Smooth muscle tumors of the gastrointestinal tract: an analysis of prognostic features in 407 cases.

Smooth muscle tumors represent the second most common mural mesenchymal neoplasm in the gastrointestinal tract, but established criteria for prognostic assessment of these tumors are lacking. A large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions was analyzed to identify potential prognostic features. Pathologic features were assessed by expert gastrointestinal and/or soft tissue pathologists at each center. Immunohistochemical confirmation was required. A total of 407 cases from the esophagus (n = 97, 24%), stomach (n = 180, 44%), small bowel (n = 74, 18%), and colorectum (n = 56, 14%) were identified. Patients ranged in age from 19 to 92 years (mean 55 years), with a slight female predominance (57%). Mean tumor size was 5.4 cm, with the largest tumor measuring 29 cm. Disease progression following surgery, defined as local recurrence, metastasis, or disease-related death, occurred in 56 patients (14%). Colorectal tumors were most likely to progress, followed by small bowel and gastric tumors. None of the esophageal tumors in this series progressed. Receiver operator characteristic analysis identified optimal cutoffs of 9.8 cm and 3 mitoses/5 mm2 for discriminating between progressive and non-progressive tumors. Histologic features strongly associated with progression by univariate analysis included moderate-to-severe atypia, high cellularity, abnormal differentiation (defined as differentiation not closely resembling that of normal smooth muscle), tumor necrosis, mucosal ulceration, lamina propria involvement, and serosal involvement (P < 0.0001 for all features). Age, sex, and margin status were not significantly associated with progression (P = 0.23, 0.82, and 0.07, respectively). A risk assessment table was created based on tumor site, size, and mitotic count, and Kaplan-Meier plots of progression-free survival for each subgroup revealed progression-based tiers. Based on our findings, it appears that nonesophageal gastrointestinal smooth muscle tumors measuring >10 cm and/or showing ≥3 mitoses/5 mm2 may behave aggressively, and therefore close clinical follow-up is recommended in these cases.

Variation in nuclear size and PD-L2 positivity correlate with aggressive chromophobe renal cell carcinoma.

Chromophobe renal cell carcinoma (CRCC) is not amenable to International Society for Urologic Pathology-endorsed nucleolar grading. Novel grading approaches were proposed, but the rarity of adverse pathology hampers their discriminatory value. We investigate simple linear micrometer measurements and a proposed immunostain in CRCCs. 32 patients' CRCCs were studied: 12 adverse cases (stage pT3, recurrence, or metastasis), 15 controls (stage ≤pT2, no recurrence or metastasis after >3 years), and 8 metastases (3 were paired with primary adverse cases). The ratio of greatest dimensions of largest and smallest nuclei, in each of 5 "worst" high-power fields, excluding those with degenerative features, was designated variation in nuclear size (VNS). Percent multinucleate cells (PMC) were also counted. Mouse anti PD-L2 monoclonal antibody immunostaining was performed. Mean VNS measured in adverse primary and control primary tumors were 3.7 ±â€¯0.5 and 2.4 ±â€¯0.4 respectively (P < .001), and 3.4 ±â€¯0.4 for metastases (P < .001). Optimal VNS cut-off was 2.5, with sensitivity and specificity 0.85 and 0.81, respectively. PMCs were 6.0 ±â€¯3.0 for adverse group, 5.7 ±â€¯2.7 for controls, and 4.1 ±â€¯1.6 for metastases (P = NS). PD-L2 could not discriminate adverse versus good primary tumors (χ21.6, P = .2), but was higher in metastases (χ2 6.9, P < .01), or metastases plus adverse primary tumors (χ2 4.8, P = .03), compared to good-pathology primary tumors. In conclusion, VNS is an easily obtained measurement that can predict adverse behavior of chromophobe RCC, and may impart value for needle biopsy reporting and the choice of active surveillance. PD-L2 was elevated in metastases but was less useful for primary tumors.

Sucrose esters of aryldihydronaphthalene-type lignans, and antitumor activity of extracts of Moltkiopsis ciliata (Forssk.) aerial parts.

