Multicenter prospective trial of total gastrectomy versus proximal gastrectomy for upper third cT1 gastric cancer.

BACKGROUND: The appropriate surgical procedure for patients with upper third early gastric cancer is controversial. We compared total gastrectomy (TG) with proximal gastrectomy (PG) in this patient population. METHODS: A multicenter, non-randomized trial was conducted, with patients treated with PG or TG. We compared short- and long-term outcomes between these procedures. RESULTS: Between 2009 and 2014, we enrolled 254 patients from 22 institutions; data from 252 were included in the analysis. These 252 patients were assigned to either the PG (n = 159) or TG (n = 93) group. Percentage of body weight loss (%BWL) at 1 year after surgery, i.e., the primary endpoint, in the PG group was significantly less than that of the TG group (- 12.8% versus - 16.9%; p = 0.0001). For short-term outcomes, operation time was significantly shorter for PG than TG (252 min versus 303 min; p < 0.0001), but there were no group-dependent differences in blood loss and postoperative complications. For long-term outcomes, incidence of reflux esophagitis in the PG group was significantly higher than that of the TG group (14.5% versus 5.4%; p = 0.02), while there were no differences in the incidence of anastomotic stenosis between the two (5.7% versus 5.4%; p = 0.92). Overall patient survival rates were similar between the two groups (3-year survival rates: 96% versus 92% in the PG and TG groups, respectively; p = 0.49). CONCLUSIONS: Patients who underwent PG were better able to control weight loss without worsening the prognosis, relative to those in the TG group. Optimization of a reconstruction method to reduce reflux in PG patients will be important.

Early results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 and docetaxel/cisplatin/S-1 as neoadjuvant chemotherapy for locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is a promising method of improving the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both effective against metastatic gastric cancer. This report clarified the impact of these regimens on early endpoints, including the pathological responses, chemotherapy-related toxicities, and surgical results. METHODS: Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as NAC. Patients then underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was the 3-year overall survival. RESULTS: Between October 2011 and September 2014, 132 patients were assigned to receive CS (n = 66; 33 in 2 courses and 33 in 4 courses) or DCS (n = 66; 33 in 2 courses and 33 in 4 courses). The respective major grade 3 or 4 hematological toxicities (CS/DCS) were leukocytopenia (14.1%/26.2%), neutropenia (29.7%/47.7%), anemia (14.1%/12.3%), and platelet reduction (3.1%/1.5%). The rate of pathological response, defined as a complete response or < 10% residual cancer remaining, was 19.4% in the CS group and 15.4% in the DCS group, and 15.6% in the two-course group and 19.0% in the 4-course group. The R0 resection rate was 72.7% in the CS group and 81.8% in the DCS group and 80.3% in the two-course group and the 74.2% in the four-course group. No treatment-related deaths were observed. CONCLUSIONS: Our results do not support three-drug therapy with a taxane over two-drug therapy, or any further treatment beyond two cycles as an attractive candidate for the test arm of NAC.

Multicenter randomized phase II study of cisplatin and fluorouracil plus docetaxel (DCF) compared with cisplatin and fluorouracil plus Adriamycin (ACF) as preoperative chemotherapy for resectable esophageal squamous cell carcinoma (OGSG1003).

BACKGROUND: This phase II trial evaluated the efficacy of cisplatin and fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an alternative regimen in a new phase III trial investigating the optimal neoadjuvant treatment of patients with ESCC. PATIENTS AND METHODS: Patients with resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 7 days) every 4 weeks or DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The primary end point was RFS, analyzed by the intention-to-treat. RESULTS: Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, all of whom were eligible and randomly assigned to the two groups (81 to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and DCF groups were equivalent (95.9% versus 96.2%, P = 0.93). The 2-year RFS and overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio 0.53, 95% confidence interval 0.33-0.83, P = 0.0057) and 78.6% versus 65.4% (P = 0.08), respectively. CONCLUSION: Compared with ACF, DCF chemotherapy was associated with prolonged RFS for patients with resectable advanced ESCC. Thus, DCF chemotherapy has potential as a standard neoadjuvant therapy for resectable ESCC. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN000004555/000004616).

Randomized clinical trial comparing standard diet with perioperative oral immunonutrition in total gastrectomy for gastric cancer.

