The clinical value of PERCIST to predict tumour response and prognosis of patients with oesophageal cancer treated by neoadjuvant chemoradiotherapy.

AIM: To examine whether Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST) is useful to predict tumour response and prognosis of patients with oesophageal cancer who received neoadjuvant chemoradiotherapy (NACRT) followed by surgery. MATERIALS AND METHODS: This multicentre retrospective study included 60 patients with oesophageal cancer who underwent 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (18F-FDG-PET/CT) before and after NACRT prior to surgery from January 2007 and June 2016. The correlation between pathological response and PERCIST was assessed by χ2 test. The prognostic significance was assessed by the Kaplan-Meier method and Cox regression analysis. RESULTS: There were 30 responders and 30 non-responders pathologically. The complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD) were seen in 22, 29, seven, and two patients, respectively. There was a significant correlation between pathological response and PERCIST (p<0.001). Forty patients showed eventual progression, and 20 patients were alive without progression between the start of NACRT and last clinical follow-up (median follow-up period; 27 months [range, 3-107]). Pathological stage and PERCIST were significant for progression-free survival (PFS; p=0.044 and 0.006, respectively) and also significant for overall survival (OS; p=0.009 and 0.001, respectively) at univariate analysis. Pathological lymph node staging was also significant for OS at univariate analysis (p=0.018). At multivariate analysis, PERCIST remained significant and independent for PFS (hazard ratio [HR]: 1.59, p=0.046) and OS (HR: 1.82, p=0.008). CONCLUSION: PERCIST may be useful for predicting tumour response and prognosis of patients with oesophageal cancer who received NACRT.

Fast-ion-induced secondary ion emission from submicron droplet surfaces studied using a new coincidence technique with forward-scattered projectiles.

A mass spectrometric study of secondary ions emitted from droplet surfaces by MeV-energy heavy ion impact was performed to investigate fast-ion-induced molecular reaction processes on liquid surfaces. Herein, a new coincidence technique was developed between secondary ions and scattered projectile ions at a small forward angle. The advantages of this technique were demonstrated by measurement of the collision between 4-MeV C3+ and ethanol droplets. Secondary ion emission probabilities were obtained directly from the coincidence data. Notably, this technique enabled positive fragment ions that had not been identified in previous measurements to be observed by suppressing the strong background originating from gas-phase molecules more than 104-fold. H+, H3O+, C2H5 +, and C2H5O+ were found to be produced as major positive fragment ions, in addition to minor fragments H2 +, C2H3 +, and CH2OH+. Production of these ions suggests that competition between rapid hydrogen ion emission from multiply ionized states and intermolecular proton transfer accompanied by fragmentation through protonated ethanol occurs after fast heavy-ion collisions. Clarification of the positive fragment ions also revealed the characteristic features of negative ions. Negative ions were realized to exhibit higher degrees of fragmentation and reactivity compared with positive ions. Furthermore, the energy loss by forward-scattered ions during droplet penetration was used to evaluate the target thickness at a submicron level. Variations in secondary ion yield, mass distribution, and kinetic energies depending on the penetration length were observed below 1 µm. These results highlight the unknown mechanism of these "submicron effects" observed in secondary ion emission processes as a new phenomenon.

Leiomyosarcoma of the broad ligament: a case report with CT and MRI images.

Primary leiomyosarcoma of the broad ligament is a very rare and highly malignant gynecological tumor. The authors report a 61-year-old postmenopausal woman with signs and symptoms of malignant ovarian tumor. Preoperative magnetic resonance imaging (MRI) was interpreted as being suspicious for malignant tumors, such as an ovarian cancer or a leiomyosarcoma of the broad ligament, so laparotomy was performed. Macroscopically, the tumor was revealed with a 18 x 13.7 x 9.5 cm degenerated, multiple cystic part and solid whitish part arising from broad ligament which on histopathology proved to be leiomyosarcoma. To the best of the authors' knowledge, primary leiomyosarcoma of the broad ligament has been documented in 21 reports or so, and no imaging findings are available. Here the authors present the MRI findings of primary leiomyosarcoma of the broad ligament.

Perioperative management of combined heart-liver transplantation in patients with cirrhosis, renal insufficiency, or pulmonary hypertension.

