Intraductal oncocytic papillary neoplasm (IOPN): two case reports and review of the literature

Background: Intraductal oncocytic papillary neoplasms (IOPNs) place at the oncocytic extreme of the intraductal pancreatic neoplasm spectrum and display typical morphological features. Their identification in 1996 by Adsay et al. has been followed by a growing number of cases, paving the way for a deeper understanding of this underestimated entity. Contrarily to intraductal papillary mucinous neoplasms (IPMNs), most IOPNs run an indolent course and surgery is usually curative. Pancreatic IOPNs tend to develop from the main pancreatic duct (MPD) and their diagnosis is either incidental or subsequent to mass-related symptoms. Up to 30% of cases show concomitant areas of minimal stromal invasion and loco-regional or systemic spread are confined to a minority of cases. Biological hallmarks of IOPNs are being identified, including recurrent kinase gene rearrangements. Morphological and biological traits of IOPNs seem to overlap with those of other malignancies. A deeper understanding of these entities is needed in order to shed light upon the nature of pancreato-biliary oncocytic neoplasms. This case report describes two patients with a diagnosis of IOPN-one of them accounting for the largest IOPN ever described-and provides a brief review of recent discoveries on the subject. Case description: We describe two cases of IOPN occurring in adult male patients, respectively in their 60s and 70s. Both patients had unremarkable clinical history. In case 1 the diagnosis was coincidental to a right renal colic; case 2 complained a right lumbar pain radiating to the homolateral groin. In both cases imaging analyses revealed a voluminous pancreatic mass, posing the indication to laparoscopic pancreatectomy. Gross and histological features were consistent with the diagnosis of IOPN. Surgical margin were free from disease and the patient did not undergo further treatment. After a 10- and 7-month follow-up respectively, patients did not experience relapse. Conclusions: Recent immunohistochemical (IHC) and molecular data reveal unique characteristics of IOPNs, highlighting the substantial differences from IPMNs. Further research is needed in order to identify novel prognostic and predictive markers applicable to oncocytic neoplasms of the pancreato-biliary tract

Fibrotic and Vascular Remodelling of Colonic Wall in Patients with Active Ulcerative Colitis

open16noIntestinal fibrosis is a complication of inflammatory bowel disease [IBD]. Although fibrostenosis is a rare event in ulcerative colitis [UC], there is evidence that a fibrotic rearrangement of the colon occurs in the later stages. This is a retrospective study aimed at examining the histopathological features of the colonic wall in both short-lasting [SL] and long-lasting [LL] UC. Surgical samples of left colon from non-stenotic SL [a parts per thousand currency sign 3 years, n = 9] and LL [a parts per thousand yen 10 years, n = 10] UC patients with active disease were compared with control colonic tissues from cancer patients without UC [n = 12] to assess: collagen and elastic fibres by histochemistry; vascular networks [CD31/CD105/nestin] by immunofluorescence; parameters of fibrosis [types I and III collagen, fibronectin, RhoA, alpha-smooth muscle actin [alpha-SMA], desmin, vimentin], and proliferation [proliferating nuclear antigen [PCNA]] by western blot and/or immunolabelling. Colonic tissue from both SL-UC and LL-UC showed tunica muscularis thickening and transmural activated neovessels [displaying both proliferating CD105-positive endothelial cells and activated nestin-positive pericytes], as compared with controls. In LL-UC, the increased collagen deposition was associated with an up-regulation of tissue fibrotic markers [collagen I and III, fibronectin, vimentin, RhoA], an enhancement of proliferation [PCNA] and, along with a loss of elastic fibres, a rearrangement of the tunica muscularis towards a fibrotic phenotype. A significant transmural fibrotic thickening occurs in colonic tissue from LL-UC, together with a cellular fibrotic switch in the tunica muscularis. A full-thickness angiogenesis is also evident in both SL- and LL-UC with active disease, as compared with controls.openIppolito, Chiara; Colucci, Rocchina; Segnani, Cristina; Errede, Mariella; Girolamo, Francesco; Virgintino, Daniela; Dolfi, Amelio; Tirotta, Erika; Buccianti, Piero; Di Candio, Giulio; Campani, Daniela; Castagna, Maura; Bassotti, Gabrio; Villanacci, Vincenzo; Blandizzi, Corrado; Bernardini, NunziaIppolito, Chiara; Colucci, ROCCHINA LUCIA; Segnani, Cristina; Errede, Mariella; Girolamo, Francesco; Virgintino, Daniela; Dolfi, Amelio; Tirotta, Erika; Buccianti, Piero; Di Candio, Giulio; Campani, Daniela; Castagna, Maura; Bassotti, Gabrio; Villanacci, Vincenzo; Blandizzi, Corrado; Bernardini, Nunzi

