Toward a new paradigm of care: a surgical leaders' Delphi consensus on the organizational factors of the new pancreas units (E-AHPBA PUECOF study).

Pancreas units represent new organizational models of care that are now at the center of the European debate. The PUECOF study, endorsed by the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), aims to reach an expert consensus by enquiring surgical leaders about the Pancreas Units' most relevant organizational factors, with 30 surgical leaders from 14 countries participating in the Delphi survey. Results underline that surgeons believe in the need to organize multidisciplinary meetings, nurture team leadership, and create metrics. Clinical professionals and patients are considered the most relevant stakeholders, while the debate is open when considering different subjects like industry leaders and patient associations. Non-technical skills such as ethics, teamwork, professionalism, and leadership are highly considered, with mentoring, clinical cases, and training as the most appreciated facilitating factors. Surgeons show trust in functional leaders, key performance indicators, and the facilitating role played by nurse navigators and case managers. Pancreas units have a high potential to improve patients' outcomes. While the pancreas unit model of care will not change the technical content of pancreatic surgery, it may bring surgeons several benefits, including more cases, professional development, easier coordination, less stress, and opportunities to create fruitful connections with research institutions and industry leaders.

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.

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.

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.

The impact of intensified staging and combined therapies in locally advanced pancreatic cancer: a secondary analysis of prospective studies.

AIM: To investigate the use of comprehensive pre-treatment staging with multiple diagnostic modalities, including functional imaging and minimally invasive surgical procedures, in locally advanced pancreatic cancer (LAPC) patients. The primary objective was to detect occult metastatic disease using staging laparoscopy and 18FFDG-PET/CT scan. The study also evaluated treatment efficacy and outcomes in LAPC patients treated with combined therapies. MATERIALS AND METHODS: This study was a secondary analysis of three prospective studies of chemoradiotherapy (CRT) with or without induction chemotherapy (IC). The inclusion period was from December 2009 until February 2023. An intensified pretreatment staging was conducted for all LAPC patients. Patients without distant disease at initial staging, with borderline resectable or unresectable LAPC, were enrolled in chemoradiotherapy combination protocols (CRT with or without IC). IC regimens included GemOx or FOLFIRINOX for four cycles, followed by concurrent CRT with gemcitabine. The primary endpoint was the detection of occult metastatic disease, and secondary objectives included resection rate, treatment toxicity, overall survival (OS), progression-free survival (PFS), local control (LC), and metastasis-free survival (MFS). RESULTS: Out of the 134 LAPC patients, 33.5% were identified with metastatic disease. Of these, 23.1% had a positive exploratory laparoscopy. Additionally, 13.4% were identified as having distant metastases by 18-FDG PET/CT. The median PFS for all patients who completed CRT was 14.3 months, and the median OS was 17.2 months. Resected patients after the combined therapies demonstrated significantly improved outcomes compared to non-resected patients (median PFS, 22.5 mo vs. 9.5 mo, P<0.001; median OS, 38.2 mo vs. 13 mo, P<0.001). Moreover, patients treated with IC followed by CRT showed significantly better outcomes compared to upfront CRT group (median PFS, 19 mo vs. 9.9 mo, P<0.001; median OS, 19.3 mo vs. 14.6 mo, P<0.001). At univariate logistic regression analysis, the adding of IC was the only predictor for resection rate (95% CI 0.12-1.02, P=0.05), and this data was confirmed at multivariate analysis (95% CI 0.09-0.98, P=0.04). Haematological and gastrointestinal toxicities were observed during treatment, with manageable adverse events. CONCLUSIONS: The use of comprehensive pre-treatment staging, including laparoscopy and 18F-FDG-PET/CT scan, is an effective approach in identifying occult metastatic disease in LAPC patients. Our findings offer valuable insights into accurate staging and treatment efficacy, providing evidence-based support for optimal management strategies in LAPC patients.

Preoperative CA19.9 level predicts lymph node metastasis in resectable adenocarcinoma of the head of the pancreas: A further plea for biological resectability criteria.

