Influence of radiologic expertise in detecting lung tumors on chest radiographs.

PURPOSE: To analyze the influence of radiologic expertise in detecting lung tumors on chest radiographs. MATERIALS AND METHODS: We retrieved posteroanterior chest radiographs and CT examination obtained from 283 patients with solitary primary malignant lung tumors who underwent surgical resection. There were 176 men and 107 women with a mean age of 67.0±9.1 (SD) years (range: 33-88 years). Thirteen first-year post-graduate (PGY-1) trainees and nine pulmonary specialists (three radiologists, three thoracic surgeons, and three pulmonologists) interpreted the chest radiographs. Detection rates among trainees and specialists were compared using Student t test. RESULTS: The total numbers of detected tumors ranged from 103 (36.4%) to 136 (48.1%) with a mean of 127.9±9.1 (45.2±3.2%) in the trainee group, and 137 (48.4%) to 182 (64.3%) with a mean of 161.6±13.1 (57.1±4.6%) in the specialist group; the intergroup difference was statistically significant (P<0.001). Significant intergroup detectability differences of >10% were noted for tumors in the peripheral zone with (i) ground glass opacity (GGO) ratio ≥10% and <70% and any size, or (ii) GGO ratio <10% and size ≤2cm; and for tumors hidden by the mediastinum, heart, or diaphragm with (i) GGO ratio ≥10% and <30% and size >3cm, or (ii) GGO ratio <10% and size >2cm. CONCLUSION: Our study demonstrates significant differences in lung tumor detectability on chest radiographs between PGY-1 trainees and pulmonary specialists according to tumor size, extent of GGO, and tumor location.

Indocyanine green fluorescence angiography of the reconstructed gastric tube during esophagectomy: efficacy of the 90-second rule.

By examining the reconstructed gastric tube during esophagectomy using indocyanine green fluorescence (ICG) angiography, we have established a '90-second rule' to confirm good blood perfusion at the anastomosis site. We examined the surgical outcome (rate of anastomotic leakage) of 70 consecutive patients who underwent esophagectomy with gastric tube reconstruction using ICG fluorescence angiography. All of the anastomoses were made in the area where less than 90 seconds was needed for enhancement using ICG fluorescence angiography (i.e. within the 90-second rule). In 18 cases for which the time until enhancement of the gastric tube tip exceeded 60 seconds, the anastomosis site was decided by reference to the ICG fluorescence angiogram, and the hypoperfused area was excised, and this significantly shortened the median time until enhancement of the gastric tube tip from 95.5 (60.0-204.0) seconds to 41.0 (9.0-77.0) seconds (P < 0.001). In three cases, the anastomosis was made at the site where more than 60 seconds was needed for ICG enhancement. In one case where ICG enhancement had taken 77 seconds, minor anastomotic leakage occurred. The overall rate of anastomotic leakage in this series was 1.4%. Blood flow in the reconstructed gastric tube is sufficient if the anastomosis is made in the area where ICG fluorescence angiography demonstrates enhancement within 60 seconds. Gastric tube necrosis can be avoided if the area showing an enhancement time exceeding 90 seconds is excised. The 90-second rule is a safe and effective method for deciding the site of anastomosis.

Endocytoscopic observation of various esophageal lesions at ×600: can nuclear abnormality be recognized?

Endocytoscopy (ECS) is a novel endoscopic technique that allows detailed diagnostic examination of the gastrointestinal tract at the cellular level. We previously reported that use of ECS at ×380 magnification (GIF-Y0002) allowed a pathologist to diagnose esophageal squamous cell carcinoma (ESCC) with high sensitivity (94.9%) but considerably low specificity (46.7%) because this low magnification did not reveal information about nuclear abnormality. In the present study, we used the same magnifying endoscope to observe various esophageal lesions, but employed digital 1.6-fold magnification to achieve an effective magnification of ×600, and evaluated whether this improved the diagnostic accuracy in distinguishing neoplastic from non-neoplastic lesions.We examined the morphology of surface cells using vital staining with toluidine blue and compared the histological features of 40 cases, including 19 case of ESCC and 21 non-neoplastic esophageal lesions (18 cases of esophagitis, 1 case of glycogenic acanthosis, 1 case of leiomyoma, and 1 case of normal squamous epithelium). One endoscopist classified the lesions using the type classification, and we consulted one pathologist for judgment of the ECS images as 'neoplastic', 'borderline', or 'non-neoplastic'. At ×600 magnification, the pathologist confirmed that nuclear abnormality became evident, in addition to the information about nuclear density provided by observation at ×380. The overall sensitivity and specificity with which the endoscopist was able to predict neoplastic lesions using the type classification was 100% (19/19) and 90.5% (19/21), respectively, in comparison with values of 94.7% (18/19 cases) and 76.2% (16/21), respectively, for the pathologist using a magnification of ×600. The pathologist diagnosed two non-neoplastic lesions and one case of ESCC showing an apparent increase of nuclear density with weak nuclear abnormality as 'borderline'. Among the 21 non-cancerous lesions, two cases of esophagitis that were misdiagnosed by the endoscopist were also misinterpreted as 'neoplastic' by the pathologist. We have shown, by consultation with a pathologist, that an ECS magnification of ×600 (on a 19-inch monitor) is adequate for recognition of nuclear abnormality. We consider that it is feasible to diagnose esophageal neoplasms on the basis of ECS images, and that biopsy histology can be omitted if a combination of increased nuclear density and nuclear abnormality is observed.

