Stability of cervical esophagogastrostomy via hand-sewn anastomosis after esophagectomy for esophageal cancer.

The aim of the present study is to evaluate the outcome of hand-sewn esophagogastric anastomosis during radical esophagectomy for esophageal cancer. The outcomes of 467 consecutive esophageal cancer patients who underwent cervical esophagogastric anastomosis using interrupted and double-layered sutures after radical esophagectomy via right thoracotomy or thoracoscopic surgery were retrospectively reviewed. Anastomotic leakage, including conduit necrosis, occurred in 11 of 467 patients (2.4%); 7 of 11 (63.6%) cases experienced only minor leakage, whereas the other four (36.4%) patients had major leakage that required surgical or radiologic intervention, including two patients of conduit necrosis. Anastomotic leakages were more frequently observed after retrosternal reconstruction compared with the posterior mediastinal route (P < 0.0001). The median time to healing of leakage was 40 days (range: 14-97 days). Two patients (2/467, 0.4%) died in the hospital due to sepsis caused by the leakage and conduit necrosis. Twelve patients (2.6%) developed anastomotic stenosis, which was improved by dilatation in all patients. Hand-sewn cervical esophagogastric anastomosis is a stable and highly safe method of radical esophagectomy for esophageal cancer.

A Distinct Subpopulation of Bone Marrow Mesenchymal Stem Cells, Muse Cells, Directly Commit to the Replacement of Liver Components.

Genotyping graft livers by short tandem repeats after human living-donor liver transplantation (n = 20) revealed the presence of recipient or chimeric genotype cases in hepatocytes (6 of 17, 35.3%), sinusoidal cells (18 of 18, 100%), cholangiocytes (15 of 17, 88.2%) and cells in the periportal areas (7 of 8, 87.5%), suggesting extrahepatic cell involvement in liver regeneration. Regarding extrahepatic origin, bone marrow mesenchymal stem cells (BM-MSCs) have been suggested to contribute to liver regeneration but compose a heterogeneous population. We focused on a more specific subpopulation (1-2% of BM-MSCs), called multilineage-differentiating stress-enduring (Muse) cells, for their ability to differentiate into liver-lineage cells and repair tissue. We generated a physical partial hepatectomy model in immunodeficient mice and injected green fluorescent protein (GFP)-labeled human BM-MSC Muse cells intravenously (n = 20). Immunohistochemistry, fluorescence in situ hybridization and species-specific polymerase chain reaction revealed that they integrated into regenerating areas and expressed liver progenitor markers during the early phase and then differentiated spontaneously into major liver components, including hepatocytes (≈74.3% of GFP-positive integrated Muse cells), cholangiocytes (≈17.7%), sinusoidal endothelial cells (≈2.0%), and Kupffer cells (≈6.0%). In contrast, the remaining cells in the BM-MSCs were not detected in the liver for up to 4 weeks. These results suggest that Muse cells are the predominant population of BM-MSCs that are capable of replacing major liver components during liver regeneration.

The reeler gene encodes a protein with an EGF-like motif expressed by pioneer neurons.

We have identified a strong candidate cDNA for the mouse reeler gene. This 5 kb transcript encodes a 99.4 kD protein consisting of 881 amino acids and possessing two EGF-like motifs. We assayed two independent mutant alleles--'Jackson reeler', which has a deletion of the entire gene, and 'Orleans reeler' which exhibits a 220 bp deletion in the open reading frame, including the second EGF-like motif and resulting in a frame shift. In situ hybridization reveals that the transcript is detected exclusively in the pioneer neurons which guide neuronal cell migration along the radial array. Our findings offer an explanation for how the reeler mutant phenotype causes a disturbance of the complex architecture of the neuronal network.

Cancer imaging: novel concepts in clinical magnetic resonance imaging.

Cancer is a major public health problem in the Western world. Imaging is of crucial importance in oncology, because it may reduce cancer-related morbidity and mortality. To improve tumour evaluation, there is a need for functional imaging modalities that go beyond gross assessment of anatomical abnormalities and allow visualization and quantification of biochemical processes in vivo. Magnetic resonance imaging (MRI) not only provides anatomical information, but also offers a wide range of functional sequences that may aid the evaluation of cancerous lesions. Furthermore, MRI provides the opportunity to guide and monitor anticancer therapies noninvasively. The aim of this review is to highlight some of the most promising developments of MRI in the functional assessment of cancer and the guidance and monitoring of (novel) anticancer therapies.