BACKGROUND: Total gastrectomy for gastric cancer is associated with excessive weight loss and decreased calorie intake. Nutritional support using eicosapentaenoic acid modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the perioperative period is unclear. METHODS: This was a randomized phase III clinical trial of addition of eicosapentaenoic acid-rich nutrition to a standard diet in patients having total gastrectomy for gastric cancer. Patients were randomized to either a standard diet or standard diet with oral supplementation of an eicosapentaenoic acid (ProSure®), comprising 600 kcal with 2·2 g eicosapentaenoic acid, for 7 days before and 21 days after surgery. The primary endpoint was percentage bodyweight loss at 1 and 3 months after surgery. RESULTS: Of 127 eligible patients, 126 were randomized; 124 patients (61 standard diet, 63 supplemented diet) were analysed for safety and 123 (60 standard diet, 63 supplemented diet) for efficacy. Across both groups, all but three patients underwent total gastrectomy with Roux-en-Y reconstruction. Background factors were well balanced between the groups. Median compliance with the supplement in the immunonutrition group was 100 per cent before and 54 per cent after surgery. The surgical morbidity rate was 13 per cent in patients who received a standard diet and 14 per cent among those with a supplemented diet. Median bodyweight loss at 1 month after gastrectomy was 8·7 per cent without dietary supplementation and 8·5 per cent with eicosapentaenoic acid enrichment (P = 0·818, adjusted P = 1·000). Similarly, there was no difference between groups in percentage bodyweight loss at 3 months (P = 0·529, adjusted P = 1·000). CONCLUSION: Immunonutrition based on an eicosapentaenoic acid-enriched oral diet did not reduce bodyweight loss after total gastrectomy for gastric cancer compared with a standard diet. Registration number: UMIN000006380 ( http://www.umin.ac.jp/).

Prospective randomized trial of preoperative enteral immunonutrition followed by elective total gastrectomy for gastric cancer.

BACKGROUND: Perioperative enteral immunonutrition is thought to reduce postoperative morbidity in patients undergoing major gastrointestinal surgery. This study assessed the clinical effects of preoperative enteral immunonutrition in well nourished patients with gastric cancer undergoing total gastrectomy. METHODS: Well nourished patients with primary gastric cancer, fit for total gastrectomy, were randomized to either a control group with regular diet, or an immunonutrition group that received regular diet supplemented with 1000 ml/day of immunonutrients for 5 consecutive days before surgery. The primary endpoint was the incidence of surgical-site infection (SSI). Secondary endpoints were rates of infectious complications, overall postoperative morbidity and C-reactive protein (CRP) levels on 3-4 days after surgery. RESULTS: Of 244 randomized patients, 117 were allocated to the control group and 127 received immunonutrition. SSIs occurred in 27 patients in the immunonutrition group and 23 patients in the control group (risk ratio (RR) 1.09, 95 per cent confidence interval 0.66 to 1.78). Infectious complications were observed in 30 patients in the immunonutrition group and 27 in the control group (RR 1.11, 0.59 to 2.08). The overall postoperative morbidity rate was 30.8 and 26.1 per cent respectively (RR 1.18, 0.78 to 1.78). The median CRP value was 11.8 mg/dl in the immunonutrition group and 9.2 mg/dl in the control group (P = 0.113). CONCLUSION: Five-day preoperative enteral immunonutrition failed to demonstrate any clear advantage in terms of early clinical outcomes or modification of the systemic acute-phase response in well nourished patients with gastric cancer undergoing elective total gastrectomy. REGISTRATION NUMBER: ID 000000648 (University Hospital Medical Information Network (UMIN) database).

Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer.

BACKGROUND: Locally advanced gastric cancer with extensive lymph node metastasis is usually considered unresectable and so treated by chemotherapy. This trial explored the safety and efficacy of preoperative chemotherapy followed by extended surgery in the management of locally advanced gastric adenocarcinoma. METHODS: Patients with gastric cancer with extensive lymph node metastasis received two or three 28-day cycles of induction chemotherapy with irinotecan (70 mg/m(2) on days 1 and 15) and cisplatin (80 mg/m(2) on day 1), and then underwent gastrectomy with curative intent with D2 plus para-aortic lymphadenectomy. Primary endpoints were 3-year overall survival and incidence of treatment-related death. RESULTS: The study was terminated because of three treatment-related deaths when 55 patients had been enrolled (mortality rate above 5 per cent). Two deaths were due to myelosuppression and one to postoperative complications. Clinical response and R0 resection rates were 55 and 65 per cent respectively. The pathological response rate was 15 per cent. Median overall survival was 14.6 months and the 3-year survival rate 27 per cent. CONCLUSION: This multimodal treatment of locally advanced gastric cancer provides reasonable 3-year survival compared with historical data, but at a considerable cost in terms of morbidity and mortality.

