REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.

A scoring system for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: a multicenter EUROPEAN validation.

PURPOSE: A preoperative estimate of the risk of malignancy for intraductal papillary mucinous neoplasms (IPMN) is important. The present study carries out an external validation of the Shin score in a European multicenter cohort. METHODS: An observational multicenter European study from 2010 to 2015. All consecutive patients undergoing surgery for IPMN at 35 hospitals with histological-confirmed IPMN were included. RESULTS: A total of 567 patients were included. The score was significantly associated with the presence of malignancy (p < 0.001). In all, 64% of the patients with benign IPMN had a Shin score < 3 and 57% of those with a diagnosis of malignancy had a score ≥ 3. The relative risk (RR) with a Shin score of 3 was 1.37 (95% CI: 1.07-1.77), with a sensitivity of 57.1% and specificity of 64.4%. CONCLUSION: Patients with a Shin score ≤ 1 should undergo surveillance, while patients with a score ≥ 4 should undergo surgery. Treatment of patients with Shin scores of 2 or 3 should be individualized because these scores cannot accurately predict malignancy of IPMNs. This score should not be the only criterion and should be applied in accordance with agreed clinical guidelines.

Nanotechnology Meets Oncology: A Perspective on the Role of the Personalized Nanoparticle-Protein Corona in the Development of Technologies for Pancreatic Cancer Detection.

In recent years nanotechnology has opened exciting opportunities in the struggle against cancer. In 2007 Dawson and coworkers demonstrated that nanomaterials exposed to biological fluids are coated with plasma proteins that form the so-called "protein corona". A few years later our joint research team made of physicists, chemists, biotechnologists, surgeons, oncologists, and bioinformaticians introduced the concept of "personalized protein corona" and demonstrated that it is unique for each human condition. This concept paved the way for the development of nano-enabled blood (NEB) tests for the diagnosis of pancreatic ductal adenocarcinoma (PDAC). These studies gave an impetus to serious work in the field that came to maturity in the late 2010s. In this special issue, we provide the reader with a comprehensive overview of the most significant discoveries of our research team in the field of PDAC detection. We focus on the main achievements with an emphasis on the fundamental aspects of this arena and how they shaped the integration of different scientific backgrounds towards the development of advanced diagnostic technologies. We conclude the review by outlining future perspectives and opportunities to transform the NEB tests into a reliable clinical diagnostic technology for early diagnosis, follow-up, and management of PDAC patients.

Prognostic role of hERG1 Potassium Channels in Neuroendocrine Tumours of the Ileum and Pancreas.

hERG1 potassium channels are widely expressed in human cancers of different origins, where they affect several key aspects of cellular behaviour. The present study was designed to evaluate the expression and clinical relevance of hERG1 protein in cancer tissues from patients suffering from neuroendocrine tumours (NETs) of ileal (iNETs) and pancreatic (pNETs) origin, with available clinicopathological history and follow-up. The study was carried out by immunohistochemistry with an anti-hERG1 monoclonal antibody. In a subset of samples, a different antibody directed against the hERG1/ß1 integrin complex was also used. The analysis showed for the first time that hERG1 is expressed in human NETs originating from either the ileum or the pancreas. hERG1 turned out to have a prognostic value in NETs, showing (i) a statistically significant positive impact on OS of patients affected by ileal NETs, regardless the TNM stage; (ii) a statistically significant positive impact on OS of patients affected by aggressive (TNM stage IV) disease, either ileal or pancreatic; (iii) a trend to a negative impact on OS of patients affected by less aggressive (TNM stage I-III) disease, either ileal or pancreatic. Moreover, in order to evaluate whether ERG1 was functionally expressed in a cellular model of pNET, the INS1E rat insulinoma cell line was used, and it emerged that blocking ERG1 with a specific inhibitor of the channel (E4031) turned out in a significant reduction in cell proliferation.

Diagnostic Accuracy and Prognostic Value of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Septic Patients outside the Intensive Care Unit.

