Tumoral presence of human cytomegalovirus is associated with shorter disease-free survival in elderly patients with colorectal cancer and higher levels of intratumoral interleukin-17.

Infectious diseases are closely related to cancer. Human cytomegalovirus (HCMV) has been implicated in the promotion of tumour growth, and is present in the tumour specimens of colorectal cancer (CRC). This study aimed to investigate whether tumoral presence of HCMV is associated with a different clinical outcome in elderly patients with CRC. We analysed archived tumour specimens from 95 CRC patients aged ≥65 years. HCMV was detected by PCR. Clinical, pathological, disease-free and overall survival data were compared between patients with HCMV-positive and HCMV-negative tumours. A quantitative RT-PCR array was used to evaluate the expression levels of cytokines genes of T-helper subpopulations in tumours. In the Kaplan-Meier analysis of the 81 patients who underwent curative surgery, 39 patients with HCMV-positive tumours had a lower disease-free survival rate (p 0.024). For patients with stage II or stage III tumours, tumoral HCMV status correlated with disease-free survival more closely than the traditional histopathological staging methods. In a multivariate Cox proportional hazard model, tumoral presence of HCMV independently predicted tumour recurrence in 5 years (hazard ratio 4.42; 95% CI 1.54-12.69, p 0.006). The qRT-PCR analysis of ten stage II tumours showed that the gene expression levels of interleukin-17-the signature cytokine of T-helper 17 cells-and its receptor, interleukin-17 receptor C, were higher in the five HCMV-positive tumours. Our results suggest that the presence of HCMV in CRC is associated with poorer outcome in elderly patients. How the virus interacts with the tumour microenvironment should be further investigated.

Imaging characteristics of primary spinal primitive neuroectodermal tumors. A report of five cases and literature review.

Primary spinal primitive neuroectodermal tumors (PNETs) are rare and classified into peripheral and central types because the treatment strategy and outcome are different. This study describes five cases of primary spinal peripheral type PNETs. Magnetic resonance imaging showed large extradural masses in the cervical and thoracic spine with bony invasion and paraspinal extension in four cases and a transdural mass in the sacral spinal canal in one case. We also briefly summarize the imaging characteristics of 36 peripheral type and six central type primary spinal PNETs in the literature.

Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma.

Perivascular epithelioid cell tumours (PEComas) are a family of tumours including classic angiomyolipoma, lymphangioleiomyomatosis, and clear epithelioid cell tumours reported under a variety of names such as epithelioid angiomyolipoma, pulmonary and extrapulmonary clear cell sugar tumour, and PEComa. Our previous comparative genomic hybridization study of PEComas demonstrated recurrent chromosomal aberrations including deletions on chromosome 16p, where the TSC2 gene is located. In this study, we focused on the alteration of chromosome 16p, including TSC2. We collected ten sporadic and two tuberous sclerosis complex-associated PEComas, as well as 14 sporadic classic hepatic and renal angiomyolipomas (AMLs) as controls. We used 16 microsatellite markers distributed along chromosome 16p to test for allelic imbalances on chromosome 16p and at TSC2, and two markers for TSC1. Furthermore, we carried out immunohistochemical staining for phospho-p706K, phospho-AKT, and phospho-S6 to evaluate the effect of TSC2 alterations on the mTOR signalling pathway. Loss of heterozygosity (LOH) was found in 11 PEComas and involved the region of the TSC2 locus in seven. Six classic angiomyolipomas had allelic changes at chromosome 16p. Microsatellite instability was detected in two PEComas. The incidence of genetic aberrations was significantly higher in the PEComa group. Only one PEComa showed LOH at the TSC1 locus. Eleven PEComas and 13 AMLs revealed elevated phospho-p70S6K accompanied by reduced phospho-AKT. Five PEComas and eight classic angiomyolipomas were positive for phospho-S6. The phosphorylation profile indicates functional activation of the mTOR pathway through a disrupted TSC1/2 complex. Our observations of frequent deletion of TSC2 and the mTOR signalling pathway provide evidence that the oncogenetic lineage of PEComa, as a distinct TSC2-linked neoplasm, is similar to that of angiomyolipoma.

Normal-phase chiral liquid chromatography-mass spectrometry of non-UV-active compounds: applications for pharmaceutically relevant racemates.

