Prognostic impact of circumferential resection margin in esophageal cancer with or without neoadjuvant chemoradiotherapy.

The prognostic impact of circumferential resection margin (CRM) in surgically resected esophageal squamous cell carcinoma (ESCC) has been controversial. This investigation assessed the prognostic impact of CRM in surgically resected pathologic T3 ESCC patients with or without neoadjuvant chemoradiotherapy (nCRT). We reviewed consecutive p/yp T3 ESCC patients undergoing esophagectomy from two medical centers between January 2009 and December 2016. The cohort was divided into two groups: upfront esophagectomy (upfront surgery) and nCRT followed by esophagectomy (nCRT + surgery). CRM status was assessed and divided into CRM > 1 mm, 0 < CRM < 1 mm, and tumor at CRM. A total of 217 p/yp T3 ESCC patients undergoing esophagectomy (138 patients in the upfront surgery group and 79 in the nCRT + surgery group) were enrolled. In the upfront surgery group, patients with 0 < CRM < 1 mm showed equivalent overall survival to those with CRM > 1 mm (log-rank P = 0.817) and significantly outlived those with tumor at CRM (log-rank P < 0.001). However, in the nCRT + surgery group, CRM > 1 mm failed to show survival superiority to CRM between 0 and 1 mm or involved by cancer (log-rank P = 0.390). In conclusion, a negative CRM, even though being <1 mm, is adequate for pT3 ESCC patients undergoing upfront esophagectomy. In contrast, the CRM status is less prognostic in ypT3 ESCC patients undergoing nCRT followed by esophagectomy.

Allergic rhinitis, rather than asthma, is a risk factor for dental caries.

OBJECTIVES: The association between AS (asthma) and dental caries is controversial, while that between allergic rhinitis (AR) and caries has not been established. This study aimed to verify the relationship among AR, AS and dental caries. DESIGN: Retrospective cohort study. SETTING: Data from Health Insurance Database of the Taiwan's National Health Insurance Research Database. PARTICIPANTS: Nine thousand and thirty-eight children born in 2004 were obtained. Their claims data were evaluated from birth to the age of 9 years. MAIN OUTCOME MEASURES: The frequencies of clinical visits for dental caries were calculated for primary teeth (age 1-5) and for dental transitional period (age 6-9). Differences in the frequencies of clinical visits for caries in AR vs non-AR and AS vs non-AS children were compared. Correlation between AR, AS and caries frequencies was studied, and the influences of AR drugs on the development of caries were evaluated. RESULTS: After adjusting for confounding factors and AS case, the frequencies of clinical visits for caries were higher in AR (increased by 13%-25% and P<.001 at different age periods). The AR frequencies significantly correlated with caries frequencies in children with AR. Different AR drugs also correlated with caries formation. After adjusting for confounding factors and AR case, there was no relationship between AS and caries in children. CONCLUSION: Asthma is not associated with dental caries, but AR can increase the frequency of clinical visits for caries. Medications for AR may also play a role in caries formation. Thus, AR may be a risk factor for childhood dental caries.

Differentiation of bacteria cell wall using Raman scattering enhanced by nanoparticle array.

We have fabricated surface-enhanced Raman scattering (SERS) substrates based on arrays of silver nanoparticles grown on porous anodic alumina templates. Using this nanotechnology platform, label-free and high-speed detection of bacteria are achieved. SERS spectra of various bacteria including Staphylococcus Aureus (Gram-positive bacterium), Klebsiella Pneumoniae (Gram-negative bacterium), and Mycobacterium Smegmatis (Mycobacterium) were recorded. The highly reproducible SERS-based technological platform is capable of differentiating different kinds of bacteria by PCA, LDA, clustering analysis, and SVM methods, which provides promising opportunity for biosensing of clinical microbes.

Host Genetic Associations with Salivary Microbiome in Oral Cancer.

