Distinct molecular profiles and shared drug vulnerabilities in pancreatic metastases of renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC) is the most common origin of pancreatic metastases (PM). Distinct genomic aberrations, favorable prognosis, and clinical observations on high angiogenesis, and succeeding tyrosine kinase inhibitor (TKI) sensitivity have been reported in PM-ccRCC. However, no functional or single-cell studies have been conducted thus far. We recruited five PM-ccRCC patients and investigated the genomic, single-cell transcriptomic, and drug sensitivity profiles of their patient-derived cells (PDCs). The PM depicted both expected and novel genomic alterations. Further, the transcriptomics differed from both primary and metastatic ccRCC, with upregulations of the PI3K/mTOR and - supporting the clinical observations - angiogenesis pathways. Data integration at pathway level showed that transcriptomics explained drug sensitivities the best. Accordingly, PM-ccRCC PDCs shared sensitivity to many PI3K/mTOR inhibitors. Altogether, we show distinct genomic and transcriptomic signatures in PM-ccRCC, highlight the superiority of transcriptomics in interpreting drug sensitivities, and encourage the use of TKIs and PI3K/mTOR inhibitors in PM-ccRCC.

Venous thromboembolism incidence and association with overall survival in pancreatic cancer: A Finnish nationwide cohort study.

INTRODUCTION: Pancreatic cancer (PC) is associated with a high risk of venous thromboembolic events (VTEs). We investigated the incidence of VTE before and after the diagnosis of PC and its association with overall survival. METHODS: We identified PC patients diagnosed in 2013-2016 from the Finnish Cancer Registry. Data on healthcare visits and death were collected, along with follow-up data through the end of 2020. We compared patients who underwent radical-intent surgery (RIS) to those who underwent palliative treatment (PT) alone. RESULTS: We identified 4086 PC patients, of whom 343 (8.4%) underwent RIS and 3743 (91.6%) received PT. VTE incidence within 1 year before a PC diagnosis was higher in the PT (4.2%, n = 156) than in the RIS group (0.6%, n = 2; p < 0.001). The cumulative incidence of VTE at 12 and 24 months after a PC diagnosis was 6% (n = 21) and 9% (n = 31), respectively, within the RIS group, and 8% (n = 286) and 8% (n = 304) within the PT group. In the PT group, a VTE within 1 year before a PC diagnosis was independently associated with a worse survival {hazard ratio, HR 1.9 [95% confidence interval (CI) 1.6-2.2]}. In both groups, VTE after a PC diagnosis was associated with a worse survival [RIS group: HR 2.6 (95%CI 1.8-3.7) vs. PT group: HR 2.2 (95%CI 1.9-2.4)]. CONCLUSIONS: A VTE within 1 year before a PC diagnosis more often occurred among PT PC patients than among patients who underwent RIS. VTE might serve as a diagnostic clue to detect PC at an earlier stage.

Surveillance after surgery for pancreatic cancer: a global scoping review of guidelines and a nordic Survey of contemporary practice.

OBJECTIVES: Most patients with pancreatic cancer who have undergone surgical resection eventually develop disease recurrence. |This study aimed to investigate whether there is evidence to support routine surveillance after pancreatic cancer surgery, with a secondary aim of analyzing the implementation of surveillance strategies in the Nordic countries. MATERIALS AND METHODS: A scoping review was conducted to identify clinical practice guidelines globally and research studies relating to surveillance after pancreatic cancer resection. This was followed by a survey among 20 pancreatic units from four Nordic countries to assess their current practice of follow-up for operated patients. RESULTS: Altogether 16 clinical practice guidelines and 17 research studies were included. The guidelines provided inconsistent recommendations regarding postoperative surveillance of pancreatic cancer. The clinical research data were mainly based on retrospective cohort studies with low level of evidence and lead-time bias was not addressed. Active surveillance was recommended in Sweden and Denmark, but not in Norway beyond the post-operative/adjuvant period. Finland had no national recommendations for surveillance. The Nordic survey revealed a wide variation in reported practice among the different units. About 75% (15 of 20 units) performed routine postoperative surveillance. Routine CA 19-9 testing was used by 80% and routine CT by 67% as part of surveillance. About 73% of centers continued follow-up until 5 years postoperatively. CONCLUSION: Evidence for routine long-term (i.e. 5 years) surveillance after pancreatic cancer surgery remains limited. Most pancreatic units in the Nordic countries conduct regular follow-up, but protocols vary.