The significance of gastrectomy in advanced gastric cancer patients with non-curative factors.

BACKGROUND: The role of gastrectomy in the treatment of advanced gastric cancer patients with non-curative factors remains controversial. We investigated prognostic factors and evaluated the role of gastrectomy in such patients. PATIENTS AND METHODS: Eighty-eight advanced gastric cancer patients with non-curative factors were prospectively studied. The patients were categorized into the following two groups: Group A: 52 patients who underwent gastrectomy and subsequently received chemotherapy, Group B: 36 patients who received chemotherapy alone. RESULTS: The median survival times of group A and B patients were 351 and 182 days, respectively (p=0.008). Multivariate analysis showed that gastrectomy was the only positive independent prognostic factor, with no effect on the results of chemotherapy. There was no significant difference in the duration of hospital stay between patients of the two groups, while significantly longer maintenance of oral intake was observed for group A. CONCLUSION: In advanced gastric cancer patients with non-curative factors, gastrectomy was beneficial for survival with longer maintenance of oral intake.

Mutations in the novel membrane protein spinster interfere with programmed cell death and cause neural degeneration in Drosophila melanogaster.

Mutations in the spin gene are characterized by an extraordinarily strong rejection behavior of female flies in response to male courtship. They are also accompanied by decreases in the viability, adult life span, and oviposition rate of the flies. In spin mutants, some oocytes and adult neural cells undergo degeneration, which is preceded by reductions in programmed cell death of nurse cells in ovaries and of neurons in the pupal nervous system, respectively. The central nervous system (CNS) of spin mutant flies accumulates autofluorescent lipopigments with characteristics similar to those of lipofuscin. The spin locus generates at least five different transcripts, with only two of these being able to rescue the spin behavioral phenotype; each encodes a protein with multiple membrane-spanning domains that are expressed in both the surface glial cells in the CNS and the follicle cells in the ovaries. Orthologs of the spin gene have also been identified in a number of species from nematodes to humans. Analysis of the spin mutant will give us new insights into neurodegenerative diseases and aging.

Multicentre observational study of quality of life after surgical palliation of malignant gastric outlet obstruction for gastric cancer.

BACKGROUND: Quality of life (QoL) is a key component in decision-making for surgical palliation, but QoL data in association with surgical palliation in advanced gastric cancer are scarce. The aim of this multicentre observational study was to examine the impact of surgical palliation on QoL in advanced gastric cancer. METHODS: The study included patients with gastric outlet obstruction caused by incurable advanced primary gastric cancer who had no oral intake or liquid intake only. Patients underwent palliative distal/total gastrectomy or bypass surgery at the physician's discretion. The primary endpoint was change in QoL assessed at baseline, 14 days, 1 month and 3 months following surgical palliation by means of the EuroQoL Five Dimensions (EQ-5D™) questionnaire and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire gastric cancer module (QLQ-STO22). Secondary endpoints were postoperative improvement in oral intake and surgical complications. RESULTS: Some 104 patients (23 distal gastrectomy, 9 total gastrectomy, 70 gastrojejunostomy, 2 exploratory laparotomy) were enrolled from 35 institutions. The mean EQ-5D™ utility index scores remained consistent, with a baseline score of 0·74 and the change from baseline within ± 0·05. Gastric-specific symptoms showed statistically significant improvement from baseline. The majority of patients were able to eat solid food 2 weeks after surgery and tolerated it thereafter. The rate of overall morbidity of grade III or more according to the Clavien-Dindo classification was 9·6 per cent (10 patients) and the 30-day postoperative mortality rate was 1·9 per cent (2 patients). CONCLUSION: In patients with gastric outlet obstruction caused by advanced gastric cancer, surgical palliation maintained QoL while improving solid food intake, with acceptable morbidity for at least the first 3 months after surgery. Registration number 000023494 (UMIN Clinical Trials Registry).

Effects of left ventricular asynchrony on time constant and extrapolated pressure of left ventricular pressure decay in coronary artery disease.

