Perioperative management of pancreatic exocrine insufficiency-evidence-based proposal for a paradigm shift in pancreatic surgery.

BACKGROUND: Despite exocrine pancreatic insufficiency (EPI) being a significant consequence of pancreatic surgery, there is still no consensus on its perioperative management. This study aimed to evaluate unselective pancreatic enzyme replacement therapy (PERT). METHODS: A prospective, observational study of patients undergoing partial pancreatectomy was conducted. EPI status was assessed pre- and postoperatively, based on three fecal-elastase measurements each. Characteristic symptoms were evaluated by questionnaire. In 85 post-surgical patients, the subjective burden of PERT was measured. RESULTS: 101 patients were followed prospectively. Preoperative EPI screening was available for 83 patients, of which 48% were diagnosed with preexisting EPI. Of those patients with regular exocrine function, 54% developed EPI de novo; this rate being higher following pancreatic head resections (72%) compared to left-sided pancreatectomies (LP) (20%) (p = 0.016). Overall postoperative EPI prevalence was significantly greater following pancreatic head resections (86%) than LP (33%) (p < 0.001). Only young and female patients described a significant burden related to PERT. CONCLUSION: For all patients undergoing pancreatic head resection PERT should be considered beginning prior to surgery, due to the subgroup's high EPI rate and the comparatively low burden of PERT. Patients with LP are at lower risk and should be pre- and postoperatively screened and supplemented accordingly.

Characteristics and Outcome Analysis for Intensive Care Patients Undergoing Decompressive Laparotomy for Abdominal Compartment Syndrome: Impact of Extracorporeal Membrane Oxygenation Support.

(1) Background: Abdominal compartment syndrome (ACS) is a life-threatening situation and is associated with high mortality in the intensive care unit (ICU). Decompressive laparotomy represents the last therapeutic option. This cohort study aims to optimize the selection of ICU patients suffering from ACS who benefit from decompressive laparotomy. (2) Methods: All available data from adult patients treated at the 12 ICUs of a university hospital between 2011 and 2019 were included. Outcome parameters for patients with and without extracorporeal membrane oxygenation (ECMO) were compared. (3) Results: 207 ICU patients with ACS undergoing surgery were identified. Laparotomy resulted in immediate improvement of organ functions in 15% of patients, who then survived more frequently. The overall mortality rate in our cohort was 69%. The group of ECMO patients-including va- and vv-ECMO-showed significantly less organ function improvement and a higher mortality rate of 79% compared to a better postoperative improvement and a lower mortality rate of 62% in non-ECMO patients. (4) Conclusions: There are ICU patients who benefit from decompressive laparotomy-nevertheless, mortality is high. Non-ECMO patients have a better prognosis than ECMO patients. Our findings can support clinical decision-making on emergency surgery and the development of future guidelines.

Career Needs Assessment for Early Career Academic Surgeons Using a Modified Accelerated Delphi Process.

INTRODUCTION: Over the past 2 decades, physicians' wellbeing has become a topic of interest. It is currently unclear what the current needs are of early career academic surgeons (ECAS). METHODS: Consensus statements on academic needs were developed during a Delphi process, including all presenters from the previous European Surgical Association (ESA) meetings (2018-2022). The Delphi involved (1) a literature review, (2) Delphi form generation, and (3) an accelerated Delphi process. The Delphi form was generated by a steering group that discussed findings identified within the literature. The modified accelerated e-consensus approach included 3 rounds over a 4-week period. Consensus was defined as >80% agreement in any round. RESULTS: Forty respondents completed all 3 rounds of the Delphi. Median age was 37 years (interquartile range 5), and 53% were female. Majority were consultant/attending (52.5%), followed by PhD (22.5%), fellowship (15%), and residency (10%). ECAS was defined as a surgeon in 'development' years of clinical and academic practice relative to their career goals (87.9% agreement). Access to split academic and clinical contracts is desirable (87.5%). Consensus on the factors contributing to ECAS underperformance included: burnout (94.6%), lack of funding (80%), lack of mentorship (80%), and excessive clinical commitments (80%). Desirable factors to support ECAS development included: access to e-learning (90.9%), face-to-face networking opportunities (95%), support for research team development (100%), and specific formal mentorship (93.9%). CONCLUSION: The evolving role and responsibilities of ECAS require increasing strategic support, mentorship, and guidance on structured career planning. This will facilitate workforce sustainability in academic surgery in the future.

