Hysterectomy through Minimally Invasive Surgery for Cervical High-grade Intraepithelial Neoplasia: Reassessment of the Specimens' Eligibility for Histological Examination.

Objectives: The objective was to investigate the microscopic artifacts made in the uterus of cervical high-grade squamous intraepithelial lesion (HSIL) resected by hysterectomy through minimally invasive (H-MI) procedures and to verify whether these specimens are suitable for histopathological assessment. Materials and Methods: This single-center retrospective study analyzed 28 patients with cervical HSIL, consisting of 21 premenopausal and seven postmenopausal women, who underwent H-MI. The proportion of the cervical mucosa covered by intact surface epithelium (residual ratio [RR]) was measured on microscopically. Surgical margin's status was also verified. Results: All cases developed detachment of the cervical surface epithelium to a varying extent. The RR was significantly higher in the premenopausal patients (median: 75.5%) than in the postmenopausal patients (median: 37.6%). Among the premenopausal patients, the RR was lower in the cases on whom uterine manipulator (UM) was used (median: 70.5%) than in the cases without UM use (median 92.7%). Among the 21 cases whose resected uterus contained HSIL, the vaginal resection margin was not assessable in three (14.2%) of the seven postmenopausal cases due to the artifact. Conclusion: Although transvaginal manipulation of the uterus causes detachment of the cervical surface epithelium, H-MI for cervical HSIL provides an acceptable specimen for histological assessment in premenopausal patients, even if UM is used. In postmenopausal women, H-MI easily develops artifactual loss of cervical surface epithelium, sometimes providing an unfavorable specimen for microscopic assessment.

Endoplasmic reticulum stress and collagenous formation anomalies in vascular-type Ehlers-Danlos syndrome via electron microscopy.

Vascular-type Ehlers-Danlos syndrome (vEDS) is an autosomal-dominant inherited disorder caused by a deficit in collagen III. It results from heterogeneous mutations in the α1 collagen III gene (COL3A1) and is associated with life-threatening complications, even in younger patients. However, the details of the pathogenesis underlying the COL3A1 mutation causing vEDS remain unclear. Here, we focus on anomalies in collagen fiber size and the endoplasmic reticulum (ER) stress response in patients with vEDS using electron microscopy (EM). We discovered that although the infants did not have vEDS, collagenous formations were similar to their samples in vEDS. Moreover, we examined the expression of activating transcription factor 6 (ATF6) as an ER stress marker and cartilage oligomeric matrix protein (COMP) as a binding partner protein for collagen fibrils in the dermis and COL3A1. The expression levels of ATF6 in the vEDS group were significantly higher than in infants and controls; COMP and COL3A1 levels were significantly lower. The fragile collagen fibrils in vEDS might form as a result of ER stress and that small, newly formed collagen fibrils may appear. This research revealed a novel prospect regarding an issue that has been unclear for a long time, which is the reason for the abnormal sizes of collagenous fibrils in vEDS.

Malignant lymphoma of the cervix in a bicollis uterus considered to be a post-transplant lymphoproliferative disorder in a patient after renal transplantation: A case report.

Post-transplant lymphoproliferative disorder (PTLD) refers to a group of diseases, characterized by abnormal proliferation of lymphocytes, that develop after organ transplantation. PTLD is associated with poor prognosis, and has become a major problem for transplant patients. In this report, we described a case of malignant lymphoma of the cervix in a bicollis uterus considered to be a PTLD in a patient after renal transplantation. The incidence of this disease is expected to increase as the survival rate of transplant patients improves. Hence, it is very important for gynecological oncologists to consider the presence of PTLD when examining such patients.

Anti-Inflammatory Effects of Potassium Iodide on SDS-Induced Murine Skin Inflammation.

