Biological treatment approach to inflammatory bowel disease is similar in academic and nonacademic centres - prime time for decentralisation of inflammatory bowel disease care?

BACKGROUND: With the increasing number of inflammatory bowel disease (IBD) patients, it is difficult to manage them within specialised IBD teams in academic medical centres: many are therefore treated in nonacademic IBD centres. It is unclear whether the time to introducing biologics is the same in both settings. AIM: We aimed to compare treatment approach with biologics in academic vs. nonacademic centres. METHODS: We analysed Slovenian national IBD registry data (UR-CARE Registry, supported by the European Crohn's and Colitis Organisation), which included 2 academic (2319 patients) and 4 nonacademic IBD (429 patients) centres. RESULTS: The disease phenotype was similar in both settings. In total, 1687 patients received 2782 treatment episodes with biologics. We observed no differences in treatment episodes with TNF-alpha inhibitors (60% vs. 61%), vedolizumab (24% vs. 23%), or ustekinumab (17% vs. 16%) in academic compared to nonacademic centres ( P  = 0.949). However, TNF inhibitors were less often the first biologic in academic centres (TNF inhibitors: 67.5% vs. 74.0%, vedolizumab: 20.3% vs. 17.9%, ustekinumab: 12.1% vs. 8.1%; P = 0.0096). Consequently, more patients received ustekinumab (29.8% vs. 18.3%) and vedolizumab (17.4% vs. 13.5%) and fewer TNF inhibitors (52.7% vs. 68.2%) for Crohn's disease in academic compared to nonacademic centres, with no such differences for ulcerative colitis. The time to initiation of the first biologic from diagnosis was short and similar in both settings (11.3 vs. 10.4 months, P  = 0.2). CONCLUSION: In this nationwide registry analysis, we observed that biological treatment choice was similar in academic and nonacademic settings. These findings support the decentralisation of IBD care.

Predictive value of preoperative albumin-bilirubin score and other risk factors for short-term outcomes after open pancreatoduodenectomy.

BACKGROUND: Pancreatoduodenectomy represents a complex procedure involving extensive organ resection and multiple alimentary reconstructions. It is still associated with high morbidity, even in high-volume centres. Prediction tools including preoperative patient-related factors to preoperatively identify patients at high risk for postoperative complications could enable tailored perioperative management and improve patient outcomes. AIM: To evaluate the clinical significance of preoperative albumin-bilirubin score and other risk factors in relation to short-term postoperative outcomes in patients after open pancreatoduodenectomy. METHODS: This retrospective study included all patients who underwent open pancreatic head resection (pylorus-preserving pancreatoduodenectomy or Whipple resection) for various pathologies during a five-year period (2017-2021) in a tertiary care setting at University Medical Centre Ljubljana, Slovenia and Cattinara Hospital, Trieste, Italy. Short-term postoperative outcomes, namely, postoperative complications, postoperative pancreatic fistula, reoperation, and mortality, were evaluated in association with albumin-bilirubin score and other risk factors. Multiple logistic regression models were built to identify risk factors associated with these short-term postoperative outcomes. RESULTS: Data from 347 patients were collected. Postoperative complications, major postoperative complications, postoperative pancreatic fistula, reoperation, and mortality were observed in 52.7%, 22.2%, 23.9%, 21.3%, and 5.2% of patients, respectively. There was no statistically significant association between the albumin-bilirubin score and any of these short-term postoperative complications based on univariate analysis. When controlling for other predictor variables in a logistic regression model, soft pancreatic texture was statistically significantly associated with postoperative complications [odds ratio (OR): 2.09; 95% confidence interval (95%CI): 1.19-3.67]; male gender (OR: 2.12; 95%CI: 1.15-3.93), soft pancreatic texture (OR: 3.06; 95%CI: 1.56-5.97), and blood loss (OR: 1.07; 95%CI: 1.00-1.14) were statistically significantly associated with major postoperative complications; soft pancreatic texture was statistically significantly associated with the development of postoperative pancreatic fistula (OR: 5.11; 95%CI: 2.38-10.95); male gender (OR: 1.97; 95%CI: 1.01-3.83), soft pancreatic texture (OR: 2.95; 95%CI: 1.42-6.11), blood loss (OR: 1.08; 95%CI: 1.01-1.16), and resection due to duodenal carcinoma (OR: 6.58; 95%CI: 1.20-36.15) were statistically significantly associated with reoperation. CONCLUSION: The albumin-bilirubin score failed to predict short-term postoperative outcomes in patients undergoing pancreatoduodenectomy. However, other risk factors seem to influence postoperative outcomes, including male sex, soft pancreatic texture, blood loss, and resection due to duodenal carcinoma.

