Practical use of the central venous access port for contrast-enhanced CT: comparison with peripheral intravenous access regarding enhancement and safety.

AIM: To evaluate the efficacy of using the central venous (CV) port compared with peripheral intravenous access for contrast-material injection for contrast enhancement during the portal venous phase. MATERIALS AND METHODS: Patients were divided into three groups: CV delay, CV routine, and peripheral access (PA) groups. Patients in the CV delay group underwent injection in the arm-down position with an additional delay, while those in the CV routine and PA groups underwent injections with the routine injection protocol for portal venous phase imaging. Contrast enhancement was evaluated by measuring the mean radiodensity (Hounsfield units) values for the aortic arch, abdominal aorta, inferior vena cava, portal vein, and spleen. The peak injection pressure was recorded and compared among the three groups. RESULTS: No complications related to power injection were observed during 119 contrast-material injections performed using the CV port device. The CV delay group showed significantly lower radiodensity values than the PA group (165.7 ± 20.1 versus 181 ± 19 HU [p<0.01] for the portal vein); however, no significant differences in mean radiodensity values were observed between the CV routine and PA groups (p>0.05). The median peak injection pressure was 73.5, 67, and 47 psi in the CV delay, CV routine, and PA groups, respectively (p<0.01). CONCLUSION: The CV port can be used for safe contrast-material injection while maintaining contrast enhancement on portal venous phase comparable to that achieved with peripheral intravenous access.

Effect of a saline flush technique for head and neck imaging in dual-energy CT: improvement of image quality and perivenous artefact reduction using virtual monochromatic imaging.

AIM: To evaluate the effect of the saline flush (SF) technique on the depiction of lesions and the reduction of perivenous artefacts in the head and neck region using dual-energy computed tomography (CT) with virtual monochromatic imaging (VMI). MATERIALS AND METHODS: Fifty patients with head and neck cancer were divided into two groups: group A, without a SF and group B, with a 30-ml SF. All images were acquired using fast kilovolt-switching CT (Revolution HD, GE Healthcare, Milwaukee, WI, USA). Contrast-to-noise ratios (CNRs) of the lesions were calculated at VMI energy levels ranging from 40 to 80 keV. Subjective analysis of overall image quality, delineation of lesions, and perivenous artefacts was conducted by two reviewers at both VMI energy level 40 keV and the optimal energy level (which showed optimal CNR by objective analysis). RESULTS: Optimal energy level was 63 keV for group A and 61 keV for group B. At VMI energy levels ranging from 40 to 80 keV, the CNR was higher for group B. The highest subjective overall image quality was shown for group B at the optimal energy level (subjective image quality mean value, 3.40). Subjective delineation of lesions was comparable. The perivenous artefact score was significantly higher for group B (2.44 versus 2.74 [p<0.05] at 40 keV, 3.20 versus 3.46 [p<0.05] at the optimal energy level). CONCLUSION: The SF technique results in an improvement of lesion CNR and a reduction of perivenous artefacts in VMI using duel-energy CT, especially at 40 keV.

Recurrence after resection with curative intent for distal cholangiocarcinoma.

BACKGROUND: Few studies have been conducted on patterns of recurrence after resection for distal cholangiocarcinoma (DCC). The aim of this study was to investigate the incidence and pattern of recurrence after resection of DCC, and to evaluate prognostic factors for time to recurrence and recurrence-free survival (RFS). METHODS: Patients who underwent pancreatoduodenectomy with curative intent for DCC between 2001 and 2010 at one of 30 hospitals in Japan were reviewed retrospectively, with special attention to recurrence patterns. The Cox proportional hazards model was used for multivariable analysis. RESULTS: In the study interval, 389 patients underwent pancreatoduodenectomy for DCC with R0/M0 status. Recurrence developed in 213 patients (54·8 per cent). The estimated cumulative probability of recurrence was 54·3 per cent at 5 years. An initial locoregional recurrence occurred in 55 patients (14·1 per cent) and initial distant recurrence in 168 (43·2 per cent), most commonly in the liver. Isolated initial locoregional recurrence occurred in 45 patients (11·6 per cent). Independent prognostic factors for time to recurrence and RFS were perineural invasion (P = 0·001 and P = 0·009 respectively), pancreatic invasion (both P < 0·001) and lymph node metastasis (both P < 0·001). RFS worsened as the number of risk factors increased: the 5-year RFS rate was 70·6 per cent for patients without any risk factors, 50·3 per cent for patients with one factor, 31·8 per cent for those with two factors, and 13·4 per cent when three factors were present. CONCLUSION: More than half of patients with DCC experienced recurrence after R0 resection, usually within 5 years. Perineural invasion, pancreatic invasion and positive nodal involvement are risk factors for recurrence.

