 30-day data. Of 440 eligible patients, 226 (51.4%) were successfully captured. Overall incidence of missing data and accuracy was 5.4% and 90.2% respectively. Post pilot modifications enhanced capture rate to 70.5% and further optimized data collection processes. CONCLUSION: The establishment of a low-cost electronic prospective perioperative registry in a low-income country represents a significant step forward in enhancing surgical care in under-resourced settings. The initial success of this registry highlights the feasibility of such endeavors when strong partnerships and local context are at the center of implementation. Continuous efforts to refine this registry are ongoing, which will ultimately lead to enhanced surgical quality, research output, and expansion to other sites.

Barriers and Facilitators to Collecting Surgical Outcome Data in Low- and Middle-Income Countries: An International Survey.

Background: Perioperative data are essential to improve the safety of surgical care. However, surgical outcome research (SOR) from low- and middle-income countries (LMICs) is disproportionately sparse. We aimed to assess practices, barriers, facilitators, and perceptions influencing the collection and use of surgical outcome data (SOD) in LMICs. Methods: An internet-based survey was developed and disseminated to stakeholders involved in the care of surgical patients in LMICs. The Performance of Routine Information Systems Management framework was used to explore the frequency and relative importance of organizational, technical, and behavioral barriers. Associations were determined using χ 2 and ANOVA analyses. Results: Final analysis included 229 surgeons, anesthesia providers, nurses, and administrators from 36 separate LMICs. A total of 58.1% of individuals reported that their institution had experience with collection of SOD and 73% of these reported a positive impact on patient care. Mentorship and research training was available in <50% of respondent's institutions; however, those who had these were more likely to publish SOD (P = 0.02). Sixteen barriers met the threshold for significance of which the top 3 were the burden of clinical responsibility, research costs, and accuracy of medical documentation. The most frequently proposed solutions were the availability of an electronic data collection platform (95.3%), dedicated research personnel (93.2%), and access to research training (93.2%). Conclusions: There are several barriers and facilitators to collection of SOD that are common across LMICs. Most of these can be addressed through targeted interventions and are highlighted in this study. We provide a path towards advancing SOR in LMICs.

Cancer research funding in South Asia.

BACKGROUND: The rising burden of cancer significantly influences the global economy and healthcare systems. While local and contextual cancer research is crucial, it is often limited by the availability of funds. In South Asia, with 1.7 million new cancer cases and 1.1 million deaths due to cancer in 2020, understanding cancer research funding trends is pivotal. METHODS: We reviewed funded cancer studies conducted between January 1, 2003, and Dec 31, 2022, using ClinicalTrials.gov, International Cancer Research Partnership (ICRP) Database, NIH World RePORT, and WHO International Clinical Trials Registry Platform (ICTRP). We included funded studies related to all cancer types, conducted in South Asian countries, namely Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. RESULTS: We identified 6561 funded cancer studies from South Asia between 2003 and 2022, increasing from 400 studies in 2003-2007 to 3909 studies in 2018-2022. India had the highest number of funded cancer studies, while Afghanistan, Bhutan, and the Maldives had minimal or no funded cancer research output. Interventional studies (67.3%) were the most common study type funded. The most common cancer sites funded were breast (17.8%), lung (9.9%), oropharyngeal (6.2%), and cervical (5.0%) cancers. On the WHO ICTRP, international funding agencies contributed to a majority of studies (57.5%), except in India where local funding agencies (58.2%) funded more studies. CONCLUSION: This study identified gaps in research funding distribution across cancer types and geographic areas in South Asia. This data can be used to optimize the distribution of cancer research funding in South Asia, fostering equitable advancement in cancer research.

Colon Cancer Survival Among South Asian Americans: A Cross-Sectional Analysis of a National Dataset.