UNLABELLED: STATING THE MAIN PROBLEM: Only few reports have detailed perioperative management and outcome of combined heart and liver transplantation (CHLT), and none describe the long-term renal function. METHODS: Three patients presented clinical signs of cardiomyopathy with reduced ejection fraction and proven cirrhosis with evidence of portal hypertension. Two of them presented renal failure, and the other pulmonary hypertension. After cardiac transplantation and closure of the sternum, liver transplantation was performed using systematically venovenous double-limb (portal and caval) bypass. RESULTS: Mean cold ischemic time for heart and liver was 2 h 46 min and 12 h 47 min, respectively. Intraoperative hemodynamics remained grossly stable during surgery. Mean transfusions were 12 red blood cell packs. All three patients received anti-R-Il2 antibodies at post-operative day 1 and 4. Mean plasma creatinine concentration was 90 ± 8 µmol/L one yr post-CHLT, vs 160 ± 62 µmol/L pre-CHLT. All three patients are alive with functional grafts after a mean follow-up of 26 months (12-38). CONCLUSION: CHLT could be performed safely through two consecutive and independent usual procedures. Perioperative hemodynamic stability, minimal blood loss, and routine splanchnic decompression are probably major determinants of a favorable outcome and good long-term renal function.

Established, emerging and future applications of FDG-PET/CT in the uterine cancer.

Integrated positron emission tomography/computed tomography (PET/CT) with 2-[¹8F]fluoro-2-deoxy-D-glucose (FDG) is a useful technique to acquire both glucose metabolic and anatomic imaging data using a single device in a single diagnostic session and has opened a new field in clinical oncologic imaging. FDG-PET/CT has been used successfully for the staging, optimization of treatment, re-staging, therapy monitoring, and prognostic prediction of uterine cervical cancer and endometrial cancer as well as various malignant tumours. The present review discusses the current role of FDG-PET/CT in the management of uterine cancer, discussing its usefulness and limitations in the imaging of these patients.

FDG PET/CT features of ovarian metastasis.

AIM: To assess the characteristics of [(18)F]-fluoro-2-deoxy-d-glucose (FDG) uptake in cases of ovarian metastasis using positron-emission tomography/computed tomography (PET/CT). MATERIALS AND METHODS: Twelve patients with 16 ovarian metastases arising from colon cancer (n=6), breast cancer (n=4), gastric cancer (n=3), and pancreatic cancer (n=3) who underwent FDG-PET/CT examination were included in this study. The effect of lesion size and morphological pattern (predominantly solid or cystic) on FDG uptake was evaluated using the quantitative standardized uptake value (SUV). RESULTS: The mean maximum SUV for the 16 lesions was 4.6±2.4 (range 1.8∼9.9). The Pearson correlation coefficient test showed no significant correlation between maximum SUV and lesion size (r=0.21, p=0.42). The maximum SUV of solid (n=5) and cystic (n=11) lesions was 5.5±2.7 and 4.3±2.2, respectively, and the difference was not significant (p=0.43). Breast cancer showed the highest maximum SUV (6.4±3.6), followed by colon cancer (5.3±1.4), gastric cancer (3.3±0.5), and pancreatic cancer (2.2±0.6). CONCLUSION: Ovarian metastases show a variable maximum SUV with mild to intense FDG uptake.

ABO blood type incompatible kidney transplantation without splenectomy prepared with plasma exchange and rituximab.

We have designed a protocol for ABO-incompatible kidney transplantations based on preoperative plasmapheresis with a tacrolimus/mycophenolate mofetil/methylprednisolone/basiliximab protocol using low-dose rituximab (200 mg/body) instead of splenectomy to prevent antibody-mediated acute rejection. Eight patients successfully received transplants with this protocol. The titers of anti-A and -B antibodies as well as the number of CD20(+) cells were readily maintained at a low level posttransplantation. There were no side effects. All patients have renal transplant function with a follow-up of 1-34 months.

Autologous blood transfusion for kidney transplant recipients.

