Total tumour volume as a prognostic factor in patients with resectable colorectal cancer liver metastases.

BACKGROUND: Although total tumour volume (TTV) may have prognostic value for hepatic resection in certain solid cancers, its importance in colorectal liver metastases (CRLM) remains unexplored. This study investigated its prognostic value in patients with resectable CRLM. METHOD: This was a retrospective review of patients who underwent hepatic resection for CRLM between 2008 and 2017 in a single institution. TTV was measured from CT images using three-dimensional construction software; cut-off values were determined using receiver operating characteristic (ROC) curve analyses. Potential prognostic factors, overall survival (OS) and recurrence-free survival (RFS) were determined using multivariable and Kaplan-Meier analyses. RESULTS: Some 94 patients were included. TTV cut-off values for OS and RFS were 100 and 10 ml respectively. Right colonic primary tumours, primary lymph node metastasis and bilobar liver metastasis were included in the multivariable analysis of OS; a TTV of 100 ml or above was independently associated with poorer OS (hazard ratio (HR) 6·34, 95 per cent c.i. 2·08 to 17·90; P = 0·002). Right colonic primary tumours and primary lymph node metastasis were included in the RFS analysis; a TTV of 10 ml or more independently predicted poorer RFS (HR 1·90, 1·12 to 3·57; P = 0·017). The 5-year OS rate for a TTV of 100 ml or more was 41 per cent, compared with 67 per cent for a TTV below 100 ml (P = 0·006). Corresponding RFS rates with TTV of 10 ml or more, or less than 10 ml, were 14 and 58 per cent respectively (P = 0·009). A TTV of at least 100 ml conferred a higher rate of unresectable initial recurrences (12 of 15, 80 per cent) after initial hepatic resection. CONCLUSION: TTV was associated with RFS and OS after initial hepatic resection for CRLM; TTV of 100 ml or above was associated with a higher rate of unresectable recurrence.

ANTECEDENTES: Aunque el volumen total del tumor (total tumour volume, TTV) puede tener valor pronóstico tras la resección hepática (hepatic resection, HR) en algunas neoplasias sólidas, no se conoce su importancia en las metástasis hepáticas de cáncer colorrectal (colorectal liver metastases, CRLMs). Este estudio analizó el valor pronóstico del TTV en pacientes con CRLMs resecables. MÉTODOS: Revisión retrospectiva de pacientes a los que se realizó una HR por CRLMs entre 2008 y 2017 en un solo centro. El TTV se estimó a partir de imágenes de tomografía computarizada utilizando un programa de reconstrucción 3D; se determinaron los valores de corte mediante un análisis de las características operativas del receptor. Se identificaron los posibles factores pronósticos y se calcularon la supervivencia global (overall survival, OS) y la supervivencia libre de recidiva (recurence-free survival, RFS) mediante análisis multivariados y de Kaplan-Meier. RESULTADOS: Se incluyeron 94 pacientes. Los valores de corte del TTV para la OS y la RFS fueron de 100 mL y 10 mL, respectivamente. En el análisis multivariable para la OS, se incluyeron los tumores del colon derecho, las metástasis linfáticas primarias y la metástasis hepática bilobar; un TTV ≥ 100 mL se asoció de forma independiente con una peor OS (cociente de riesgos instantáneos, hazard ratio, HR, 6,34, i.c. del 95% 2,08-17,9; P = 0,002). En el anáisis para la RFS, se incluyeron tumores primarios de colon derecho y las metástasis linfáticas primarias; un TTV ≥ 10 mL predijo de forma independiente una peor RFS (HR 1,90, i.c. del 95% 1,12-3,57; P = 0,017). Las tasas de OS a los 5 años con TTVs ≥ 100 mL versus < 100 mL fueron del 41% versus 67% (P = 0,006); las tasas de RFS respecto a TTVs ≥ 10 mL versus < 10 mL fueron del 14% versus 58% (P = 0,009). Un TTV ≥ 100 mL conllevó una tasa más elevada (80%) de recidivas no resecables después de la HR inicial. CONCLUSIÓN: El TTV se asoció con la RFS y la OS tras la HR por CRLMs; unos valores ≥ 100 mL conllevan una tasa más elevada de recidiva irresecable.

[Myxoid type of malignant fibrous histiocytoma in the anterior mediastinum; report of a case].