The Prognostic Significance of Collagen VI in Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis and lack of biomarkers. A rich desmoplastic tumor stroma is considered a hallmark of PDAC and previous studies have indicated upregulated expression of collagen VI (COL6) in PDAC. COL6 is shown to associate with prognosis in many cancers but has been less extensively studied in PDAC. MATERIALS AND METHODS: The expression of COL6 was analyzed by immunohistochemistry in tissue microarrays containing resected tumor tissue samples from PDAC patients (n = 164). Significance of COL6 was estimated with Kaplan-Meier survival estimates and multivariable Cox regression analysis. COL6 protein and mRNA expression patterns were further investigated in publicly available datasets. RESULTS: There were no statistically significant ( P < 0.05) differences in survival when comparing high and low protein expression of any of the analyzed COL6 α-chains (α1(VI): hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.64-1.28; α2(VI): HR 1.28, 95% CI 0.86-1.89; α3(VI): HR 0.91, 95% CI 0.64-1.29). Similar results were obtained when assessing public data from the Cancer Proteome Atlas, Clinical Proteomic Tumor Analysis Consortium, and The Cancer Genome Atlas. CONCLUSIONS: In contrast with previous studies and some other cancers, we did not find any association of COL6 tissue expression and PDAC survival.

E2F transcription factors promote tumorigenicity in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with limited treatment options, illustrating an urgent need to identify new drugable targets in PDACs. OBJECTIVE: Using the similarities between tumor development and normal embryonic development, which is accompanied by rapid cell expansion, we aimed to identify and characterize embryonic signaling pathways that were reinitiated during tumor formation and expansion. METHODS AND RESULTS: Here, we report that the transcription factors E2F1 and E2F8 are potential key regulators in PDAC. E2F1 and E2F8 RNA expression is mainly localized in proliferating cells in the developing pancreas and in malignant ductal cells in PDAC. Silencing of E2F1 and E2F8 in PANC-1 pancreatic tumor cells inhibited cell proliferation and impaired cell spreading and migration. Moreover, loss of E2F1 also affected cell viability and apoptosis with E2F expression in PDAC tissues correlating with expression of apoptosis and mitosis pathway genes, suggesting that E2F factors promote cell cycle regulation and tumorigenesis in PDAC cells. CONCLUSION: Our findings illustrate that E2F1 and E2F8 transcription factors are expressed in pancreatic progenitor and PDAC cells, where they contribute to tumor cell expansion by regulation of cell proliferation, viability, and cell migration making these genes attractive therapeutic targets and potential prognostic markers for pancreatic cancer.

Minimally invasive robot-assisted and laparoscopic distal pancreatectomy in a pan-European registry a retrospective cohort study.

