Usefulness of real-time elastography for diagnosing lymph node metastasis of skin cancer: does elastography potentially eliminate the need for sentinel lymph node biopsy in squamous cell carcinoma?

BACKGROUND: The metastatic involvement of regional lymph nodes is the most important prognostic factor for overall survival of skin cancer patients. The sonographic technique of freehand real-time tissue elastography (RTE), which displays tissue rigidity as a colour overlay of the tissue image, was developed. OBJECTIVE: Our purpose was to evaluate the benefit of RTE for detecting lymph node metastases of skin cancer non-invasively before operation. METHODS: We first selected lymph nodes of skin cancer patients which had already been diagnosed by biopsy as being reactive or metastatic, and then retrospectively collected images of RTE and B-mode and colour Doppler ultrasound on those lymph nodes performed preoperatively. Twenty-one lymph nodes from 12 patients with squamous cell carcinoma (SCC), 23 lymph nodes from 14 patients with malignant melanoma (MM) and 14 lymph nodes from six patients with extramammary Paget disease (Paget) were investigated. Elastographic images were assessed on a scale of one to four according to the percentage of high elasticity (hard) area (HEA) in the lymph node. RESULTS: In all three skin cancers, lymph nodes evaluated as grade 3 or 4 by RTE were metastatic. All lymph nodes evaluated as grade 1 or 2 by RTE were reactive in SCC, whereas some lymph nodes evaluated as grade 1 or 2 were metastatic in MM and Paget. CONCLUSION: Real-time tissue elastography may aid in distinguishing reactive lymph nodes from metastatic ones especially in SCC.

Serum IL-33 levels are increased in patients with psoriasis.

BACKGROUND: Interleukin (IL)-33 is a recently identified cytokine, which is a member of the IL-1 family and binds to a heterodimeric receptor comprising ST2 (suppression of tumorigenicity 2) and IL-1 receptor accessory protein. Serum levels of IL-33 have been reported to be upregulated in various T helper (Th)1/Th17-mediated diseases, such as rheumatoid arthritis and inflammatory bowel disease. IL-33 expression is increased in lesional skin in patients with psoriasis, but serum levels in patients with psoriasis have not yet been studied. AIM: To study serum IL-33 levels in patients with psoriasis, a Th1/Th17-mediated skin disease, before and after anti-tumour necrosis factor (TNF)-α therapy. METHODS: Serum IL-33 levels were measured in patients with psoriasis vulgaris (PV), psoriatic arthritis (PsA) or pustular psoriasis (PP), and compared with those of healthy controls. Associations between serum IL-33 levels and serum TNF-α, IL-6, vascular endothelial growth factor and C-reactive protein levels were also studied. In addition, the effect of IL-33 stimulation on IL-6, IL-8, TNF-α and VEGF secretion by human keratinocyte was analysed. RESULTS: Serum IL-33 levels in patients with PV, PsA and PP were significantly higher than those in healthy controls. Serum IL-33 levels correlated with serum TNF-α levels in patients with psoriasis, and decreased after anti-TNF-α therapy. IL-33 stimulated IL-6 and IL-8 secretion by human keratinocytes. CONCLUSIONS: These results suggest that serum IL-33 levels generally reflect increased inflammation in patients with psoriasis.

Predictive factors for pericardial effusion identified by heart dose-volume histogram analysis in oesophageal cancer patients treated with chemoradiotherapy.

OBJECTIVE: To identify predictive factors for the development of pericardial effusion (PCE) in patients with oesophageal cancer treated with chemotherapy and radiotherapy (RT). METHODS: From March 2006 to November 2012, patients with oesophageal cancer treated with chemoradiotherapy (CRT) using the following criteria were evaluated: radiation dose >50 Gy; heart included in the radiation field; dose-volume histogram (DVH) data available for analysis; no previous thoracic surgery; and no PCE before treatment. The diagnosis of PCE was independently determined by two radiologists. Clinical factors, the percentage of heart volume receiving >5-60 Gy in increments of 5 Gy (V5-60, respectively), maximum heart dose and mean heart dose were analysed. RESULTS: A total of 143 patients with oesophageal cancer were reviewed retrospectively. The median follow-up by CT was 15 months (range, 2.1-72.6 months) after RT. PCE developed in 55 patients (38.5%) after RT, and the median time to develop PCE was 3.5 months (range, 0.2-9.9 months). On univariate analysis, DVH parameters except for V60 were significantly associated with the development of PCE (p < 0.001). No clinical factor was significantly related to the development of PCE. Recursive partitioning analysis including all DVH parameters as variables showed a V10 cut-off value of 72.8% to be the most influential factor. CONCLUSION: The present results showed that DVH parameters are strong independent predictive factors for the development of PCE in patients with oesophageal cancer treated with CRT. ADVANCES IN KNOWLEDGE: A heart dosage was associated with the development of PCE with radiation and without prophylactic nodal irradiation.

