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Endoscopic ultrasound-guided tissue acquisition (EUS-TA), including fine-needle aspiration (EUS-FNA) and fine-needle biopsy (EUS-FNB), has revolutionized specimen collection from intra-abdominal organs, especially the pancreas. Advances in personalized medicine and more precise treatment have increased demands to collect specimens with higher cell counts, while preserving tissue structure, leading to the development of EUS-FNB needles. EUS-FNB has generally replaced EUS-FNA as the procedure of choice for EUS-TA of pancreatic cancer. Various techniques have been tested for their ability to enhance the diagnostic performance of EUS-TA, including multiple methods of sampling at the time of puncture, on-site specimen evaluation, and specimen processing. In addition, advances in next-generation sequencing have made comprehensive genomic profiling of EUS-TA samples feasible in routine clinical practice. The present review describes updates in EUS-TA sampling techniques of pancreatic lesions, as well as methods for their evaluation.

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Purpose: Photodynamic therapy (PDT) induces anti-tumor immune responses by triggering immunogenic cell death in tumor cells. Previously, we demonstrated that novel QDs-RGD nanoparticles exhibited high efficiency as photosensitizers in the treatment of pancreatic cancer. However, the underlying mechanism of the anti-tumor immune effects induced by the photosensitizer remains unknown. This study assessed the anticancer immune effect of QDs-RGD, as well as the conventional photosensitizer chlorine derivative, YLG-1, for comparison, against pancreatic cancer in support of superior therapeutic efficacy. Methods: The pancreatic cancer cell line, Panc02, was used for in vitro studies. C57BL/6 mice bearing pancreatic cancer cell-derived xenografts were generated for in vivo studies to assess the anti-tumor effects of QDs-RGD-PDT and YLG-1-PDT. The immunostimulatory ability of both photosensitizers was examined by measuring the expression of damage-associated molecular patterns (DAMP), such as calreticulin (CRT), assessing dendritic cell (DC) maturation, and analyzing cytokine expression. The specific immunity of QDs-RGD and YLG-1-PDT on distant tumor were determined by combining PDT with anti-CTLA-4 antibody. Results: QDs-RGD-PDT and YLG-1-PDT significantly inhibited pancreatic cancer cell growth in a dose- and time-dependent manner. While both photosensitizers significantly promoted CRT release, DC maturation, and interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) expression, QDs-RGD exerted a stronger immunostimulatory effect than YLG-1. Combination treatment with QDs-RGD and CTLA-4 blockade was able to significantly inhibit the growth of distant tumors. Conclusion: QDs-RGD is a novel and effective PDT strategy for treating pancreatic tumors by inducing anti-tumor immune responses.

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BACKGROUND/OBJECTIVES: Pancreatic cancer is characterized by tissue stiffness due to the high concentration of cancer-associated fibroblasts and extracellular matrix. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is performed to diagnose pancreatic cancer but yields false-negative results attributed to inadequate specimens. EUS-elastography is a real-time assessment method to pancreatic tissue stiffness. This study aims to investigate the correlation between diagnostic yield and the number of needle passes based on the stiffness measured by elastography. METHODS: Patients who underwent EUS-TA for pancreatic solid mass were retrospectively reviewed and included in this study. The number of needle passes during EUS-TA was determined based on macroscopic on-site evaluation. Tissue stiffness measurements were taken using EUS-elastography. The primary study outcome was the diagnostic yield. The secondary outcome included the number of needle passes required for a diagnosis. RESULTS: A total of 652 patients were included. The average stiffness differed depending on the location of the tumor, and high-stiffness group had more malignant lesions. Although the diagnostic yield was not significantly different between groups, the number of needle passes was significantly higher in the high-stiffness group (3.6 ± 1.0 vs. 3.2 ± 0.9, p < 0.001). CONCLUSIONS: The higher the stiffness of the pancreatic mass in EUS-elastography, the more needle passes are required to achieve a comparable diagnostic yield.

