Two synchronous primary mesenteric neuroendocrine tumors in a patient: a case report

Primary mesenteric neuroendocrine tumors represent a rare clinical entity, challenging to manage, while a combination of imaging is demanded in order to differentiate it from metastatic disease, and set the diagnosis. If the tumor is resectable, surgery is the fundament of the therapeutic approach. The appearance of a second primary mesenteric tumor suggests an unacquainted scenario. The current article presents a case of a 40-year-old woman, who underwent laparoscopic excision of a mesenteric tumor located close to the left pararenal space. Pathology with immunohistochemistry examination reported neuroendocrine tumor grade 2. No further treatment was necessary. Seven months later, 68-Gallium DOTATATE detected another primary neuroendocrine tumor located at the right retroperitoneal space without other lesions. The second tumor was also resected laparoscopically, and the pathology confirmed the diagnosis of another neuroendocrine tumor G2. The postoperative course was uneventful, and six months later the patient is disease-free. The adequacy of 68-Gallium DOTATATE for the preoperative diagnosis of primary mesenteric tumors, the role of the laparoscopic approach, and the extent of lymph node resection are matters addressed in this article

The genomic landscape of ANCA-associated vasculitis: Distinct transcriptional signatures, molecular endotypes and comparison with systemic lupus erythematosus

IntroductionAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) present with a complex phenotype and are associated with high mortality and multi-organ involvement. We sought to define the transcriptional landscape and molecular endotypes of AAVs and compare it to systemic lupus erythematosus (SLE).MethodsWe performed whole blood mRNA sequencing from 30 patients with AAV (granulomatosis with polyangiitis/GPA and microscopic polyangiitis/MPA) combined with functional enrichment and network analysis for aberrant pathways. Key genes and pathways were validated in an independent cohort of 18 AAV patients. Co-expression network and hierarchical clustering analysis, identified molecular endotypes. Multi-level transcriptional overlap analysis to SLE was based on our published data from 142 patients.ResultsWe report here that “Pan-vasculitis” signature contained 1,982 differentially expressed genes, enriched in leukocyte differentiation, cytokine signaling, type I and type II IFN signaling and aberrant B-T cell immunity. Active disease was characterized by signatures linked to cell cycle checkpoints and metabolism pathways, whereas ANCA-positive patients exhibited a humoral immunity transcriptional fingerprint. Differential expression analysis of GPA and MPA yielded an IFN-g pathway (in addition to a type I IFN) in the former and aberrant expression of genes related to autophagy and mRNA splicing in the latter. Unsupervised molecular taxonomy analysis revealed four endotypes with neutrophil degranulation, aberrant metabolism and B-cell responses as potential mechanistic drivers. Transcriptional perturbations and molecular heterogeneity were more pronounced in SLE. Molecular analysis and data-driven clustering of AAV uncovered distinct transcriptional pathways that could be exploited for targeted therapy.DiscussionWe conclude that transcriptomic analysis of AAV reveals distinct endotypes and molecular pathways that could be targeted for therapy. The AAV transcriptome is more homogenous and less fragmented compared to the SLE which may account for its superior rates of response to therapy

Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment

We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers). Eight were difficult targets for which only distantly related templates were found for the individual subunits. Twenty-five CAPRI groups including eight automatic servers submitted ~1250 models per target. Twenty groups including six servers participated in the CAPRI scoring challenge submitted ~190 models per target. The accuracy of the predicted models was evaluated using the classical CAPRI criteria. The prediction performance was measured by a weighted scoring scheme that takes into account the number of models of acceptable quality or higher submitted by each group as part of their five top-ranking models. Compared to the previous CASP-CAPRI challenge, top performing groups submitted such models for a larger fraction (70–75%) of the targets in this Round, but fewer of these models were of high accuracy. Scorer groups achieved stronger performance with more groups submitting correct models for 70–80% of the targets or achieving high accuracy predictions. Servers performed less well in general, except for the MDOCKPP and LZERD servers, who performed on par with human groups. In addition to these results, major advances in methodology are discussed, providing an informative overview of where the prediction of protein assemblies currently stands.Cancer Research UK, Grant/Award Number: FC001003; Changzhou Science and Technology Bureau, Grant/Award Number: CE20200503; Department of Energy and Climate Change, Grant/Award Numbers: DE-AR001213, DE-SC0020400, DE-SC0021303; H2020 European Institute of Innovation and Technology, Grant/Award Numbers: 675728, 777536, 823830; Institut national de recherche en informatique et en automatique (INRIA), Grant/Award Number: Cordi-S; Lietuvos Mokslo Taryba, Grant/Award Numbers: S-MIP-17-60, S-MIP-21-35; Medical Research Council, Grant/Award Number: FC001003; Japan Society for the Promotion of Science KAKENHI, Grant/Award Number: JP19J00950; Ministerio de Ciencia e Innovación, Grant/Award Number: PID2019-110167RB-I00; Narodowe Centrum Nauki, Grant/Award Numbers: UMO-2017/25/B/ST4/01026, UMO-2017/26/M/ST4/00044, UMO-2017/27/B/ST4/00926; National Institute of General Medical Sciences, Grant/Award Numbers: R21GM127952, R35GM118078, RM1135136, T32GM132024; National Institutes of Health, Grant/Award Numbers: R01GM074255, R01GM078221, R01GM093123, R01GM109980, R01GM133840, R01GN123055, R01HL142301, R35GM124952, R35GM136409; National Natural Science Foundation of China, Grant/Award Number: 81603152; National Science Foundation, Grant/Award Numbers: AF1645512, CCF1943008, CMMI1825941, DBI1759277, DBI1759934, DBI1917263, DBI20036350, IIS1763246, MCB1925643; NWO, Grant/Award Number: TOP-PUNT 718.015.001; Wellcome Trust, Grant/Award Number: FC00100

Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives

The role of activated protein C in severe acute pancreatitis

Introduction: Acute pancreatitis is an inflammatory disease of the pancreas with significant morbidity and mortality. The aetiology of the disease is multiple, and its pathogenesis is multifactorial; however, inflammation and thrombosis seem to play a cardinal role. Up to now, no specific treatment for acute pancreatitis is available. Aim: The aim of this experimental study was to evaluate the efficacy and safety of activated protein C in animals with severe acute pancreatitis. Patients-Methods: In total, 30 rats were randomized in 3 groups. In Group A only surgical procedure was performed, in Group B sodium taurocholate was infused to provoke pancreatitis in addition to the surgery, while in Group C, on top of the previous, activated protein C was administrated. Routine laboratory testing was performed, while interleukin-6 was also measured. Finally, euthanasia was conducted 24 hours after surgery and histological analysis of the pancreas was performed. Results: The infusion of sodium taurocholate induced severe acute pancreatitis in Groups B and C. In Group B, acute pancreatitis was associated with significant increase of inflammatory markers, both rough markers (leukocytes, platelets, fibrinogen, CRP) and specific markers (interleukin-6) (p<0.05 for all markers). In parallel, a significant prothrombotic state was observed in Group B, as shown by shortening of prothrombin and modified prothrombin time (p<0.05). The administration of activated protein C in Group C attenuated the increase in inflammatory markers and reversed the prothrombotic tendency (p<0.05 between the two groups). Histology confirmed the laboratory findings, with severe acute pancreatitis in Group B, and milder alterations in Group C (p<0.05 between the two groups). The administration of activated protein C was safe in Group C, and no hemorrhagic events were observed. Conclusions: The administration of activated protein C in rats with severe acute pancreatitis exerts significant anti-inflammatory and anti-thrombotic effects, and seems to be safe.Εισαγωγή: Η οξεία παγκρεατίτιδα είναι μία φλεγμονώδης νόσος του παγκρέατος με σημαντική νοσηρότητα και θνητότητα. Η αιτιολογία της είναι πολλαπλή και η παθογένεια της πολυπαραγοντική, αλλά η φλεγμονή και η θρόμβωση φαίνεται ότι διαδραματίζουν κομβικό ρόλο. Σκοπός: Σκοπό της πειραματικής αυτής μελέτης αποτέλεσε η αξιολόγηση της αποτελεσματικότητας και της ασφάλειας της ενεργοποιημένης πρωτεΐνης C σε πειραματόζωα με βαριά οξεία παγκρεατίτιδα. Υλικό – Μέθοδοι: Χρησιμοποιήθηκαν 30 επίμυες που τυχαιοποιήθηκαν σε 3 ομάδες. Στην ομάδα Α έγινε χειρουργική επέμβαση μόνο, στην ομάδα Β έγινε η επέμβαση και έγινε έγχυση ταυροχολικού νατρίου για την πρόκληση παγκρεατίτιδας, ενώ στην ομάδα Γ επιπρόσθετα χορηγήθηκε ενεργοποιημένη πρωτεΐνη C. Έγινε βιοχημικός, αιματολογικός και πηκτικός έλεγχος, καθώς και προσδιορισμός της ιντερλευκίνης–6. Τέλος, 24 ώρες μετά την επέμβαση έγινε ευθανασία στα πειραματόζωα και παθολογοανατομική εξέταση του παγκρέατος. Αποτελέσματα: Η έγχυση ταυροχολικού νατρίου προκάλεσε βαριά οξεία παγκρεατίτιδα στις ομάδες Β και Γ. Η οξεία παγκρεατίτιδα στην ομάδα Β συνοδεύθηκε από αύξηση των δεικτών φλεγμονής, τόσο των αδρών (λευκά αιμοσφαίρια, αιμοπετάλια, ινωδογόνο, CRP), όσο και των εξειδικευμένων (ιντερλευκίνη –6) (p<0,05 για όλους τους δείκτες). Παράλληλα, παρατηρήθηκε προθρομβωτική διάθεση με σμίκρυνση του χρόνου προθρομβίνης και του τροποποιημένου χρόνου προθρομβίνης (p<0,05). Επιπρόσθετα, η χορήγηση ενεργοποιημένης πρωτεΐνης C στην ομάδα Γ είχε ως αποτέλεσμα τον μετριασμό της αύξησης των δεικτών φλεγμονής και την ανάσχεση της προθρομβωτικής διάθεσης (p<0,05, μεταξύ των δύο ομάδων). Η ιστοπαθολογική εξέταση του παγκρέατος επιβεβαίωσε τα εργαστηριακά ευρήματα, με εικόνα βαριάς οξείας παγκρεατίτιδας στην ομάδα Β και ηπιότερες αλλοιώσεις στην ομάδα Γ (p<0,05 μεταξύ των δύο ομάδων). Η χορήγηση της ενεργοποιημένης πρωτεΐνης C στην ομάδα Γ ήταν ασφαλής και δεν παρατηρήθηκαν αιμορραγικά επεισόδια. Συμπεράσματα: Η χορήγηση ενεργοποιημένης πρωτεΐνης C σε επίμυες με βαριά οξεία παγκρεατίτιδα εμφάνισε αντιφλεγμονώδεις και αντιθρομβωτικές επιδράσεις και φάνηκε ότι είναι ασφαλής