Autologous blood transfusion (ABT) is rarely employed in patients with end-stage renal disease (ESRD); these patients are usually anemic. Since 1998, we have attempted ABT for ESRD patients undergoing living-related kidney transplantation. Among 20 patients enrolled in this study the preoperative hemoglobin and hematocrit levels were 10.0 +/- 1.2 mg/dL (range, 8.1-11.7) and 30.0 +/- 3.7% (range, 24.7-34.3), respectively. Blood volume collected on each occasion was 235.7 +/- 57.7 mL (range, 200-400), and the number of blood collections was 2.45 +/- 0.9 (range, 1-4). Total collected volume was 567.5 +/- 157.5 mL (range, 400-800). Symptomatic hypotension was seen in two patients, but vital signs recovered spontaneously. No other problems related to blood collection were observed. Allogeneic transfusion was need in only one patient (5%). ABT was safe and efficacious in ESRD patients scheduled for living-related kidney transplantation.

Sonographic preoperative assessment of liver volume before major liver resection.

OBJECTIVE: The use of ultrasonography is widespread for both the diagnosis and treatment of liver tumors. However, the measurement of liver volume by ultrasonography is not commonly done. We report an original method of liver volumetry using ultrasonography and an investigation into the usefulness of ultrasonography in this context. METHODS: The data for 50 patients undergoing various types of major hepatectomy were collected. We preoperatively measured liver volume using ultrasonography, dividing the liver into three main compartments according to precise anatomical landmarks, and then made comparisons with the volume of the actual specimen after hepatectomy, for all of the study participants. RESULTS: Total volume correlation between the two groups was good (r = 0.916, P < 0.001). However, the correlation was weaker in cases of right hepatectomy compared with other types of hepatectomy. CONCLUSION: This study demonstrates the possibility of doing liver volumetry using an ultrasound device. Further investigation to establish the reliability of this easily available and noninvasive approach is needed.

Chromosome abnormalities of leukemia cells in adult patients with T-cell leukemia.

Chromosomes of 30 patients with adult T-cell leukemia were analyzed. Chromosome abnormalities were found in all the patients examined. The modal chromosome number of abnormal cells was hypodiploid in 2 patients, diploid in 14, and hyperdiploid in 9. The remaining 5 patients had bimodal chromosome numbers (diploid and hyperdiploid modes). Although all the patients showed various numerical or structural chromosome abnormalities, they also had common chromosome abnormalities. Aberrations of chromosome 1 were noted in 20 of the 30 patients, aberrations of chromosome 3 were seen in 20, trisomy 6 or 6q- was found in 17, aberrations of chromosome 10 were noted in 16, aberrations of the long arm of chromosome 14 were seen in 9, and trisomy 18 was seen in 7. There was no particular relationship between the difference in clinical symptoms and disparity in chromosome abnormalities.

Loss of amplified c-myc genes in the spontaneously differentiated HL-60 cells.

Amplification of the c-myc gene in the human promyelocytic leukemia cell line HL-60 is considered to be one of the major causes of its malignant phenotype. It is also well known since the establishment of the cell line that a culture of HL-60 cells contains a small but fixed percentage of spontaneously differentiated cells. We show that the spontaneous differentiation could be a result of extensive losses of amplified c-myc genes by the findings: (a) the spontaneously differentiated HL-60 cells express Mac-1 (CR3, CD11b/CD18) antigen, irreversibly stop the uptake of [3H]thymidine, and die by apoptosis; (b) these cells, when isolated, and when the copy number of c-myc genes is precisely quantitated, show extensive losses of c-myc genes; and (c) low concentrations of hydroxyurea increase the percentage of spontaneously differentiated cells in which the number of c-myc genes is further decreased. A simple theoretical consideration suggests that an active elimination process(es) must be operating besides the stochastic losses of the extrachromosomally amplified c-myc genes by unequal partition at mitosis.

Follow-up rates of living kidney donor in Japan: A single center study.

