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軟部肉腫に対する温熱療法併用化学放射線療法（以下RHC）の短期成績について検討した．当科において2004年11月よりRHCを施行した15例のうち，他の化学療法を併用しなかった12例を対象とした．疾患の内訳は粘液型脂肪肉腫3例，滑膜肉腫2例，MPNST 2例，MFH 2例，間葉系軟骨肉腫，血管肉腫，GISTが各1例であった．予定の5コースを完遂できた症例は8例であり完遂率66.6％，MRI画像評価はPR 2例，NC 6例でPDはなかった．完遂できた8症例中で生検，摘出術が行われた6例の組織学的奏効率はgrade 2以上が4例で奏効率66.6％であった．RHC完遂症例8例の転帰はCDF 5例，AWD 3例であった．有害事象については，RHCは全身化学療法に比べ局所への侵襲性が高く，三者併用に伴う合併症に十分に注意し管理していく必要性があると考えられた．

Visual disturbances occur more frequently during preeclampsia than during pregnancy in general, but visual disturbances due to cranial nerve palsy are rare. We present the case of a 35-year-old preeclamptic woman with left third nerve palsy and left serous retinal detachment. The patient complained of visual disturbance and double vision soon after cesarean section. Left third nerve palsy and left serous retinal detachment were diagnosed by urgent ophthalmologic evaluation. Aneurysm and organic brain lesion were ruled out by diagnostic imaging. By 2 months postpartum, the visual disturbance had improved spontaneously.

The purpose of this study was to determine the proportion of fetal nucleated red blood cells (NRBCs) among enriched NRBCs and to evaluate the effectiveness of enriching NRBCs in maternal blood using fluorescence-activated cell sorting (FACS) to separate NRBCs. The origin of enriched NRBCs was determined using fluorescence in situ hybridization (FISH) methods. Y-specific signals were observed in 4.6 +/- 1.5 per cent of the enriched cells from 14 of 16 (87.5 per cent) pregnant women who gave birth to boys. In this series, the specificity of the fetal sex diagnosis was 100 per cent, the sensitivity 88 per cent, and the negative predictive value 86 per cent. Fetal NRBCs are present in maternal blood and FACS has the potential to enrich fetal NRBCs. Fetal cells were estimated to be enriched more than 10,000-fold in the first trimester and more than 100-fold in the third trimester. Average frequencies of fetal cells in maternal blood were 8.1 x 10(-5) and 1.6 x 10(-5) in the first trimester and the second/third trimesters. However, most of the NRBCs in maternal blood are maternal in origin.

We present the first report on the use of helical computed tomography (CT), a new, non-invasive diagnostic technique that produces three-dimensional (3-D) images, in prenatal diagnosis. This technique was used to construct 3-D images in the prenatal diagnosis of two anomalous fetuses. The 3-D images provided clear information about the anomalies: trisomy 18 in one case and cystic hygroma in the other. In one case, rapid intervention after a planned Caesarean section prevented respiratory distress. Surgery to correct the anomaly was performed 2 days postnatally; the infant recovered uneventfully.

We present a 28-year-old pregnant woman who exhibited intolerance to lysinuric protein. However, she gave birth to a normal child without serious maternal complications. Since four of seven similar patients reported previously developed serious complications such as hemorrhage and eclampsia, patients with lysinuric protein intolerance are considered to be at high risk during pregnancy. A successful outcome can be achieved, provided that the anemia, thrombocytopenia, toxemia and hyperammonemia are well controlled.

We report the case of a 32-year-old male with adult-onset diffuse nesidioblastosis causing hypoglycemia. Under the tentative diagnosis of insulinoma, localization procedures were carried out but no tumor was found. The presence of an insulinoma in the tail of the pancreas was suggested by selective intra-arterial calcium stimulation with hepatic venous sampling (ASVS). A distal pancreatectomy was performed under the assumed diagnosis of insulinoma in the tail based upon the ASVS. Diffuse nesidioblastosis was diagnosed by histopathological evaluation. During the post-operative course, the patient’s glucose and insulin levels were well controlled and uneventful without any medications or insulin for 7 months.

OBJECTIVE: The purpose of this study was to determine the frequency of fetal nucleated cells and their serial changes in maternal peripheral blood after delivery. STUDY DESIGN: A total of 135 blood samples were investigated by means of fluorescence in situ hybridization by observing cells with Y chromosomes. Polymerase chain reaction amplifying two different Y-specific fragments were also carried out for genomic deoxyribonucleic acid from the same samples. RESULTS: The mean frequency of the Y-positive cells detected by fluorescence in situ hybridization in mothers who gave birth to male children was about 1 in 17,500 1 day after delivery. The frequency of these cells decreased with time, dropping below detectable levels 3 months after delivery. The frequency estimated by polymerase chain reaction experiments was significant and positively correlated with those found by fluorescence in situ hybridization. CONCLUSION: Fetal nucleated cells in maternal peripheral blood decrease in frequency with time after delivery. These cells disappear from maternal circulation 3 months after delivery in most, if not all, mothers. (AM J OBSTET GYNECOL 1994;170:1188-93.)

Few reports of fetal cystic lymphangioma have described assessment in utero by magnetic resonance imaging (MRI). We evaluated a fetus with cystic lymphangioma by this method. Complementing the characteristic features of cystic lymphangioma in ultrasonographic images, prenatal MRI provided a detailed view of anatomic relationships of cysts to surrounding tissues in this case. This anatomic evaluation facilitated planning of perinatal management and choice of manner of delivery. We found MRI very helpful in antepartum assessment of fetal cystic lymphangioma.