A 58-year-old man was admitted to our hospital complaining of right chest pain. Chest X-ray and chest computed tomography (CT) disclosed a 9 cm mass in the right anterior mediastinum. The tumor demonstrated low signal intensity on T1-weighted images, and high signal intensity on T2-weighted images. It showed delayed enhancement on dynamic magnetic resonance (MR). The operation was performed and the tumor including the infiltrated pericardium and upper and middle lobe of right lung was resected. Histologically, the tumor showed a multinodular proliferation of spindle-shaped or polygonal tumor cells with abundant myxoid background. The histopathological diagnosis of the tumor was myxoid malignant fibrous histiocytoma (MFH). This is a case report of primary myxoid MFH in the anterior mediastinum. The case is rare in its primary site, but it is typical in CT and MR findings.

Cesarean section and primary pulmonary hypertension: the role of intravenous dexmedetomidine.

Primary pulmonary hypertension is a fatal disease that frequently becomes evident in pregnancy. The management of pregnant women with primary pulmonary hypertension poses a number of difficult problems, especially where regional anesthesia is considered to be contraindicated. A 30-year-old woman who developed primary pulmonary hypertension at 23 weeks of pregnancy was transferred to our hospital. Systolic pulmonary artery pressure and plasma brain natriuretic peptide levels were markedly elevated. Nitric oxide inhalation and prostacyclin prevented the progression of cardiac failure and reduced both plasma brain natriuretic peptide and pulmonary artery pressure. Cesarean section was performed at 32 weeks under general anesthesia. A combination of nitric oxide, prostacyclin, nitroglycerin, and dobutamine were administered during surgery. Intravenous dexmedetomidine was specifically used during emergence and recovery from anesthesia. This provided effective pain relief and hemodynamic stability. Throughout the clinical course, brain natriuretic peptide levels was monitored and used as an indicator of cardiac failure.

Characterization of islet-infiltrating immunocytes after pancreas preservation by two-layer (UW/perfluorochemical) cold storage method.

Clinical islet transplantation offers the prospect of good blood glycemic control without major surgical risks. Nevertheless, long-term function of the transplanted islets is seldom appreciated because rejection is followed by the graft failure. Although it has been implicated that islets have high immunogenicity, characterization of the islet-infiltrating immunocytes, such as leukocytes and macrophages, has not been extensively studied. Rat islets were isolated by the collagenase digestion method and separated by handpicking under the microscope. The islets were further dispersed into individual cells for flow cytometric analysis. Monoclonal antibodies directed toward T cells, B cells, and macrophages as well as ICAM-1, and MHC class I and II were used to enumerate cells. Pancreatic islets contained 6.3 +/- 2.9% immunocytes; T cells (39.6 +/- 4.2%), B cells (44.7 +/- 5.8%), and macrophages (1.7 +/- 0.6%). MHC class I was expressed on 85.6 +/- 2.8%, MHC class II on 36.8 +/- 2.9%, and ICAM-1 on 39.9 +/- 7.0%. The results of islets from preserved pancreas also showed the same tendency. As these islet-infiltrating immunocytes within the grafts may contribute to the rejection, one potential strategy to prevent early graft loss might start to eliminate or inactivate the islet-infiltrating immunocytes.

NADH dehydrogenase of Corynebacterium glutamicum. Purification of an NADH dehydrogenase II homolog able to oxidize NADPH.

NADPH oxidase activity, in addition to NADH oxidase activity, has been shown to be present in the respiratory chain of Corynebacterium glutamicum. In this study, we tried to purify NADPH oxidase and NADH dehydrogenase activities from the membranes of C. glutamicum. Both the enzyme activities were simultaneously purified in the same fraction, and the purified enzyme was shown to be a single polypeptide of 55 kDa. The N-terminal sequence of the enzyme was consistent with the sequence deduced from the NADH dehydrogenase gene of C. glutamicum, which has been sequenced and shown to be a homolog of NADH dehydrogenase II. In addition to high NADH-ubiquinone-1 oxidoreductase activity at neutral pH, the purified enzyme showed relatively high NADPH oxidase and NADPH-ubiquinone-1 oxidoreductase activities at acidic pH. Thus, NADH dehydrogenase of C. glutamicum was shown to be rather unique in having a relatively high reactivity toward NADPH.

The effect of additional autopolyploidization in a slow growing cellulase hyperproducer of Trichoderma.