Mixtures of hexane-like ethoxynonafluorobutane with alcohols were used as MS-friendly mobile phases for separation and efficient detection of non-UV-active enantiomers and diastereomers using normal-phase HPLC-APCI-MS. Racemic muscone, camphorsulfonamide, camphorsultam, BOC-protected 1-(3-aminopropyl)-2-pipecoline and diastereomeric 2-methylhexanoyl camphorsultams were resolved on Chiralpak AS and AD and achiral Luna CN columns. The responses of UV and APCI-MS detectors were compared under separation conditions studied, with MS detection achieving lowest detectable quantity in the range of 0.5-2 ng per chromatographic peak. The absolute configuration of crystalline derivatives of racemic 2-methylhexanoic acid with (S)-(-)-2,10-camphorsultam was determined by X-ray analysis after their automatic purification by preparative LC-MS. The technique described can be used to purify and determine the absolute stereochemistry of compounds of unknown structure which contain free carboxy group and lack sufficient UV absorbance.

Intraspinal leakage of bone cement after vertebroplasty: a report of 3 cases.

We report 3 cases of vertebroplasty-induced intraspinal leakage of bone cement that were referred to us for management. Two patients received decompressive surgery, and one received rehabilitation. The gross surgical finding of yellowish dura mater and intradural fibrosis, adhesion, and microscopic finding of arachnoid membrane fibrosis are suggestive of late effect of thermal injury. These patients had residual lower extremity weakness and urinary and stool problems 13 months, 3 years, and 4.75 years post-vertebroplasty, respectively.

Neuroradiological findings in atypical teratoid/rhabdoid tumor of the central nervous system.

PURPOSE: To evaluate the computed tomography (CT) and magnetic resonance imaging (MRI) findings of atypical teratoid tumor/rhabdoid tumor (AT/RT) of the central nervous system (CNS). MATERIAL AND METHODS: Twenty cases of CNS AT/RT have been found over the past 23 years in our hospital; these involving 11 boys and 9 girls whose mean age at diagnosis was 5.5 years. Their clinical data, the CT, and MRI findings were reviewed retrospectively. RESULTS: AT/RT was located in the cerebellum in 15 cases. Four cases arose from the supratentorial region, while only one occurred primarily in the lumbar spinal cord. Almost all cases revealed heterogeneous intensity and heterogeneous enhancement. Peripheral cystic components were common. Survival time ranged from 2 months to 3 years, with a mean survival of 11.6 months. CONCLUSION: Most cases of AT/RT are located in the cerebellum. The radiologic manifestations are non-specific. The diagnosis mainly depends on the pathologic findings. However, AT/RT should still remain in the differential diagnosis of brain tumors in young children, especially those located in the cerebellar hemisphere and with eccentric cysts.

Disorder in organic charge-transfer single crystals: dipolar disorder in ClMePD-DMeDCNQI.

The unusual electronic, vibrational, and structural properties of the title compound are associated with the polar donor D=2-chloro-5-methyl-p-phenylenediamine, which is twofold disordered in single crystals. Its 3 D dipole generates random site energies with standard deviation sigma=0.35 eV that significantly alter the standard description of charge-transfer (CT) salts with nonpolar donors and acceptors. The average structure at 298 and 150 K is centrosymmetric, space group P1, and consistent with increasing degree of CT (or ionicity rho) on cooling. Vibrational spectra indicate that rho increases from approximately 0.3 at 400 K to approximately 0.6 at 80 K, with coincident Raman and infrared (IR) molecular modes in contrast with the centrosymmetric structure. Dipolar disorder is modeled by adding random site energies to Peierls-Hubbard models of CT salts, and sigma=0.35 eV is shown to suppress the Peierls instability for typical bandwidth and lattice stiffness, in agreement with the structural data. Disorder also breaks inversion symmetry and rationalizes coincident Raman and IR modes. The combination of site energies xp and the dipole operator P for systems with periodic boundary conditions leads at molecule p to (partial differentialP/ partial differentialxp)2 for the IR intensity polarized along the DA stack. The ensemble average of (partial differentialP/ partial differentialxp)2 for sigma=0.35 eV as a function of the ground-state ionicity rho accounts for the intensity variations of totally symmetric molecular modes of D and A, either on cooling at ambient pressure or on squeezing at ambient temperature.

The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases.