Histologic changes of porcine portal vein anastomosis after electrochemotherapy with bleomycin.

Electrochemotherapy (ECT1) is used for treatment of unresectable abdominal malignancies. This study aims to show that ECT of porcine portal vein anastomosis is safe and feasible in order to extend the indications for margin attenuation after resection of locally advanced pancreatic carcinoma. No marked differences were found between the control group and ECT treated groups. Electroporation thus caused irreversible damage to the vascular smooth muscle cells in tunica media that could bedue to the narrow irreversible electroporation zone that may occur near the electrodes, or due to vasa vasorum thrombosis in the tunica externa. Based on the absence of vascular complications, and similar histological changes in lienal veinanastomosis, we can conclude that ECT of portal vein anastomosis is safe and feasible.

Radiological assessment of skeletal muscle index and myosteatosis and their impact postoperative outcomes after liver transplantation.

BACKGROUND: Liver transplantation offers curative treatment to patients with acute and chronic end-stage liver disease. The impact of nutritional status on postoperative outcomes after liver transplantation remains poorly understood. The present study investigated the predictive value of radiologically assessed skeletal muscle index (SMI) and myosteatosis (MI) on postoperative outcomes. PATIENTS AND METHODS: Data of 138 adult patients who underwent their first orthotopic liver transplantation were retrospectively analysed. SMI and MI in computer tomography (CT) scan at the third lumbar vertebra level were calculated. Results were analyzed for the length of hospitalisation and postoperative outcomes. RESULTS: In 63% of male and 28.9% of female recipients, low SMI was found. High MI was found in 45(32.6%) patients. Male patients with high SMI had longer intensive care unit (ICU) stay (P < 0.025). Low SMI had no influence on ICU stay in female patients (P = 0.544), length of hospitalisation (male, P > 0.05; female, P = 0.843), postoperative complication rates (males, P = 0.883; females, P = 0.113), infection rate (males, P = 0.293, females, P = 0.285) and graft rejection (males, P = 0.875; females, P = 0.135). The presence of MI did not influence ICU stay (P = 0.161), hospitalization (P = 0.771), postoperative complication rates (P = 0.467), infection rate (P = 0.173) or graft rejection rate (P = 0.173). CONCLUSIONS: In our study, changes in body composition of liver transplant recipients observed with SMI and MI had no impact on postoperative course after liver transplantation. CT body composition analysis of recipients and uniformly accepted cut-off points are crucial to producing reliable data in the future.

Is Surgery in Autoimmune Pancreatitis Always a Failure?

Autoimmune pancreatitis is a rare form of chronic pancreatitis of presumed autoimmune etiology. Due to significant overlap in clinical and imaging characteristics, misdiagnosis as a pancreatic malignancy is common. As a result, a significant number of patients undergo a major pancreatic resection, associated with considerable morbidity, for a disease process that generally responds well to corticosteroid therapy. In the past ten years, important advances have been made in understanding the disease. Several diagnostic criteria have been developed to aid in diagnosis. Despite this, pancreatic resection may still be required in a subset of patients to reliably exclude pancreatic malignancy and establish a definite diagnosis of autoimmune pancreatitis. This article aimed to define the role of surgery in autoimmune pancreatitis, if any. For this purpose, published case series of patients with a diagnosis of autoimmune pancreatitis, based on the histopathological examination of surgical specimens, were reviewed and patients' clinical, radiological and serological details were assessed. At the end, histopathologic examinations of patients who underwent pancreatic resection at our department in the last 10 years were retrospectively reviewed in order to identify patients with autoimmune pancreatitis and assess their clinical characteristics.