Intrauterine fetal demise due to streptococcal toxic shock syndrome: a case report.

BACKGROUND: Toxic shock syndrome caused by group A streptococci (GAS) is rare around the time of delivery, but it may predispose pregnant women to a life-threatening condition. CASE: A 32-year-old primigravida at 21 weeks of gestation was taken to our hospital with acute severe abdominal pain following fever. On admission the fetus was found to be dead, and intrauterine fetal demise due to placental abruption was suspected. An emergency cesarean section found no sign of placental abruption. Soon after the surgery, the patient went into shock but was successfully treated with intensive care. Although repeated blood cultures failed to detect microorganisms, the patient was positive for streptococcal pyrogenic toxin A, which is a superantigen of GAS. CONCLUSION: Once GAS infection is suspected, regardless of negative blood cultures, supportive care in the intensive care unit is mandatory.

Curative colectomy via minilaparotomy approach without utilizing specific instruments.

BACKGROUND: This study evaluated the need for specific instruments when performing a curative resection of colon cancer via a minilaparotomy approach, which has been reported to be a minimally invasive alternative to a laparoscopic approach. METHODS: The feasibility, safety, and early oncological outcome were compared among 73 patients (first group), in whom a curative resection of colon cancer was performed via a minilaparotomy (skin incision < or =7 cm) utilizing specific instruments (North-bridge retractor system) between September 2002 and March 2005, and 94 patients (second group), in whom a similar procedure was performed without utilizing specific instruments between April 2005 and October 2007. RESULTS: The two groups did not differ significantly in terms of age, sex, body mass index, site of tumor, level of lymph node dissection, blood loss, UICC stage, number of harvested lymph nodes, incidence of postoperative complications, length of postoperative hospital days, or overall survival, although the frequency of prior abdominal surgery was higher (38.3 vs. 21.9%; P = 0.03) and the median operating time required for a standard lymph node dissection was shorter (120 vs. 135 min; P = 0.03) in the second group. CONCLUSION: With improved techniques and experience, specific instruments are not necessary for the performance of a curative colectomy via a minilaparotomy approach.

Gene trapping identifies chloride channel 4 as a novel inducer of colon cancer cell migration, invasion and metastases.

BACKGROUND: To date, there are few reports on gene products contributing to colon cancer progression. METHODS: We used a gene trap comprised of an enhanced retroviral mutagen (ERM) cassette that includes a tetracycline-responsive promoter upstream of a haemagglutinin (HA) tag and a splice donor site. Integration of the ERM within an endogenous gene yields a tetracycline-regulated HA-tagged transcript. We transduced RKO colon cancer cells expressing a tetracycline trans-activator-off with the ERM-encoding retrovirus and screened for enhanced migration. RESULTS: One clone showed fivefold enhanced migration with tetracycline withdrawal. Rapid amplification of cDNA ends identified the trapped gene as the chloride channel 4 (CLCN4) exchanger. Stable expression of a CLCN4 cDNA enhanced motility, whereas cells knocked down or null for this transcript showed reduced migration/invasion. CLCN4-overexpressing RKO colon cancer cells were more resistant than controls to proton load-induced cytotoxicity, consistent with the H(+)-extruding function of this antiporter. Intra-splenic delivery of RKO-CLCN4 transfectants, but not controls, yielded liver metastases, and transcript levels were higher in colon cancer metastases to the liver when compared with primary tumours. CONCLUSIONS: CLCN4 is a novel driver of colon cancer progression.

