Search

Objectives: Our aim was to compare perioperative patient controlled epidural analgesia (PCEA) versus patient controlled intravenous analgesia (PCA) after gynecologic oncology laparotomy., Methods: This was a prospective cohort study where perioperative pain management was decided through patient-centered discussion by anesthesia and surgical teams. The study was designed to accrue 224 patients, to test for equivalence in pain control on postoperative day 1, defined as less than a 10% difference in the proportion of patients with a visual analog scale pain score of <2 (0-10 scale)., Results: Two hundred forty patients were enrolled, with 205 patients evaluable for outcomes: 98 received PCA, while 107 received a thoracic level PCEA. Utilization of PCEA was associated with longer anesthesia time pre-op (means: 60 vs. 44 min, p<0.0001), as well as more likely use of pressors during surgery (78% vs. 57%, p=0.002). Pain control was comparable between groups on postoperative day 1 (mean VAS: 2.4 vs. 2.5, p=0.56), but patients with PCEA tended to require more supplemental pain medications. Time to first ambulation was longer in the PCEA patients (means: 49 vs. 36 h post-op, p=0.03), with no difference in time to tolerating regular diet (means: 89 vs. 77 h post-op, 0.17) and no difference in readiness for discharge (means: 144 vs. 145 h post-op, p=0.95)., Conclusions: In this nonrandomized prospective study, selection of a PCEA for perioperative pain management did not improve pain management for patients undergoing gynecologic oncology surgery.

Posterior interosseous nerve (PIN) palsy, presenting with a loss of digital extension, is a rare neurological complication of rheumatoid arthritis (RA). It may be caused by nerve entrapment, vasculitis or drug toxicity. There is no consensus regarding the treatment of PIN palsy in RA. We present a case in which the diagnosis of PIN palsy was confounded by previous surgical intervention. It represents the first report of PIN palsy treated with anti-TNF-alpha therapy leading to full recovery without surgical intervention. We highlight the importance of electrophysiological studies in elucidating the underlying cause and hence the treatment. We suggest that the apparent success of surgical intervention in the literature may be misleading, but new pharmacological advances may obviate the need for surgery where electrophysiology demonstrates vasculitis as the cause. A literature review is presented and a treatment algorithm proposed.

IgG4-related sclerosing disease is a syndrome characterized by the involvement of a wide variety of tissues by lymphoplasmacytic infiltrates and sclerosis, elevated serum IgG4 titer, and increased IgG4+ plasma cells in tissues. This report describes 2 cases with skin involvement, a feature not well documented in the literature. The patients had plaques or nodules in the skin of the cheek, temporal or periauricular region. Histologically, there was dermal and subcutaneous involvement by a nodular lymphoid infiltration often interspersed with lymphoid follicles and sclerotic stroma. The infiltrate was rich in plasma cells, small lymphocytes, and sometimes plasmablasts. The IgG4+ cell count was high (342 to 425 per high power field), with an IgG4/IgG proportion from 68% to 100%. As the morphology was compatible with pseudolymphoma, 14 cases of cutaneous pseudolymphoma were retrieved from the archives for IgG4 and IgG immunostaining. Two cases exhibited marked increase in IgG4+ cells, and showed many similarities with cutaneous manifestation of IgG4-related sclerosing disease, but the limited available clinical information precluded a conclusion on their nosologic nature. In summary, IgG4-related sclerosing disease can manifest with skin lesions, and is also one of the potential etiologies of cutaneous pseudolymphomas.

Myopericytoma is an uncommon, benign perivascular myoid cell tumor that occurs almost exclusively in somatic soft tissues. We report 2 cases occurring in patients with acquired immunodeficiency syndrome who show unusual clinical and biologic features. One patient presented with a bronchial mass and the other developed mass lesions of the tongue, vocal cord, and brain. Histologically, oval to plump spindly tumor cells with uniform nuclei and scanty cytoplasm formed sheets or cuffs around gaping or narrow vascular spaces. Focally, these areas merged into fascicles of more elongated cells with eosinophilic cytoplasm. The tumor cells were immunoreactive for actin but not desmin, and showed uniform labeling for Epstein-Barr virus (EBV) encoded RNAs on in-situ hybridization. Both patients were alive 5 years after incomplete excision of the lesions. In conjunction with another case reported in the literature, myopericytoma occurring in acquired immunodeficiency syndrome patients exhibits several features distinct from sporadic myopericytoma: presentation in anatomic sites other than somatic soft tissues, frequent presence of multifocal disease, and association with EBV. This tumor type therefore also broadens the spectrum of neoplasms associated with EBV.

Objectives: To determine the association of adjuvant radiotherapy and outcomes of women with stage III node-positive uterine cancer., Methods: All patients with surgically-staged stage III node-positive uterine cancer from the Surveillance Epidemiology and End Results database of the US National Cancer Institute from 1988 to 2001 were identified. Data were analyzed using Kaplan-Meier and logistic regression methods., Results: Of 943 women, the median age was 64 years (range: 28-93). 82.1%, 8.6%, and 6.8% were White, Black, and Asian respectively. The median number of removed nodes was 11. 54.9% had a single positive node and 45.1% had 2-5 positive nodes. Endometrioid, papillary serous, sarcomas, and clear cell carcinomas comprised of 69.7%, 16.3%, 9.9%, and 4.1% of histologies, respectively. 67.3% of the women underwent adjuvant radiotherapy with a 5-year disease-specific survival of 67.9% compared to 53.4% in those without radiotherapy (p<0.001). Adjuvant radiotherapy improved the survival from 54.4% to 74.3% (p<0.001) in those with a single positive node and from 52.4% to 59.7% (p=0.089) in those with 2-5 positive nodes. On multivariate analysis, older age, non-endometrioid histology, and lack of adjuvant radiotherapy remained as significant independent prognostic factors for worsened survival., Conclusions: Our data suggest that adjuvant radiotherapy is associated with a significant survival benefit in women with single-positive node endometrioid uterine cancers. Prospective clinical trials are warranted to confirm these findings.