BACKGROUND: International guidelines recommend monitoring the use and outcome of minimally invasive pancreatic surgery (MIPS). However, data from prospective international audits on minimally invasive distal pancreatectomy (MIDP) are lacking. This study examined the use and outcome of robot-assisted (RDP) and laparoscopic (LDP) distal pancreatectomy in the E-MIPS registry. PATIENTS AND METHODS: Post-hoc analysis in a prospective audit on MIPS, including consecutive patients undergoing MIDP in 83 centers from 19 European countries (01-01-2019/31-12-2021). Primary outcomes included intraoperative events (grade 1: excessive blood loss, grade 2: conversion/change in operation, grade 3: intraoperative death), major morbidity, and in-hospital/30-day mortality. Multivariable logistic regression analyses identified high-risk groups for intraoperative events. RDP and LDP were compared in the total cohort and high-risk groups. RESULTS: Overall, 1672 patients undergoing MIDP were included; 606 (36.2%) RDP and 1066 (63.8%) LDP. The annual use of RDP increased from 30.5% to 42.6% ( P <0.001). RDP was associated with fewer grade 2 intraoperative events compared with LDP (9.6% vs. 16.8%, P <0.001), with longer operating time (238 vs. 201 min, P <0.001). No significant differences were observed between RDP and LDP regarding major morbidity (23.4% vs. 25.9%, P =0.264) and in-hospital/30-day mortality (0.3% vs. 0.8%, P =0.344). Three high-risk groups were identified; BMI greater than 25 kg/m 2 , previous abdominal surgery, and vascular involvement. In each group, RDP was associated with fewer conversions and longer operative times. CONCLUSION: This European registry-based study demonstrated favorable outcomes for MIDP, with mortality rates below 1%. LDP remains the predominant approach, whereas the use of RDP is increasing. RDP was associated with fewer conversions and longer operative time, including in high-risk subgroups. Future randomized trials should confirm these findings and assess cost differences.

Cholangitis and Interruptions of Neoadjuvant Chemotherapy Associate with Reduced Overall and Progression-Free Survival in Pancreatic Cancer.

BACKGROUND: Interrupting chemotherapy may explain the reduced overall survival (OS) in patients with pancreatic cancer (PC) with cholangitis. Endoscopic biliary decompression (BD) with metallic stents results in fewer chemotherapy interruptions and a lower cholangitis rate compared with plastic stents. We aimed to determine the impact of cholangitis, neoadjuvant treatment (NAT) interruptions and biliary stent choice on PC patients' survival. METHODS: We conducted a retrospective analysis of 162 patients with cancer of the head of the pancreas undergoing pancreatoduodenectomy after NAT and BD documenting progression-free survival (PFS) and OS. Data on BD, cholangitis, stent type, surgical radicality, and chemotherapy were collected. Survival was estimated based on the Kaplan-Meier method by using the log-rank test and multivariate Cox regression analysis. RESULTS: Median OS and PFS for patients with cholangitis (n = 33, 20%) were 26 and 8 months (95% confidence interval [CI] 20-32 and 5-10 months), respectively, compared with 36 and 17 months (95% CI 31-41 and 12-21 months; p < 0.001 for OS; p = 0.002 for PFS) for patients without cholangitis. Among patients without NAT interruptions median OS and PFS were 35 and 17 months (95% CI 31-40 and 12-21 months), falling to 26 and 7 months (95% CI 18-30 and 5-10 months) among those who experienced an NAT interruption caused by biliary stent failure (n = 26, 16%) (p = 0.039 for OS; p < 0.001 for PFS). We found no difference in OS or PFS between stent types. CONCLUSIONS: Cholangitis and NAT interruptions reduce OS and PFS among PC patients.

The possible dual role of Ang-2 in the prognosis of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) features a dense desmoplastic stroma, which raises the intratumoral interstitial pressure leading to vascular collapse and hypoxia, inducing angiogenesis. Vascular growth factors, such as vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), increase in PDAC. A high VEGF and a high circulating Ang-2 associate with shorter survival in PDAC. In addition to the circulatory Ang-2, PDAC endothelial and epithelial cells express Ang-2. No correlation between tumor epithelial nor endothelial cell Ang-2 expression and survival has been published. We aimed to examine Ang-2 expression and survival. This study comprised PDAC surgical patients at Helsinki University Hospital in 2000-2013. Ang-2 immunohistochemistry staining was completed on 168 PDAC patient samples. Circulating Ang-2 levels were measured using ELISA in the sera of 196 patients. Ang-2 levels were assessed against clinical data and patient outcomes. A low tumor epithelial Ang-2 expression predicted shorter disease-specific survival (DSS) compared with a high expression (p = 0.003). A high serum Ang-2 associated with shorter DSS compared with a low circulating Ang-2 (p = 0.016). Ang-2 seemingly plays a dual role in PDAC survival. Further studies are needed to determine the mechanisms causing tumor cell Ang-2 expression and its positive association with survival.