Plasma Extracellular Vesicle Characteristics as Biomarkers of Resectability and Radicality of Surgical Resection in Pancreatic Cancer-A Prospective Cohort Study.

Due to possible diagnostic misjudgment of tumor resectability, patients with pancreatic ductal adenocarcinoma (PDAC) might be exposed to non-radical resection or unnecessary laparotomy. With small extracellular vesicles (sEV) obtained by liquid biopsy, we aimed to evaluate their potential as biomarkers of tumor resectability, radicality of resection and overall survival (OS). Our prospective study included 83 PDAC patients undergoing surgery with curative intent followed-up longitudinally. sEV were isolated from plasma, and their concentration and size were determined. Fifty patients underwent PDAC resection, and thirty-three had no resection. Preoperatively, patients undergoing resection had higher sEV concentrations than those without resection (p = 0.023). Resection was predicted at the cutoff value of 1.88 × 109/mL for preoperative sEV concentration (p = 0.023) and the cutoff value of 194.8 nm for preoperative mean diameter (p = 0.057). Furthermore, patients with R0 resection demonstrated higher preoperative plasma sEV concentrations than patients with R1/R2 resection (p = 0.014). If sEV concentration was above 1.88 × 109/mL or if the mean diameter was below 194.8 nm, patients had significantly longer OS (p = 0.018 and p = 0.030, respectively). Our proof-of-principle study identified preoperative sEV characteristics as putative biomarkers of feasibility and radicality of PDAC resection that also enable discrimination of patients with worse OS. Liquid biopsy with sEV could aid in PDAC patient stratification and treatment optimization in the future.

Intra­tumor heterogeneity of cancer stem cell­related genes and their potential regulatory microRNAs in metastasizing colorectal carcinoma.

Intra­tumor heterogeneity (ITH) is related to cancer progression, therapy resistance and recurrences, and is one of the challenging fields in cancerogenesis research. Cancer stem cells (CSC) are thought to be crucially involved in the pathogenesis of several cancer types, including colorectal carcinoma (CRC), and associated with ITH. In the present study, the expression gradient of four genes related to CSC (L1TD1, SLITRK6, ST6GALNAC1 and TCEA3) and their potential regulatory microRNAs (miRNAs) were investigated in the central part and invasive front of the primary tumor, as well as in lymph node and liver metastases. In total, 63 formalin­fixed paraffin­embedded biopsy samples of primary tumor (central part, invasive tumor front), as well as lymph node and liver metastases from 19 patients with CRC, were analyzed. The expression of selected genes (L1TD1, SLITRK6, ST6GALNAC1 and TCEA3) and miRNAs (miR­199a­3p, miR­425­5p, miR­1225­3p, miR­1233­3p and miR­1303) was evaluated using reverse transcription­quantitative PCR. Significant differences in expression were identified for all investigated genes in lymph node metastasis, but not in the liver metastases. All investigated miRNAs were significantly differentially expressed in lymph node metastasis, and miR­199a­3p, miR­425­5p and miR­1233­3p in liver metastasis. Furthermore, a negative correlation between the expression of miR­199a­3p and expression of its potential target gene SLITRK6 was confirmed. The present results provide further evidence that expression of CSC­related genes and their potential regulatory miRNAs contribute to ITH in CRC, lymph node and liver metastasis. The SLITRK6 gene and its regulatory miRNA miR­199a­3p are promising for further validation in functional studies to deepen the present understanding of the regulation of CSC­related genes in CRC.

Intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma: A case report.