INTRODUCTION: Lymph-nodal involvement (N+) represents an adverse prognostic factor after pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). Preoperative diagnostic and staging modalities lack sensitivity for identifying N+. This study aimed to investigate preoperative CA19.9 in predicting the N+ stage in resectable-PDAC (R-PDAC). METHODS: Patients included in a multi-institutional retrospective database of PDs performed for R-PDAC from January 2000 to June 2021 were analyzed. A preoperative laboratory value of CA19.9 >37 U/L was used in univariate and multivariate logistic regression analysis to determine a possible association with N+. Additionally, different cut-offs of CA19.9 related to the preoperative clinical T (cT) stage was assessed to evaluate the risk of N+. RESULTS: A total of 2034 PDs from thirteen centers were included in the study. CA19.9>37 U/L was significantly associated with higher N+ at univariate and multivariate analysis (P<0.001). CA19.9 levels >37 U/L were associated with N+ in 75.9%, 81.3%, and 85.7% of patients, respectively, in cT1, cT2, and cT3 tumors and with higher cut-off values for all cT stages. CONCLUSION: Lymph nodal involvement is strongly related to preoperative CA19.9 levels. Specially in patients staged as cT3 the CA 19.9 could represent a valid and easy tool to suspect nodal involvement. Due to these findings, R-PDAC patients with elevated CA19.9 values should be considered in a more biologically advanced stage.

Prospective minimally invasive pancreatic resections from the IGOMIPS registry: a snapshot of daily practice in Italy on 1191 between 2019 and 2022.

This retrospective analysis of the prospective IGOMIPS registry reports on 1191 minimally invasive pancreatic resections (MIPR) performed in Italy between 2019 and 2022, including 668 distal pancreatectomies (DP) (55.7%), 435 pancreatoduodenectomies (PD) (36.3%), 44 total pancreatectomies (3.7%), 36 tumor enucleations (3.0%), and 8 central pancreatectomies (0.7%). Spleen-preserving DP was performed in 109 patients (16.3%). Overall incidence of severe complications (Clavien-Dindo ≥ 3) was 17.6% with a 90-day mortality of 1.9%. This registry analysis provided some important information. First, robotic assistance was preferred for all MIPR but DP with splenectomy. Second, robotic assistance reduced conversion to open surgery and blood loss in comparison to laparoscopy. Robotic PD was also associated with lower incidence of severe postoperative complications and a trend toward lower mortality. Fourth, the annual cut-off of ≥ 20 MIPR and ≥ 20 MIPD improved selected outcome measures. Fifth, most MIPR were performed by a single surgeon. Sixth, only two-thirds of the centers performed spleen-preserving DP. Seventh, DP with splenectomy was associated with higher conversion rate when compared to spleen-preserving DP. Eighth, the use of pancreatojejunostomy was the prevalent reconstruction in PD. Ninth, final histology was similar for MIPR performed at high- and low-volume centers, but neoadjuvant chemotherapy was used more frequently at high-volume centers. Finally, this registry analysis raises important concerns about the reliability of R1 assessment underscoring the importance of standardized pathology of pancreatic specimens. In conclusion, MIPR can be safely implemented on a national scale. Further analyses are required to understand nuances of implementation of MIPR in Italy.

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.

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.

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.

Advances in pre-treatment evaluation of pancreatic ductal adenocarcinoma: a narrative review.

Background and Objective: Despite advances in the multidisciplinary management of pancreatic cancer, overall prognosis remains poor, due to early progression of the disease. There is a need to also take action in staging, to make it increasingly accurate and complete, to define the setting of the therapeutic strategy. This review was planned to update the current status of pre-treatment evaluation for pancreatic cancer. Methods: We conducted an extensive review, including relevant articles dealing with traditional imaging, functional imaging and minimally invasive surgical procedures before treatment for pancreatic cancer. We searched articles written in English only. Data in the PubMed database, published in the period between January 2000 and January 2022, were retrieved. Prospective observational studies, retrospective analyses and meta-analyses were reviewed and analysed. Key Content and Findings: Each imaging modality (endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography, computed tomography, positron emission tomography/computed tomography, staging laparoscopy) has its own diagnostic advantages and limitations. The sensitivity, specificity and accuracy for each image set are reported. Data that support the increasing role of neoadjuvant therapy (radiotherapy and chemotherapy) and the meaning of a patient-tailored treatment selection, based on tumour staging, are also discussed. Conclusions: A multimodal pre-treatment workup should be searched as it improves staging accuracy, orienting patients with resectable tumors towards surgery, optimizing patient selection with locally advanced tumors to neoadjuvant or definite therapy and avoiding surgical resection or curative radiotherapy in those with metastatic disease.

