Pancreatic ductal adenocarcinoma and distal cholangiocarcinoma: a proposal of preoperative diagnostic score for differential diagnosis.

PURPOSE: The differential diagnosis between primary adenocarcinoma of the pancreas head and distal cholangiocarcinoma remains a clinical challenge. Recent studies have shown important differences in terms of survival between these tumors. Therefore, different treatments should be considered, but the preoperative histological diagnosis is still difficult. Aim of this study is to create a preoperative diagnostic score for differential diagnosis between primary pancreatic adenocarcinoma and primary distal cholangiocarcinoma. METHODS: One hundred eighty consecutive patients who underwent pancreaticoduodenectomy at Sapienza University of Rome from January 2010 to December 2019 were retrospectively analyzed. Inclusion criteria were pancreatic or biliary histologic origin obtained by definitive postoperative histological examination. Exclusion criteria were diagnosis of ampullary carcinoma, non-ampullary duodenal adenocarcinoma, pancreatic metastasis, and benign disease. One hundred one patients were considered eligible for the retrospective study. Preoperative biological, clinical, and radiological parameters were considered. RESULTS: CRP > 10 mg/dL (p = 0.001), modified Glasgow Prognostic Score 2 (p = 0.002), albumin < 35 g/L (p = 0.05), CA 19-9 > 230 U/mL (p = 0.001), and Wirsung diameter > 3 mm (p < 0.001) were significant at univariate logistic analysis. Multivariate logistic analysis has shown that parameters independently associated with primary pancreatic adenocarcinoma were CRP > 10 mg/dL (p = 0.012), CA 19-9 > 230 U/mL (p = 0.043), and diameter of the Wirsung > 3 mm (p = 0.005). Through these parameters, a diagnostic score has been developed to predict a primary pancreatic adenocarcinoma when > 1 and a primary distal cholangiocarcinoma when < 1. CONCLUSION: This feasible and low-cost diagnostic score could have a potential impact to differentiate pancreatic cancer histologic origin and to improve target therapeutic strategy.

Cinnamic acid derivatives from welsh onion (Allium fistulosum) and their antibacterial and cytotoxic activities.

INTRODUCTION: Cinnamic acids are a class of compounds based on phenyl propanoid backbone (C6-C3) isolated from plants and microorganisms, exhibiting interesting biological activities. OBJECTIVE: To characterise cinnamic acids through the phytochemical study of welsh onion, Allium fistulosum, and to evaluate their antibacterial and cytotoxic properties. MATERIAL AND METHODS: The phytochemical study of A. fistulosum was performed through chromatographic techniques, including reversed phase medium-pressure liquid chromatography (MPLC) and high-pressure liquid chromatography (HPLC). Preliminary analysis of crude chromatographic fractions from the organic extracts was carried out by proton nuclear magnetic resonance (1 H-NMR) in order to prioritise the study of those having phenyl propanoid skeleton. The structural identification of the isolated compounds was performed through analysis of spectroscopic data, mainly one-dimensional (1D) and two-dimensional (2D) NMR. The antibacterial activity was assessed against gram negative (Escherichia coli) and gram positive (Staphylococcus aureus) bacteria while the cytotoxic property was evaluated on breast cancer cell line (MCF-7). RESULTS: The 1 H-NMR study of crude fractions and application of a straightforward method to purify the phenyl propanoid compounds by reversed phase MPLC and HPLC, allowed the effortless isolation of several cinnamic acids, including two new rare phenolic imidates (1 and 2). The use of an entirely NMR approach for structural elucidation of the isolated metabolites allowed the isolated material to be kept for further pharmacological tests. CONCLUSION: These results corroborate the importance of the use of 1D and 2D NMR to the identification of new phenyl propanoids, potential lead compounds against bacteria and cancer cells.

Furostanol Saponins from the Bulbs of Welsh Onion, Allium fistulosum L.

