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Objectives: To compare respiratory-triggered, free-breathing, and breath-hold DWI techniques regarding (1) image quality, and (2) signal intensity (SI) and ADC measurements in pancreatic ductal adenocarcinoma (PDAC).Methods: Fifteen patients with histopathologically proven PDAC underwent DWI prospectively at 1.5 T (b = 0, 50, 300, 600 and 1,000 s/mm(2)) with the three techniques. Two radiologists, independently and blindly, assigned total image quality scores [sum of rating diffusion images (lesion detection, anatomy, presence of artefacts) and ADC maps (lesion characterisation, overall image quality)] per technique and ranked them. The lesion SI, signal-to-noise ratio, mean ADC and coefficient of variation (CV) were compared.Results: Total image quality scores for respiratory-triggered, free-breathing and breath-hold techniques were 17.9, 16.5 and 17.1 respectively (respiratory-triggered was significantly higher than free-breathing but not breath-hold). The respiratory-triggered technique had a significantly higher ranking. Lesion SI on all b-values and signal-to-noise ratio on b300 and b600 were significantly higher for the respiratory-triggered technique. For respiratory-triggered, free-breathing and breath-hold techniques the mean ADCs were 1.201, 1.132 and 1.253 × 10(-3) mm(2)/s, and mean CVs were 8.9, 10.8 and 14.1 % respectively (respiratory-triggered and free-breathing techniques had a significantly lower mean CV than the breath-hold technique).Conclusion: In both analyses, respiratory-triggered DWI showed superiority and seems the optimal DWI technique for demonstrating PDAC.Key Points: • Diffusion-weighted magnetic resonance imaging is increasingly used to detect pancreatic cancer • Images are acquired using various breathing techniques and multiple b-values • Breathing techniques used: respiratory-triggering, free-breathing and breath-hold • Respiratory-triggering seems the optimal breathing technique for demonstrating pancreatic cancer. [ABSTRACT FROM AUTHOR]

We investigated whether cells expressing hypoxia-inducible factor-1α (HIF-1α) are specially related to blood vessels in human pancreatic tumors. HIF-1α and blood vessels were stained in 7 pancreatic ductal adenocarcinomas (PDAC) and 3 nonmalignant tumors. HIF-1α+ cells accounted for 37 ± 5% of the total PDAC cells and increased to 52 ± 4% in perivascular PDAC cells and to 67 ± 4% in PDAC cells found in intratumoral blood vessels. In nonmalignant tumors, 12 ± 3% of the total tumoral cells examined were HIF-1α+, and HIF-1α+ cells decreased to 2 ± 0.3% in perivascular cells examined in the tumors. In conclusion, HIF-1α+ cells in PDAC and nonmalignant pancreatic tumors differ not only in their amounts but also in their relation to intratumoral blood vessels. HIF-1α+ cells usually are adjacent to intratumoral blood vessels in PDAC tumors, but are farther away from the vessels in nonmalignant pancreatic tumors. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Curing type 1 diabetes by transplanting pancreatic islets into the liver is associated with poor long-term outcome and graft failure at least partly due to inadequate graft revascularization. The aim of the current study was to evaluate striated muscle as a potential angiogenic site for islet transplantation.Research Design and Methods: The current study presents a new experimental model that is found to be applicable to clinical islet transplantation. Islets were implanted into striated muscle and intraislet vascular density and blood flow were visualized with intravital and confocal microscopy in mice and by magnetic resonance imaging in three autotransplanted pancreatectomized patients. Mice were rendered neutropenic by repeated injections of Gr-1 antibody, and diabetes was induced by alloxan treatment.Results: Contrary to liver-engrafted islets, islets transplanted to mouse muscle were revascularized with vessel densities and blood flow entirely comparable with those of islets within intact pancreas. Initiation of islet revascularization at the muscular site was dependent on neutrophils, and the function of islets transplanted to muscle was proven by curing diabetic mice. The experimental data were confirmed in autotransplanted patients where higher plasma volumes were measured in islets engrafted in forearm muscle compared with adjacent muscle tissue through high-resolution magnetic resonance imaging.Conclusions: This study presents a novel paradigm in islet transplantation whereby recruited neutrophils are crucial for the functionally restored intraislet blood perfusion following transplantation to striated muscle under experimental and clinical situations. [ABSTRACT FROM AUTHOR]

