Tumor dormancy resulting from subcutaneous injection to SCID mice with cultured nasopharyngeal carcinoma cells is mediated via IFN-γ induction of a highly differentiated phenotype.

The mechanisms underlying tumor dormancy in human primary lesions and bone marrow metastases of nasopharyngeal carcinoma (NPC) are still not completely understood. The aim of this study was to determine differences in the fates of cultured primary NPC (P-NPC) cells, interferon-γ-transduced primary NPC (IFN-γ-P-NPC) cells, bone marrow metastatic NPC (BM-NPC), and IFN-γ-transduced BM-NPC (IFN-γ-BM-NPC) cells following xenotransplantation into these four groups of SCID mice through subcutaneous injection of 5×10(6) cells/site/animal (4 animals/group). The injected mice were monitored for tumor development at the sites of injection. In only the group injected with IFN-γ-P-NPC cells, the resulting nodules remained small throughout the 60-day observation period after injection, but gradually became palpably prickly. Histopathological examination revealed that these lesions invariably consisted of mostly structures of horny pearls and keratin bridges with occasional apoptotic and degenerative cells. In contrast, animals injected with nontransduced-P-NPC cells developed tumors progressively with occasional central necroses. In the two groups injected with IFN-γ-NPC-BM and NPC-BM cells, progressive growths of tumors were noted, with the latter being at slightly faster rates, whereas the xenografts of both groups showed a poorly differentiated phenotype with abundant vascularity. The study results highlight the high susceptibility of P-NPC but not BM-NPC following IFN-γ gene transfer to the induction of tumor dormancy, which is mediated via induced cell differentiation. Thus, induced cell differentiation could provide a new mechanism by which tumor dormancy is induced.

Induction of metastatic cancer stem cells from the NK/LAK-resistant floating, but not adherent, subset of the UP-LN1 carcinoma cell line by IFN-γ.

As an advanced status of cancer stem cells (CSCs), metastatic CSCs (mCSCs) have been proposed to be the essential seeds that initiate tumor metastasis. However, the biology of mCSCs is poorly understood. In this study, we used a lymph node (LN) metastatic CEA-producing carcinoma cell line, UP-LN1, characterized by the persistent appearance of adherent (A) and floating (F) cells in culture, to determine the distribution of CSCs and mechanisms for the induction of mCSCs. F and A cells displayed distinct phenotypes, CD44(high)/CD24(low) and CD44(low)/CD24(high), respectively. The CSC-rich nature of F cells was typified by stronger expression of multiple drug resistance genes and a 7.8-fold higher frequency of tumor-initiating cells in NOD/SCID mice when compared with A cells. F cells showed a greater depression in HLA class I expression and an extreme resistance to NK/LAK-mediated cytolysis. Moreover, the NK/LAK-resistant F cells were highly susceptible to IFN-γ-mediated induction of surface CXCR4, with concomitant downregulation of cytoplasmic CXCL12 expression, whereas these two parameters remained essentially unchanged in NK/LAK-sensitive A cells. Following the induction of surface CXCR4, enhanced migratory/invasive potential of F cells was demonstrated by in vitro assays. Confocal immunofluorescence microscopy showed the two distinct phenotypes of F and A cells could be correspondingly identified in monodispersed and compact tumor cell areas within the patient's LN tumor lesion. In response to IFN-γ or activated NK/LAK cells, the CXCR4(+) mCSCs could be only induced from the CSCs, which were harbored in the highly tumorigenic CD44(high)/CD24(low) F subset. Our results revealed the complexity and heterogeneity of the CSC of this cell line/tumor and the differential immunomodulatory roles of F and A cells. A better understanding of the interactions among different classes of CSCs and their niches may assist us in eradicating the CSCs/mCSCs through targeted immunotherapy, chemotherapy, or both.

Differential baseline and response profile to IFN-gamma gene transduction of IL-6/IL-6 receptor-alpha secretion discriminate primary tumors versus bone marrow metastases of nasopharyngeal carcinomas in culture.

