Extended-Hours Hemodialysis without Dietary Restrictions Is Associated with Lower Risk for Developing of Dialysis-Related Amyloidosis.

Dialysis-related amyloidosis (DRA) is characterized by the deposition of amyloid consisting of beta2-microglobulin in the musculoskeletal system, causing carpal tunnel syndrome, destructive spondyloarthropathy, and/or bone cysts. Increased cystic radiolucency of the bones and tendon thickening due to inflammation are common findings in DRA. We have developed a new dialysis method, extended-hours hemodialysis without dietary restrictions for the aim of improving both hypertension and malnutrition. We retrospectively evaluated the clinical effects of dialysis time on the risk for developing of DRA. The study subjects were all of the 30 patients who had received this treatment for more than 11 years. They were divided into two groups according to the weekly dialysis hours: 15 patients ≥ 16.5 hours/week (L-group) and 15 patients ≤ 15.5 hours/week (S-group). Plain x-ray imaging and ultrasonography were used to assess cystic radiolucency of the bones and thickness/diameter of the soft tissues. The proportion of the carpal bone cystic radiolucency was lower in the L-group. The severity of median nerve compression at the wrist was significantly less in the L-group (right hand: p = 0.0082, left hand: p = 0.0137). Multivariate regression analysis showed that dialysis time was a predictor of median nerve compression (ß = -0.559, p = 0.005). In conclusion, extended-hours hemodialysis without dietary restrictions contributes to lower the risk for developing of DRA at the wrist. We therefore propose that extended-hours hemodialysis without dietary restrictions is a preferred method which maintains the patients' quality of life compared with the conventional hemodialysis method.

Abdominal Myomectomy for Huge Uterine Myomas with Intra-arterial Balloon Occlusion: Approach to Reduce Blood Loss.

Abdominal myomectomy for a huge myomas, especially uterine cervical myoma, is difficult because of risks, such as intraoperative bleeding or injury to adjacent organs. Therefore, understanding of the positional relationships among a huge myoma, especially cervical or intraligamental myoma, and the vascular plexuses in the right and left cardinal ligaments is important for prevention of massive bleeding during myomectomy. While sufficiently performing preoperative assessment with pelvic examination, ultrasonography, magnetic resonance imaging (MRI), etc., surgeons should always keep in mind how they can reduce the blood loss volume, while safely and surely performing resections. For a cervical myoma of the uterus and giant uterine leiomyoma that leave no intrapelvic space and prevent palpation and identification of the uterine arteries and the internal iliac arteries, surgery can be performed safely by preoperatively placing balloon catheters in the internal iliac arteries. Hemostaic strategies for myomectomy and tips of subsequent pregnancy following myomectomy are also described.

Prognostic factors and optimal therapy for stages I-II neuroendocrine carcinomas of the uterine cervix: A multi-center retrospective study.

PURPOSE: We aimed to determine appropriate treatment guidelines for patients with stages I-II high-grade neuroendocrine carcinomas (HGNEC) of the uterine cervix in a multicenter retrospective study. PATIENTS AND METHODS: We reviewed the clinicopathological features and prognoses of 93 patients with HGNEC of International Federation of Gynecology and Obstetrics (FIGO) stages I and II. All patients were diagnosed with HGNEC by central pathological review. RESULTS: The median overall survival (OS) and disease-free survival (DFS) were 111.3months and 47.4months, respectively. Eighty-eight patients underwent radical surgery, and five had definitive radiotherapy. The hazard ratio (HR) for death after definitive radiotherapy to death after radical surgery was 4.74 (95% confidence interval [CI], 1.01-15.90). Of the surgery group, 18 received neoadjuvant chemotherapy. Pathological prognostic factors and optimal adjuvant therapies were evaluated for the 70 patients. Forty-one patients received adjuvant chemotherapy with etoposide-platinum (EP) or irinotecan-platinum (CPT-P). Multivariate analyses identified the invasion of lymphovascular spaces as a significant prognostic factor for both OS and DFS. Pelvic lymph node metastasis was also a prognostic factor for DFS. Adjuvant chemotherapy with an EP or CPT-P regimen appeared to improve DFS (HR=0.27, 95% CI, 0.10-0.69). A trend toward improved OS was also observed, but was not statistically significant (HR=0.39, 95% CI, 0.15-1.01). CONCLUSION: Radical surgery followed by adjuvant chemotherapy with an EP or CPT-P regimen was optimal treatment for stages I and II HGNEC of the uterine cervix.