AIMS: To demonstrate the diagnostic utility of MOC31, BerEP4, renal cell carcinoma marker (RCC Ma) and CD10 in the classification of RCC and renal oncocytoma, based upon a comprehensive immunohistochemical analysis. METHODS AND RESULTS: Immunohistochemistry was performed on 328 samples consisting of 256 clear cell/conventional, 27 papillary, 28 chromophobe, five collecting duct, five unclassified RCCs and seven renal oncocytomas using antibodies MOC31, BerEP4 and antibodies against cytokeratins (KL-1, CAM5.2, 34betaE12, cytokeratin 7), RCC Ma, epithelial membrane antigen, E-cadherin, CD10, CD15 and vimentin. Multivariate analysis showed that MOC31, BerEP4, RCC Ma and CD10 have discriminatory value. MOC31 and BerEP4 chiefly labelled distal tubules of normal kidney while RCC Ma and CD10 labelled the proximal tubules. Twenty-three chromophobe RCCs (82%) were reactive for MOC31, while only four clear cell RCCs and three papillary RCCs were positive for this marker. Clear cell RCCs were characterized by a high positive rate for CD10 (82%) and a low positive rate for BerEP4 (27%). Papillary RCCs frequently coexpressed RCC Ma and BerEP4 (51%). All renal oncocytomas were negative for MOC31 and CD10. CONCLUSIONS: MOC31 has diagnostic merit in discerning chromophobe RCC. The CD10+/BerEP4- profile and RCC Ma+/BerEP4+ profile achieve moderate sensitivity and good specificity for clear cell RCC and papillary RCC, respectively. The non-reactivity for both MOC31 and CD10 is helpful in distinguishing renal oncocytoma from RCC. When properly selected, antibodies have immunohistochemical diagnostic utility for the classification of renal cortical epithelial tumours.

Synthesis of an extremely crowded naphthalene via a stable norbornadienone.

Computational studies at the HF/3-21G and B3LYP/6-31G(d) levels suggest that 5,6,8-tri(tert-butyl)-1,2,3,4-tetraphenylnaphthalene (2) is perhaps the most crowded naphthalene derivative that will show normal stability; more highly congested naphthalenes will prefer to exist as the corresponding Dewar isomers. Initial attempts to prepare 2 by reacting 3,4,5,6-tetraphenylbenzyne with 2,3,5-tri(tert-butyl)cyclopentadienone at 83 degrees C gave instead a stable norbornadienone, 1,2,4-tri(tert-butyl)-5,6,7,8-tetraphenyl-9-oxo-1,4-dihydro-1,4-methanonaphthalene (3), which was characterized by X-ray crystallography. The experimental and calculated (HF/3-21G) activation energies (E(a)) for the decarbonylation of 3 were quite high: 39 and 46 kcal/mol, respectively, a manifestation of the substantially increased strain in the transition state as the tert-butyl groups are forced together. The naphthalene 2 was obtained in good yield by heating 3 in refluxing toluene, and its X-ray structure showed exceptional distortions from a normal naphthalene geometry. However, 2 is not completely stable, and it decomposes upon prolonged heating in xylenes.

A metastatic pituitary carcinoid tumor successfully treated with gamma knife radiosurgery.

Intracranial metastasis occurs in a certain number of patients with carcinoid tumor. However, carcinoid tumor with metastasis to the pituitary gland is extremely rare. Up to the present, no effective treatment for either a metastatic intracranial carcinoid tumor or a metastatic pituitary lesion of any origin has been documented. We have treated a case of metastatic carcinoid tumor of the pituitary gland with transsphenoidal tumor resection followed by gamma knife radiosurgery. A 59-year-old man presented with headache and left oculomotor palsy. He was treated at the same hospital for bronchial atypical carcinoid tumor one and a half years ago. Magnetic resonance image of the brain showed a pituitary tumor. There were no signs of recurrent or metastatic lesion elsewhere despite thorough investigation. Transsphenoidal approach for removal of tumor was done and the pathology turned out to be a metastatic carcinoid tumor. Subsequent gamma knife radiosurgery was given for residual tumor. The oculomotor palsy improved after radiosurgery. No neurological deficit occurred. Follow-up CT scan of the brain showed complete resolution of the tumor. We concluded that gamma knife radiosurgery could be used to treat a metastatic intracranial carcinoid tumor. It can also be used to treat a metastatic lesion of the pituitary gland without causing neurological deficit.

A comparative MR and pathological study on fetal CNS disorders.