Ciclosporin A inhibits production of interleukin-12/23p40 and interleukin-23 by the human monocyte cell line, THP-1.

Ciclosporin (Cs)A is an effective treatment for psoriasis. However, to date, the effect of CsA on the production of interleukins (ILs) is unknown. We investigated how CsA affects production of IL-12/23p40 and IL-23 production by the human monocyte cell line, THP-1, which is able to differentiate into macrophage-like cells or normal human keratinocytes (NHKs). THP-1 cells were preincubated with CsA, then stimulated with lipopolysaccharide (LPS), polyinosinic:polycytidylic acid or adenosine triphosphate. The levels of IL-12/23p40 and IL-23 released into the supernatant were assayed by ELISA. CsA significantly reduced both IL-12/23p40 and IL-23 production by LPS-stimulated THP-1 cells, but not in LPS-stimulated macrophage-like differentiated THP-1 cells. None of the stimuli used significantly induced either IL-12/23p40 or IL-23 production in NHKs. CsA inhibits not only IL-12/23p40 and IL-12p70, but also heterodimeric IL-23 production by human monocytes, which may be one possible mechanism for the therapeutic efficacy of CsA in psoriasis.

Serum soluble CD26 levels: diagnostic efficiency for atopic dermatitis, cutaneous T-cell lymphoma and psoriasis in combination with serum thymus and activation-regulated chemokine levels.

BACKGROUND: CD26 is a multifunctional type II transmembrane glycoprotein, which also exists as a secreted isoform, soluble CD26 (sCD26). The CD26 expression on circulating T cells is decreased in some skin diseases such as cutaneous T-cell lymphoma (CTCL) and psoriasis. It remains to be determined whether sCD26 can be used as a marker of skin diseases or not. OBJECTIVE: To investigate utility of sCD26 as a diagnostic marker of skin diseases in combination with thymus and activation-regulated chemokine (TARC). METHODS: Serum sCD26 levels were measured using enzyme-linked immunosorbent assay in 130 participants including 32 patients with atopic dermatitis (AD); 45 patients with CTCL; 26 patients with psoriasis; and 27 healthy controls. RESULTS: Serum sCD26 levels in patients with CTCL and psoriasis (162.1 ± 80.2 ng/mL and 125.4 ± 82.1 ng/mL respectively) were significantly lower than those of healthy controls (392.6 ± 198.7 ng/mL; P < 0.01 and 0.01 respectively). In patients with CTCL, serum sCD26 levels of patients with advanced stage were 135.0 ± 51.5 ng/mL and they were significantly lower than those with early stage (193.1 ± 96.0 ng/mL; P < 0.05). When we used serum sCD26 and TARC levels for diagnostic criteria, sensitivity, specificity, positive predictive value and negative predictive value for AD, CTCL and psoriasis were 65.2-73.7%, 81.4-97.6%, 65.2-94.4%, and 81.4-88.9% respectively. CONCLUSION: Serum sCD26 levels, combined with serum TARC levels, are helpful in diagnosis of AD, CTCL and psoriasis.

Irsogladine maleate reduces the incidence of fluorouracil-based chemotherapy-induced oral mucositis.

BACKGROUND: Oral mucositis is one of the most common side-effects of 5-fluorouracil (5-FU)-based chemotherapy. The objective of this study was to evaluate the effects of irsogladine maleate (IM) on fluorouracil-induced oral mucositis through a double-blind, placebo controlled trial. PATIENTS AND METHODS: Patients (N = 66) were randomly assigned to receive either placebo or IM (4 mg/day for 14 consecutive days). The incidence and maximum severity of fluorouracil-induced oral mucositis and safety of the irsogladine dosing regimen were evaluated. RESULTS: A cohort of 33 patients received placebo and 33 patients received IM. The incidence of oral mucositis was significantly lower for IM than for placebo (27% versus 73%; P < 0.001 by chi-square test). Specific adverse events considered related to IM were not found. CONCLUSION: IM significantly reduced the incidence and maximum severity of oral mucositis in patients treated with 5-FU-chemotherapy.