Background and Objectives: The aim of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios and to compare them with other biomarkers and clinical scores of sepsis outside the intensive care unit. Materials and methods: In this retrospective study, 251 patients with sepsis and 126 patients with infection other than sepsis were enrolled. NLR and PLR were calculated as the ratio between absolute values of neutrophils, lymphocytes, and platelets by complete blood counts performed on whole blood by Sysmex XE-9000 (Dasit, Italy) following the manufacturer's instruction. Results: The best NLR value in diagnosis of sepsis was 7.97 with sensibility, specificity, AUC, PPV, and NPV of 64.26%, 80.16%, 0.74 (p < 0.001), 86.49%, and 53.18%, respectively. The diagnostic role of NLR significantly increases when PLR, C-reactive protein (PCR), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) values, as well as systemic inflammatory re-sponse syndrome (SIRS), sequential organ failure assessment (SOFA), and quick-sequential organ failure assessment (qSOFA) scores, were added to the model. The best value of NLR in predicting 90-day mortality was 9.05 with sensibility, specificity, AUC, PPV, and NPV of 69.57%, 61.44%, 0.66 (p < 0.0001), 28.9%, and 89.9%, respectively. Sensibility, specificity, AUC, PPV, and NPV of NLR increase if PLR, PCR, PCT, MR-proADM, SIRS, qSOFA, and SOFA scores are added to NLR. Conclusions: NLR and PLR represent a widely useful and cheap tool in diagnosis and in predict-ing 90-day mortality in patients with sepsis.

Procalcitonin and MR-proAdrenomedullin combination in the etiological diagnosis and prognosis of sepsis and septic shock.

Procalcitonin and Mid-regional pro Adrenomedullin have been proposed for sepsis diagnosis, antibiotic therapy guidance and prognosis. A retrospective analysis of PCT and MR-proADM on 571 consecutive patients with sepsis diagnosis was performed. Median values were compared using the non-parametric Mann-Whitney's test. Receiver operating characteristic analysis was performed to define cutoff points for sepsis diagnosis. Pretest odds, posttest odds, and posttest probability have been calculated. Data were analyzed using Med-Calc 11.6.1.0 software. PCT resulted excellent in gram-negative, but less performant in gram-positive and fungal etiologies. MR-proADM values resulted homogenously distributed within the different microbial classes and increased significantly in septic shock. PCT highest PPV value was found to distinguish gram-negative from fungal sepsis and septic shock (>3. 57 ng/mL, PPV 0.96 and > 8.77 ng/mL, PPV 0.96, respectively). Good diagnostic accuracy was evidenced to discriminate gram-negative from gram-positive septic shock (>3.88 ng/mL PPV 0.89). Lower diagnostic accuracy was evidenced to discriminate gram-negative and gram-positive sepsis (>0.80 ng/mL, PPV 0.78) and gram-positive from fungal septic shock (>1.74 ng/mL PPV 0.75). The lowest PCT PPV (0.28) was found in gram-positive and fungal sepsis distinction. MR-proADM discriminating cut-offs were homogeneously distributed in Gram-negative and Gram-positive sepsis and were higher in septic shock, but not influenced by pathogen etiologies. MR-proADM cut-off values > 3.39 nmol/L in sepsis and >4.33 nmol/L in septic shock were associated with significant higher risk of 90-days mortality. In conclusion, PCT and MR-proADM combination represents an advantage for sepsis diagnosis and for 90-days mortality risk stratification.

Neutrophil to Lymphocyte Ratio (NLR) and Derived Neutrophil to Lymphocyte Ratio (d-NLR) Predict Non-Responders and Postoperative Complications in Patients Undergoing Radical Surgery After Neo-Adjuvant Radio-Chemotherapy for Rectal Adenocarcinoma.

In order to evaluate neutrophil-to-lymphocyte ratio (NLR) and derived neutrophil-to-lymphocyte ratio (d-NLR) in predicting response and complications in rectal cancer patients who underwent surgery after neo-adjuvant radio-chemotherapy, 87 patients were evaluated. Cutoffs before and after radio-chemotherapy were respectively 2.8 and 3.8 for NLR, and 1.4 and 2.3 for d-NLR. They were analyzed in relation to clinical and pathological outcomes. Patients with preoperative NLR and d-NLR higher than cutoffs had significantly higher rates of tumor regression grade response (TRG ≥ 4) and postoperative complications. Elevated NLR and d-NLR after radio-chemotherapy are associated with worse pathological and clinical outcome.