Outcomes in two patients with vocal fold palsy who underwent revision arytenoid adduction surgery.

OBJECTIVE: This study investigated the position of adduction thread attachment, pulling direction and fixation position in revision arytenoid adduction surgery performed in two patients with left vocal fold palsy in whom satisfactory speech improvement had not been obtained by arytenoid adduction and type 1 thyroplasty. METHODS: Revision arytenoid adduction surgery was performed with the vocal fold in the midline position in both cases. A type 1 thyroplasty procedure was subsequently added in one case because of worsened quality of speech following arytenoid adduction. RESULTS AND CONCLUSION: Although the arytenoid adduction procedure is conceptually well established, there is still room for debate concerning the actual surgical procedures used. The technique described in this report is effective, suggesting that it is worthy of recognition as an index procedure.

Stage specific expression of milk fat globule membrane glycoproteins in mouse mammary gland: comparison of MFG-E8, butyrophilin, and CD36 with a major milk protein, beta-casein.

The expression of mouse milk fat globule membrane (MFGM) glycoproteins, MFG-E8, butyrophilin, CD36 was analyzed by Northern blot analyses. MFG-E8 and butyrophilin mRNAs were specifically detected in the mammary gland of lactating mice, whereas CD36 mRNA was detected in the heart and lung as well as in the mammary gland of lactating mice. The mRNAs of the three MFGM glycoproteins accumulated at mid-lactation were about 2-10-times as much as those of the early and late gestation stages, whereas beta-casein mRNA accumulation was dramatically increased; the mRNA at mid-lactation was no less than 40-times as much as that before lactation. In mouse mammary epithelial cell lines, HC11 and COMMA-1D, only a slight or almost no enhancement for the expression of MFG-E8, butyrophilin and CD36 mRNAs was induced simply by the treatment with the lactogenic hormones such as prolactin, insulin and dexamethasone, whereas the beta-casein mRNA expression was remarkably enhanced only by that treatment. Furthermore, while the beta-casein protein was constantly detected in milk throughout the lactation stage, the content of MFG-E8 and butyrophilin proteins increased during the lactation with an increase in the milk fat content. These results suggest that the stage-specific expression of milk fat globule membrane glycoproteins in mammary epithelial cells is regulated in a similar but not necessarily identical mechanism to that of a major milk protein, beta-casein.

Expression and activation of MAP kinases, ERK1/2, in the human villous trophoblasts.

Mitogen-activated protein kinase (MAP kinase) plays a central role in the signal transduction for diverse cellular responses, such as proliferation, differentiation, stress response and cell death, via activation after binding of growth factors to the respective receptors on the cell membrane. In the human placental tissues, however, little is known about the expression and activation of the classical MAP kinases, extracellular signal-regulated kinase1/2 (ERK1/2). We therefore examined the expression of ERK1/2 in the human chorionic and placental tissues between 5 and 41 weeks of gestation, using Western blotting, immunohistochemistry and in situ hybridization. To explore the activation of ERK1/2 protein, we used an antibody that reacts with both phosphorylated and non-phosphorylated ERK1/2 (total ERK1/2), as well as antibodies that react only with phosphorylated ERK1/2. The expression pattern of phosphorylated ERK1/2 in the trophoblasts was compared with that of various growth factor receptors, such as c-met, IGF-1R, flt-1, EGFR, PDGFR, Bek, and flg. Total ERK1/2 was immunolocalized in the villous cytotrophoblasts (CTs), but not in the syncytiotrophoblasts (STs), throughout pregnancy. In situ hybridization also showed the localization of ERK1 mRNA in the villous CTs. Interestingly, however, phosphorylated ERK1/2 was immunolocalized in the villous CTs only up to 12 weeks of gestation. Western blot also showed the stronger bands of phosphorylated ERK1/2 in the tissues of the first trimester. Among the growth factor receptors, c-met was strongly expressed in the villous CTs during the first trimester, and resembled the expression pattern of phosphorylated ERK1/2. These findings suggest that the MAP kinase pathway is activated in the villous CTs during the first trimester in the human placenta.