Despite the growing recognition of a host genetic effect on shaping gut microbiota composition, the genetic determinants of oral microbiota remain largely unexplored, especially in the context of oral diseases. Here, we performed a microbiome genome-wide association study in 2 independent cohorts of patients with oral squamous cell carcinoma (OSCC, n = 144 and 67) and an additional group of noncancer individuals (n = 104). Besides oral bacterial dysbiosis and signatures observed in OSCC, associations of 3 loci with the abundance of genus-level taxa and 4 loci with ß diversity measures were detected (q < 0.05) at the discovery stage. The most significant hit (rs10906082 with the genus Lachnoanaerobaculum, P = 3.55 × 10-9 at discovery stage) was replicated in a second OSCC cohort. Moreover, the other 2 taxonomical associations, rs10973953 with the genus Kingella (P = 1.38 × 10-9) and rs4721629 with the genus Parvimonas (P = 3.53 × 10-8), were suggestive in the meta-analysis combining 2 OSCC cohorts. Further pathway analysis revealed that these loci were enriched for genes in regulation of oncogenic and angiogenic responses, implicating a genetic anchor to the oral microbiome in estimation of casual relationships with OSCC. Our findings delineate the role of host genotypes in influencing the structure of oral microbial communities.

Impact of HOTAIR Gene Polymorphism and Environmental Risk on Oral Cancer.

Genetic and acquired factors are thought to be interrelated and imperative to estimate the risk and prognosis of oral squamous cell carcinoma (OSCC). HOX transcript antisense intergenic RNA ( HOTAIR) plays crucial roles in gene regulation and is regulated in a variety of cancers. Polymorphisms in HOTAIR have been recently linked to the predisposition to diverse malignancies. In the present study, we aimed to evaluate the influences of HOTAIR gene polymorphisms, combined with environmental triggers, on the susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms of the HOTAIR gene- rs920778, rs1899663, rs4759314, and rs12427129-were tested in 1,200 control participants and 907 patients with OSCC. We detected a significant association of rs1899663 with the risk of OSCC (adjusted odds ratio, 2.227; 95% confidence interval [95% CI], 1.197 to 4.146; P = 0.012) after adjustment for 3 potential confounders: smoking, betel quid chewing, and alcohol consumption. In further analyses where habitual exposure to each of 3 environmental factors was excluded, we found that, in addition to rs1899663, non-betel quid users who carried the polymorphic allele of rs920778 were more prone to develop OSCC than were those homozygous for wild-type allele (TC: odds ratio [OR], 1.472; 95% CI, 1.069 to 2.029; P = 0.018; TC+CC: OR, 1.448; 95% CI, 1.060 to 1.977; P = 0.020). Moreover, in exploring the relationship between HOTAIR gene polymorphisms and the clinical status of only patients with OSCC who were non-betel quid chewers (excluding the advanced clinical stage), we found that rs920778 and rs4759314 were correlated with the development of large-size tumors (OR, 1.891; 95% CI, 1.027 to 3.484; P = 0.04) and increased lymph node metastasis (OR, 4.140; 95% CI, 1.785 to 9.602; P = 0.001), respectively. Further functional assessments link rs920778 to the regulation of HOTAIR expression and epigenetic status. Our results reveal an interactive effect of HOTAIR gene polymorphisms and betel quid chewing on the development and progression of oral cancer.

Life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy.

BACKGROUND: Limited data are available on the life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy (HAART). AIM: To provide such an estimate using a semi-parametric projection. DESIGN: Statistical analysis. METHODS: Follow-up data for patients newly diagnosed with HIV infection in Taiwan (HIV/AIDS Cohort) from 1 May 1997 to 30 April 2003 (n = 3351, only 1% are injecting drug users) were analysed using the Kaplan-Meier method. The survival function for an age- and gender-matched reference population was generated by the Monte Carlo method from the life-table of the general population. A constant excess hazard model was used to project long-term survival of HIV-infected patients, with linear extrapolation of a logit-transformed curve of survival ratio between HIV-infected patients and the reference population. RESULTS: The 5-year survival rate was 58% in patients who had already developed AIDS at diagnosis (AIDS group), and 89% in those who had not (non-AIDS group). Extrapolation yielded an expected mean survival time of 10.6 years after diagnosis for the AIDS group, and 21.5 years after diagnosis for the non-AIDS group. DISCUSSION: Our results support the expansion of HIV screening programs to minimize delay in diagnosis. With continuing advances in HAART, this estimate of survival in initially asymptomatic patients may be conservative. Their long life expectancy raises questions about what kind of preventive heath services should be offered. These should be addressed through further analysis of overall benefit and cost-effectiveness.