Potassium iodide (KI), initially derived from seaweed in the early 19th century, is used for treating sporotrichosis in dermatological practice. KI has also been used to treat several noninfectious inflammatory skin diseases. However, the mechanisms underlying the improvement in such skin diseases remain unknown, and KI is not used widely. Thus, although KI is an old drug, physicians may not prescribe it frequently because they lack knowledge about it. Although KI is very inexpensive and causes few side effects, it has been superseded by new powerful and expensive drugs, such as biological agents. We applied 3% KI topically to areas of inflammation induced by SDS in mice. The levels of IL-1 and TNF-α gene expression were reduced, whereas that of IL-10 gene expression was increased. Small interfering RNA that was designed to reduce IL-10 gene expression levels was injected into the same mice, and the anti-inflammatory effects of KI were not observed. Thus, the pharmacologic action of KI is based on its anti-inflammatory effects caused by the increase in IL-10 levels. This information would increase dermatologists' awareness of KI as an efficacious and cost-effective treatment.

Diagnostic value of a nested polymerase chain reaction for diagnosing cutaneous sporotrichosis from paraffin-embedded skin tissue.

BACKGROUND: The gold standard for diagnosis of cutaneous sporotrichosis involves the isolation of the fungus, Sporothrix, by a culture test. Generally, the sampling for the culture test is performed at the same time as skin biopsy under local anaesthesia. However, the culture test may occasionally return a false negative result. OBJECTIVE: The aim of our study was to investigate the diagnostic value of a molecular method for diagnosing cutaneous sporotrichosis from formalin-fixed and paraffin-embedded (FFPE) tissues. METHODS: Over a 30-year period, we collected 52 cases of cutaneous sporotrichosis from biopsied specimens that had been positively diagnosed by a culture test. A nested PCR specific for Sporothrix detection was applied using FFPE tissue as template. The results were compared with control samples from 79 patients diagnosed with other cutaneous diseases according to histopathological, clinical findings and a cutler test. RESULTS: Of the 52 patients who were tested positive on the culture test, all cutaneous diseases were detected by PCR. Of the 59 patients in the control group, 58 tested negative by PCR. Under our conditions, the calculated sensitivity of this method was 100%, the specificity was 98.7% and the kappa coefficient was 0.984 (95% CI: 0.953-1.000). CONCLUSIONS: The specific PCR assay used appears to be a useful tool for the prompt and accurate diagnosis of sporotrichosis. Using this method, it would be possible to diagnose cutaneous sporotrichosis for patients who were suspected of cutaneous sporotrichosis but tested negative on culturing, and for pathologically suspected cutaneous sporotrichosis patients for whom the culture test was not undertaken.

Long-term oncological outcomes of minimally invasive radical hysterectomy for early-stage cervical cancer: A retrospective, single-institutional study in the wake of the LACC trial.

AIM: The objective of this study was to investigate the long-term oncological outcomes of minimally invasive radical hysterectomy (MIRH) for the treatment of early-stage cervical cancer retrospectively in the wake of the laparoscopic approach to cervical cancer (LACC) trial. METHODS: A total of 109 patients with stage IA1 with lymphovascular space involvement, IA2, and IB1 cervical cancers were included in this study. The surgical and oncological outcomes were retrospectively evaluated. All patients underwent type C MIRH with a no-touch isolation technique for cervical tumor. RESULTS: The median number of resected pelvic lymph nodes was 36 (range, 14-94), and 10 patients (9.2%) had positive nodes. One patient (0.9%) had positive surgical margins. Forty-six patients (42%) underwent adjuvant therapy. The median follow-up time was 73 months (range, 30-146 months). Five patients (4.6%) developed recurrent disease, and 3 patients (2.8%) died of cervical cancer. The 5-year disease-free survival and overall survival rates were 96.3% and 97.2%, respectively. A comparison between patients with tumor diameter ≤ 2 cm (n = 59) and those with tumor diameter > 2 cm (n = 50) did not identify any significant differences, with 5-year disease-free survival 96.6% versus 94.0% and 5-year overall survival 98.3% versus 96.0%, respectively. CONCLUSION: In this retrospective study, MIRH with a no-touch isolation technique for stage IA to IB1 cervical cancer was a safe approach in terms of oncological outcomes. However, every surgeon who treats early-stage cervical cancer should inform each patient of the results of the LACC trial because it has an exceedingly high impact.

Palmoplantar pustulosis and pustulotic arthro-osteitis treatment with potassium iodide and tetracycline, a novel remedy with an old drug: a review of 25 patients.