Serum lipocalin-2 levels are increased in patients with psoriasis.

The protein lipocalin (LCN)-2 is known to be related to insulin resistance, obesity and atherosclerotic diseases. Psoriasis is an inflammatory skin disease related to metabolic syndrome. The aim of this study was to examine the relationship between serum LCN2 levels and indicators for metabolic syndrome and inflammatory cytokine levels in patients with psoriasis. Serum LCN2 levels were measured in patients with psoriasis, atopic dermatitis (AD) or bullous pemphigoid (BP), and compared with those of healthy controls. Serum LCN2 levels were also compared with several indicators for metabolic syndrome, and with serum levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α, two markers of inflammation. Serum LCN2 levels in patients with psoriasis were significantly higher than those of healthy controls, but there was no significant correlation between serum LCN2 and body mass index. Serum LCN2 levels also correlated with serum IL-6 and TNF-α levels in patients with psoriasis. Serum LCN2 levels are a general indicator for increased inflammation in the patients with psoriasis.

Efficacy of perfusion cooling of the epidural space and cerebrospinal fluid drainage during repair of extent I and II thoracoabdominal aneurysm.

AIM: The aim of this study was to evaluate spinal cord injury and mortality resulting from repair of extent I and II thoracoabdominal aneurysm. The authors compared patients operated under mild hypothermia with or without epidural perfusion cooling (EPC) and cerebrospinal fluid drainage (CSFD). METHODS: From 1988 to 2007, 116 patients underwent replacement of the thoracoabdominal aorta; the procedure was performed in 38 patients with the aid of mild hypothermia alone (group A), and in 78 patients with the aid of EPC, mild hypothermia and CSFD (group B). Two catheters for epidural perfusion cooling were inserted in group B, in which one catheter was inserted into the epidural space to infuse chilled saline, and the other was inserted into the subdural space to drain the cerebrospinal fluid and to measure temperature and pressure. There were no significant differences in mean age, etiology of aortic disease, and aneurysm extent between the two groups. RESULTS: There were no significant differences in cardiopulmonary bypass time, the lowest nasopharyngeal temperature and operation time between the two study groups. The incidence of spinal cord injury in group A (16.2%) was significantly higher than in group B (3.8%, P=0.03). Hospital mortality in groups A and B was 10.5% and 2.6%, respectively (P=0.08). There was no significant difference in postoperative complications between the two study groups. CONCLUSION: The combination of EPC and CSFD was effective in lowering the incidence of postoperative spinal cord injury in the repair of extent I and II thoracoabdominal aortic aneurysm.

Cervical oesophageal stent placement via a retrograde transgastric route.

During attempted oesophageal stent placement in a patient with cervical oesophageal cancer in whom swallowing of even saliva was impossible, transoral access to the cervical oesophagus was unsuccessful. Under ultrasound and fluoroscopy guidance, percutaneous gastric puncture was performed, and using an angiographic catheter and guidewire, access to the oesophagus by a retrograde transgastric route was successfully achieved. The obstructed segment of the oesophagus was traversed. It was then possible to pull the guidewire through the mouth and place an oesophageal stent via an antegrade approach.

Continuous selective intraarterial chemotherapy in combination with irradiation for locally advanced cancer of the tongue and tongue base.

We retrospectively evaluated the results of the concurrent combination therapy of selective continuous intraarterial chemotherapy and radiotherapy in 39 patients with locally advanced cancer of the tongue and tongue base between September 1992 and January 2000. Thirty patients were fresh cases (stage II, 10 patients; stage III, 15; stage IV, five) and nine were recurrent cases. The primary lesion was present in the mobile tongue in 33 patients and the tongue base in six. External irradiation (median dose, 48.6 Gy) was performed in all patients, and interstitial brachytherapy using an Au grain or Cs needle (median dose, 50 Gy) in 21. In intraarterial chemotherapy, a catheter was selectively inserted into the lingual artery via the superficial temporal artery, and carboplatin (CBDCA) was continuously infused (median dose, 460 mg/m(2)) concurrently with radiotherapy. In 13 patients with cervical lymph node metastasis, two courses of systemic chemotherapy with 5-FU (700 mg/m(2) x 5 days) and cisplatin (40-50 mg/m(2)x2 days) or its analog was also performed. In 37 (94.9%) of the 39 patients in whom this combination therapy was completed, the response rate was 94.6%. The 3-year local control rate, progression-free survival rate, and overall survival rate by Kaplan-Meier's method were 79.2, 53.2, and 58.9%, respectively. This combination therapy was effective for locally advanced cancer of the tongue and tongue base without causing severe adverse side effects, and a local control rate comparable to that by surgery can be expected.