Background: A majority of patients with pancreatic cancer have obstructive jaundice and diabetes with skeletal muscle insulin resistance. Surgery for these patients is associated with significant morbidity. Uncoupling protein 2 (UCP2) has been proposed to regulate energy expenditure and promote liver vulnerability. The effects of obstructive jaundice on muscle glucose metabolism and expression of UCP2 in liver and muscle are unknown. Methods: Rats were operated with bile duct ligation (BDL). After 7 days, UCP2 mRNA levels were determined in liver and muscle. Simultaneously, insulin-stimulated glucose transport and glycogen synthesis in skeletal muscle were analyzed in vitro. Results: The jaundiced rats lost more weight than pair-fed controls. UCP2 mRNA levels were increased 5-fold in liver but not in muscle in jaundiced rats compared to pair-fed controls. The jaundiced rats were hypoglycemic and hypoinsulinemic but demonstrated intact or enhanced insulin action on skeletal muscle glucose transport and glycogen synthesis in vitro. Muscle glycogen content was increased in the jaundiced rats. Conclusions: Experimental obstructive jaundice in the rat is associated with increased liver expression of UCP2, rapid weight loss, and intact insulin action on skeletal muscle glucose metabolism. Obstructive jaundice, by upregulated liver UCP2, may contribute to the cachexia and high surgical morbidity observed in these patients, but not to skeletal muscle insulin resistance in pancreatic cancer patients. [ABSTRACT FROM AUTHOR]

Background: Studies in patients with acute pancreatitis have shown a correlation between obesity and serious complications or a fatal outcome. However, the mechanisms by which obesity aggravates acute pancreatitis are not known. In the present study we used the sodium taurocholate model of pancreatitis to examine the effect of obesity on severity and outcome in acute experimental pancreatitis (AEP). Methods: AEP was induced at two degrees of severity by retrograde infusion of sodium taurocholate (0.2 ml × 3% or 0.4 ml × 3.5%) into the pancreatic duct of rats with obesity induced by high-fat diet, genetically obese (GO) rats or lean control rats. Surviving animals were sacrificed 72 h after induction of pancreatitis. Results: In the low-dose experiment, there were no significant differences in pancreatic histology or survival rate between the groups. In the high-dose experiment, the GO rats had a significantly lower 72-h survival rate than the high-fat obese (HFO) or lean control (LC) groups (GO 25% versus HFO 73%, P < 0.05; GO 25% versus LC 100%, P < 0.001). Survival rates in the high-dose experiment correlated strongly with basal liver fat content (R[sup 2] = 0.86). Pancreatic histology showed significantly more fat necrosis and a higher total pathological mean score in the HFO rats than in the LC animals (both P < 0.05). Conclusions: Obesity had a negative influence on the outcome of necrotizing pancreatitis that was related to the magnitude of the pancreatic insult. The sodium taurocholate model in obese rats would be useful for future mechanistic studies of the effect of obesity on pancreatitis. [ABSTRACT FROM AUTHOR]

B Background: b Despite improvement in the perioperative care and adjuvant chemotherapy regimens over the past decades, pancreatic cancer still has a poor overall survival. B Methods: b Since 2010 all patients with pancreatic and periampullary cancer should be registered in the Swedish National Periampullary and Pancreatic Cancer registry. B Results: b 7048 patients with malignant periampullary cancer are entered in the registry. [Extracted from the article]