BACKGROUND: The ampulla of Vater is an anatomically and histologically complex region giving rise to a heterogenous group of tumors. This is, to the best of our knowledge, the first case of intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma reported in the literature. CASE SUMMARY: A 61-year-old woman presented to the emergency department for evaluation of painless jaundice. Contrast-enhanced computed tomography (CT) of the abdomen and chest showed a periampullary tumor mass measuring 15 mm × 12 mm × 14 mm, with no evidence of locoregional and distant metastases, for which she underwent pancreatoduodenectomy. Histopathologic examination of a resected specimen revealed an intra-ampullary papillary tubular neoplasm with high-grade dysplasia in combination with poorly differentiated grade 3 neuroendocrine carcinoma with a mitotic count of more than 20 mitoses per 10 high power fields and Ki-67 index of 100%. No positive lymph nodes were identified. Her postoperative course was uneventful. Postoperatively, she remained under close surveillance. Multiple liver metastases were observed on follow-up CT 8 mo after the surgery, so systemic therapy with cisplatin and etoposide was initiated. CONCLUSION: The simultaneous occurrence of neuroendocrine and non-neuroendocrine tumors in the ampulla of Vater is rare and the pathogenesis of such tumors is largely unknown. Due to unpredictable clinical behavior and lack of solid evidence on optimal treatment strategy, close patient surveillance is advised after radical resection of the primary tumor.

Neuroendocrine Tumor Arising within Mature Cystic Teratoma of the Pancreas: Literature Review and Case Report.

Cystic teratomas are germ cell tumors most commonly found in the ovaries and testes. The pancreas, however, is very rare as a site of occurrence. Moreover, only two cases of cystic teratoma with concomitant neuroendocrine tumor have been reported to date. We report the case of a 33-year-old female who presented with abdominal pain. Computed tomography and magnetic resonance imaging of the upper abdomen revealed an 85 mm cystic tumor in the head of the pancreas. Cystic teratoma and mucinous cystadenoma were suggested as differential diagnoses. Cytopathologic analysis of endoscopic ultrasound-guided fine needle aspiration was consistent with mucinous cystadenoma. Therefore, the patient underwent surgical resection. Histologic analysis revealed a mature cystic teratoma of the pancreas with a concomitant neuroendocrine tumor. The patient is in great condition at 8 months follow-up. Cystic teratoma of the pancreas with a concomitant neuroendocrine tumor is an extremely rare condition. Surgical resection remains the mainstay of treatment as it provides a definitive diagnosis and no recurrences have been reported to date.

Simultaneous robotic resection of pheochromocytoma and gastrointestinal stromal tumour in an adult neurofibromatosis type 1 patient: A single-docking procedure using da Vinci XI platform.

The risk of tumours, including pheochromocytoma and gastrointestinal stromal tumour is higher in patients with neurofibromatosis Type 1 (NF1). The co-occurrence of these two tumours is rare, and most patients are symptomatic. In this case report we describe the case of an asymptomatic 42-year-old female patient with left adrenal mass and concurrent lesion in the jejunum, just distal to the ligament of Treitz. Both tumours were successfully simultaneously removed by totally robotic transperitoneal technique using da Vinci Robotic Surgical System Xi.

Clinical Outcomes After Total Pancreatectomy: A Prospective Multicenter Pan-European Snapshot Study.