OBJECT: We used MR after sonography to help us in prenatal counseling in 58 complicated pregnancies from 1998 to 2000. METHODS: All fetal MR examinations were undertaken with a 1.5-T magnet using a body-phased-array coil and an ultrafast imaging technique, half-Fourier single-shot turbo spin-echo (HASTE). Twelve fetuses were found to have major anomalies, and in each of these cases either delivery was induced or the pregnancy was terminated. In 6 of the fetuses, with anomalies of the central nervous system, postmortem examinations were then performed after they failed to survive, and these constitute the patient sample investigated in the current study. The fetal gestational ages in these 6 cases ranged from 24 to 32 weeks. MR imaging demonstrated morphological details of the anomalies. They were: alobar holoprosencephaly in 2, middle interhemispheric fusion in 1, alobar holoprosencephaly with Dandy-Walker malformations in 1, a Dandy-Walker variant in 1 and twin-twin transfusion syndrome with hypoxic-ischemic injury to the brain in 1. CONCLUSIONS: Postmortem examinations confirmed the MR diagnoses, and these observations support us in improving our understanding of the pathogenesis of fetal CNS anomalies.

Plurihormonal pituitary adenomas: immunostaining of all pituitary hormones is mandatory for correct classification.

AIMS: We studied the clinicopathological characteristics of plurihormonal pituitary adenomas. METHODS AND RESULTS: The study material included 167 plurihormonal adenomas, which consisted of 31% of the surgically removed pituitary adenomas that we collected during a 12-year period. The mean age of patients with plurihormonal adenoma was 45.7 years (range 13-75 years). There were 86 men and 81 women. All tumours were fully classified by immunohistochemical staining for seven pituitary hormones or subunits. Thirty immunohistochemical subtypes of plurihormonal adenomas were recognized. Hormonal symptoms were present in 70% of patients, while serum hormonal levels were increased in 89% of patients. Most patients had symptoms related to only one of the hormones and only 7% of patients had symptoms related to two hormones. The most common hormonal symptom was acromegaly (50%); symptoms related to hyperprolactinaemia ranked second (20%). Double immunostaining of all the possible combinations of the hormones was performed in 30 selected tumours, and they all showed mixtures of hormones in individual adenoma cells in any hormonal combinations studied. The latter finding supported the view that plurihormonal adenomas are monomorphous adenomas. CONCLUSIONS: Plurihormonal adenomas are common pituitary adenomas. Immunohistochemical staining of all pituitary hormones is mandatory for correct classification.

Determining absolute configuration in flexible molecules: a case study.

Assigning absolute configuration of molecules continues to be a major problem. Determining absolute configuration in conformationally flexible systems is challenging, even for experts. Here, we present a case study in which we use a combination of molecular modeling, solution NMR, and X-ray crystallography to illustrate why it is difficult to use solution methods alone for configuration assignment. For the case examined, a comparison of calculated and experimental optical rotatory dispersion (ORD) data provides the most straightforward way to assign the absolute configuration.

A clinicopathologic study of 81 patients with ependymomas and proposal of diagnostic criteria for anaplastic ependymoma.

Optimal histologic criteria for the classification of and grading of ependymomas, including their anaplastic forms, remain elusive. This is especially true because of the poor correlation of these criteria with clinical outcome. The aim of this study was to identify the histopathologic parameters that could distinguish different prognostic groups of patients with ependymomas. Eighty-one patients with ependymal tumors, including those originally diagnosed ependymomas, anaplastic ependymomas and myxopapillary ependymomas, were enrolled in this study. Thirteen histologic parameters, including hypercellularity, nuclear pleomorphism, mitoses, endothelial proliferation, necrosis, clear cell, thrombi, dystrophic calcification, psammoma bodies, bone, cartilage, Rosenthal fibers and MIB-1 labeling index (LI), were evaluated in each patient and correlated with clinical outcome. We assigned one score for each histopathologic parameter evaluated and used a stepwise selection method with entry model based on the significance of the log-rank statistic to formulate a scoring model. Four parameters were chosen in this process, including mitoses > or = 4/10 hpf (1.7/mm2), hypercellularity, endothelial proliferation and necrosis. The sum of these four parameters (scores) was the histopathologic score of the tumor. The progression-free survival (PFS) and overall survival (OS) of patients with histopathologic scores 0 and 1 were significantly better than those with histopathologic scores 2, 3 and 4 (p < 0.001 and p = 0.005, respectively). Because of the latter finding, we proposed that anaplastic ependymoma could be diagnosed by the presence of any two of the aforementioned four parameters. Multivariate analyses including clinical and histopathologic variables showed that histopathologic score > or = 2 and subtotal resection were the factors related to increased risk of recurrence, while histopathologic score > or = 2 was the only factor related to overall survival. Based on the above findings, we concluded that histopathology is an important prognostic indicator for patients with ependymomas.