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INTRODUCTION: Predictive markers of LV5FU2 maintenance benefit after first-line induction with FOLFIRINOX in patients with metastatic pancreatic cancer are necessary to select patients who will not be harmed by this strategy. PATIENTS AND METHODS: We focused on patients who received 12 cycles of FOLFIRINOX (arm A, N = 88) or 8 cycles of FOLFIRINOX followed by LV5FU2 maintenance in controlled patients (arm B, N = 91) from the PRODIGE-35 trial. Prognostic factors and predictors of efficiency were identified by using Cox regression. Median progression-free survival (PFS), overall survival (OS), and time to deterioration of quality of life (TTD-QoL) were evaluated. RESULTS: Poor independent prognostic factors were primary tumor in place, age <65 years and the presence of liver metastases for PFS, a baseline neutrophil/lymphocyte ratio (NLR) ≥5 and CA19.9 ≥500 UI/L for OS, independent of the treatment arm. Patients with one metastatic site had a longer PFS in arm A, whereas patients with ≥2 metastatic sites had a longer PFS in arm B. We also identified predictors of OS and TTD-QoL in arm B but these differences were not statistically significant. CONCLUSION: Except for patients with one metastatic site who benefited more from 12 cycles of FOLFIRINOX, a maintenance strategy with LV5FU2 should be widely offered to mPC patients whose survival and QoL are preserved after 4 months of FOLFIRINOX. (ClinicalTrials.gov: NCT02352337).

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We present a 49-year-old woman requiring living donor liver transplantation after liver metastasis from a pancreatic solid pseudopapillary tumor. After identifying a pancreatic mass and liver lesions, she underwent extensive surgical resection. Pathology revealed a solid pseudopapillary neoplasm of the head and body of the pancreas, extending into the peripancreatic soft tissues and confirmed to have spread to the liver. Subsequently, she underwent adjuvant chemotherapy and radiofrequency ablations of the new liver lesions. Despite immunotherapy and chemotherapy, there was a progression of the lesions. With interval growth of liver lesions, without evidence of extrahepatic disease, she underwent living donor liver transplantation.

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Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of death in the United States and is expected to be ranked second in the next 10 years due to poor prognosis and a rising incidence. Distant metastatic PDAC is associated with the worst prognosis among the different phases of PDAC. The diagnostic options for PDAC are convenient and available for staging, tumor response evaluation, and management of resectable or borderline resectable PDAC. However, imaging is crucial in PDAC diagnosis, monitoring, resectability appraisal, and response evaluation. The advancement of medical technologies is evolving, hence the use of imaging in PDAC treatment options has grown as well as the utilization of ctDNA as a tumor marker. Treatment options for metastatic PDAC are minimal with the primary goal of therapy limited to symptom relief or palliation, especially in patients with low functional capacity at the point of diagnosis. Molecular profiling has shown promising potential solutions that would push the treatment boundaries for patients with PDAC. In this review, we will discuss the latest updates from evidence-based guidelines regarding diagnosis, therapy response evaluation, prognosis, and surveillance, as well as illustrating novel therapies that have been recently investigated for PDAC, in addition to discussing the molecular profiling advances in PDAC.

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Pancreatic primary squamous cell carcinoma (PPSCC) is very uncommon. The major diagnostic method is histology, and it requires the exclusion of a metastasis from a different primary location (lung, esophagus…). Herein, we describe two cases of a PPSCC (one in the head and the other one in the tail and the body of the pancreas) with a brief review of literature. When it comes to the poorly differentiated PPSCC, immunohistochemistry (IHC) is crucial. Regretfully, there is currently no unanimity on treatment, and the outcome is dismal.

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Recent years have brought to light newly developed therapeutic modalities for the treatment of premalignant and malignant pancreatic lesions. The role of EUS-guided radiofrequency ablation (EUS-RFA) as a treatment modality for malignant pancreatic lesions is still under evaluation. Several animal studies and human studies have demonstrated the safety and efficacy of EUS-RFA in the management of premalignant and malignant pancreatic lesions. EUS-RFA therapy can potentially ablate these lesions safely and with minimally invasive techniques. In this article, we provide an updated review of the application of EUS-RFA of pancreatic lesions. We also review the clinical efficacy and safety of this technique and future directions.