Ipilimumab and immune-mediated adverse events: a case report of anti-CTLA4 induced ileitis.

BACKGROUND: Ipilimumab is a fully human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 , a key negative regulator of T-cell activation approved by the Food and Drug Administration as of March 2011 for the treatment of metastatic melanoma. As a result of the up-regulation of the immune system, several immune-mediated adverse effects have been reported including colitis, dermatitis, hepatitis and rarely hypophysitis. The most frequent immune-mediated adverse effects described in literature include gastrointestinal toxicity such as diarrhea, colitis and case of colitis and ileitis. CASE PRESENTATION: In this paper we report an interesting case of immune-mediate ileitis without colitis in a 54 years old woman with metastatic melanoma treated with ipilimumab. We also discuss about case management and the possible pathological mechanisms considering also previous reports. CONCLUSIONS: The aim of this article is to support further investigations concerning epigenetic and genetic analysis in order to personalize biological therapy and to reduce immune related adverse events observed after ipilimumab administration.

Novel Biomarkers in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) represents a neoplasm with an increasing incidence in both sexes [...].

Full robotic cholecystectomy: first worldwide experiences with HUGO RAS surgical platform.

BACKGROUND: The Hugo RAS™ system (Medtronic, Minneapolis, MN, USA), approved for gynaecological and urological procedures, has been recently certified for the use in few general surgeries. Only bariatric and colorectal procedures have been described so far. METHODS: Here, we report the first worldwide experience with three cases of full-robotic cholecystectomies with the Hugo RAS™ system. RESULTS: A description of the operative room setup, of the docking angles and details of the procedures is reported. Docking time was 12, 10, and 6 min, respectively. The total operative time was 105 min in the first case, 100 min in the second and 88 in the third case. Intra- and post-operative courses were uneventful. CONCLUSIONS: With this pre-defined set up, the innovative conformation of Hugo RAS™ system can safely allow performing full robotic cholecystectomy avoiding the need for additional ports.

First worldwide report on rectal resections with Hugo™ surgical system: description of docking angles and tips for an effective setup.

BACKGROUNDS: Rectal robotic surgery gained momentum in the last decade, but it is still associated with not-negligible costs. In order to reduce costs, recently different robotic systems have received approval for clinical use. This study aims to present the first case series of rectal resection with the novel cost-effective platform Robotic Assisted Surgery (RAS) Hugo™. Tips for effective set up of the system and detailed configuration of tilt and docking angles are also provided. METHODS: Three cases of rectal resection with Hugo RAS™ system are reported. After the first two cases of resection with partial mesorectal excision in which surgeries were performed with the setup proposed by the vendor company, in the third case we tested a novel setup that allowed a full robotic low rectal resection performing vascular ligations, TME and colonic splenic flexure mobilization without the need of any de-docking. RESULTS: Our first three robotic rectal resections with the Hugo RAS™ system were completed without complications with a median docking time of 12 min (range 8-15) and a median console time of 345 minutes (range 271-475). In the first two cases, hybrid robotic and laparoscopic surgeries were performed to obtain an adequate haemostasis and traction during the pelvic phase. In the third case, a full robotic TME was successfully accomplished. CONCLUSION: Our experience demonstrates that a full robotic low rectal resection with TME with Hugo™ RAS system is feasible, safe and associated with satisfactory postoperative outcomes.

Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy.

Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection. Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89). Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

Aberrant promoter methylation of beta-1,4 galactosyltransferase 1 as potential cancer-specific biomarker of colorectal tumors.