INTRODUCTION: Colon cancer (CC) is one of the most common cancers among South Asian Americans (SAAs). The objective of this study was to measure differences in risk-adjusted survival among SAAs with CC compared to non-Hispanic Whites (NHWs) using a representative national dataset from the United States. METHODS: A retrospective analysis of patients with CC in the National Cancer Database (2004-2020) was performed. Differences in presentation, management, median overall survival (OS), three-year survival, and five-year survival between SAAs and NHWs were compared. Kaplan-Meier analysis and multivariable Cox regression were used to assess differences in survival outcomes, adjusting for demographics, presentation, and treatments received. RESULTS: Data from 2873 SAA and 639,488 NHW patients with CC were analyzed. SAAs were younger at diagnosis (62.2 versus 69.5 y, P < 0.001), higher stage (stage III [29.0% versus 26.2%, P = 0.001] or Stage IV [21.4% versus 20.0%, P = 0.001]), and experienced delays to first treatment (SAA 5.9% versus 4.9%, P = 0.003). SAAs with CC had higher OS (median not achieved versus 68.1 mo for NHWs), three-year survival (76.3% versus 63.4%), and five-year survival (69.1% versus 52.9%). On multivariable Cox regression, SAAs with CC had a lower risk of death across all stages (hazard ratio: 0.64, P < 0.001). CONCLUSIONS: In this national study, SAA patients with CC presented earlier in life with more advanced disease, and a higher proportion experienced treatment delay compared to NHW patients. Despite these differences, SAAs had better adjusted OS than NHW, warranting further exploration of tumor biology and socioeconomic determinants of cancer outcomes in SAAs.

The global burden of cervical cancer requiring surgery: database estimates.

BACKGROUND: Scaling up surgical services for cervical cancer in low and middle income countries requires quantification of the need for those services. The aim of this study was to estimate the global burden of cervical cancer for which access to surgery is required. METHODS: This was a retrospective analysis of publicly available data. Cervical cancer incidence was extracted for each country from the World Health Organization, International Agency for Research, Global Cancer Observatory. The proportion of cases requiring surgery was extrapolated from the United States Surveillance, Epidemiology and End-Result database. The need for cervical cancer surgery was tested against development indicators. RESULTS: Data were available for 175 countries, representing 2.9 billion females aged 15 and over. There were approximately 566,911 women diagnosed with cervical cancer (95% CI 565,462-568,360). An estimated 56.9% of these women (322,686) would require surgery for diagnosis, treatment or palliation (95% CI 321,955 - 323,417). Cervical cancers for which surgery is required represent less than 1% of cancers in high income countries, and nearly 10% of cancers in low income countries. CONCLUSIONS: At least 300,000 cervical cancer cases worldwide require access to surgical services annually. Gathering data on available cervical cancer surgery services in LMIC are a critical next step.

When The Unexpected Happens: The Intriguing Retrieval of a Broken Epidural Catheter.

Introduction: The accidental breakage of an epidural catheter during placement or removal poses a rare but challenging situation in clinical practice. This case report presents the successful removal of a broken epidural catheter and highlights the management strategies employed. Case Report: A 41-year-old male patient underwent a planned orthopedic implant removal surgery under epidural anesthesia. During catheter removal, a portion of the catheter fractured and remained lodged within the epidural space. The patient experienced persistent pain and concern regarding the retained fragment, necessitating immediate intervention. A multidisciplinary team comprising an orthopedic surgeon, neurosurgeon, anesthesiologist, and radiologists collaborated to develop a tailored retrieval strategy. Magnetic resonance imaging aided in localizing the fractured catheter fragment. Using a standard midline posterior approach, the catheter was safely removed without any complications. Post-retrieval monitoring revealed no adverse events, and the patient reported resolution of pain and improved satisfaction. Conclusion: Retrieving a broken epidural catheter requires a systematic and individualized approach. This case report contributes to the existing literature by providing insights into managing this rare complication, highlighting the importance of a multidisciplinary team, appropriate imaging, and meticulous retrieval techniques to ensure patient safety and optimal outcomes.

Multilevel Pre-extensively Drug-resistant Tubercular Spondylodiscitis: Underdiagnosed or Overlooked? A Case Report.

