Surgically treated genital chronic graft‐versus‐host disease in women: A report of three cases

Hematopoietic stem cell transplantation (HSCT) is a crucial treatment for hematological malignancy. Gonadal dysfunction occurs at an early stage after this treatment, and such patients may require hormone replacement therapy. Genital chronic graft-versus-host disease is a lesser-known complication of HSCT that begins with vulvar discomfort and dysuria and progresses to sexual dysfunction and retention of menstrual blood due to vaginal stenosis and obstruction; thus, significantly impairing the patient's quality of life. We describe three women who underwent vaginal reconstruction because of genital chronic graft-versus-host disease. We discuss the surgical techniques, including double cross plasty that were performed in each case. Surgical interventions enabled the continuation of HRT and facilitated sexual intercourse. In conclusion, gynecologists should be aware that genital chronic graft-versus-host disease can occur after HSCT, and that surgical treatment options are available to improve patients' symptoms and quality of life

Slow Fetal Heart Rate before Miscarriage in the Early First Trimester Predicts Fetal Aneuploidy in Women with Recurrent Pregnancy Loss

Establishing whether miscarriages result from fetal aneuploidy or other factors is important for treating recurrent pregnancy loss. We examined the relationship between fetal heart rate (FHR) before miscarriage in the early first trimester and fetal karyotype, analyzing 223 pregnant women with recurrent pregnancy loss. Among the pregnancies, 110 resulted in live births regarded as normal karyotype (the Norm-group). The other 113 pregnancies ended in miscarriage, and we categorized them into groups based on fetal karyotype, determined by chorionic villus sampling: the Misc-NK (normal karyotype) group, n=35 euploid cases; the Misc-CA1 (chromosomal abnormality) group, n=18 cases of aneuploidy with trisomies 13/18/21, Turner’s syndrome, or Klinefelter’s syndrome; and the Misc-CA2 subgroup, n=60 cases of other aneuploidies excluding those in the Misc-CA1 group. We compared the groups’ regression line slopes and intercepts for FHR by an analysis of covariance. The FHRs of the Norm, Misc-NK and Misc-CA1 groups increased from 36 to 49 days after fertilization, but did not significantly differ across these groups. The Misc-CA2 group’s FHR did not increase and significantly differed from the other three groups (p<0.01). These results suggest that the absence of an increase in FHR in early pregnancy may indicate the presence of chromosomal abnormalities causing miscarriage

Locoregional therapy with α-emitting trastuzumab peritoneal metastasis of human epidermal growth factor receptor 2-positive gastric cancer in mice

Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found, however, that locoregionally administered trastuzumab armed with astatine-211 (211At-trastuzumab) is effective against human epidermal growth factor receptor 2 (HER2)-positive PMGC in a xenograft mouse model. We first observed that 211At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in s.c. tumors. We established a PMGC mouse model using N87 xenografts stably expressing luciferase to test a-particle radioimmunotherapy with 211At-trastuzumab against PMGC. Biodistribution analysis in this PMGC mouse model revealed that the i.p. administration of 211At-trastuzumab (1 MBq) was a more efficient means of delivery of 211At into metastatic tumors than i.v.injection; the maximum tumor uptake with i.p. administration was over 60% injected dose per gram of tissue (%ID/g) compared to approximately 18%ID/g with i.v. injection. Surprisingly, a single i.p. injection of 211At-trastuzumab (1 MBq) was sufficient to completely eradicate intraperitoneally disseminated HER2-positive GC xenografts in two of six treated mice by inducing DNA doublestrand breaks, and to drastically reduce the tumor burden in another three mice.No bodyweight loss, leukocytopenia, or significant biochemical changes in liveror kidney function were observed in the treatment group. Accordingly, locoregionally administered 211At-trastuzumab significantly prolonged the survival time of HER2-positive PMGC mice compared with control treatments. Our results provide a proof-of-concept demonstration that locoregional therapy with 211At-trastuzumab may offer a new treatment option for HER2-positive PMGC

Whole gamma imaging: a new concept of PET combined with Compton

We proposed a concept of whole gamma imaging (WGI) that utilizes all detectable gamma rays for imaging. An additional detector ring, which is used as the scatterer, is inserted in the field-of-view of a PET ring so that single gamma rays can be detected by the Compton imaging method. In particular, for the non-pure positron emitters which emit an additional gamma ray almost at thesame time, triple gamma imaging will be enabled; localization on each line-of-response (LOR) is possible by using the Compton cone of the additional gamma ray. We developed a prototype to show a proof of the WGI concept. The diameters of scatterer ring and PET ring were set as 20 cm and 66 cm, respectively. For Compton imaging of the 662-keV gamma ray from a 137Cs point source, spatial resolution obtained by the list-mode OSEM algorithm was 4.4 mm FWHM at the 8 cm off-center position and 13.1 mm FWHM at the center position. For PET imaging of a 22Na point source, spatial resolution was about 2 mm FWHM at all positions. For the triple gamma imaging, 5.7 mm FWHM (center) and 4.8 mm FWHM (8 cm off-center) were obtained for the22Na point source just by plotting the intersecting points between each LOR and each Compton cone of the 1275-keV gamma ray. No image reconstruction was applied. Scandium-44 was produced as a practical candidate of the non-pure positron emitters, and 6.6 mm FWHM (center) and 5.8 mm FWHM (8 cm off-center) were obtained in the same manner. This direct imaging approach which neither requires time-consuming event integration nor iterative imagereconstruction may allow in vivo real-time tracking of a tiny amount of activity. Our initial results showed the feasibility of the WGI concept, which is a novel combination of PET and Compton imaging