Alternating chemoradiotherapy for nasopharyngeal cancer using cisplatin and 5-fluorouracil: a preliminary report of phase II study.

Alternating chemoradiotherapy was performed in 35 patients with locally advanced nasopharyngeal cancer. The median duration of follow-up was 20 months, and the 2-year progression free and overall survival rates were 83% (95% confidence interval: 66~101%) and 94% (95% CI: 84~105%), respectively. This method may be useful in treating nasopharyngeal cancer.

Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (A beta ); retards A beta aggregation, deposition, fibril formation; and inhibits cytotoxicity.

We have demonstrated that the angiotensin-converting enzyme (ACE) genotype is associated with Alzheimer's disease (AD) in the Japanese population (). To determine why ACE affects susceptibility to AD, we examined the effect of purified ACE on aggregation of the amyloid beta-peptide (A beta) in vitro. Surprisingly, ACE was found to significantly inhibit A beta aggregation in a dose response manner. The inhibition of aggregation was specifically blocked by preincubation of ACE with an ACE inhibitor, lisinopril. ACE was confirmed to retard A beta fibril formation with electron microscopy. ACE inhibited A beta deposits on a synthaloid plate, which was used to monitor A beta deposition on autopsied brain tissue. ACE also significantly inhibited A beta cytotoxicity on PC12 h. The most striking fact was that ACE degraded A beta by cleaving A beta-(1-40) at the site Asp(7)-Ser(8). This was proven with reverse-phase HPLC, amino acid sequence analysis, and MALDI-TOF/MS. Compared with A beta-(1-40), aggregation and cytotoxic effects of the degradation products A beta-(1-7) and A beta-(8-40) peptides were reduced or virtually absent. These findings led to the hypothesis that ACE may affect susceptibility to AD by degrading A beta and preventing the accumulation of amyloid plaques in vivo.

Therapeutic effects of simultaneous intraluminal irradiation and intraluminal hyperthermia on oesophageal carcinoma.

An applicator enabling simultaneous intraluminal radiotherapy and intraluminal hyperthermia delivery was developed to improve the treatment results for locally advanced oesophageal carcinoma. Eight inoperable cases were treated by this method. Six cases received 40 Gy external irradiation followed by simultaneous intraluminal hyperthermia and radiotherapy (3 Gy and 4 Gy in three cases each) once weekly for 3 weeks; the remaining two cases received 50 Gy external irradiation followed by simultaneous intraluminal hyperthermia and radiotherapy (4 Gy) once weekly for 2 weeks. Hyperthermia was delivered by a radiofrequency current thermotherapy instrument for 30 min at an output that raised the oesophageal mucosal surface temperature to 42-43 degrees C. Intraluminal radiotherapy was delivered with a microSelectron to a submucosal depth of 5 mm after the first 15 min of hyperthermia. Four cases achieved complete response, with all demonstrating local control. Partial response was obtained in four cases, and three of these patients died of local recurrence. There were no significant adverse side effects apart from fistula in one case. In conclusion, simultaneous intraluminal radiotherapy and hyperthermia may improve the current treatment results for locally advanced oesophageal carcinoma.

T cell apoptosis causes peripheral T cell depletion in mice transgenic for the HIV-1 vpr gene.

Vpr, an accessory protein of HIV, is known to affect viral replication as well as cell growth, differentiation, and apoptosis in vitro. To investigate its pathogenicity in vivo, we have produced mice transgenic for the HIV-1 vpr gene with the CD4 enhancer/promoter. Interestingly, apoptotic death of T lymphocytes was enhanced in those mice, causing marked reduction of T cells in lymphatic organs and peripheral blood. Involvement of Bcl-x, Bax, and Caspase-1, but not of the Fas-Fas ligand system, was suggested in the apoptotic processes. These observations suggest that Vpr is involved in the pathogenesis of T cell depletion in HIV-infected people.

