A case of hemoperitoneum after percutaneous radiofrequency ablation in a patient with hepatocellular carcinoma.

We report a case of hemoperitoneum after percutaneous radiofrequency ablation in a patient with hepatocellular carcinoma. A 60-year-old female was hospitalized for the treatment of thrombasthenia and cirrhosis caused by chronic Hepatitis C, and computed tomography revealed hepatocellular carcinoma, which was treated by percutaneous radiofrequency ablation. After the ablation, hemoperitoneum was suspected because of the low hemoglobin level with abdominal pain. Approximately 6 h after the ablation treatment, the patient suddenly fell into a shock state and died. In this case, medical treatment-related death including malpractice was suspected, and forensic autopsy was performed. The abdominal cavity contained 910 mL of dark red fluid blood and 210 g of soft hemocoagula. Moreover, several puncture marks were observed on the liver surface and diaphragm, and there was no clear damage to the main arteries and veins. Considering the macroscopic and microscopic findings, the cause of death was assumed as hemorrhagic shock due to the hemoperitoneum caused by the damage to the liver by radiofrequency ablation. It is important to consider all the indications and adverse effects of radiofrequency ablation.

Clinical characteristics of itch in cutaneous lupus erythematosus: A prospective, multicenter, multinational, cross-sectional study.

OBJECTIVE: Pruritus is an important symptom frequently accompanying various inflammatory skin conditions and some recent data indicated that it may be associated with autoimmune connective tissue diseases. The aim of this study was to assess the frequency and clinical presentation of itch in CLE. METHODS: A multinational, prospective, cross-sectional study was performed to assess the prevalence, intensity and clinical characteristic of pruritus in various subtypes of CLE. A total of 153 patients with active CLE lesions were included. Their age ranged between 17 and 82 years (mean 49.8 ± 15.4 years), and 115 patients (75.2%) were women. The disease activity and damage were assessed according to the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Pruritus severity was assessed with Numeric Rating Scale (NRS) and the 12-Item Pruritus Severity Scale. Dermatology Life Quality Index and EQ-5D questionnaire were used to measure quality of life. RESULTS: Pruritus was present in 116 (76.8%) of patients of whom half had NRS scoring equal or above 4 points indicating moderate or severe pruritus. Most commonly itch was localized on the scalp, face (excluding ears and nose) and arms (40.5%, 36.2%, 31.9%, respectively). Sensations connected with pruritus were most frequently described as burning, tingling and like ants crawling feeling, but 31.9% patients described it as "pure itch". More than half of patients reported that pruritus was present every day, and it was most frequent during the evenings. The pruritus scoring and the CLASI activity score were significantly correlated (r = 0.42, p = 0.0001), while no correlation was found with the CLASI damage score (p = 0.16). Both the maximum and average itch intensity were correlated with systemic lupus erythematosus (SLE) activity measured with the Systemic Lupus Erythematosus Disease Activity Index. CONCLUSIONS: Pruritus is a common, but frequently overlooked symptom of CLE. Its intensity correlates with the activity of CLE, but not with the skin damage. In more than a half of patients it occurs on a daily basis. The correlation between the intensity of pruritus and the activity of the skin lesions and the systemic involvement indicate that pruritus could be an individual indicator of both SLE and CLE activity.

Intrathrombotic appearances of AQP-1 and AQP-3 in relation to thrombus age in murine deep vein thrombosis model.

Aquaporins (AQPs) are membrane-bound proteins for water transportation and are useful for diagnosing drowning and wound vitality in forensic pathology. Here, we examined intrathrombotic expression of AQP-1 and AQP-3 using deep vein thrombosis models in mice. To perform immunohistochemical analyses, we used anti-AQP-1 and anti-AQP-3 antibodies. In thrombus samples with the post-ligation intervals of 1 to 5 days, AQP-1+ areas were over 70%. At 7 days after the IVC ligation, AQP-1+ areas became less than 50%, eventually decreasing to 11% at 21 days. At 3 days after the IVC ligation, AQP-3+ cells started to appear from the peripheral area. Thereafter, the positive cell number progressively increased and reached to a peak at 10 days after the IVC ligation. When the intrathrombotic AQP-1+ area was as large as the intrathrombotic collagen area or smaller, it would indicate a thrombus age of ≥ 10 days. AQP-3+ cell number of > 30 would indicate a thrombus age of 10-14 days. Collectively, our study implied that the detection of AQP-1 and AQP-3 would be useful for the determination of thrombus age.