The impact of implementing current treatment modalities and female sex on gastric cancer outcomes, 2000-2016: a longitudinal nationwide cohort study.

BACKGROUND: The implementation of current treatment modalities and their impact on nationwide gastric cancer outcomes remain poorly understood. Biological differences between females and males could impact survival. We aimed to analyze rates of gastric surgery, chemotherapy, and radiotherapy as well as changes in overall survival among gastric cancer patients diagnosed between 2000-2008 and 2009-2016, respectively, in Finland. MATERIAL AND METHODS: Data on gastric cancer patients were collected from national registries. Cox regression analysis and the Kaplan-Meier method were used to analyze differences in survival. RESULTS: We identified 9223 histologically confirmed gastric cancer patients. The rate of gastric surgery decreased from 44% (n = 2282) to 34% (n = 1368; p < 0.001). The proportion of gastric surgery patients who underwent preoperative oncological treatment increased from 0.5% (n = 12) to 16.2% (n = 222) between the calendar periods (p < 0.001) and stood at 30% in 2016. The median overall survival (OS) improved from 30 months [95% confidence interval (CI) 28-33] to 38 months (95%CI 33-42; p = 0.006) and the period 2009-2016 independently associated with a lower risk of death [hazard ratio (HR) 0.78, 95%CI 0.70-0.87] among patients who underwent gastric surgery. Females exhibited a lower risk of death (HR 0.88, 95%CI 0.81-0.97) among patients who underwent gastric surgery. CONCLUSION: Preoperative oncological treatment was gradually introduced into clinical practice and OS among gastric surgery patients improved. Moreover, female surgical patients exhibited a better survival than male patients.

N-glycosylation in non-invasive and invasive intraductal papillary mucinous neoplasm.

Intraductal papillary mucinous neoplasms (IPMNs), often found incidentally, are potentially malignant cystic tumors of the pancreas. Due to the precancerous nature, IPMNs lacking malignant features should be kept on surveillance. The follow-up relies on magnetic resonance imaging, which has a limited accuracy to define the high-risk patients. New diagnostic methods are thus needed to recognize IPMNs with malignant potential. Here, aberrantly expressed glycans constitute a promising new area of research. We compared the N-glycan profiles of non-invasive IPMN tissues (n = 10) and invasive IPMN tissues (n = 10) to those of non-neoplastic pancreatic controls (n = 5) by matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry. Both IPMN subgroups showed increased abundance of neutral composition H4N4 and decrease in H3N5F1, increase in sialylation, and decrease in sulfation, as compared to the controls. Furthermore, invasive IPMN showed an increase in terminal N-acetylhexosamine containing structure H4N5, and increase in acidic complex-type glycans, but decrease in their complex fucosylation and sulfation, as compared to the controls. In conclusion, the N-glycan profiles differed between healthy pancreatic tissue and non-invasive and invasive IPMNs. The unique glycans expressed in invasive IPMNs may offer interesting new options for diagnostics.

Serum cytokine profiles in patients with pancreatic cancer and chronic pancreatitis.

BACKGROUND: Chronic pancreatitis (CP) may cause tumor-like lesions, creating a challenge in distinguishing between CP and pancreatic ductal adenocarcinoma (PDAC) in a patient. Given that invasive surgery is a standard cancer treatment, we aimed to examine whether a noninvasive diagnostic tool utilizing serum cytokines could safely differentiate between PDAC and CP. METHODS: A pre-operative serum panel comprising 48 inflammatory cytokines, CA19-9, and C-reactive protein (CRP) was analyzed, consisting of 231 patients, 186 with stage I-III PDAC and 45 with CP. We excluded PDAC patients who underwent neoadjuvant therapy and those CP patients with other active malignancies. The laboratory variables most associated with PDAC diagnosis were assessed using logistic regression and selected using the lasso method. RESULTS: The cytokines CTACK, GRO-α, and ß-NGF were selected alongside CA19-9 and CRP for our differential diagnostic model. The area under the curve (AUC) for our differential diagnostic model was 0.809 (95% confidence interval [CI] 0.738-0.880), compared with 0.791 (95% CI 0.728-0.854) for CA19-9 alone (not significant). CONCLUSIONS: We found that inflammatory cytokines CTACK, GRO-α, and ß-NGF alongside CA19-9 and CRP may help distinguish PDAC from CP.