Ten-year experience of totally laparoscopic liver resection in a single institution.

BACKGROUND: Recent developments in liver surgery include the introduction of laparoscopic liver resection. The aim of the present study was to review a single institution's 10-year experience of totally laparoscopic liver resection (TLLR). METHODS: Between May 1997 and April 2008, 82 patients underwent TLLR for hepatocellular carcinoma (HCC) (37 patients), liver metastases (39) and benign liver lesions (six). Operations included 69 laparoscopic wedge resections, 11 laparoscopic left lateral sectionectomies and two thoracoscopic wedge resections. Nine patients underwent simultaneous laparoscopic resection of colorectal primary cancer and synchronous liver metastases. RESULTS: Median operating time was 177 (range 70-430) min and blood loss 64 (range 1-917) ml. Median tumour size and surgical margin were 25 (range 15-85) and 6 (range 0-40) mm respectively. One procedure was converted to a laparoscopically assisted hepatectomy. Three patients developed complications. Median postoperative stay was 9 (range 3-37) days. The overall 5-year survival rate after surgery for HCC and colorectal metastases was 53 and 64 per cent respectively. CONCLUSION: TLLR can be performed safely for a variety of primary and secondary liver tumours, and seems to offer at least short-term benefits in selected patients.

Lymph node detection by MRI before and after a systematic pelvic lymphadenectomy.

OBJECTIVE: Pelvic lymphadenectomy is considered the gold standard to diagnose and possibly treat lymphatic metastases in gynaecological cancer patients. The aim of this study is to evaluate whether all presurgical MRI detected lymph nodes were removed during the systematic pelvic lymph node dissection (PLND) in cervical cancer patients. METHODS: 21 consecutive cervical cancer patients who were scheduled to undergo a PLND were evaluated by a MRI scan prior to surgery and 6 weeks afterwards. All patients had tumour metastasis negative lymph nodes at histopathological examination. RESULTS: On average, 10 pelvic lymph nodes (range 5-17) per patient were detected by presurgical MRI. Postsurgical MRI scans showed that on average 1 (range 0-3) pelvic node per patient was not removed by surgery. In total, 14% of the presurgical MR detected nodes were not removed by surgery (31/225). Approximately half of all lymph nodes that remained after surgery were located in the obturator region. In spite of the remaining nodes, surgery and histopathological examination did detect more nodes than MRI: on average 21 lymph nodes per patient (range 9-59) were removed. Another 2 lymph nodes (range 0-6 per patient) were judged to be newly developed after surgery. CONCLUSION: Although surgery was able to remove many more lymph nodes than those detected by presurgical MRI, 14% of presurgical MRI detected lymph nodes were not removed by PLND. The value of MRI prior to surgery for the detection of pathological lymph nodes is a subject of further research.

A unique downregulation of h2-calponin gene expression in Down syndrome: a possible attenuation mechanism for fetal survival by methylation at the CpG island in the trisomic chromosome 21.

To understand the effect of trisomic chromosome 21 on the cause of Down syndrome (DS), DNA methylation in the CpG island, which regulates the expression of adjacent genes, was investigated with the DNAs of chromosome 21 isolated from DS patients and their parents. A methylation-sensitive enzyme, BssHII, was used to digest DNAs of chromosome 21, and the resulting DNA fragments were subjected to RLGS (restriction landmark genomic scanning). Surprisingly, the CpG island of the h2-calponin gene was shown to be specifically methylated by comparative studies with RLGS and Southern blot analysis. In association with this methylation, h2-calponin gene expression was attenuated to the normal level, although other genes in the DS region of chromosome 21 were expressed dose dependently at 1.5 times the normal level. These results and the high miscarriage rate associated with trisomy 21 embryos imply that the altered in vivo methylation that attenuates downstream gene expression, which is otherwise lethal, permits the generation of DS neonates. The h2-calponin gene detected by the RLGS procedure may be one such gene that is attenuated.

Hyperbaric oxygenation therapy enhances the protective effect of moderate hypothermia against forebrain ischemia in the gerbil hippocampus.