Introduction: Pre-extensively drug-resistant tuberculosis (TB) is characterized by resistance to either a fluoroquinolone (FQ) or a second-line injectable but not both. The urgent need for prompt diagnosis and targeted treatment is emphasized. This report aims to spotlight a case of spinal TB with insufficient assessment, resulting in delayed definitive treatment and an oversight contributing to heightened morbidity. Case Report: An 18-year-old female who was initially diagnosed to have multidrug-resistant TB leading to a 2-year treatment which eventually resulted in multifocal involvement of the spine revealing TB relapse with FQ resistance, categorized as pre-extensively drug-resistant TB. Treatment was shifted to newer drugs, addressing challenges like bilateral psoas abscess, which lead to clinical improvement, allowing the patient to make a good recovery. Conclusion: This case report emphasizes the significance of conducting culture and drug sensitivity testing in patients with tubercular spondylodiscitis. The aim is to prevent misdiagnosis and ensure informed decisions regarding definitive medical treatment or surgical management when necessary.

Association of Neighborhood Disadvantage with Short- and Long-Term Outcomes After Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: While lower socioeconomic status has been shown to correlate with worse outcomes in cancer care, data correlating neighborhood-level metrics with outcomes are scarce. We aim to explore the association between neighborhood disadvantage and both short- and long-term postoperative outcomes in patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We retrospectively analyzed 243 patients who underwent resection for PDAC at a single institution between 1 January 2010 and 15 September 2021. To measure neighborhood disadvantage, the cohort was divided into tertiles by Area Deprivation Index (ADI). Short-term outcomes of interest were minor complications, major complications, unplanned readmission within 30 days, prolonged hospitalization, and delayed gastric emptying (DGE). The long-term outcome of interest was overall survival. Logistic regression was used to test short-term outcomes; Cox proportional hazards models and Kaplan-Meier method were used for long-term outcomes. RESULTS: The median ADI of the cohort was 49 (IQR 32-64.5). On adjusted analysis, the high-ADI group demonstrated greater odds of suffering a major complication (odds ratio [OR], 2.78; 95% confidence interval [CI], 1.26-6.40; p = 0.01) and of an unplanned readmission (OR, 3.09; 95% CI, 1.16-9.28; p = 0.03) compared with the low-ADI group. There were no significant differences between groups in the odds of minor complications, prolonged hospitalization, or DGE (all p > 0.05). High ADI did not confer an increased hazard of death (p = 0.63). CONCLUSIONS: We found that worse neighborhood disadvantage is associated with a higher risk of major complication and unplanned readmission after pancreatectomy for PDAC.

Global Cancer Surgery: pragmatic solutions to improve cancer surgery outcomes worldwide.

The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location.

Evaluating Hyperbolic Dispersion Materials for Cancer Detection.

Current biosensors have limited application in clinical diagnostics as they lack the high order of specificity needed to detect low molecular analytes, especially in complex fluids (such as blood, urine, and saliva). In contrast, they are resistant to the suppression of non-specific binding. Hyperbolic metamaterials (HMMs) offer highly sought- after label-free detection and quantification techniques to circumvent sensitivity issues as low as 105 M concentration in angular sensitivity. This review discusses design strategies in detail and compares nuances in conventional plasmonic techniques to create susceptible miniaturized point-of-care devices. A substantial portion of the review is devoted to developing low optical loss reconfigurable HMM devices for active cancer bioassay platforms. A future perspective of HMM-based biosensors for cancer biomarker detection is provided.

Barriers to Surgical Outcomes Research in Low- and Middle-Income Countries: A Scoping Review.

INTRODUCTION: Systematic collection and analysis of surgical outcomes data is a cornerstone of surgical quality improvement. Unfortunately, there remains a dearth of surgical outcomes data from low- and middle-income countries (LMICs). To improve surgical outcomes in LMICs, it is essential to have the ability to collect, analyze, and report risk-adjusted postoperative morbidity and mortality data. This study aimed to review the barriers and challenges to developing perioperative registries in LMIC settings. METHODS: We conducted a scoping review of all published literature on barriers to conducting surgical outcomes research in LMICs using PubMed, Embase, Scopus, and GoogleScholar. Keywords included 'surgery', 'outcomes research', 'registries', 'barriers', and synonymous Medical Subject Headings derivatives. Articles found were subsequently reference-mined. All relevant original research and reviews published between 2000 and 2021 were included. The performance of routine information system management framework was used to organize identified barriers into technical, organizational, or behavioral factors. RESULTS: Twelve articles were identified in our search. Ten articles focused specifically on the creation, success, and obstacles faced during the implementation of trauma registries. Technical factors reported by 50% of the articles included limited access to a digital platform for data entry, lack of standardization of forms, and complexity of said forms. 91.7% articles mentioned organizational factors, including the availability of resources, financial constraints, human resources, and lack of consistent electricity. Behavioral factors highlighted by 66.6% of the studies included lack of team commitment, job constraints, and clinical burden, which contributed to poor compliance and dwindling data collection over time. CONCLUSIONS: There is a paucity of published literature on barriers to developing and maintaining perioperative registries in LMICs. There is an immediate need to study and understand barriers and facilitators to the continuous collection of surgical outcomes in LMICs.