Even though skeletal muscle, making up about 40% of body weight, is the largest organ in the human body, metastasis from malignant lesions is rare. Among reports of metastasis, those involving the iliopsoas muscle are numerous but few reports involve resection. Reported here is one example we experienced where metastasis developed in the iliopsoas muscle following colectomy, resection was then made possible by radiotherapy and chemotherapy. The case involved a 71-year- old male in which a Hartmann procedure was performed for sigmoid colon cancer. The pathology was Type 3 (8 × 7 cm, adenocarcinoma( mod), ss or more, ly1, v1, n0, ow(-), aw or ew(+), stage II). Upon additional sampling, thermal degredation of neoplastic cells was shown and outpatient oral UFT was performed. Five years following surgery, lymphoadenopathy was noted in the area of the left iliac artery upon US and CT. PET showed a probable metastasis to the left iliopsoas muscle. Early esophageal and stomach cancer were diagnosed by GFT. The esophageal cancer was located 30-32 cm from the incisors, unstained, Borrmann type 1, penetrating deeper than the muscularis propria. Biopsy revealed a diagnosis of tubular adenocarcinoma. ESD was performed for the esophageal cancer and one month later, a total gastrectomy D1+β was performed. During surgery, the iliopsoas muscle tumor was determined to be large and impossible to resect. Radiotherapy of 10MV X-ray, 8 fields, 65-70 Gy/26 times for 6 . 5 weeks was performed for residual tumor but had no effect on tumor size. Fifteen courses of FOLFOX+bevacizumab were then performed. The tumor was markedly reduced in size, unidentifiable upon CT but showed slight uptake on PET and resection of the suspected residual tumor was performed. Histologically, atypical cells were shown in scarred muscle and connective tissue, however, degradation by chemotherapy was high. Residual tumor at resection margins was found, findings consistent with metastasis form sigmoid colon cancer. Taking into account the age and condition of the patient following surgery, chemotherapy was changed to S-1. Currently, 5 months after resection, there has been no recurrence.

Cloacal dysgenesis sequence (CDS) is a rare and lethal malformation. We report such a case of long-term survival, currently to 12 years of age. In the fetal period, she received a timely placement of vesico-amniotic shunt for a megabladder due to a severe urethral obstruction. Postnatally, cystostomy and colostomy were created because of no perineal opening of urethra, vagina, and anus. Anorectoplasty, construction of efferent conduit, and colostomy closure were performed at 4 years of age. Ileovaginoplasty and ileovesicostomy which was a Mitrofanoff-type of conduit, and labioplasty were performed at the age of 11 years. To the best of our knowledge, only five survivors with CDS over 1 year of age have been reported.

The effects of hyperthermia (HT) on multidrug-resistant human hepatocellular carcinoma (HCC) were evaluated experimentally. This tumor, an AFP-producing human HCC, in which MDR1 mRNA and P-glycoprotein were overexpressed, was transplanted subsequently on nude mice. Ten days after the inoculation of the tumor into the rear section of the nude mice, either or both an intra-peritoneal injection of 8 mg/kg of adriamycin (ADR) was administered or hyperthermia (HT) was induced. HT was performed immediately by immersing the mice into a water bath at a temperature of 42-degrees-C for a period of 30 minutes. Hyperthermic therapy combined with ADR significantly inhibited the tumor growth compared with ADR or HT alone. Using ADR in combination with HT, the ADR concentration in the tumor remained at a significantly higher level for a prolonged period compared with ADR alone. The results indicate that HT enhanced the anti-tumor effect of chemotherapy even for multidrug-resistant HCC.

We report a case of alveolar capillary dysplasia, wherein duodenal atresia was diagnosed during the third trimester. A 36-year-old mother was referred to our hospital for polyhydramnios at 31 weeks' gestation. Duodenal atresia was suspected from the ultrasonographic findings, which showed gastric dilation. Other findings noted were enlarged, highly echogenic lungs, a spherical heart and an increased lung-thorax transverse area ratio. A male infant was born at 37 weeks' gestation. The findings of serial radiography of the infant's upper gastrointestinal tract were compatible with the diagnosis of duodenal atresia; however, he developed persistent pulmonary hypertension of the newborn eight hours after birth and died at five days of age. The autopsy revealed alveolar capillary dysplasia and duodenal obstruction. We propose that the detection of duodenal atresia should prompt the physician to conduct a thorough ultrasonographic examination to rule out associated anomalies, such as alveolar capillary dysplasia, which can be detected by the presence of highly echogenic lungs.

Background Classical phenylketonuria (PKU) arises from a deficiency of phenylalanine hydroxylase (PAH) that catalyses phenylalanine oxidation in the liver. Lack of PAH activity causes massive hyperphenylalaninemia and consequently severe brain damage. Preclinical studies showed that conventional adeno-associated virus (AAV) vectors could correct hyperphenylalaninemia in a mouse model of PKU, although limitations such as very large dose requirement and relative inefficiency in female animals were recognized. Method An AAV8-pseudotyped vector was constructed with a self-complementary AAV (scAAV) genome for efficient liver transduction and expression. Following vector injection to PKU mice, blood Phe was periodically measured by an enzymatic fluorometric assay. In vivo Phe oxidation was evaluated by a non-invasive breath test using [1-13C]Phe. Vector copy number in the host tissues was determined by quantitative polymerase chain reaction. Results A single injection of 1 × 1011–1 × 1012 particles of the scAAV8 vector resulted in a reduction of blood Phe to normal or near-normal levels for more than 1 year in both genders. The treated animals showed normal level of in vivo Phe oxidation. The presence of > 1 copy of vector DNA per diploid genome in the liver was associated with normal blood Phe in the AAV-treated PKU mice. Conclusions Complete phenotypic correction of PKU mice was achieved by the scAAV8 vector for the longest duration reported to date. The vector overcame the female-specific disadvantage in AAV-mediated liver transduction; thus, it offers a promising platform of long-lasting gene therapy for PKU. Copyright © 2011 John Wiley & Sons, Ltd.