Angiomatoid fibrous histiocytoma is an uncommon soft tissue tumor most frequently affecting the deep dermis and subcutis of the extremities in children and young adults. We report the first case presenting as a primary pulmonary tumor in a 46-year-old man. Histologically, the tumor was composed of multiple cellular nodules surrounded by a fibrous pseudocapsule and peritumoral lymphoplasmacytic infiltrates. The nodules were composed of histiocytoid cells with a diffuse, whorled, or vague storiform pattern, with the intervening areas densely packed with plasma cells and lymphocytes. The tumor cells were immunoreactive for epithelial membrane antigen, and focally desmin, CD68, and CD163. Fluorescence in-situ hybridization revealed EWS gene translocation, which was further confirmed on polymerase chain reaction to result from EWS/ATF1 gene fusion. It is important to recognize that angiomatoid fibrous histiocytoma can occur in the lung because its histologic features are rather nondescript and thus can be mistaken for other tumors such as meningioma, inflammatory myofibroblastic tumor, and follicular dendritic cell sarcoma.

Hematopoietic stem cells (HSCs) from the human placenta and umbilical cord blood (UCB) provide a rich source of highly proliferative cells for many clinical uses with advantages over traditional sources like the bone marrow and periphery blood. However, the key current constraint with this source of HSCs is the inadequate number of HSCs cells that can be harvested in a single collection using current approaches, which render a large number of collections unusable on their own, even for pediatric patients. This paper will present the development of a device to enable more efficient harvesting of HSCs from placentas, which can be used ex utero, upon the discharge of placentas after deliveries. The device can be used to facilitate a two-fraction collection process. Results, in terms of mononucleated cells (MNCs) count, CD34+ cells count, as well as flow cytometry, will be furnished to verify the effectiveness of the developed system.

IgG4-related sclerosing disease is a distinctive mass-forming lesion with frequent systemic involvement, most frequently the pancreas, salivary glands, and lacrimal glands. This report describes a case manifesting with a previously unrecognized form of central nervous system involvement. The 37-year-old man presented with signs and symptoms of spinal cord compression at the thoracic level 9. Magnetic resonance imaging revealed an elongated dural mass extending from the fifth to tenth thoracic vertebra. Laminectomy and excision of the mass revealed dura expanded by a dense lymphoplasmacytic infiltrate accompanied by stromal fibrosis and phlebitis. IgG4+ plasma cells were increased and the proportion of IgG4+/IgG+ plasma cells was 85%. The patient also had a 1-year history of bilateral submandibular swelling due to chronic sialadenitis. Thus, IgG4-related sclerosing pachymeningitis represents a new member of the IgG4-related sclerosing disease family affecting the central nervous system. It seems that at least a proportion of cases described in the literature as idiopathic hypertrophic pachymeningitis belong to this disease, especially as some patients have other clinical manifestations compatible with IgG4-related sclerosing disease, such as cholangitis and orbital pseudotumor.

Pleomorphic adenoma with foci of squamous and mucinous differentiation can potentially be misdiagnosed as low-grade mucoepidermoid carcinoma. The circumscribed borders of the tumor, gradual merging of mucoepidermoid foci into areas typical of pleomorphic adenoma, and presence of keratinization are features against the latter diagnosis.

Immunoglobulin G (IgG)4-related sclerosing disease is a recently described syndrome characterized by mass-forming lesions in various organs due to dense lymphoplasmacytic infiltrates and stromal sclerosis, elevated serum IgG4 titer, increased tissue IgG4 plasma cells, and favorable clinical outcome. We describe 4 patients with IgG4-related sclerosing mastitis, which represents a new member of this family of diseases. All patients were female with a mean age of 47.5 years, presenting with painless masses in 1 or both breasts. One patient had concurrent IgG4-related lymphadenopathy, and another had eyelid swelling of undetermined cause. The serum IgG4 titer was elevated in 1 tested patient, and circulating autoantibodies were found in 3 tested patients. All patients were well with no recurrence after excision or biopsy of the mass. Histologically, the breast masses featured dense lymphoplasmacytic infiltrates, prominent stromal sclerosis and loss of breast lobules. Phlebitis was present in 1 case. IgG4 cells ranged from 272 to 495 per high-power field, constituting 49% to 85% of all IgG cells. IgG4 cells were scarce in 9 of 9 cases of lymphocytic mastitis and 6 of 7 cases of granulomatous mastitis studied as controls. In summary, IgG4-related sclerosing mastitis appears to be a distinctive form of mastitis, sometimes accompanied by other components of IgG4-related sclerosing disease, and shows a favorable clinical outcome.

Cytotoxic T-lymphocyte (CTL) epitopes within the HIV genome are subject to negative and positive selective pressures, the balance of which influences CTL escape at a given epitope. We investigated whether viral fitness requirements dictate conservation of the HLA-A2 restricted immunodominant epitope SLYNTVATL (SL9). Viral clones incorporating changes throughout the SL9 epitope region were compared to consensus SL9 virus in terms of replication kinetics and relative viral fitness. Constructs recapitulating in vivo SL9-CTL escape variants showed markedly little effect on replication and fitness, as did non-natural conservative mutations targeting immunologically relevant positions of the epitope. Although certain residues of the epitope were constrained by viral requirements, our research reveals that there are multiple SL9 variants that are well tolerated virologically but fail to arise in vivo. In light of this data, assumptions regarding the balance of immune and viral selective pressures on this immunodominant epitope sequence need to be reassessed.

Background: Exposure to air pollution is an important risk factor for cardiovascular morbidity and mortality, and is associated with increased blood pressure, reduced heart rate variability, endothelial dysfunction and myocardial ischaemia. Our objectives were to assess the cardiovascular effects of reducing air pollution exposure by wearing a facemask., Methods: In an open-label cross-over randomised controlled trial, 15 healthy volunteers (median age 28 years) walked on a predefined city centre route in Beijing in the presence and absence of a highly efficient facemask. Personal exposure to ambient air pollution and exercise was assessed continuously using portable real-time monitors and global positional system tracking respectively. Cardiovascular effects were assessed by continuous 12-lead electrocardiographic and ambulatory blood pressure monitoring., Results: Ambient exposure (PM2.5 86 +/- 61 vs 140 +/- 113 mug/m3; particle number 2.4 +/- 0.4 vs 2.3 +/- 0.4 x 104 particles/cm3), temperature (29 +/- 1 vs 28 +/- 3 degrees C) and relative humidity (63 +/- 10 vs 64 +/- 19%) were similar (P > 0.05 for all) on both study days. During the 2-hour city walk, systolic blood pressure was lower (114 +/- 10 vs 121 +/- 11 mmHg, P < 0.01) when subjects wore a facemask, although heart rate was similar (91 +/- 11 vs 88 +/- 11/min; P > 0.05). Over the 24-hour period heart rate variability increased (SDNN 65.6 +/- 11.5 vs 61.2 +/- 11.4 ms, P < 0.05; LF-power 919 +/- 352 vs 816 +/- 340 ms2, P < 0.05) when subjects wore the facemask., Conclusion: Wearing a facemask appears to abrogate the adverse effects of air pollution on blood pressure and heart rate variability. This simple intervention has the potential to protect susceptible individuals and prevent cardiovascular events in cities with high concentrations of ambient air pollution.