The utility and effectiveness of an internal iliac artery balloon occlusion catheter in surgery for large cervical uterine fibroids.

OBJECTIVE: Surgery for uterine cervical fibroids is difficult because of restricted surgical access and risks such as intraoperative bleeding or injury to other organs. The internal iliac artery balloon occlusion catheter (IIABOC) provides effective hemostasis for placenta previa and atonic hemorrhage, and is increasingly used in surgery for uterine fibroids for controlling intraoperative hemorrhage. We investigated the efficacy and safety of the IIABOC for controlling intraoperative bleeding in total abdominal hysterectomies (TAH) and abdominal myomectomies (AM) for large cervical fibroids. MATERIAL AND METHODS: From 2007 to 2014, the IIABOC was used in 22 cases (12 for TAH and 10 for AM) in which cervical fibroids fully occupied the pelvic cavity. Intraoperative blood loss, operating time, sample weight, use of blood transfusion, and injury to other organs were assessed. RESULT: Mean blood loss, operative time, and sample weight in the IIABOC cases were 510 mL, 178 min, and 2550 g for TAH; and 727.5 mL, 157.5 min, and 1850 g for AM. Blood loss divided by sample weight in IIABOC cases was significantly lower than that in non-IIABOC cases during the same time period, for both TAH and AM. Allogeneic blood transfusion was not necessary, and complications of injury to other organs did not occur in any of the 22 cases. CONCLUSIONS: For large cervical fibroids with limited operating space, surgery was performed under bleeding control by occlusion of the internal iliac artery with an IIABOC. This technique enables control of hemorrhage and safe operative management in gynecological surgery.

Efficacy of PET/CT to exclude leiomyoma in patients with lesions suspicious for uterine sarcoma on MRI.

OBJECTIVE: To analyze the efficacy of positron emission tomography/computed tomography (PET/CT) for the diagnosis of uterine sarcoma. MATERIALS AND METHODS: Thirty-four patients evaluated between January 2010 and March 2015 were retrospectively enrolled. All patients in whom uterine sarcoma was suspected based on contrast-enhanced magnetic resonance imaging (MRI) findings (heterogeneous, high signal intensity on T2-weighted images and/or high intensity on T1-weighted images) underwent PET/CT for further assessment. Patients were divided into 2 groups based on postoperative pathological findings: uterine sarcoma (n = 15) and leiomyoma (n = 19). The maximum standardized uptake value (SUVmax) of all lesions was measured using PET/CT; we calculated the optimal cutoff value for diagnosing sarcoma. RESULTS: The median SUVmax for uterine sarcoma and leiomyoma was 12 and 4.1, respectively; these values were significantly different. An SUVmax of greater than 7.5 was able to exclude leiomyoma with 80.8% sensitivity and 100% specificity (area under the curve, 95.3%). A cutoff SUVmax of 7.5 yields 100% specificity, and a cutoff SUVmax of 4.4 yields a 100% negative predictive value (NPV). The combination of PET/CT and lactate dehydrogenase (LDH) levels had a sensitivity of 86.6%, specificity of 100%, positive predictive value of 100%, and an NPV of 90.4%. No relation between histopathology or International Federation of Gynecology and Obstetrics (FIGO) stage and 18-fluoro-2-deoxy-d-glucose uptake value on PET/CT was seen. The surgical outcome trended toward a correlation with the SUVmax, although this was not statistically significant. CONCLUSIONS: In patients with MRI findings consistent with either uterine sarcoma or leiomyoma, PET/CT can decrease the false-positive rate by setting an optimal cutoff SUVmax of 7.5. Using this cutoff can avoid unnecessary surgery.

Analysis of positron emission tomography/computed tomography in patients to differentiate between malignant transformation of endometrioma and endometrioma.