Moderate hypothermia may have a beneficial effect on the neurological outcome. However, ischemic deterioration such as brain swelling during rewarming has been reported as a notable complication after successful therapeutic cerebral hypothermia. In this study, we investigated the effects of hyperbaric oxygenation during rewarming. Forebrain ischemia was produced in 24 gerbils and sham ischemia in 8 animals. Then ischemia-treated animals were divided into 3 groups, whole-body moderate hypothermia (31 degrees C for 60 min) and hyperbaric oxygenation (HBO2) (2- atmosphere absolute for 60 min using 100% oxygen) during rewarming group (n = 8), moderate hypothermia without HBO2 group (n = 8), and sham treatment without hypothermia and without HBO2 group (n = 8). Both the hypothermia group (77.9 +/- 48.1 neurons per mm, mean +/- SD) and hypothermia + HBO2 group (127.6 +/- 29.7 neurons per mm,) showed significant preservation of CA1 pyramidal neurons in the hippocampus compared to that in the sham treatment group (6.4 +/- 2.7) (p < 0.01). Furthermore, the hypothermia + HBO2 group showed significantly greater preservation of CA1 pyramidal neurons than the hypothermia group (p < 0.05). These results suggest that HBO2 during rewarming preserves the protective effect of hypothermia against ischemic neuronal damage.

Bcl-3, a member of the I kappa B proteins, has distinct specificity towards the Rel family of proteins.

Expression of the bcl-3 gene is demonstrated to be elevated in some B-cell chronic lymphocytic leukemias with a chromosomal translocation, t(14;19)(q32;q13.1). Bcl-3 protein has seven tandem ankyrin repeats that are also found in I kappa B proteins, inhibitors of Rel/NF kappa B transcription factors. In this paper, we demonstrate that Bcl-3 is a member of I kappa B family of proteins with a novel specificity. Bcl-3 preferentially associates with the p50 of NF kappa B, and the nuclear localization signal of p50 is required for this association. Bcl-3 inhibits the DNA-binding activity of p50 homodimers but not that of p50-p65 heterodimers. Transient transfection experiments revealed that appropriate expression of Bcl-3 results in inhibition of the function of p50 homodimers but not that of p50-p65 heterodimers, whereas pp40 and I kappa B gamma inhibit the function of both p50 homodimers and p50-p65 heterodimers. These studies suggest that Bcl-3 could modulate the transcription in a way different from pp40 and I kappa B gamma.

Therapeutic basis of glycyrrhizin on chronic hepatitis B.

Glycyrrhizin, a major component of a herb (licorice), has been intravenously used for the treatment of chronic hepatitis B in Japan and improves liver function with occasional complete recovery from hepatitis. This substance modifies the intracellular transport and suppresses sialylation of hepatitis B virus (HBV) surface antigen (HBsAg) in vitro. This study was designed to clarify the pharmacological basis for its effectiveness. The structure-bioactivity relationship of glycyrrhizin, glycyrrhetic acid 3-O-monoglucuronide and glycyrrhetic acid was determined, and glycyrrhetic acid was found to be the most active of them. The amounts of three substances bound to the liver were evaluated in guinea pigs after intravenous administration of glycyrrhizin. Glycyrrhizin and glycyrrhetic acid 3-O-monoglucuronide were detected at concentrations of 31.8-1.3 micrograms/g of liver, but glycyrrhetic acid was not detected. When glycyrrhizin attained these concentrations in the cellular fraction of the PLC/PRF/5 cell culture, it suppressed the secretion of HBsAg as reported previously. These results indicated that glycyrrhizin administered intravenously might bind to hepatocytes at the concentration at which glycyrrhizin could modify the expression of HBV-related antigens on the hepatocytes and suppress sialylation of HBsAg.

Fatal traumatic subarachnoid hemorrhage due to rupture of the vertebral artery.

An unusual case of traumatic subarachnoid hemorrhage (SAH) due to rupture of the intracranial vertebral artery is reported. A drunk 51-year-old man received blows with a fist to the face and lost consciousness. A massive basal SAH was identified by CT-scan. Autopsy revealed a rupture of the vertebral artery but no skull fracture or cerebral contusion.

Gastric duplication cyst: evaluation by endoscopic ultrasonography and magnetic resonance imaging.

Endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) are becoming popular methods for examining tumorous lesions along the upper gastrointestinal tract. Though duplication cysts are uncommon, EUS findings from gastric duplication cysts have accumulated and proven very useful for preoperative diagnosis. There have been few reports, however, concerning MRI findings from these cysts. We report herein the case of a 25-year-old man with a gastric duplication cyst. EUS demonstrated a cystic mass adjacent to the fourth layer of the stomach wall. MRI revealed a cyst containing low signal-intensity fluid and high signal-intensity fluid separated by levels. In addition to the characteristic findings from preoperative examinations, the unique histological findings from the cyst are also described.