Accuracy of models to prognosticate survival after surgery for pancreatic cancer in the era of neoadjuvant therapy.

BACKGROUND: Outcomes for pancreatic adenocarcinoma (PDAC) remain difficult to prognosticate. Multiple models attempt to predict survival following the resection of PDAC, but their utility in the neoadjuvant population is unknown. We aimed to assess their accuracy among patients that received neoadjuvant chemotherapy (NAC). METHODS: We performed a multi-institutional retrospective analysis of patients who received NAC and underwent resection of PDAC. Two prognostic systems were evaluated: the Memorial Sloan Kettering Cancer Center Pancreatic Adenocarcinoma Nomogram (MSKCCPAN) and the American Joint Committee on Cancer (AJCC) staging system. Discrimination between predicted and actual disease-specific survival was assessed using the Uno C-statistic and Kaplan-Meier method. Calibration of the MSKCCPAN was assessed using the Brier score. RESULTS: A total of 448 patients were included. There were 232 (51.8%) females, and the mean age was 64.1 years (±9.5). Most had AJCC Stage I or II disease (77.7%). For the MSKCCPAN, the Uno C-statistic at 12-, 24-, and 36-month time points was 0.62, 0.63, and 0.62, respectively. The AJCC system demonstrated similarly mediocre discrimination. The Brier score for the MSKCCPAN was 0.15 at 12 months, 0.26 at 24 months, and 0.30 at 36 months, demonstrating modest calibration. CONCLUSIONS: Current survival prediction models and staging systems for patients with PDAC undergoing resection after NAC have limited accuracy.

Readiness for implementation of novel digital health interventions for postoperative monitoring: a systematic review and clinical innovation network analysis.

An increasing number of digital health interventions (DHIs) for remote postoperative monitoring have been developed and evaluated. This systematic review identifies DHIs for postoperative monitoring and evaluates their readiness for implementation into routine health care. Studies were defined according to idea, development, exploration, assessment, and long-term follow-up (IDEAL) stages of innovation. A novel clinical innovation network analysis used coauthorship and citations to examine collaboration and progression within the field. 126 DHIs were identified, with 101 (80%) being early stage innovations (IDEAL stage 1 and 2a). None of the DHIs identified had large-scale routine implementation. There is little evidence of collaboration, and there are clear omissions in the evaluation of feasibility, accessibility, and the health-care impact. Use of DHIs for postoperative monitoring remains at an early stage of innovation, with promising but generally low-quality supporting evidence. Comprehensive evaluation within high-quality, large-scale trials and real-world data are required to definitively establish readiness for routine implementation.

Irreversibility analysis of radiative flow of Prandtl nanofluid over a stretched surface in Darcy-Forchheimer medium with activation energy and chemical reaction.

This communication elaborates the irreversibility analysis of the flow of Prandtl nanofluid along with thermal radiation past a permeable stretched surface embedded in a Darcy-Forchheimer medium. The activation and chemical impressions along with effects of thermophoretic and Brownian motion are as well examined. The flow symmetry of the problem is modeled mathematically and leading equations are rehabilitated into nonlinear ordinary differential equations (ODEs) through the assistance of suitable similarity variables. The Keller-box technique in MATLAB is employed to draw the impacts of the contributing elements on the velocity field, temperature distribution, and concentration. The impact of the Prandtl fluid parameter has mounting performance for the velocity whereas conflicting behavior is examined in the temperature profile. The achieved numerical results are matched correspondingly with the present symmetrical solutions in restrictive cases and fantastic agreement is scrutinized. In addition, the entropy generation uplifts for the growing values of the Prandtl fluid parameter, thermal radiation, and Brinkman number and decreases for growing numbers of the inertia coefficient parameter. It is also discovered that the coefficient of friction decreases for all parameters involved in the momentum equation. Features of nanofluids can be found in a variety of real-world fields, including microfluidics, industry, transportation, the military, and medicine.

Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study.

BACKGROUND: We hypothesised that zanubrutinib, a highly selective next-generation Bruton tyrosine kinase (BTK) inhibitor, would be a safe and active treatment for patients intolerant of ibrutinib, acalabrutinib, or both. We aimed to assess whether zanubrutinib would prolong treatment duration by minimising treatment-related toxicities and discontinuations in patients with previously treated B-cell malignancies. METHODS: This ongoing, phase 2, multicentre, open-label, single-arm study was done in 20 centres in the USA. Patients aged 18 or older with previously treated B-cell malignancies (chronic lymphocytic leukaemia, small lymphocytic lymphoma, mantle cell lymphoma, Waldenström macroglobulinaemia, or marginal zone lymphoma) who became intolerant of ibrutinib, acalabrutinib, or both, were orally administered zanubrutinib 160 mg twice daily or 320 mg once daily per investigator. The primary endpoint was recurrence and change in severity of ibrutinib or acalabrutinib intolerance events based on investigator-assessed adverse events. Secondary endpoints were investigator-assessed overall response rate; duration of response; disease control rate; and progression-free survival. Analyses included all patients who received any dose of the study drug. This study is registered with ClinicalTrials.gov, NCT04116437. FINDINGS: Between Oct 14, 2019, and Sept 8, 2021, 67 patients (36 [54%] men and 31 [46%] women) who were intolerant of ibrutinib (n=57; cohort 1) or of acalabrutinib or acalabrutinib and ibrutinib (n=10; cohort 2) were enrolled. 63 (94%) patients were White, one (2%) had multiple ethnicities, and three (5%) had unreported or unknown ethnicity. Most intolerance events (81 [70%] of 115 for ibrutinib; 15 [83%] of 18 for acalabrutinib) did not recur with zanubrutinib. Of the recurring events, seven (21%) of 34 ibrutinib intolerance events and two (67%) of three acalabrutinib intolerance events recurred at the same severity with zanubrutinib; 27 (79%) ibrutinib intolerance events and one (33%) acalabrutinib intolerance event recurred at a lower severity with zanubrutinib. No events recurred at higher severity. No grade 4 intolerance events recurred. 64 (96%) of 67 patients had one or more adverse events with zanubrutinib; the most common adverse events were contusion (in 15 [22%] of 67 patients), fatigue (14 [21%]), myalgia (ten [15%]), arthralgia (nine [13%]), and diarrhoea (nine [13%]). Atrial fibrillation occurred in three (4%) patients (all grade 2). Eight (12%) of 67 patients had serious adverse events (anaemia, atrial fibrillation, bronchitis, COVID-19, COVID-19 pneumonia, febrile neutropenia, salmonella gastroenteritis, transfusion reaction, trigeminal nerve disorder, and urinary tract infection). No treatment-related deaths occurred. The median follow-up time was 12·0 months (IQR 8·2-15·6). Among the 64 efficacy-evaluable patients, disease control rate was 93·8% (60; 95% CI 84·8-98·3) and overall response rate was 64·1% (41; 95% CI 51·1-75·7). The median duration of response was not reached; the 12-month event-free duration of response rate was 95·0% (95% CI 69·5-99·3). Similarly, median progression-free survival was not reached; 18-month progression-free survival was 83·8% (95% CI 62·6-93·6). INTERPRETATION: Patients intolerant of previous BTK inhibitors have limited treatment options. These results suggest that zanubrutinib, a safe and viable treatment for patients with B-cell malignancies, might fill that unmet need for those who exhibit intolerance to ibrutinib or acalabrutinib. FUNDING: BeiGene.