OBJECTIVE: To assess outcomes among patients undergoing total pancreatectomy (TP) including predictors for complications and in-hospital mortality. BACKGROUND: Current studies on TP mostly originate from high-volume centers and span long time periods and therefore may not reflect daily practice. METHODS: This prospective pan-European snapshot study included patients who underwent elective (primary or completion) TP in 43 centers in 16 European countries (June 2018-June 2019). Subgroup analysis included cutoff values for annual volume of pancreatoduodenectomies (<60 vs ≥60).Predictors for major complications and in-hospital mortality were assessed in multivariable logistic regression. RESULTS: In total, 277 patients underwent TP, mostly for malignant disease (73%). Major postoperative complications occurred in 70 patients (25%). Median hospital stay was 12 days (IQR 9-18) and 40 patients were readmitted (15%). In-hospital mortality was 5% and 90-day mortality 8%. In the subgroup analysis, in-hospital mortality was lower in patients operated in centers with ≥60 pancreatoduodenectomies compared <60 (4% vs 10%, P = 0.046). In multivariable analysis, annual volume <60 pancreatoduodenectomies (OR 3.78, 95% CI 1.18-12.16, P = 0.026), age (OR 1.07, 95% CI 1.01-1.14, P = 0.046), and estimated blood loss ≥2L (OR 11.89, 95% CI 2.64-53.61, P = 0.001) were associated with in-hospital mortality. ASA ≥3 (OR 2.87, 95% CI 1.56-5.26, P = 0.001) and estimated blood loss ≥2L (OR 3.52, 95% CI 1.25-9.90, P = 0.017) were associated with major complications. CONCLUSION: This pan-European prospective snapshot study found a 5% inhospital mortality after TP. The identified predictors for mortality, including low-volume centers, age, and increased blood loss, may be used to improve outcomes.

Minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma (DIPLOMA): study protocol for a randomized controlled trial.

BACKGROUND: Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease showed a 2-day reduction in time to functional recovery after MIDP. However, for pancreatic ductal adenocarcinoma (PDAC), concerns have been raised regarding the oncologic safety (i.e., radical resection, lymph node retrieval, and survival) of MIDP, as compared to ODP. Therefore, a randomized controlled trial comparing MIDP and ODP in PDAC regarding oncological safety is warranted. We hypothesize that the microscopically radical resection (R0) rate is non-inferior for MIDP, as compared to ODP. METHODS/DESIGN: DIPLOMA is an international randomized controlled, patient- and pathologist-blinded, non-inferiority trial performed in 38 pancreatic centers in Europe and the USA. A total of 258 patients with an indication for elective distal pancreatectomy with splenectomy because of proven or highly suspected PDAC of the pancreatic body or tail will be randomly allocated to MIDP (laparoscopic or robot-assisted) or ODP in a 1:1 ratio. The primary outcome is the microscopically radical resection margin (R0, distance tumor to pancreatic transection and posterior margin ≥ 1 mm), which is assessed using a standardized histopathology assessment protocol. The sample size is calculated with the following assumptions: 5% one-sided significance level (α), 80% power (1-ß), expected R0 rate in the open group of 58%, expected R0 resection rate in the minimally invasive group of 67%, and a non-inferiority margin of 7%. Secondary outcomes include time to functional recovery, operative outcomes (e.g., blood loss, operative time, and conversion to open surgery), other histopathology findings (e.g., lymph node retrieval, perineural- and lymphovascular invasion), postoperative outcomes (e.g., clinically relevant complications, hospital stay, and administration of adjuvant treatment), time and site of disease recurrence, survival, quality of life, and costs. Follow-up will be performed at the outpatient clinic after 6, 12, 18, 24, and 36 months postoperatively. DISCUSSION: The DIPLOMA trial is designed to investigate the non-inferiority of MIDP versus ODP regarding the microscopically radical resection rate of PDAC in an international setting. TRIAL REGISTRATION: ISRCTN registry ISRCTN44897265 . Prospectively registered on 16 April 2018.

Robotic versus laparoscopic surgery for colorectal cancer: a case-control study.