Objective: To estimate the potential cost-effectiveness of a hypothetical test to screen for lymph node metastases in women with newly diagnosed, apparent early stage endometrial cancer., Methods: A decision model was constructed to inform a choice between the following strategies: (1) Usual care, in which the probability of undergoing full surgical staging (29%) is based on literature review; (2) Non-invasive diagnostic testing for metastasis (Testing), in which patients with abnormal test results undergo full surgical staging; (3) 100% referral, in which all patients are referred for full surgical staging. Survival was modeled using Surveillance Epidemiology and End Results (SEER) database. Base case diagnostic test characteristic estimates (sensitivity 0.90, specificity 0.90) were varied for sensitivity analysis. Cost of the diagnostic test was set at $500 and varied; costs of treatment for endometrial cancer (surgery, adjuvant therapies, diagnosis of recurrence, salvage therapies and palliative care) were incorporated., Results: Usual care was the least expensive strategy, while Testing was more expensive and more effective, with an incremental cost-effectiveness ratio (ICER) of $18,785 per year of life saved (YLS) compared to Usual care. 100% referral was the most expensive and most effective strategy, with an ICER of $35,358 per YLS compared to Testing. Results are relatively sensitive to variation in test characteristics and the cost of the diagnostic test but insensitive to cost of treatment and probability of adjuvant therapies. Testing remains cost-effective compared to Usual care unless the usual rate of referral to a Gynecologic Oncologist for full staging exceeds 90%., Conclusions: Given the current low rates of full surgical staging and/or referral to a Gynecologic Oncologist, a diagnostic test to detect nodal metastasis for endometrial cancer has potential to be cost-effective when compared to usual care. Testing is also potentially cost-effective compared to 100% referral at very high test sensitivities and at the lower range of test costs.

A fusion gene, echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK), with transforming activity has recently been identified in a subset of non-small cell lung cancer (NSCLC), but its pathogenetic, diagnostic, and therapeutic roles remain unclear. Both frequency and type of EML4-ALK transcripts were investigated by reverse transcription PCR in 120 frozen NSCLC specimens from Italy and Spain; non-neoplastic lung tissues taken far from the tumor were used as controls. In cases carrying the fusion transcript, we determined EML4-ALK gene and protein levels using fluorescence in situ hybridization, Western blotting, and immunoprecipitation. We also analyzed ALK protein levels in paraffin samples from 662 NSCLC specimens, including the 120 cases investigated in the molecular studies. EML4-ALK transcripts (variants 1 and 3) were detected in 9 of 120 NSCLC samples but were not specific for NSCLC since they were also found in non-cancerous lung tissues taken far from the tumor. Notably, no transcripts were detected in matching tumor samples from these patients. Fluorescence in situ hybridization analysis of cases expressing EML4-ALK transcripts showed that only a minority of cells harbored the EML4-ALK gene. None of these cases was found to express the EML4-ALK protein as examined by immunohistochemistry, Western blotting, and immunoprecipitation. The EML4-ALK transcript cannot be regarded as a specific diagnostic tool for NSCLC. Our results show therefore that the causal role and value of EML4-ALK as a therapeutic target remain to be defined.

Background: Laribacter hongkongensis is a newly discovered, facultative anaerobic, Gram-negative, motile, sea gull-shaped rod associated with freshwater fish borne gastroenteritis and traveler's diarrhea. A highly reproducible and discriminative typing system is essential for better understanding of the epidemiology of L. hongkongensis. In this study, a multilocus sequence typing (MLST) system was developed for L. hongkongensis. The system was used to characterize 146 L. hongkongensis isolates, including 39 from humans and 107 from fish., Results: Fragments (362 to 504 bp) of seven housekeeping genes were amplified and sequenced. Among the 3068 bp of the seven loci, 332 polymorphic sites were observed. The median number of alleles at each locus was 34 [range 22 (ilvC) to 45 (thiC)]. All seven genes showed very low d(n)/d(s) ratios of < 0.04, indicating that no strong positive selective pressure is present. A total of 97 different sequence types (STs) were assigned to the 146 isolates, with 80 STs identified only once. The overall discriminatory power was 0.9861. eBURST grouped the isolates into 12 lineages, with six groups containing only isolates from fish and three groups only isolates from humans. Standardized index of association (I(S)(A)) measurement showed significant linkage disequilibrium in isolates from both humans and fish. The I(S)(A) for the isolates from humans and fish were 0.270 and 0.636, indicating the isolates from fish were more clonal than the isolates from humans. Only one interconnected network (acnB) was detected in the split graphs. The P-value (P = 0) of sum of the squares of condensed fragments in Sawyer's test showed evidence of intragenic recombination in the rho, acnB and thiC loci, but the P-value (P = 1) of maximum condensed fragment in these gene loci did not show evidence of intragenic recombination. Congruence analysis showed that all the pairwise comparisons of the 7 MLST loci were incongruent, indicating that recombination played a substantial role in the evolution of L. hongkongensis. A website for L. hongkongensis MLST was set up and can be accessed at http://mlstdb.hku.hk:14206/MLST&#95;index.html., Conclusion: A highly reproducible and discriminative MLST system was developed for L. hongkongensis.

PCB levels in fish (collected from local rivers), atmosphere and human milk samples have been studied to determine the exposure levels of PCBs for local residents and e-waste workers in Guiyu, a major electronic waste scrapping center in China. The source appointment and correlation analyses showed that homologue composition of PCBs in 7 species of fish were consistent and similar to commercial PCBs Aroclor 1248. PCB levels in air surrounding the open burning site were significantly higher than those in residential area. Inhalation exposure contributed 27% and 93% to the total body loadings (the sum of dietary and inhalation exposure) of the local residents, and e-waste workers engaged in open burning respectively. Total PCB concentrations in human milk ranged from N.D. to 57.6 ng/g lipid, with an average of 9.50 ng/g lipid. The present results indicated that commercial PCBs derived from e-waste recycling are major sources of PCBs accumulating in different environmental media, leading to the accumulation of high chlorinated biphenyls in human beings.