Pitfalls during the Embolization and Evaluation after the Embolization for the Skull Base Meningiomas.

SUMMARY: Pitfall during the embolization and evaluation after the embolization for skull base meningiomas supplied by meningeal arteries of internal carotid artery (ICA) are reported. This study includes 15 cases of skull base meningiomas (two males and 13 females) that supplied by meningeal branches of internal carotid artery. The preoperative embolization was performed by these feeders. MRI findings and serum levels of C-reactive protein (CRP) after the embolization were examined. In ten patients among 15 patients the meningeal branches of ICA were dominant feeders. In ten patients out of 15 patients, the embolization from the meningeal branches of ICA was possible. Eight patients out of these ten patients were suffered from high fever and increase of serum level of CRP after the embolization. During the embolization for skull base meningiomas, the existence of collateral pathways between the ICA system and external carotid artery system were identified. The increase of serum levels of CRP might be recognized in the patients that effective embolization were performed.

Urethral transitional cell carcinoma in a cat.

A 15-year-old, male neutered cat was referred for investigation of dysuria. A retrograde urethrography was performed which showed two space-occupying masses within the lumen of the mid-to-proximal urethra. Exploratory coeliotomy revealed two urethral masses. Segmental urethrectomy was performed to resect the mass, and the lower urinary tract was reconstructed by vesico-urethral anastomosis. Histopathology showed the mass to be a transitional cell carcinoma with incomplete surgical margins. Tumour regrowth was suspected when dysuria was found approximately 318 days after surgery. Clinical signs were palliated by radiation using weekly fractions of 6 Gy for three weeks. The cat died of unknown causes 386 days postoperatively.

Successful liquid storage of peripheral blood stem cells at subzero non-freezing temperature.

Although non-frozen storage of peripheral blood stem cells (PBSC) has been extensively studied and utilized clinically, the optimal storage conditions have not been determined. In order to improve the maintenance of clonogenic capacity during storage, we evaluated the feasibility of subzero non-freezing preservation of PBSC and attempted to determine the optimal conditions. Human PBSC were stored in different non-cryopreserved conditions. University of Wisconsin (UW) solution was used as the storage medium for PBSC. The stem cell integrity was optimally maintained when PBSC were preserved in a supercooled state at -2 degrees C in UW solution without any cryoprotectants, and the highest values for nucleated cell survival (91.6%), CFU-GM survival (67.3%) and trypan blue viability (92%) were achieved at 72 h. CFU-GM survival in our storage conditions was significantly better than the survival achieved with hypothermic preservation in autologous serum and ACD-A solution at 4 degrees C (67.3 +/- 9.2% vs 42.9 +/- 15.3%; P < 0.01) or cryopreservation at -80 degrees C (67.3 +/- 9.2% vs 52.7 +/- 10.7%; P < 0.01). Thus, the combination of supercooling and UW solution was the optimal non-freezing method of preserving transplantable PBSC tested here. This method is of clinical utility in peripheral blood stem cell transplantation (PBSCT) for its simplicity and storage efficiency, and has value as a short-term storage method for PBSC to support dose-intensive multicyclic chemotherapy.

Transfemoral, transvenous embolisation of dural arteriovenous fistula involving the isolated transverse-sigmoid sinus from the contralateral side.

BACKGROUND: A dural arteriovenous fistula (AVF) involving the transverse-sigmoid (T-S) sinus which is occluded at its proximal and distal ends i.e., an isolated sinus, runs the risk of haemorrhaging or causing serious neurological deficits as a result of its retrograde leptomeningeal venous drainage. While lesions of this type have not been considered to be treatable by percutaneous, transvenous embolisation, this paper challenges this view. CASE PRESENTATION: Two middle-aged men with dural AVFs involving the isolated left T-S sinus presented with motor aphasia due to focal brain edema or haemorrhage. Under local anaesthesia, transfemoral, transvenous embolisation was performed with a microcatheter that was passed through the occluded proximal transverse sinus from the right (contralateral) side. The isolated sinus was then occluded with platinum coils. This embolisation resulted in angiographic and clinical cure of dural AVFs in both patients. INTERPRETATION: Transfemoral, transvenous embolisation is a therapeutic alternative for the treatment of dural AVFs involving the isolated T-S sinus. Embolisation obviates the need for craniotomy and general anaesthesia, which are required for the established modes of treatment, i.e., direct surgery or direct percutaneous sinus packing.