Approaches and Assessment of Drama Prosodic Tools in Live Performance

(Abstract to follow

Gastrointestinal stromal tumors (gist)

With the opportunity of five patients we treated in our department we discuss the diagnostic and therapeutic problems that can occur with the management of stromal tumors.Materials and methods: In the time period 2001-2005 we treated 5 patients with GIST, three females and two males, with median age 58,2 years. The patients presented with non-specific dull abdominal pain (2 patients), epigastric pain, gastric distention/dyspepsia (1 patient), and lower gastrointestinal hemorrhage/anaemia (2 patients). The imaging techniques that we used as an aid for the diagnosis were: computed tomography in all patients, barium radiography of the small intestine in one patient, scintigraphy of the abdomen with Technetium 99m-labeled RBCs in one patient, endoscopy of the upper GI tract in 2 patients and colonoscopy in 2 patients. The tumors were located in the small intestine (ileum) in three patients, the stomach in one patient and the mesocolon in one patient. We performed three enterectomies with end to end anastomosis, one subtotal gastrectomy and one removal of the transverse colon and mesocolon. Three of the tumors were mainly spindle cell type, one epithelioid cell type and one mixed spindle and epithelioid cell type. 4 of the patients were CD117 and CD34 positive and one patient negative for both andibodies. One patient deceased 16 days after the operation. Two patients with tumors of the small intestine are alive at the present time 5 and 4 years respectively but we have no records of postoperative follow up. One patient 3,5 years later has no indication of tumor recurrence of the small intestine on CT. The patient with the tumor of the stomach is the only patient that received Imatinib Mesylate and continues to be diseasefree after 9 months of treatment.Conclusion: Through the review of the literature we observe that the use of imatinib represents an effective, revolutionary, target therapy for GIST. Stromal tumors is a simple form of cancer with limited genetic abnormalities and mutations and it still remains to be seen if this type of therapeutic procedure can be used in more complex and common tumors, such as the cancer of the colon and others. Also, further clinical investigation must determine the ideal dose and duration of imatinib treatment and the combination with surgical treatment and other new target therapies

Work-Up and Outcome of Hepatic Resection for Peri-Hilar Cholangiocarcinoma (PH-CCA) without Staging Laparoscopy.