Blood pressure, insulin, and haematocrit values in Japanese subjects over 60 years of age.

Many studies have suggested an association between blood pressure (BP) and both insulinaemia and haematocrit values in Western populations. However, relatively few data regarding such associations for the Japanese population are available. We investigated the relationship between BP and various parameters, including insulin and haematocrit, in 269 healthy Japanese individuals (113 men and 156 women) over 60 years of age. The data were analysed by stepwise multiple regression analysis. In men, the most important determinant of systolic BP (SBP) and diastolic BP (DBP) was the plasma insulin concentration (beta = 0.32, F = 12.4, P < 0.001 and beta = 0.32, F = 13, P < 0.001, respectively), and haematocrit was found to be associated with DBP (beta = 0.21, F = 5.3, P < 0.05). In women, fasting insulins were unrelated to BP, but fasting plasma glucose and triglyceride concentrations and age were associated with SBP (beta = 0.29, F = 15.5, P < 0.001, beta = 0.27, F = 14.3, P < 0.001, and beta = 0.2, F = 7.8, P < 0.01, respectively), and haematocrit, fasting plasma glucose concentration and age were associated with DBP (beta = 0.29, F = 14, P < 0.001, beta = 0.2, F = 6.9, P < 0.01 and beta = 0.2, F = 6.3, P < 0.05, respectively). These results suggest that the insulin-BP associations in healthy Japanese subjects over 60 years of age differ according to sex, and that haematocrit is an important determinant of DBP in both sexes in our population.

Chemosensitivity testing of clinical gastrointestinal cancers using histoculture and the MTT end-point.

Three-dimensional histoculture with the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) end-point was utilized for chemosensitivity testing of 100 clinical gastrointestinal cancers and the results were compared with those obtained with cell-suspension culture with the MTT end-point. Of the 100 surgical specimens, 91 were evaluable using histoculture assay and 66 were evaluable using the cell-suspension assay. When the assay results were compared with historical frequency of clinical response to chemotherapy, the results of the histoculture assay showed a closer correlation than those of the cell-suspension assay. Therefore, the histoculture assay seems to have a higher evaluability rate and a closer correlation with clinical chemosensitivity of gastrointestinal cancers than the cell-suspension assay.

Three-dimensional reconstruction of the temporal bone from a case of E trisomy syndrome.

Computer-assisted three-dimensional reconstruction was performed from histologic sections of the left temporal bone removed from a case of E trisomy syndrome. The reconstructions included structures such as the bony and membranous labyrinths, ossicles, ossicular muscles, tympanic membrane, and facial and eighth nerves. The structures could be observed individually or simultaneously in combination. Prominent abnormalities observed in these reconstructions included enlargement of the utricle, absence of the posterior semicircular canal, slight hypoplasia of the cochlea, anomaly of the stapes, abnormally shaped stapedius muscle, abnormal course of the facial nerve, and flattening of the tympanic membrane. The results were useful for the visual and stereoscopic understanding of abnormal configurations and the spatial orientations of these abnormalities.

Ti breast cancer associated with Von Recklinghausen's neurofibromatosis.

A rare case of breast cancer associated with von Recklinghausen's neurofibromatosis is reported. This case and review of the literature illustrate the problems of clinical diagnosis.A 66-year-old woman who had undergone sigmoidectomy for sigmoid colon cancer two years previously, was admitted to the hospital because of a left breast skin retraction in October, 1998. The patient had von Recklinghausen's disease (neurofibromatosis type 1). The TNM clinical staging was TlcNOMO. Modified radical mastectomy was performed. The histopathological diagnosis of the breast tumor was invasive ductal carcinoma and the skin tumor was neurofibroma. The pTNM pathological staging was pTlcNlaMO.Among patients similar to our case, almost all were staged higher than T2. This may be because multiple neurofibromas obscure breast mass at palpation, leading to delayed detection of the cancer. Systemic and careful exploration is essential for patients with von Recklinghausen's neurofibromatosis to detect breast cancer at an early stage.

Mesenchyme remaining in human temporal bones.