Immunological diagnosis of IgD paraprotein.

IgD monoclonal peaks are relatively small, with broad bases, and are preferentially of gamma-1 or beta mobility. Often IgDgamma paraproteins can only be detected after proper dilution or reduction of the patient's serum. Assay for Bence Jones protein should not be neglected, and if it is present, the co-existence of IgD monoclonal gammopathy should be suspected.

The study of anticardiolipin antibodies and interleukin-6 in cerebrospinal fluid and blood of Chinese patients with systemic lupus erythematosus and central nervous system involvement.

Anticardiolipin (ACL) antibodies and interleukin-6 (IL-6) in cerebrospinal fluid (CSF) may be involved in the mechanism of lupus patients with central nervous system (CNS) involvement. ACL antibodies of 3 isotypes and IL-6 were measured in paired CSF and serum samples from 14 lupus patients with CNS involvement, 5 lupus patients without CNS involvement and 7 patients with non-inflammatory neurological diseases. ACL antibodies, IgG and IgM isotypes, and IL-6 were significantly increased in CSF from lupus patients with CNS involvement as compared with other 2 groups of patients. Both ACL antibodies and IL-6 decreased after neurological activity subsided. These results suggest increased ACL antibodies and IL-6 in CSF are involved in immune responses within CNS in lupus patients. Quantitation of CSF ACL antibodies may be helpful in evaluating neurological activity of lupus patients with CNS involvement.

Experiences in thoracoscopic sympathectomy for axillary hyperhidrosis and osmidrosis: focusing on the extent of sympathectomy.

HYPOTHESIS: A more selective sympathectomy can improve the outcome of axillary hyperhidrosis and osmidrosis and minimize the potential sequelae. DESIGN: Retrospective cohort. SETTING: Tertiary care center. PATIENTS: Between July 1, 1996, and May 30, 2000, 171 patients with axillary hyperhidrosis and osmidrosis were studied. INTERVENTIONS: T3-4 sympathectomies were performed in 40 patients (group 1), T4 sympathectomies were performed in 56 patients (group 2), and T4-5 sympathectomies were performed in 75 patients (group 3). MAIN OUTCOME MEASURES: The surgical outcomes were evaluated by direct patient interview in the outpatient clinic or by telephone or mail questionnaires. The results were categorized as excellent (significant or complete disappearance of symptoms), good (>/=50% improvement), or poor (<50% improvement). RESULTS: There were no surgical mortalities in this study. Twenty-eight group 1 patients (70%), 16 group 2 patients (29%), and 22 group 3 patients (29%) developed compensatory perspiration (P<.001). Six group 1 patients (15%), 1 group 2 patient (2%), and 1 group 3 patient (1%) developed dry hands (P =.02). In the group 1 patients, the surgical outcomes were excellent in 21 (52%), good in 6 (15%), and poor in 13 (32%). In the group 2 patients, the surgical outcomes were excellent in 29 (52%), good in 10 (18%), and poor in 17 (30%). In the group 3 patients, the surgical outcomes were excellent in 53 (71%), good in 11 (15%), and poor in 11(15%) (P =.04). (Percentages may not sum to 100 because of rounding.) CONCLUSION: T4-5 sympathectomies provide higher patient satisfaction rates in treating axillary hyperhidrosis and osmidrosis, with fewer sequelae.

