Recovery of health-related quality of life after laparoscopic versus open distal pancreatectomy.

BACKGROUND: Limited data comparing recovery of health-related quality of life (HRQoL) after laparoscopic (LDP) versus open distal pancreatectomy (ODP) are available. The aim of this study was to assess the impact of laparoscopy on postoperative HRQOL after DP using the Patient-Reported Outcomes Measurement Information System (PROMIS). METHODS: Data from consecutive patients who underwent DP (2020-2022) enrolled in a prospective clinical trial were reviewed. Patients completed PROMIS-29 plus 2 profile preoperatively, at postoperative day (POD) 15, 30, 90, and 180. Linear regression analysis adjusting for confounders including preoperative PROMIS scores, age, gender, ASA score, diagnosis, and multivisceral resection was used to estimate mean between-group differences (MD) in postoperative PROMIS domains T scores. RESULTS: Overall, 202 patients (118 laparoscopic, 86 open) underwent DP (median age 66 years, pancreatic cancer 41%, multivisceral resection 10%, median LOS 6 days). At POD15, LDP was associated with higher physical function (MD 5.6) and participation in social roles and activities scores (MD 3.8), reduced fatigue (MD - 2.7) and sleep disturbance (MD - 3.8) compared to ODP. At POD30, LDP patients had higher physical function (MD 5.2) and participation in social roles and activities scores (MD 6.0), reduced fatigue (MD - 3.5), and anxiety (MD - 4.0) compared to ODP. No between-group differences were found in HRQoL domains at POD90 and 180. Six months after surgery, the proportions of patients who had not recovered to preoperative physical function, participation in social roles and activities, fatigue, pain interference, sleep disturbance, cognitive function, depression, and anxiety were 31%, 31%, 28%, 20%, 15%, 14%, 8%, and 7%, respectively. CONCLUSIONS: According to PROMIS, LDP resulted in improved physical and social functioning and reduced anxiety and fatigue up to 30 days after surgery compared to ODP. At 6 months after surgery, recovery of physical domains is still incomplete in up to 30% of patients.

Validation of the PROMIS-29 Questionnaire as a Measure of Recovery After Pancreatic Surgery.

OBJECTIVE: To contribute evidence for the reliability, construct validity, and responsiveness of the Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) profile questionnaire as a measure of recovery after pancreatic surgery. BACKGROUND: PROMIS questionnaires have been recommended to evaluate postdischarge recovery after surgery. Evidence supporting their measurement properties in pancreatic surgery is missing. METHODS: An observational validation study designed according to the COSMIN checklist was conducted including data from a prospective clinical trial. Patients undergoing pancreatectomy completed PROMIS-29 preoperatively and on postoperative days (PODs) 15, 30, 90, and 180. Reliability was assessed by internal consistency using Cronbach α. Construct validity was assessed by known-groups comparison. Responsiveness was evaluated hypothesizing that scores would be higher (1) preoperatively versus POD15, (2) on POD30 versus POD15, (3) on POD90 versus POD30, and (4) on POD180 versus POD90. RESULTS: Overall, 510 patients were included in the study. Reliability was good to excellent (α values ranged from 0.82 to 0.97). Data supported 4 of 5 hypotheses tested for construct validity for 5 domains (physical function, anxiety, depression, fatigue, and ability to participate in social roles) at most time points. Responsiveness hypotheses 1, 2, and 3 were supported by the data for physical function, fatigue, sleep disturbance, pain interference, and ability to participate in social roles domains. CONCLUSIONS: PROMIS had excellent reliability, discriminated between most groups expected to have different recovery trajectories and was responsive to the expected trajectory of recovery up to 90 days after surgery. Our findings support the use of PROMIS-29 profile as a patient-reported outcome measure of postdischarge recovery after pancreatectomy.

Management of clinically relevant postoperative pancreatic fistula-related fluid collections after distal pancreatectomy.

BACKGROUND: Distal pancreatectomy is burdened by a high rate of clinically relevant postoperative pancreatic fistula (CR-POPF). The presence of a fistula-related abdominal collection often requires additional treatment such as antibiotics, percutaneous drainage, and endoscopic drainage thus prolonging patient recovery. Aim of this study was to describe the management of abdominal collections related to CR-POPF and identify variables associated with the need for invasive procedures. METHODS: A retrospective review of clinical data for patients who underwent distal pancreatectomy between 2015 and 2020 was conducted. All postoperative CT-scan imaging performed for clinical signs related to POPF was reviewed. The main outcome of the study was the need for procedural management (percutaneous or endoscopic) of CR-POPF-related fluid collections at 90 days after surgery. A multivariate regression analysis was adopted to analyze factors influencing procedural management of the collection. RESULTS: Five hundred sixteen patients were included in the study. Laparoscopic resection was performed in 290 patients (56%). At 90 days after surgery, CR-POPF occurred in 207 (40.1%) patients. A symptomatic collection related to fistula was observed in 130 patients (25.2%). Factors associated with fluid collections were increased body mass index (BMI) (25.5 versus 24, p = 0.001) and intraoperative blood loss (median of 250 versus 200 ml, p < 0.001). Procedural management was required in 70 patients (13.6%); 52 patients required interventional radiology and 18 endoscopic drainage. At multivariate analysis, risk factors for invasive procedures were the following CT-scan parameters: fluid collection diameter greater than 5 cm (OR 6.366, 95%CI 2.29-17.66, p = 0.001), presence of blood in the fluid collection (OR 10.618, 95%CI 1.94-58.09, p = 0.006), and enhancement of its walls (OR 4.073, 95%CI 1.22-13.57, p = 0.022). CONCLUSION: CR-POPF-related fluid collections affect about a quarter of patients undergoing distal pancreatectomy. CT-scan provides important information which can guide the management of the collection in a "step-up" fashion.

M2 Receptor Activation Counteracts the Glioblastoma Cancer Stem Cell Response to Hypoxia Condition.

Glioblastoma multiforme (GBM) is the most malignant brain tumor. Hypoxic condition is a predominant feature of the GBM contributing to tumor growth and resistance to conventional therapies. Hence, the identification of drugs able to impair GBM malignancy and aggressiveness is considered of great clinical relevance. Previously, we demonstrated that the activation of M2 muscarinic receptors, through the agonist arecaidine propargyl ester (Ape), arrests cell proliferation in GBM cancer stem cells (GSCs). In the present work, we have characterized the response of GSCs to hypoxic condition showing an upregulation of hypoxia-inducible factors and factors involved in the regulation of GSCs survival and proliferation. Ape treatment in hypoxic conditions is however able to inhibit cell cycle progression, causing a significant increase of aberrant mitosis with consequent decreased cell survival. Additionally, qRT-PCR analysis suggest that Ape downregulates the expression of stemness markers and miR-210 levels, one of the main regulators of the responses to hypoxic condition in different tumor types. Our data demonstrate that Ape impairs the GSCs proliferation and survival also in hypoxic condition, negatively modulating the adaptive response of GSCs to hypoxia.