Purpose: Dynamic contrast-enhanced magnetic resonance imaging (MRI) has been established as a valuable tool for the detection of breast cancer. There is evidence suggesting that diffusion-weighted imaging (DWI) may be useful to distinguish between malignant and benign breast lesions. We seek to evaluate the ability of DWI to differentiate between malignant and benign breast lesions at 3 T., Methods: Dynamic contrast-enhanced MRI and DWI of the breasts were performed in 31 female patients (age: mean, 46 years; range, 34-69 years) with suspected breast lesions on mammography and ultrasound using a 3-T scanner (MAGNETOM Tim Trio; Siemens Medical Solutions, Erlangen, Germany). Each lesion was assigned as either malignant or benign, blinded to the results of mammography and ultrasound, according to their imaging characteristics on contrast-enhanced MRI, DWI, and apparent diffusion coefficient (ADC) measurements. Tissue samples were obtained from all lesions by either needle or excision biopsy. Using histological results as the gold standard, the diagnostic accuracies of the dynamic contrast-enhanced MRI, DWI, and ADC were calculated and compared., Results: All breast lesions (n = 31) were identified on both the dynamic contrast-enhanced MRI and DWI scans. The threshold ADC value was determined to be 0.00121 mm2/s, below which a lesion was considered malignant. The sensitivities/specificities of the dynamic contrast-enhanced MRI, qualitative DWI, and quantitative ADC were 95%/91%, 95%/63.6%, and 90%/91%, respectively. The differences in sensitivities, specificities, positive and negative predictive values, and diagnostic accuracies between the 3 examinations were statistically insignificant., Conclusions: Diffusion-weighted imaging at 3 T is highly sensitive in the detection of malignant breast lesions even with qualitative assessment alone, whereas ADC measurement offers quantitative assessment and increases the specificity to more than 90%. Further studies involving a larger cohort size and a wider spectrum of breast lesions are indicated.

Bioaccessibility of organic pollutants in food is important for exposure estimation and risk assessment. An in vitro enzyme digestion experiment was carried out to analyze the bioaccessibility of PCBs in different foods including freshwater fish (bighead carp and oriental weather fish) and vegetables (spinach and cabbage). The results indicated that the bioaccessibility of PCBs in freshwater fish (3%) was much lower than that in leafy vegetables (25%). Based on field survey, the daily exposure TEQ value from these two types of food was 17.9 pg/kg bw/day. However, when bioaccessibility was taken into consideration, the value decreased to 0.61 pg/kg bw/day. Therefore, the forms of PCBs existing in food strongly influenced the bioavailability for humans, which may have important implications on dietary exposure. To our knowledge, this is the first paper to illustrate the bioaccessibility of PCBs in different foods using an in vitro digestion method.

Distinguishing follicular variant of papillary carcinoma (FVPC) from follicular adenoma and follicular carcinoma can be difficult if nuclear features of papillary carcinoma are not well developed or only focally present. We assessed interobserver and intraobserver agreement among 6 thyroid experts by using 15 cases in which original pathologists suspected FVPC. There was unanimous expert agreement in diagnosing FVPC in only 2 cases (13%) and majority agreement in 6 cases (40%). Unanimous agreement on benign and malignant diagnoses was seen in 4 cases (27%) and majority agreement on malignancy in 8 cases (53%). Intraobserver agreement ranged from 17% to 100%. Histologic features considered most helpful in diagnosing FVPC were nuclear clearing, nuclear grooves, nuclear overlapping and crowding, nuclear membrane irregularity, and nuclear enlargement. This considerable interobserver and intraobserver variability in the diagnosis of FVPC seems to result from lack of agreement on the minimal criteria needed to diagnose FVPC, even among experts.

To determine independent prognostic factors for the survival of patients with endometrial stromal sarcoma (ESS), data were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute from 1988 to 2003. Kaplan-Meier and Cox proportional hazards models were used for analyses. Of 831 women diagnosed with ESS, the median age was 52 years (range: 17-96 years). In total, 59.9% had stage I, 5.1% stage II, 14.9% stage III, and 20.1% had stage IV disease. Overall, 13.0, 36.1, and 34.7% presented with grades 1, 2, and 3, respectively. Patients with stage I-II vs III-IV disease had 5 years DSS of 89.3% vs 50.3% (P<0.001) and those with grades 1, 2, and 3 cancers had survivals of 91.4, 95.4, and 42.1% (P<0.001). In multivariate analysis, older patients, black race, advanced stage, higher grade, lack of primary surgery, and nodal metastasis were independent prognostic factors for poorer survival. In younger women (<50 years) with stage I-II disease, ovarian-sparing procedures did not adversely impact survival (91.9 vs 96.2%; P=0.1). Age, race, primary surgery, stage, and grade are important prognostic factors for ESS. Excellent survival in patients with grade 1 and 2 disease of all stages supports the concept that these tumors are significantly different from grade 3 tumors. Ovarian-sparing surgeries may be considered in younger patients with early-stage disease.

We report 3 cases of a previously uncharacterized form of histiocytosis presenting in early infancy and showing ALK immunoreactivity. The patients presented with pallor, massive hepatosplenomegaly, anemia, and thrombocytopenia. Liver biopsy showed infiltration of the sinusoids by large histiocytes with markedly folded nuclei, fine chromatin, small nucleoli, and voluminous lightly eosinophilic cytoplasm that sometimes was vacuolated or contained phagocytosed blood cells. One patient developed cutaneous infiltrates that morphologically resembled juvenile xanthogranuloma. The histiocytes were immunoreactive for histiocytic markers (CD68, CD163, lysozyme), S100 protein, ALK (membranous and cytoplasmic pattern), and dendritic cell markers (fascin, factor XIIIa), but not CD1a and langerin. One case successfully analyzed by molecular techniques revealed TPM3-ALK fusion. Thus the spectrum of diseases exhibiting ALK translocation should be expanded to include ALK(+) histiocytosis. The disease in the 3 patients (2 having been given chemotherapy) resolved slowly over many months.