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Progressive functional decline is a key element of cancer-associated cachexia. Major barriers to translating preclinical therapies into the clinic include lack of cancer models that accurately mimic functional decline, which develops over time, and use of nonspecific measures, like grip strength, as surrogates for physical function. In this study, we aimed to extend the survival and longevity of a cancer model, to investigate cachexia-related function at the basic science level. Survival extension studies were performed by testing multiple cell lines, dilutions, and vehicle-types in orthotopic implantation of K-rasLSL.G12D/+; Trp53R172H/+; Pdx-1-Cre (KPC)-derived cells. One hundred twenty-eight animals in this new model were assessed for cachexia syndrome phenotype using a battery of anatomical, biochemical, and behavioral techniques. We extended the survival of the KPC orthotopic model to 8-9 wk postimplantation using a relatively low 100-cell dose of DT10022 KPC cells (P < 0.001). In this low-dose orthotopic (LO) model, progressive muscle wasting was detected in parallel to systemic inflammation; skeletal muscle atrophy at the fiber level was detected as early as 3 wk postimplantation compared with controls (P < 0.001). Gait speed in LO animals declined as early as 2 wk postimplantation, whereas grip strength change was a late event. Principal component and regression analyses revealed distinct cachectic and noncachectic animal populations, which we leveraged to show that the gait speed decline was specific to cachexia (P < 0.01), whereas grip strength decline was not (P = 0.19). Gait speed represents an accurate surrogate for cachexia-related physical function as opposed to grip strength.NEW & NOTEWORTHY Previous studies of cancer-induced cachexia have been confounded by the relatively rapid death of animal subjects. Using a lower dose of cancer cells in combination with a battery of behavioral, structural, histological, and biochemical techniques, we show that gait speed is actually the best indicator of functional decline due to cachexia. Future studies are required to define the underlying physiological basis of these findings.

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BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are relatively rare but rank as the second most common pancreatic neoplasm. They can be functional, causing early metabolic disturbances due to hormone secretion, or non-functional and diagnosed later based on tumor size-related symptoms. Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management; some practitioners advocate for surgical removal and others suggest observation due to the tumors' lower potential for malignancy. However, it is unclear whether managing these small tumors expectantly is truly safe. AIM: To evaluate poor prognostic factors in PNETs based on tumor size (> 2 cm or < 2 cm) in surgically treated patients. METHODS: This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín, Colombia. To assess patient survival, quarterly follow-ups were conducted during the first year after surgery, followed by semi-annual consultations at the hospital's hepatobiliary surgery department. Qualitative variables were described using absolute and relative frequencies, and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion. RESULTS: The presence of lymph node involvement, neural involvement, and lymphovascular invasion were all associated with an increased risk of mortality, with hazard ratios of 5.68 (95%CI: 1.26-25.61, P = 0.024), 6.44 (95%CI: 1.43-28.93, P = 0.015), and 24.87 (95%CI: 2.98-207.19, P = 0.003), respectively. Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter. The recurrence rates between the two tumor groups were furthermore similar: 18.2% for tumors smaller than 2 cm and 21.4% for tumors larger than 2 cm. Patient survival was additionally comparable between the two tumor groups. CONCLUSION: Tumor size does not dictate prognosis; lymph node and lymphovascular involvement affect mortality, which highlights that histopathological factors-rather than tumor size-may play a role in management.