Purpose: To examine differences in health-related quality of life (HRQoL) between native and foreign-born gynaecological cancer patients in Sweden, taking into account clinical, demographic, and socioeconomic factors., Methods: The 30-item European Organisation for Research and Treatment of Cancer quality of life questionnaire (QLQ-C30) and a study-specific questionnaire covering demographic and socioeconomic factors were answered by 684 women aged ≥ 18 years old, diagnosed in 2014, 2016, or 2018 with gynaecological cancer in the Stockholm-Gotland health care region, Sweden. Clinical data were obtained from the Swedish Cancer Register. Data were analysed using the Kruskal-Wallis test and linear regression., Results: The women had a mean age of 65.4 years, with 555 (81.1%) born in Sweden, 54 (7.9%) in other Nordic countries (ONC), 43 (6.3%) in other European countries (OEC), and 32 (4.7%) in non-European countries (NEC). HRQoL differed significantly between the four groups for 14 of the 15 QLQ-C30 scales/items. On average, Swedish-born women scored 2.0, 15.2, and 16.7 points higher for QoL/functioning scales/items and 2.2, 14.1, and 18.7 points lower for symptom scales/items, compared with ONC-, OEC-, and NEC-born women, respectively. In adjusted analyses, none of the differences between Swedish-born and ONC-born women were significant, while for OEC- and NEC-born women the differences were significant for most QLQ-C30 scales/items., Conclusion: HRQoL differs between native and foreign-born gynaecological cancer patients in Sweden, with lower HRQoL the further from Sweden the women are born. A more individualised cancer care, with tailored support to optimize HRQoL is needed for this vulnerable group of patients., (© 2023. The Author(s).)

Objectives: The purpose was to analyze trends in intensity of care at End-of-life (EOL), in two cohorts of patients with lung or pancreatic cancer., Setting: We used population-based registry data on health care utilization to describe proportions and intensity of care at EOL comparing the two cohorts (deceased in the years of 2010 and 2017 respectively) in the region of Stockholm, Sweden., Primary and Secondary Outcomes: Main outcomes were intensity of care during the last 30 days of life; systemic anticancer treatment (SACT), emergency department (ED) visits, length of stay (LOS) > 14 days, intensive care (ICU), death at acute care hospital and lack of referral to specialized palliative care (SPC) at home. The secondary outcomes were outpatient visits, place of death and hospitalizations, as well as radiotherapy and major surgery. A multivariable logistic regression analysis was used for associations. A moderation variable was added to assess for the effect of SPC at home between the cohorts., Results: Intensity of care at EOL increased over time between the cohorts, especially use of SACT, increased with 10%, p<0.001, (n = 102/754 = 14% to n = 236/972 = 24%), ED visits with 7%, p<0.001, (n = 25/754 = 3% to n = 100/972 = 10%) and ICU care, 2%, p = 0.04, (n = 12/754 = 2% to n = 38/972 = 4%). High intensity of care at EOL were more likely among patients with lung cancer. The difference in use of SACT between the years, was moderated by SPC, with an increase of SACT, unstandardized coefficient β; 0.87, SE = 0.27, p = 0.001, as well as the difference between the years in death at acute care hospitals, that decreased (β = 0.69, SE = 0.26, p = 0.007)., Conclusion: These findings underscore an increase of several aspects regarding intensity of care at EOL, and a need for further exploration of the optimal organization of EOL care. Our results indicate fragmentation of care and a need to better organize and coordinate care for vulnerable patients., Competing Interests: The authors have declared that no competing interests exist.