Purpose of Review: The significant increase in cutaneous melanomas over the past 30 years has led to studies resulting in advances in their diagnosis, staging, surgical treatment, and adjuvant therapies. Similar approaches have been investigated in patients with far rarer malignant melanomas of the female genital tract. This review will summarize the current state of knowledge on the incidence, causes, presenting symptoms, prognostic factors, therapeutic approaches, and outcomes, site-by-site, for primary melanomas of the vulva, vagina, urethra, ovary, and the uterine cervix., Recent Findings: Surgery remains the initial treatment of choice for localized melanomas of the female genital tract, with less radical, organ function preserving resections demonstrating similar control rates compared with more radical surgical approaches in vulva and possibly vaginal melanomas. Radiation therapy may play a role in the treatment of patients with close resection margins, regional nodal metastasis, or unresectable tumors. Sentinel lymph node studies, positron emission tomography and computed tomography scans for staging and evaluation of response, and adjuvant chemo or biochemotherapy warrant further investigation., Summary: The results of treatment for female genital tract melanomas remain poor. Although surgery remains the initial treatment of choice for localized disease, adjuvant local-regional, and systemic therapies are needed.

Objective: To evaluate demographics, survival, and surgical trends for patients with malignant ovarian germ cell tumors., Methods: SEER data abstracted from 1988 to 2001 and analyzed using Kaplan-Meier and Cox regression models., Results: Of 760 patients, the median age was 23 years. Seventy-six percent of patients presented with stage I-II disease, and 24% with stage III-IV. Fifty-five percent were immature teratomas, 32% dysgerminomas, and 13% yolk sac tumors. Fertility-preserving surgery was performed in 41.2% (n = 313) of patients. In those <45 years old, the use of fertility-preserving surgery increased from 40.5% to 44.5% to 48.4% over the time periods 1988-1992, 1993-1997, 1998-2001 (P = 0.25). The survival of patients who underwent fertility-preserving surgery was not statistically different compared to those who underwent standard surgery (P = 0.26). Patients with stage I-II disease had improved survival compared to stage III-IV disease (97.6% vs. 85.5%, P < 0.001). The overall survival of women with dysgerminomas, immature teratomas, and yolk sac tumors was 99.5%, 94.3%, and 85.4%, respectively (P < 0.001). In multivariate analysis, older age, advanced stage, and yolk sac tumor histology predicted for poorer survival., Conclusion: Our data suggests that the use of fertility-preserving surgery with concomitant surgical staging for germ cell cancers has increased without compromising survival.

IgG4-related sclerosing disease is a recently recognized inflammatory lesion frequently involving pancreas, submandibular gland, lacrimal gland, and lymph node. We report 3 cases of ocular adnexal lymphoma arising in IgG4-related chronic sclerosing dacryoadenitis, a phenomenon that has not been previously reported. The patients presented with bilateral or unilateral ocular adnexal mass usually present for many years. One patient also had asymptomatic diffuse lymphadenopathy. Two patients had biopsy-proven IgG4-related chronic sclerosing dacryoadenitis before the current presentation, and 1 had systemic involvement by IgG4-related sclerosing disease as evidenced by increased IgG4+ cells in a prior nasopharyngeal biopsy. Two cases showed features of extranodal marginal zone lymphoma of mucosa-associated lymphoid-tissue type (1 with large cell transformation) and 1 follicular lymphoma. Thus, the lymphoid hyperplasia of IgG4-related sclerosing disease can provide a substrate for the emergence of lymphoma. In addition, we report 3 cases of ocular adnexal extranodal marginal zone B-cell lymphoma that show sclerosing inflammation in the background and numerous IgG4+ monotypic plasma cells. In the absence of prior biopsies or information on serum IgG4 titer, it is unclear whether these cases represent lymphoma complicating IgG4-related sclerosing disease or de novo lymphoma. Nonetheless, these cases are distinctive in that the neoplastic cells express IgG4 (light chain restricted), whereas unselected cases of ocular adnexal lymphomas do not show IgG4 expression.

Objective: To compare the clinico-pathologic characteristics and survival of women with clear cell versus other epithelial ovarian cancers., Methods: Data were obtained from the Surveillance, Epidemiology and End Results Program between 1988 and 2001 and analyzed using Kaplan-Meier and Cox proportional hazards models., Results: Of 28,082 women with epithelial ovarian cancer, 1411 (5%) had clear cell, 13,835 (49.3%) papillary serous, 3655 (13%) endometrioid, 2711 (9.7%) mucinous, and 6470 (23%) had unspecified histologies. The median age of overall patients was 64 years; with clear cell patients presenting at younger age (55 years). The proportion of clear cell histology was significantly higher in Asians versus Whites, Blacks, and others (11.1% versus 4.8%, 3.1%, and 5.5%; p<0.001). Clear cell carcinoma is more likely to be diagnosed at early-stage (67.3%) compared to 19.2% in serous, 61.6% endometrioid, and 61.3% in mucinous carcinomas (p<0.005). Retroperitoneal lymph node metastases were found in 13.6% of serous carcinomas, 7.9% clear cell, 7.3% endometrioid, and 3.8% of mucinous (p<0.001). Adjusted for stage, the 5-year disease-specific survival of patients with clear cell carcinoma is worse compared to serous: 85.3% vs. 86.4% for stage I, 60.3% vs. 66.4% stage II, 31.5% vs. 35.0% stage III, and 17.5% vs. 22.2% for stage IV, respectively (p<0.001). On multivariate analysis, age, stage, grade, histology, and surgical treatment were independent predictors of disease-specific survival., Conclusions: Our data suggest that women with clear cell ovarian cancer present at a younger age, are more likely to be Asian, and have a poorer prognosis compared to serous cancers.