BACKGROUND: Robotic resections represent a novel approach to treatment of colorectal cancer. The aim of our study was to critically assess the implementation of robotic colorectal surgical program at our institution and to compare it to the established laparoscopically assisted surgery. PATIENTS AND METHODS: A retrospective case-control study was designed to compare outcomes of consecutively operated patients who underwent elective laparoscopic or robotic colorectal resections at a tertiary academic centre from 2019 to 2020. The associations between patient characteristics, type of operation, operation duration, conversions, duration of hospitalization, complications and number of harvested lymph nodes were assessed by using univariate logistic regression analysis. RESULTS: A total of 83 operations met inclusion criteria, 46 robotic and 37 laparoscopic resections, respectively. The groups were comparable regarding the patient and operative characteristics. The operative time was longer in the robotic group (p < 0.001), with fewer conversions to open surgery (p = 0.004), with less patients in need of transfusions (p = 0.004) and lower reoperation rate (p = 0.026). There was no significant difference between the length of stay (p = 0.17), the number of harvested lymph nodes (p = 0.24) and the overall complications (p = 0.58). CONCLUSIONS: The short-term results of robotic colorectal resections were comparable to the laparoscopically assisted operations with fewer conversions to open surgery, fewer blood transfusions and lower reoperation rate in the robotic group.

Health-related quality of life after curative resection for gastric adenocarcinoma.

BACKGROUND: With improved survival in gastric cancer patients, health-related quality of life has become an important clinical endpoint alongside primary oncological outcomes. AIM: To investigate health-related quality of life after various surgical procedures for gastric cancer treatment. METHODS: The validated Slovenian version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (QLQ-C30) and its gastric cancer-specific module (QLQ STO-22) was sent for self-completion to patients that underwent curative resection for gastric adenocarcinoma between January 2014 and December 2018 at our centre. In total, 116 patients responded. Scores were compared between patients after subtotal distal vs total gastrectomy and patients after subtotal distal gastrectomy with Billroth II vs Roux-en-Y reconstruction. RESULTS: Interestingly, the extent of resection did not influence daily functioning; however, more dysphagia and eating restrictions were reported in patients after total gastrectomy when compared to patients after subtotal distal gastrectomy. Moreover, patients with Billroth II reconstruction after subtotal distal resection experienced worse physical and role functioning and reported more pain, fatigue and reflux compared to Roux-en-Y reconstruction. CONCLUSION: Based on our results, Roux-en-Y reconstruction after subtotal distal gastrectomy should be preferred over Billroth II reconstruction. The data obtained from this study will help surgeons when preoperatively informing their patients about expected functional outcomes after gastrectomy and enable them to ensure proper supportive care of their patients in the postoperative period.

Robotic left colectomy with double indocyanine green guidance and intracorporeal anastomoses.

Radical surgery is the mainstay of treatment of colon cancer. Lymphatic drainage of splenic flexure colon cancer is variable, and the exact site of lymphatic dissection is uncertain. Hence, a true consensus of what kind of colectomy should be performed for tumours of the splenic flexure is lacking. Segmental left colectomy (splenic flexure colectomy) (extended), left colectomy as well as subtotal colectomy (extended right colectomy) all have their proponents. Robotic colectomy addresses the limitations of straight laparoscopic colon resections. We report our technique of single-docking totally robotic left hemicolectomy for splenic flexure adenocarcinoma using Da Vinci Xi® Surgical System (Intuitive Surgical, USA) with indocyanine green near-infrared fluorescence for the assessment of both the lymph nodes and intestinal blood flow in real time.

Contemporary snapshot of tumor regression grade (TRG) distribution in locally advanced rectal cancer: a cross sectional multicentric experience.

Pre-operative chemoradiotherapy (CRT) followed by surgical resection is still the standard treatment for locally advanced low rectal cancer. Nowadays new strategies are emerging to treat patients with a complete response to pre-operative treatment, rendering the optimal management still controversial and under debate. The primary aim of this study was to obtain a snapshot of tumor regression grade (TRG) distribution after standard CRT. Second, we aimed to identify a correlation between clinical tumor stage (cT) and TRG, and to define the accuracy of magnetic resonance imaging (MRI) in the restaging setting. Between January 2017 and June 2019, a cross sectional multicentric study was performed in 22 referral centers of colon-rectal surgery including all patients with cT3-4Nx/cTxN1-2 rectal cancer who underwent pre-operative CRT. Shapiro-Wilk test was used for continuous data. Categorical variables were compared with Chi-squared test or Fisher's exact test, where appropriate. Accuracy of restaging MRI in the identification of pathologic complete response (pCR) was determined evaluating the correspondence with the histopathological examination of surgical specimens.In the present study, 689 patients were enrolled. Complete tumor regression rate was 16.9%. The "watch and wait" strategy was applied in 4.3% of TRG4 patients. A clinical correlation between more advanced tumors and moderate to absent tumor regression was found (p = 0.03). Post-neoadjuvant MRI had low sensibility (55%) and high specificity (83%) with accuracy of 82.8% in identifying TRG4 and pCR.Our data provided a contemporary description of the effects of pre-operative CRT on a large pool of locally advanced low rectal cancer patients treated in different colon-rectal surgical centers.