Peripheral and Portal Venous KRAS ctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: KRAS circulating tumor DNA (ctDNA) has shown biomarker potential for pancreatic ductal adenocarcinoma (PDAC) but has not been applied in clinical routine yet. We aim to improve clinical applicability of ctDNA detection in PDAC and to study the impact of blood-draw site and time point on the detectability and prognostic role of KRAS mutations. METHODS: 221 blood samples from 108 PDAC patients (65 curative, 43 palliative) were analyzed. Baseline peripheral and tumor-draining portal venous (PV), postoperative, and follow-up blood were analyzed and correlated with prognosis. RESULTS: Significantly higher KRAS mutant detection rates and copy numbers were observed in palliative compared to curative patients baseline blood (58.1% vs 24.6%; P = 0.002; and P < 0.001). Significantly higher KRAS mutant copies were found in PV blood compared to baseline (P < 0.05) samples. KRAS detection in pre- and postoperative and PV blood were significantly associated with shorter recurrence-free survival (all P < 0.015) and identified as independent prognostic markers. KRAS ctDNA status was also an independent unfavorable prognostic factor for shorter overall survival in both palliative and curative cohorts (hazard ratio [HR] 4.9, P = 0.011; HR 6.9, P = 0.008). CONCLUSIONS: KRAS ctDNA detection is an independent adverse prognostic marker in curative and palliative PDAC patients-at all sites of blood draw and a strong follow-up marker. The most substantial prognostic impact was seen for PV blood, which could be an effective novel tool for identifying prognostic borderline patients-guiding future decision-making on neoadjuvant treatment despite anatomical resectability. In addition, higher PV mutant copy numbers contribute to an improved technical feasibility.

Potential role of the bitter taste receptor T2R14 in the prolonged survival and enhanced chemoresponsiveness induced by apigenin.

Bitter taste receptors (T2Rs) are G protein­coupled receptors originally detected in the gustatory system. More recently, T2Rs have been shown to be expressed in extra­oral cells eliciting non­gustatory functions. Emerging evidence has suggested a potential role for T2R signaling in diverse pathophysiological conditions, including cancer. -The aim of the present study was to evaluate the expression of T2R14 in pancreatic ductal adenocarcinoma (PDAC) and to assess its involvement in the anticancer effects induced by apigenin, a natural ligand of T2R14. For this purpose, T2R14 expression was explored in PDAC tumor tissue and tumor­derived cell lines. Using the cell lines expressing the highest levels of T2R14, its effects on chemoresponsiveness and migration upon activation with apigenin were investigated in vitro. To the best of our knowledge, the present study was the first to confirm the expression of the T2R family member T2R14 in PDAC. Patients with relatively high levels of T2R14 expression exhibited significantly prolonged overall survival compared with that of patients with low T2R14 expression. Furthermore, novel functions for apigenin were revealed; notably, apigenin was shown to elicit cytotoxic, anti­migratory and chemosensitizing effects to 5­fluoruracil (5­FU) and to 5­FU, leucovorin, irinotecan and oxaliplatin in pancreatic cancer cells. In conclusion, the present study extended the evidence for the anticancer effects of apigenin and strongly indicated the functional relevance of T2R14 in PDAC, even though their respective underlying pathways appear to be independent of each other.

Circulating Cancer Associated Macrophage-like Cells as a Potential New Prognostic Marker in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Circulating Cancer Associated Macrophage-like cells (CAMLs) have been described as novel liquid biopsy analytes and unfavorable prognostic markers in some tumor entities, with scarce data for Pancreatic Ductal Adenocarcinomas (PDAC). METHODS: Baseline and follow-up blood was drawn from resected curative (n = 36) and palliative (n = 19) PDAC patients. A microfluidic size-based cell enrichment approach (ParsortixTM) was used for CAML detection, followed by immunofluorescence staining using pan-keratin, CD14, and CD45 antibodies to differentiate between CAMLs, circulating tumor cells (CTCs), and leukocytes. RESULTS: CAMLs were detectable at baseline in 36.1% of resected patients and 47.4% of palliative PDAC patients. CAML detection was tumor stage independent. Follow-up data indicated that detection of CAMLs (in 45.5% of curative patients) was an independent prognostic factor for shorter recurrence-free survival (RFS) (HR: 4.3, p = 0.023). Furthermore, a combined analysis with CTCs showed the detectability of at least one of these cell populations in 68.2% of resected patients at follow-up. The combined detection of CAMLs and CTCs was also significantly associated with short RFS (HR: 8.7, p = 0.003). CONCLUSIONS: This pilot study shows that detection of CAMLs in PDAC patients can provide prognostic information, either alone or even more pronounced in combination with CTCs, which indicates the power of liquid biopsy marker analyses.

