The Experience and the Characteristics of Patients With Tele-ICU Implementation in a Rural Community Hospital.

Background Tele-ICUs are increasingly being used in the US. In Japan, young physicians mainly operate rural community hospitals to manage severely ill patients. However, the introduction of the tele-ICU system in Japan is still uncommon. We introduced a tele-ICU system to a community hospital. The objective of this study is to determine if the newly introduced tele-ICU system is being effectively utilized. Methods This is a single-center, retrospective observational study. We introduced the tele-ICU system to the NachiKatsuura Town Onsen Hospital, Japan, in 2019. Thereafter, we retrospectively explored the characteristics of the consulted cases, the time of consultation, the Sequential Organ Failure Assessment (SOFA) score, and the number of consultations by month from 1st July 2019 to 31st March 2020. The main outcome was the monthly number of consultations, and other measures included the clinical characteristics of the consulted cases. Results A total of 81 cases were referred to the tele-ICU system within nine months. Sixty-two cases, excluding those with missing data, were included in the analysis. The number of consultations was almost constant during the study period and was most frequent during the day. The recommendations from tele-ICU physicians were mostly "advice on the treatment plan." The mean SOFA score was 2.56. Conclusions We introduced a Japanese-type tele-ICU system for Japanese rural community hospitals. Many cases from rural community hospitals that were referred to the tele-ICU systems were moderately severe and did not require urgent transportation. These cases are not indicated for emergency transportation and should be treated in rural community hospitals.

Mucinous Carcinoma of the Breast: Clinicopathological Features and Long-term Prognosis in Comparison with Invasive Ductal Cancer; A Single Hospital's 30+-Year Experience.

Mucinous carcinoma (MC) of the breast is a rare and special type of malignancy, with a substantial amount of extracellular mucin. We compared the clinicopathological features and the long-term survival of MC patients with those of invasive ductal carcinoma-no special type (IDC-NST) patients, and we examined prognostic factors of MC. A total of 116 patients with mucinous carcinoma and 3,258 patients with IDC-NST who underwent surgery at our hospital (1977-2008) were enrolled. The 10-year overall survival rate and breast cancer-specific survival rate (BSS) of the MC patients (88.3%, 93.7%) were both significantly higher than those of IDC-NST patients (81.6%, 85.0%) (p=0.015, p=0.005, respectively). A Cox regression analysis demonstrated that MC tended to be an independent prognostic factor (hazard ratio 0.44, p=0.098). The BSS of the MC patients with positive lymph node (LN) metastasis was significantly poorer than that of the patients without it, by univariate analysis (p=0.002). The tumor size in the MC patients with positive LN metastasis (mean 3.2 cm) was significantly larger than that in the patients without it (mean 1.9 cm) (p=0.0004). Although a Cox regression analysis revealed no independent factor, MC patients with positive LN metastasis should be treated for advanced invasive ductal breast cancer.

Significance of Microcalcifications on Mammography in the Surgical Treatment of Breast Cancer Patients with a Preoperative Diagnosis of Ductal Carcinoma in Situ by Core Needle Biopsy.

To clarify the surgical outcomes of breast cancer patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS) by core needle biopsy (CNB) (abbreviated as CNBDCIS), we retrospectively analyzed the cases of 131 patients with CNBDCIS who underwent surgery at Oomoto Hospital (32 total mastectomies, 99 conservative mastectomies). Our analysis of underestimation and predictors of invasive breast cancer of CNBDCIS revealed that the underestimation rate of CNBDCIS was 40.5% (53/131). A logistic regression analysis revealed that palpable tumors (yes to no, odds ratio [OR] 3.25), mammography (MMG) category group (category 4 or 5 to categories 1 , 2, or 3, OR 4.69) and MMG microcalcifications (no to yes, OR 0.24) were significant predictive factors for CNBDCIS invasion. In our analysis of the predictors of positive margins during CNBDCIS surgery, 36 (27.5%) of the 131 patients had positive margins after postoperative pathological examination. A logistic regression analysis revealed that the operative procedure (conservative surgery to total mastectomy, OR 21.4) and MMG microcalcifications (yes to no, OR 3.35) were significant factors related to positive margins during CNBDCIS surgery. Thus, MMG microcalcifications are a negative predictor of upgrading of CNBDCIS and a positive predictor of positive surgical margins for CNBDCIS.

Impact of the surgical modality for axillary lymph node dissection on postoperative drainage and seroma formation after total mastectomy.