Lymphoepithelioma-like hepatocellular carcinoma: Case report and review of the literature

Lymphoepithelioma-like hepatocellular carcinoma (LELHCC) is a rare form of undifferentiated carcinoma of the liver characterized by the presence of an abundant lymphoid infiltrate. Here, a case of LEL-HCC is described. An 81-year-old woman with a chronic hepatitis C infection was referred to the general surgery department of our hospital in August 2013 with a diagnosis of HCC. A past ultrasound examination had revealed a 60 mm-diameter nodular lesion in the third segment of the liver. After a needle biopsy, the lesion was diagnosed as HCC. The patient underwent surgery with a liver segmentectomy. Two additional nodes on the gastric wall were detected during the surgical operation. The histology of the removed specimen showed a poorly differentiated HCC with significant lymphoid stroma. Immunohistochemical studies revealed that the epithelial component was reactive for CK CAM5.2, CK8, CK18, CEA (polyclonal) and was focally positive for hepar-1 and that the lymphoid infiltrate was positive for CD3, CD4 and CD8. The tumor cells were negative for Epstein-Barr virus. The gastric nodes were ultimately determined to be two small gastrointestinal stromal tumors (GISTs). The synchronous occurrence of HCC and GIST is another very uncommon finding rarely described in the literature. Here, we report the clinicopathological features of our case, along with a review of the few cases present in the literature

Membranous Nephropathy Associated with Eosinophilic Gastroenteritis: First Report

Membranous nephropathy represents the most common cause of nephrotic syndrome in adult patients. In 85% of cases the disease is classified as idiopathic membranous nephropathy, and in the remainder 15 % as secondary membranous nephropathy (systemic lupus erythematosus, infections, drugs, tumors, inorganics salts). Treatment of secondary membranous nephropathy is guided by therapy of the original disease, or by elimination of the responsible cause. Eosinophilic gastroenteritis is a rare uncommon disease of unknown origin affecting the gastrointestinal apparatus and is characterized by diffuse eosinophilic infiltration of the gastro-enteric wall. Any segment of gastrointestinal tract can be interested, but the stomach results to be the most commonly affected organ, followed by the small intestine and the colon. The diagnosis is based on the presence of gastrointestinal symptoms, documented eosinophilic gut infiltration and the exclusion of intestinal parasites or extraintestinal disease. To date there are no randomized prospective therapeutic trials. The mainstay of treatment is represented by use of corticosteroids (with 90% of remission rate in some reports). We describe for the first time the case of a 43-year-old man affected by eosinophilic gastroenteritis who developed a nephrotic syndrome due to membranous nephropathy after he voluntarily stopped the steroidal oral therapy. Reintroduction of corticosteroid treatment led to the complete remission of the nephrotic syndrome within 6 months treatment

Magnetic carbon nanotubes: a new tool for shepherding mesenchymal stem cells by magnetic fields

We investigated the interaction between magnetic carbon nanotubes (CNTs) and mesenchymal stem cells (MSCs), and their ability to guide these intravenously injected cells in living rats by using an external magnetic field. MATERIALS & METHODS: Multiwalled CNTs were used to treat MSCs derived from rat bone marrow. Cytotoxicity induced by nanotubes was studied using the WST-1 proliferation and Hoechest 33258 apoptosis assays. The effects of nanotubes on MSCs were evaluated by monitoring the effects on cellular growth rates, immunophenotyping and differentiation, and on the arrangement of cytoskeletal actin. MSCs loaded with nanotubes were injected in vivo in the portal vein of rats driving their localization in the liver by magnetic field. An histological analysis was performed on the liver, lungs and kidneys of all animals. RESULTS: CNTs did not affect cell viability and their ability to differentiate in osteocytes and adipocytes. Both the CNTs and the magnetic field did not alter the cell growth rate, phenotype and cytoskeletal conformation. CNTs, when exposed to magnetic fields, are able to shepherd MSCs towards the magnetic source in vitro. Moreover, the application of a magnetic field alters the biodistribution of CNT-labelled MSCs after intravenous injection into rats, increasing the accumulation of cells into the target organ (liver). CONCLUSION: Multiwalled CNTs hold the potential for use as nanodevices to improve therapeutic protocols for transplantation and homing of stem cells in vivo. This could pave the way for the development of new strategies for the manipulation/guidance of MSCs in regenerative medicine and cell transplantation

The Titanium Surface Modulates the Expression of Beta-Catenin and DLX5 Genes in Pancreatic Ductal Carcinoma in Vitro. Can the Metallic Stent Increase PDAC Aggressiveness?