The competence of neonatal intensive care nurses: A systematic review.

OBJECTIVE: The objective was to conduct a systematic review describing the competencies required from nurses working in neonatal intensive care settings. DESIGN: Systematic review. DATA SOURCES: A total of eight databases, including PubMed, Scopus, CINAHL, MEDLINE, Mednar, Web of Science, ProQuest and Medic, were screened for relevant literature during February and September 2022. REVIEW METHODS: The systematic review process followed Joanna Briggs Institute guidelines. The inclusion criteria were: 1) (P = population) registered nurses; 2) (C = concept) the competence; 3) (C = context) nursing in neonatal intensive care units; and 4) cross-sectional study as study method. A critical appraisal tool for cross-sectional studies from Joanna Briggs Institute was used by two independent reviewers. After data extraction, thematic analysis was performed. RESULTS: The database searches yielded a total of 8887 studies and after two independent evaluations, a total of 50 eligible studies were identified comprising of 7536 registered nurses working in neonatal intensive care units across 19 countries. The studies described four main competence themes: 1) neonatal care interventions; 2) caring for a dying infant; 3) family-centered care; and 4) neonatal intensive care interventions. CONCLUSION: Previous research has focused on evaluating specific competencies that are necessary in the neonatal intensive care setting. There is a need for research concerning the overall competence of nurses working in neonatal intensive care units. There was a lot of variety within the quality of the eligible studies and within the used instruments. PROTOCOL REGISTRATION: This systematic review was registered in Prospero (PROSPERO 2022 CRD42022308028).

Efficacy and Safety of Glycosphingolipid SSEA-4 Targeting CAR-T Cells in an Ovarian Carcinoma Model.

Chimeric antigen receptor (CAR) T-cell immunotherapies for solid tumors face critical challenges such as heterogeneous antigen expression. We characterized stage-specific embryonic antigen-4 (SSEA-4) cell-surface glycolipid as a target for CAR T-cell therapy. SSEA-4 is mainly expressed during embryogenesis but is also found in several cancer types making it an attractive tumor-associated antigen. Anti-SSEA-4 CAR-T cells were generated and assessed preclinically in vitro and in vivo for antitumor response and safety. SSEA-4 CAR-T cells effectively eliminated SSEA-4-positive cells in all the tested cancer cell lines, whereas SSEA-4-negative cells lines were not targeted. In vivo efficacy and safety studies using NSG mice and the high-grade serous ovarian cancer cell line OVCAR4 demonstrated a remarkable and specific antitumor response at all the CAR T-cell doses used. At high T-cell doses, CAR T cell-treated mice showed signs of health deterioration after a follow-up period. However, the severity of toxicity was reduced with a delayed onset when lower CAR T-cell doses were used. Our data demonstrate the efficacy of anti-SSEA-4 CAR T-cell therapy; however, safety strategies, such as dose-limiting and/or equipping CAR-T cells with combinatorial antigen recognition should be implemented for its potential clinical translation.

Goal-directed fluid management associates with fewer postoperative fluid collections in pancreatoduodenectomy patients.

