Sialendoscopic removal of metastatic adenocarcinoma in a mucous plug from Stensen's duct.

Sialendoscopy is a minimally invasive technique used mainly in the diagnosis and treatment of obstructive salivary gland disorders. There has yet to be a report on its use in the diagnosis of metastatic disease. While metastatic cancer has been described in numerous head and neck anatomic subsites, it has not been reported to be found in a mucous plug in Stensen's duct. Sialendoscopy was performed in a 68-year-old female patient who presented with symptoms of ductal obstruction. Basket removal of a mucous plug was done and histopathological analysis of this specimen found adenocarcinoma. The overall clinical picture, imaging, and final histopathological results suggested that this patient had metastatic breast carcinoma to a mucous plug in Stensen's duct, the diagnosis of which was made with the aid of interventional sialendoscopy. This is the first report in which metastatic cancer was identified in a mucous plug in Stensen's duct. Sialendoscopy can be a useful tool to aid in the diagnosis of metastatic diseases in rare and unusual clinical situations.

Oral Epstein-Barr virus-positive mucocutaneous ulcer: gingival presentation of a benign lymphoproliferative lesion.

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a benign lymphoproliferative lesion related to iatrogenic or age-related immunosuppression in patients with prior Epstein-Barr virus (EBV) infection. Although the clinical presentation may resemble malignant disease, the course of EBVMCU is indolent, and regression is expected when immunosuppression is reduced. We present a case of EBVMCU in the gingiva of a 59-year-old male patient with long-standing pemphigus vulgaris. The initial presentation was suspicious for oral cavity cancer, which was ruled out by biopsy. After reduction of immunosuppression, the ulceration regressed and an area of exposed necrotic bone remained. Complete healing was achieved after sequestrectomy and primary closure with a local gingival flap.

Concordance of immune checkpoints within tumor immune contexture and their prognostic significance in gastric cancer.

Checkpoint blockade therapy has emerged as a novel approach for cancer immunotherapy in several malignancies. However, patient prognosis and disease progression relevant to immune checkpoints in gastric tumor microenvironment are not defined. This study aims to investigate the expression and prognostic significance of immune checkpoints within gastric cancer. In the study, a cohort of 398 cancer tissues from stage I to IV gastric cancer patients were assessed for programmed cell death 1 ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) infiltration using immunohistochemistry to ascertain their survival correlation. The data revealed that higher TIL density correlated with less risk of disease progression, and exhibited survival benefits in gastric cancer patients, and PD-L1 positivity showed a significant association with the presence of high TIL infiltration. Furthermore, real-time quantitative polymerase chain reaction was performed to detect expression of multiple immune checkpoints with the relation to clinical outcome in 139 samples randomly selected from the same cohort, and higher messenger RNA levels of most immune checkpoints were associated with favorable outcome, while consistently showing a positive correlation with interferon gamma levels. In situ hybridization was used to determine the localization of Epstein-Barr virus (EBV) in 97 specimens, and showed EBV-positive gastric cancer samples correlated with PD-L1 expression and increased TIL density. These results suggest that induction of immune checkpoint within gastric cancer patients reflects a high immune infiltration density, especially in those with EBV-associated gastric cancer, which may direct patient selection for checkpoint blockade therapy.

Under pressure: a contribution to the pathogenesis of acquired ileal atresia.

An acquired ileal atresia is a rare occurrence. A 3-week-old neonate is presented, who developed postnatally a type 2 ileal atresia and an ileal stenosis within a pre-existing internal hernia secondary to an adhesion band. The literature reports a total of eight cases (4 females) with acquired ileal atresia in babies ranging in age from 3 weeks to 2 years (median 4 months). Mechanical forces (eg, adhesion band, intussusception and volvulus) onto the intestine are most frequently (75%) implicated as the primary event. The distal ileum is most often affected and a type 3A atresia is identified in six of eight (75%) cases.

Reference ranges for lymphocyte subsets among healthy Hong Kong Chinese adults by single-platform flow cytometry.

Race, age, sex, and environmental conditions have significant impacts on lymphocyte subset values. It is important to establish the local reference ranges from healthy and non-HIV-positive adults in the local population for clinical decision making. In this study, the reference ranges for lymphocyte subsets among Chinese adults were established by analysis by single-platform flow cytometry of the lymphocyte compositions of 273 healthy adult blood donors between 17 and 59 years of age. The 95% reference ranges for CD3(+) T cells, CD3(+) CD4(+) T helper cells, and CD3(+) CD8(+) T suppressor cells are 723 to 2,271 cells/µl, 396 to 1,309 cells/µl, and 224 to 1,014 cells/µl, respectively. The 95% reference ranges for CD19(+) B cells and CD56(+) NK cells are 118 to 645 cells/µl and 61 to 607 cells/µl, respectively. Significant gender and age differences in the lymphocyte subsets have been demonstrated. Our results have also shown that the T-lymphocyte compositions in Hong Kong Chinese were comparable to those of other Asian populations but were different from those of Caucasians.