An extensive phytochemical analysis of the polar extracts from bulbs of Welsh onion Allium fistulosum L. led to the isolation of nine saponins, four of them, named fistulosaponins G (1a/1b), H (2), I (3a/3b), and J (4), have never been reported previously. Fistulosaponins G and I were isolated as a couple of isomers in equilibrium. On the basis of 2D NMR and mass spectrometry data, the structure of the novel compounds were elucidated as (25R)-26-[(ß-D-glucopyranosyl)oxy]-3ß,22ß-dihydroxyfurost-5-en-1ß-yl O-α-L-rhamnopyranosyl-(1 → 4)-O-α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucopyranoside (1a) with its 22α epimer (1b), (25R)-26-[(ß-D-glucopyranosyl)oxy]-3ß-hydroxyfurost-5,20-dien-1ß-yl O-α-L-rhamnopyranosyl-(1 → 4)-O-α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucopyranoside (2), (25R)-26-[(ß-D-glucopyranosyl)oxy]-3ß,22ß-dihydroxyfurost-5-en-1ß-yl O-α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucopyranoside (3a) with its 22α epimer (3b), and (25R)-26-[(ß-D-glucopyranosyl)oxy]-3ß-hydroxyfurost-5,20-dien-1ß-yl O-α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucopyranoside (4). This is the first report of furostanol saponins in A. fistulosum bulbs. In addition, data on the antibacterial tests of the isolated saponins against Escherichia coli and Enterococcus faecalis are reported.

Vavilosides A1/A2-B1/B2, new furostane glycosides from the bulbs of Allium vavilovii with cytotoxic activity.

A phytochemical analysis of the bulbs of Allium vavilovii M. Pop. & Vved. was attained for the first time extensively, affording to the isolation of four new furostanol saponins, named vavilosides A1/A2-B1/B2 (1a/b-2a/2b), as two couple of isomers in equilibrium, together with ascalonicoside A1/A2 (3a/3b) and 22-O-methyl ascalonicoside A1/A2 (4a/4b), previously isolated from shallot, Allium ascalonicum. High concentrations of kaempferol, kaempferide, and kaempferol 4(I)-glucoside were also isolated. The chemical structures of the new compounds, established through a combination of extensive nuclear magnetic resonance, mass spectrometry and chemical analyses, were identified as (25R)-furost-5(6)-en-1ß,3ß,22α,26-tetraol 1-O-α-L-rhamnopyranosyl-(1→2)-O-ß-D-galactopyranosyl 26-O-α-L-rhamnopyranoside (vaviloside A1), (25R)-furost-5(6)-en-1ß,3ß,22ß,26-tetraol 1-O-α-L-rhamnopyranosyl-(1→2)-O-ß-D-galactopyranosyl 26-O-α-L-rhamnopyranoside (vaviloside A2), (25R)-furost-5(6)-en-1ß,3ß,22α,26-tetraol 1-O-α-L-rhamnopyranosyl-(1→2)-O-ß-D-xylopyranosyl 26-O-α-L-rhamnopyranoside (vaviloside B1), (25R)-furost-5(6)-en-1ß,3ß,22ß,26-tetraol 1-O-α-L-rhamnopyranosyl-(1→2)-O-ß-d-xylopyranosyl 26-O-α-L-rhamnopyranoside (vaviloside B2). The isolated saponins showed cytotoxic activity on J-774, murine monocyte/macrophage, and WEHI-164, murine fibrosarcoma, cell lines with the following rank: vaviloside B1/B2>ascalonicoside A1/A2>vaviloside A1/A2.

How to reduce the colorectal anastomotic leakage? The MIRACLe protocol experience in a cohort in a single high-volume centre.

This article reports the results of a novel perioperative treatment implementing the gut microbiota to prevent anastomotic fistula and leakage (AL) in patients undergoing laparoscopic colorectal resections for cancer and represents the continuation of our pilot study on 60 cases. A series of 131 patients underwent elective colorectal surgery at the S. Eugenio Hospital (Rome-Italy) between December 1, 2020, and November 30, 2022, and received a perioperative preparation following the Microbiota Implementation to Reduce Anastomotic Colorectal Leaks (MIRACLe) protocol comprising oral antibiotics, mechanical bowel preparation and perioperative probiotics. The results obtained in the MIRACLe group (MG) were compared to those registered in a Control group (CG) of 500 patients operated on between March 2015 and November 30, 2020, who received a standard ERAS protocol. Propensity score-matching (PSM) analysis was performed to overcome patients' selection bias. Patients were categorised according to perioperative preparation (MIRACLe protocol vs standard ERAS protocol) into two groups: 118 patients were in post-matched MIRACLe group (pmMG) and 356 were in post-matched Control group (pmCG). In the pmMG, only 2 anastomotic leaks were registered, and the incidence of AL was just 1.7% vs. 6.5% in the pmCG (p = 0.044). The incidence of surgical site infections (1.7% vs. 3.1%; p = 0.536), reoperations (0.8% vs. 4.2%; p = 0.136) and postoperative mortality (0% vs. 2.0%; p = 0.200) was lower in pmMG. Additionally, the postoperative outcomes were better: the times to first flatus, to first stool and to oral feeding were shorter (1 vs. 2, 2 vs. 3 and 2 vs. 3 days, respectively; p < 0.001). The postoperative recovery was faster, with a shorter time to discharge (5 vs. 6 days; p < 0.001). The MIRACLe protocol was confirmed to be safe and significantly able to reduce anastomotic leaks in patients receiving elective laparoscopic colorectal surgery for cancer.