Complete decapitation by a self-constructed guillotine in a burned body - complex suicide or postmortem burning?

We report a suicide case of complete decapitation using a self-constructed guillotine. A 45-year-old man, whose body was severely burned, was found dead. The head was completely separated from the middle level of the neck, and a sharp blade with a steel frame was placed between the head and neck. The severance plane passed between the C4 and C5 vertebrae. Vital reactions such as hemorrhage could not be confirmed at the decapitated skin edge because the body was severely burned. Both common carotid arteries were sharply transected. Subendocardial hemorrhage was detected in the left ventricle. Only a little blood, but no soot, was detected in the respiratory tract, including the trachea and bilateral bronchi. Subarachnoid hemorrhage was noted at the edge of the cervical spinal cord. The saturation level of CO-Hb was 5.7% in the left cardiac blood, 5.9% in the right cardiac blood, and 5.8% in the peripheral blood from the femoral vein. Cervical transection was diagnosed as the cause of death. We believe that he was unintentionally burned by spread fire from an automobile after decapitation by a self-constructed guillotine.

The application of autophagy to thrombus age estimation in murine deep vein thrombosis model.

We immunohistochemically examined the intrathrombotic dynamics of autophagy during thrombogenesis using murine deep vein thrombosis (DVT) models. To perform the immunohistochemical analyses, we used anti-LC3 antibody and anti-p62 antibody for detecting the intrathrombotic autophagic functions. We estimated dynamics of the intrathrombotic autophagy as LC3+ cell number (×1000, five fields) with the thrombus ages (each group n = 5). The number of LC3+ cells was once decreased at 3 days, and then increased until 10 days. On the contrary, the number of p62+ cells progressively increased until 10 days after the inferior vena cava (IVC) ligation, and then gradually decreased. Especially, in all of thrombus samples with the postligation intervals of 5-10 days, both numbers were larger than 10. Subsequently, we compared the number of LC3+ cells to that of p62+ cells. Although, at 1 day after the IVC ligation, LC3+ cell number significantly exceeded p62+ cell number, the former was significantly or relatively less than the latter at 3 days or more after the IVC ligation. Thus, positive cells of > 10 in both LC3 and p62 indicated the thrombus age of 5-10 days. Upon comparison of immunopositive cells in LC3 and p62, the p62/LC3 ratio was > 1.0 in 29 out of 30 thrombus samples aged 3-21 days, and all of 1-day-old thrombus had the p62/LC3 ratio of < 0.5. Thus, the ratio of > 1.0 and that of < 0.5 could indicate thrombus age of 3 days or more and that of 1 day, respectively. Collectively, our study implied that the detection of autophagy-related molecules such as LC3 and p62 would be useful for the determination of thrombus age.

A case of complex suicide due to acute nicotine intoxication caused by cigarette ingestion.

This paper presents an unusual complex suicide case that died of nicotine addiction. The deceased was a 40-year-old male who was found lying dead on the floor in his room. In external findings, many incision wounds on his forearms and skin discoloration with epidermolysis on his cervical region could be seen. In the room, a blood-stained scissors and electric cord hanged on the exercise bike were found. Moreover, nine cigarette residues which were only the filter part and empty bottle of coffee were found on his side. At autopsy, we found that those injuries were not serious enough to lead him to the death. Toxicologically, caffeine, nicotine, cotinine, mirtazapine, and olanzapine could be detected, and the concentrations of nicotine were 3.740, 2.140, 3.100, and 451.100 µg/ml in cardiac blood, peripheral blood, urine, and stomach contents, respectively. These concentrations were evaluated as the fatal levels, and the cause of his death was diagnosed as acute nicotine intoxication.

Forensic pathological study on temporal appearance of dendritic cells in skin wounds.