Objective: Neoadjuvant therapy (NAT) has become part of the multimodality treatment for borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC)., Summary Background Data: It is currently uncertain which are the preferable NAT regimens, who benefits from surgery, and whether more aggressive surgical strategy is motivated., Methods: A retrospective cohort analysis was performed for all patients with BRPC/LAPC discussed and planned for NAT at multidisciplinary conference at Karolinska University Hospital from 2010 to 2017., Results: Of 233 patients eligible, 168 (72%) received NAT and were reevaluated for possibility of resection. A total of 156 (67%) patients (mean 64 yrs, 53% male) had pancreatic adenocarcinoma, comprising the study group for survival analysis. LAPC was diagnosed in 132 patients (85%), BRPC in 22 (14%), and resectable tumor in 2 (1.3%). Fifty patients (40.3%) received full-dose NAT. Only 54 (34.6%) had FOLFIRINOX. The overall survival among resected patients was similar for BRPC and LAPC (median survival 15.0 vs 14.5 mo, P = 0.4; and 31.9 vs 21.8 mo, P = 0.7, respectively). Resected patients had better survival than nonresected, irrespective of the type or whether full-dose NAT was given (median survival 22.4 vs 12.7 mo; 1-, 3-, and 5-yr survival: 86.4%, 38.9%, 26.9% vs 52.2%, 1.5%, 0%, respectively (P < 0001). For all preoperative values of Ca 19-9, surgical resection had positive impact on survival., Conclusions: All patients with BRPC/LAPC who do not progress during NAT should be considered for surgical resection, irrespective of the type or dose of NAT given. Higher levels of Ca 19-9 should not be considered an absolute contraindication for resection., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients with pancreatic and periampullary cancer have poor prognoses, experience multiple symptoms following surgery and sometimes lack knowledge of self-care activities. Consequently, it is vital to develop systems that support self-management, improvement of health-related quality of life and reduction of symptoms. Therefore, the aim was to evaluate the impact on health-related quality of life and self-care activity when using the Interaktor app following pancreaticoduodenectomy due to cancer. Material and Methods: Patients in the intervention group used Interaktor up to six months after surgery. They reported symptoms daily at home and received support for self-management by continuous access to written self-care advice and to their healthcare professionals. Descriptive data from the app were collected. Health-related quality of life and self-care activity were collected before surgery, and six weeks and six months after surgery. Comparisons between the intervention group ( n  = 26) and a historical control group ( n  = 33) were made. Decline/dropout rate was 37% in the intervention group and 10% in the control group. Results: Six weeks after surgery the intervention group rated significantly higher emotional functioning and less nausea/vomiting, pain, appetite loss, constipation, pancreatic pain, flatulence and worry about low weight. Twenty-five subscales/items showed non-statistical differences. Six months after surgery the intervention group rated significantly fewer hepatic symptoms, less worry about low weight, and higher self-care activity level. Thirty subscales/items showed non-statistical differences. The first four weeks, patients reported symptoms in a median 95% of the intended days, and for the rest of the period in median 83%. Conclusion: The use of an app for management of patient-reported outcomes reduces symptom burdens six weeks after pancreaticoduodenectomy due to cancer. Interaktor is well accepted for patients choosing to participate and appears to facilitate supportive care needs and timely symptom management for this patient group. Future studies should also include cost-benefits and objective measures.

Background: Patients who have undergone pancreaticoduodenectomy because of pancreatic cancer experience distressing symptoms and unmet supportive care needs after discharge. To meet these needs, we have developed a mobile health app (Interaktor) for daily assessment of symptoms and access to self-care advice that includes a risk assessment model for alerts with real-time interactions with professionals., Objective: The study aim was to develop and test a version of the Interaktor app adapted for patients who have undergone pancreaticoduodenectomy., Methods: The app was developed and tested for feasibility in 6 patients during 4 weeks. One nurse monitored and responded to alerts. Logged data from the app were collected, and all participants were interviewed about their experiences., Results: Adherence to reporting daily was 84%. Alerts were generated in 41% of the reports. The patients felt reassured and cared for and received support for symptom management. The app was easy to use, had relevant content, and had few technical problems, although suggestions for improvement were given., Conclusions: The daily reporting of symptoms and having access to a nurse in real time in the case of an alarming symptom seem to enhance symptom management and render a feeling of security in patients. Some modifications of the app are needed before use in a larger sample., Implications for Practice: Daily reporting of symptoms after pancreaticoduodenectomy enhances symptom management, self-care, and participation without being a burden to patients, indicating that mobile health can be used in clinical practice by patients with poor prognosis who experience severe symptoms.