Colorectal Cancer: Current Updates and Future Perspectives.

Colorectal cancer is a frequent neoplasm in western countries, mainly due to dietary and behavioral factors. Its incidence is growing in developing countries for the westernization of foods and lifestyles. An increased incidence rate is observed in patients under 45 years of age. In recent years, the mortality for CRC is decreased, but this trend is slowing. The mortality rate is reducing in those countries where prevention and treatments have been implemented. The survival is increased to over 65%. This trend reflects earlier detection of CRC through routine clinical examinations and screening, more accurate staging through advances in imaging, improvements in surgical techniques, and advances in chemotherapy and radiation. The most important predictor of survival is the stage at diagnosis. The screening programs are able to reduce incidence and mortality rates of CRC. The aim of this paper is to provide a comprehensive overview of incidence, mortality, and survival rate for CRC.

Lymphadenopathies before and during the Pandemic COVID-19: Increasing Incidence of Metastases from Solid Tumors.

Since December 2019, the world has experienced a pandemic caused by SARS-CoV-2, a virus which spread throughout the world. Anti-COVID19 measures were applied to limit the spread of the infection, affecting normal clinical practice. In 2020, studies on the possible impact of the pandemic considering the screening programs for early diagnosis of cancer were conducted, resulting in a prediction of delayed diagnosis of cancer. We performed a retrospective monocentric study on patients who present with the onset of lymphadenomegalies evaluated at our Hematological Department from February 2019 to October 2021 and undergoing excisional lymph-node biopsy. Three periods were considered: pre-pandemic, first pandemic period and second pandemic period (Group A, B and C). We included 258 patients who underwent a surgical biopsy and received a histological diagnosis. Hematological evaluation of outpatients sent by the general practitioner and surgical biopsies did not decrease among the three groups, despite limitations placed during this pandemic as well as new diagnoses of hematological malignancies. However, the diagnosis of metastatic cancer significantly increased from 2019 (7.8%) to 2021 (22.1%) (p = 0.042). Our data supports the hypothesis that the pandemic affected the national screening programs of early cancer detection.

A Prognostic Score for Predicting Survival in Patients With Pancreatic Head Adenocarcinoma and Distal Cholangiocarcinoma.

BACKGROUND/AIM: Survival of patients with pancreatic cancer remains poor despite improvements in therapeutic strategies. This study aims to create a novel preoperative score to predict prognosis in patients with tumors of the pancreaticobiliary head. PATIENTS AND METHODS: Data on 190 patients who underwent to pancreaticoduodenectomy at Sapienza University of Rome from January 2010 to December 2018 were retrospectively analyzed. After exclusion criteria, 101 patients were considered eligible for retrospective study. Preoperative biological, clinical and radiological parameters were considered. RESULTS: Pancreatic ductal adenocarcinoma [hazard ratio (HR)=1.995, 95% confidence intervaI (CI)=1.1-3.3; p=0.01], carbohydrate antigen 19.9 (CA 19.9) >230 U/ml (HR=2.414, 95% CI=2.4-1.5, p<0.0001) and Wirsung duct diameter >3 mm (HR=1.592, 95% CI=1.5-0.9; p=0.08) were the only parameters associated with poor prognosis. Through these parameters, a prognostic score (PHT score) was developed which predicted worst survival when exceeding 2 and better survival when ≤2. CONCLUSION: The PHT score may have a potential impact on predicting overall survival and consequently modulate the timing and type of treatment (up-front surgery vs. neoadjuvant therapy) patients are offered.