Down-regulation of protein tyrosine phosphatase gene expression in lactating mouse mammary gland.

Detailed analysis of protein tyrosine phosphatase (PTP) expression in mouse mammary gland and mammary epithelial cells using a set of degenerate primers corresponding to the PTP core domain sequence revealed the presence of 16 different receptor-type and intracellular PTPs. Northern blot and RT-PCR analyses revealed that some PTPs were up-regulated during gestation, suggesting that these enzymes are involved in development of mammary gland. However, expression of most PTPs dramatically decreased during lactation, whereas the beta-casein gene expression was increased and remained at a high level. At the involution stage after weaning, most PTPs were up-regulated and their expression returned almost to the virgin level. Such up-regulation was also induced by forced weaning in lactating mother mice. These results suggest the possible contribution of PTPs to the development, involution, and remodeling of mammary gland and their possible inhibitory action on maintaining high expression of milk genes during lactation.

Calcium-free hemodialysis is useful for evaluating parathyroid function and bone disease in chronic hemodialysis patients.

By serum concentration of c-PTH, 18 hemodialysis patients were divided into 3 groups: group I (< 2.0 ng/ml, n = 8), group II (2.0-10.0 ng/ml, n = 5), group III (> 10.0 ng/ml, n = 5). When patients were dialyzed with Ca-free dialysate during the first 2 hours intact PTH level in serum shows no or slight increase in 5 out of 8 in group I.

[Combination therapy with low dose adriamycin for advanced or recurrent breast cancer. Hokkaido Breast Cancer Treatment Study Group].

Comparative clinical trials among 3 regimens for patients with advanced or recurrent breast cancer were performed as a multi-institutional joint study. Arm-I of 3 regimens consisted of a 3-day consecutive administration of adriamycin (ADM) at 10 mg/body every 4 weeks, a daily oral administration of cyclophosphamide (CPA), 5-FU and tamoxifen (TAM) at 100 mg, 200 mg, and 20 mg, respectively, and a once-a-week intramuscular or subcutaneous injection of OK-432 (OK) gradually increased from the initial dose of 1 KE to the maintenance dose of 5 KE. Arm-II contained methotrexate (MTX) at 10 mg/body for 3 consecutive days every 4 weeks in place of ADM in Arm-I. Arm-III contained neither ADM nor MTX. Of 69 cases registered, 52 were eligible, leaving 6 non-eligible and 11 incomplete cases. The results of the overall evaluation of 48 complete cases other than 4, in which the tumor was not exactly measured, were as follows. Arm-I resulted in 2 CR and 3 PR out of 19 cases, the response rate being 23.6% (5/19). Arm-II resulted in 1 CR out of 15, the response rate being 6.7% (1/15). In Arm-III, no response cases were found. No significant difference was observed among three treatment groups (p = 0.055), but in Arm-I, the response rate was higher than in the other treatment groups, suggesting that there is a probability of useful combined use of ADM.

[Consideration of surgical treatment for recurrence after the resection of hepatic metastases from colorectal cancer].