Characterization of RARRES1 Expression on Circulating Tumor Cells as Unfavorable Prognostic Marker in Resected Pancreatic Ductal Adenocarcinoma Patients.

BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), the characterization of circulating tumor cells (CTCs) opens new insights into cancer metastasis as the leading cause of cancer-related death. Here, we focused on the expression of retinoic acid receptor responder 1 (RARRES1) on CTCs as a novel marker for treatment failure and early relapse. METHODS: The stable isotope labeling of amino acids in cell culture (SILAC)-approach was applied for identifying and quantifying new biomarker proteins in PDAC cell lines HPDE and its chemoresistant counterpart, L3.6pl-Res. Fifty-five baseline and 36 follow-up (FUP) peripheral blood samples were processed via a marker-independent microfluidic-based CTC detection approach using RARRES1 as an additional marker. RESULTS: SILAC-based proteomics identified RARRES1 as an abundantly expressed protein in more aggressive chemoresistant PDAC cells. At baseline, CTCs were detected in 25.5% of all PDAC patients, while FUP analysis (median: 11 months FUP) showed CTC detection in 45.5% of the resected patients. CTC positivity (≥3 CTC) at FUP was significantly associated with short recurrence-free survival (p = 0.002). Furthermore, detection of RARRES1 positive CTCs was indicative of an even earlier relapse after surgery (p = 0.001). CONCLUSIONS: CTC detection in resected PDAC patients during FUP is associated with a worse prognosis, and RARRES1 expression might identify an aggressive subtype of CTCs that deserves further investigation.

Tumor-Stroma Interaction in PDAC as a New Approach for Liquid Biopsy and its Potential Clinical Implications.

The extremely poor prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) has remained unchanged for decades. As a hallmark of PDAC histology, the distinct desmoplastic response in the tumor microenvironment is considered a key factor exerting pro- and antitumor effects. Increasing emphasis has been placed on cancer-associated fibroblasts (CAFs), whose heterogeneity and functional diversity is reflected in the numerous subtypes. The myofibroblastic CAFs (myCAFs), inflammatory CAFs (iCAFs) and antigen presenting CAFs (apCAFs) are functionally divergent CAF subtypes with tumor promoting as well as repressing effects. Precise knowledge of the underlying interactions is the basis for a variety of treatment approaches, which are subsumed under the term antistromal therapy. Clinical implementation is still pending due to the lack of benefit-as well as paradoxical preclinical findings. While the prominent significance of CAFs in the immediate environment of the tumor is becoming clear, less is known about the circulating (c)CAFs. cCAFs are of particular interest as they seem not only to be potential new liquid biopsy biomarkers but also to support the survival of circulating tumor cells (CTC) in the bloodstream. In PDAC, CTCs correlate with an unfavorable outcome and can also be employed to monitor treatment response, but the current clinical relevance is limited. In this review, we discuss CTCs, cCAFs, secretomes that include EVs or fragments of collagen turnover as liquid biopsy biomarkers, and clinical approaches to target tumor stroma in PDAC.

A novel risk-scoring system conducing to chemotherapy decision for patients with pancreatic ductal adenocarcinoma after pancreatectomy.

Background: Chemotherapy is suggested to use in all stages of pancreatic cancer. Is it reasonable to recommend chemotherapy for all PDAC patients? It is necessary to distinguish low-risk PDAC patients underwent pancreatectomy, who may not lose survival time due to missed chemotherapy and not need to endure pain, nausea, tiredness, drowsiness, and breath shortness caused by chemotherapy. Methods: Nomograms were constructed with basis from the multivariate Cox regression analysis. X-tile software was utilized to perform risk stratification. Survival curves were used to display the effect of chemotherapy in different risk-stratification. Results: All of the significant variables were used to create the nomograms for overall survival (OS). The total risk score of each patient was calculated by summing the scores related to each variable. X-tile software was utilized to classify patients into high-risk (score >283), median-risk (197

Hypocalcemia as an important differential diagnosis in patients suffering from stridor following thyroidectomy.