CD40 ligand promotes priming of fully potent antitumor CD4(+) T cells in draining lymph nodes in the presence of apoptotic tumor cells.

The presence or absence of CD4(+) T cell help can determine the direction of adaptive immune responses toward either cross-priming or cross-tolerance. It has been demonstrated that interactions of CD40-CD40 ligand can replace CD4(+) T cell help and enable dendritic cells to prime cytotoxic T cells. Here, we demonstrate that antitumor reactivity induced in regional lymph nodes (LNs) by s.c. injection of CD40 ligand (CD40L)-transduced tumor (MCA205 CD40L) showed far superior therapeutic efficacy against established brain tumors of a weakly immunogenic fibrosarcoma, MCA205, when adoptively transferred. Coinjection of apoptotic, but not necrotic parental tumor cells with CD40L-expressing tumor cells caused a strong synergistic induction of antitumor reactivity in tumor-draining LNs. Freshly isolated T cells from LNs immunized with apoptotic parental tumor cells and MCA205 CD40L were capable of mediating regression of the parental tumor in vivo. In contrast, T cells derived from LNs immunized without MCA205 CD40L required ex vivo anti-CD3/IL-2 activation to elicit therapeutic activity. On anti-CD3/IL-2 activation, cells from LNs immunized with MCA205 CD40L exhibited superior per cell antitumor reactivity. An in vitro depletion study revealed that either CD4(+) or CD8(+) T cells could mediate therapeutic efficacy but that the antitumor efficacy mediated by CD4(+) T cells was far superior. Cytosolic flow cytometric analyses indicated that priming of CD4(+) cells in LNs draining CD40L-expressing tumors was polarized to the Th1 type. This is the first report that fully potent antitumor CD4(+) T cell priming was promoted by s.c. injection of CD40L-transduced tumor in the presence of apoptotic tumor cells.

ATF3 gene regulates cell form and migration potential of HT29 colon cancer cells.

We formally reported that ATF3 gene regulated HT29 colon cancer cell metastasis through cell adhesion and invasion. We report here our findings that, on wound filling assay, the ATF3 antisense oligonucleotide changed cell form to a rounder shape and suppressed the cell migration ability of HT29, although FACScan analysis showed that it had no effect on the cell cycle. The growing area of HT29 cells treated with the antisense oligonucleotide decreased, compared with that treated with the sense oligonucleotide. These factors were thought to relate to adhesion and invasion of HT29 cells, hence they influenced metastatic potential.

Establishment and characterization of a new canine mast cell tumor cell line.

A new cell line (CoMS) was established from a 3-year-old male mongrel dog with mast cell tumor of the oral mucosa. CoMS cells grow in suspension with a doubling time of 27.0 +/- 0.7 hr. The cytoplasmic granules were formalin-sensitive, showed diverse appearances in their ultrastructural findings and contained heparin proteoglycan and neutral protease chymase. Calcium ionophore A23187, substance P and concanavalin A caused significant histamine release from CoMS cells, while compound 48/80 failed to release histamine. This cell line will make an available source for studies on canine mast cell tumors.

Angiosarcoma of the breast: report of a case and its findings of MRI.

A 67-year-old woman with angiosarcoma of the left breast is presented. Physical findings showed a hard mass in the left breast with skin discoloration and erythema. Mammography showed a high density shadow in the mass without microcalcification and spicula. On ultrasonography, a hypoechoic mass with an ill-defined boundary was detected. On MRI, the tumor had low signal intensity on T1-weighted images, and higher signal intensity on T2-weighted images. MRI with Gd-DTPA images showed higher signal intensity on T1-weighted images with relatively lower intensity in the central area of the tumor. The artery supplying the tumor derived from the left inner thoracic artery and was visualized on three-dimensional dynamic MRI angiography. Initially misdiagnosed as inflammatory breast cancer, an arterial injection of CPA (100 mg) and 5-FU (500 mg) had been performed preoperatively. The definitive diagnosis of angiosarcoma was established by intraoperative frozen section examination. She underwent modified radical mastectomy and is now free of recurrence. This case emphasizes the difficulties in the clinical diagnosis of angiosarcoma of the breast.

Distal stump of an occluded intracranial vertebral artery at the vertebrobasilar junction mimicking a basilar artery aneurysm.