Plasma Extracellular Vesicle Characteristics Correlate with Tumor Differentiation and Predict Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Curative Intent.

Better preoperative characterization of patients with pancreatic ductal adenocarcinoma (PDAC) would aid in treatment optimization. Extracellular vesicles (EV) are promising, largely unexplored biomarkers in PDAC. This study aimed to evaluate if plasma EV characteristics are associated with PDAC clinical characteristics and overall survival (OS). The prospective cohort included 34 PDAC patients undergoing surgery with curative intent. Patient data and plasma samples were collected preoperatively, intraoperatively and one month postoperatively. Small plasma EV (sEV) concentration and size were determined by nanoparticle-tracking analysis. A Mann-Whitney test, Spearman's rho and Cox regression were used in statistical analysis. Preoperatively, patients with poorly differentiated tumors had significantly larger plasma sEVs when compared to patients with well/moderately differentiated tumors (mean diameter 176.9 vs. 149.2 nm, p = 0.021), the sEV size even enabling discrimination of the two groups (AUC = 0.742, 95% CI = 0.560-0.923). Plasma sEV characteristics were also a predictor of OS in multivariable analysis. Patients with a more than 33.8% increase in sEV concentration after one month had 7.2 months shorter median OS (p = 0.002), while patients with a more than 28.0% decrease in sEV size had 9.2 months shorter median OS (p = 0.045). Plasma sEV concentration and size correlate with tumor differentiation and may predict OS in PDAC patients. In the future, plasma sEV characteristics could contribute to improved patient stratification for optimized treatment.

Ileocecal valve syndrome and vitamin b12 deficiency after surgery: a multicentric prospective study.

Patients undergoing colon resection are often concerned about their functional outcomes after surgery. The primary aim of this prospective, multicentric study was to assess the intestinal activity and health-related quality-of-life (HRQL) after ileocecal valve removal. The secondary aim was to evaluate any vitamin B12 deficiency. The study included patients undergoing right colectomy, extended right colectomy and ileocecal resection for either neoplastic or benign disease. Selected items of GIQLI and EORTC QLQ-CR29 questionnaires were used to investigate intestinal activity and HRQL before and after surgery. Blood samples for vitamin B12 level were collected before and during the follow-up period. The empirical rule effect size (ERES) method was used to explain the clinical effect of statistical results. Linear mixed effect (LME) model for longitudinal data was applied to detect the most important parameters affecting the total score. A total of 158 patients were considered. Applying the ERES method, the analysis of both questionnaires showed clinically and statistically significant improvement of HRQL at the end of the follow-up period. Applying the LME model, worsening of HRQL was correlated with female gender and ileum length when using GIQLI questionnaire, and with female gender, open approach, and advanced cancer stage when using the EORTC QLQ-CR29 questionnaire. No significant deficiency in vitamin B12 levels was observed regardless of the length of surgical specimen. In our series, no deterioration of HRQL and no vitamin B12 deficiency were found during the follow-up period. Nevertheless, warning patients about potential changes in bowel habits is mandatory. In our series, no deterioration of HRQL and no vitamin B12 deficiency were found during the follow-up period. Nevertheless, warning patients about potential changes in bowel habits is mandatory.