To elucidate the effects of ventricular asynchrony with or without myocardial ischemia on the time constant of left ventricular pressure decay and asymptote, that is, the level to which pressure would decrease if isovolumic pressure decrease continued infinitely, left ventriculography and pressure measurements were investigated in 14 normal subjects and 25 patients with coronary artery disease. Ventricular asynchrony was quantitated by the segmental area-time curve. This study consisted of two parts. 1) After a right atrial pacing stress test, the time constant and asymptote remained unchanged in eight normal subjects. In 18 patients with coronary artery disease and pacing-induced angina, asynchrony increased, the time constant was prolonged (64 +/- 13 to 94 +/- 17 ms, p less than 0.01) and the asymptote decreased (-22 +/- 10 to -46 +/- 20 mm Hg, p less than 0.01) after the pacing. 2) During right ventricular pacing at 80, 100 and 120 beats/min in the patients, asynchrony increased and the time constant was prolonged (55 +/- 7 versus 70 +/- 10, 47 +/- 11 versus 66 +/- 19, 36 +/- 7 versus 53 +/- 13 ms, respectively, p less than 0.01 versus right atrial pacing), whereas the asymptote was unchanged in six normal subjects compared with the value during right atrial pacing at each pacing rate. In seven patients with coronary artery disease, right ventricular pacing at 80, 100 and 120 beats/min also produced an increase in the time constant, while the asymptote was unchanged. Thus, prolongation of the time constant of left ventricular pressure decay may result from ventricular asynchrony even in the absence of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

From behavior to development: genes for sexual behavior define the neuronal sexual switch in Drosophila.

The isolation and analysis of Drosophila mutants with altered sexual orientation lead to the identification of novel branches in the sex-determination cascade which govern the sexually dimorphic development of the nervous system. One such example is the fruitless (fru) gene, the mutation of which induces male-to-male courtship and malformation of a male-specific muscle, the muscle of Lawrence (MOL). Since the MOL is formed in wild-type flies when the innervating nerve is male, regardless of the sex of the MOL itself, the primary site of Fru function is likely to be the motoneurons controlling the MOL. The fru gene produces multiple transcripts including sex-specific ones. A female-specific mRNA from the fru locus has a putative Transformer (Tra) binding site in its 5' untranslated region, suggesting that fru is a direct target of Tra. The fru transcripts encode a set of proteins similar to the BTB (Bric à brac, Tramtrack and Broad-complex)-Zn finger family of transcription factors. Mutations in the dissatisfaction (dsf) gene result in male-to-male courtship and reduced sexual receptivity of females. The dsf mutations also give rise to poor curling of the abdomen in males during copulation and failure of egg-laying by females. The latter phenotypes are ascribable to aberrant innervation of the relevant muscles. A genetic analysis reveals that expression of the dsf phenotypes depends on Tra but not on Doublesex (Dsx) or Fru, suggesting that dsf represents another target of Tra. Taken together, these findings suggest that the sex-determination protein Tra has at least three different targets, dsx, fru and dsf, each of which represents the first gene in a branch of the sex-determination hierarchy functioning in a mutually-exclusive set of neuronal cells in the Drosophila central nervous system.

cDNA cloning of a novel rainbow trout SRY-type HMG box protein, rtSox23, and its functional analysis.

We have isolated a cDNA clone for a new member of Sox genes, termed rtSox23, from a rainbow trout ovary cDNA library. rtSox23 mRNA was notably expressed in ovary and brain. rtSox23 contains a leucine zipper in addition to an SRY-type HMG box. Although the recombinant HMG box region protein of rtSox23 could bind to an AACAAT sequence, the full-length rtSox23 could form a homodimer and did not bind to the sequence. Furthermore, using a two-hybrid system, we have isolated a cDNA clone encoding a protein that bound to the leucine zipper region of rtSox23. This protein was the rainbow trout homologue of mouse nucleoporin p62, which is a component of the nuclear pore complex in nuclear envelope. The rainbow trout p62 mRNA was also prominent in ovary and brain. Taken together, these results suggest that the rainbow trout p62 associates with rtSox23 in vivo and modulates the function of rtSox23.

Different target-site specificities of the hairpin ribozyme in cis and trans cleavages.

The hairpin ribozyme cleaves a phosphodiester bond at the 5' side of a 5'GUC3' sequence of an RNA with high efficiency. An RNA having a 5'GUA3' sequence instead of the GUC sequence is a poor substrate for this ribozyme. Here, we show that this is indeed so in a trans-acting ribozyme system, but in a cis-acting ribozyme system this ribozyme cleaves the 5' side of a GUA sequence as efficiently as the wild-type cleaves the GUC sequence. One base substitution in the ribozyme also affected the target-site specificity in the cis-acting system.

