Although bullous pemphigoid and cicatricial pemphigoid are sometimes associated with malignancy, it remains uncertain whether such an association is pathogenetically related or just a coincidence attributable to the advanced age of the patients. We report a 61-year-old patient with antiepiligrin (laminin 5) cicatricial pemphigoid (AeCP) associated with an advanced gastric carcinoma. The gastric carcinoma cells in this patient were shown to produce laminin 5 by immunofluorescence microscopy, and the patient's serum contained autoantibodies directed against laminin 5 on immunoprecipitation. Furthermore, the blistering symptoms and the titre of antibasement membrane zone antibodies coordinately changed with the resection and subsequent relapse of the gastric cancer. These observations suggest that the gastric carcinoma producing laminin 5 may have induced the production of autoantibodies to this laminin, which were pathogenic to the skin and mucous membranes in this patient. This report demonstrates a link between this autoimmune subepithelial blistering disease and malignancy. It is of interest and potential great importance to examine other cases of AeCP for such a potential association.

Teratogenic effects of azosemide, a loop diuretic, were investigated in rats, mice and rabbits. Azosemide was given orally to pregnant rats, mice and rabbits during organogenesis. The pregnant animals were killed at term and their fetuses were examined for external, visceral and skeletal abnormalities. In rats, azosemide at 10-30 mg/kg/day did not affect intrauterine growth, resorptions and rates of external and visceral malformations. Treatment with 90 mg/kg/day resulted in a significant increase in skeletal abnormalities such as wavy ribs, bent scapula and bent humerus. However, the skeletal abnormalities observed in term fetuses could not be found in adult offspring, indicating that they were temporary. In mice, 1250 mg/kg/day of azosemide caused maternal death, abortion, and retarded maternal and fetal weight. Treatment with 200-500 mg/kg/day did not induce fetal mortalities, external and visceral malformations. Skeletal abnormalities increased in dose-dependent fashion. The type of abnormalities was identical to that encountered in rat fetuses. Furosemide as a positive control also produced similar types of skeletal abnormalities in mouse fetuses. In rabbits, azosemide did not have embryolethal or teratogenic effects even at the highest dose (6 mg/kg/ day), which caused maternal death.Treatment for a different 3-day period and then a different day during organogenesis in rats and mice showed that the sensitive period was days 15-17 of gestation with a peak on day 16 in rats, and days 12-15 with a peak on day 13 in mice.

Azosemide produced bent long bones such as wavy ribs in rat fetuses, but these abnormalities could not be found in the adult offspring. In the present study, the morphological sequence from appearance to disappearance of wavy ribs was examined in cartilage‐bone double stained specimens of fetuses and pups from mothers treated with azosemide on day 16 of gestation. The first detected change of the skeletal abnormalities was inhibition of bone deposition in the ossification centers of fetuses on day 17 of gestation. A bend first appeared on day 18 of gestation, and consisted of cartilage and portion stained neither alcian blue nor alizarin red S. Ossification began at this stage. From day 19 of gestation onward, ossification progressed toward the ends of the cartilage model including the bent region. The bend disappeared in most pups as bone in the bent region grew on days 10–14 postpartum. The present findings imply that the bend may be caused by difference in growth between cartilaginous and unstained portions, and a surface remodeling of bones may straighten the bend in the subsequent bone growth.

The present case differed from past cases by lacking inferior conjunctival sac shortening and by showing erosive lesions solely at the mucocutaneous junctions. The ocular involvement in this case correlated very well with the severity of gastric carcinoma.

Radiation doses to the heart are potentially high in patients undergoing radiotherapy for thymoma or thymic carcinoma because of their origin site and propensity for pericardial invasion. We investigated potential relationships between radiation pneumonitis (Rp) and the dosimetric parameters of lung and heart substructures in patients with thymic epithelial tumors. this retrospective study included 70 consecutive patients who received definitive or postoperative radiotherapy at a median dose of 58.3 Gy. Heart substructures were delineated according to a published atlas. The primary end point of ≥ grade 2 RP was observed in 13 patients (19%) despite a low lung dose; median lung V20 (i.e. percentage of the volume receiving at least 20 Gy) was only 16.6%. In a univariate analysis, four lung parameters, heart V35, three pulmonary artery (PA) parameters, two left ventricle parameters, and left atrium V35 were associated with the development of RP. In a multivariate analysis, only PA V35 remained significant (hazard ratio 1.04; 95% CI 1.01-1.07, p = 0.007). PA V35 of the RP versus non-RP groups were 84.2% versus 60.0% (p = 0.003). The moderate dose sparing of PA could be a candidate as a planning constraint for reducing the risk of Rp in thoracic radiotherapy. Thymic epithelial tumors (TET) generally originate within the thymus of the anterior mediastinal region, and these advanced tumors are more likely to invade the pericardial space. When patients with advanced thymoma or thymic carcinoma receive radiotherapy (RT), doses to the heart may be markedly higher than in those with locally advanced (LA) non-small-cell lung cancer (NSCLC). The RTOG 0617 study recently reported a relationship between heart doses and overall survival (OS) in LANSCLC patients treated with chemoradiotherapy (CRT) 1. Thus, heart V5 and V30 (i.e. the percentage of the normal structure volume receiving more than the indicated dose) were both identified as important predictors of OS 1. Similar findings were reported by Speirs et al. 2 ; the heart dose was associated with both OS and cardiac toxicity in LANSCLC patients treated with CRT. Potential relationships between doses to heart substructures and non-cancer death have also been investigated in early-stage NSCLC patients treated with stereotactic body radiation therapy (SBRT) 3. However, these studies left one shared question unanswered: the uncertainty of the cause of death. Difficulties are often associated with distinguishing among death due to RT-associated cardiac toxicity, other treatment-related death, and death due to comorbidities, particularly in retrospective studies 2,3. Several types of RT-associated cardiac toxicities have been identified: e.g. ischemic, pericardial, valvular, and arrhythmic 4,5. Each type of RT-associated cardiac toxicity has a different underlying mechanism 4,5 ; however, tissue fibrosis is a common mediator. For example, patients with breast cancer and lymphoma are at risk of ischemic