Dendritic cells (DCs) can essentially contribute to innate and adaptive immune system in various organs. A double-color immunofluorescence analysis was carried out with anti-CD11c and -HLA-DRα antibodies to detect DCs in 53 skin wounds (their postinfliction intervals: group I, 0-3 days; group II, 4-7 days; group III, 9-14 days; and group IV, 17-21 days). CD11c+HLA-DRα+ DCs were first observed in skin wounds with postinfliction intervals of 3 days, and the DC numbers were found to be elevated in skin wounds with the subsequent increase in postinfliction intervals. Semi-quantitative morphometric analyses showed that the DC number was the highest in the 12-day-old wound. More than 50 DCs were present in 8 of 10 samples (80%) in group II and 14 of 16 samples (87.5%) in group III, and there was no difference between the two groups. Thus, the presence of DCs in a skin wound was possibly estimated as postinfliction intervals of at least 3 days. Furthermore, when a skin wound contained > 50 DCs, its age would be judged as 4-14 days. Collectively, the appearance of DCs in human skin wounds may provide useful information in determining the age of a wound.

A case of alopecia as IgG4-related skin disease.

A 53-year-old man with autoimmune pancreatitis as IgG4-related disease presented alopecia. Immunostaining showed perifollicular infiltration of IgG4-positive cells and perifollicular/intrafollicular infiltration of predominantly CD4-positive cells, especially in the upper and lower parts. Alopecia areata is characterized by perifollicular/intrafollicular lymphocyte infiltration of the lower bulb and inflammation in the upper dermis. We determined the patient had IgG4-related skin disease, rather than alopecia areata. Alopecia as IgG4-related skin disease has not been reported previously.

A case of rheumatoid vasculitis with acquired reactive perforating collagenosis.

A 55-year-old man with rheumatoid arthritis (RA) presented hyperkeratotic erythematous papules with crusts or blisters on his limbs and buttocks. A histological study showed acquired reactive perforating collagenosis. Soon, skin lesions changed to umbilicated lesions with black necrosis, and the scar from his skin biopsy ulcerated with induration due to rheumatoid vasculitis. Systemic corticosteroids and tacrolimus administration resolved the RA and skin lesions. Rheumatoid vasculitis with acquired reactive perforating collagenosis has not been reported previously.

Forensic application of epidermal AQP3 expression to determination of wound vitality in human compressed neck skin.

In forensic practices, it is often difficult to determine wound vitality in compression marks of the neck with naked eyes. AQP1 and AQP3 are the major water channels associated with skin. Thus, we immunohistochemically examined the expression of AQP1 and AQP3 in neck skin samples to discuss their forensic applicability to determination of the wound vitality. Skin samples were obtained from 56 neck compression cases (hanging, 35 cases; strangulation, 21 cases). The intact skin from the same individual was taken as a control. Although AQP1 was immnunostained in dermal capillaries in both the neck compression marks and intact skin samples, there was no significant difference in the magnitude of AQP1 expression between both groups. On the contrary, AQP3-positive signals could be faintly detected in uninjured skin samples, and the positive signals seemed more intense in the keratinocytes in compression regions. Morphometrical analyses revealed that the ratio of AQP3-expressed keratinocytes was significantly enhanced in neck compression regions, compared with control groups. From the viewpoints of forensic pathology, immunohistochemical detection of AQP3 in the neck skin can be considered a valuable marker to diagnose the trace of antemortem compression.

Immunohistochemical analysis on aquaporin-1 and aquaporin-3 in skin wounds from the aspects of wound age determination.

Immunohistochemical investigation of aquaporin (AQP)1 and AQP3 was performed in human skin wounds obtained from forensic autopsy cases. A total of 55 human skin wounds of different postinfliction intervals were collected as follows: group I, 0-3 days (n = 16); II, 4-7 days (n = 11); III, 9-14 days (n = 16); and IV, 17-21 days (n = 12). In uninjured skin samples, AQP1 and AQP3 could be slightly detected in dermal vessels and keratinocytes, respectively. The percentage of AQP1+ vessels and the number of AQP3+ keratinocytes were apparently elevated in accordance with wound ages. The number of AQP3+ keratinocytes was distinctly evident in groups II and III. Morphometrically, both AQP1+ vessel area and AQP3+ cell number were markedly increased in group II, compared with other three groups. With regard to forensic safety, AQP1+ vessel area of over 5% would imply wound ages of 4-12 days. Moreover, the positive area of > 15% would suggest wound age of 7-10 days. Especially, most samples of skin wounds aged 5-10 days except for only one sample (a 10-day-old wound) showed AQP3+ cell number of > 300, and the remaining other samples had that of < 300. Thus, the AQP3+ cell number of > 300 would indicate wound ages of 5-10 days. Collectively, immunohistochemical analyses of AQP1 and AQP3 in human skin wounds would support the objective accuracy of wound age determination.