One new compound (3f-[(7'R,8'R)-4,4'-dihydroxy-5-methoxy-2,7'-cycloligna-7-en-9-methoxycarbonyl, 9'-carbonyl-O-] -ß- D-fructofuranosyl- (2→1)-α- D-glucopyranoside) (Moltkiopsin A) (2) was isolated and identified from the extract of aerial parts of the wild Egyptian plant Moltkiopsis ciliata (Frossk.), family Boraginaceae, for the first time, along with two aryldihydronaphthalene lignans 3f→9':6f→9-[(7'R,8'R)-4,4'- dihydroxy-3,3',5-trimethoxy-2,7'-cycloligna-7-en-9,9'-dicarbonyl]-6g-acetyl-α-D-gluco pyranosyl-(1→2) -ß-D-fructofuranoside (Trigonotin A) (1) which was reported for the first time from this plant species and a known compound 3f→9':6f→9-[(7'R,8'R)-4,4'- dihydroxy-3,3',5-trimethoxy-2,7'-cycloligna-7-en-9,9'-dicarbonyl]-α-D-gluco pyranosyl - (1→2)- ß-D- fructofuranoside (Trigonotin C) (3). These compounds were separated and purified using different chromatographic techniques and their structures were elucidated by extensive 1D (1H and 13C NMR), and 2D NMR (COSY, HSQC, and HMBC), besides ESI-MS spectral methods. Extracts were screened as antioxidant, antitumor and antibacterial. The different extracts showed moderate to strong antioxidant capacities in DPPH assays. Ethyl acetate, methylene chloride and crude methanol extracts exhibited the most significant free radicals scavenging activity when compared to the standard antioxidant vitamin C. Hexane and butanol fractions showed the highest cytotoxicity against the cancer cell lines HepG2 and MCF-7.

Quadrangulosides A-F: new pregnane glycosides from Caralluma quadrangula.

The phytochemical investigation of Caralluma quadrangula aerial parts yielded six new pregnane glycosides, quadrangulosides A-F (1-6), in addition to nine known pregnane glycosides and three known flavone glycosides. Structures of isolated phyto-constituents were elucidated via spectroscopic 1D-, 2D-NMR and spectrometric ESI-MS spectra.

Thermal pyrolysis and kinetic parameter determination of mango leaves using common and new proposed parallel kinetic models.

TG/DTG thermal pyrolysis analysis is performed under nitrogen from 100 to 1000 °C at three different heating rates for three types of most famous Egyptian mango leaves to be used as a biomass fuel. Proximate and ultimate analysis, organic composition, metallic components as well as thermal degradation and their characteristic properties are determined and deeply investigated to recognize the possibility to use them as a source of renewable energy. A maximum volatile released method and three isoconversional kinetic models were used to analyze the dependence of the activation energy (E α ) on the degree of conversion. A double parallel random pore model (DRPM), mixed volumetric random pore model (MVRPM) and a new proposed double parallel volumetric model (DVM) were used to investigate the kinetic parameters of the produced volatile and char. Three zones were chosen based on the organic composition and the temperature range of each mango leaf type. The maximum rate loss and second derivative of conversion of volatile matter (α) with temperature are used in the maximum volatile method at peak temperature for determining the kinetic parameters. The three isoconversional kinetic methods give almost closest values of E av for all sub-zones and especially for a whole volatile zone of Sukari momtaz. The estimated E av from the isoconversional methods are more dependable than the maximum volatile release method. Compared with previous multireaction models, the new proposed double parallel model can effectively investigate the pyrolysis kinetics of biomass materials.

Dimethylfumarate ameliorates hepatic injury and fibrosis induced by carbon tetrachloride.

The current study was designed to assess the antifibrotic effect of dimethylfumarate (DMF) on CCl4-induced hepatic injury in rats. Hepatic injury was induced by intraperitoneal twice weekly injection of CCl4 for 2 and 3 months. DMF was administered orally during the last 4 weeks in each model. Liver injury was estimated using biochemical parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), total serum bilirubin (TSB), total protein, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Additionally, oxidative stress parameters such as superoxide dismutase (SOD), reduced glutathione (GSH), nitric oxide (NOx), and malondialdehyde (MDA) were studied. Collagen IV (Col IV), alpha-smooth muscle actin (α-SMA), transforming growth factor beta1 (TGF-ß1) and nuclear factor kappa B (NF-κB) were also assessed as markers of fibrosis and inflammation. Histopathological examination of liver tissues was performed and compared with control. The obtained results showed that DMF ameliorated the elevated markers of liver injury and oxidative stress in addition to hepatic necroinflammation scoring induced by CCl4. Furthermore, DMF ameliorated CCl4-induced fibrosis as evidenced by histopathological scoring and collagen IV content. Besides, we investigated the possible underlying mechanisms for these effects which include: (1) attenuating oxidative stress as designated by decreased MDA and NOx as well as increased GSH and SOD levels; (2) anti-inflammatory effect as evidenced by inhibitory effect on NF-κB; (3) preventing hepatic stellate cells (HSCs) activation as indicated by blunting the expression of α-SMA; and (4) downregulating the fibrogenesis response of HSCs as denoted by inhibiting TGF-ß1 secretion and Col IV deposition. In conclusion, this study clarified the antifibrotic effect of DMF that might serve as a new candidate for management of liver fibrosis.

Papillary Carcinoma of Stensen's Duct with Intestinal Differentiation.

Stensen's duct carcinoma (StDC) is an extremely rare neoplasm, with fewer than 40 cases reported in the literature. We report a unique case of primary StDC with papillary features and intestinal differentiation of a 74-year-old male. We discuss the radiologic and pathologic correlation along with the differential diagnosis of this rare entity.