Systemic delivery of enkephalin peptide through eyes.

Leu-enkephalin is one of the important peptides which could become useful drugs in the clinics because of its analgesic action and its availability in mass quantity through biotechnology production. It is found in this study that enkephalin can be effectively absorbed systemically through eyes without using a surfactant as absorption enhancer. Enkephalin at 0.125% (31.25 micrograms/25 microliter) reached a plateau of blood concentration at 11.5 ng/ml in 3-4 hrs and stayed high for 8-9 hrs. In contrast, the blood concentration of enkephalin declined rapidly after i.v. administration with a T1/2 of less than 30 min and reached the lowest point at 22 ng/ml in 5 hrs. With higher concentrations at 1% (.25 mg/25 microliter) and 5% (1.25 mg/25 microliter) similar absorption kinetics was observed except that they reached higher plateau of blood concentration at 72 ng/ml and 233 ng/ml, respectively.

Anticardiolipin antisera from lupus patients with seizures reduce a GABA receptor-mediated chloride current in snail neurons.

The effects of circulating anticardiolipin (ACL) antisera in lupus patients on the LP5 central neuron of snail were studied. Both GABA and glutamate increased a chloride conductance of the LP5 neuron. The ACL antisera decreased the GABA-elicited responses in a concentration dependent manner while it had no effect on glutamate-elicited responses. The ACL antisera affected neither the resting membrane current, nor the membrane conductivity of neuron. Antisera without the activity of anticardiolipin did not decrease the GABA-elicited responses. The seizure incidence of the patients with higher ACL antisera levels is also higher. It is concluded that ACL antisera inhibited the GABA ionophore receptor complex in a snail central neuron.

Anticardiolipin antibodies and interleukin-6 in cerebrospinal fluid and blood of Chinese patients with neuro-Behçet's syndrome.

Anticardiolipin antibodies of the IgG, IgM and IgA isotypes and soluble IL-6 were measured in paired serum and cerebrospinal fluid samples from five patients with neuro-Behçet's syndrome. Another five patients with non-inflammatory neurological diseases were also studied as a control group. Anticardiolipin antibodies, especially the IgM isotype, and IL-6 were highly elevated in the cerebrospinal fluid of patients with neuro-Behçet's. Levels of both IgM isotype anticardiolipin antibodies and IL-6 in the cerebrospinal fluid dropped after disease activity subsided. These results suggest that the increase in IgM isotype anticardiolipin antibodies and IL-6 in cerebrospinal fluid may be involved in the immune response of neuro-Behçet's within the central nervous system. Serial measurements of IgM isotype anticardiolipin antibodies and IL-6 in the cerebrospinal fluid may be useful in evaluating disease activity in neuro-Behçet's.

Improvement of systemic absorption of insulin through eyes with absorption enhancers.

A painless, simple, and practical method has been developed for systemic delivery of peptide drugs through eyes. In order to increase the amount of peptides absorbed into systemic circulation, effects of enhancers on insulin absorption into systemic circulation and reduction of blood glucose concentration have been studied. Saponin showed the highest potency to enhance insulin absorption, while Tween 20 was the least effective. The efficacy order of seven compounds studied can be arranged as follows: saponin greater than fusidic acid greater than BL-9 = EDTA greater than glycocholate = decamethonium greater than Tween 20. Since 1% of saponin reached the maximum effect to enhance insulin absorption and decrease blood glucose concentration, not more than 1% of saponin should be used for enhancing peptide absorption through eyes.

Epstein-Barr virus-associated antibodies and serum biochemistry in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma is difficult to diagnose in its early stages. It also has frequent recurrences and/or distant metastases after radiotherapy. Extensive clinical, serological and biochemical studies were done during 1980-1982 on 351 patients to aid in the diagnosis of the disease, especially with recurrence or metastasis. Seropositive rates of the antibody titers against viral capsid antigens (VCA) and early antigens (EA) of Epstein-Barr virus (EBV) in IgG and IgA classes were 41.7%-100%. They ranked, in order of frequency: anti-VCA/IgA, anti-VCA/IgG, anti-EA/IgG, and anti-EA/IgA. Mean total serum IgG and IgA levels were moderately increased in all patients. Serum GOT, GPT, alkaline phosphatase, lactate dehydrogenase and mucoprotein were elevated either alone or in combination in a few patients before treatment, in many patients with recurrence or metastases, and in all patients with liver metastasis.