We considered treatment for recurrence following the resection of hepatic metastases from colorectal cancer. The subjects of this study were 15 of 29 patients who had undergone WHF arterial infusion following resection of hepatic metastases from colorectal cancer, in whom there was a recurrence. Of these 15 cases, 6 involved recurrence in a single organ (residual liver, 4; lung, 1; local area, 1), 7 involved two organs (residual liver and lung, 2; residual liver and local area, 2; residual liver and bone, 1; spleen and intra-abdominal lymph node, 1; intra-abdominal lymph node and peritoneum, 1) and 2 involved three organs (lung, bone and abdominal wall, 1; lung, peritoneum and distal lymph node, 1). Reresection was performed in all cases in which recurrence occurred in a single organ. For those cases in which recurrence occurred in two or more organs, reresection and infusion were performed in the 4 cases of recurrence in the residual liver and reresection was performed in the case of recurrence in the spleen and intra-abdominal lymph node (No. 16), the case of local recurrence and the case involving the abdominal wall. The 5-year survival rate of the 29 cases who underwent initial hepatic resection was 61.9%. Five years following resection, the recurrence rate in the residual liver was 38.3%. The survival rates following treatment for recurrence were 76.9, 51.3 and 25.6% for 1, 3 and 5 years, respectively. Of the 8 deaths which have occurred to date, only one was directly related to an increase in hepatic metastases. Following resection of hepatic metastases from colorectal cancer, WHF provides a high rate of prevention as well as a high survival rate. Furthermore, with regard to recurrence following WHF treatment, if the recurrence is in only one organ, there is the possibility of achieving effective treatment by reresection (WHF = 5-FU 1,000 mg/m2 5 hrs qw).

[Clinical study of eel calcitonin for relief of pain from metastatic bone lesions].

Thirty patients with bone metastasis were treated with eel calcitonin (CT) to relieve severe pain from metastatic bone lesions. Patients were two males and twenty-eight females with a mean age of 52.8. CT was administered intramuscularly in twenty-seven patients and intravenously in three. CT was effective on 55.6% of patients to reduce severe bone pain but did not decrease the amount of analgesics in most patients. Serum Ca and P were not changed markedly. As side-effects, two patients complained of nausea and vomiting after administration of CT but they weren't severe. These results indicate that CT is quite useful drug for relief of severe bone pain from metastatic lesions in patients with breast or digestive tract carcinomas.

[Three cases in which CR was obtained in residual metastatic lesions by intrahepatic arterial infusion after resection of hepatic metastases from colorectal carcinoma].

We report three cases in which CR was maintained after infusion (WHF) was performed for residual metastatic lesions following resection of hepatic metastases from colorectal cancer. (Case 1) A 55-year-old female with sigmoidal cancer and hepatic metastases, H2 (4 lesions). Right lobectomy and partial resection of the left lobe were performed. On the third month following surgery, CT showed two lesions in the lateral segment of the left lobe, and WHF was then begun. One month after the start of infusion, the lesions calcified and following that, disappeared. Infusion was performed for 12 months and the total amount of 5-FU was 52.8 g. Eight years and nine months following surgery, the patient is currently alive and without recurrence. (Case 2) A 65-year-old male with rectal cancer and hepatic metastases, H3 (6 lesions). Four lesions were removed by hepatic resection; however, 2 deep lesions in S4 and S5 were left unresected. WHF was begun one month following surgery, following which the lesions were undetectable by either CT or US. Infusion was performed for 18 months and the total amount of 5-FU was 81 g. Two years and ten months after surgery an isolated lung metastasis was discovered in the right lung and a thoracoscopic partial resection was performed. Eight years and four months following the original surgery and five years and four months following the lung operation the patient is alive and without recurrence. (Case 3) A 55-year-old male with rectal cancer and subsequently discovered hepatic metastases, H3 (5 lesions). Resection of the lateral segment and a partial resection of the right lobe were performed; however, one deep lesion in S7 was left unresected. WHF was begun on the 10th day following surgery. At about eight months there was a change in shape and shrinkage of the lesion. Infusion was performed for 11 months and the total amount of 5-FU was 48 g. Ten months following surgery, CT showed a new lesion in S7 and a partial resection was performed. Intraoperative US confirmed the disappearance of the previous residual lesion in S7. One year and one month following the original surgery, the patient is alive and without recurrence. From these results, it is suggested that with postoperative WHF it is possible to obtain a complete cure in cases of colorectal cancer with hepatic metastases without the resection of all lesions. (*WHF: 5-FU 1,000 mg/m2/5 hrs/week).

[A case of giant hepatocellular carcinoma successfully treated by arterial administration of SMANCS].