BACKGROUND: The most common complications after total mastectomy with axillary lymph node treatment are prolonged drainage and seroma formation. The aim of this study was to find factors correlated with prolonged fluid discharge (prolonged drainage or seroma formation after 20th operative day or later), including surgical techniques or devices and clinical factors. PATIENTS AND METHODS: A total of 202 conclusive primary breast cancer patients underwent total mastectomy with axillary lymph node treatment between January 7, 2014 and June 20, 2018 at our hospital. The factors that correlated with the total fluid discharge volume and prolonged fluid discharge were examined statistically. The surgical modalities for total mastectomy with axillary treatment were classified into the following three groups:, Group A; skin flap formation by EC and axillary lymph node dissection by EC with ligation of the arteries and veins, Group B; skin flap formation by EC and axillary lymph node dissection by ultrasonic dissector (UD) without ligation of the vessels. Group D; skin flap formation by electrocautery (EC) and axillary lymph node dissection by picking up using forceps and ligation (PL). RESULTS: The total fluid discharge volume and prolonged fluid discharge after total mastectomy with sentinel node retrieval (33 patients) were significantly lower than those after total mastectomy with axillary lymph node dissection (169 patients). In patients treated without drainage, a high rate of seroma formation and prolonged fluid discharge were observed, and 1 patient developed seroma infection.In the total mastectomy with axillary lymph node dissection group, logistic regression analysis revealed that body mass index, 1-week drainage volume, and surgical modality were independently correlated with prolonged fluid discharge. CONCLUSIONS: The surgical procedure for axillary lymph node dissection should be considered to avoid prolonged fluid discharge, and the lymph vessels should be ligated in axillary lymph node dissection. An ultrasonic dissector was not effective in reducing the total fluid discharge volume. An optimal axillary lymph node dissection technique should be developed. For the patients without drainage, careful postoperative treatment should be given to avoid infectious seroma formation, even for patients who underwent total mastectomy with sentinel lymph node retrieval.

Safety and effectiveness of eribulin in Japanese patients with locally advanced or metastatic breast cancer: a post-marketing observational study.

Background This large-scale study was conducted to evaluate the safety and effectiveness of eribulin for the treatment of inoperable or recurrent breast cancer in real-world settings in Japan. Methods Between July and December 2011, eligible patients with inoperable or recurrent breast cancer receiving eribulin for the first time were centrally registered and observed for 1 year. Eribulin was administered intravenously (1.4 mg/m2) on days 1 and 8 of every 3-week cycle. The primary endpoint was the frequency and intensity of adverse drug reactions (ADRs). Secondary endpoints included overall response rate (ORR) and time to treatment failure (TTF). Results Of 968 patients registered at 325 institutions, 951 and 671 were included in the safety and effectiveness analyses, respectively. In the safety population, ADRs were observed in 841 patients (88.4%). The most common (≥15% incidence) were neutropenia (66.6%), leukopenia (62.4%), lymphopenia (18.4%), and peripheral neuropathy (16.8%). The most common grade ≥ 3 ADRs (>5% incidence) were neutropenia (59.8%), leukopenia (50.5%), lymphopenia (16.1%), and febrile neutropenia (7.7%). In the effectiveness population, ORR was 16.5% (95% confidence interval: 13.7, 19.4). The median TTF was 127 days (95% confidence interval: 120, 134). Conclusions The safety and effectiveness profile of eribulin was consistent with prior studies. Eribulin had a favorable risk-benefit balance when used in real-world clinical settings.

Primary osteosarcoma of the breast.

Presented herein is a case of primary pure osteosarcoma of the breast. A 59-year-old woman noticed a left breast tumor. Mammography showed a cluster of crushed stone-like calcifications, which gave the tumor a raw cotton-like appearance. Malignancy was suspected on fine-needle aspiration cytology of the tumor. An excisional biopsy was performed. The tumor was 2.0 x 2.4 cm in size. Histopathologically the tumor was composed of diffuse atypical cells with mitosis and a lot of bone. Atypical cells were thought to be neoplastic osteoblasts. Multinucleated osteoclastic cells were interspersed with osteoblasts. Spindle cells were found at the verge of the tumor. A few entrapped tubular structures were seen. Immunohistochemistry indicated that neoplastic osteoblastic cells of the tumor were stained positively for vimentin, but negatively for epithelial markers; which suggested that the tumor cell elements originated from epithelial cells. This tumor was diagnosed as primary extraskeletal osteosarcoma. Partial resection was additionally performed around the excisional biopsy without dissection of the axillary lymph nodes. Bone radionuclide scan after operation showed no abnormal uptake. At 5 years after surgery no recurrence was seen.