Background: Few studies have investigated the outcome of pancreatectomy associated with artery resection (PAR)., Methods: Retrospective analysis of a cohort of operated borderline or locally advanced pancreatic cancer patients with surgically confirmed arterial involvement. Short and long-term outcome were analyzed and compared in patients who underwent PAR (Group 1) and palliative surgery (Group 2)., Results: Of 73 patients who underwent surgical exploration with intent of resection, 34 underwent PAR (±venous resection) (Group 1) and 39 underwent palliation (Group 2). 23 patients (67.7%) in Group 1 underwent combined artery-vein resection (AVR). Operation time was longer and blood loss higher in group 1 compared to group 2. There were no differences in post-operative mortality (2.9% vs 2.6%, p = 0.9) and post-operative surgical complications (38.2% vs 25.6%, p = 0.2). The 1, 3 and 5 years survival in Group 1 was superior to Group 2 (63.7%, 23.4% and Q3 23.4% vs 41.7%, 3.2% and 0, p = 0.003)., Conclusion: PAR seems to be safe and feasible in well selected patients and associated with an advantage of survival compared to palliation, in patients affected by locally advanced pancreatic cancer., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: To date, there still is a lack of specific acute pancreatitis markers and specifically an early marker that can reliably predict disease severity. The inflammatory response in acute pancreatitis is mediated in part through oxidative stress and calcineurin-NFAT (Nuclear Factor of Activated T-cells) signaling, which is inducing its own negative regulator, regulator of calcineurin 1 (RCAN1). Caerulein induction is a commonly used in vivo model of experimental acute pancreatitis. Caerulein induces CN-NFAT signaling, reactive oxygen species and inflammation., Methods: To screen for potential markers of acute pancreatitis, we used the caerulein model of experimental acute pancreatitis (AP) in C57Bl/6 J mice. Pancreata from treated and control mice were used for expression profiling. Promising gene candidates were validated in cell culture experiments using primary murine acinar cells and rat AR42J cells. These candidates were then further tested for their usefulness as biomarkers in mouse and human plasma., Results: We identified a number of novel genes, including Regulator of calcineurin 1 (Rcan1) and Sestrin 2 (Sesn2) and demonstrated that they are induced by oxidative stress, by stimulation with H 2 O 2 and by inhibiting caerulein stimulated expression with the antioxidant N-acetylcysteine. We found Rcan1 protein to be significantly elevated in AP-induced mouse plasma as well as in plasma from AP patients., Conclusion: We demonstrated that Rcan1 is regulated by oxidative stress and identified RCAN1 as a potential diagnostic marker of AP., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess the interreader agreement and reader performance in the evaluation of patients with pancreatic cancer (PC) in two classification systems of local resectability status prior to initiation of therapy, namely the National Comprehensive Cancer Network (NCCN) and Karolinska classification system (KCS)., Methods: In this ethics review board-approved retrospective study, six radiologists independently evaluated pancreatic CT-examinations of 30 patients randomly selected from a tertiary referral centre's multidisciplinary tumour board database. Based on well-defined criteria of tumour-vessel relationship, each patient was assigned to one of three NCCN and six KCS categories. We assessed the intraclass correlation coefficient (ICC) and compared the percentages of correct tumour classification of the six readers in both systems (Chi-square test; a P-value <0.05 was considered significant). The standard of reference was a consensus evaluation of CT-examinations by three readers not involved in the image analysis., Results: The ICC for NCCN and KCS was 0.82 and 0.84, respectively (very strong agreement). The percentages of correct tumour classification at NCCN and KCS were 53-83% and 30-57%, respectively, with no statistically significant differences in the overall reader comparison per classification system. In pair-wise comparison between readers for NCCN/KCS, there were statistically significant differences between reader 5 vs. readers 4 (P = 0.012) and 3 (P = 0.045)/ reader 5 vs. reader 4 (P = 0.037)., Conclusion: Interreader agreement in both PC classification systems is very strong. NCCN may be advantageous in terms of reader performance compared to KCS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: There are very few data in the current literature regarding the short- and long-term outcome of surgery for pediatric pancreatic tumors (PPT). No data are available on the impact of pancreatic surgery on the children's growth., Methods: This is a retrospective cohort study on a consecutive series of pediatric/adolescent patients who underwent pediatric surgery at Karolinska University Hospital from January 2005 to July 2017., Results: Overall 14 pancreatic operations were performed in 13 patients. The median age was 11.4 years (range 3-15). Six pancreaticoduodenectomies (42.8%), 5 distal pancreatectomies (35.7%), and 3 enucleations (21.5%) were performed. The final histology revealed a solid pseudopapillary tumor in 9 cases (69.2%), neuroblastoma in 1 (7.7%), ganglioneuroma in 1 (7.7%), pancreatoblastoma in 1 (7.7%), and insulinoma in 1 (7.7%). Overall, 3 patients developed post-operative complications (23%). There was no peri-operative mortality. All patients are alive after a median follow-up time of 80 months. Exocrine insufficiency was detected post-operatively in 4 patients (30.7%) Endocrine insufficiency requiring insulin treatment developed in one patient (7.7%). No significant impact on growth was detected in any of the patients after pancreatic resection., Conclusions: In our series, surgery performed for PPTs seems to be safe and effective. The effect of pancreatic surgery on children's growth does not seem to be significant., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT. Both TAAs were highly expressed in the original tumor tissue suggesting that HSCT promoted a clinically relevant, long-lasting cellular immune response. In contrast to untreated controls, who succumbed to progressive disease, both patients are tumor-free 9 years after diagnosis. Radical surgery combined with HSCT may cure pancreatic adenocarcinoma and change the cellular immune repertoire capable of responding to clinically and biologically relevant TAAs.