BACKGROUND: The association between perioperative fluid management and complications in pancreatoduodenectomy patients remains controversial. We explored the association between fluid management and radiological signs of complications. METHODS: We examined pancreatoduodenectomy patients operated between July 2014 and December 2015 (n = 125) and between January 2017 and June 2018 (n = 124). The first cohort received intraoperative fluid management according to a goal-directed strategy and the second cohort was treated conventionally. We analyzed fluid administration, edema visible in computed tomography (CT) scans seven days postoperatively, and radiological signs of complications occurring up to 30 days. We performed multivariable logistic regression analyses to identify risk factors for fluid collections. RESULTS: No statistically significant difference in postoperative edema via CT scans emerged between the fluid management groups. However, the intraperitoneal space expanded in patients with severe Clavien-Dindo complications compared with patients experiencing mild or no complications (19.1% (IQR 10.4-40.5) vs 2.5% (IQR -7.9-16.6), p = 0.004). Fluid collections were less frequent in the goal-directed group than in the conventional fluid management group (16.8% vs 34.7%, p = 0.001). Risk factors for fluid collections included main pancreatic duct size ≤3 mm, less intraoperative fluid volume accompanying conventional fluid management, a lower postoperative urine output, and postoperative congestive heart failure. The goal-directed group received more intraoperative fluids than the conventional fluid management group and postoperative urine output was higher in the goal-directed group on postoperative days 1-3. CONCLUSIONS: Optimization of intraoperative fluid management through target-controlled strategies and early diuresis were associated with a lower frequency of fluid collections in postoperative CT.

Use and outcome of minimally invasive pancreatic surgery in the European E-MIPS registry.

BACKGROUND: The European registry for minimally invasive pancreatic surgery (E-MIPS) collects data on laparoscopic and robotic MIPS in low- and high-volume centers across Europe. METHODS: Analysis of the first year (2019) of the E-MIPS registry, including minimally invasive distal pancreatectomy (MIDP) and minimally invasive pancreatoduodenectomy (MIPD). Primary outcome was 90-day mortality. RESULTS: Overall, 959 patients from 54 centers in 15 countries were included, 558 patients underwent MIDP and 401 patients MIPD. Median volume of MIDP was 10 (7-20) and 9 (2-20) for MIPD. Median use of MIDP was 56.0% (IQR 39.0-77.3%) and median use of MIPD 27.7% (IQR 9.7-45.3%). MIDP was mostly performed laparoscopic (401/558, 71.9%) and MIPD mostly robotic (234/401, 58.3%). MIPD was performed in 50/54 (89.3%) centers, of which 15/50 (30.0%) performed ≥20 MIPD annually. This was 30/54 (55.6%) centers and 13/30 (43%) centers for MIPD respectively. Conversion rate was 10.9% for MIDP and 8.4% for MIPD. Overall 90 day mortality was 1.1% (n = 6) for MIDP and 3.7% (n = 15) for MIPD. CONCLUSION: Within the E-MIPS registry, MIDP is performed in about half of all patients, mostly using laparoscopy. MIPD is performed in about a quarter of patients, slightly more often using the robotic approach. A minority of centers met the Miami guideline volume criteria for MIPD.

Pancreatic imaging in MEN1-comparison of conventional and somatostatin receptor positron emission tomography/computed tomography imaging in real-life setting.

OBJECTIVE: Pancreatic neuroendocrine tumors (panNETs) are the leading cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). The role of somatostatin receptor positron emission tomography/computed tomography (SSTR PET/CT) in MEN1 has not been established. The aim was to assess pancreatic imaging in MEN1 in a real-life setting. DESIGN: Fifty-eight patients with MEN1 [median age 40 (range 16-72) years] underwent SSTR PET/CT imaging; either as a screening tool regardless of disease stage (n = 47) or to further characterize known panNETs (n = 11). SSTR PET/CT and matched conventional imaging were blindly analyzed. We assessed the findings and the impact of SSTR PET/CT during a median follow-up of 47 months. RESULTS: SSTR PET/CT detected three times as many panNETs as conventional imaging (P < .001). SSTR PET/CT altered the management of 27 patients (47%). Seven patients (12%) were referred for surgery, and five (9%) received systemic treatment. In 15/25 (60%) patients with no previous panNET (n = 22) or in remission after surgery (n = 3), SSTR PET/CT identified a panNET (n = 14) or recurrence (n = 1). In eight patients, SSTR PET/CT revealed a panNET not immediately visible on conventional imaging. During a median follow-up of 47 months, three became visible on conventional imaging, but none required intervention. When SSTR PET/CT was negative, no panNETs were identified on conventional imaging during 38 months of follow-up. CONCLUSIONS: SSTR PET/CT demonstrates high accuracy in the detection of panNETs and alters the clinical management in nearly half of the MEN1-patients. SSTR PET/CT enables timely diagnosis and staging of MEN1-related panNETs.