BACKGROUND: Understanding of immunobiology of bone marrow metastases (designated BM-NPC) versus primary tumors (P-NPC) of the nasopharynx is far from complete. The aim of this study was to determine if there would be differences between cultured P-NPCs and BM-NPCs with respect to (i) constitutive IL-6 and the IL-6 receptor gp80 subunit (IL-6Ralpha) levels in the spent media of nontransduced cells, and (ii) IL-6 and IL-6Ralpha levels in the spent media of cells transduced with a retroviral vector containing the IFN-gamma gene. METHODS: A panel of NPC cell lines were transduced with the IFN-gamma gene through a retroviral vector. Four clonal sublines were isolated via limiting dilution methods. Cytofluorometric analysis was performed for the detection of cell surface antigens of HLA class I, HLA class II and ICAM-1. ELISA was used to assay for IFN-gamma, IL-6 and IL-6Ralpha in the spent media of cultured cell lines. RESULTS: Our results showed that in day 3 culture supernatants, low levels of soluble IL-6 were detected in 5/5 cultured tumors derived from P-NPCs, while much higher constitutive levels of IL-6 were detected in 3/3 metastasis-derived NPC cell lines including one originated from ascites; the difference was significant (p = 0.025). An inverse relationship was found between IL-6Ralpha and IL-6 in their release levels in cultured P-NPCs and metastasis-derived NPCs. In IFN-gamma-transduced-P-NPCs, IL-6 production increased and yet IL-6Ralpha decreased substantially, as compared to nontransduced counterparts. At variance with P-NPC cells, the respective ongoing IL-6 and IL-6Ralpha release patterns of BM-NPC cells were not impeded as much following IFN-gamma transduction. These observations were confirmed by extended kinetic studies with representative NPC cell lines and clonal sublines. The latter observation with the clonal sublines also indicates that selection for high IL-6 or low IL-6Ralpha producing subpopulations did not occur as a result of IFN-gamma-transduction process. P-NPCs, which secreted constitutively only marginal levels of IFN-gamma (8.4 ~ 10.5 pg/ml), could be enhanced to produce higher levels of IFN-gamma (6.8- to 10.3-fold increase) after IFN-gamma transduction. Unlike P-NPCs, BM-NPCs spontaneously released IFN-gamma at moderate levels (83.8 ~ 100.7 pg/ml), which were enhanced by 1.3- to 2.2-fold in the spent media of their IFN-gamma-transduced counterparts. CONCLUSION: Our results showed that cultured P-NPCs and BM-NPCs could be distinguished from one another on the basis of their differential baseline secretion pattern of IFN-gamma, IL-6 and IL-6Ralpha, and their differential response profiles to IFN-gamma gene transfer of the production of these three soluble molecules. These results suggest that the IL-6 and IFN-gamma pathways in a background of genetic instability be involved in the acquisition of metastatic behaviour in BM-NPCs.

Computed tomography findings of gossypiboma.

Gossypiboma is composed of non-absorbable surgical material with a cotton matrix. Gossypiboma is usually under-reported and is a severe medicolegal issue. Thus, we describe the computed tomography (CT) findings of gossypiboma in our institution. From January 2003 to June 2006, gossypibomas diagnosed in our institution and their data regarding sex, age, previous operation, location, the interval between the operation and the diagnosis of gossypiboma, clinical presentation, indication of CT, CT findings and further management were collected. There were 6 cases of gossypiboma, 4 men and 2 women. Three of our cases had previous chest surgery and the other 3 cases had previous abdominal surgery. The locations of 3 (50%) cases were in the left anterior subphrenic space. The mean interval between original operation and diagnosis was 24.6 +/- 33.4 months (range, 17 days to 8 years). With regard to CT findings, 3 (50%) cases had an isodense mass and 3 (50%) had a typical mass containing curvilinear opaque structures. The mean size of the gossypibomas was 62 x 62 x 67 mm. Because gossypiboma is due solely to human factors and is a severe medicolegal issue, continuous education should be considered.

Tracheal incision for elective tracheotomy in oral cavity cancer.