Spuriously high CK-MB isoenzyme activity mimicking acute myocardial infarction in a patient with adenocarcinoma of the rectum.

A 58-year-old Chinese male presented with precordial distress and was found to have elevated creatine kinase (CK)-myocardial bound (MB) (determined by the Kodak Ektachem Clinical Chemistry Slide method) activity and an abnormal electrocardiogram. Eventually, the patient was diagnosed with an annular ulcerative tumor 10 cm above the anal orifice. The tumor was an adenocarcinoma of the rectum and was immunoreactive for CK-BB (brain type). CK isoenzyme electrophoresis disclosed both BB and MM (muscle type) bands. We concluded that the level of CK-MB determined using the Kodak Ektachem Clinical Chemistry Slide method was spuriously elevated in our patient with adenocarcinoma of the rectum, without evidence of myocardial injury. Institutions using the Kodak Ektachem Clinical Chemistry Slide system for CK should be aware of this possibility.

Atypical teratoid/rhabdoid tumor of the central nervous system: a comparative study with primitive neuroectodermal tumor/medulloblastoma.

Eleven atypical teratoid/rhabdoid tumors (AT/RT) and 121 primitive neuroectodermal tumors/medulloblastomas (PNET/MB) were included in this study for evaluation of the histopathological features of AT/RT and comparison between AT/RT and PNET/MB. Histopathological studies of AT/RT showed that in addition to the commonly recognized components, i.e., rhabdoid cells, small (PNET/MB) cells, spindle cells and epithelial components, there was a previously unrecognized component, sickle-shaped embracing cells, which were present in all cases and could be useful as a histological marker of this tumor. Immunohistochemical studies showed divergent differentiation of the tumor cells and among the 16 antibodies studied, vimentin, neuron-specific enolase, epithelial membrane antigen and glial fibrillary acidic protein were most commonly reactive. The frequency of AT/RT expressed as a ratio of AT/RT to PNET/MB was 1:11 in general and increased to 1:3.8 among patients younger than 3 years old. The AT/RT patients were younger than those with PNET/MB and had a female predominance. The MIB-1 labeling index of AT/RT was significantly higher than that of PNET/MB (mean 63.9 vs 40.1), which correlated with a shorter survival in patients with AT/RT than those with PNET/MB (median survival time 15.4 months vs 156.4 months).

MIB-1 labeling index as a prognostic indicator for survival in patients with FIGO stage IB squamous cell carcinoma of the cervix.

OBJECTIVE: The goal of this study was to assess whether the MIB-1 labeling index (LI) and conventional parameters could distinguish between a good and a poor prognosis in patients with squamous cell cervical carcinoma of the same FIGO stage. METHODS: The study included 97 cases of stage IB squamous cell cervical carcinoma which were treated with radical hysterectomy between 1989 and 1991. The relation of the MIB-1 LI, conventional clinicopathologic parameters, and survival was evaluated. RESULTS: The MIB-1 LI of the entire group of tumors was 57.1 +/- 15.9 (mean +/- SD). The MIB-1 LI was significantly different only in living and dead patients, while it was not related to conventional clinicopathologic prognostic parameters. The 5- and 10-year survival rates of patients with an MIB-1 LI 55, which were 73.1 and 66%, respectively. Multivariate analyses showed that MIB-1 LI >55, lymph node metastasis, and tumor size >/=40 mm were powerful predictors of shorter survival. CONCLUSIONS: Lymph node metastasis, tumor size, and MIB-1 LI were significant prognostic markers in patients with stage IB squamous cell cervical carcinoma.

Abdominal wall necrosis following transcatheter arterial chemoembolization for hepatocellular carcinoma.

A 76-year-old man, who had inoperable hepatocellular carcinoma, had been treated with transcatheter arterial chemoembolization (TACE) 11 times, percutaneous ethanol injection therapy three times and conformal radiotherapy once, all in other hospitals. At this admission, he developed myocutaneous necrosis in the right abdominal wall after TACE, via the collateral of the right internal mammary artery (IMA). Necrosis of the abdominal wall was due to ischemic changes caused by embolization of the distal branches of the IMA, which were aggravated by previous radiation therapy. We advise that embolization of the IMA in patients who have received radiotherapy should be avoided, if possible.