Health-related quality of life and anxiety levels among patients under surveillance for intraductal papillary mucinous neoplasm.

BACKGROUND: Because of the premalignant nature of intraductal papillary mucinous neoplasms (IPMNs), patients should undergo surveillance as long as they remain fit for surgery. This surveillance, with imaging and laboratory tests every 6 to 12 months, is expensive and may psychologically burden patients. This study aimed to determine the effects of IPMN surveillance on patients´ health-related quality of life (HRQoL) and anxiety levels. METHODS: We included a random subgroup of all IPMN patients undergoing a follow-up check-up at Helsinki University Hospital (HUH) between August 2017 and November 2018. Patients were asked to complete the 15D HRQoL and state-trait anxiety inventory (STAI) questionnaires just before and three months after an IPMN control. RESULTS: Among 899 patients in IPMN follow-up, 232 participated. The 15D HRQoL results showed differences in some IPMN patients' 15 analyzed dimensions compared to a sex- and age-standardized general population cohort, but the clinical relevance of these differences appear doubtful. We detected no significant difference in the anxiety levels determined using the STAI questionnaires before or three months after the IPMN control. CONCLUSION: Surveillance should be less harmful than the risk of disease. Among our patients, the recommended IPMN follow-up carried minimal negative impact on patients' HRQoL or anxiety levels. This result is important, because the number of patients under IPMN surveillance is rapidly increasing and the cancer risk among the majority of these patients remains small. TRIAL REGISTRATION: The Surgical Ethics Committee of Helsinki University Hospital approved this study (Dnro HUS 475/2017) and it was registered at ClinicalTrials.gov (NCT03131076) before patient enrollment began.

Optimal Perioperative Fluid Therapy Associates with Fewer Complications After Pancreaticoduodenectomy.

BACKGROUND: Optimal fluid management in pancreaticoduodenectomy patients remains contested. We aimed to examine the association between perioperative fluid administration and postoperative complications. METHODS: We studied 168 pancreaticoduodenectomy patients operated in 2015 (n = 93) or 2017 (n = 75) at Helsinki University Hospital. In 2015, patients received intraoperative fluids following a goal-directed approach and, in 2017, according to anesthesiologist's clinical practice (conventional fluid management). We analyzed the differences in perioperative fluid administration between the groups, specifically examining the occurrence of severe complications (Clavien-Dindo ≥ III), pancreatic fistulas, cardiovascular complications, and the length of hospital stay. RESULTS: The goal-directed group received more intraoperative fluids than the conventional fluid management group (12.0 ml/kg/h vs. 8.3 ml/kg/h, p < 0.001). Urine output (770 ml vs. 575 ml, p = 0.004) and intraoperative fluid balance (9.4 ml/kg/h vs. 6.3 ml/kg/h, p < 0.001) were higher in the goal-directed group than in the conventional fluid management group. Severe surgical complications (19.4% vs. 38.7%, p = 0.009) as well as clinically relevant pancreatic fistulas (1.1% vs. 10.7%, p = 0.011) occurred more frequently in patients receiving conventional fluid management. Moreover, the conventional fluid management group experienced longer hospital stays (9.0 vs. 11.5 days, p = 0.02). Lower intraoperative fluid volume accompanying conventional fluid management was associated with a higher risk of severe postoperative complications compared with higher volume in the goal-directed group (odds ratio 2.58 (95% confidence interval 1.04-6.42), p = 0.041). CONCLUSIONS: The goal-directed group experienced severe complications less frequently. Our findings indicate that optimizing the intraoperative fluid administration benefits patients, while adopting a too-restrictive approach represents an inferior choice.