Epigenetic alterations, such as CpG islands methylation and histone modifications, are recognized key characteristics of cancer. Glycogenes are a group of genes which epigenetic status was found to be changed in several tumors. In this study, we determined promoter methylation status of the glycogene beta-1,4-galactosyltransferase 1 (B4GALT1) in colorectal cancer patients. Methylation status of B4GALT1 was assessed in 130 colorectal adenocarcinomas, 13 adenomas, and in paired normal tissue using quantitative methylation specific PCR (QMSP). B4GALT1 mRNA expression was evaluated in methylated/unmethylated tumor and normal specimens. We also investigated microsatellite stability and microsatellite instability status and KRAS/BRAF mutations. Discriminatory power of QMSP was assessed by receiving operating curve (ROC) analysis on a training set of 24 colorectal cancers and paired mucosa. The area under the ROC curve (AUC) was 0.737 (95% confidence interval [CI]:0.591-0.881, P = 0.005) with an optimal cutoff value of 2.07 yielding a 54% sensitivity (95% CI: 35.1%-72.1%) and a specificity of 91.7% (95% CI: 74.1%-97.7%). These results were confirmed in an independent validation set where B4GALT1 methylation was detected in 52/106 patients. An inverse correlation was observed between methylation and B4GALT1 mRNA expression levels (r = -0.482, P = 0.037). Significant differences in methylation levels and frequencies was demonstrated in invasive lesions as compared with normal mucosa (P = 0.0001) and in carcinoma samples as compared with adenoma (P = 0.009). B4GALT1 methylation is a frequent and specific event in colorectal cancer and correlates with downregulation of mRNA expression. These results suggest that the glycogene B4GALT1 represent a valuable candidate biomarker of invasive phenotype of colorectal cancer.

Hot topics in pancreatic cancer management.

Pancreatic ductal adenocarcinoma (PDAC) is a sneaky and lethal disease burdened by poor prognosis. PDAC is often detected too late to be successfully cured, and it has been estimated that it will be a leading cause of cancer-related deaths in the near future. During the last decade, multimodal treatments involving surgery, chemotherapy and radiotherapy have contributed to improving the prognosis of this disease; however, long-term results are still not satisfactory. Postoperative morbidity and mortality rates remain high, and systemic treatments are burdened by toxicity in both neoadjuvant and adjuvant settings. Advancements in technologies, targeted therapies, immunotherapy and PDAC microenvironment modulation strategies may represent useful potential weapons in the future. Nevertheless, in the fight against this dreadful disease, there is an urgent need for new, cheap and user-friendly tools for early detection. In this field, promising results have been found in nanotechnologies and "omics" analyses that search for new biomarkers to be used in primary and secondary prevention. However, there are many issues that need to be solved before considering these tools in daily clinical practice. This editorial reported the state of the art of pancreatic cancer management.

Stratifying Risk for Pancreatic Cancer by Multiplexed Blood Test.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease, for which mortality closely parallels incidence. So far, the available techniques for PDAC detection are either too invasive or not sensitive enough. To overcome this limitation, here we present a multiplexed point-of-care test that provides a "risk score" for each subject under investigation, by combining systemic inflammatory response biomarkers, standard laboratory tests, and the most recent nanoparticle-enabled blood (NEB) tests. The former parameters are routinely evaluated in clinical practice, whereas NEB tests have been recently proven as promising tools to assist in PDAC diagnosis. Our results revealed that PDAC patients and healthy subjects can be distinguished accurately (i.e., 88.9% specificity, 93.6% sensitivity) by the presented multiplexed point-of-care test, in a quick, non-invasive, and highly cost-efficient way. Furthermore, the test allows for the definition of a "risk threshold", which can help clinicians to trace the optimal diagnostic and therapeutic care pathway for each patient. For these reasons, we envision that this work may accelerate progress in the early detection of PDAC and contribute to the design of screening programs for high-risk populations.

Right hepatic artery anomalies in pancreatoduodenectomy-a risk for arterial resection but not for postoperative outcomes.