In vivo corneal confocal microscopy is useful for observing stromal abnormalities in cornea farinata. Further investigation of posterior stromal opacities using confocal microscopy may be useful to understand and differentiate various corneal conditions involving primarily deep stromal layers.

AimWe aimed to identify the optimal candidates for early salvage radiotherapy (SRT) among patients with biochemical recurrence (BCR) after radical prostatectomy (RP).MethodsThis multi‐institutional retrospective study included 371 patients treated using SRT after RP. The median (range) PSA level at BCR was 0.36 (0.10‐2.00) ng/mL. The association between early SRT (ie, starting PSA level < 0.50) and BCR after SRT was tested in each subgroup according to our own risk stratification.ResultsThe median follow‐up time was 51 months. By multivariate analysis, pT3b, Gleason score ≥ 8, negative surgical margins, PSA doubling time < 6 months, and non‐early SRT were associated with BCR after SRT. Patients were stratified by four risk factors other than non‐early SRT: (1) low risk (0 risk factor), (2) intermediate risk (1 risk factor), and (3) high risk (≥2 risk factors). The BCR‐free survival was higher in the early SRT group than the nonearly SRT group in the high‐risk subgroup (P = 0.020), whereas that was similar between two groups in the low‐risk and intermediate‐risk subgroups (P = .79 and .18, respectively). Multivariate analysis revealed that early SRT was beneficial for the high‐risk subgroup (P = .032), whereas early SRT was not associated with improved outcomes in the low‐risk and intermediate‐risk subgroups (P = .92 and 1.0, respectively).ConclusionsThis study suggested that early SRT seemed to contribute to better biochemical control for patients with more adverse features, whereas no benefit was observed in men with no adverse features.

The safety and efficacy of dose-escalated radiotherapy with intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) remain unclear in salvage radiotherapy (SRT) after radical prostatectomy. We examined the impact of these advanced radiotherapy techniques and dose intensification on the toxicity of SRT. This multi-institutional retrospective study included 421 patients who underwent SRT at the median dose of 66 Gy in 2-Gy fractions. IMRT and IGRT were used for 225 (53%) and 321 (76%) patients, respectively. At the median follow-up of 50 months, the cumulative incidence of late grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicities was 4.8% and 24%, respectively. Multivariate analysis revealed that the non-use of either IMRT or IGRT, or both (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.8-5.4, p < 0.001) and use of whole-pelvic radiotherapy (HR 7.6, CI 1.0-56, p = 0.048) were associated with late GI toxicity, whereas a higher dose ≥68 Gy was the only factor associated with GU toxicities (HR 3.1, CI 1.3-7.4, p = 0.012). This study suggested that the incidence of GI toxicities can be reduced by IMRT and IGRT in SRT, whereas dose intensification may increase GU toxicity even with these advanced techniques.Prostate cancer patients with biochemical recurrence (BCR) after radical prostatectomy (RP) have a risk of metastasis and cancer death 1 . Approximately 30% of patients with an adverse feature, such as high Gleason score, develop BCR after RP 2 . Salvage radiotherapy (SRT) is the only curative option for these patients 3,4 . The target volume of SRT is the prostate bed with or without the seminal vesicle 5 , which is situated precisely between the bladder and rectum. In a dosimetric study using consensus guidelines for target volume delineations of SRT, intensity-modulated radiation therapy (IMRT) enabled dose increase within acceptable dose constraints of the organs at risk (OARs) such as the bladder and rectum 6 . Regarding definitive radiotherapy (RT) without RP, the ratio of IMRT markedly increased in the 2000s 7 due to benefits of high-dose prescription 8 . As systematic reviews and meta-analyses revealed that dose escalation improved biochemical control even in SRT 9,10 , dose escalation with IMRT has been employed for patients with BCR after RP [11][12][13] . However, dose-escalated RT, even with the IMRT technique, may increase toxicity. Image-guided radiation therapy (IGRT) enables more accurate setup by computed tomography (CT) immediately before treatment. IGRT is also one of the recent advanced RT techniques, as is IMRT, and is used more commonly with IMRT. However, the safety and efficacy of dose-escalated RT with IMRT and IGRT remain unclear. In addition, whether IMRT and IGRT reduce toxicity in SRT is still unknown. Thus, we examined the impact of advanced RT techniques and dose intensification on the toxicity of SRT after RP. Methods patient selection. We identified 421 patients who received SRT for BCR after RP between 2005 and 2017 at 15 institutions....