Adverse response to nifedipine in unstable angina pectoris.

A patient had accelerated attacks of chest pain associated with transient ST elevation or depression in the anterior leads. Coronary angiogram revealed severe multi-vessel disease. Anginal attacks with conspicuous ST depression were induced repeatedly by both oral and sublingual administration of nifedipine. Among various vasodilator drugs tested on this patient, dipyridamole and hydralazine induced anginal attacks. These observations suggest that anginal attacks induced by administration of nifedipine may be related to the augmentation of myocardial oxygen consumption due to increases in cardiac output and heart rate, the coronary steal phenomenon, or an increase in venous return accompanied by the subendocardial underperfusion.

Genetic dissection of sexual orientation: behavioral, cellular, and molecular approaches in Drosophila melanogaster.

Insertional mutagenesis using P-element vectors yielded several independent mutations that cause male homosexuality in Drosophila melanogaster. Subsequent analyses revealed that all of these insertions were located at the same chromosomal division, 91B, where one of the inversion breakpoints responsible for the bisexual phenotype of the fruitless (fru) mutant has been mapped. In addition to the altered sexual orientation, the fru mutants displayed a range of defects in the formation of a male-specific muscle, the muscle of Lawrence. Since the male-specific formation of this muscle was dependent solely on the sex of the innervating nerve and not on the sex of the muscle itself, the primary site of action of the fru gene should be in the neural cells. satori, one of the P-insertion alleles of fru which we isolated, carried the lacZ gene of E. coli as a reporter, and beta-galactosidase expression was found in a subset of brain cells including those in the antennal lobe in the satori mutant. Targeted expression of a sex determination gene, transformer (tra), was used to produce chromosomally male flies with certain feminized glomeruli in the antennal lobe. Such sexually mosaic flies courted not only females but also males when the DM2, DA3 and DA4 glomeruli were feminized, indicating that these substructures in the antennal lobe may be involved in the determination of the sexual orientation of flies. Molecular cloning and analyses of the genomic and complementary DNAs indicated that transcription of the fru locus yields several different transcripts, one of which encodes a putative transcription regulator with a BTB domain and two zinc finger motifs. In the 5' non-coding region, three putative Transformer binding sites were identified. It appears plausible therefore that the fru gene is one of the elements in the sex determination cascade that controls sexual fates of certain neuronal cells. Improper sex determination in these neural cells may lead to altered sexual orientation and malformation of the male-specific muscle. Some implications of the results of our study on sexual orientation in other organisms will be discussed based on the Drosophila research.

Structure-activity relationships of 4'-O-substituted 1-benzylisoquinolines with respect to their actions on the cell membrane of blood platelets and erythrocytes.

4'-O-Substituted 1-benzyl-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines inhibited the collagen-induced activation (aggregation and ATP secretion) of rabbit platelets and transformed the shape of human erythrocytes in a dose-dependent manner. Both effects increased with increasing number of carbon atoms of the 4'-substituted hydrocarbon moiety. The incorporation of these compounds into the erythrocyte membrane was also dependent on the number of carbon atoms of the 4'-substituted radical. The most potent phenoxy derivative suppressed arachidonic acid release from membrane phospholipids but had no effect on arachidonic acid metabolism in platelets. This indicated that the effects are comparable to those of a natural bisbenzylisoquinoline, cepharanthine. These effects appear to be due to a perturbing action on the membrane lipid bilayer.

The effects of calpeptin (a calpain specific inhibitor) on agonist induced microparticle formation from the platelet plasma membrane.

Platelets activated by various agonists produce formation of vesicles shed from the plasma membrane (microparticles). However, the mechanism of microparticle (MP) formation has not been clarified yet. The aim of the present study was to determine the possibility of involvement of calpain (a Ca(2+)-dependent thiol protease) in MP formation. Washed platelets preincubated with calpeptin, a cell permeable calpain specific inhibitor, or with a vehicle were activated by thrombin plus collagen or by calcium ionophore A23187. Flow cytometry was used to detect the amount of microparticle formation by using murine monoclonal antibodies against GP IIb-IIIa or GP IIb and fluorescein 5-isothiocyanate labeled goat anti-mouse IgG. MP formation stimulated either by thrombin plus collagen or by A23187 was inhibited by calpeptin in a dose dependent manner. The microparticle formation from platelets activated by A23187 reached a plateau in approximately 5 min after activation, whereas that from platelets activated by thrombin plus collagen reached a plateau at 30 min following the stimulation. These time sequences corresponded well with those of degradation of actin-binding protein (ABP), a well known substrate of calpain, of platelets activated by these two stimulations. However, the inhibition of MP formation by calpeptin was more marked in the early stage (within 10 min) than in the late stage (after 30 min) of platelet activation. At 30 min after platelet activation by either two stimulations, a significant amount of microparticle formation was observed in the presence of 30 microM calpeptin, which inhibited hydrolysis of ABP almost completely. Our data suggest the involvement of calpain in the early stage (especially within 10 min) of microparticle formation.