Long-term follow-up of kidney donors is needed not only for the individual donor's benefit but also to establish analyzable databases to improve the selection criteria for future donors. We collected data including the date of transplantation, the date of the last follow-up, donor's age, sex, their relationship to the recipient, renal function, proteinuria, and the prevalence of hypertension. Of 124 donors, 52 donors were not being followed up. The mean duration of follow-up was 4.3 ± 3.6 years. Follow-up rates were 83.9%, 74.6%, and 59.2% at 1 year, 2 years, and 5 years postdonation, respectively. Of those not being followed up, 75% dropped out. Follow-up rates did not differ between parent and spouse donors 5 years (57.1% vs. 71.4%; P = 0.4) postdonation. Similarly, follow-up rates at 5 years did not differ between donors aged 60 years or older and those younger than 60 (57.5% vs. 61.3%; P = 0.6). Of 72 donors being followed up, 75.0% had estimated glomerular filtration rate of <60 mL/min/1.73 m2, 8.3% had proteinuria, and 41.7% had hypertension requiring medication. There is a limitation to the endeavor of each transplant center to follow-up all their donors. Long-term donor follow-up in Japan requires a national registration system and mandates transplant center participation.

Carbon and sulfur isotopic signatures of ancient life and environment at the microbial scale: Neoarchean shales and carbonates.

An approach to coordinated, spatially resolved, in situ carbon isotope analysis of organic matter and carbonate minerals, and sulfur three- and four-isotope analysis of pyrite with an unprecedented combination of spatial resolution, precision, and accuracy is described. Organic matter and pyrite from eleven rock samples of Neoarchean drill core express nearly the entire range of δ(13) C, δ(34) S, Δ(33) S, and Δ(36) S known from the geologic record, commonly in correlation with morphology, mineralogy, and elemental composition. A new analytical approach (including a set of organic calibration standards) to account for a strong correlation between H/C and instrumental bias in SIMS δ(13) C measurement of organic matter is identified. Small (2-3 µm) organic domains in carbonate matrices are analyzed with sub-permil accuracy and precision. Separate 20- to 50-µm domains of kerogen in a single ~0.5 cm(3) sample of the ~2.7 Ga Tumbiana Formation have δ(13) C = -52.3 ± 0.1‰ and -34.4 ± 0.1‰, likely preserving distinct signatures of methanotrophy and photoautotrophy. Pyrobitumen in the ~2.6 Ga Jeerinah Formation and the ~2.5 Ga Mount McRae Shale is systematically (13) C-enriched relative to co-occurring kerogen, and associations with uraniferous mineral grains suggest radiolytic alteration. A large range in sulfur isotopic compositions (including higher Δ(33) S and more extreme spatial gradients in Δ(33) S and Δ(36) S than any previously reported) are observed in correlation with morphology and associated mineralogy. Changing systematics of δ(34) S, Δ(33) S, and Δ(36) S, previously investigated at the millimeter to centimeter scale using bulk analysis, are shown to occur at the micrometer scale of individual pyrite grains. These results support the emerging view that the dampened signature of mass-independent sulfur isotope fractionation (S-MIF) associated with the Mesoarchean continued into the early Neoarchean, and that the connections between methane and sulfur metabolism affected the production and preservation of S-MIF during the first half of the planet's history.

Alteration of cell adhesion and cell cycle properties of ES cells by an inducible dominant interfering Myb mutant.

The Myb transcription factors, c-Myb, A-Myb, and B-Myb, regulate cell differentiation and/or proliferation. To investigate the role of B-Myb in embryogenesis, we introduced an inducible dominant interfering Myb protein (MERT) into embryonic stem (ES) cells, which express B-Myb as an exclusive member of Myb family. Disruption of normal B-Myb function by the conditional activation of MERT caused a drastic morphological alteration of ES cells and G(1)-S cell cycle arrest. The inhibition of B-Myb function by MERT dissociated tightly packed ES cell colonies into dispersed single cells that subsequently detached from the culture dish. Cell adhesion analyses revealed that suppression of B-Myb function reduced the adhesion with extracellular matrix proteins, such as laminin, collagen, and fibronectin. This reduction was presumably due to decreased cell surface expression of beta1 integrin. Embryoid body formation was also severely retarded by the activation of MERT. This impairment was attributed to reduced expression of E-cadherin, which functions as a homophilic intercellular adhesion molecule. Simultaneously, blocking B-Myb function did not alter the expression of differentiation markers. Our data indicate that B-Myb plays important roles in regulating cell adhesion and cell cycle progression. These results are well consistent with the recent report on the phenotype of B-Myb null mice and show that the regulation of cell adhesion is an important B-Myb function that has not yet been assumed.