Extremely low exposure of a community to severe acute respiratory syndrome coronavirus: false seropositivity due to use of bacterially derived antigens.

Estimates of seropositivity to a new infectious agent in a community are useful to public health. For severe acute respiratory syndrome (SARS), the figures are conflicting. Herein, we screened 12,000 people in a community stricken by SARS 10 months previously and found 53 individuals (0.44%) who had immunoglobulin G antibodies to the SARS coronavirus (SARS-CoV) nucleocapsid (N) produced in bacteria. However, only seven of these (group 1) had sera which also reacted with the native N antigen expressed in SARS-CoV-infected Vero cells, N-transfected 293T cells, and tissues of infected SARS patients. Of these, six individuals had had SARS previously. The remaining person, as well as the 46 other individuals (group 2), were healthy and had no history of SARS. Group 1 antibodies recognized epitopes located slightly differently in N from those of group 2 antibodies, and a mouse hybridoma antibody resembling the former type was generated. Unusually, group 2 antibodies appeared to recognize cross-reactive bacterial epitopes that presumably were posttranslationally modified in eukaryotes and hence were probably not induced by SARS-CoV or related coronaviruses but rather by bacteria. The N antigen is thus highly unique. The extremely low rate (0.008%) of asymptomatic SARS infection found attests to the high virulence of the SARS-CoV virus.

Specific epitopes of the structural and hypothetical proteins elicit variable humoral responses in SARS patients.

BACKGROUND: Severe acute respiratory syndrome (SARS) is an infectious disease which was caused by a novel coronavirus (SARS-CoV). SARS has caused an outbreak in the world during 2003 and 2004, with 8098 individuals being infected and a death toll of 774 in 28 regions around the world. Specific humoral responses to viral infection remain unclear. OBJECTIVE: To analyse the antigenicity of the SARS-CoV genome and identify potential antigenic epitopes in the structural proteins. METHODS: Potential antigenic epitopes were identified in the structural proteins (nucleocapsid, membrane, spike, and small envelope proteins) and hypothetical proteins (SARS3a, 3b, 6, 7a, and 9b) that are specific for SARS-CoV. A peptide chip platform was created and the profiles of antibodies to these epitopes were investigated in 59 different SARS patients' sera obtained 6-103 days after the onset of the illness. Serial sera from five additional patients were also studied. RESULTS: Epitopes at the N-terminus of the membrane protein and the C-terminus of nucleocapsid protein elicited strong antibody responses. Epitopes on the spike protein were only moderately immunogenic but the effects were persistent. Antibodies were also detected for some putative proteins, noticeably the C-termini of SARS3a and SARS6. CONCLUSIONS: Important epitopes of the SARS-CoV genome that may serve as potential markers for the viral infection are identified. These specific antigenic sites may also be important for vaccine development against this new fatal infectious disease.

Stromal nitric oxide synthase (NOS) expression correlates with the grade of mammary phyllodes tumour.

BACKGROUND: Nitric oxide synthase (NOS), particularly endothelial and inducible forms (e/i-NOS), are expressed in various cancers, including breast cancer. In mammary fibroepithelial lesions, NOS expression in stromal cells has been reported to be lower in fibroadenomas than in phyllodes tumours. AIMS: To investigate NOS expression in phyllodes tumours of varying degrees of malignancy. METHODS: One hundred and sixty seven mammary phyllodes tumours (97 benign, 47 borderline malignant, and 23 frankly malignant) were evaluated for e-NOS and i-NOS expression by immunohistochemistry. Correlations with previously reported expression of stromal vascular growth factor (VEGF) and microvessel density were also performed. RESULTS: Stromal expression of e-NOS was absent, weak, moderate, and strong in 43%, 31%, 13%, and 13% of benign tumours; 17%, 26%, 13%, and 44% of borderline malignant tumours; and 17%, 35%, 13%, and 35% of frankly malignant tumours, respectively. Stromal expression of i-NOS was 77%, 18%, 4%, and 1% in benign tumours; 42%, 28%, 19%, and 11% in borderline malignant tumours; and 43%, 13%, 26%, and 18% in frankly malignant tumours, respectively. Stromal expression of both i-NOS and e-NOS was significantly different between the benign and malignant (borderline and frank) groups of phyllodes tumours (p < 0.0001). Furthermore, the expression of i-NOS correlated with stromal VEGF expression and microvessel density. The expression of NOS in the epithelial cells was strong, and showed no differences between the different groups of tumours. CONCLUSIONS: Higher stromal expression of NOS in phyllodes tumours is associated with malignancy, suggesting a possible role in malignant progression, particularly metastasising potential.