Effective utilization of C. difficile PCR and identification of clinicopathologic factors associated with conversion to a positive result in symptomatic patients.

OBJECTIVES: We assess the diagnostic yield of repeat testing for C. difficile using molecular methods within 7days of a negative test and identify specific factors associated with conversion from negative to positive test result within a 7-day period to aid in selective test utilization. METHODS: A retrospective chart review of 20,866 laboratory test orders for C. difficile PCR was conducted. The test result, clinicopathologic patient features, and previous test results were recorded. Univariate and multivariate analysis was conducted to compare patients with initial and repeat negative results (n=248) to a group of patients with conversion from negative to positive results within 7days. RESULTS: Univariate analysis demonstrated a history of C. difficile infection, receipt of antibiotics within 14days, and duration of hospital stay as factors significantly different between patients with repeat negative and conversion to positive C. difficile test result. Only history of C. difficile infection was significantly different upon multivariate analysis. CONCLUSIONS: Identification of prior C. difficile infection as the only factor significantly correlated with conversion from negative to positive C. difficile test result within 7days aids in selective test utilization and reduces the costs associated with unnecessary laboratory testing.

Pathologic classification of "pancreatic cancers": current concepts and challenges.

As the most common and most important cancer of the pancreas, with rapid mortality and now also as the third leading cause of cancer-related deaths in the United States, pancreatic ductal adenocarcinoma (PDAC) has become synonymous with "pancreas cancer". PDAC is also the prototype of the "pancreatobiliary-type" adenocarcinomas, along the biliary tract, ampullary and gallbladder cancers with the similar morphology and behavior. Recent molecular profiling studies have identified distinct subsets of PDAC, potentially with different behaviors and targetability. Moreover, while PDAC is by far the most common cancer of the pancreas, there are various other types that occur in this organ and are erroneously classified together with PDAC. Many of these have different molecular and biologic characteristics that warrant their management separately although they are also technically "pancreatic cancers". While some are closely related to PDAC and have as aggressive behavior (such as adenosquamous carcinomas which are recently recognized under "basal" like category in profiling studies, which are actually even worse prognostically than PDACs), in the meantime, others such as colloid carcinoma has a much better behavior than PDAC, and as a carcinoma with intestinal lineage (MUC2/CDX2) colloid carcinoma may require an entirely different treatment approach as well. Similarly, medullary carcinomas also appear to have different biology. Additionally, non-ductal cancers such as acinar, neuroendocrine, solid-pseudopapillary neoplasms and pancreatoblastoma have their respective clinicopathologic and molecular associations and warrant careful elimination in the management and study protocols. Another very problematic aspect in the classification of "pancreas cancer" is its delineation from the cancers of neighboring organs, in particular, ampullary/duodenal and common bile duct (CBD) cancers, for which recently more refined criteria have been provided. Additionally, the possibility of metastasis from another site and lymphomas also need to be considered. In summary, there is a whole host of cancers that occur in the pancreas that ought to be considered carefully before a case is classified as an ordinary "pancreas cancer" (PDAC).

Effect of chronic low-dose tadalafil on penile cavernous tissues in diabetic rats.

OBJECTIVE: To assess the effect of chronic low-dose administration of tadalafil (Td) on penile cavernous tissue in induced diabetic rats. METHODS: The study investigaged 48 adult male albino rats, comprising a control group, sham controls, streptozotocin-induced diabetic rats, and induced diabetic rats that received Td low-dose daily (0.09 mg/200 g weight) for 2 months. The rats were euthanized 1 day after the last dose. Cavernous tissues were subjected to histologic, immunohistochemical, morphometric studies, and measurement of intracavernosal pressure and mean arterial pressure in anesthetized rats. RESULTS: Diabetic rats demonstrated dilated cavernous spaces, smooth muscles with heterochromatic nuclei, degenerated mitochondria, vacuolated cytoplasm, and negative smooth muscle immunoreactivity. Nerve fibers demonstrated a thick myelin sheath and intra-axonal edema, where blood capillaries exhibited thick basement membrane. Diabetic rats on Td showed improved cavernous organization with significant morphometric increases in the area percentage of smooth muscles and elastic tissue and a significant decrease of fibrous tissue. The Td-treated group showed enhanced erectile function (intracavernosal pressure/mean arterial pressure) at 0.3, 0.5, 1, 3, and 5 Hz compared with diabetic group values at the respective frequencies (P <.05) that approached control values. CONCLUSION: Chronic low-dose administration of Td in diabetic rats is associated with substantial improvement of the structure of penile cavernous tissue, with increased smooth muscles and elastic tissue, decreased fibrous tissue, and functional enhancement of the erectile function. This raises the idea that the change in penile architecture with Td treatment improves erectile function beyond its half-life and its direct pharmacologic action on phosphodiesterase type 5.