Molecular cloning and characterization of Kremen, a novel kringle-containing transmembrane protein.

Kringle domain, a triple-disulfide-linked domain, is conserved in diverse proteins which play important roles in various biological processes. We cloned Kremen, a novel member of kringle-containing proteins, using a newly developed unique strategy, 'Kringle-SAGE (serial analysis of gene expression)', which enables comprehensive analysis of kringle-containing proteins. Kremen is likely to be a type-I transmembrane protein composed of 473 amino acid residues. Kremen has a kringle domain, a WSC domain, and CUB domains in the extracellular region, while the intracellular region has no conserved motif involved in signal transduction. In the mouse embryo, the Kremen mRNA level, which was increased during embryonic development, was localized in the apical ectodermal ridge of limb buds, myotome, and sensory organs (e.g. optic vesicle, otic vesicle, nasal pit). In the adult mouse, Kremen mRNA was expressed in a variety of tissues with a relatively strong expression in the lung, heart, and skeletal muscle. Kremen mRNA expression in C2C12 and NIE-115 cells increased during respective differentiation into muscular and neural cells. These results suggest a potential role for Kremen in the regulation of cellular responses upon extracellular stimulus or cell-cell interaction in neuronal and/or muscle cells. Kringle-SAGE is expected to facilitate further elucidation of structure and functions of kringle proteins.

Organogenesis of the liver, thymus and spleen is affected in jumonji mutant mice.

The recessive mutant mouse jumonji (jmj), obtained by a gene trap strategy, shows neural tube defects in approximately half of homozygotes with a Balb/cA and 129/Ola mixed background. Here, we show that no neural tube defects are observed with a Balb/cA background. We also found hypoplasia of the liver, thymus and spleen with full penetrance with a Balb/cA background. In the livers of homozygous embryos we found excessive cell death in the peripheral region. In both the thymus and spleen, the accumulation of hematopoietic cells is affected in mutant embryos. These phenotypes were also observed with C57BL/6J and DBA/2J backgrounds, suggesting that the jmj gene plays an essential role in the organogenesis of these tissues.

Stimulation of human peripheral blood polymorphonuclear cell iodination by lignin-related substances.

Lignin is a heterogenous natural product composed of phenylpropane units and is usually associated with hemicellulose in its native state. Until now little attention has been paid to the potential therapeutic utility of lignified products. Natural lignified products are demonstrated in the present study to stimulate iodination significantly (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN). This stimulation was significantly inhibited in the presence of myeloperoxidase inhibitors. These materials were almost completely deprived of their stimulation capacity by treatment with NaCIO2, but this capacity was not affected by severe treatment with H2SO4 or trifluoroacetic acid. Similar stimulating activity by chemically defined tannin-related polyphenolic compounds was observed. Degradation products or component units of lignin, and natural antitumor polysaccharides and their chemically modified derivatives (introduced with negatively or positively charged groups) and polysialoglycoproteins had little or no activity. The results indicate the importance of a polymerized phenolic structure for the stimulation of PMN iodination. Possible physiological relevance of the stimulation of iodination by lignified substances is discussed.

A role of jumonji gene in proliferation but not differentiation of megakaryocyte lineage cells.

In this study, megakaryocytopoiesis was investigated in the recessive mutant mouse, jumonji, obtained by a gene-trap strategy. We investigated the number of megakaryocyte progenitors in the fetal liver, yolk sac, and peripheral blood of jumonji homozygous embryos by in vitro colony forming assay and monitored colony formation from single megakaryocyte progenitors. We also investigated the differentiation of jumonji-deficient megakaryocytes in terms of the expression of megakaryocyte differentiation markers PF4, CD62P, and GATA-1, proplatelet formation, cytoplasmic maturation, and endomitosis. We found that the population of megakaryocyte progenitors in the fetal liver, yolk sac, and peripheral blood of jumonji homozygotes increased. A fraction of megakaryocyte progenitors derived from the fetal liver of jumonji homozygotes formed larger colonies in vitro when compared with controls. This abnormality is caused by delayed growth arrest in the progeny. Immature megakaryocyte progenitors showed this abnormality. The megakaryocytes of jumonji homozygotes expressed PF4, CD62P, and GATA-1, obtained cytoplasmic maturation, extended proplatelet-like processes, and underwent endomitosis. The loss of the jumonji gene causes an increase in the number of megakaryocyte lineage cells. Our data suggest that the jumonji gene regulates proliferation but not differentiation of megakaryocyte lineage cells.