It is essential to consider hypocalcemia as a cause of stridor, especially following postoperative thyroidectomy, as hypocalcemia secondary to hypoparathyroidism is an important differential diagnosis. Advances in intraoperative technology to optimize the vascularization of the parathyroid glands can help to predict and prevent patients from a postoperative hypoparathyroidism.

How to prioritise in quality improvement? Targeted implementation as a key for quality improvement in Kenyan health facilities.

BACKGROUND: Data from national surveys of low- and middle income countries indicates that there is still a need to improve the quality of healthcare in resource-poor settings. This study aims to understand the benefit of an integral, facility-driven, indicator-based approach used as a decision-making tool to define effective quality improvement interventions in Kenya. OBJECTIVE: The aim of the study is to understand whether the integral approach developed leads to effective interventions. METHODS: Categorical data is collected from ten health facilities covered by the Integrated Quality Management System (IQMS) project in Kenya. First the information on concrete improvement interventions implemented within the facilities is collected and merged into five different intervention topics. Second, groups of facilities with similar quality improvement interventions are selected to compare between the first and second quality assessment rounds. Those IQMS indicators matching the content of the intervention topic are extracted from the software VISOTOOL. In a third step, the data is summarised using means and SD. A one sample T-test is applied on the mean changes and SD. Frequency counts and percentages were used for the presentation of categorical data. RESULTS: All improvement interventions resulted in positive and higher change values (T2-T1). Four of five intervention topics, show statistically significant improvements including neonatal mortality (42%; p<0.0001), waiting time (39%; p=0.0490), infection prevention control (28%; p=0.0007) and with shortages of staffing and transport in remote areas (32%; p=0.0194). CONCLUSIONS: In all facilities the interventions selected have a positive impact, some of which markedly improved. It demonstrates that this integral quality improvement approach in Kenya can serve as an effective decision-making tool for identification and prioritisation of interventions. Those targeted interventions, being performed under institutionalisation in form of coaching and tutoring, effectively contribute to improving the quality of care in resource poor settings.

If you can't measure it- you can't change it - a longitudinal study on improving quality of care in hospitals and health centers in rural Kenya.

BACKGROUND: The Kenyan Ministry of Health- Department of Standards and Regulations sought to operationalize the Kenya Quality Assurance Model for Health. To this end an integrated quality management system based on validated indicators derived from the Kenya Quality Model for Health (KQMH) was developed and adapted to the area of Reproductive and Maternal and Neonatal Health, implemented and analysed. METHODS: An integrated quality management (QM) approach was developed based on European Practice Assessment (EPA) modified to the Kenyan context. It relies on a multi-perspective, multifaceted and repeated indicator based assessment, covering the 6 World Health Organization (WHO) building blocks. The adaptation process made use of a ten step modified RAND/UCLA appropriateness Method. To measure the 303 structure, process, outcome indicators five data collection tools were developed: surveys for patients and staff, a self-assessment, facilitator assessment, a manager interview guide. The assessment process was supported by a specially developed software (VISOTOOL®) that allows detailed feedback to facility staff, benchmarking and facilitates improvement plans. A longitudinal study design was used with 10 facilities (6 hospitals; 4 Health centers) selected out of 36 applications. Data was summarized using means and standard deviations (SDs). Categorical data was presented as frequency counts and percentages. RESULTS: A baseline assessment (T1) was carried out, a reassessment (T2) after 1.5 years. Results from the first and second assessment after a relatively short period of 1.5 years of improvement activities are striking, in particular in the domain 'Quality and Safety' (20.02%; p < 0.0001) with the dimensions: use of clinical guidelines (34,18%; p < 0.0336); Infection control (23,61%; p < 0.0001). Marked improvements were found in the domains 'Clinical Care' (10.08%; p = 0.0108), 'Management' (13.10%: p < 0.0001), 'Interface In/out-patients' (13.87%; p = 0.0246), and in total (14.64%; p < 0.0001). Exemplarily drilling down the domain 'clinical care' significant improvements were observed in the dimensions 'Antenatal care' (26.84%; p = 0.0059) and 'Survivors of gender-based violence' (11.20%; p = 0.0092). The least marked changes or even a -not significant- decline of some was found in the dimensions 'delivery' and 'postnatal care'. CONCLUSIONS: This comprehensive quality improvement approach breathes life into the process of collecting data for indicators and creates ownership among users and providers of health services. It offers a reflection on the relevance of evidence-based quality improvement for health system strengthening and has the potential to lay a solid ground for further certification and accreditation.