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Background: We retrospectively evaluated the usefulness of an elevated glucose-to-lymphocyte ratio (GLR) as a sensitive prognostic biomarker of disease-specific survival in 338 patients who underwent surgical resection of pancreatic ductal adenocarcinoma (PDAC). Methods: The optimal GLR cutoff value was determined using the method of Contal and O'Quigley. Patient demographics, clinical information, and imaging data were analyzed to identify preoperative predictors of long-term survival outcomes. Results: Elevated GLR correlated significantly with aggressive tumor biologic behaviors, such as a high carbohydrate antigen (CA) 19-9 level (p = 0.003) and large tumor size (p = 0.011). Multivariate analysis identified (1) GLR > 92.72 [hazard ratio (HR) = 2.475, p < 0.001], (2) CA 19-9 level > 145.35 (HR = 1.577, p = 0.068), and (3) symptoms (p = 0.064) as independent predictors of long-term, cancer-specific survival. These three risk factors were used to group patients into groups 1 (0 factors), 2 (1-2 factors), and 3 (3 factors), which corresponded to significantly different 5-year overall survival rates (50.2%, 34.6%, and 11.7%, respectively; p < 0.001). Conclusions: An elevated preoperative GLR is associated with aggressive tumor characteristics and is an independent predictor of poor postoperative prognosis in patients with PDAC. Further prospective studies are required to verify these findings.

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This case study reports a rare case of a non-functioning metastatic pancreatic neuroendocrine tumor (pNET) transforming into a functioning pNET. A 59-year-old male, previously treated with distal pancreatectomy, splenectomy, lymph node dissection, liver metastasectomy, and pharmacotherapy, presented with weakness, hypoglycemia, and daily episodes of watery diarrhea. A functioning neuroendocrine liver metastasis expressing insulin and gastrin was identified. Surgical intervention, including left lateral hepatectomy and microwave ablation of multiple intrahepatic lesions, resulted in symptom resolution and uneventful recovery. However, metastatic liver disease re-emerged seven months post-surgery, necessitating chemotherapy. This case highlights the importance of vigilance for symptom development in non-functioning pNETs, signaling potential disease relapse and phenotype transformation, and suggests surgical treatment as a viable option in select cases.

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(1) Background: The aim of this study was to compare the survival benefit of radical antegrade modular pancreatosplenectomy (RAMPS) with conventional distal pancreatosplenectomy (cDPS) in left-sided pancreatic cancer. (2) Methods: A retrospective propensity score matching (PSM) analysis was conducted on 333 patients who underwent RAMPS or cDPS for left-sided pancreatic cancer at four tertiary cancer centers. The study assessed prognostic factors and compared survival and operative outcomes. (3) Results: After PSM, 99 patients were matched in each group. RAMPS resulted in a higher retrieved lymph node count than cDPS (15.0 vs. 10.0, p < 0.001). No significant differences were observed between the two groups in terms of R0 resection rate, blood loss, hospital stay, or morbidity. The 5-year overall survival rate was similar in both groups (cDPS vs. RAMPS, 44.4% vs. 45.2%, p = 0.853), and disease-free survival was also comparable. Multivariate analysis revealed that ASA score, preoperative CA19-9, histologic differentiation, R1 resection, adjuvant treatment, and lymphovascular invasion were significant prognostic factors for overall survival. Preoperative CA19-9, histologic differentiation, T-stage, adjuvant treatment, and lymphovascular invasion were independent significant prognostic factors for disease-free survival. (4) Conclusions: Although RAMPS resulted in a higher retrieved lymph node count, survival outcomes were not different between the two groups. RAMPS was a surgical option to achieve R0 resection rather than a standard procedure.

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The presence of lymphoma in the gastrointestinal tract is most frequently manifested in the stomach and intestines. Pancreatic lymphomas consist of only 0.5% of all pancreatic neoplasms. In this case, we present a patient afflicted by follicular lymphoma with pancreatic involvement. To monitor the progression of this patient's lymphoma, endoscopic ultrasound was used to observe its transformation to large B-cell lymphoma and guide therapy.