Context Adenoductal pancreas (PDAC) is a fatal cancer. Its aggressiveness is associated in part with the EMT process of metastasis. Two genes specifically involved in these phenomena are b-catenin and DLX5. While the first gene has been widely studied also in pancreatic cancer, few data are associated with DLX5. However, its over-expression has been recently associated with the formation of metastases in breast cancer in vivo. An exogenous factor involved in the modulation of the expression of these genes seems to be titanium. This compound is usually employed for the pallia action of patients with PDAC, to reduce choledochal stenosis due to compression. Objective The purpose of this study was to assess whether titanium is able to modulate the expression of these two genes in vitro. Methods We used a primary cell culture of PADC (PP78). The cells were seeded and cultivated in contact with two different titanium surfaces for 10 days. After this period the total mRNA was extracted and the quantification of β-catenin and DLX5 genes was performed by RT-PCR according to the ΔΔCt analysis. Then cells were stained using the immunofluorescence technique (IF) to quantify the b-catenin protein expression .using a computerized high-resolution acquisition system (D-Sight, Menarini, Florence, Italy) The cells were scored evaluating the cytoplasmic positivity as follows (0 absent, 1 low, 2 middle, 3 strong). The experiment was carried out in triplicate and untreated cells (without titanium contact) were used as control. Results Quantitative analyses showed that both titanium surfaces positively affected beta-catenin (mean 2.8 fold) and DLX5 (2.0 fold) mRNA expressions with respect to the controls (P<0.0007). Both titanium surfaces also increased the protein score 3 values of β-catenin in treated cells with respect to their controls (P=0.0158). Conclusion Our data showed that several titanium surfaces positively modulated the expression of two genes associated with the increase of the aggressiveness of PDAC in vitro. Clinical studies are needed to find out which type of stent can be used in the surgical operation with palliative intent

Robot-assisted pancreaticoduodenectomy with vascular resection: technical details and results from a high-volume center

Background: Pancreaticoduodenectomy with vein resection (PD-VR) is widely accepted as a standard procedure to achieve a higher rate of R0 resections in borderline resectable pancreatic tumors. Thanks to the availability of newer technologies, such as the da Vinci Surgical System, several high-volume centers are reporting small series of minimally invasive PD-VR. Methods: A retrospective review of a prospectively maintained database was performed to identify patients who underwent robot-assisted PD-VR (RAPD-VR) between May 2011 and December 2019. The following factors were specifically analyzed: intraoperative results, post-operative complications, mortality at 90 days, patency of vascular reconstructions, overall survival (OS) and disease-free survival (DFS). Results: During the study period 184 patients underwent RAPD, including 22 who received a RAPDVR (12.0%). The superior mesenteric vein was resected in 9 patients (40.9%), the portal vein in 3 patients (13.6%) and the spleno-mesenteric junction in 10 patients (45.5%). Based on the classification provided by the International Study Group on Pancreatic Surgery these procedures were classified as follows: 1 type I (4.5%), 3 type II (13.6%), 10 type III (45.5%) and 8 type IV (36.4%). In no patient the splenic vein was ligated and left behind. The splenic vein was always reimplanted either on the porto-mesenteric axis or in the inferior vena cava. All but one procedure, were completed under robotic assistance (conversion rate 1/22; 4.5%) after a mean operative time of 610.0±83.5 minutes. Median estimated blood loss was 899.7 mL (719.4–1,430.2 mL), with 2 patients (9.1%) receiving intraoperative blood transfusions. Sixteen patients developed post-operative complications (72.7%), graded ≥III (according to Clavien-Dindo) in 5 patients (22.7%). Two patients died within 90 days, accounting for a postoperative mortality of 9.1%. Interestingly, post-operative pancreatic fistula (grade B) occurred in only 1 patient (4.5%). Repeat surgery was required in 4 patients (18.2%) and hospital readmission in 1 patient (4.5%). At the longest available follow-up, vein reconstruction was patent in 19 patients (86.4%). Eighteen patients had a final diagnosis of pancreatic ductal adenocarcinoma (81.8%). After circumferential study of resection margins, microscopic tumor residual ≤1 mm was found in 11 patients (50.0%). The mean number of examined lymph nodes was 42.2 (±16.3), and vascular infiltration was confirmed in 13 patients (59.1%). Median OS was 39.7 (27.5–not available) and DFS 32.9 (11.5–45.8). Tumor recurrence was identified in 6 patients (27.3%). One patient (4.5%) developed isolated local recurrence. Conclusions: We have shown the feasibility of RAPD-VR. The results reported herein need to be confirmed in larger series and their generalizability remains to be established

Salmonella typhimurium and Escherichia coli dissimilarity: closely related bacteria with distinct metabolic profiles