Combination Therapy with a Bispecific Antibody Targeting the hERG1/ß1 Integrin Complex and Gemcitabine in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) represents an unmet medical need. Difficult/late diagnosis as well as the poor efficacy and high toxicity of chemotherapeutic drugs result in dismal prognosis. With the aim of improving the treatment outcome of PDAC, we tested the effect of combining Gemcitabine with a novel single chain bispecific antibody (scDb) targeting the cancer-specific hERG1/ß1 integrin complex. First, using the scDb (scDb-hERG1-ß1) in immunohistochemistry (IHC), Western blot (WB) analysis and immunofluorescence (IF), we confirmed the presence of the hERG1/ß1 integrin complex in primary PDAC samples and PDAC cell lines. Combining Gemcitabine with scDb-hERG1-ß1 improved its cytotoxicity on all PDAC cells tested in vitro. We also tested the combination treatment in vivo, using an orthotopic xenograft mouse model involving ultrasound-guided injection of PDAC cells. We first demonstrated good penetration of the scDb-hERG1-ß1 conjugated with indocyanine green (ICG) into tumour masses by photoacoustic (PA) imaging. Next, we tested the effects of the combination at either therapeutic or sub-optimal doses of Gemcitabine (25 or 5 mg/kg, respectively). The combination of scDb-hERG1-ß1 and sub-optimal doses of Gemcitabine reduced the tumour masses to the same extent as the therapeutic doses of Gemcitabine administrated alone; yielded increased survival; and was accompanied by minimised side effects (toxicity). These data pave the way for a novel therapeutic approach to PDAC, based on the combination of low doses of a chemotherapeutic drug (to minimize adverse side effects and the onset of resistance) and the novel scDb-hERG1-ß1 targeting the hERG1/ß1 integrin complex as neoantigen.

Cardiac Surgery in Nonagenarians Following the TAVI/TMVI Era: A Multicenter 23-Year Comparative Analysis.

BACKGROUND: Studies reporting on the outcome of 90-year-old patients undergoing cardiac surgery are scant in literature; and currently, those regarding the implementation of trans-catheter techniques number even fewer. METHODS: We compared patients aged >89 years operated on between 1998 and 2008 at 8 Italian cardiac surgery centers, with patients of the same age operated on between 2009 and 2021. All of the patients were operated on with "open" surgery, with the exclusion of percutaneous valve repair/implantation procedures. RESULTS: The patients of the two groups (group 98-08-127 patients, and group 09-21-101 patients) had comparable preoperative risk factors in terms of the LogEuroSCORE (98-08: 21.3 ± 6.1 vs. 09-21: 20.9 ± 11.1, p = 0.12). There was a considerable difference in the type of surgery (isolated valve, isolated coronary, and combined surgery, 46.5, 38.5, and 15% vs. 52, 13, and 35% in 98-08 and 09-21, respectively, p = 0.01). Analogous operating durations were recorded (cross-clamp time: 98-08: 46 ± 28 min vs. 09-21: 51 ± 28 min, p = 0.06). The number of packed bypasses was lower in 09-21 (1.3 ± 0.6 vs. 2.4 ± 1.2, p = 0.001). In the postoperative period, there was a statistically significant difference in the 30-day survival in favor of the "more recent" patients (98-08: 17 deaths (13.4%) versus 09-21: 6(5.9%); p = 0.001), also confirmed in the subgroups (12.2% vs. 0% in isolated coronary surgery, p < 0.001; and 12.3% vs. 0% in isolated valve surgery, p < 0.001). CONCLUSIONS: Accurate pre-, intra-, and post-operative evaluation/management to reduce biological impacts facilitate significant improvements in the outcomes in nonagenarian patients when compared to the results recorded in previous years.

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.

Multiplexed Detection of Pancreatic Cancer by Combining a Nanoparticle-Enabled Blood Test and Plasma Levels of Acute-Phase Proteins.

The development of new tools for the early detection of pancreatic ductal adenocarcinoma (PDAC) represents an area of intense research. Recently, the concept has emerged that multiplexed detection of different signatures from a single biospecimen (e.g., saliva, blood, etc.) may exhibit better diagnostic capability than single biomarkers. In this work, we develop a multiplexed strategy for detecting PDAC by combining characterization of the nanoparticle (NP)-protein corona, i.e., the protein layer that surrounds NPs upon exposure to biological fluids and circulating levels of plasma proteins belonging to the acute phase protein (APPs) family. As a first step, we developed a nanoparticle-enabled blood (NEB) test that employed 600 nm graphene oxide (GO) nanosheets and human plasma (HP) (5% vol/vol) to produce 75 personalized protein coronas (25 from healthy subjects and 50 from PDAC patients). Isolation and characterization of protein corona patterns by 1-dimensional (1D) SDS-PAGE identified significant differences in the abundance of low-molecular-weight corona proteins (20-30 kDa) between healthy subjects and PDAC patients. Coupling the outcomes of the NEB test with the circulating levels of alpha 2 globulins, we detected PDAC with a global capacity of 83.3%. Notably, a version of the multiplexed detection strategy run on sex-disaggregated data provided substantially better classification accuracy for men (93.1% vs. 77.8%). Nanoliquid chromatography tandem mass spectrometry (nano-LC MS/MS) experiments allowed to correlate PDAC with an altered enrichment of Apolipoprotein A-I, Apolipoprotein D, Complement factor D, Alpha-1-antichymotrypsin and Alpha-1-antitrypsin in the personalized protein corona. Moreover, other significant changes in the protein corona of PDAC patients were found. Overall, the developed multiplexed strategy is a valid tool for PDAC detection and paves the way for the identification of new potential PDAC biomarkers.