A 68-year-old male was referred to our hospital for the precise examination of a giant hepatic tumor detected in a mass survey. The lesion occupied most of the right hepatic lobe, further advancing to the medial segment of the left lobe. However, hepatic functions were well preserved (ICG K = 0.141). Considering the characteristic images of the lesion with positive anti-HCV and high titer of PIVKA II (0.860 AU/ml), the diagnosis was hepatocellular carcinoma. First arterial administration of SMANCS was performed on May in 1994, followed by 6 successive procedures with an interval of about 2 months (total dosage 36 mg), resulting in remarkable tumor shrinkage and tumor marker normalization. On January in 1995, a metastatic lesion to the right rib was controlled by 2 mg of SMANCS administered to the intercostal artery combined with radiation therapy (60 Gray). Frequent administrations of SMANCS caused no serious complications, and tumor feeders were well preserved. Therefore, arterial administration of SMANCS is thought to be one choice for the therapy of giant HCC with good functional reserve.

[Intra-arterial preventive chemotherapy for residual liver after resection of hepatic metastasis from colorectal cancer].

We treated 18 cases with intra-hepatic arterial infusion chemotherapy after resection of hepatic metastasis from colorectal cancer (June 1991-September 1997). Eight cases were H1, 7 were H2, and 3 were H3. Hepatic lobectomy was done in 3 cases, lobectomy + partial resection in 2 cases, and partial resection in 13 cases. All cases received high-dose intermittent 5-FU infusion (WHF = 5-FU 1,000 mg/m2/5 hrs/w) on an outpatient basis. The total frequency of WHF was 4-54 times (average 29), and total 5-FU doses ranged from 6.0 to 81.0 g (average 40 g). The 1- and 5-year cumulative survival rates were 100% and 77.5% in all patients 100% and 87.5% in H1 group and 100% and 64.3% in H2 + H3 group, respectively. There was no significant difference of survival between the H1 and H1 + H3 groups. The 1- and 5-year recurrence rates in residual liver were 5.9% and 14.4%, respectively. One of 2 cases with residual liver recurrence was resected for metastasis again, and the patient is now in a disease-free state. WHF after resection of hepatic metastasis from colorectal cancer has a preventive effect for their survival, not only in H1 group but also in H2 + H3 group.

[Correlation between the age-dependent changes in caloric response and in pure tone hearing].

Previous reports have examined the age-dependent changes of the auditory system or the caloric response, but results have been inconsistent. No study to date has correlated the age-dependent changes in caloric response with those in pure tone hearing in the same subjects. In this study a caloric test and a pure tone audiometry test were performed in 86 subjects (172 ears), age range 24 to 84 years of age, including 12 otoneurologically healthy volunteers (24 ears), and 74 tinnitus patients without subjective hearing loss (148 ears). The maximal slow phase eye velocity (SPEV) of caloric nystagmus response and the mean hearing level at high frequencies were measured and the age-dependent changes in these scores were compared. The following results were obtained. 1) The SPEV of caloric nystagmus, which remained unchanged until markedly advanced age, decreased significantly from 65 years of age in men and from 75 years in women; the change occurring earlier in men than in women. 2) The hearing level at high frequencies decreased abruptly from 50 years of age with a more gradual change from 75 years was significantly lower in men than in women over 65 years of age. 3) There was a weak but significant correlation between the age-dependent changes in SPEV and those in hearing level at high frequencies.

[Statistical analyses on over ten years survivals in Hokkaido under chronic dialysis therapy].

In Hokkaido, there were 305 chronic dialysis patients surviving more than ten years as of July 31, 1985. All patients except for one (CAPD) have been placed under hemodialysis. About 73% of them were introduced into a dialysis therapy in their thirties and chronic glomerulonephritis was extremely predominant as for the underlying disease. 93.2% of the cases possessed internal AV-fistulae using own vessels and other types of blood access remained only 6.8%. Hematocrit (Hct) was 27.5% on average of 305 cases. The value was fairly satisfactory but it must be noted that Hct of 33 patients (10.8% of all) was less than 20%. Severe anemia is still one of major complication in chronic dialysis patients. Characteristic complications, which have been increasing in frequency in parallel with prolonged dialysis length, became clarified: renal osteodystrophy, secondary hyperparathyroidism, carpal tunnel syndrome, persistent hypotension and so on. The former two are strongly related to Ca & P metabolism and some of the long-term survivals require parathyroidectomy. It is now estimated that carpal tunnel syndrome is induced by accumulation and deposition of beta 2-microglobulin, which increases in blood progressively if used Cuprophane membrane dialyser. Patients with CTS must be placed under surgical intervention, which relieves the symptoms effectively and the prophylaxis might require protein-permeating dialyser.