Severer lupus erythematosus-like skin lesions in MRL/lpr mice with homozygous Kitwsh/wsh mutation.

OBJECTIVE: To clarify the roles of mast cells (MCs) on the pathogenesis of lupus erythematosus (LE)-like skin lesions on MRL/lpr mice. METHODS: MRL/lpr mice were mated with C57BL/6-Kitwsh/wsh mice and the heterozygous F1 mice were 10 times backcrossed with the parental MRL/lpr to generate MRL/lpr-Kitwsh/wsh mice. MC-deficient MRL/lpr-Kitwsh/wsh mice were compared with MRL/lpr-Kit+/+ and MRL/lpr-Kitwsh/+ mice with intact MCs. RESULTS: MRL/lpr-Kitwsh/wsh mice developed skin lesions without infiltrating MCs. As similar skin lesions on MRL/lpr-Kit+/+ mice and MRL/lpr-Kitwsh/+ mice contain comparable number of MCs, these mice were collectively analyzed as MRL/lpr mice with MCs. Compared with MRL/lpr mice with MCs, skin lesions developed earlier and showed consistently higher severity, with significantly higher mRNA expressions of many inflammatory cytokines in the dorsal skin on MRL/lpr mice without MCs. Furthermore, survival rate was significantly lower in MRL/lpr mice without MCs. The number of infiltrating MCs significantly increased in association with the severity of skin lesions in MRL/lpr mice with MCs. CONCLUSIONS: These results demonstrated that MCs are infiltrated to suppress the progression of LE-like skin lesions in MRL/lpr mice.

Disease severity and prophylactic measures in patients with cutaneous lupus erythematosus: results of a worldwide questionnaire-based study.

INTRODUCTION: Due to a wide array of dermatologic manifestations, assessment of disease severity in cutaneous lupus erythematosus (CLE) remains challenging. Given a need for some standardization in this field, we conducted a worldwide questionnaire-based study among physicians experienced in CLE management. AIM: We asked about CLE assessment, their prophylactic measures advised to patients, and treatment recommendations. MATERIAL AND METHODS: A total of 83 completed questionnaires were received. Participating physicians recommended assessing disease severity at each patient's visit (39.1%), monthly (4.9%) or at least every third month (17.3%). Almost half of the responding physicians (47.0%) waited 2-3 months before identifying a specific treatment option as not effective. RESULTS: The vast part of the participants informed their patients about of the risks of sun exposure and advised adequate preventive measures. Smoking was less frequently a matter of discussion between physicians and their patients. Recommendations for the timing of CLE severity assessment likely depends on disease severity and the type of therapeutic intervention. CONCLUSIONS: Proper patient education about effective prophylactic measures should be included during routine CLE patient consultations.

Development of classification criteria for discoid lupus erythematosus: Results of a Delphi exercise.

BACKGROUND: No classification criteria currently exist for discoid lupus erythematosus (DLE), which has led to problematic heterogeneity in both observational and interventional research efforts. OBJECTIVES: We sought to develop DLE classification criteria based on consensus of international expert opinion of relevant stakeholders in the field. METHODS: Using a Delphi consensus process and nominal group techniques, potential items for classification criteria were generated. Experts ranked items in terms of their appropriateness and ability to discriminate DLE from other diagnoses, and items were subsequently eliminated using consensus exercises. RESULTS: A final list of 12 clinical and histopathologic items was generated for potential inclusion into a set of DLE classification criteria through a formal ongoing validation process. LIMITATIONS: The participants are predominantly composed of DLE experts in North America and Europe. CONCLUSION: This work represents a key step toward the development of formal DLE classification criteria.