Background: Pancreatoduodenectomy (PD) is a complex surgical procedure known for its significant morbidity rates, and the presence of an aberrant hepatic artery (AHA) introduces additional challenges. The impact of AHA on post-PD outcomes has been a subject of conflicting findings in the medical literature. This study aimed to investigate how variations in hepatic arterial anatomy influence intra-operative variables and postoperative morbidity. Methods: A retrospective analysis was conducted on 113 PD cases. Patients with variant hepatic arterial anatomy (n=38) were categorized as Group 1, while those without vascular abnormalities comprised Group 2. Perioperative and postoperative outcomes were examined. Results: Patients in Groups 1 and 2 exhibited similar characteristics, and no notable differences in surgical complications were observed. There was, however, a noticeable trend towards a higher incidence of postpancreatectomy hemorrhage (PPH) in Group 1 (31.6% vs. 20.0%; P=0.17). Furthermore, a statistically significant increase in the rate of arterial resections was noted in patients with vascular anomalies (10.5% vs. 1.33%; P=0.02). Conclusions: The prevalence of vascular abnormalities in the hepatic arterial circulation is more frequent than initially anticipated. These anomalies present additional complexities to the already intricate PD procedure, leading to a heightened necessity for arterial resection, albeit without any discernible impact on postoperative complications.

Neoadjuvant Treatments for Pancreatic Ductal Adenocarcinoma: Where We Are and Where We Are Going.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) represents a challenging disease for the surgeon, oncologist, and radiation oncologist in both diagnostic and therapeutic settings. Surgery is currently the gold standard treatment, but the role of neoadjuvant treatment (NAD) is constantly evolving and gaining importance in resectable PDACs. The aim of this narrative review is to report the state of the art and future perspectives of neoadjuvant therapy in patients with PDAC. METHODS: A PubMed database search of articles published up to September 2022 was carried out. RESULTS: Many studies showed that FOLFIRINOX or Gemcitabine-nab-paclitaxel in a neoadjuvant setting had a relevant impact on overall survival (OS) for patients with locally advanced and borderline resectable PDAC without increasing post-operative complications. To date, there have not been many published multicentre randomised trials comparing upfront surgery with NAD in resectable PDAC patients, but the results obtained are promising. NAD in resectable PDAC showed long-term effective benefits in terms of median OS (5-year OS rate 20.5% in NAD group vs. 6.5% in upfront surgery). NAD could play a role in the treatment of micro-metastatic disease and lymph nodal involvement. In this scenario, given the low sensitivity and specificity for lymph-node metastases of radiological investigations, CA 19-9 could be an additional tool in the decision-making process. CONCLUSIONS: The future challenge could be to identify only selected patients who will really benefit from upfront surgery despite a combination of NAD and surgery.

Inflammatory biomarkers and nanotechnology: new insights in pancreatic cancer early detection.

BACKGROUND: Poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is mainly due to the lack of effective early-stage detection strategies. Even though the link between inflammation and PDAC has been demonstrated and inflammatory biomarkers proved their efficacy in predicting several tumours, to date they have a role only in assessing PDAC prognosis. Recently, the studies of interactions between nanosystems and easily collectable biological fluids, alone or coupled with standard laboratory tests, have proven useful in facilitating PDAC diagnosis. Notably, tests based on magnetic levitation (MagLev) of biocoronated nanosystems have demonstrated high diagnostic accuracy in compliance with the criteria stated by WHO. Herein, the author developed a synergistic analysis that combines a user-friendly MagLev-based approach and common inflammatory biomarkers for discriminating PDAC subjects from healthy ones. MATERIALS AND METHODS: Plasma samples from 24 PDAC subjects and 22 non-oncological patients have been collected and let to interact with graphene oxide nanosheets.Biomolecular corona formed around graphene oxide nanosheets have been immersed in a Maglev platform to study the levitation profiles.Inflammatory biomarkers such as neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), and platelet to lymphocyte ratio have been calculated and combined with results obtained by the MagLev platform. RESULTS: MagLev profiles resulted significantly different between non-oncological patients and PDAC and allowed to identify a MagLev fingerprint for PDAC. Four inflammatory markers were significantly higher in PDAC subjects: neutrophils ( P =0.04), NLR ( P =4.7 ×10 -6 ), dNLR ( P =2.7 ×10 -5 ), and platelet to lymphocyte ratio ( P =0.002). Lymphocytes were appreciably lower in PDACs ( P =2.6 ×10 -6 ).Combining the MagLev fingerprint with dNLR and NLR returned global discrimination accuracy for PDAC of 95.7% and 91.3%, respectively. CONCLUSIONS: The multiplexed approach discriminated PDAC patients from healthy volunteers in up to 95% of cases. If further confirmed in larger-cohort studies, this approach may be used for PDAC detection.