The prognosis of type 4 advanced gastric cancer is extremely poor, even the use of multidisciplinary treatment cannot provide satisfactory results. Presented here is a case of highly advanced gastric cancer in which preoperative chemotherapy was effective and resection possible.A 64-year-old female complained of epigastric distress. Current medical history included: hypertension, hyperlipemia, diabetes, chronic heart disease and development of epigastric distress. Endoscopy was performed upon examination in the Gastroenterology Department. Visual inspection showed a lesion extending from the greater curvature of the fundus to the antrum. Type 4 advanced gastric cancer was strongly suspected. Biopsy samples taken from the antral lesser curvature and from the ulcer border on the upper anterior wall of the body were diagnosed as Group V, adenocarcinoma. Abdominal CT revealed no hepatic mass, but overall thickening of the gastric wall was noticeable and the lymph nodes in the area of the lesser curvature of the stomach and celiac artery were identified. Abdominal ultrasound showed an overall thickening of the gastric wall, and invasion into a portion of the left hepatic lobe and pancreas was suspected. Swelling of the lymph nodes surrounding the stomach was suspected.Because of gastric cancer with suspected invasion of the left hepatic lobe and pancreas, it was decided to perform preoperative chemotherapy (S-1 + CDDP) and then perform a total gastrectomy. Four courses were performed.Endoscopy revealed no change in the lesion within the stomach. Only scarring in the body and antrum was found, the enlargement was greatly reduced and visual inspection revealed no esophageal infiltration. Biopsy samples were taken from 2 sites, the body center on the lesser curvature side and the greater curvature of the antrum. Scar-like fibrosis was significant and it was not possible to distinguish an increase in poorly differentiated adenocarcinoma. Abdominal CT showed a reduction in gastric wall thickening. These findings showed preoperative chemotherapy to be effective. Following the chemotherapy, a total gastrectomy in addition to splenectomy and cholecystectomy were performed. Histopathological findings showed MLU, type 5, approx. 8.5 × 13 cm, poorly differentiated adenocarcinoma (por 2), INF γ, sci, pT2 (SS), ly2, v0, pN2 (#1: 2/8, #6: 1/6, #11p: 2/5), pPM (-), pDM (-), Stage IIIA. Along with the formation of fibrous scar tissue, an invasive growth of por 2 poorly differentiated adenocarcinoma was found from the submucosal layer to just beneath the serosal layer. Therapeutic effect of the chemotherapy was Grade 2. Post operative S-1 + CDDP was begun but nausea developed and S-1 was reduced. Because of a decrease of neutrophils and nausea, the therapy was changed to UFT. It is currently 6 months after surgery and there are no signs of recurrence.Preoperative chemotherapy (S-1 + CDDP) is a therapy which shows promise in reducing tumor size even in highly advanced gastric cancer.

We present two cases of transient abnormal myelopoiesis associated with trisomy 21 that had hypoechoic hepatomegaly during the late fetal period. Fetal chromosomal abnormality and fetal myeloproliferative disorder should be suspected in such cases.

Human placenta is an attractive source of mesenchymal stem cells (MSC) for regenerative medicine. The cell surface markers expressed on MSC have been proposed as useful tools for the isolation of MSC from other cell populations. However, the correlation between the expression of MSC markers and the ability to support tissue regeneration in vivo has not been well examined. Here, we established several MSC lines from human placenta and examined the expression of their cell surface markers and their ability to differentiate toward mesenchymal cell lineages. We found that the expression of CD349/frizzled-9, a receptor for Wnt ligands, was positive in placenta-derived MSC. So, we isolated CD349-negative and -positive fractions from an MSC line and examined how successfully cell engraftment repaired fractured bone and recovered blood flow in ischemic regions using mouse models. CD349-negative and -positive cells displayed a similar expression pattern of cell surface markers and facilitated the repair of fractured bone in transplantation experiments in mice. Interestingly, CD349-negative, but not CD349-positive cells, showed significant effects on recovering blood flow following vascular occlusion. We found that induction of PDGFβ and bFGF mRNAs by hypoxia was greater in CD349-negative cells than in CD349-positive cells while the expression of VEGF was not significantly different in CD349-negative and CD349-positive cells. These findings suggest the possibility that CD349 could be utilized as a specialized marker for MSC isolation for re-endothelialization.

Background. Chronic inflammation in haemodialysis (HD) patients indicates a poor prognosis. However, therapeutic approaches are limited. Hydrogen gas (H2) ameliorates oxidative and inflammatory injuries to organs in animal models. We developed an HD system using a dialysis solution with high levels of dissolved H2 and examined the clinical effects. Methods. Dialysis solution with H2 (average of 48 ppb) was produced by mixing dialysate concentrates and reverse osmosis water containing dissolved H2 generated by a water electrolysis technique. Subjects comprised 21 stable patients on standard HD who were switched to the test HD for 6 months at three sessions a week. Results. During the study period, no adverse clinical signs or symptoms were observed. A significant decrease in systolic blood pressure (SBP) before and after dialysis was observed during the study, and a significant number of patients achieved SBP

Aim: We aimed to assess the efficacy and safety of midtrimester termination of pregnancy using gemeprost in combination with laminaria in women who had previously undergone cesarean section and in women who had not. Methods: Between January 1999 and December 2006, we carried out a retrospective study of termination of pregnancy at 12–21 weeks of gestation at the University of Tsukuba Hospital. Termination of pregnancy was carried out by three-step uterine cervical dilation using laminaria followed by vaginal administration of 1 mg gemeprost every 3 h for up to four doses over 24 h. Results: A total of 173 women underwent midtrimester termination of pregnancy. The women were categorized into two groups: those who had previously undergone cesarean section (n = 26) (previous cesarean section group) and those who had not (n = 147) (control group). Seven women had undergone cesarean section at least twice. The gemeprost dose administered was 2.8 ± 1.4 mg for the previous cesarean section group and 2.4 ± 1.6 mg for the control group (difference in doses not significant). Although abnormal vaginal bleeding (>500 mL) was more likely to occur in the previous cesarean section group than in the control group (odds ratio, 2.61; 95% confidence interval, 0.63–10.82), none of the woman required blood transfusion. Uterine rupture and failed abortion were not observed. Conclusion: The efficacy and safety of our laminaria-gemeprost protocol for termination of pregnancy during the midtrimester are similar for women who have previously undergone cesarean section and those who have not.

We here report a case of trisomy 21 with congenital chylothorax. The patient was a male newborn who had been diagnosed as having trisomy 21 with congenital chylothorax. This is the fifth case of the both conditions in English literature. Congenital chylothorax is very rare in a trisomy 21 patient. There, however, may be causal relationship between the two conditions.