This study was conducted in order to gain basic information about mesenchyme remaining in the middle ear cleft in normal infants. Because no previous report has objectively described the quantity or quality of such postnatal remnants in normal infants, it has not been possible to accurately evaluate the significance of mesenchyme remaining in the middle ears of infants with pathologic conditions, such as otitis media and congenital anomalies. Thus, 53 temporal bones obtained from 41 individuals reported upon here--from 26 weeks' gestation to 8 years of age--will be controls for future studies of pathologic conditions. The children from whom these temporal bones were obtained had no anomalies of the ear (or any other known part of the body); nor did they have any pathologic conditions in the ear. The temporal bones were prepared for histologic study with hematoxylin and eosin staining and were examined under the light microscope. After areas of the mesenchyme in the histologic sections were projected and illustrated for each of 19 portions in the middle ear cleft under the microprojector, those areas were measured by compensating polar planimetry. The findings obtained in this study were as follows: The amount of mesenchyme remaining in the days after birth seemed to gradually decrease in volume with increased maturity and had nearly disappeared within the first year in normal infants. Where mesenchyme was noted in the temporal bones of infants over 1 year of age, it was usually present only in small niches.(ABSTRACT TRUNCATED AT 250 WORDS)

Il-1, EGF, and HGF suppress the antiviral activity of interferon in primary monkey hepatic parenchymal cells.

The purpose of this study was to elucidate the mechanism behind low efficacy of interferon therapy to hepatitis C virus infected patients by using primary monkey hepatic parenchymal cells as a surrogate of primary human liver cells. The effects of various cytokines on the antiviral activity of IFNs in the monkey hepatic cells were studied to search for physiological inhibitors. Interleukin-1 alpha, EGF, and HGF showed suppressive effects on the antiviral activity of IFN-alpha, -beta in primary monkey hepatic cells when examined by the yield reduction method using vesicular stomatitis virus (VSV). In contrast, 50 ng/ml of TNF and IL-6 had no suppressive effect on the IFN-induced antiviral state in the hepatic cells.

Mesenchyme remaining in temporal bones from patients with congenital anomalies. A quantitative histopathologic study.

Our hypothesis that more mesenchyme remains for a longer time in the middle ear clefts of infants with congenital anomalies in the ear and/or other parts of the body than in the ears of infants without such anomalies has been tested. One hundred four human temporal bones obtained from 81 individuals with congenital anomalies in the ear and/or other parts of the body, with ages ranging from 24 weeks' gestation to 35 years, were processed histologically, stained with H & E, and examined under the light microscope. The slides were projected under a microprojector, and the mesenchyme remaining in each of 19 portions of the middle ear cleft was measured by compensating polar planimetry and expressed as a percentage of the total potential middle ear space in that histologic section. By comparing the findings in the present study with those of a previous study in which mesenchyme remaining in ears from normal age-matched controls was measured, we found that more mesenchyme remained for a longer time in the middle ear cavities of infants with congenital anomalies than in those of control infants (p less than .01). In addition, the amount of mesenchyme remaining was in direct proportion to the degree to which development of the middle ear was anomalous.

Postnatal development of the eustachian tube and its surrounding structures. Preliminary study.

The postnatal development of the eustachian tube and its surrounding structures (tubal cartilage, tubal gland, tensor veli palatini muscle, and levator veli palatini muscle) was investigated in serial vertical histologic sections from 12 normal temporal bones of individuals whose ages ranged from 39 weeks' gestation to 19 years of age. After projecting tissue sections onto paper and tracing the structures, several measurements were made in order to analyze this development. Findings revealed that the eustachian tube and its accessory structures developed postnatally up to the age of 19 years. The lumen area in a 19-year-old specimen was 4.7 times that of the 1-day-old infant. The development of the tube was greatest in the pharyngeal part. Postnatal development of the eustachian tube appears to be related to growth of the face. The cartilage area in the 19-year-old specimen was 3.6 times that of the 1-day-old infant. The mucosal acinar cells were predominant in infants but no greater than the number of serous acinar cells by the age of 19 years. The areas of the tensor and levator veli palatini muscles in a 19-year-old specimen were 5.1 and 11.1 times, respectively, those of the 1-day-old infant. This preliminary study reports the postnatal development of the eustachian tube and its accessory structures, a subject never thoroughly investigated to date. However, because of the limited number of cases available, further investigation of a greater number of cases should be performed so that the relationship between tubal development and alterations in function that occur with age can be understood clearly.