Adipophilin expression in cutaneous malignant melanoma.

BACKGROUND: The lipogenic pathway is upregulated in cancer cells, including melanomas. However, the pathological significance of cellular lipids in melanocytic lesions has yet to be determined. In this study, we evaluated intracytoplasmic lipid droplets in melanocytic nevi (MNs) and malignant melanomas via immunohistochemical analysis of adipophilin (ADP), which coats lipid droplets. METHODS: One hundred primary cutaneous melanocytic lesions [33 MNs, 17 melanomas in situ (MIS), and 50 invasive melanomas (IMs)] were immunostained for ADP. The intensity score (IS) and proportion score (PS) of ADP staining in each case was recorded semiquantitatively on a scale of 0 to 3+. RESULTS: High ADP expression (IS2/3+ and PS2/3+) was observed in 27 primary cutaneous melanocytic lesions that consisted of 23 IMs, three MISs, and one MN. Consequently, high ADP expression was associated with malignancy (38.8% vs. 3.0%; p < 0.0001). Among the IMs, high ADP expression was more prevalent in pT3/4 than pT1/2 (63.3% vs. 23.8%; p = 0.01) and Stage 3/4 than Stage 1/2 (76.9% vs. 36.8%; p = 0.02). CONCLUSIONS: The majority of the melanocytic lesions with high ADP expression were malignant melanomas in our cohort. Therefore, ADP expression may serve as a sensitive diagnostic marker for malignant melanoma.

Protective effects of Aloe sterols against UVB-induced photoaging in hairless mice.

BACKGROUND: Aloe vera is a traditional medical plant whose gel has been widely used in skin care. Previously, we have identified Aloe sterols from Aloe vera as active ingredients. This study investigated the protective effects of Aloe sterols without polysaccharides, against ultraviolet B (UVB)-induced skin photoaging in mice using Aloe vera gel extract (AVGE) obtained by supercritical fluid extraction. METHODS: Aloe vera gel extract was supplemented in the diet (12 or 120 ppm), and HR-1 hairless mice were exposed to UVB irradiation for 7 weeks. Skin measurements and histological and analytical studies were performed. RESULTS: Repeated UVB irradiation induced rough wrinkling of skin with water content reduction and hyperkeratosis. AVGE administration resulted in the significant improvement of UVB-induced skin dryness, epidermal thickness, and wrinkle formation. The AVGE group also suppressed the degenerations of dermal collagen fibers and the appearance of cutaneous apoptosis cells induced by UVB. Furthermore, AVGE administration reduced the excess elevation of pro-inflammatory cytokines (IL-1ß and TNF-α) and matrix metalloproteinases (MMP-2, MMP-9, MMP-12, and MMP-13) in UVB-exposed skin. CONCLUSION: The dietary ingestion of Aloe sterols protected against chronic UVB damage in mouse skin, and our results suggest that Aloe sterols may prevent skin photoaging through the anti-inflammation and MMP regulation.

The first nationwide surveillance of antibacterial susceptibility patterns of pathogens isolated from skin and soft-tissue infections in dermatology departments in Japan.

To investigate the trends of antimicrobial resistance in pathogens isolated from skin and soft-tissue infections (SSTI) at dermatology departments in Japan, a Japanese surveillance committee conducted the first nationwide survey in 2013. Three main organisms were collected from SSTI at 30 dermatology departments in medical centers and 10 dermatology clinics. A total of 860 strains - 579 of Staphylococcus aureus, 240 of coagulase-negative Staphylococci, and 41 of Streptococcus pyogenes - were collected and shipped to a central laboratory for antimicrobial susceptibility testing. The patient profiles were also studied. Among all 579 strains of S. aureus, 141 (24.4%) were methicillin-resistant (MRSA). Among 97 Staphylococcus epidermidis strains, 54 (55.7%) were methicillin-resistant (MRSE). MRSA and MRSE were more frequently isolated from inpatients than from outpatients. Furthermore, these methicillin-resistant strains were also isolated more frequently from patients with histories of taking antibiotics within 4 weeks and hospitalization within 1 year compared to those without. However, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains between patients with a history of hospitalization within 1 year and those without. Therefore, most of the isolated MRSA cases at dermatology departments are not healthcare-acquired, but community-acquired MRSA. S. pyogenes strains were susceptible to most antibiotics except macrolides. The information in this study is not only important in terms of local public health but will also contribute to an understanding of epidemic clones of pathogens from SSTI.