The extracellular matrix (ECM) is a complex of macromolecules that includes collages, proteoglycans, and complex glycoproteins. In fibrotic liver tissue there is an increase in all of these matrix components, and they increase in serum in the patients with alcoholic hepatitis or liver cirrhosis. These ECM components have been used as a serum marker of hepatic fibrosis. Prolonged obstruction of bile flow results in morphologic and biochemical changes and the development of secondary biliary cirrhosis. In congenital biliary atresia (CBA) there is a close correlation between the degree of the hepatic fibrosis and bile flow after the operation. We estimated that, in CBA, ECM increased in serum, and it would reflect the degree of the hepatic fibrosis. To clarify this we examined the serum procollagen-III-peptide (P-III-P) and laminin in CBA patients. P-III-P was elevated in all preoperative patients but in two of the three postoperative patients whose jaundice disappeared P-III-P was in the normal range. In the all 3 patients whose jaundice continued, P-III-P was in normal range. Serum laminin was elevated in 12 preoperative patients with CBA, but there is no correlation between day of diagnosis and level of laminin. Mean concentration in CBA without jaundice after operation was 3.18 U/mL, 3.226 U/mL in CBA with jaundice and 3.3 U/mL in infantile hepatitis. There were no significant differences among three groups. With the elevation of serum alanine aminotransferase, aspartate aminotransferase, and total biliburin, serum laminin level was also increased. Immunohistochemistry demonstrated that laminin deposits were found faintly in Disse's space and strongly in the portal area in CBA liver tissue, but there was no significant difference between serum laminin concentration and the degree of hepatic fibrosis. Hepatic fibrosis and cirrhosis due to obstructive jaundice that progress concurrently with lasting inflammation cause the elevation of serum ECM in CBA. Hepatic fibrosis resulted from increase of ECM in liver and is one of the causes for disturbed bile flow in CBA. To control the production of ECM will be essential in the future.

From 1960 to 1989, 563 cases of primary breast cancer in our clinic were divided into the young group (under 35 years of age) and the elder group (over 35 years of age), and compared for clinicopathological features.The results were: 1) Breast cancer in young patients represented 10.5% (59 cases) of all 563 breast cancer in young patients; 2) there was no significant difference in the cumulative survival rate between young and elder groups; and 3) There was a tendency to have poor prognosis in the young group compared to the other when they had a tumor occupying the total area of the breast, or an advanced cancer of n1β, n2, Stage IIIa, or Stage IIIb.

Pheochomocytoma is not a common disease. Neurofibromatosis means any of various clinically and genetically heterogenous disordes associated with multiple neurofibromas, especially neuroendocrine neoplasma. Among these neoplasms pheochromocytoma is most common.A recent experience with a case of neurofibromatosis associated with pheochromocytoma and multiple small intestinal leiomyomas in a 59-year-old is reported. The patient was diagnosed as neurofibromatosis fourty years before admission. Peochoromocytoma and multiple small intestinal leiomyomas were found during operation.We must consider a possible associon of pheochoromocytoma when we see the patient with neurofibromatosis complaining of hypertension. There are a few reports of duodenal carcinoid found in such a patient, so upper gastrointestinal examination is also indispendable before operation.

The prognosis of most hepatic and lymph node metastases in AFP-producing gastric cancer is poor, and despite the use of multimodal therapy, the average survival period is reported to be approximately one year. Described here is one example in which intra-arterial chemotherapy for simultaneous hepatic metastases in AFP-producing gastric cancer achieved a marked improvement. The patient is a 65-year-old female. Distal gastrectomy was performed for Type II gastric cancer. L, type 2, 5.5x2.4 cm, tub 2por 1, pT2 (MP), int, INF b, ly2, v1, pN1, pPM (-), pDM (-), pH1: stage IV. The AFP level before surgery was 801.4 ng/mL and lowered to 65.8 ng/mL after surgery, AFP-producing gastric cancer and simultaneous hepatic metastases (S4, single lesion) was diagnosed based upon imaging examinations. 5-FU+epirubicin+MMC (FEM)intra-arterial chemotherapy was started one month following surgery, but because CT showed multiple new hepatic lesions(S4, S5)four months following surgery, DSM therapy was performed with hepatic arterial injections of MMC 10 mg, DSM 300 mg. Dynamic CT showed a reduction in size of the tumors in both S4 and S5, and at five months following surgery, hepatic arterial infusion chemotherapy FP (CDDP 5 mg+5-FU 250 mg weekly) was started and performed 45 times in a 14-month period. During therapy, CR was achieved for the hepatic metastases and tumor marker levels were also normal. Because an introduction of contrast medium into the hepatic reservoir showed a narrowing of the hepatic artery and inflow of contrast medium into the splenic artery, arterial infusion was terminated. Following this, from the 20th month following surgery, S-1 (100 mg/day: 4 weeks administration, 2 weeks rest) was started and from the third course (50 mg/ day: 4 weeks administration, 2 weeks rest), and the patient is currently undergoing a sixth course. Currently, 2 years and 4 months after surgery, there have been no recurrences. This suggests the possibility that intra-arterial chemotherapy is an effective treatment method for hepatic metastases in AFP-producing gastric cancer.

The nuclear DNA content of 15 hepatoblastoma cases was determined in paraffin-embedded tissues by flow cytometry. The DNA index (DI) was calculated, and the ploidy pattern of nuclear DNA was estimated. The correlation between the ploidy pattern and clinicopathologic findings was studied, and the prognostic significance of the ploidy pattern was investigated. An aneuploid pattern was seen in 50% of the lesions with histologic embryonal and anaplastic types. It was not seen in the fetal type. In the tumors with combined epithelial components, the fetal-type component had a diploid pattern in all five cases. The embryonal-type component was associated with aneuploidy in two of five cases. In aneuploid tumors, vascular invasion (tumor emboli in the vessels) was observed more frequently. The prognosis of the patients with an aneuploid tumor was significantly poorer. These results indicate that nuclear DNA ploidy pattern analysis might be useful in investigating the prognosis of hepatoblastoma.

胃カルチノイドの3例を経験したので報告する.年齢は52歳が1例, 55歳が2例で, 性別は全例男性である.主訴は心窩部痛あるいは心窩部不快感であった.術前診断可能例は1例のみであった.S状結腸同時性重複癌例が1例, 肝転移は初回手術時, 再発時に各1例認められた.手術は胃全摘を2例, 胃亜全摘術を1例に施行し, S状結腸癌併存例ではS状結腸切除術を, 同時性肝転移例では肝部分切除も施行した.組織学的に深達度は同時性肝転移例ではsm, ほかの2例はssβ, sであった.リンパ節転移, 銀親和性細胞の出現が各2例に認められた.転帰は, 1例が術後1年8か月時に肝再発し, 増大しつつあるが術後4年の現在, 担癌生存中で, 他の2例は術後10か月, 8か月の現在, 再発なく健在である.本症では高率にリンパ節および肝転移が認められるため, 手術は胃癌に準じた胃切除とリンパ節郭清が必要である.