[Clinical assessment of CAPD (continuous ambulatory peritoneal dialysis) for chronic end-stage renal failure].

Eight patients of end stage renal failure were placed under CAPD (Continuous Ambulatory Peritoneal Dialysis) therapy in our institution. The main indications were difficulty or lack of vascular access. The therapeutic duration ranged from 15 to 2 months and the results described-below were obtained. BUN, Serum Creatinine were well controlled. Hemoglobin & hematocrit increased significantly in most cases. Removal of water and salt was satisfactory. Consequently, limitation of water and salt became unnecessary in all cases. So far protein loss seemed to be a lesser problem, which could be overcome by an adequate protein intake. Catheter troubles and peritonitis were observed in 3 cases respectively but none became the reason for an immediate interruption of CAPD. General well-beings of the CAPD patients improved in a definite degree subjectively and objectively CAPD has been gaining surprisingly fast popularity all over the world but many questions remain presently unanswered: (1) Catheter trouble and peritonitis (long-term survival of the technique) (2) Adequacy of the dialysate constitution (3) Physiological changes of the peritoneum in long-term CAPD (4) Metabolic changes of CAPD patients (5) Drug Kinetics etc. These problems were briefly discussed.

[Evaluation of 18F-FDG positron emission tomography (PET) in the detection of unknown primary tumors].

18F-fluorodeoxyglucose positron emission tomography was able to identify previously unknown primary tumors in 2 of 4 patients after an unsuccessful conventional diagnostic workup such as chest radiography, ultrasound, computed tomography, MRI and various endoscopies. The 2 patients in which the primary tumors were detected proved to have a carcinoma of the lung, one of the patients received radiotherapy and chemotherapy after the detection of the primary tumor by FDG PET. The primary tumor of the lung demonstrated no focal FDG uptake after the successive treatment. On the other hand, in one patient with prostatic carcinoma and another in which the primary tumor has yet to be detected, FDG PET was unable to identify the primary tumor. This suggests a limitation of PET studies in detecting cancers. Because of increased glycolysis in cancer cells, FDG PET can be used to detect cancers with its high sensitivity, surveying the entire body non-invasively in one session. PET has the advantage of detecting primary tumors of an unknown origin when compared to conventional diagnostic studies.

Lipocalin2 enhances the matrix metalloproteinase-9 activity and invasion of extravillous trophoblasts under hypoxia.

OBJECTIVES: The invasion of extravillous trophoblasts (EVTs) to the decidua and spiral arteries in early pregnancy is a crucial step for a successful pregnancy; however, its mechanisms are not fully understood. Lipocalin2 (LCN2), a multifunctional secretory protein known as neutrophil gelatinase-associated lipocalin (NGAL), reportedly enhanced invasiveness via the activation of matrix metalloproteinase-9 (MMP-9) in several cancer cells. In this study, the expression and function of LCN2 in early placenta were analyzed. METHODS: Early placental tissues between 7 and 10 weeks of gestation were obtained from normal pregnant women who underwent elective termination. The expression of LCN2 was examined using immunostaining and RT-PCR. EVTs isolated from these placental tissues and a choriocarcinoma cell line (JAR) were used to investigate the effects of LCN2 on proliferation, invasion potential, and MMP-9 activity under hypoxia using a WST-1 assay, Matrigel invasion assay, and gelatin gel zymography, respectively. RESULTS: The immunohistochemical expression of LCN2 was observed in the cytoplasm of EVTs, cytotrophoblasts and the decidua, but not in syncytiotrophoblasts. The addition of recombinant LCN2 did not affect proliferation, but enhanced the invasiveness (500 ng/mL, p < 0.01) and MMP-9 activity of primary cultured EVTs and JAR in a dose-dependent manner. Silencing LCN2 using shRNA reduced the invasiveness (p < 0.01) and MMP-9 activity of JAR. In addition, the hypoxic condition (2% O2) increased LCN2 expression (p < 0.01), MMP-9 activity, and invasive ability (p < 0.01). CONCLUSIONS: LCN2 was involved in the invasiveness of EVTs, especially under hypoxia, via increased MMP-9 activity.