Role of CA 19.9 in the Management of Resectable Pancreatic Cancer: State of the Art and Future Perspectives.

BACKGROUND: Surgery still represents the gold standard of treatment for resectable pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant treatments (NAT), currently proposed for borderline and locally advanced PDACs, are gaining momentum even in resectable tumors due to the recent interesting concept of "biological resectability". In this scenario, CA 19.9 is having increasing importance in preoperative staging and in the choice of therapeutic strategies. We aimed to assess the state of the art and to highlight the future perspectives of CA 19.9 use in the management of patients with resectable pancreatic cancer. METHODS: A PubMed database search of articles published up to December 2021 has been carried out. RESULTS: Elevated pre-operative levels of CA 19.9 have been associated with reduced overall survival, nodal involvement, and margin status positivity after surgery. These abilities of CA 19.9 increase when combined with radiological or different biological criteria. Unfortunately, due to strong limitations of previously published articles, CA 19.9 alone cannot be yet considered as a key player in resectable pancreatic cancer patient management. CONCLUSION: The potential of CA 19.9 must be fully explored in order to standardize its role in the "biological staging" of patients with resectable pancreatic cancer.

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.

Validations of new cut-offs for surgical drains management and use of computerized tomography scan after pancreatoduodenectomy: The DALCUT trial.

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most fearful complication after pancreatic surgery and can lead to severe postoperative complications such as surgical site infections, sepsis and bleeding. A previous study which identified cut-offs of drains amylase levels (DALs) determined on postoperative day (POD) 1 and POD3, was able to significantly predict POPF, abdominal collections and biliary fistulas, when related to specific findings detected at the abdominal computerized tomography (CT) scan routinely performed on POD3. AIM: To validate the cut-offs of DALs in POD1 and POD3, established during the previous study, to assess the risk of clinically relevant POPF and confirm the usefulness of abdominal CT scan on POD3 in patients at increased risk of abdominal collection. METHODS: The DALCUT trial is an interventional prospective study. All patients who will undergo pancreatoduodenectomy (PD) for periampullary neoplasms will be considered eligible. All patients will receive clinical staging and, if eligible for surgery, will undergo routine preoperative evaluation. After the PD, daily DALs will be evaluated from POD1. Drains removal and possible requirement of abdominal CT scans in POD3 will be managed on the basis of the outcome of DALs in the first three postoperative days. RESULTS: This prospective study could validate the role of DALs in the management of surgical drains and in assessing the risk or relevant complications after PD. Drains could be removed in POD3 in case of POD1 DALs < 666 U/L and POD3 DALs < 207 U/L. In case of POD3 DALs ≥ 252, abdominal CT scan will be performed in POD3 to identify abdominal collections ≥ 5 cm. In this latter category of patients, drains could be maintained beyond POD3. CONCLUSION: The results of this trial will contribute to a better knowledge of POPF and management of surgical drains.

Factors Predicting Pathological Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer: The Experience of a Single Institution with 269 Patients (STONE-01).

AIMS: The aim of this study was to define a potential benefit of pathological complete response rate (pCR) and downstaging rate after neoadjuvant chemoradiotherapy (CRT) in relation to treatment and patient factors in locally advanced rectal cancer. METHODS: We performed a retrospective cohort study. Patients were divided according to chemotherapy regimens concurrent to radiotherapy (1-drug vs. 2-drug) and according to the time interval between the end of CRT and surgery (≤8 weeks vs. >8 weeks), as well as in relation to specific relevant clinical factors. Logistic regression was used to estimate the independent factors for pCR and downstaging. RESULTS: 269 patients were eligible for this study. Overall, pCR and downstaging rates were 26% and 75.4%, respectively. Univariate analysis showed that female gender (p = 0.01) and time to surgery >8 weeks (p = 0.04) were associated with pCR; age > 70 years (p = 0.05) and time to surgery >8 weeks (p = 0.002) were correlated to downstaging. At multivariate analysis, interval time to surgery of >8 weeks was the only independent factor for both pCR and downstaging (p = 0.02; OR: 0.5, CI: 0.27-0.93 and p = 0.003; OR: 0.42, CI: 0.24-0.75, respectively). CONCLUSIONS: This study indicates that, in our population, an interval time to surgery of >8 weeks is an independent significant factor for pCR and downstaging. Further prospective studies are needed to define the best interval time.