M14-2 is a cellulase hyperproducer derived from Trichderma reesei QM 6a, but with a growth rate lower than that of the original strain. When M14-2 was autopolyploidized followed by haploidization and selection, the strain with both a higher cellulase productivity per mycelia and a higher growth rate could be obtained as M14-2B. This strain seemed to be constructed using gene sources amplified by additional autopolyploidization.

Differential expression of RAGE in human pancreatic carcinoma cells.

BACKGROUND/AIMS: Amphoterin is a key protein in normal neurite outgrowth and that its receptor on the cell surface, RAGE, is an important molecule for invasion. RAGE induces neurite outgrowth and regulate gene expression through NF-kappa B. Because the pancreatic cancer shows the constitutively activated NF-kappa B, the involvement of RAGE could be possible as a determinant for the metastatic ability. METHODOLOGY: To see the involvement of RAGE in pancreatic cancer, three representative human pancreatic carcinoma cells were rendered for the study which have different metastatic potential, PANC-1 and MIA PaCa-2 as the cells with high ability, BxPC-3 as those with low. The expression of RAGE (receptor for advanced glycation end-products) was examined by Western blot. RESULTS: The expression of RAGe was strong in MIA PaCa-2 and PANC-1 that have high metastatic ability. On the contrary, RAGE is expressed little in BxPC-3 whose ability is low. CONCLUSIONS: RAGE is expressed in concordant to the metastatic ability of the human pancreatic cancer cells. Control of this molecule could be a key to regulate the metastatic ability of pancreatic cancer.

Simple and low-cost tele-nuclear medicine conference system with the e-mail protocol.

PURPOSE: Because of the recent innovative growth in computer technology, digital imaging, and the Internet, we can take advantage of these facilities for education and clinical work in nuclear medicine. We developed a tele-nuclear medicine conference system with electronic mail (e-mail) on the Internet. METHODS: Twenty-one physicians (20 radiologists, 1 neurologist), 6 technologists and 2 medical students in six university hospitals (Japan 5, Canada 1), 5 local hospitals in Japan participated in this project. We used digital still cameras (330 k pixels) equipped with a floppy disk drive and 10 x optical zoom to digitize images with JPEG compression (640 x 480 matrix). The images were attached to e-mail messages (containing a brief description of each case). The mail was sent simultaneously to all members on the mailing list. Scintigram and SPECT images as well as other radiological images were sent by e-mail. Reply mails about each case were sent to all members via the mailing list. RESULTS: During a period of 6 months, 18 cases (tumor/infection: 7, bone: 6, cardiovascular: 1, neurology; 3, endocrine: 1) with 144 e-mails (average 5.6/case) were submitted to the conference. The average period of discussion was 15.6 days. The number of attached images was 1 to 9 (average, 4.2/e-mails). JPEG compression rate was 1/10 to 1/20. The quality of the images was good enough for discussion. Some cases required additional images for further discussion. CONCLUSION: Our tele-nuclear medicine conference with an electronic mailing list and digital camera was simple and low-cost. The conference system was useful for education and clinical work.

Relief from pain after Bombelli's valgus-extension osteotomy, and effectiveness of the combined shelf operation.

Between 1979 and 1993, we treated 67 hips in 58 patients with severe osteoarthritis caused by congenital dislocation of the hip, employing Bombelli's valgus-extension osteotomy. The mean age of the patients was 43.6 years (range, 23-59 years). The mean follow-up period was 9.7 years (range, 5-16 years). Thirty-three of the 67 joints were followed-up for more than 10 years after the operation. Of the 67 joints, 31 were operated on by Bombelli's valgus-extension osteotomy combined with a shelf operation (combined group), and 36 by Bombelli's valgus-extension osteotomy alone (single group). Clinical evaluation was made according to the Japanese Orthopaedic Association (JOA) hip score system (JOA hip score). In order to assess the effectiveness of this operation in regard to sustained relief from pain after the operation, Kaplan-Meier survivor analysis was performed on the basis of pain score on the JOA hip score. The end-point of the Kaplan-Meier analysis was defined as a score of less than 20 points on the pain score at the time of follow-up or conversion to total hip arthroplasty. In order to analyze the factors that exacerbated pain and to assess the effectiveness of the combined shelf operation, the degree of superior displacement of the femoral head (measured from roentgenograms) after the operation was examined in relation to the pain score. The mean JOA hip score improved, from 56.1+/-11.0 before the operation to 77.0+/-16.1 at the latest follow-up. Kaplan-Meier analysis showed a survival rate of 79.4% 10 years after the operation. Superior displacement of the femoral head had gradually progressed with time after the operation in patients with and without the combined shelf operation. Displacement of the femoral head was positively correlated with the acetabular angle of the weight-bearing surface (WBS angle) (sourcil) preoperation. The mean pain score in the combined group was significantly higher than that in the single group 6 to 9 years after the operation. The results of our assessments led us to conclude that Bombelli's valgus-extention osteotomy is satisfactory as far as clinical and radiological evaluations are concerned, as relief from the pain has continued for more than 10 years after the operation. The combined shelf operation is effective for relieving pain in severe osteoarthritis caused by congenital dislocation of the hip.