Purpose: While surveillance of the majority of patients with IPMN is considered best practice, consensus regarding the duration of follow-up is lacking. This study assessed the survival rate and risk for progression of IPMN under surveillance., Methods: All patients diagnosed with and surveyed for IPMN between January 2008 and December 2013 were identified and assigned to two groups: patients without indication for surgery (Group 1), and patients whose IPMN required surgery but were inoperable for general reasons (Group 2). Disease progression and survival data were compared between both groups., Results: In total 503 patients were identified, of whom 444 (88.3%) were followed up. Group 1 included 395 patients, and Group 2 had 49. In Group 1, IPMN-specific 1-, 5-, and 10-year survival rates were 100, 100, and 94.2%, respectively. Four patients died of associated or concomitant pancreatic cancer, and 230 patients (58.2%) experienced disease progression. The 1-, 4-, 10-year cumulative risk for progression and for surgery was 11.2, 70.6, 97.5, and 2.9, 26.2, 72.1%, respectively. In Group 2, the 1-, 5-, 10-year IPMN-specific survival rate was 90.7, 74.8, and 74.8%, respectively., Conclusions: This study confirmed the safety of surveillance for patients with IPMN who do not require surgery. However, the risk for disease progression and for surgery increases significantly over time. The study results support International and European guidelines not to discontinue IPMN surveillance and validate the European recommendation to intensify follow-up after 5 years. The fairly good prognosis of patients whose IPMN requires surgery but cannot undergo resection suggests a relatively indolent disease biology.

Purpose: Poor prognosis and a problematic recovery period after pancreaticoduodenectomy means that patients may benefit from early detection of symptoms and support for self-management. Interactive Information and Communication Technology tools can be used for this purpose, but the content needs to be relevant to patients as well as healthcare professionals. To facilitate development of the content of an application for this purpose, the aim of this study was to explore common symptoms and self-care in the first six months after pancreaticoduodenectomy, as identified by patients and healthcare professionals., Method: Data were collected through individual interviews with patients (n = 14), along with two focus group interviews and one individual interview with healthcare professionals (n = 10). Data were analysed using qualitative content analysis., Results: Common symptoms after surgery were those related to eating, bowel function and emotional wellbeing, along with fatigue and pain. Some self-care activities and advice were mentioned in the interviews. The patients often experienced a lack of advice on self-care at discharge., Conclusions: The results render knowledge of the symptoms it is important to be aware of and to assess regularly after pancreaticoduodenectomy. The results also contribute to knowledge about specific self-care related to these symptoms, even though it was not extensively described, and further research is needed to define evidence-based self-care advice., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The recent development of new neo-adjuvant treatment regimens associated with a higher success rate of down-staging has increased the interest of pancreatic surgeons on the role of extended surgery for patients affected by locally advanced pancreatic cancer. Pancreatectomy together with resection of the portal/superior mesenteric vein is considered nowadays standard of care for patients affected by pancreatic cancer. However, the resection of major abdominal arteries is still debatable. In particular, the short- and long-term results after resection of the superior mesenteric artery (SMA) remain controversial and only few cases have been described in literature. The present paper describes a new, quick, and easy technique for resection of the SMA., Clinical Case: A 71-year-old patient affected by IPMN cancer with infiltration of the SMA received FOLFIRINOX-based neo-adjuvant treatment. After 4 months of treatment, the patient underwent total pancreatectomy with en bloc resection of the SMA and direct end-to-end anastomosis. The vascular resection was performed combining a complete Cattell-Braasch maneuver with local bowel hypothermia in an attempt to avoid graft interposition by facilitating an end-to-end anastomosis and to reduce the warm ischemia time. The post-operative course was uneventful and the patient was discharged 8 days post-operatively.