Live attenuated strains of Salmonella typhimurium have been extensively investigated as vaccines for a number of infectious diseases. However, there is still little information available concerning aspects of their metabolism. S. typhimurium and Escherichia coli show a high degree of similarity in terms of their genome contents and metabolic networks. However, this work presents experimental evidence showing that significant differences exist in their abilities to direct carbon fluxes to biomass and energy production. It is important to study the metabolism of Salmonella in order to elucidate the formation of acetate and other metabolites involved in optimizing the production of biomass, essential for the development of recombinant vaccines. The metabolism of Salmonella under aerobic conditions was assessed using continuous cultures performed at dilution rates ranging from 0.1 to 0.67 h1, with glucose as main substrate. Acetate assimilation and glucose metabolism under anaerobic conditions were also investigated using batch cultures. Chemostat cultivations showed deviation of carbon towards acetate formation, starting at dilution rates above 0.1 h1. This differed from previous findings for E. coli, where acetate accumulation was only detected at dilution rates exceeding 0.4 h1, and was due to the lower rate of acetate assimilation by S. typhimurium under aerobic conditions. Under anaerobic conditions, both microorganisms mainly produced ethanol, acetate, and formate. A genome-scale metabolic model, reconstructed for Salmonella based on an E. coli model, provided a poor description of the mixed fermentation pattern observed during Salmonella cultures, reinforcing the different patterns of carbon utilization exhibited by these closely related bacteria. This article is protected by copyright. All rights reserved.Special thanks to Amadeus Azevedo for the HPLC analyses and technical assistance. The authors acknowledge the national funding received from CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil), the international cooperation project CAPES-FCT (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/Brazil-Fundacao para a Ciencia e a Tecnologia/Portugal-Process 315/11), CAPES (Atracao de Jovens Talentos-Process 064922/2014-01) and to Fundacao para a Ciencia e Tecnologia the strategic funding of UID/BIO/04469/2013 unit

An Unexpected Case of Opisthorchis felineus Infection Revealed during Liver Transplantation

A man with hepatitis B infection was admitted to Pisa University Hospital for hepatological evaluation, which revealed multiple cystic lesions and suggested a cirrhotic evolution. Treatment with Entecavir 0.5 mg/day was started, resulting in rapid viral load suppression and alanine aminotransferase normalization. After 10 years, imaging documented a single nodule of hepatocellular carcinoma (HCC), and a robot-assisted nodule resection was performed. One year later, HCC recurrence prompted orthotopic liver transplantation, during which the patient died because of the sudden rupture of the donor's organ and rapid multiorgan deterioration before retransplantation. During post-mortem liver examination, adult worms were evidenced within large biliary ducts, suggesting infection with Opisthorchis or Clonorchis spp. flukes. Sequencing of the ITS2 locus, following PCR amplification of DNA extracted from liver tissue, revealed 100% identity with the reference sequence of O. felineus. Infection of the patient with O. felineus was confirmed by the presence of specific IgG detected by ELISA in the patient's sera. Two major alkaline phosphatase serum levels peaks observed during the first two years of antiviral therapy support the hypothesis that O. felineus infection worsened liver function. This case report highlights the importance of a very careful screening of parasitic infections in solid organ transplantation candidates

Immunohistochemical Analysis of Myenteric Ganglia and Interstitial Cells of Cajal in Ulcerative Colitis

Ulcerative colitis (UC) is an inflammatory bowel disease with alterations of colonic motility, which influence clinical symptoms. Although morpho-functional abnormalities in the enteric nervous system have been suggested, in UC patients scarce attention has been paid to possible changes in the cells that control colonic motility, including myenteric neurons, glial cells, and interstitial cells of Cajal (ICC). This study evaluated the neural-glial components of myenteric ganglia and ICC in the colonic neuromuscular compartment of UC patients by quantitative immunohistochemical analysis. Full-thickness archival samples of the left colon were collected from 10 patients with UC (5 M, 5 F; age range, 45-62 years) who underwent elective bowel resection. The colonic neuromuscular compartment was evaluated immunohistochemically in paraffin cross-sections. The distribution and number of neurons, glial cells and ICC were assessed by anti-HuC/D, -S100β and -c-Kit antibodies, respectively. Data were compared with findings on archival samples of normal left colon from 10 sex- and age-matched control patients, who underwent surgery for uncomplicated colon cancer. Compared to controls, patients with UC showed: (a) reduced density of myenteric HuC/D-positive neurons and S100β-positive glial cells, with a loss over 61% and 38%, respectively, and increased glial cell/neuron ratio; (b) ICC decrease in the whole neuromuscular compartment. The quantitative variations of myenteric neuro-glial cells and ICC indicate considerable alterations of the colonic neuromuscular compartment in the setting of mucosal inflammation associated with UC, and provide a morphological basis for better understanding the motor abnormalities often observed in UC patients