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PURPOSE: Accurate staging of disease is vital in determining appropriate care for patients with pancreatic ductal adenocarcinoma (PDAC). It has been shown that the quality of scans and the experience of a radiologist can impact computed tomography (CT) based assessment of disease. The aim of the current study was to evaluate the impact of the rereading of outside hospital (OH) CT by an expert radiologist and a repeat pancreatic protocol CT (PPCT) on staging of disease. METHODS: Patients evaluated at the our institute's pancreatic multidisciplinary clinic (2006 to 2014) with OH scan and repeat PPCT performed within 30 days were included. In-house radiologists staged disease using OH scans and repeat PPCT, and factors associated with misstaging were determined. RESULTS: The study included 100 patients, with a median time between OH scan and PPCT of 19 days (IQR: 13-23 days.) Stage migration was mostly accounted for by upstaging of disease (58.8 % to 83.3 %) in all comparison groups. When OH scans were rereviewed, 21.5 % of the misstaging was due to missed metastases, however, when rereads were compared to the PPCT, occult metastases accounted for the majority of misstaged patients (62.5 %). Potential factors associated with misstaging were primarily related to imaging technique. CONCLUSION: A repeat PPCT results in increased detection of metastatic disease that rereviews of OH scans may otherwise miss. Accessible insurance coverage for repeat PPCT imaging even within 30 days of an OH scan could help optimize delivery of care and alleviate burdens associated with misstaging.

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BACKGROUND: Minimally invasive distal pancreatectomy (MIDP), including laparoscopic and robotic distal pancreatectomy, has gained widespread acceptance over the last decade owing to its favorable short-term outcomes. However, evidence regarding its oncologic safety is insufficient. In March 2023, a randomized phase III study was launched in Japan to confirm the non-inferiority of overall survival in patients with resectable pancreatic cancer undergoing MIDP compared with that of patients undergoing open distal pancreatectomy (ODP). METHODS: This is a multi-institutional, randomized, phase III study. A total of 370 patients will be enrolled from 40 institutions within 4 years. The primary endpoint of this study is overall survival, and the secondary endpoints include relapse-free survival, proportion of patients undergoing radical resection, proportion of patients undergoing complete laparoscopic surgery, incidence of adverse surgical events, and length of postoperative hospital stay. Only a credentialed surgeon is eligible to perform both ODP and MIDP. All ODP and MIDP procedures will undergo centralized review using intraoperative photographs. The non-inferiority of MIDP to ODP in terms of overall survival will be statistically analyzed. Only if non-inferiority is confirmed will the analysis assess the superiority of MIDP over ODP. DISCUSSION: If our study demonstrates the non-inferiority of MIDP in terms of overall survival, it would validate its short-term advantages and establish its long-term clinical efficacy. TRIAL REGISTRATION: This trial is registered with the Japan Registry of Clinical Trials as jRCT 1,031,220,705 [ https://jrct.niph.go.jp/en-latest-detail/jRCT1031220705 ].

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BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS FNAB) is a well established diagnostic method in adult patients, but is rarely used in the paediatric population. The Clinical Department of Gastroenterology at the University Clinical Centre Ljubljana and the Department of Cytopathology at the Institute of Pathology, Faculty of Medicine, University of Ljubljana, Slovenia, have been closely collaborating on EUS FNAB since the introduction in 2010. The aim of the study was to review the cases of EUS FNAB of pancreatic neoplasms in children. PATIENTS AND METHODS: In the digital archive of the Institute of Pathology (IP), Faculty of Medicine (FM), University of Ljubljana (UL), we found 6 cases of EUS FNAB in children, 3 had EUS FNAB of the pancreas, 2 of whom had a cytopathologic diagnosis of a tumour. In the first case, the lesion was ultrasonographically solid, and the cell sample contained branching papillary structures surrounded by aggregates of small cells with nuclear grooves. In the second case, the lesion was ultrasonographically cystic, and predominantly necrosis was seen, with only single preserved cells. Positive nuclear reaction for ß-catenin was found in both cases by immunohistochemical staining. RESULTS: In both cases, the cytopathological diagnosis of solid pseudopapillary neoplasm of the pancreas was made, the cases represent the totality of paediatric cases of pancreatic neoplasms from the Children's Hospital Ljubljana since 2010. There were no adverse events during and after EUS FNAB. A histopathological examination of the tumour resection specimens confirmed the cytopathological diagnosis. CONCLUSIONS: Our experience indicates that EUS FNAB is a safe and effective method for diagnosing pancreatic neoplasms in the pediatric population, as supported by the findings in the literature.