We report a case of thyroid cancer with primary hyperparathyroidism (1°-PHP) which was found accidentally during the examination of thyroid cancer. A 56-year-old woman was pointed out to have an anterior cervical mass, and was admitted to our department under a diagnosis of thyroid cancer. The patient complained of no subjective symptoms. Preoperative examination for thyroid cancer revealed an increased serum calcium (11.2 mg/dl). Increased serum parathyroid hormone level and urinary output of calcium were also observed, leading to a diagnosis of 10-PTH. Total thyroidctomy with bilateral modified neck dissection and extirpation of right lower parathyroid gland were performed. Histopathological diagnosis was bilateral papillary thyroid cancer and parathyroid adenoma. Serum calcium level decreased soon after operation.It is usual that thyroid tumors are found during the examination or operation of 10-PHP. On the contrary, we must take care of serum calcium level not be overlook probable 1°-PHP when we treat the thyroid tumors.

Treatment results of pancreatic head carcinoma are not good and long-term survival, especially in nonresectable cases is extremely difficult to obtain. The case reported here is of nonresectable pancreatic head carcinoma in which S-1+gemcitabine (GEM) proved to be effective.A 70-year-old male. The patient initially complained of epigastralgia. Jaundice was also noted and upon further study, pancreatic head carcinoma, portal vein and common hepatic artery infiltration along with duodenal infiltration were diagnosed. Gastrojejunostomy and cholecystectomy were performed with a preoperative diagnosis of Phb, TS2 infiltrative type T4, CH (+), DU (+), S (+), RP (-), PV (+), Ach (+), PLX, OO (-), N0, M0, and Stage IVa. Perioperative findings showed no hepatic or peritoneal metastases. Following surgery, S-1+ GEM (S-1 100 mg/day, day 1-14; GEM 1,000 mg/m(2) was administered on day 8 and day 15 for 2 weeks followed by one week of no administration) was started. After completing 2 courses, there was no change in the tumor, but after finishing the sixth course, there was a notable reduction in tumor size, and after finishing the 10th course, a further reduction was noted. Currently at the end of the 14th course, the tumors are unidentifiable upon imaging. At 1 year and 5 months from the initial diagnosis, there has been no recurrence and chemotherapy is being continued. In the case reported here, there have been no adverse side-effects from the S-1+GEM therapy, it is a safe method which does not lower QOL in patients with unresectable pancreatic carcinoma, and we can look forward to the possibility of extended survival times.In the case of unresectable pancreatic carcinoma, S-1+GEM therapy may be able to provide an improved long-term prognosis.

Glomerular podocytes are known to regulate proteinuria and podocyturia correlated with proteinuria. Podocyturia, the urinary excretion of viable podocytes (glomerular epithelial cells), has been associated with proteinuria in preeclampsia. This study is the first to investigate the time course alterations of podocyturia in patients with preeclampsia (11 cases) and normotensive pregnant women (45 cases). Urinalysis was performed at 35 weeks of gestation, 4 days after delivery, and 1 month after delivery. In patients with preeclampsia, podocyturia was evident at 35 weeks of gestation and 4 days after delivery, while proteinuria had already decreased at 4 days after delivery. At 1 month after delivery, almost no patients exhibited podocyturia. In control cases, proteinuria was not significant throughout the study period. However, 9 of the 45 controls exhibited transient and mild podocyturia at 4 days after delivery without proteinuria or hypertension. Statistics indicated a correlation between urinary podocyte number and blood pressure, but not with proteinuria. In conclusion, podocyturia in preeclampsia is transient and almost synchronous with heavy proteinuria. The results suggest that acute podocyte loss implicates podocyturia as the possible mechanism of proteinuria in women with preeclampsia.

There are numerous reports on the subject of effectiveness in radio-chemotherapy with regard to esophageal cancer, suggesting especially the combination therapy of 5-FU + CDDP aimed for recovery. Treatment becomes difficult when distal metastases appear during an adjuvant therapy followed by surgery. Our report here is a case in which a complete recovery was obtained after changing to S-1, a prodrug of 5-FU, in response to multiple lung metastases which appeared during the combined 5-FU + CDDP therapy followed by surgery for esophageal cancer.The patient was a 71-year-old male. Endoscopy during a physical examination showed a Type 1 tumor 27-30 cm from the anterior teeth. Detailed tests provided a preoperative diagnosis of esophageal cancer: Ut Type 1, T2-T3, N2, MO, IMO. A right thoracolaparotomic subtotal esophagectomy and retrosternal reconstruction were performed. Pathological findings showed well-differentiated squamous cell carcinoma, pT1b (sm), pN1 (106-rec R), pStage II. Postoperative combination of 5-FU + CDDP (day 1-5, 5-FU 500 mg; CDDP 10 mg/body) was started. Because of the appearance of multiple lung metastases after the completion of 3 courses, 2 courses of S-1 + CDDP (S-1 120 mg/body day 1-14; CDDP 5 mg/body day 1-5, day 8-12) were performed. After completing the chemotherapy, CT revealed the resolution of the lung metastases and complete recovery was diagnosed. Following this, a treatment with S-1 alone was continued until the appearance of bone metastases at which time radiotherapy was performed. The treatment is currently ongoing and no recurrence of the lung metastases has been shown.There have been numerous reports of the combination of S-1 + CDDP in esophageal cancer for NAC or in inoperable cases. However, our report suggests that this method may be effective in cases of recurrence or distal metastases.

In 12 cases of well differentiated thyroid carcinoma infiltrating into the larynx and trachea, one total laryngectomy and 11 partial resections of the thyroid were performed. Anterior cervical tumor was the most common compliant. The half of the cases had symptoms such as dyspnea and hoarseness indicating infiltration into the larynx, trachea and recurrent nerve. CT scan and tracheal endoscopy were useful for cases in which the tumor invaded the tracheal mucosa, but for the other cases it was difficult to diagnose the tracheal invasion before operation. In the one case undergone laryngectomy, 3 circular resection and 8 luminar resection, the tumor was found to invade the mucosa in 3, circular ligamentum in 3, and external ligamentum in 3. Other 3 cases had no pathological invasion. Their prognoses are favorable that all the patients are still alive with no local recurrence. Resection of the thyroid carcinoma with the larynx and the trachea are considered to be useful to control the local area.