The aim of this prospective study was to compare operative procedure and postoperative complications between horizontal tracheal incision and window-type tracheal excision for elective tracheotomy in patients with oral cavity cancer. Between February 2003 and April 2004, 40 patients with advanced-stage oral cavity cancer were consecutively seen at our tumor clinic. All patients underwent elective tracheotomy before wide excision of the tumor and free flap reconstruction. Either horizontal tracheal incision (H group) or window-type tracheal excision (W group) was randomly carried out in two groups comprising 20 patients each. The post-tracheotomy tracheal stenosis was evaluated by tracheal computed tomography (CT) coupled with advantage workstation 4.0 software for reconstruction. Both groups had the following similar characteristics: age, gender, tracheotomy days, or interval between decannulation and CT scan evaluation. However, the incision time was statistically less in the H group (16.4s) compared with the W group (43.4s). Tracheal stenosis was found in five patients (25%) in the H group and four patients (20%) in the W group, with no significant differences. Nevertheless, neither dyspnea or stridor after decannulation, difficulty in tube exchange, nor accidental extrusion was reported in either groups. The horizontal incision for elective tracheotomy is simpler and faster than the window-type tracheal excision. The complication rate is not significantly different in both groups. We therefore, recommend using horizontal incision for elective tracheotomy in patients with oral cavity cancer.

Utility of ambulatory pH monitoring and videofluoroscopy for the evaluation of patients with globus pharyngeus.

Globus pharyngeous is not an uncommon disorder. The precise pathophysiology remains unclear. The aim of this study was to assess the clinical value of videofluoroscopy and ambulatory pH monitoring in patients with globus pharyngeus. Twenty-three patients (11M/12F, age range = 21-74 yr, mean = 50 yr) with globus pharyngeus entered the study. Radiographic examination of the pharynx and esophagus included videofluoroscopy and static radiography. A dual probe to measure the proximal and distal intraesophageal pH was inserted for 24 h. The results of dual-probe pH monitoring were normal in all patients. Videofluoroscopic results were abnormal in 8 patients, with 5 patients having laryngeal aspiration, 2 having stasis of barium in the vallecula and pyriform sinuses, and 4 having poor pharyngeal elevation. Cervical osteophytes were found in 13 patients with a frequent location at the C5-6 level. Ambulatory pH monitoring seemed to be less helpful for the evaluation of globus pharyngeus without reflux-like symptoms. Pharyngeal dysfunction is detected in a substantial proportion of patients by videofluoroscopy and radiography.

Immunophenotypic and molecular cytogenetic features of the cell line UP-LN1 established from a lymph node metastasis of a poorly-differentiated carcinoma.

A lymph node metastatic cell line (UP-LN1) was established in vitro from a poorly-differentiated epithelial tumor, and characterized for immunobiological and molecular cytogenetic profiles. The morphology of UP-LN1 cells when grown as monolayers was unique in that, apart from typical colonies of adherent epithelial cells, many loosely attached round cell colonies emerged on and around the patches of epithelial cells. By means of immunofluorescence/flow cytometric analysis, UP-LN1 cells showed selective expression of cytokeratin markers AE1 and CK20, but expressed AE3 and CK7 poorly. The expression of CEA and CK20 but not CK7 in UP-LN1 cells was also exhibited in the tumor biopsy by immunohistochemistry, suggesting a gastrointestinal origin of this tumor. Down-regulation of HLA-class I and other surface molecules including ICAM-1, CD44s, CD44v5, CD44v6 and E-cadherin were observed, which all pointed to a progressive/invasive phenotype of the tumor. Spectral karyotyping revealed a hypertriploid (approximately 3n) chromosome content with 73-76 chromosomes, including numerical alterations and translocated derivative chromosomes. Seven different translocation chromosomes were observed, four of which involved chromosome 19. Numerical imbalances were also assessed by comparative genomic hybridization. This cell line should be useful for further studies of tumor invasion and metastatic processes because of the unusual in vitro and in vivo immunobiological and genetic characteristics observed.

Left paraduodenal hernia presenting as recurrent small bowel obstruction.

Internal herniation of the small bowel is a relatively rare cause of intestinal obstruction. Left paraduodenal hernia resulting from abnormal rotation of the midgut during embryonic development is the most common form of congenital internal hernia. We report our experience in the diagnosis and management of a young male with left paraduodenal hernia presenting as recurrent intestinal obstruction. Correct preoperative diagnosis of left paraduodenal hernia had been difficult due to non-specific clinical presentations, but the advent of modern imaging technology makes early and correct diagnosis possible. Due to the risk of obstruction and strangulation, surgical treatment is indicated; however, timely intervention increases the likelihood of a favorable outcome.

Risk factors of pneumothorax and bleeding: multivariate analysis of 660 CT-guided coaxial cutting needle lung biopsies.