Background: This study reports the outcome of a work-up programme for resection of peri-hilar cholangiocarcinoma (PH-CCA) without the use of staging laparoscopy. Methods: This is a clinical case cohort series of patients undergoing surgical resection of PH-CCA without the use of staging laparoscopy in the work-up algorithm. During the 13 years from 1 January 2009 to 1 January 2022, 32 patients underwent laparotomy for planned surgical resection of PH-CCA. Data were collected on demographic profile, admission biochemistry, radiology, pre-operative intervention, operation and outcome, together with post-operative complications and disease-free and overall survival. Results: All patients underwent pre-operative contrast-enhanced CT. Twenty-four (75%) underwent pre-operative MR. Twenty-three (72%) underwent pre-operative biliary drainage. Twenty-nine patients (91%) had either type III or IV peri-hilar cholangiocarcinoma. One patient (3%) in this series underwent a non-resectional laparotomy. Twenty-nine (91%) had a final histopathological diagnosis of PH-CCA. One further patient had a final diagnosis of an intraductal papillary neoplasm of the biliary tree (IPNB) with high-grade dysplasia but no invasive cancer. Eleven patients (36%) received chemotherapy after surgery. The median (95% CI) time to recurrence was 14 (7-31) months. The median survival was 25 (18-upper limit not reached) months. Conclusion: This cohort of 32 patients undergoing attempted resection for PH-CCA without the use of staging laparoscopy in the work-up algorithm indicates that with careful attention to patient fitness and cross-sectional and interventional radiologic/endoscopic imaging, a very low non-therapeutic laparotomy rate of 3% can be achieved and sustained

Dealing with Pheochromocytoma during the First Trimester of Pregnancy

Purpose. Pheochromocytoma in association with pregnancy is a very rare, without specific symptoms, life-threatening condition, increasing both maternal and fetal mortality up to 50%. The present paper illustrates the case of a pregnant woman, diagnosed with pheochromocytoma, aiming to demonstrate and discuss the difficulties that arouse during the diagnosis and the problems concerning the treatment. Patient. A 34-year-old woman, in the 9th week of pregnancy, complained for headache, sweating, and a feeling of heavy weight on the right renal area. A tumor of 10 cm diameter at the site of the right adrenal was found. Twenty-four-hour urine catecholamine and VMA excretion levels were well raised. Results. Multidisciplinary approach treated the patient conservatively. Surgical resection of the tumor was performed after the 14th week of pregnancy at the completion of organogenesis. Neither postoperative complications occurred nor hypertension relapse was recorded. The fetus was delivered without complications at the 36th week. Conclusions. There are no consensus and guidelines for treating pheochromocytoma during pregnancy, especially when it is diagnosed in the first trimester. The week of pregnancy and a multidisciplinary approach will determine whether the pregnancy should be continued or not, as well as the time and the approach of surgical treatment

Work-Up and Outcome of Hepatic Resection for Peri-Hilar Cholangiocarcinoma (PH-CCA) without Staging Laparoscopy

Background: This study reports the outcome of a work-up programme for resection of peri-hilar cholangiocarcinoma (PH-CCA) without the use of staging laparoscopy. Methods: This is a clinical case cohort series of patients undergoing surgical resection of PH-CCA without the use of staging laparoscopy in the work-up algorithm. During the 13 years from 1 January 2009 to 1 January 2022, 32 patients underwent laparotomy for planned surgical resection of PH-CCA. Data were collected on demographic profile, admission biochemistry, radiology, pre-operative intervention, operation and outcome, together with post-operative complications and disease-free and overall survival. Results: All patients underwent pre-operative contrast-enhanced CT. Twenty-four (75%) underwent pre-operative MR. Twenty-three (72%) underwent pre-operative biliary drainage. Twenty-nine patients (91%) had either type III or IV peri-hilar cholangiocarcinoma. One patient (3%) in this series underwent a non-resectional laparotomy. Twenty-nine (91%) had a final histopathological diagnosis of PH-CCA. One further patient had a final diagnosis of an intraductal papillary neoplasm of the biliary tree (IPNB) with high-grade dysplasia but no invasive cancer. Eleven patients (36%) received chemotherapy after surgery. The median (95% CI) time to recurrence was 14 (7&ndash;31) months. The median survival was 25 (18-upper limit not reached) months. Conclusion: This cohort of 32 patients undergoing attempted resection for PH-CCA without the use of staging laparoscopy in the work-up algorithm indicates that with careful attention to patient fitness and cross-sectional and interventional radiologic/endoscopic imaging, a very low non-therapeutic laparotomy rate of 3% can be achieved and sustained