PURPOSE: Of those patients who undergo open surgery for a suspicion of malignant transformation of endometrioma (MTOE) due to solid nodule enhancement identified by contrast-enhanced magnetic resonance imaging (MRI), some benign endometrioma cases are included. The aim of this retrospective study was to determine the value and diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) using 18-fluoro-2-deoxy-D-glucose (FDG) to differentiate between MTOE and endometrioma. PATIENTS AND METHODS: We retrospectively analyzed 1599 consecutive patients who underwent laparoscopic surgery for the diagnosis of endometrioma preoperatively and 31 patients who underwent open surgery for a suspicion of MTOE preoperatively from January 2003 to December 2011. We analyzed the age, serum CA125 levels, and MRI findings of the patients and calculated the optimal cut-off value for PET/CT using receiver operating characteristic curve analysis. RESULTS: Of the 1,599 patients who underwent laparoscopic surgery for a suspicion of endometrioma preoperatively, malignancy was identified in one (0.062 %) patient. Of the 31 patients who underwent open surgery for a suspicion of MTOE preoperatively, 11 were diagnosed with endometrioma (false positive group) and 20 with MTOE stage I (positive group). Age, tumor size, presence of shading on MRI and maximum standardized uptake values (SUVmax) on PET/CT were significantly different between the two groups. A SUVmax cut-off >4.0 is capable of excluding endometrioma cases, with 75 % sensitivity and 100 % specificity (area under the curve 90 %). CONCLUSION: PET/CT is a good diagnostic tool for MTOE using the optimal SUVmax cut-off of 4.0 (75 % sensitivity and 100 % specificity).

Outcome of Neoadjuvant Intra-Arterial Chemotherapy and Radical Hysterectomy for Treatment of Bulky Stage IB to Stage IIB Uterine Cervical Cancer: Can Postoperative Irradiation Be Avoided?

OBJECTIVES: We evaluated whether our neoadjuvant intra-arterial chemotherapy (NAIC) effectively precludes the need for postoperative radiation therapy in patients treated by radical hysterectomy for IB2 to IIB cervical cancer. MATERIALS AND METHODS: Study subjects were 52 patients with a bulky cervical tumor diagnosed and treated at Juntendo University Hospital or Juntendo Nerima Hospital. The NAIC combined cisplatin, epirubicin, mitomycin-C, and 5-fluorouracil; and radical hysterectomy was to be performed after 2 cycles. The main variables analyzed were clinical and histologic response to NAIC, NAIC-related adverse events, adjuvant chemotherapies, relapse-free and overall survival, recurrence, and prognostic factors. RESULTS: Patients were judged eligible for radical hysterectomy, and 51 underwent the surgery. The overall positive response (complete response [CR] + partial response [PR]) to NAIC was 88.5%. Median follow-up time was 84 months (5-136 months). Three-year relapse-free survival and overall survival were 80.5% and 77.8%, respectively. The recurrence rate was 19.2% (10/52 patients). Seven (13.5%) of the 52 patients died from the disease during follow-up. Lymph node status (positive vs negative) and the histologic effect of NAIC (grades 0-1 vs grades 2-3) were shown to be prognostic factors (P = 0.024 and P = 0.021, respectively). CONCLUSIONS: Our NAIC strategy seems to be well tolerated and beneficial for patients with bulky IB2 to IIB cervical cancer. With this strategy, radiation therapy remains an option in cases of recurrence. For cases in which lymph node metastasis is found or the histologic effect of NAIC is low, our adjuvant chemotherapy regimen may need adjustment to improve prognosis.

The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells.

GOALS: We previously demonstrated that side-population (SP) cells in human endometrial cancer cells (Hec1 cells) and in rat endometrial cells expressing oncogenic human K-Ras protein (RK12V cells) have features of cancer stem cells (CSCs). Hec1-SP cells showed enhanced migration and the potential to differentiate into the mesenchymal cell lineage. In this study, we analyzed the association of the epithelial-mesenchymal transition (EMT) with the properties of these endometrial CSCs. We also assessed the effects of salinomycin (a compound with EMT-specific toxicity) on the proliferative capacity, migration and invasiveness of these endometrial CSCs using Hec1-SP cells. METHOD: We performed microarray expression analysis to screen for up-regulated genes in CSCs using a set of RK12V-SP cells and -non-SP(NSP) cells and used the Metacore package to identify the Gene GO pathway MAPs involved in the up-regulated genes. To analyze their association with EMT, the expression of several EMT associated genes in Hec1-SP cells was investigated by real time PCR and compared with that in Hec1-NSP cells. We assessed the expression of BAX, BCL2, LEF1, cyclinD and fibronectin by real time PCR. We also evaluated the viabilities, migration and invasive activities, and tumorigenicities of these SP cells and NSP cells in the presence or absence of salinomycin. RESULTS: We demonstrated that i) EMT processes were observed in both RK12V-SP cells and Hec1-SP cells, ii) the level of fibronectin was enhanced in Hec1-SP cells and salinomycin reduced the level of fibronectin expression, iii) salinomycin induced apoptosis and inhibited Wnt signaling, and iv) salinomycin inhibited the proliferation, migration, invasiveness and tumorigenicity of these SP cells. CONCLUSION: This is the first report of an inhibitory effect of salinomycin on the properties of endometrial CSCs.