[Evaluation of combination therapy of high-dose toremifene and oral chemotherapy].

High-dose toremifene therapy (120 mg/day) is useful for the recurrence of receptor-positive breast cancer. However, some reports show that combination therapy of high-dose toremifene and chemotherapy exhibits additive effects. Twelve patients were given oral chemotherapy (capecitabine, 5'-DFUR+CPA, S-1) with high-dose toremifene. The overall response rate was 41.7%, in addition to 58.3% with no change beyond three months. Adverse events were restricted to headache, stomatitis and nausea. Average time to progressive (TTP) was 5.8 months. It was shown that high-dose toremifene and oral chemotherapy were useful for breast cancer recurrence without severe side effects.

COX-2 induction by heparanase in the progression of breast cancer.

Breast cancer confined within the lactiferous duct or lobule, without invading the stroma, is called ductal carcinoma in situ (DCIS), whereas breast cancer that has invaded the stroma through the basal membrane is called invasive cancer. Heparanase, an endo-beta-D-glucuronidase that specifically degrades heparan sulfate proteoglycans (HSPGs) in the extracellular matrix (ECM), plays an important role when breast cancer cells breach the basal membrane. Recently, we have reported that heparanase is involved in angiogenesis through direct induction of cyclo-oxygenase-2 (COX-2). COX-2 induces vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and is thus involved in neovascularization. The present study was undertaken to analyze surgically resected breast cancer specimens for heparanase and COX-2 expression, using specimens from 59 patients with invasive cancer and 85 patients with DCIS (including 41 cases of DCIS adjacent to invasive cancer). This study yielded the following results: a) the distribution of heparanase within tumor tissue was identical to that of COX-2; b) heparanase expression was more frequent in invasive cancer than in non-invasive cancer; c) a close positive correlation was noted between heparanase and COX-2 expression (this correlation was particularly strong in cases of invasive cancer); and d) COX-2 expression was always seen in cases positive for heparanase expression. Our results indicate that heparanase expression increases during the progression of breast cancer into invasive cancer, and that this change is accompanied by increased COX-2 expression. They also suggest that heparanase may play a novel role for COX-2 mediated tumor angiogenesis in breast-cancer progression.

Serum adiponectin is associated with fasting serum C-peptide in non-obese diabetic patients.

Circulating adiponectin (ADP) level in diabetic patients was mainly studied from a viewpoint of insulin action, with little being known about the regulation by pancreatic beta-cell function. We thus investigated the relationship between the serum ADP concentration and pancreatic beta-cell function in non-obese [body mass index (BMI) <30 kg/m(2)] diabetic patients. Serum ADP was measured in 239 type 2 diabetic patients, 61 type 1 diabetic patients and 159 non-obese and non-diabetic subjects with enzyme-linked immunosorbent assay. Serum ADP was analyzed separately by gender. In both males and females, the ADP level increased in conjugation with beta-cell dysfunction, estimated by fasting serum C-peptide, and showed marked increase in type 1 diabetic patients. Multivariate analysis in type 2 diabetic patients showed that the fasting serum C-peptide was extracted as an independent and significantly negative modulator for serum ADP in addition to BMI. The ADP level was not associated with the daily dose of injected insulin in the multivariate analysis using insulin treated patients with types 1 and 2 diabetes. These results indicate that pancreatic beta-cell function is one of a significant negative modulator for the circulating ADP level in non-obese diabetic patients and support the presence of an adipoinsular axis.

Age as a limiting factor for successful sperm retrieval in patients with nonmosaic Klinefelter's syndrome.

OBJECTIVE: To determine factors affecting successful sperm retrieval by testicular sperm extraction in patients with nonmosaic Klinefelter's syndrome. DESIGN: Medical record analysis for nonmosaic Klinefelter's syndrome patients who underwent testicular sperm extraction. SETTING: Three university-based tertiary centers. PATIENT(S): Fifty-one patients with nonobstructive azoospermia related to nonmosaic Klinefelter's syndrome. INTERVENTION(S): Testicular sperm extraction. MAIN OUTCOME MEASURE(S): Correlation of patient characteristics; serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T); as well as testicular volume with success in testicular sperm extraction. RESULT(S): We succeeded in obtaining spermatozoa in 26 patients and failed in 25. Levels of LH, FSH, and T and testicular volume did not differ between patient groups defined by success and failure. Median ages for successful and failed testicular sperm extraction were 31 and 38 years, respectively (statistically significant difference). When we analyzed success rates of testicular sperm extraction between two patient groups (<35 and > or =35 years old), the percentage of successful recovery of spermatozoa decreased after the age of 35 years (statistically significant difference). CONCLUSION(S): Testicular sperm extraction should be recommended before the critical age of 35 years.