Hemostasis activation during sclerotherapy of lower extremity varices.

The influence of compression sclerotherapy upon hemostasis activation was investigated in 41 consecutive patients with lower extremity varices by serial measurement of thrombin-antithrombin III complexes (TAT), D-dimer, fibrinogen and C-reactive protein (CRP). Blood sampling was carried out before operation and on the 7th and 28th post-operative day in patients randomly assigned to either the control group (n = 18), in which high ligation of sapheno-femoral junction and local excision of varices were performed, or the sclerotherapy group (n = 23) in which the comparable surgical intervention and compression sclerotherapy using hypertonic saline were performed simultaneously. In both groups, the TAT, D-dimer and fibrinogen concentrations at day 7 were significantly elevated compared to the value before operation while CRP showed no significant change during the observation period. In the sclerotherapy group, higher incidence of superficial thrombosis was observed and the TAT concentration at day 7 was significantly higher than that in the control group (p < 0.01), and the TAT at day 28 was still significantly elevated compared to the pre-operative level (p < 0.05). However, no relationship between TAT and D-dimer concentrations and the extent of superficial thrombosis was observed. We conclude that compression sclerotherapy for lower extremity varices causes latent activation of coagulation system and can be a risk factor for venous thromboembolism.

Moyamoya disease and pregnancy: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Many female patients with moyamoya disease are of childbearing years, including those who were diagnosed before entering their childbearing years. However, there have been no extensive reviews of the management of pregnancy and delivery in association with moyamoya disease. The purpose of this report is to describe the case of a patient with moyamoya disease complicated by pregnancy and to review the literature on other such cases. CLINICAL PRESENTATION AND INTERVENTION: We report a 23-year-old primipara with moyamoya disease who delivered uneventfully by cesarean section under spinal anesthesia at 38 weeks of gestation. In the literature, 30 cases were reported of patients who had been diagnosed with moyamoya disease before pregnancy and delivery, and 23 patients who were symptomatic and were diagnosed for the first time with moyamoya disease in association with pregnancy. CONCLUSION: There is no evidence that pregnancy increases the risk of cerebrovascular accident or that bypass surgery decreases its risk. Poor prognosis of the patient or the newborn is mostly caused by cerebral hemorrhage and not by cerebral ischemia. It is important to control blood pressure and especially to avoid toxemia during pregnancy. Either cesarean section or vaginal delivery can be accomplished safely. Any anesthetic method can be used, provided special attention is given to avoiding hypocapnia, hypotension, and hypertension. Oral contraceptives should be avoided.

Surgical treatment of the retethered spinal cord after repair of lipomyelomeningocele.

In a series of 75 patients with surgically treated lipomyelomeningoceles, the neurological condition of six patients deteriorated 6 months to 14 years after the operation due to repeat tethering of the spinal cord. The tethering resulted from postoperative dense adhesion between the cord and the overlying dura mater. Two of the six patients underwent conventional repeat untethering procedures, and the remaining four were successfully treated with a new surgical technique developed by the authors to prevent such dural adhesion. For this procedure, after complete untethering of the spinal cord, the lumbosacral cord is retained in the center of the dural sac by fine stay sutures between the pia mater of the conus medullaris and the ventral dura mater. In addition, the dura mater is tacked to the posterior arch which is reconstructed with bone grafts at one or two bifid vertebral levels. During a postoperative follow-up period of 1 to 3 years, no further deterioration has been observed and magnetic resonance studies have demonstrated a space filled with cerebrospinal fluid (CSF) around the lumbosacral cord. The authors conclude that long-term observation, both neurological and radiological, is essential even after successful repair of a lipomyelomeningocele. This new surgical procedure can maintain a CSF bath around the lumbosacral cord, thus preventing dural adhesion. Application of this technique will hopefully be beneficial in lipomyelomeningocele patients with a high risk of cord retethering after initial repair.