Acase of breast cancer in the fibroadenoma is reported in this paper. The case was a 42-year-old woman having a right breast mass 2.2×2.0cm in size which located at A region. No skin change nor lymphnode adenopathies were found. On palpation, this mass was diagnosed provisionaly as benign. Mammography showed noabnormal signs. As ultrasonography revealed an irregulality in the wall of the mass, biopsy was taken to exclude a probability of malignancy. Pathological findings resulted in a fibroadenoma, containing lobular carcinoma in situ. The patient was treated with quadrantectomy of the breast and postoperative irradiation. At present she is living well without any recurrence. Five cases of fibroadenoma containing a carcinoma have been reported in Japan. To find the cancer arised in abenign tumor, fibroadenoma, if it is found in the middleaged women, should be biopsied preferably. Prognosis of such breast cancer in a benign breast tumor is not different from that of other breast cancers, accordingly we think it reasonable to treat this kind of cancer with breast-preserving operation.

Peroral direct cholangioscopy (PDCS) is endoscopic method for diagnosis in the common bile duct (CBD) utilizing an ultra-slim upper endoscope. Clinical utility and problem of this method were investigated in ten patients who had stenosis or obstruction in the CBD with stones or a tumor. Scope shaft had to become the form of a U loop by counterclockwise rotation, to advance the scope in the direction of intrahepatic bile duct. As for one case, although the scope was formed alpha loop without U loop, direct observation of total CBC was possible. Large working channel of the endoscope could take adequate tissue sample by large biopsy forceps. Electrohydraulic lithotripsy and stone extraction with a basket could be accomplished easily and safely by direct visualization with a clear image. Pneumobilia was noted in all cases with insertion of PDCS. Although the abdominal pain and pyrexia with regard to PDCS did not occur, transient leukocytosis was noted.

CASE 1: A 30-year-old male with a loss of appetite and hematemesis was diagnosed with scirrhous gastric cancer upon detailed examination. Laparoscopic biopsy showed it to be Group V. Pre-operative diagnosis was T3N3P1HOM1, Stage V. Three courses of pre-operative chemotherapy (NAC) of TS-1+CDDP were performed. Laparoscopic examination as well as imaging showed a clear reduction in tumor size. Total gastrectomy, resection of the small intestine and cholecystectomy were performed. Pathological findings were type 4, por 2, pT3 (ss), ly1, v0, pN0, pM1 (gall bladder, small intestine): pStage IV. CASE 2: A 55-year-old male with epigastric pain was diagnosed with scirrhous gastric cancer upon detailed examination. Pre-operative diagnosis was T3N1P1H0M0, Stage IIIA. Upon surgery, gastro-jejunal anastomosis was performed as resection was not an optional. Three courses of TS-1+CDDP were performed. A clear reduction of tumor size was noted upon laparoscopic examination as well as imaging and distal gastrectomy was performed. The pathological findings shown were type 4, por 2, pT3 (ss), ly2, v1, pN1, p1, pStage IV. The prognosis for inoperable gastric cancer is not promising and there is no established treatment guideline, however, there are cases in which TS-1+CDDP therapy has made surgery possible, and with the anticipation of extended survival, can be considered a useful therapy method.

We present an infant with the lethal Ellis-van Creveld syndrome who was diagnosed prenatally from the sonographic detection of a narrow chest, postaxial hexadactyly of the hands and feet, short limbs and a single atrium. The postnatal radiographic features of the skeleton favoured the diagnosis of Verma-Naumoff type or Saldino-Noonan type short rib-polydactyly syndrome (SRPS). We discuss the criteria for the differential diagnosis of patients with SRPS, which can be difficult because of the overlap of the various phenotypes.

We considered the appropriateness of RFA, which was performed in three cases of colorectal cancer with hepatic metastases accompanied by liver cirrhosis. Case 1 involved a patient with sigmoid colon cancer ss, n1 (+) with severe hepatic dysfunction and synchronous hepatic metastases (S5, S6, S8) in which RFA was performed. After 1 year and 6 months, recurrence (S3, S4) was detected in the residual liver, and the patient is currently undergoing the IFL (CPT-11/5-FU/Leucovorin) treatment. In case 2, following a partial hepatic resection, RFA was performed for cecal cancer ss, n2(+) with synchronous hepatic metastases (S5, S6, S8). After 11 months, recurrence (S5, S6, S7) occurred in residual liver and again RFA was performed following a partial hepatic resection. Lung metastases have occurred and currently IFL (CPT-11/5-FU/Leucovorin) and WHF treatments are underway. In case 3, 4 years and 8 months after cancer of the descending colon ss, n1 (+), RFA was performed on asynchronous hepatic metastases (S5, S7, S8). The patient died of peritonitis carcinomatosa one year after RFA. In all three cases, metastases were identified by dynamic CT as low density masses with no blood flow. Necrosis in all three metastases and local control had been achieved. There were no severe complications. Under the current conditions, local coagulation methods including RFA are appropriate in those cases in which resection are not possible such as multiple metastases with severe hepatic dysfunction, etc.

We studied one case in which the application of RFA was used for colorectal liver metastases with cirrhosis. The patient was a 51-year-old male. Sigmoid colon cancer and hepatocellular cancer (S5, S6, S8) were diagnosed before surgery. RFA was planned, as resection was determined to be impossible, because of reduced reserve liver function due to hepatitis B and cirrhosis. Resection of the Sigmoid colon was performed. Rapid pathological diagnosis was performed on the liver tumor and it was determined to be metastases from the sigmoid colon cancer. RFA was performed on the liver tumor with the expectation of local control. After the operation, WHF arterial infusion was performed as an outpatient, but the blood platelet count decreased and that resulted in impaired liver function making the continuation of WHF arterial infusion at a regular pace difficult. After 11 months from the operation, multiple recurrences appeared and the infusion was restarted. Consequently, the tumor size was reduced. Following the infusion, however, the liver function became impaired and there was no choice but to discontinue the infusion. After one year and 9 months from the operation, multiple recurrences appeared in the residual liver and WHF arterial infusion was restarted. The tumor size gradually reduced after the infusion and only S3 currently remains with good local control. Because this example was a case with multiple metastases along with a high level of liver function impairment, RFA was tested and good local control was achieved. In cases such as these where liver resection is not possible, local ablation therapies including RFA are applicable.