The distal stump of an occluded intracranial vertebral artery (VA) can mimic a basilar artery aneurysm of the vertebrobasilar junction. Their differentiation is crucial to establishing the appropriate treatment. We report two cases with occlusion of the distal stump of the VA due to atherosclerosis and arterial dissection. Magnetic resonance images with three-dimensional constructive interference in steady state sequences are useful in revealing the occluded segment as a continuous anatomical structure from the proximal VA to the basilar artery. This information may prevent unnecessary exploratory surgery for a suspected basilar artery aneurysm.

Inflammatory pseudotumor of the liver complicated with recurrent gouty arthritis.

Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion of unknown etiology and is often accompanied by fever. Unexplained persistent fever unresponsive to antibiotics developed in a 70-year-old man suffering from intractable recurrent gouty arthritis. 67Ga-scintigraphy disclosed intense focal uptake in the upper abdomen. The lesion in the left lobe of the liver was an ill-defined hypodensity mass on computed tomographic scan and was enhanced on dynamic magnetic resonance imaging. The tumor was surgically removed and a diagnosis of IPT was made. Fever and arthritis resolved completely after surgery. Possible interaction between IPT of the liver and gouty arthritis was suggested.

Directly linked soluble IL-6 receptor-IL-6 fusion protein induces astrocyte differentiation from neuroepithelial cells via activation of STAT3.

Signals of interleukin 6 (IL-6) are transduced by binding of IL-6 to its cell surface receptor (IL-6R) and subsequent association of the resultant IL-6/IL-6R complex with gp130, the signal transducing receptor component utilized in common by all the IL-6 family of cytokines. A soluble form of IL-6R (sIL-6R), which lacks transmembrane and cytoplasmic regions, retains the ability to bind IL-6 and signal through gp130. We show here that a fusion protein of sIL-6R and IL-6 without a polypeptide linker, termed FP6, induces differentiation of astrocytes from fetal mouse neuroepithelial cells as potently as a representative IL-6 family cytokine, leukaemia inhibitory factor (LIF). FP6 has a potential to activate a transcription factor, signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinases, ERK1 and ERK2, in these cells as does LIF. FP6 activates a promoter of the gene for an astrocytic marker, glial fibrillary acidic protein (GFAP), in neuroepithelial cells. This activation is virtually abolished by ectopic expression of a dominant-negative form of STAT3, or by introducing a point mutation into the STAT3 response element located in the GFAP promoter. These results suggest that FP6 induces astrocyte differentiation from neuroepithelial cells through STAT3 activation and that FP6 could be of use as a substitute for natural IL-6 family cytokines.

Role of macrophage scavenger receptors in response to Listeria monocytogenes infection in mice.

Type I and type II macrophage scavenger receptors (SR-A I/II) recognize a variety of polyanions including bacterial cell-wall products such as lipopolysaccharide, suggesting a role for SR-A I/II in immunity against bacterial infection. SR-A I/II-deficient (MSR-A-/-) mice were more susceptible to infection with listeriolysin-O (LLO)-producing Listeria monocytogenes. After infection, Kupffer cells in wild-type (MSR-A+/+) mice phagocytized larger numbers of Listeria than those in MSR-A-/- mice. The number and the diameter of hepatic granulomas were larger in MSR-A-/- mice than MSR-A+/+ mice. L. monocytogenes replicated at higher levels in the liver of MSR-A-/- mice compared with MSR-A+/+ mice, and macrophages from MSR-A-/- mice showed impaired ability to kill Listeria in vitro. However, macrophages from MSR-A+/+ and MSR-A-/- mice showed similar levels of listericidal activity against isogenic mutant L. monocytogenes with an inactivated LLO gene. The listerial phagocytic activities of MSR-A+/+ macrophages treated with an anti-SR-A I/II antibody (2F8) and MSR-A-/- macrophages were significantly impaired compared with untreated MSR-A+/+ macrophages, indicating that SR-A I/II function as a receptor for L. monocytogenes. Electron microscopy revealed that most L. monocytogenes had been eliminated from the lysosomes of MSR-A+/+ macrophages in vivo and in vitro. In contrast, L. monocytogenes rapidly lysed the phagosomal membrane and escaped to the cytosol in MSR-A-/- macrophages and in MSR-A+/+ macrophages treated with 2F8 before phagosome-lysosome fusion. These findings imply that SR-A I/II plays a crucial role in host defense against listerial infection not only by functioning as a receptor but also by mediating listericidal mechanisms through the regulation of LLO-dependent listerial escape from the macrophages.