Intraductal papillary neoplasm of the bile duct – A comprehensive review

BackgroundIntraductal papillary neoplasm of the bile ducts is a rare tumor type. Management decisions are currently based upon a small case series. The authors have large own experience with IPNB.ObjectiveThe review aims at reporting on clinicopathological features of IPNB in order to provide guidance for management.MethodsWe searched PubMed, Medline, Microsoft Academic and Embase databases to identify studies of relevance. The analysis of own experience was also included.ResultsWe analyzed 59 retrospective series and 25 cases from authors’ clinical experience. The main sign was jaundice and cholangitis, 33% and 48%, respectively. CT’s were performed in 63–76% and MR in 40–56%. Intraductal mass was found in 31–32% and duct dilatation in 27–30%. Endoscopic Retrograde Cholangio-Pancreatography (ERCP) was performed in 48–62%. IPNB with invasive carcinoma was found in 35.7–60% and IPNB with intraepithelial neoplasia in 36–60%. Histopathological confirmation before surgery was rare. The main treatment of IPNB is resection, in our material, both, hepatectomy and hepatectomy plus bile duct resections were performed in 40% of patients. The percentage of postoperative complications was 20%. The 5-year survival rate of all IPNB’s patients was 53.6%; in patients with associated invasive carcinoma - 22.2% and without invasive carcinoma - 100% (p ​= ​0.001).ConclusionsEarly surgery is advisable for radiologically suspected IPNB. The results of treatment depend on histopathology. They are worse at intraductal invasive carcinoma than at neoplasm with neoplasia.     

Is there a relationship between tissue inhibitor of metalloproteinase-1 and transforming growth factor-beta 1 with respect to malignant melanoma progression?

Recent articles about the roles and relationships of tissue inhibitor of metalloproteinase-1 and transforming growth factor-beta 1 in various types of normal tissues and malignancies give rise to the question: ‘Is there a relationship between them with regard to malignant melanoma progression?’ In the light of many references, it seems to be highly probable that the tissue inhibitor of metalloproteinase-1, – being a multifunctional protein – functions as a growth factor with possible stimulation by transforming growth factor-beta 1 in progression of malignant melanoma, rather than its other existing functions in many different normal and cancer tissues (e.g. inhibition of the matrix metalloproteinases or functioning as an insignificant inhibitor of angiogenesis).     

Pontosubicular apoptosis (“necrosis”) in human neonates with intrauterine growth retardation and placental infarction

In a previous study of 37 autopsied stillbirths with non-dysmorphic intrauterine growth retardation (IUGR), 26 cases were associated with placental infarction, a morphologic marker of uteroplacental insufficiency. Nine of the 26 cases with both IUGR and placental infarction, where archival tissue was available, had grey matter ischaemic lesions that were subsequently identified as pontosubicular necrosis. This lesion is now regarded as a localized form of apoptosis. A further eight third trimester stillbirth cases with both IUGR and placental infarction were ascertained prospectively. Sixteen of these 17 cases showed pontosubicular apoptosis, identified morphologically and verified using activated caspase-3 and TUNEL. Five of the 17 cases showed apoptosis in the frontal or temporal cortex as well. In this current study, pontosubicular apoptosis was strongly associated with IUGR and placental infarction in third trimester stillborns, suggesting that uteroplacental insufficiency leading to chronic fetal hypoxaemia may cause cerebral apoptosis.     

Clinicopathological analysis of a type of “low grade” poorly cohesive gastric adenocarcinoma not otherwise specified with a good prognosis

Poorly cohesive carcinoma not otherwise specified (PCGCA-NOS) is regarded in the most recent WHO classification as a high-grade malignancy; however, some cases may be associated with a relatively good prognosis. We have studied a series of 115 cases of PCGCA-NOS and were able to identify low-grade features in 14 cases based on three morphological manifestations. Immunohistochemical staining, EBER in situ hybridization, Feulgen staining and flow cytometry were employed. Among the 115 cases of PCGAC-NOS, 14 cases met the criteria of “low grade”, accounting for 12.2 %. The “low grade” cases exhibited more shallow invasion and less lymph node metastasis (both P < 0.05); showed less frequent expression of MUC5AC, E-cadherin and p53 (all P < 0.05). Moreover, “low grade” PCGAC-NOS had a lower proliferative index(P < 0.001). We also found that the DNA content was lower in the “low grade” group, and aneuploidy was not detected in the “low grade” group, which was sharply different from the control group (50 %). Last, “low grade” PCGAC-NOS had a more favorable prognosis. A small subset of PCGAC-NOS cases have a low grade nature, and the clinicopathological features, immunophenotypes, and cytogenetics of these “low grade” cases differ from those of traditional PCGAC-NOS.     

Malignant mesenchymomas of soft tissue associated with numerous osteoclast-like giant cells mimicking the so-called giant cell variant of “malignant fibrous histiocytoma”

Three cases of malignant mesenchymoma with numerous osteoclast-like giant cells, arising in deep soft tissue, and which mimicked the so-called giant cell variant of malignant fibrous histiocytoma have been studied. All three neoplasms arose in adults; two patients were male and one was female. Two tumours arose in the thigh, and one in the right shoulder. Two patients died within 2 years of the primary excision while the third is alive and well at 2.5 years. Histologically, one case showed leiomyosarcoma plus liposarcoma, one leiomyosarcoma plus osteosarcoma, and one tumour consisted of liposarcoma plus osteosarcoma; all components were assessed morphologically as high-grade malignant. All three cases showed prominent osteoclast-like giant cells in the leiomyosarcomatous or osteosarcomatous areas, thereby closely mimicking the phenotype of so-called giant cell variant of malignant fibrous histiocytoma. We discuss briefly differences in soft tissue sarcomas demonstrating this distinctive osteoclast-rich phenotype.     