Preeclampsia is a pregnancy-specific syndrome and a major cause of maternal mortality. The pathophysiology of preeclampsia is unknown, and no proteome analysis of preeclampsia has been reported. We sought to identify proteins associated with preeclampsia using a proteomic technique and performed two-dimensional electrophoresis (2-DE) on sera from six patients with preeclampsia and six normal pregnant women, followed by comparison of the SYPRO Ruby-stained 2-DE profiles. A group of overexpressed spots was identified in the limited study set. Overexpressed spots were identified as clusterin by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) followed by peptide mass fingerprinting, a protein database search, and Western blot analysis. Additionally, sera of 80 preeclamptic women and 80 normal pregnant women were processed by immunoassay methods to confirm changes in clusterin concentrations quantitatively. Immunoassays showed that clusterin levels in the 80 preeclamptic women were significantly higher than those in the 80 controls (mean +/- SD; 1.62 +/- 0.46 times reference level in preeclamptic women vs. 1.30 +/- 0.46 times reference level in controls, P < 0.001). Proteomic analysis of serum proteins is a promising tool for studying preeclampsia pathophysiology and identifying proteins associated with preeclampsia.

Objective: To determine how long fetal nucleated cells can be detected in maternal peripheral blood after delivery in cases of fetomaternal hemorrhage, using fluorescence in situ hybridization or polymerase chain reaction. Methods: Nucleated cells with Y chromosomes were analyzed in 90 blood samples using fluorescence in situ hybridization with a Y-chromosome-specific DNA probe. The samples were obtained from 15 mothers (gravida 1), who were delivered of normal male neonates at University of Tsukuba Hospital, Japan, with fetomaternal hemorrhage 1 and 7 days, and 1, 3, 6, and 12 months after delivery. The 15 mothers were selected if fetal cells were detected above the ratio of one fetal cell per 3000 mothers' cells at 1 day after delivery. Polymerase chain reaction amplifying two different Yspecific fragments (a 102 base-pair fragment in the pHY10 vector, which was a highly repetitive sequence, and a singlecopy, Y-specific 198 base-pair fragment) was also carried out for the analysis of genomic DNA from the same samples. Results: Seven days and 1 month after delivery, Y-positive cells were detected in nine and four of 15 samples, respectively. No cells with the hybridization signal were detected in any of the 45 samples obtained 3 months or more after delivery. When we performed the polyrnerase chain reaction experiment amplifying the single-copy Y-specific fragment, none of the 45 samples after 3 months or more showed the expected band. However, from the same 45 samples, four obtained from different mothers showed positive results by amplification of the fragment in the pHY10 vector. Because multiple samples taken from these mothers before the collection of the positive samples showed negative results in the three experiments, these findings strongly suggest that the observed positive results were false-positives. Conclusion: Fetal nucleated cells in maternal peripheral blood become undetectable 3 months after delivery in most, if not all, cases of fetomaternal hemorrhage.

We evaluated the effectiveness of FEM (5-FU, epirubicin, MMC) therapy.Data for 111 patients with liver metastasis from gastric cancer were collected from January 1977, until June 2003 (synchronous: 74 cases, asynchronous: 37 cases). Thirty patients were H1, 20 were H2 and 61 were classified as H3.The patients were divided into the following groups: Group A: Resection of the primary lesion and hepatic resection (n = 10), Group A1: Hepatic resection only (5 cases), Group A2: Hepatic resection and intraarterial infusion (5 cases). Group B: Resection of the primary lesion (n = 67), Group B1: Resection of the primary lesion only (46 cases), Group B2: Intraarterial infusion (21 cases). In Groups A2 and B2, FEM therapy was applied to A2a (4 cases) and B2a (8 cases). Non-FEM therapy was applied to A2b (1 case) and B2b (13 cases). Group C consisted of 34 cases in which resection of the primary lesion was not undertaken. Survival rates were then compared.1-year survival rates and 50% survival period for each group were as follows: Group A: 33%, 5.9 months; Group B: 22%. 4.8 months; and Group C: 6%, 3.9 months, respectively. One case from Group A2a and 2 cases from Group B2a have survived for 3 years or longer.1) We treated 3 patients with liver metastasis from gastric cancer who survived for 3 years or longer. 2) Resection of the primary lesion along with hepatic intraarterial infusion therapy (in addition to hepatic resection), especially in combination with FEM therapy, provided an extended length of survival.

Background. Successful engraftment of human hematopoietic stem and progenitor cells (HSPCs) in a large animal may serve not only as a model to study human hematopoiesis but also as a bioreactor to expand human HSPCs in vivo. The aim of this study was to accomplish xenotransplantation of human HSPCs into pig. Methods. Total mononuclear or CD34-positive HSPCs obtained from human cord blood were xenotransplanted percutaneously under an ultrasonographic guidance into preimmune pig fetuses. Peripheral blood and bone marrow (BM) cells of recipient pigs were collected and analyzed for the presence of human cells by a polymerase chain reaction to detect human specific Alu sequence on DNA extracted from those cells. Fluorescence-activated cell sorting (FACS) analysis was also performed to detect human hematopoietic cells. Results. Transplantation of human cord blood cells into pig fetuses aged less than 52 days postcoitus resulted in a good engraftment rate. In one case, engraftment was detected up to 315 days posttransplantation by polymerase chain reaction. Human hematopoietic cells were detectable also by FACS in peripheral blood and BM. Furthermore, human CD34 + HSPCs were also observed in the BM of recipients. Those CD34 + cells in BM were sorted by FACS and subjected to further analyses. First, in vitro colony formation assay resulted in formations of multilineage colonies. Second, when they were transplanted into an immunodeficient mouse they were engrafted in the mouse. Conclusions. These data indicate an engraftment of human HSPCs in pig BM. In utero transplantation of human HSPCs into a preimmune pig fetus is useful to establish a pig reproducing human hematopoiesis.

A 31-year-old nulligravida woman developed an acquired factor VIII inhibitor associated with severe ovarian hyperstimulation syndrome (OHSS). She developed haematouria, ecchymosis, and intramuscular bleeding following the severe OHSS. Laboratory examinations showed a markedly prolonged activated partial thromboplastin time and a low level of factor VIII activity. Treatment with prothrombin complex concentrate and factor VIII inhibitor bypassing agent was successful in reducing the inhibitor so that she delivered a healthy baby via spontaneous vaginal delivery. Acquired haemophilia is a life-threatening disorder. This is the first case report of acquired haemophilia in OHSS.