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BACKGROUND: Sarcopenia is associated with poor outcomes in many malignancies. However, the relationship between sarcopenia and the prognosis of pancreatic cancer has not been well understood. The aim of this meta-analysis was to identify the prognostic value of preoperative sarcopenia in patients with pancreatic cancer after curative-intent surgery. METHODS: Database from PubMed, Embase, and Web of Science were searched from its inception to July 2023. The primary outcomes were overall survival (OS), progression-free survival (PFS), and the incidence of major complications. The hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CIs) were used to assess the relationship between preoperative sarcopenia and the prognosis of patients with pancreatic cancer. All statistical analyses were conducted by Review Manager 5.3 and STATA 17.0 software. RESULTS: A total of 23 retrospective studies involving 5888 patients were included in this meta-analysis. The pooled results demonstrated that sarcopenia was significantly associated with worse OS (HR = 1.53, P < 0.00001) and PFS (HR = 1.55, P < 0.00001). However, this association was not obvious in regard to the incidence of major complications (OR = 1.33, P = 0.11). CONCLUSION: Preoperative sarcopenia was preliminarily proved to be associated with the terrible prognosis of pancreatic cancer after surgery. However, this relationship needs to be further validated in more prospective studies.

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Undifferentiated carcinoma of the pancreas (UPC) is a rare, aggressive pancreatic cancer subtype. In addition, there is limited data on optimal management and patients tend to present with unresectable disease. This highlights the need to explore non-surgical treatments, such as chemotherapy and radiotherapy. In 2017, a 40-year-old male was diagnosed with UPC, presenting with a 6 cm mass in the pancreas, encasing the major arteries, indicative of a locally advanced stage. Histopathology confirmed UPC with osteoclast-like giant cells. After nine cycles of modified FOLFIRINOX chemotherapy and concurrent chemoradiotherapy, treatment was stopped in 2018 because of his declining health. Remarkably, despite the cessation of treatment, by 2023, the tumor had shrunk to 3.5 cm with no metabolic activity indicated by FDG-PET/CT. This six-year survival and response to non-surgical treatment highlight potential new avenues for managing unresectable pancreatic cancer, underscoring the need for further comprehensive studies to evaluate these therapeutic strategies.

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Background: Distal pancreatectomy (DP) represents the best therapeutic option for patients with body-tail pancreatic neoplasms (PNs). The enhanced recovery after surgery protocol is widely used for treating patients with PN to speed up postoperative recovery. This study aims to describe our institute's experience in the application of fast recovery protocol in a cohort of patients treated with DP, identifying predictors facilitating a decrease in the length of hospital stay. Patient and Methods: Were retrospectively enrolled 60 consecutive cases of DP performed from January 2016 to June 2022 in patients treated with enhanced recovery protocol, 25% of them were treated with spleen preserving procedure. Single-variable logistic regression models were used to evaluate the potential association between patient characteristics and the probability of postoperative complications. Standard linear regression models were used for length of stay, number of postoperative days (PODs) from surgery to full bowel function recovery, and PODs to the interruption of intravenous analgesia administration. Results: Thirty-four (57%) patients underwent open surgery and 26 (43%) laparoscopic surgery. Patients who underwent laparoscopic surgery and spleen-preserving procedures experienced a lower complication rate (P = .037), shorter length of stay, and time of analgesic requirements. With single-variable logistic regression models patients treated with laparoscopic surgery had statistically significant higher recovery times in terms of nasogastric tube removal (P = .004) and early enteral nutrition (P = .001). Conclusion: Continual refinement with enhanced recovery protocol for treating PN patients based on perioperative counseling and surgical decision-making is crucial to reduce patient morbidity and time for recovery.

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