The poly(c)-binding protein-1 regulates expression of the androgen receptor.

The androgen receptor (AR) is a ligand-dependent transcription factor, expressed in male and female reproductive organs, and essential for normal reproduction in both sexes. The levels of AR are tightly controlled in androgen-responsive cells in which it plays a central role in the regulation of target gene expression. The AR is abundantly expressed in human endometrial stromal cells (HESCs), but levels decline markedly after differentiation into decidual cells in vivo and in primary cultures. Decidualization profoundly down-regulated AR protein levels with no discernible effect on either AR mRNA or protein stability, suggesting that loss of the receptor was a consequence of translational inhibition. Here we show that HESCs express three RNA-binding proteins, Hu antigen R and the poly(C)-binding proteins PCBP1 and PCBP2, that reportedly target the 3'-untranslated region of AR transcripts. Only PCBP1 expression was enhanced in secretory endometrium in vivo and in decidualizing HESCs. Furthermore, knockdown of PCBP1 in decidualizing cells was sufficient to restore AR protein levels, indicating that loss of the AR protein is primarily the consequence of a translational block. PCBP1 also blocked AR translation in a cell-free system, although this did not require binding to the 3'-untranslated region of the receptor mRNA. Furthermore, knockdown of PCBP1 in the prostate cancer LNCaP cell line also increased AR protein. Therefore, PCBP1 plays a major role in the dynamic expression of AR in both male and female androgen-responsive cells.

NKG2A inhibits invariant NKT cell activation in hepatic injury.

Activation of invariant NKT (iNKT) cells in the liver is generally regarded as the critical step for Con A-induced hepatitis, and the role of NK cell receptors for iNKT cell activation is still controversial. In this study we show that blockade of the NKG2A-mediated inhibitory signal with antagonistic anti-NKG2A/C/E mAb (20d5) aggravated Con A-induced hepatitis in wild-type, Fas ligand (FasL)-mutant gld, and IL-4-deficient mice even with NK cell and CD8 T cell depletion, but not in perforin-, IFN-gamma-, or IFN-gamma- and perforin-deficient mice. Consistently, 20d5 pretreatment augmented serum IFN-gamma levels and perforin-dependent cytotoxicity of liver mononuclear cells following Con A injection, but not their FasL/Fas-dependent cytotoxicity. However, blockade of NKG2A-mediated signals during the cytotoxicity effector phase did not augment cytotoxic activity. Activated iNKT cells promptly disappeared after Con A injection, whereas NK1(-) iNKT cells, which preferentially expressed CD94/NKG2A, predominantly remained in the liver. Pretreatment with 20d5 appeared to facilitate disappearance of iNKT cells, particularly NK1(-) iNKT cells. Moreover, Con A-induced and alpha-galactosylceramide-induced hepatic injury was very severe in CD94/NKG2A-deficient DBA/2J mice compared with CD94/NKG2A-intact DBA/2JJcl mice. Overall, these results indicated that a NKG2A-mediated signal negatively regulates iNKT cell activation and hepatic injury.

[A case with advanced carcinoma of the gallbladder responding to UFT monotherapy].

Gallbladder carcinoma is a fatal disease with highly metastatic potential, and the chemotherapeutic regimen has not been established yet. We reported here a case of gallbladder carcinoma with lung and liver meatstases responding to a single agent, UFT. A 70-year-old female with advanced carcinoma of the gallbladder and bilateral pulmonary metastases were treated with UFT 600 mg/day weekday for half a year. Pulmonary metastases disappeared completely, and the primary lesion shrank markedly 6 months after. Unfortunately, the patient died 1.5 years after the start of treatment due to relapse of liver and lung lesions.

[A case of recurrent breast cancer with bone metastasis causing pancytopenia--efficacy of low-dose CPT-11+ MPA].