A PET study of adenosine A1 receptor in anesthetized monkey brain.

We demonstrated the distribution of adenosine A1 receptors in the anesthetized monkey brain with positron emission tomography (PET) using [(11)C]KF15372 ([1-propyl-(11)C]8-dicyclopropylmethyl-1, 3-dipropylxanthine). [(11)C]KF15372 was injected intravenously. The regional standardized uptake values and the distribution volume were calculated. We also investigated the effect of carrier on the uptake and regional brain distribution of [(11)C]KF15372. The use of [(11)C]KF15372 with dynamic PET scanning could be an appropriate method to analyze the regional binding potential of adenosine A1 receptors in living brain.

Successive construction of cellulase hyperproducers of Trichoderma using hyperpolyploids.

When the swollen conidia of Trichoderma reesei QM 6a are treated with 0.1% (w/v) colchicine solution, huge autopolyploid nuclei can be formed in those swollen conidia. When a mycelial mat derived from such a conidum is treated with a haploidizing reagent, benomyl, many fan-shaped sectors are produced from the colony, and cellulase hyperproducers are selected from conidia on the colony. When colchicine and benomyl treatments are repeated on cellulase hyperproducers, new hyperproducers can be constructed successively and systematically. Moreover, when conidia derived from autopolyploids are treated with ethylmethanesulfonate solution, another type of cellulase hyperproducers (polyploids) can be obtained.

In vivo imaging of adenovirus-mediated over-expression of dopamine D2 receptors in rat striatum by positron emission tomography.

PET was used to provide in vivo imaging of the over-expression of dopamine D2 receptor (D2R) induced by adenovirus vector-mediated gene transfer in rat striatum. The uptake of three kinds of D2R-specific ligands, [11C]raclopride, [11C]nemonapride and [11C]N-methylspiperone, measured by PET was higher in the striatum injected with the vectors for D2R than the contralateral striatum injected with a control vector 2-3 days after injection. However, the uptake of [11C]SCH 23390, a dopamine D1 receptor specific ligand, or [11C]beta-CIT-FP, a dopamine transporter specific tracer, was not different between bilateral striata. Co-injection of excess unlabeled raclopride inhibited the uptake of [11C]raclopride. At day 16 the increased uptake of [11C]raclopride declined to basal level, consistent with past in vitro assessment of this vector. In vivo imaging of D2R will permit longitudinal assessment of the efficiency of this and similar vectors in rat brain that can be related to functional changes being observed.

Early and delayed Tc-99m ECD brain SPECT in SLE patients with CNS involvement.

We compared early and delayed Tc-99m ECD SPECT scans in 32 SLE patients (Group 1, definite neuropsychiatric disorders; Group 2, minor neurologic symptoms or normal) with those of normal controls by visual inspection and semi-quantitative evaluation. With visual interpretation, 13 out of 14 patients in Group 1 (93%) and 7 out of 18 patients in Group 2 (39%) had diffuse uneven decrease in early scans. Seven patients in Group 2 (39%) who had normal early scans demonstrated focal decrease in the medial frontal lobe in delayed scans. With cerebral region to cerebellar ratios, in early scans, the medial frontal lobe in Group 1 and Group 2 was significantly lower than in normal controls, and lateral frontal lobe and occipital lobes in Group 1 were significantly lower than in normal controls. Nevertheless, in delayed scans, every cortical region except for the parietal lobe in Groups 1 and 2 was significantly lower than in normal controls. The retention rates in all regions in SLE patients were significantly lower than in normal controls. No case showed SPECT improvement on follow-up studies in either group in spite of clinical improvement. Delayed Tc-99m ECD brain SPECT of high sensitivity might be useful in detecting CNS involvement. Although the SPECT findings did not correlate with the neuropsychiatric symptoms, early and delayed Tc-99m ECD SPECT seems to provide useful objective diagnostic information in SLE patients.