We evaluated the effectiveness of FEM (5-FU, Epirubicin, MMC) therapy.One hundred ten cases of liver metastasis from gastric cancer were collected from January, 1977 until June, 2001 (synchronous: 74 cases, asynchronous: 36 cases). Twenty-nine cases were H1, 20 cases were H2 and 61 cases were H3.The patients were divided into the following groups: Group A: Resection of the primary lesion and hepatic resection (n = 9); Group A1: Hepatic resection only (5 cases), Group A2: Hepatic resection and intra-arterial infusion (4 cases). Group B: Resection of the primary lesion (n = 67); Group B1: Resection of the primary lesion only (46 cases), Group B2: Intra-arterial infusion (21 cases). In Groups A2 and B2, FEM therapy was applied to A2a (3 cases) and B2a (8 cases). Non-FEM therapy was applied to A2b (1 case) and B2b (13 cases). Group C consisted of 34 cases in which resection of the primary lesion was not undertaken. Survival rates were then compared.One-year survival rates and 50% survival period for each group were as follows: Group A: 33%, 5.9 months; Group B: 22%, 4.8 months; and Group C: 6%, 3.9 months, respectively. Five patients from Groups A2a and B2a survived for one year or longer.1. The prognosis with liver metastasis from gastric cancer, even with a number of therapies, is not promising. 2. Resection of the primary lesion along with hepatic intra-arterial infusion therapy (in addition to hepatic resection), especially in combination with FEM therapy, provided an extended survival.

Of 66 examples of hepatic metastases from colorectal cancer, 30 cases in which resection was performed had 3- and 5-year cumulative survival rates of 66.7% and 56.8%, while in 36 cases in which resection was not possible, the percentages were 8.7% and 2.9%, respectively. In two of the latter cases, resection was possible following WHF (5-FU 1,000 mg/m2 5 h qw). Case 1: A 58-year-old male, with rectal cancer and multiple metastases (H3, synchronous). Arterial infusion was performed 21 times, with the total volume of 5-FU administered being 31.5 g. The size of the lesions was reduced and hepatic resection was performed. The patient later died due to local recurrence and intra-abdominal lymph node metastases. He had survived 2 years and 11 months following hepatic resection and was free from recurrence of hepatic metastases. Case 2: An 82-year-old female, with cancer of the ascending colon, sigmoidal colon and multiple hepatic metastases (H3, metachronous). Arterial infusion was performed 16 times, with the total amount of 5-FU administered being 20 g. A lowering of CEA levels and reduction of tumor size were achieved, and hepatic resection was performed. Seven months following hepatic resection, CEA levels are normal and no distant metastases or recurrence in the residual liver have been found: possibly a complete cure. Even among cases of unresectable hepatic metastases from colorectal cancer, there are some in which resection is possible following hepatic arterial infusion chemotherapy, with the possibility of complete cure.

OBJECTIVE: To develop a polymerase chain reaction (PCR)-based diagnostic method for bacterial vaginosis using bacterial vaginosis-associated anaerobes. METHODS: A multiple PCR assay was developed using primers specific to 16S ribosomal deoxyribonucleic acid (DNA) ( Mobiluncus mulieris and Mobiluncus curtisii ), nanH ( Bacteroides fragilis ), and an internal spacer region of ribosomal DNA ( Gardnerella vaginalis ). The vaginal swabs from pregnant and nonpregnant women were examined by Gram stain-based Nugent scoring system. One hundred seventy-two samples of 853 Gram stain-interpretable samples were randomly selected and subjected to multiplex PCR assay. RESULTS: The sensitivity of the PCR assay ranged from 10 3 to 10 4 colony-forming units per vaginal swab. The prevalence of the bacterial vaginosis, intermediate, and normal categories was found by Nugent scoring system to be 21.6% (184/853), 26.0% (222/853), and 52.4% (447/853), respectively. By the multiplex PCR-based diagnostic method, 20.3% (35/172) of the samples were identified as bacterial vaginosis. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of multiplex PCR in comparison with Gram stain examination were 78.4% (95% confidence interval [CI] 65.1%, 91.6%), 95.6% (95% CI 92.1%, 99.0%), 82.9% (95% CI 70.4%, 95.4%), and 94.2% (95% CI 90.3%, 98.1%), respectively. CONCLUSION: This multiplex PCR can be used as a diagnostic or screening test for bacterial vaginosis.

Objective: The aim of this study was to determine whether fetal trisomy is associated with altered levels of second-trimester maternal pregnancy-associated plasma protein A (PAPP-A) and inhibin A. Methods: Maternal serum PAPP-A and inhibin A concentrations were measured at 15–17 weeks of gestation in 14 singleton pregnancies with fetal trisomy and in 56 matched pregnant controls. Results: PAPP-A levels in the trisomy group were significantly lower than in controls. The inhibin A level with fetal trisomy 21 was slightly higher than the control group, but levels were not different between trisomies 18 and 13 and controls. Conclusion: Fetal trisomies 21, 18, and 13 are associated with a reduction in second-trimester maternal PAPP-A levels; trisomies 18 and 13 are not associated with increased inhibin A levels, unlike trisomy 21.

Objective: The purpose of this study was to assess the accuracy, informative rate, detection rate, and clinical utility of prenatal interphase fluorescence in situ hybridization (FISH) analysis of amniotic fluid samples from Japanese women. Methods:Amniotic fluid specimens from 2,639 Japanese women were received for prenatal interphase FISH and chromosome analysis. A questionnaire was designed to evaluate FISH clinical utility by collaboration sites. Results:Based on 2,319 tested samples, the accuracy (100%), informative (94%), and detection (87.6%) rates were all high. The accuracy (100%), informative (90.2%), and detection (90.0%) rates were also remarkable in third-trimester pregnancies. We perceive significant advantages from this test regarding medical management and patient satisfaction. Conclusions:This novel report shows that in Japan prenatal interphase FISH testing is highly informative and accurate, not only in second-trimester pregnancies but also in third-trimester pregnancies. This test provides advantages to both physicians and patients, provided that its capabilities and limitations are understood.