BACKGROUND: The use of potassium iodide (KI) to treat palmoplantar pustulosis (PPP) and pustulotic arthro-osteitis (PAO) has not previously been reported. Here, we report the first successful treatment of PPP and PAO with KI. PATIENT AND METHODS: Among 25 patients with PPP, seven had an associated PAO. All patients were administered 900 mg KI three times per day for 3 months. Overall, 12 patients received this medical treatment for the first time or had >6 months interval since the last therapy for PPP. The other 13 patients who were nonresponsive to tetracycline for >3 months prior to KI treatment were treated with a combination of KI and tetracycline. All seven patients with PAO were included in the tetracycline and KI-treated group. RESULTS: More than 70% of patients demonstrated complete clearance or ≥50% improvement in palmoplantar pustular psoriasis area and severity index (PPPASI) from baseline. In the group with <50% improvement in PPPASI from baseline, all except one patient were smokers. In the KI with tetracycline treatment group, approximately 80% demonstrated improvement. At the end of 3 months, there was remission of arthralgia in five out of seven PPP patients with PAO. CONCLUSIONS: Treatment with KI and/or its combination with tetracycline may be a useful treatment for PPP/PAO. Smoking may affect the effectiveness of these treatment modalities.

Effects of Gadodiamide on cell proliferation and collagen production in cultured human dermal fibroblasts.

Nephrogenic systemic fibrosis (NSF) is a disease characterized by fibrosis of the systemic organs in patients with renal failure. Following the findings of recent epidemiological studies and the finding of gadolinium (Gd) in the skin tissue of NSF patients, it is now definitely known that the use of Gd contrast agents can trigger NSF. To date, however, the exact mechanism underlying the induction of fibrosis in various organs by Gd remains unexplained. This study was undertaken to evaluate the influence of Gd on the proliferation activity and collagen production of cultured fibroblasts. Normal human dermis-derived fibroblasts were incubated in the presence of gadodiamide (GA) in the concentration range of 5 × 10-7 to 5 × 10-3 M. The proliferation activity of the cells was assessed on the basis of the cell counts in the fibroblast growth curve and the DNA-synthetic activity of the cells (indicator; level of 3H-thymidine uptake by cells). The collagen production was evaluated by densitometric measurement of the quantity of collagen through electrophoresis and fluorography after incorporation of 3H-proline into the procollagens. Furthermore, the expression levels of the genes for type I and III collagen were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) assay. The cell count tended to be higher when the fibroblasts were incubated in medium containing GA in the concentration range of 5 × 10-7 to 5 × 10-4M as compared to that in the GA-free control cultures; furthermore, the DNA-synthetic activity also rose in a concentration-dependent manner in the GA-treated group as compared to that in the control group. No significant changes in either the collagen production or the collagen gene expression levels were noted in cultures containing GA at concentrations between 5 × 10-7 and 5 × 10-3 M. These results suggest that the formation of sclerosing lesions in patients with NSF may be attributable to the effect of GA of enhancing the growth activity of fibroblasts.

Quantitative fluorescence in situ hybridization measurement of telomere length in skin with/without sun exposure or actinic keratosis.

Chromosomal and genomic instability due to telomere dysfunction is known to play an important role in carcinogenesis. To study telomere shortening in the epidermis surrounding actinic keratosis, we measured telomere lengths of basal, parabasal, and suprabasal cells in epidermis with actinic keratosis (actinic keratosis group, n = 18) and without actinic keratosis (sun-protected, n = 15, and sun-exposed, n = 13 groups) and in actinic keratosis itself as well as in dermal fibroblasts in the 3 groups, using quantitative fluorescence in situ hybridization. Among the 3 cell types, telomeres of basal cells were not always the longest, suggesting that tissue stem cells are not necessarily located among basal cells. Telomeres of basal cells in the sun-exposed group were shorter than those in the sun-protected group. Telomeres in the background of actinic keratosis and in actinic keratosis itself and those of fibroblasts in actinic keratosis were significantly shorter than those in the controls. Our findings demonstrate that sun exposure induces telomere shortening and that actinic keratosis arises from epidermis with shorter telomeres despite the absence of any histologic atypia.