The Clinical and Histological Effect of a Low-Fluence Q-Switched 1,064-nm Neodymium: Yttrium-Aluminum-Garnet Laser for the Treatment of Melasma and Solar Lentigenes in Asians: Prospective, Randomized, and Split-Face Comparative Study.

BACKGROUND: The low-fluence Q-switched 1,064-nm neodymium:yttrium-aluminum-garnet laser (QSNYL) is popular for melasma treatment among Asians. OBJECTIVE: This study was to evaluate the clinical and histological effects of the low-fluence QSNYL for treatment of melasma and solar lentigenes. MATERIALS AND METHODS: In this randomized split-face clinical study, 22 patients with melasma or solar lentigo received low-fluence QSNYL weekly for 10 sessions on one cheek. The treatment efficacy was determined by Mexameter skin colorimetry, physician and patient assessment, and by evaluating histological changes. RESULTS: The treated sides had statistically significant reductions in the melanin and erythema indices (EI); 50.0% of melasma and 62.5% of solar lentigo patients had >50% clearance after the final treatment. The increased EI, vascularity, and mast cell activity in patients with melasma and large-sized solar lentigo showed no improvement. The recurrence rates were 16.7% and 12.7% for melasma and solar lentigo, respectively. Postinflammatory hyperpigmentation developed in 1 patient, but no serious side effects were noted. CONCLUSION: Low-fluence QSNYL is effective in treating melasma and small type solar lentigo in Asians. The authors' study also demonstrated that lesion thickness, vascularity, and mast cell activity can be used to predict the efficacy of the treatment of these lesions.

The continued use of sunscreen prevents the development of actinic keratosis in aged Japanese subjects.

It is well known that the trigger for actinic keratosis (AK) mainly depends on UV exposure. We evaluated the effects of long-term use of sunscreen on the histopathological and dermoscopic changes of AK in aged patients. Eighteen months use of sunscreen produced no change in the number of actinic keratoses or the advancement of histological grade. Although a significant decrease was not observed in the number of positive cells of p53, Ki-67 and COX-2 of the subjects who used sunscreen for 18 months, the downward tendencies of these proteins were observed. The continued use of sunscreen decreased the number of CD31-positive vessels significantly using the Chalkley method, and a significant improvement in scaling and vessel dots was found by dermoscopic study. Moreover, a relationship was found in the amount of sunscreen use and the number of actinic keratoses. Considering these results, it was thought that application of sunscreen reduces the risk of advancement of AK to higher grade AK and squamous cell carcinoma.

Tumor budding is an independent risk factor for lymph node metastasis in cutaneous squamous cell carcinoma: a single center retrospective study.

BACKGROUND: Although tumor budding is acknowledged as a risk factor for lymph node metastasis in certain types of carcinoma, it is not well investigated in cutaneous squamous cell carcinomas (SCCs). In this study, we analyzed the correlation between tumor budding and nodal metastasis in cutaneous SCC. METHODS: Histopathologic specimens of 15 metastasizing and 144 non-metastasizing cutaneous SCC were retrospectively reviewed. Cut-off point for tumor budding was determined at five or more foci of an isolated cancer cell or a cluster comprising <5 cells /1.23 mm(2) in the invasive front of the tumor under hematoxylin and eosin sections. RESULTS: Tumor budding was positive in 93.3% of metastasizing cutaneous SCC and 25.7% of non-metastasizing cutaneous SCC, respectively (p < 0.0001). In multivariate analysis, tumor budding was an independent risk factor for nodal metastasis among the other risk factors (tumor size, tumor thickness, Clark level and poor differentiation) (p = 0.0021). In combination with tumor thickness >4 mm, tumor budding became a better marker for predicting nodal metastasis (sensitivity 93.3%, specificity 84.7%). CONCLUSIONS: In our cohort, tumor budding was an independent risk factor for nodal metastasis. Our data suggests the promising role of tumor budding in risk evaluation of cutaneous SCC.