Transplantation of Restored Kidneys From Unrelated Donors After Resection of Renal Cell Carcinoma: Results From 10 Patients.

PURPOSE: To relieve the chronic shortage of donor kidneys, we conducted a prospective kidney transplantation trial using kidneys removed from 10 unrelated patients (51 to 79 years of age) who had undergone nephrectomy for small renal cell carcinoma (1.5 to 3.9 cm) of low-to-moderate complexity based on RENAL (radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior/posterior location relative to polar lines) nephrometry (objective description helpful for operative indication and planning). METHODS: Donors were selected from among 15 patients who opted to undergo nephrectomy for small renal cell carcinoma. A total of 76 dialysis patients 34 to 85 years of age who agreed to undergo restored kidney transplantation were recruited as transplant candidates. RESULTS: In stage 1 (5 cases), high-risk patients were selected without human leukocyte antigen testing, and accelerated acute rejection occurred in 4 of 5 recipients. This trial was subsequently extended with human leukocyte antigen testing, and an additional 5 patients were enrolled in stage 2. Eight recipients, including 4 recipients with a history of renal transplantation, experienced rejection; 1 patient resumed dialysis 35 months after transplantation. The most recent serum creatinine levels ranged from 1.10 to 3.19 mg/dL in the 9 recipients with functioning grafts and from 0.84 to 4.68 mg/dL in the 10 donors. No tumor recurrence was noted at 32 to 58 months after surgery in either the recipients or the donors. CONCLUSIONS: Restored kidney transplantation using kidneys with a small renal tumor seems suitable for carefully selected high-risk recipients and, in particular, elderly kidneys can also function well. Avoiding cancer transmission, fair recipient selection, close follow-up, and a well-organized tracking system warrant further study.

Computed diffusion-weighted MRI for prostate cancer detection: the influence of the combinations of b-values.

OBJECTIVE: To evaluate the influence of the combinations of b-values on computed diffusion-weighted images (cDWIs) for prostate cancer (PCa) detection at b = 2000 s mm(-2). METHODS: Diffusion-weighted imaging (DWIs) for 31 patients with PCa (65.2 ± 7.1 years) were obtained pre-operatively at different b-values (0, 100, 500, 1000 and 2000 s mm(-2)) on a 3-T MRI. cDWIs at b = 2000 were generated by using six b-value combinations: 0-100 s mm(-2) (cDWI0-100); 0-500 s mm(-2) (cDWI0-500); 100-500 s mm(-2) (cDWI100-500); 0-1000 s mm(-2) (cDWI0-1000); 100-1000 s mm(-2) (cDWI100-1000); and 500-1000 s mm(-2) (cDWI500-1000). These cDWIs and measured DWIs with b = 2000 s mm(-2) (mDWI2000) were evaluated in this setting. To assess image quality for each DWI, contrast ratios (CRs) of cancerous and non-cancerous lesions were evaluated. To compare the detectability of PCa for each DWI, receiver operating characteristic analysis was used. RESULTS: CRs of all cDWIs were significantly higher than those of mDWI2000 (p < 0.05). Areas under the curve of cDWI0-100 (0.62) and cDWI0-500 (0.65) were significantly smaller (p < 0.05) than those of others (cDWI100-500, 0.72; cDWI0-1000, 0.73; cDWI100-1000, 0.71; cDWI500-1000, 0.74; mDWI2000, 0.72). CONCLUSION: The combinations of b-values influenced image quality and diagnostic ability of cDWIs for PCa detection. The combinations of b ≥ 100 and b ≥ 500 s mm(-2), as well as b = 0 and b = 1000 s mm(-2), were optimal in this study. ADVANCES IN KNOWLEDGE: For generating the useful cDWI for PCa detection, radiologists should take care of the combination of b-values when including low b-values.