Molecular biology of human immunodeficiency virus type 1.

Since the discovery of human immunodeficiency virus (HIV) as the etiologic agent of acquired immune deficiency syndrome (AIDS) more than a decade ago, tremendous progress has been made in various aspects of this virus and its interplay with the host immune system. The advent of potent combination therapy has made it possible to achieve effective and durable control of HIV-1 replication in vivo, yet the persistence of the latent reservoirs pose a new challenge. The recent identifications of several cellular proteins interacting with different viral gene products have not only shed new insights into our understanding of the HIV-1 and the host cell biology, but also provided the bases for developing novel strategies to block HIV-1 replication. It is from this perspective that we review the current understanding of the molecular mechanisms governing the HIV-1 life cycle.

Comparison between the right side and subxiphoid bilateral approaches in performing video-assisted thoracoscopic extended thymectomy for myasthenia gravis.

BACKGROUND: This study aimed to compare the efficacy of the right thoracoscopic (RtT) approach and the subxiphoid bilateral thoracoscopic (SxBiT) approach in performing thymectomy for myasthenia gravis. METHODS: Between March 2001 and April 2003, 27 myasthenic patients were enrolled in this prospective study. The operations were conducted by two surgical teams in a single institute. The surgical procedures included RtT for 12 patients and SxBiT for 15 patients. The operation time, resected thymus weights, and thoracic drainage periods were compared. RESULTS: Subxiphoid video-assisted thoracoscopic extended thymectomy (SxVATET) and right-side thoracoscopic extended thymectomy (RtVATET) were performed for 27 consecutive myasthenic patients. The mean operation time, weights of resected specimens, and duration of hospital stay for the SxVATET and RtVATET groups were, respectively, 151.3 min (range, 120-200 min) versus 191.5 min (range, 120-225 min) (p = 0.0012), 73.3 g (range, 40-90 g) versus 50.8 g (range, 5-90 g) (p = 0.0029), and 3.1 days (range, 2-4 days) versus 3.8 days (range, 2-4 days) (p = 0.914). Ten patients (37%) had complete remission, observed during a mean follow-up period of 18.5 months (range, 6-30 months). CONCLUSIONS: During this consecutive experience, both the RtT and SxBiT approaches showed satisfactory results for nonthymomatous myasthenic patients. However, a better view of the bilateral pleural cavities and more radical thymectomy could be achieved only by the SxBiT approach.

Expression of apoptosis-regulating proteins p53, Bcl-2, and Bax in primary resected esophageal squamous cell carcinoma.

Apoptosis plays a key role in the pathogenesis, aggressiveness, and therapy responsiveness of cancer. Proteins of the Bcl-2 family as well as p53 are important regulators of apoptosis. The present study retrospectively examines the expression of apoptosis-regulating proteins in primary resected esophageal squamous cell carcinoma (ESCC) and the correlation between the outcome of patients' treatment and the expression of the proteins. We used antibodies specific for the human p53, Bcl-2 and Bax proteins to examine the expression of these apoptosis-regulating proteins in 40 archival specimens of patients with primary resected esophageal squamous cell carcinoma. The overall expression of p53, Bcl-2, and Bax was 73%, 18%, and 100%, respectively. No significant correlations were found between the expression of p53, Bcl-2, and Bax. The expression of Bcl-2 had a negative influence on survival in this population of primary resected ESCC patients (p=0.03). But no differences in survival were observed in relation to the expression of p53 or Bax. In conclusion, Bcl-2 expression may provide additional and prognostic information for the clinical course of the disease and therefore to be developed as a prognostic indicator for primary resected esophageal squamous cell carcinoma.