Background: The purpose was to identify the factors predictive of recurrence and survival in patients with high-risk (stage I, grade 3; stage IC, stage II, or clear cell) epithelial ovarian cancer after adjuvant therapy., Methods: Data was extracted from patients who underwent primary surgery followed by adjuvant therapy in 2 randomized trials by the Gynecologic Oncology Group (Protocols 95 and 157). Kaplan-Meier survival estimates and Cox proportional hazards model adjusted for covariates were used for analyses., Results: Of 506 patients (median age = 56.2 years), 347 (68.6%) had stage I and 159 (31.4%) had stage II cancers. The 5-year recurrence-free (RFS) and overall survivals (OS) were 75.5% and 81.7%, respectively. On multivariate analysis, older age, higher stage, higher grade, and malignant cytology were independent prognostic factors predictive for recurrence and poorer survival. The risk of recurrence was higher for those >/=60 versus < 60 years (hazards ratio [HR] = 1.57, 95% confidence interval [CI], 1.12-2.19), stage II (stage II: HR = 2.70, 95% CI, 1.41-5.16) versus stage IA or IB, grade 2 (HR = 1.84, 95% CI, 1.04-3.27) and grade 3 (HR = 2.47, 95% CI, 1.39-4.37) versus grade 1, and positive versus negative cytology (HR = 1.72, 95% CI, 1.21-2.45). By using these factors in a prognostic index, those with low-risk (no or 1 risk factor), intermediate-risk (2 factors), and high-risk (3-4 risk factors) disease had survivals of 88%, 82%, and 75%, respectively (P < .05)., Conclusions: Age, stage, grade, and cytology are important prognostic factors in high-risk early-stage epithelial ovarian cancer. This information may be used in the design of future clinical trials., ((c) 2008 American Cancer Society.)

IgG4-related sclerosing disease is a recently recognized syndrome characterized by mass-forming lesions in exocrine glands or extranodal tissues due to lymphoplasmacytic infiltrates and sclerosis, a raised serum IgG4 level and increased IgG4+ plasma cells in the involved tissues. We report the morphologic features of the enlarged regional (n=3) and nonregional lymph nodes (n=3) in patients with this syndrome. The patients presented with autoimmune pancreatitis, lymphoplasmacytic sclerosing cholangitis, chronic sclerosing dacryoadenitis, or chronic sclerosing sialadenitis. The histologic features of the lymph nodes could be categorized into 3 patterns: Castleman diseaselike, follicular hyperplasia, and interfollicular expansion by immunoblasts and plasma cells. The percentage of IgG4+/IgG+ plasma cells was markedly elevated (mean 62% vs. 9.9% in 54 control lymph nodes comprising a wide variety of reactive conditions). We also report 6 cases of primary lymphadenopathy characterized by increased IgG4+/IgG+plasma cells (mean 58%). These cases share many clinical and pathologic similarities with IgG4-related sclerosing disease. In fact, 2 of these patients developed lymphoplasmacytic sclerosing cholangitis or lacrimal and submandibular gland involvement during the clinical course. These cases therefore probably represent primary lymph node manifestation of the disease. The importance of recognition of the lymphadenopathic form of IgG4-related sclerosing disease lies in the remarkable response to steroid therapy, and the potential of mistaking the disease for lymphoma either clinically or histologically.

The objective of this study is to determine the progress and trends in the treatment and survival of women with early-stage (I-II) epithelial ovarian cancer. Data were obtained from the SEER database between 1988 and 2001. Kaplan-Meier and Cox regressions methods were employed for statistical analyses. Of the 8372 patients, the median age was 57 years (range: 12-99 years). A total of 6152 patients (73.4%) presented with stage I and 2220 (26.5%) with stage II disease. Over the periods 1988--1992, 1993--1997, and 1998-- 2001, 3-year disease-specific survivals increased from 86.1 to 87.2 to 88.8% (P=0.076). The number of patients that underwent lymphadenectomy has increased significantly from 26.2 to 38.7 to 54.2% over the study period (P<0.001). Of those patients who underwent staging procedures with lymphadenectomy, there was no improvement in survival over the three study periods (from 93.2 to 93.5 to 93.1%; P=0.978). On multivariate analysis, younger age, nonclear cell histology, earlier stage, lower grade, surgery, and lymphadenectomy were significant independent prognostic factors for improved survival. After adjusting for surgical staging with lymphadenectomy, the year of diagnosis was no longer an important prognostic factor. In conclusion, the use of lymphadenectomy during surgery for early-stage ovarian cancer has doubled over the last 14 years. The marginal improvement in survival demonstrated over time is potentially attributed to the increased use of staging procedures with lymphadenectomy.

Context: Nasopharyngeal carcinoma (NPC), common in southern China and North Africa, has a complex etiology involving interplay between viral, environmental, and hereditary factors and is almost constantly associated with the Epstein-Barr virus. Since the prognosis of locally advanced and metastatic diseases is poor, increased understanding of the pathogenesis of NPC would be important for discovering novel markers for patients' management., Objectives: To compare the proteomic expression profile between an Epstein-Barr virus-associated NPC cell line (C666-1) and a normal NP cell line (NP69). The proteins with differential expression were analyzed in 40 undifferentiated NPC paraffin-embedded specimens., Design: Differentially expressed proteins discovered between the two cell lines were identified by mass spectrometry. After confirmation by immunocytochemical staining, their expression in patient samples was measured using 40 pairs of undifferentiated NPCs together with their adjacent normal epithelia., Results: Proteomic findings indicated that adenosine triphosphate synthase alpha chain was up-regulated, whereas annexin II, annexin V, beta(2)-tubulin, and profilin 1 were down-regulated. After confirming the results in agar-processed cell lines, annexin II and beta(2)-tubulin expression were found to be lower in tumor cells than in adjacent normal epithelial cells in 100% and 90% of the patients' specimens, respectively. Finally, annexin II down-regulation was positively associated with lymph node metastasis, suggesting that it may be a prognostic factor in NPC., Conclusions: The results suggest that annexin II and beta(2)-tubulin down-regulation is important in NPC formation and may represent potential targets for further investigations.

Objectives: To evaluate the feasibility of whole body imaging using a 3 Tesla magnetic resonance scanner without a contrast agent, and to study the prevalence of abnormal findings among a cohort of asymptomatic doctors., Design: Prospective study., Setting: Private hospital, Hong Kong., Participants: A total of 132 asymptomatic medical doctors (111 men, 21 women), with a mean age of 56 (range, 38-82) years, volunteered for the study. They underwent corresponding whole body imaging at our hospital between October 2005 and February 2006. Imaging involved a 3 Tesla magnetic resonance scanner with 32 channels, parallel imaging, Total Imaging Matrix technology, a maximum gradient amplitude of 40 mT/m and a slew rate of 200 mT/m/ms (Magnetom Tim Trio, Siemens Medical Solution, Erlangen, Germany). The use of matrix coils enabled coverage of the whole body. No contrast agent was used., Main Outcome Measures: Detection of abnormalities in asymptomatic, apparently healthy adults., Results: All examinations were completed successfully. The mean scan time per subject was 33 (standard deviation, 4) minutes. All subjects tolerated the examination well and overall imaging quality was satisfactory. A total of 124 (94%) subjects had positive findings, of whom 24 (18%) had further workup. Five (4%) subjects were found to have tumours, of which two (1.5%) were proven malignant. Our cancer detection rate was comparable to that of other reported whole body screening studies using contrast magnetic resonance imaging and positron emission tomography., Conclusion: We demonstrated the feasibility of performing whole body imaging in 30 minutes, using 32-channel magnetic resonance imaging at 3 Tesla without a contrast agent or any ionising radiation.