Generation of fractal dimension images and its application to automatic edge detection in brain MRI.

We have developed four methods to generate a fractal dimension image and have applied them to the brain MRI. We have adopted four types of scanning methods, "CONVENTIONAL", "OVERLAPPING", "SYMMETRIC" and "FOLDED" to estimate the fractal dimension. The first three methods show almost the same fractal dimension images and their values were between two and three. In the "FOLDED" method, we were able to obtain the images in which the edge of a narrow region including dura and scalp surrounding the brain was selectively enhanced in the T1-weighted MRI. This is found to be a new edge-enhancing filter. We could remove the surrounding structure of the brain by using these filtered images and detect the edge of the brain surface automatically. The brain surface data can be used for various applications such as three-dimensional surface display and registration of inter-modal brain images.

Cellulase hyperproducers constructed from polyploids of Lentinus edodes.

A mycelial mat of Lentinus edodes was treated with 0.01% (w/v) colchicine solution for 240 h at 26 degrees C and autopolyploidization occurred. The mycelia were treated subsequently with the haploidizing reagent, benomyl, and fanshaped sectors were produced from colonies. Among such sectors, cellulase hyperproducers could be selected. The cellulase productivity of the hyperproducer, L1, did not decrease through five generations.

Construction of cellulase hyperproducing strains derived from polyploids of Trichoderma reesei.

The mycelial mat of Trichoderma reesei strain QM 6a was treated with 0.1% (w/v) colchicine solution for 14 days and designated M14. The cellulase productivity of strain M14 was not much higher than that of the original strain. When conidia of M14 were treated with ethylmethane sulphonate (EMS) solution, the cellulase hyperproducers, M14-1 and M14-2, were isolated using a selection medium containing Avicel. The DNA content of M14-1 and M14-2 was higher than that of the original strain. Cellulase productivity per mycelium of these strains increased and was higher than that of the original strain. The cellulase productivity did not change through ten generations when these strains were cultivated successively on a medium containing Avicel. It was concluded that cellulase hyperproducers, whose cellulase productivity per mycelium increased, could be obtained when the conidia of strain M14 were treated with EMS.

Arthrodesis of the hip joint using an external fixator.

Arthrodesis of the hip has been plagued by high rates of nonunion, and by complications associated with prolonged cast immobilization. To prevent these problems, we devised a procedure for hip arthrodesis using an external fixator in combination with internal fixation at the fusion site. We have treated nine patients with this technique. All of the arthrodeses were solidly united without wound infections at the most recent follow-up. Patients were able to leave their hospital bed and walk on the affected limb with a cane shortly after surgery. This was possible because the external fixator was low in profile, as it was applied from the anterosuperior iliac spine to the femoral shaft, and provided rigid stabilization of the arthrodesis. The technique resulted in a reduction in the period of bed rest, immediate postoperative mobilization, shorter periods of hospitalization, no limitation in the range of knee and ankle motion, improvement in the patient's ability to carry out the personal hygiene, and fewer complications.

Bentall operation, total aortic replacement and mitral valve replacement for a young adult with Marfan syndrome: a case of three-staged operation.

In Marfan syndrome, the most common cardiovascular abnormalities are dilatation of the aorta and aortic valve regurgitation in adult patients. Mitral valve dysfunction is the most common cause of morbidity and mortality in infants and children with Marfan syndrome, and is not frequently operated on in adult Marfan patients who undergo surgery for diseases of the aortic root and total aorta. This report describes a successfully three-staged operation for a 24 year-old man with Marfan syndrome who underwent an emergent Bentall operation and aortic arch replacement, total aortic replacement and mitral valve replacement over 2 years. Mitral valve regurgitation was mild but increased after the second operation. The graft was tightly adhesive and invasive to the sternum. Endoscopic view was helpful to avoid graft damage at resternotomy. The postoperative course was uneventful in each operation. Microscopic examination of the mitral valve leaflets showed abnormal increase of mucopolysaccharides, and disruption and fragmentation of elastic fibers.