Evaluation of the resistance to bacterial growth of star-shaped poly(ε-caprolactone)-co-poly(ethylene glycol) grafted onto functionalized carbon nanotubes nanocomposites

Nanocomposites of functionalized carbon nanotubes (CNTs_f) as nanofillers, and a copolymer of star-shaped poly(ε-caprolactone) (stPCL) and poly(ethylene glycol) (PEG) as a polymeric matrix were synthesized, characterized, and their resistance to the growth of Staphylococcus aureus and Pseudomonas aeruginosa was evaluated. CNTs_f contain hydroxyl, carboxyl and acyl chloride groups attached to their surface. Nanocomposites were prepared by mixing CNTs_f to a solution of stPCL-PEG copolymer. Raman and FT-IR spectroscopies confirm the functionalization of carbon nanotubes (CNTs). Star-shaped PCL-PEG copolymer was characterized by Gel permeation chromatography (GPC), and ¹H-NMR and ¹³C-NMR spectroscopies. X-ray photoelectron spectroscopy (XPS) shows that CNTs_f are grafted to the stPCL-PEG copolymer. Crystallization behavior of the nanocomposites depends on the amount of CNTs_f used in their preparation, detecting nucleation (nanocomposites prepared with 0.5?wt.% of CNTs_f) or anti-nucleation (nanocomposites prepared with 1.0?wt.% of CNTs_f) effects. Young’s Moduli and thermal stability of nanocomposites were higher, but their resistence to the proliferation of Staphylococcus aureus and Pseudomonas aeruginosa was lower than the observed for their pure polymer matrix.     

Molecular characterization of “sessile serrated” adenoma to carcinoma transition in six early colorectal cancers

Colorectal cancer (CRC) is a heterogeneous group of diseases both from the morphological and molecular point of view. The sessile serrated adenoma/polyp (SSA/P) has been proposed as the precursor lesion of CRCs characterized by CpG island methylator phenotype (CIMP), DNA mismatch repair (MMR) system deficiency, and BRAF gene mutations. However, no study so far investigated the molecular landscape of “sessile serrated” adenoma to carcinoma transition in early CRCs. Six formalin-fixed paraffin-embedded CRCs developed within SSA/P were profiled for the immunohistochemical expression of MMR proteins (MLH1, MSH2, MSH6, PMS2, and Ep-CAM), p16, and β-catenin. DNA was extracted from the two components of each sample, after microdissection, and characterized for CIMP status and by applying a custom hotspot multigene mutational profiling of 164 hotspot regions of eleven CRC-associated genes (AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN, and TP53). Five out of the six CRCs shared the same molecular profile (i.e. CIMP positive, MSI status, and BRAF mutation) with their SSA/P components. One out of five CRCs was also APC mutated, whereas another one showed an additional TP53 mutation. The remaining case was CIMP negative and MMR proficient in both the components, harbored a BRAF mutation in the SSA/P counterpart, whereas the CRC one was APC and TP53 mutated and showed p16 and β-catenin dysregulation. This study provides the molecular evidence that SSA/P, even without cytological dysplasia, is a precursor lesion of CRC and that conventional CRC might arise from mixed polyp.     

Synthesis and characterization of poly(methyl methacrylate)-based experimental bone cements reinforced with TiO2–SrO nanotubes

In an attempt to overcome existing limitations of experimental bone cements we here demonstrate a simple approach to synthesizing strontium-modified titania nanotubes (n-SrO–TiO₂ tubes) and functionalize them using the bifunctional monomer methacrylic acid. Then, using ‘grafting from’ polymerization with methyl methacrylate, experimental bone cements were produced with excellent mechanical properties, radiopacity and biocompatibility. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive spectroscopy mapping and backscattered SEM micrographs revealed a uniform distribution of SrO throughout the titanium matrix, with retention of the nanotubular morphology. Nanocomposites were then reinforced with 1, 2, 4 and 6 wt.% of the functionalized metal oxide nanotubes. Under the mixing and dispersion regime employed in this study, 2 wt.% appeared optimal, exhibiting a more uniform dispersion and stronger adhesion of the nanotubes in the poly(methyl methacrylate) matrix, as shown by TEM and SEM. Moreover, this optimum loading provided a significant increase in the fracture toughness (K_IC) (20%) and flexural strength (40%) in comparison with the control matrix (unfilled) at P < 0.05. Examination of the fracture surfaces by SEM showed that toughening was provided by the nanotubes interlocking with the acrylic matrix and crack bridging during fracture. On modifying the n-TiO₂ tubes with strontium oxide the nanocomposites exhibited a similar radiopacity to a commercial bone cement (CMW® 1), while exhibiting a significant enhancement of osteoblast cell proliferation (242%) in vitro compared with the control at P < 0.05.     

Reactions of Rabbit Antisera to Human β2-Microglobulin (β2-M) with Platelets

Reactions of rabbit antisera to human β₂^?M against human platelets and man-mouse hybrid cells were studied by MA. tests and cytolvsis tests. Evidence is presented that the β₂-M act as species-specific cell surface antigens, some of which are most likely shared bv cell surface proteins determined by genes on chromosomes other than the chromosome 15.