A 46-year-old woman underwent breast-conserving surgery. The patient was treated with six cycles of CMF and, subsequently, combination therapy with UFT and CPA. However, multiple metastases were detected in the thoracic vertebrae after two years and two months of surgery. Weekly administration of paclitaxel was initiated, but the drug could not be continued due to pancytopenia. CPT-11 (40 mg/body) once a week and medroxyprogesterone acetate (MPA) 600 mg a day was substituted for paclitaxel. During the treatment with CPT-11, no severe adverse reactions, such as myelosuppression and diarrhea, were observed, and the patient's condition was stable without discontinuing the chemotherapy. The results suggest that the low-dose CPT-11 and MPA therapy should improve the prognosis of advanced and recurrent breast cancers with only slight adverse effects.

ICOS costimulates invariant NKT cell activation.

It has been reported that costimulatory molecules, CD80/86-CD28 and CD154-CD40, critically contribute to activation of CD1d-restricted invariant NKT (iNKT) cells. Here we have demonstrated that ICOS, a new member of the CD28 family, plays a substantial role in iNKT cell activation. iNKT cells constitutively expressed ICOS as well as CD28 independently, and ICOS expression was further up-regulated 2-3 days after alpha-galactosylceramide (alpha-GalCer) treatment. Blockade of ICOS-mediated costimulation by administration of anti-ICOS ligand (B7RP-1) mAb or by ICOS gene knockout substantially inhibited alpha-GalCer-induced IFN-gamma and IL-4 production, cytotoxic activity, and anti-metastatic effect. Moreover, blockade of both B7RP-1-ICOS and CD80/86-CD28 interactions mostly abolished the alpha-GalCer-induced immune responses. These findings indicate that iNKT cell activation is regulated by CD28 and IOCS independently.

Arresting dialysis-related amyloidosis: a prospective multicenter controlled trial of direct hemoperfusion with a beta2-microglobulin adsorption column.

We investigated the clinical efficacy of direct hemoperfusion with a beta2-microglobulin (beta2-m) adsorption column for the treatment of patients with dialysis-related amyloidosis. A 2-year prospective controlled study was performed to compare the effects of passaging blood through a (beta2-m) adsorption column (Lixelle) before it is passaged through the dialysis polysulfone membrane on the severity of amyloidosis in these individuals. Patients (n = 22) whose blood went through the Lixelle column prior to dialysis had a higher beta2-m removal rate compared to an equal number of controls, and they showed earlier improvement in their symptoms which included impaired daily activities, joint stiffness, and pain. The appearance of additional bone cysts was prevented in pre-adsorbed patients but not in the controls. Thus, the Lixelle column is useful in preventing the progression of dialysis-related amyloidosis and in ameliorating or arresting the progression of the symptoms of this disorder.

Repeated femoral vein puncturing for maintenance haemodialysis vascular access.

BACKGROUND: When access cannot be achieved using a native arteriovenous fistula or a synthetic prosthetic graft, central venous catheters are usually placed. This mode of access is short-lived, prone to infection, stenosis and thrombosis of central veins. To overcome access problems, we developed a new native vascular access ('femoral vein access') and devices. We report here on our experience with the availability, longevity, procedure and morbidity of haemodialysis (HD) using femoral vein access. METHODS: Repeated (three times a week) patient's native femoral vein puncturing has been used as the vascular access (femoral vein access) for maintenance HD in 30 patients (mean age +/- SD: 61.70 +/- 15.27 years old; 18 female/12 male). The femoral vein was punctured beneath the inguinal ligament (on a length ranging from 30 to 100 mm) after disinfection and local anaesthesia. Long (effective length 56 mm) 19- and 18-gauge needles with four side holes were used for the femoral vein puncture as an arterial site of the extracorporeal circuit of HD and shorter (effective length 40 mm) similar gauge needles for the subcutaneous vein puncture used as the return site. The needle is inserted blind into the femoral vein after the femoral artery has been located by palpation and the perception of a pulse. Patients returned home the same day. RESULTS: The mean duration of HD treatment using femoral vein repeated puncture was 4.99 +/- 3.42 years (up to 16.0 years). This represented a total experience of 23 369 femoral vein punctures. The mean blood flow achieved on dialysis was 165 +/- 20 ml/min. The average Kt/V was 1.74 +/- 0.48 per session. CONCLUSIONS: The femoral vein repeated puncture technique has substantial advantages over venous catheters. It does not require surgery, while permitting adequate blood flow. This method can be used as a long-term (over 10 years) blood access. Apart from a few local haematomas, no serious complications have been observed. Moreover, it does not carry a heavy financial burden.