Total pancreatectomy is associated with short- and long-term high complication rate and without evidence of oncologic advantages. Several metabolic consequences are co-related with the apancreatic state. The unstable diabetes related to the total resection of the pancreas expose the patients to short- and long-term life-threatening complications. Severe hypoglycemia is a short-term dangerous complication that can also cause patients' death. Chronic complications of severe diabetes (cardiac and vascular diseases, neuropathy, nephropathy, and retinopathy) are also cause of morbidity, mortality and worsening of quality of life. For this reasons the number of total pancreatectomies performed has certainly decreased over time. However, today there are still some indications for this kind of procedures. Chronic pancreatitis untreatable with conventional treatments, surgical treatment of precancerous pancreatic lesions, surgical treatment of locally advanced pancreatic cancer and the management of patients with extraordinary high-risk pancreatic texture after pancreaticoduodenectomy represent possible indications for total pancreatectomy and are analyzed in the present paper., Competing Interests: The authors declare that they have no conflict of interest. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.

Background: The time course of plasma albumin concentration (P-alb) and cumulative perioperative albumin shift as a measure of albumin extravasation in major abdominal surgery is not well described. Knowledge of these indices of the vascular barrier and vascular content are important for our understanding of fluid physiology during surgery and anesthesia., Methods: Patients (n = 10) were studied during esophageal or pancreatic surgery. P-alb was repeatedly measured over 72 h, and the mass balance of albumin and hemoglobin were obtained from measures of P-alb, blood hemoglobin and hematocrit., Results: P-alb decreased rapidly from baseline (32.8 ± 4.8 g/L) until the start of surgical reconstruction (18.7 ± 4.8 g/L; p < 0.001), and was thereafter stable until postoperative day 3. Cumulative perioperative albumin shift increased until 1 h after the end of surgery, when 24 ± 17 g (p < 0.001) had been lost from the circulation., Conclusions: The rapid fall in P-alb of more than 40 % consistently occurred during the first part of the surgical procedure, but albumin leakage progressed until 1 h after the end of surgery. After the initial drop, P-alb was stable for 72 h.