3-Keto umbilicagenin A and B, new sapogenins from Allium umbilicatum Boiss.

Two sapogenins, named 3-keto umbilicagenin A and B (1 and 2), possessing a novel chemical structure with a 3-keto group on the spirostane skeleton, have been isolated from Allium umbilicatum Boiss. Their chemical structure has been established through a combination of extensive spectroscopic analysis, mainly nuclear magnetic resonance and mass spectrometry, and chemical methods as (25R)-3-keto-spirostan-2α,5α,6ß-triol (1) and (25R)-3-keto-spirostan-2α,5α-diol (2). The isolated compounds were tested for cytotoxic activity on J-774, murine monocyte/macrophage, and WEHI-164, murine fibrosarcoma cell lines.

Filiferol, a chalconoid analogue from Washingtonia filifera possibly involved in the defence against the Red Palm Weevil Rhynchophorus ferrugineus Olivier.

A chalconoid analogue, 1,3,5-benzentriol 2-[(2S,3R)-3-(3,4-dihydroxylphenyl)-2,3-dihydroxylpropyl], named filiferol (1), has been isolated and purified for the first time from the leaf basal tissues of the palm species Washingtonia filifera. The chemical structure of the isolated compound has been elucidated unambiguously by spectroscopic and chemical methods. Filiferol has been based on a flavonol structure with the reduction of the common flavonoid keto group to give an unprecedented methylene carbon on the three carbon chain. An analogous compound with S stereochemistry at C3 has been obtained as synthetic intermediate for developing an enantioselective synthesis of (2R,3S)-(+)-catechin. Even though 1 proved to be deprived of antifungal properties, it displays a very effective larvicidal activity against Red Palm Weevil, Rhynchophorus ferrugineus, an important pest affecting cultivated and ornamental palms. 1 has been isolated from leaf tissues of W. filifera, a species resistant to this pest, but this molecule seems instead undetectable in tissues of other palm species susceptible to the parasite. The presence of 1 could therefore account for W. filifera natural resistance to the attacks of the Red Palm Weevil (R. ferrugineus).

Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation.

BACKGROUND: Celiac Disease (CD) is both a frequent disease (1:100) and an interesting model of a disease induced by food. It consists in an immunogenic reaction to wheat gluten and glutenins that has been found to arise in a specific genetic background; however, this reaction is still only partially understood. Activation of innate immunity by gliadin peptides is an important component of the early events of the disease. In particular the so-called "toxic" A-gliadin peptide P31-43 induces several pleiotropic effects including Epidermal Growth Factor Receptor (EGFR)-dependent actin remodelling and proliferation in cultured cell lines and in enterocytes from CD patients. These effects are mediated by delayed EGFR degradation and prolonged EGFR activation in endocytic vesicles. In the present study we investigated the effects of gliadin peptides on the trafficking and maturation of endocytic vesicles. METHODS/PRINCIPAL FINDINGS: Both P31-43 and the control P57-68 peptide labelled with fluorochromes were found to enter CaCo-2 cells and interact with the endocytic compartment in pulse and chase, time-lapse, experiments. P31-43 was localised to vesicles carrying early endocytic markers at time points when P57-68-carrying vesicles mature into late endosomes. In time-lapse experiments the trafficking of P31-43-labelled vesicles was delayed, regardless of the cargo they were carrying. Furthermore in celiac enterocytes, from cultured duodenal biopsies, P31-43 trafficking is delayed in early endocytic vesicles. A sequence similarity search revealed that P31-43 is strikingly similar to Hrs, a key molecule regulating endocytic maturation. A-gliadin peptide P31-43 interfered with Hrs correct localisation to early endosomes as revealed by western blot and immunofluorescence microscopy. CONCLUSIONS: P31-43 and P57-68 enter cells by endocytosis. Only P31-43 localises at the endocytic membranes and delays vesicle trafficking by interfering with Hrs-mediated maturation to late endosomes in cells and intestinal biopsies. Consequently, in P31-43-treated cells, Receptor Tyrosine Kinase (RTK) activation is extended. This finding may explain the role played by gliadin peptides in inducing proliferation and other effects in enterocytes from CD biopsies.