Nine short tandem repeat loci analysis in aged semen stains using the AmpFLSTR Profiler Kit and description of a new vWA variant allele.

Nine short tandem repeat (STR) loci, D3S1358, D5S818, vWA, TH01, D13S317, TPOX, FGA, D7S820 and CSF1PO, were investigated in semen stains of various ages using the AmpFLSTR Profiler Kit. The nine STR loci were typed from semen stains stored for up to 25 years with the application of 1-10 ng DNA. This system provides a useful tool in medicolegal individualization of aged semen stains. During this investigation we found a new variant allele 18.1 at the vWA locus.

Detection of serum proteins by native polyacrylamide gel electrophoresis using Blue Sepharose CL-6B-containing stacking gels.

Analysis of serum proteins by native polyacrylamide gel electrophoresis is difficult because albumin is abundant in serum and interferes with the resolution of other proteins, especially alpha-antitrypsin which has mobility that is very similar to that of albumin. We present here a method in which serum proteins are separated by polyacrylamide gel electrophoresis using stacking gels containing Blue Sepharose CL-6B, which has a high affinity for albumin, lipoproteins, kinases, and pyridine-nucleotide-dependent oxidoreductases. During electrophoresis, proteins that bind to Blue Sepharose CL-6B stay in the stacking gel and do not migrate into the separating gel. As a consequence, certain proteins, including alpha(1)-antitrypsin, can be detected as clear bands. This method overcomes the requirement for fractionation of serum samples prior to electrophoresis to remove albumin and allows the simultaneous analysis of many samples.

Morphometric and cytogenetic characteristics of testicular germ cells and Sertoli cell secretory function in men with non-mosaic Klinefelter's syndrome.

BACKGROUND: Klinefelter's syndrome is the most frequent chromosomal abnormality in infertile men. In this study, the chromosomes of round spermatids and spermatogonia/primary spermatocytes from men with non-mosaic Klinefelter's syndrome were examined, together with the Sertoli cell secretory function and sperm morphometry. METHODS: Twenty-four men with non-mosaic Klinefelter's syndrome and nine men with obstructive azoospermia underwent therapeutic testicular biopsy. When spermatozoa in the final filtrate were present, they were processed for sperm morphometry or ICSI. Sperm morphometry was evaluated by the maximal length and width of the sperm head, the length of the midpiece and the ratio of the acrosomal region to the total surface area of the head. When round spermatids were present, they were processed for fluorescent in-situ hybridization (FISH). FISH was also applied to fragments of seminiferous tubules. Sertoli cell secretory function was measured by the amount of androgen binding protein (ABP) secreted in vitro. RESULTS: More than 93% of the evaluated round spermatids were normal. The proportions of 24,XY and of 24,XX round spermatids to the total number were significantly larger in men with Klinefelter's syndrome than in obstructed azoospermic men. Men with Klinefelter's syndrome who had spermatozoa in their testicular tissue (n = 12) were positive for both 46,XY and 47,XXY spermatogonia in their seminiferous tubules. In contrast, men with Klinefelter's syndrome without spermatozoa in their testicular tissue (n = 12) were positive for 47,XXY spermatogonia but negative for 46,XY spermatogonia in their seminiferous tubules. ABP profiles were significantly smaller in men with Klinefelter's syndrome who were negative for spermatozoa compared with men who were positive. Four pregnancies were achieved and five healthy babies were born. CONCLUSIONS: This study suggests that few 46,XXY spermatogonia undergo meiosis with an XX pairing and a Y univalent type of pairing. Hyperhaploid round spermatids (24,XY and 24,XX) may be produced by meiosis of 47,XXY spermatogonia. Men with Klinefelter's syndrome who are negative for testicular spermatozoa have a greater degree of Sertoli cell secretory dysfunction compared with men with Klinefelter's syndrome who are positive for spermatozoa. There are several defects in sperm morphometry with functional significance in men with Klinefelter's syndrome.