Generation of T lymphocytes with reactivity against cancer is a prerequisite for effective adoptive cellular therapies. We established a protocol for tumor-infiltrating lymphocytes (TILs) from patients with pancreatic ductal adenocarcinoma. Tumor samples from 17 pancreatic cancer specimens were cultured with cytokines (IL-2, IL-15, and IL-21) to expand TILs. After 10 days of culture, TILs were stimulated with an anti-CD3 antibody (OKT3) and irradiated allogeneic peripheral blood mononuclear cells. Reactivity of TILs against tumor-associated antigens (mesothelin, survivin, or NY-ESO-1) was detected by intracellular cytokine production by flow cytometry. Cytotoxicity was measured using a Chromium 51 release assay, and reactivity of TILs against autologous tumor cells was detected by INF-[gamma] production (ELISA). TIL composition was tested by CD45RA, CCR7, 4-1BB, LAG-3, PD-1, TIM3, and CTLA-4 marker analysis. TCR V[beta] was determined by flow cytometry and TCR clonality was gauged measuring the CDR3 region length by PCR analysis and subsequent sequencing. We could reliably obtain TILs from 17/17 patients with a majority of CD8(+) T cells. CD3(+)CD8(+), CD3(+)CD4(+), and CD3(+)CD4(-)CD8(-)[double-negative (DN) T cells] resided predominantly in central (CD45RA(-)CCR7(+)) and effector (CD45RA-CCR7-) memory subsets. CD8(+) TILs tested uniformly positive for LAG-3 (about 100%), whereas CD4(+) TILs showed only up to 12% LAG-3(+) staining and PD-1 showed a broad expression pattern in TILs from different patients. TILs from individual patients recognized strongly (up to 11.9% and 8.2% in CD8(+)) NY-ESO-1, determined by ICS, or mesothelin, determined respectively by TNF-[alpha] and IFN-[gamma] production. Twelve of 17 of CD8(+) TILs showed preferential expansion of certain TCR V[beta] families (eg, 99.2% V[beta]13.2 in CD8(+) TILs, 77% in the V[beta]1, 65.9% in the V[beta]22, and 63.3% in the V[beta]14 family). TCR CDR3 analysis exhibited monoclonal or oligoclonal TCRs, some of them (eg, CD8(+) V[beta]13.2) reacting strongly against autologous tumor defined by INF-[gamma] production or by cytotoxicity. We have optimized methods for generating pancreatic cancer–specific TILs that can be used for adoptive cellular therapy of patients with pancreatic cancer.

Pancreatectomy associated with superior mesenteric-portal vein (SMPV) resection is currently considered the standard of care for patients with pancreatic tumors involving the major peripancreatic veins. However, a standard approach for resection and reconstruction is not defined yet. The aim of this study is to analyze the feasibility and short-term results of an original Cattell-Braasch artery-first approach (CBAF) for the resection of SMPV during pancreatectomy. Of 144 pancreatectomies with vascular resection undertaken from 2008 to 2013 at Karolinska University Hospital, 45 (31.2 %) were performed combining a Cattell-Braasch maneuver with an artery-first approach (from 2011 to 2013). The mean patient age was 65.2 years. Thirty-seven (82.2 %) patients underwent pancreatoduodenectomy and 8 (17.8 %) total pancreatectomy. Histology showed pancreatic ductal adenocarcinoma in 42 patients (93.3 %). The median length of the resected SMPV segment was 4.6 cm (range 3-7). In all patients, a direct end-to-end anastomosis was performed without graft interposition. In nine cases (20 %), an arterial resection was also performed. There was no mortality in this series, and the morbidity rate was 35.5 %. Combined CBAF for the resection of SMPV during pancreatectomy seems to be safe and effective. The reconstruction of the resected vessels is possible in many cases without graft interposition, even if the resected vein segment is of considerable length.

Background: Diagnosis of pre-malignant and malignant lesions in the bile duct and the pancreas is sometimes cumbersome. This applies in particular to intraductal papillary mucinous neoplasia (IPMN) and bile duct strictures in primary sclerosing cholangitis (PSC)., Aims: To evaluate in a prospective cohort study the sensitivity and specificity of probe-based confocal laser microscopy (pCLE) during endoscopic retrograde cholangiopancreatography (ERCP)., Methods: We performed pCLE together with mother-baby endoscopy (SpyGlass) during 50 ERCP sessions in 45 patients. The Miami and Paris criteria were applied. Clinical diagnosis via imaging was compared to pCLE and the final pathological diagnosis from surgically-resected, biopsy, or cytology specimens. Patients were followed up for at least 1 year., Results: We were able to perform pCLE in all patients. Prior to endoscopy, the diagnosis was benign in 23 patients and undetermined (suspicious) in 16 patients, while six patients had an unequivocal diagnosis of malignancy. Sensitivity was 91% and specificity 52%. The positive (PPV) and negative predictive value (NPV) was 82% and 100%, respectively. Apart from mild post-ERCP pancreatitis in two patients, no complications occurred., Conclusions: Our study showed that pCLE is a safe, expert endoscopic method with high technical feasibility, high sensitivity and high NPV. It provided diagnostic information that can be helpful for decisions on patient management, especially in the case of IPMN and unclear pancreatic lesions, in individuals whom are at increased risk for pancreatic cancer.