BACKGROUND: The results of studies identifying the risk factors for pneumothorax and bleeding in CT-guided coaxial lung needle biopsies were inconsistent and some were even contradictory. All reported series were small with patient populations averaging about 200. STUDY OBJECTIVES: To determine the risk factors for pneumothorax and bleeding after CT-guided coaxial cutting needle biopsy of lung lesions. DESIGN: Retrospective analysis. METHODS: We reviewed 660 biopsy procedures. The risk factors for pneumothorax and bleeding were determined by multivariate analysis of variables related to patient demographics, lung lesions, biopsy procedures, and the individual radiologist. RESULTS: The main complications were pneumothorax (23%; 155 of 660 procedures), chest tube insertion (1%; 9 of 660 procedures), and hemoptysis (4%; 26 of 660 procedures), with no patient mortality. The highest pneumothorax rate correlated with a lesion size of /= 2.1 cm, and the absence of pleural effusion. CONCLUSIONS: The risk factors for highest pneumothorax rate are lesion size /= 2.1 cm, and lung lesions not associated with a pleural effusion.

Primary medulla oblongata germinoma: a case report and review of the literature.

We describe a case of primary intracranial medulla oblongata germinoma in a 16-year-old girl who presented with progressive headache and blurred vision. Magnetic resonance imaging demonstrated a heterogeneous exophytic mass arising from dorsal aspect of medulla oblongata with extension into fourth ventricle. The differential diagnosis for this patient had included ependymoma, exophytic glioma, medulloblastoma and choroid plexus papilloma. After surgical resection and radiation therapy, she remains alive and recurrence-free for 7 years.

Factors affecting diagnostic accuracy of CT-guided coaxial cutting needle lung biopsy: retrospective analysis of 631 procedures.

PURPOSE: To analyze variables affecting diagnostic accuracy of computed tomography (CT)-guided percutaneous coaxial cutting needle biopsy of lung lesions. MATERIALS AND METHODS: A retrospective analysis of factors affecting diagnostic accuracy of CT-guided percutaneous coaxial cutting needle lung biopsy was performed in 631 consecutive procedures with confirmed final diagnoses. Benign and malignant needle biopsy results were cross-examined with correct and incorrect final outcomes to determine diagnostic accuracy. Factors affecting diagnostic accuracy were determined by multivariate logistic regression analysis of variables thought to affect diagnostic accuracy. A P value less than 0.05 was interpreted as statistically significant. RESULTS: The overall diagnostic accuracy of CT-guided percutaneous coaxial cutting needle biopsy of lung lesions was 95% (95% CI: 92.7%-96.2%). Sensitivity was 93%, specificity 98%, negative predictive value 6%, positive predictive value 99%, false-positive rate 0.7%, and false-negative rate 15%. The factors affecting diagnostic accuracy were final diagnoses (benign, 86%; malignant, 99%; chi(2) test, P < 0.001) and lesion size (lesions <1.5 cm, 84%; lesions 1.5-5.0 cm, 96%; lesions >5 cm, 93%; chi(2) test, P = 0.06). CONCLUSION: Benign lung lesions, lung lesions smaller than 1.5 cm (which pose technical difficulty), and lung lesions larger than 5 cm (which are associated with a higher necrosis rate) affect diagnostic accuracy of CT-guided percutaneous coaxial cutting needle biopsy of lung lesions.

Pseudoaneurysm of the deep circumflex iliac artery: a rare complication at an anterior iliac bone graft donor site treated by coil embolization.

Pseudoaneurysm formation of the deep circumflex iliac artery (DCIA) after harvesting an anterior iliac bone graft for spinal fusion is reported herein. A 76-year-old man with cervical myelopathy underwent anterior cervical decompression and fusion with a left anterior iliac bone graft. A painful left inguinal mass was noted 1 month later. He was admitted to our emergency ward. Angiography of the left external iliac artery was performed which showed a pseudoaneurysm of the DCIA. Selective transarterial coil embolization of the artery was performed, and bleeding was arrested. In a review of the previous literature, only 1 pseudoaneurysm of the DCIA was reported to be associated with anterior iliac bone graft. In conclusion, vascular injury after anterior iliac bone harvesting is rare but can occur. Selective transarterial coil embolization is a prompt and effective solution.