Here we report an unusual case of mixed Wilms' tumour and angiosarcoma in a 38-year-old female patient who presented with haematuria and right lower back pain. A computed tomographic (CT) scan confirmed a massive renal tumour associated with extensive retroperitoneal lymph node involvement, bony metastases and a right hip fracture. She was initially managed with palliative nephrectomy, which was followed by rapid postoperative deterioration. Histopathology revealed differentiated adult Wilms' tumour with renal angiosarcoma, whereas the pathology of the para-aortic lymph node and bone metastasis revealed angiosarcoma only. In view of her cachexia and cytopaenia, emergency chemotherapy was initiated using a modified regimen of carboplatin, etoposide and vincristine (CEO) in preference to the more traditional but less well-tolerated VAC (vincristine, actinomycin D, cyclophosphamide). Four cycles of this protocol yielded a dramatic response on re-staging CT scan. This case suggests that highly angiogenic tumours such as angiosarcoma may be effectively palliated using agents usually reserved for refractory Wilms' tumour, and supports the view that adult Wilms' tumour is more sensitive to such agents.

Micrometastases in lymph nodes and blood may provide important prognostic information. In this study, cytokeratin 20 (CK20) positive cells in lymph nodes and circulating CK20 mRNA were studied using 57 paraffin-embedded lymph node specimens and blood from 24 patients with pN0 colorectal cancer (CRC), respectively. Results showed that 29 out of 56 (52%) lymph node specimens had CK20-positive cells (range: 1-35). Follow-up of the patients for 12 months indicated that 4 patients (7%) had CRC metastases to liver, lung, and bone. In addition, 8 out of 24 (33%) samples had at least 2-fold circulating CK20 mRNA expression higher than the pooled normal sample. This study provides evidence that CK20-positive cells were found in the lymph nodes and differentially expressed circulating CK20 mRNA was also detected in the blood from patients with pN0 CRC. Long-term follow-up is necessary to study their prognostic use in patients with non-metastatic CRC.

EBV-associated T/natural killer (NK)-cell lymphoproliferative disorder (EBV-T/NK LPD) of children and young adults is generally referred to with the blanket nosological term of severe chronic active EBV infection (CAEBV). This disease is rare, associated with high morbidity and mortality, and appears to be more prevalent in East Asian countries. But because there is no grading or categorization system for CAEBV, pathologists and clinicians often disagree regarding diagnosis and therapy. EBV-T/NK LPD includes polyclonal, oligoclonal, and monoclonal proliferation of cytotoxic T and/or NK cells. Moreover, a unique disease previously described as infantile fulminant EBV-associated T-LPD has been identified and overlaps with EBV-T/NK LPD. In the present review a clinicopathological categorization of EBV-T/NK LPD is proposed, based on pathological evaluation and molecular data, as follows: (i) category A1, polymorphic LPD without clonal proliferation of EBV-infected cells; (ii) category A2, polymorphic LPD with clonality; (iii) category A3, monomorphic LPD (T-cell or NK cell lymphoma/leukemia) with clonality; and (iv) category B, monomorphic LPD (T-cell lymphoma) with clonality and fulminant course. Categories A1, A2, and A3 possibly constitute a continuous spectrum and together are equivalent to CAEBV. Category B is the exact equivalent of infantile fulminant EBV-associated T-LPD. It is expected that this categorization system will provide a guide for the better understanding of this disorder. This proposal was approved at the third meeting of the Asian Hematopathology Association (Nagoya, 2006).

Purpose: To identify the characteristics of phase II studies that predict for subsequent "positive" phase III trials (those that reached the proposed primary end points of study or those wherein the study drug was superior to the standard regimen investigating targeted agents in advanced tumors., Methods: We identified all phase III clinical trials of targeted therapies against advanced cancers published from 1985 to 2005. Characteristics of the preceding phase II studies were reviewed to identify predictive factors for success of the subsequent phase III trial. Data were analyzed using the chi(2) test and logistic regression models., Results: Of 351 phase II studies, 167 (47.6%) subsequent phase III trials were positive and 184 (52.4%) negative. Phase II studies from multiple rather than single institutions were more likely to precede a successful trial (60.4% v 39.4%; P < .001). Positive phase II results were more likely to lead to a successful phase III trial (50.8% v 22.5%; P = .003). The percentage of successful trials from pharmaceutical companies was significantly higher compared with academic, cooperative groups, and research institutes (89.5% v 44.2%, 45.2%, and 46.3%, respectively; P = .002). On multivariate analysis, these factors and shorter time interval between publication of phase II results and III study publication were independent predictive factors for a positive phase III trial., Conclusion: In phase II studies of targeted agents, multiple- versus single-institution participation, positive phase II trial, pharmaceutical company-based trials, and shorter time period between publication of phase II to phase III trial were independent predictive factors of success in a phase III trial. Investigators should be cognizant of these factors in phase II studies before designing phase III trials.