Constitutional activation of IL-6-mediated JAK/STAT pathway through hypermethylation of SOCS-1 in human gastric cancer cell line.

The interleukin-mediated Janus kinase (JAK)/STAT pathway plays a crucial role in carcinogenesis. Recently, increased STAT3 activity was found in hepatocellular carcinoma and multiple myeloma in which there was silencing of SOCS-1 (suppressor of cytokine signalling-1) by gene promoter hypermethylation. We investigated the expression level of interleukin-6 (IL-6) and SOCS-1 in gastric cancer cell lines. Expression of SOCS-1 correlated with IL-6 level in most of the cell lines, except for AGS cells in which SOCS-1 was absent despite a high level of IL-6 production. Methylation analysis by methylation-specific polymerase chain reaction and bisulphite sequencing revealed that CpG island of SOCS-1 was densely methylated in AGS cells. Demethylation treatment by 5'aza-deoxycytidine restored SOCS-1 expression and also suppressed constitutive STAT3 phosphorylation in AGS cells. Moreover, methylation of SOCS-1 was detected in 27.5% (11 of 40) of primary gastric tumours samples, 10% (one of 10) of adjacent noncancer tissues but not in any (zero of nine) normal gastric mucosa. Methylation of SOCS-1 also correlated with the loss of mRNA expression in some primary gastric cancers. In conclusion, this is the first report to demonstrate that hypermethylation of SOCS-1 led to gene silencing in gastric cancer cell line and primary tumour samples. Downregulation of SOCS-1 cooperates with IL-6 in the activation of JAK/STAT pathway in gastric cancer.

Sputum cytology of patients with severe acute respiratory syndrome (SARS).

BACKGROUND: Severe acute respiratory syndrome (SARS) is a newly described form of atypical pneumonia linked to a novel coronavirus. AIMS: To review the sputum cytology of 15 patients who fulfilled the World Health Organisation clinical criteria for SARS in an attempt to evaluate whether early diagnosis is feasible with routine sputum examination. METHODS: All sputum samples from patients with SARS from the four major hospitals in Hong Kong were reviewed; abnormalities were sought in the cellular component, including abnormal numbers and morphology of the component cells compared with those from age matched controls taken over the same period one year ago. RESULTS: Fifteen sputum samples from patients were compared with 25 control samples. In the patients with SARS, loose aggregates of macrophages were seen more frequently in the sputum. These macrophages frequently showed morphological changes, such as cytoplasmic foaminess, vacuole formation, and nuclear changes (including multinucleation and a ground glass appearance) when compared with the control samples. CONCLUSIONS: The cytological features of SARS are non-specific, but the observation of any of the described features should prompt further investigations, especially in patients with suspicious clinical features.

Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS).

BACKGROUND: Severe acute respiratory syndrome (SARS) became a worldwide outbreak with a mortality of 9.2%. This new human emergent infectious disease is dominated by severe lower respiratory illness and is aetiologically linked to a new coronavirus (SARS-CoV). METHODS: Pulmonary pathology and clinical correlates were investigated in seven patients who died of SARS in whom there was a strong epidemiological link. Investigations include a review of clinical features, morphological assessment, histochemical and immunohistochemical stainings, ultrastructural study, and virological investigations in postmortem tissue. RESULTS: Positive viral culture for coronavirus was detected in most premortem nasopharyngeal aspirate specimens (five of six) and postmortem lung tissues (two of seven). Viral particles, consistent with coronavirus, could be detected in lung pneumocytes in most of the patients. These features suggested that pneumocytes are probably the primary target of infection. The pathological features were dominated by diffuse alveolar damage, with the presence of multinucleated pneumocytes. Fibrogranulation tissue proliferation in small airways and airspaces (bronchiolitis obliterans organising pneumonia-like lesions) in subpleural locations was also seen in some patients. CONCLUSIONS: Viable SARS-CoV could be isolated from postmortem tissues. Postmortem examination allows tissue to be sampled for virological investigations and ultrastructural examination, and when coupled with the appropriate lung morphological changes, is valuable to confirm the diagnosis of SARS-CoV, particularly in clinically unapparent or suspicious but unconfirmed cases.

Pulmonary tumour microembolism clinically mimicking alveolitis.

A 56 year old man with previously unsuspected recurrence of squamous cell carcinoma of the oesophagus presented with dyspnoea. Bronchoscopy and computed tomography suggested bronchopneumonic changes with an infectious cause. He suffered a rapidly deteriorating course and died despite active treatment, including antibiotics and mechanical ventilation. Necropsy revealed a florid pulmonary tumour microembolism mimicking alveolitis. No bronchopneumonia was seen. The emboli arose from loosely attached tumour vegetations in the tricuspid valve. In a patient with known malignancy, tumour microembolism should be considered as an uncommon cause of rapid respiratory failure, refractory to antibiotic treatment.