Postoperative procalcitonin is a biomarker for excluding the onset of clinically relevant pancreatic fistula after pancreaticoduodenectomy.

Background: Early detection and therapy of pancreatic fistula after pancreaticoduodenectomy is crucial to improve outcomes of this surgery. Since it is not clear if procalcitonin (PCT), can predict the onset of clinically relevant post-operative pancreatic fistula (CR-POPF), we aimed to investigate this ability. Methods: One-hundred-thirty pancreaticoduodenectomies (PD) were analyzed. Receiver Operating Characteristic curves analysis defined the optimal cut-offs for PCT and drains amylase levels (DAL). Complications were compared using chi-square for proportions test. Results: DAL ≥2,000 U/L in postoperative day (POD) 2 had 71% positive predictive value (PPV) and 91% negative predictive value (NPV) for CR-POPF (P<0.001). In POD2, PCT ≥0.5 ng/mL showed NPV 91% (P<0.045) and increased DAL PPV for CR-POPF to 81%. In POD3, POD4 and POD5, DAL (cut-offs 780, 157 and 330 U/L, respectively) showed NPV for CR-POPF >90% (P<0.0001). PCT ≥0.5 ng/mL showed NPV for CR-POPF of about 90%. In POD5, combining DAL (cut-off 330 U/L) and PCT (cut-off 0.5 ng/mL), a PPV for CR-POPF of 81% was detected. A progressive increased risk of CR-POPF from POD2 [odds ratio (OR) =3.05; P=0.0348] to POD5 (OR =4.589; P=0.0082) was observed. In POD2 and 5, PCT ≥0.5 ng/mL, alone and in combination with DAL, may be a reliable marker for identifying patients at highest risk of CR-POPF after PD. Conclusions: This association could be proposed to select high risk patients that could benefit of "intensive" postoperative management.

Role of preoperative sarcopenia in predicting postoperative complications and survival after pancreatoduodenectomy for pancreatic cancer.

AIM: The aim of this monocentric retrospective study was to investigate the relation between sarcopenia, postoperative complications and survival in patients undergoing radical surgery for pancreatic ductal adenocarcinoma (PDAC). MATERIAL OF STUDY: From a prospective collected database of 230 consecutive pancreatoduodenectomies (PD), data regarding patient's body composition, evaluated on diagnostic preoperative CT scans and defined as Skeletal Muscle Index (SMI) and Intramuscular Adipose Tissue Content (IMAC), postoperative complications and long-term outcomes were retrospectively analysed. Descriptive and survival analyses were performed. RESULTS: Sarcopenia was found in 66% of study population. The majority of patients who developed at least one postoperative complication was sarcopenic. However, sarcopenia did not statistically significantly relate with the development of postoperative complications. However, all pancreatic fistula C occurs in sarcopenic patients. Moreover, there was no significant difference in median Overall Survival (OS) and Disease Free Survival (DFS) between sarcopenic and nonsarcopenic patients (31 versus 31.8 months and 12.9 and 11.1 months respectively). DISCUSSION: Our results showed that sarcopenia was not related to short- and long-term outcomes in PDAC patients undergoing PD. However, the quantitative and qualitative radiological parameters are probably not enough to study the sarcopenia alone. CONCLUSIONS: The majority of early stage PDAC patients undergoing PD were sarcopenic. Cancer stage was a determinant factor of sarcopenia while BMI seems less important. In our study, sarcopenia was associated with postoperative complications and in particular with pancreatic fistula. Further studies will need to demonstrated that sarcopenia can be considered an objective measure of patient frailty and strongly associated with short- and long-term outcomes. KEY WORDS: Pancreatic ductal adenocarcinoma, Pancretoduodenectomy, Sarcopenia.