Circulating intercellular adhesion molecules-1 and autoantibodies including anti-endothelial cell, anti-cardiolipin, and anti-neutrophil cytoplasma antibodies in patients with vasculitis.

Circulating intercellular adhesion molecule-1 (ICAM-1) and 3 types of autoantibodies were measured in 30 patients with angiographical or pathological proved vasculitis. There were 18 patients with systemic vasculitis and 12 patients with cutaneous vasculitis. The measured antibodies included anti-endothelial cell antibodies (AECA), anti-cardiolipin (ACL) antibodies of 3 isotypes and anti-neutrophil cytoplasma antibodies (ANCA). The results showed that patients with systemic vasculitis had elevated levels of ICAM-1, AECA and IgG isotype antibody as compared with none or lower in patients with cutaneous vasculitis. Levels of ICAM-1 and IgG isotype ACL antibodies also decreased significantly after disease activity subsided in patients with systemic vasculitis. Measurement of ICAM-1 and autoantibodies may be useful in evaluating the extent of involvement and in following the disease activity of patients with vasculitis.

The study of circulating CD5 positive B lymphocytes in Chinese patients with rheumatoid arthritis.

Circulating CD5+ B lymphocytes were studied in 39 Chinese patients with rheumatoid arthritis (RA). Blood cells were stained with anti-CD5 and anti-CD19 monoclonal antibodies and were analyzed by flow cytometry. The results showed that there was no elevation of CD5+ B cells in RA patients when compared with 41 healthy control subjects. The circulating levels of CD5+ B cell correlated neither with serum titers of rheumatoid factor (RF) nor with disease activities in these patients. The CD5+ B cell levels remained relatively constant after a serial follow-up for 12 months. The similar pattern of epitope density of CD5 antigens also existed in the same patients. Although most studies in Caucasians revealed increased levels of CD5+ B cells in RA patients, measurements of this marker were not useful for the evaluation of disease activities in Chinese patients. Levels of CD5+ B cells may reflect more individual genetic background and may play a minor role in the flare-up of activities in Chinese patients with RA.

Timing and necessity of endoscopy in AIDS patients with dysphagia or odynophagia.

BACKGROUND/AIMS: Dysphagia and odynophagia are common problems with significant morbidity in acquired immunodeficiency syndrome (AIDS) patients. Endoscopy in AIDS patients with esophageal symptoms is valuable for diagnosis, but the timing and necessity of routine endoscopy remains controversial. METHODOLOGY: We retrospectively studied 40 AIDS patients undergoing upper gastrointestinal endoscopy. Among them, 25 patients were enroled with dysphagia and/or odynophagia and were put on empirical fluconazole treatment before endoscopic evaluation. RESULTS: Fourteen (56%) of 25 patients improved after fluconazole treatment, while 11 patients had persistent symptoms. Among the 14 patients with symptomatic improvement, 7 were found to have esophageal candidiasis which improved after continuation of fluconazole for 1-2 more weeks. The other 7 patients had a normal endoscopic appearance. In contrast, among 11 patients with persistent symptoms, there were 3 patients with azole-resistant candidiasis, 3 with cytomegalovirus esophagitis, 1 with herpes simplex virus esophagitis with candidiasis, 1 with Kaposi's sarcoma, and 3 with idiopathic esophageal ulcer. They were successfully treated with Amphotericin B, Ganciclovir, Acyclovior, and oral steroids, except for the patient with Kaposi's sarcoma. CONCLUSIONS: Routine endoscopy may not necessarily be indicated in every AIDS patient with dysphagia or odynophagia. Empirical fluconazole treatment can improve symptoms in 50% of patients. It is only indicated when patients have persistent symptoms after empirical treatment. With endoscopic examination, etiologic agents other than common candidiasis can be determined and the patients can thus be put on specific treatment.