Background: The objectives of the current study were to determine the prognostic factors associated with disease-specific survival (DSS) and to analyze the role of lymphadenectomy (LND) and oophorectomy in the management of uterine leiomyosarcomas (LMS)., Methods: Data were abstracted from the Surveillance, Epidemiology, and End Results database (1988-2003). Kaplan-Meier and Cox proportional hazards regression models were used for analyses., Results: The median age of the 1396 patients was 52 years. There were 951 patients (68.1%) with International Federation of Gynecology and Obstetrics (FIGO) stage I disease, 43 patients (3.1%) with stage II disease, 99 patients (7.1%) with stage III disease, and 303 patients (21.7%) with stage IV disease. Distribution by tumor grade included 87 patients with grade 1 tumors, 208 with grade 2, and 509 patients with grade 3 tumors. The 5-year DSS rates for patients with stage I, II, III, and IV disease were 75.8%, 60.1%, 44.9%, and 28.7%, respectively. Lymph node metastases were identified in 23 of 348 patients (6.6%) who underwent LND. The 5-year DSS rate was 26% in patients who had positive lymph nodes compared with 64.2% in patients who had negative lymph nodes (P < .001). Of 341 patients aged <50 years with stage I or II disease, 240 (70.4%) underwent oophorectomy. There was no difference in 5-year DSS based on oophorectomy. On multivariate analysis, older age at diagnosis, more recent year of diagnosis, African-American race, higher tumor grade, higher stage of disease, and lack of primary surgical treatment all were associated significantly with worse survival., Conclusions: Independent predictors of DSS in patients with uterine LMS included age, race, stage, grade, and primary surgery. Oophorectomy was not found to have an independent impact on survival., (Cancer 2008. (c) 2008 American Cancer Society.)

Objective: The purpose of this study was to evaluate the role of surgical staging in patients with grade 1 endometrioid uterine cancer., Study Design: Data were extracted from Surveillance, Epidemiology, and End Results Program from 1988 to 2001. Kaplan-Meier and Cox proportional hazards analyses were used to determine predictors for disease-specific survival., Results: Twelve thousand seven hundred and twelve women were reported with endometrioid carcinoma, including 3867 with grade 1 disease, of which 25.5% had stage IC or more advanced disease, 15.4% with disease extending beyond the uterine corpus, 7.3% with extrauterine metastases, and 3.3% with lymph node metastases. On multivariate analysis, younger age and earlier stage remained as significant prognostic factors for improved survival., Conclusion: Since grade 1 endometrioid uterine cancers have a 15.4% risk of extrauterine spread, a complete surgical staging procedure is recommended when clinically feasible. Younger age and earlier stage are significant prognostic factors for improved survival.

Purpose of Review: We review the demographic and clinicopathologic characteristics, and prognosis of women diagnosed with uterine papillary serous carcinoma, with a focus on clinical management., Recent Findings: Pathologic evaluation of postmenopausal bleeding is preferred for patients who fit the profile of a high-risk endometrial cancer such as uterine papillary serous carcinoma. Women diagnosed with endometrial cancer who fit this profile and all women with uterine papillary serous carcinoma should undergo comprehensive surgical staging and aggressive cytoreduction of extrauterine disease. Adjuvant therapy remains controversial. Several recent investigations reported on the potential benefit of adjuvant chemotherapy, with many recommending additional loco-regional radiation., Summary: Despite the lack of randomized trials on uterine papillary serous carcinoma, several recent reports have provided insight into the diagnosis, surgical management, and adjuvant treatment of this high-risk endometrial cancer.

Objective: To compare the racial differences in treatment and survival of epithelial ovarian cancer patients., Methods: Data were obtained from the Surveillance, Epidemiology, and End Results Program between 1988 and 2001 and analyzed using Kaplan-Meier methods and Cox proportional hazards regression., Results: Of the 24,038 women, 22,407 (93.2%) were non-Hispanic White, and 1,631 (6.8%) were African-American. Median age of Whites versus African-Americans was 65 versus 63 years, respectively (P < 0.001). Of the patients with early-stage (I-II) disease, 38.8% of Whites underwent lymphadenectomy with their primary surgery compared to only 32.8% of African-Americans (P = 0.005). In the overall study group, the 5-year disease-specific survival of Whites was significantly higher compared to the African-Americans (44.1% vs. 40.7%, P = 0.001). On multivariable analysis, age, race, stage, cell type, and grade of disease were all independent prognostic factors for survival., Conclusion: Our data suggest that race is an independent prognostic factor for survival in epithelial ovarian cancer. In addition, African-Americans with early-stage cancer were less likely to undergo lymphadenectomy with their staging procedure. Furthermore, patient/physician education is needed to increase the number of patients undergoing surgical staging procedures for epithelial ovarian cancer.

Objective: The purpose of this study was to determine factors responsible for the increasing number of deaths from corpus cancer over three time periods., Study Design: Data were collected from the Surveillance, Epidemiology and End Results database from 1988-2001. Kaplan-Meier and Cox proportional hazards regression analyses were performed., Results: Of 48,510 women with corpus cancer, there was an increase in the proportion of patients dying from advanced cancers (52.1% to 56.0% to 68.8%; P < .001), grade 3 disease (47.5% to 53.3% to 60.6%; P < .001), serous tumors (14.3% to 18.4% to 16.6%; P < .001), and sarcomas (19.1% to 20.4% to 27.2%; P < .001) over time. On multivariate analysis, older age, African American race, lack of primary staging procedures, advanced-stage, high-grade, and non-endometrioid histology were independent prognostic factors for worse survival., Conclusion: Our data suggest that the increase in mortality in women with corpus cancer over the last 14 years may be related to an increased rate of advanced-stage cancers and high-risk histologies.

An unusual case of small bowel obstruction in a patient with "virgin abdomen" was successfully diagnosed and the localized pathology was elucidated by a computed tomography scan, and the case was successfully treated by laparoscopy.

We present a case of autoimmune lymphoproliferative syndrome (ALPS) caused by a previously undescribed minimal deletion in the death domain of the FAS gene. ALPS is an uncommon disease associated with an impaired Fas-mediated apoptosis. The patient presented with a history of splenomegaly since 4 months of age, associated with cervical lymphadenopathy, which improved with oral corticosteroid treatment. Relevant laboratory findings were the presence of anemia, thrombocytopenia, and positive direct and indirect Coombs tests. He was not an offspring of consanguineous parents. Two cervical lymph node biopsies were performed, at 4 years and at 6 years of age. In both lymph nodes, there was marked paracortical expansion by lymphocytes in variable stages of immunoblastic transformation and a very high cell proliferating index. Some clear cells were also present, raising the suspicion of malignant lymphoma. In one of the lymph nodes, there was also a focus rich in large histiocytes with round nuclei and emperipolesis, consistent with focal Rosai-Dorfman disease. Immunostaining showed numerous CD3+ cells, many of which were double-negative (CD4- CD8-) and expressed CD57, especially around the follicles. Molecular studies of the lymph node biopsy showed a point deletion (4-base pair deletion) in exon 9 of the FAS gene (930del TGCT), which results in 3 missense amino acids.