[A case of infected subdural hematoma due to Campyrobacter fetus].

A 20-year-old male presented fever, nausea and headache 1 week after eating uncooked liver. On admission, it was revealed he had suffered a closed head injury 3 months before without unconsciousness. On admission, computed tomography scan showed a left chronic subdural hematoma. Gd-DTPA magnetic resonance images revealed unusual enhancement of the capsule and linear enhancement of the subarachnoid space. The patient underwent burr hole irrigation and drainage. The culture of the hematoma content showed Campylobacter fetus. Therefore, the diagnose was infected subdural hematoma. A drainage operation and administration of antibiotics were effective. Our case suggests that enhanced magnetic resonance images are useful for diagnosis and follow-up of infected subdural hematoma.

Aichi Cancer Center 10-year experience with conservative breast treatment of early breast cancer: retrospective analysis regarding failure patterns and factors influencing local control.

PURPOSE: We analyzed the clinical results of conservative breast therapy in our institute to determine the risk factors influencing local and distant disease recurrence. METHODS AND MATERIALS: From 1989 to 1997, 301 breasts of 295 women with early breast cancer were treated with conservative surgery and adjuvant radiotherapy. There were 212 incidences of Stage I breast cancer, and 89 of Stage II. Patients were routinely treated with local resection, axillar dissection, and 46--50 Gy irradiation given in 23--25 fractions. Some also received a radiation boost to the tumor bed. RESULTS: The 5-/8-year overall survival, disease-free survival, and local control rates were 93.2/91.5%, 86.0/80.6%, and 95.1/92.5%, respectively. Using both univariate and multivariate analyses, tumor volume, estrogen receptor status, and age < 40 years were significant prognostic factors for disease-free survival. Both age < 40 years and surgical method had a strong effect on local control by uni- and multivariate analysis. Surgical margin status was a significant prognostic factor for local control at the univariate level (p < 0.0001), though it had only borderline significance at the multivariate level (p = 0.08). No patient experienced severe morbidity due to radiotherapy. CONCLUSION: The results obtained are comparable to previously reported data. Although the follow-up period was too short to draw definite conclusions about long-term outcomes, the outcome from conservative breast treatment was acceptable.

[Two cases of squamous cell carcinoma of the anal canal treated with chemoradiotherapy].

We recently treated 2 patients with squamous cell carcinoma in the anal canal with bilateral inguinal nodal metastases using chemoradiotherapy. Chemotherapy (CT) consisted of 5-fluorouracil 700 mg/m2/day (continuous intravenously) on days 1-5 and cisplatin 50 mg/m2/day (continuous intravenously) on days 6-7. Chemotherapy was administered before the beginning of radiotherapy. In one patient, 2 cycles of CT were performed, and in the other patient 1 cycle only. The total radiation dose was 57.6 Gy to the primary lesion in each patient, and 53.6 Gy, 55.8 Gy to the nodal metastases, respectively. As a primary treatment response, CR was obtained in both patients. Acute grade 3-4 hematologic toxicities were observed in one patient. The patients have had 7 and 9 months survival without disease, and excellent function of the anal sphincter after treatment.

External irradiation and intraluminal irradiation using middle-dose-rate iridium in patients with roentgenographically occult lung cancer.

PURPOSE: Therapeutic results were analyzed in 39 patients with roentgenographically occult lung cancer (ROLC), and the significance and optimal dose of this therapy were evaluated. METHODS AND MATERIALS: The subjects were 39 patients who underwent intraluminal irradiation between May 1987 and August 1999. Radiotherapy was performed by combining external irradiation with intraluminal irradiation using middle-dose-rate iridium (four 370-MBq wires) through a catheter with a spacer, which held the source in the center of the bronchus. The doses of radiation were 22-66 Gy (median value 45 Gy) by external irradiation and 10-46 Gy (median value 28 Gy) by intraluminal irradiation. RESULTS: The therapeutic effect was CR in 38 patients and PR in 1, and local recurrence was observed in a PR case and 3 of the 38 patients who showed CR. The 3-year and 5-year relapse-free survival rates were both 87%. No severe radiation injury was observed. CONCLUSIONS: Considering that ROLC often occurs as multiple cancers and that many patients with ROLC have reduced lung function, radiation therapy by a combination of intraluminal irradiation and external irradiation is expected to replace surgery as the first choice for the treatment of this disease in the twenty-first century.