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Emergent surgery is necessary in patients with strangulation ileus. However, such procedures are associated with high morbidity and mortality. A retrospective analysis was performed to determine whether the preoperative C-reactive protein/albumin ratio (CAR); neutrophil/lymphocyte ratio (NLR); and prognostic nutritional index (PNI) are good indicators of mortality or morbidity in patients undergoing emergent operations for treatment of strangulation ileus. Emergent surgery was performed for 1698 patients at Tottori Prefectural Central Hospital from 2012 and 2015. Among them, 45 patients (2.7%) were preoperatively diagnosed with strangulation ileus. We evaluated the clinical importance of the preoperative CAR, NLR, and PNI in these patients. We excluded pediatric patients from this study. Postoperative complications developed in 14 of 45 (31.1%) patients. The mean postoperative hospital stay among the 14 patients with postoperative complications was significantly longer than that of the 31 patients without postoperative complications (44.0 versus 11.3 days, respectively; P = 0.006). Three patients died of postoperative complications. The overall operative mortality and morbidity rates were 6.7% and 31.1%, respectively. We found strong correlations of postoperative complications with older age, a longer operation time, and an abnormal preoperative CAR, NLR, and PNI. Not only inflammation, but also a patients' nutritional and immune status appear to be strongly correlated with mortality or morbidity after emergent operations for strangulation ileus. Patients with a high CAR and NLR and low PNI preoperatively must be closely monitored for the occurrence of postoperative complications such as surgical site infections or pulmonary complications.

Depressive disorders are partly caused by chronic inflammation through the kynurenine (KYN) pathway. Preventive intervention using anti-inflammatory reagents may be beneficial for alleviating the risk of depression. In this study, we focused on the Japanese local citrus plant, Citrus tumida hort. ex Tanaka (C. tumida; CT), which contains flavonoids such as hesperidin that have anti-inflammatory actions. The dietary intake of 5% immature peels of CT fruits slightly increased stress resilience in a subchronic and mild social defeat (sCSDS) model in mice. Moreover, the dietary intake of 0.1% hesperidin significantly increased stress resilience and suppressed KYN levels in the hippocampus and prefrontal cortex in these mice. In addition, KYN levels in the hippocampus and prefrontal cortex were significantly correlated with the susceptibility to stress. In conclusion, these results suggest that dietary hesperidin increases stress resilience by suppressing the augmentation of KYN signaling under sCSDS.

Key Clinical Massage Here, we report a case with successful treatment of inferior pancreaticoduodenal artery aneurysm rupture due to celiac artery trunk compression caused by the median arcuate ligament. When clinicians see visceral aneurysms, the possibility of arcuate midline ligament compression syndrome (MALS) and ligamentectomy for MALS should be considered.

Purpose: We evaluated the clinical importance, such as the occurrence of postoperative pancreatic fistula (POPF) or prognosis, of preoperative serum markers of chronic inflammation, nutrition, and immunity, as well as that of serum tumor markers after curative resection of pancreatic ductal adenocarcinomas (PDACs). Methods: Between 2006 and 2015, 43 patients with PDACs underwent curative resection at Tottori Prefectural Central Hospital. We analyzed which preoperative indicators (i.e., C-reactive protein/albumin ratio [CAR], neutrophil/lymphocyte ratio [NLR], prognostic nutritional index [PNI], carcinoembryonic antigen [CEA], and carbohydrate antigen 19-9 [CA 19-9]) were the most relevant risk factors for occurrence of POPF and poor patient survival. Results: POPF was detected in 8/43 (18.6%) patients. One patient died of pancreatic fistula at 2 months postoperatively. Among nine candidate factors (operative procedure, operation time, tumor stage, preoperative serum amylase, preoperative CAR, NLR, PNI, CEA, and CA 19-9), we did not identify any significant risk factor for the occurrence of POPF. The 5-year overall survival (OS) rate of the 43 patients was 22.4%, and the overall median survival time was 21 months. The multivariate OS analysis demonstrated that high CAR and low PNI were strong preoperative markers of poor prognosis independently of tumor stage. Conclusions: Preoperative CAR and PNI are useful prognostic markers for patients with operable PDACs.

TAK-063 is a selective phosphodiesterase 10A (PDE10A) inhibitor that produces potent antipsychotic-like and pro-cognitive effects at 0.3 mg/kg (26% PDE10A occupancy in rats) or higher in rodents through the balanced activation of the direct and indirect pathways of striatal medium spiny neurons (MSNs). In this study, we evaluated the specific binding of TAK-063 using in vitro autoradiography (ARG) and the modulation of brain activity using pharmacological magnetic resonance imaging (phMRI) and electroencephalography (EEG). [3H]TAK-063 significantly accumulated in the caudate—putamen (CPu), ventral pallidum (VP), substantia nigra (SN), hippocampus (Hipp), and amygdala (Amy), but not in the frontal cortex (Fcx), brainstem (Bs), or cerebellum (Cb) in an ARG study using rat brain sections. [3H]TAK-063 accumulation in the CPu was more than eighteen-fold higher than that in the Hipp and Amy. TAK-063 at 0.3 mg/kg increased the blood oxygenation level-dependent (BOLD) signal in the striatum and Amy, and decreased it in the Fcx in a phMRI study with anesthetized rats. TAK-063 at 0.3 mg/kg significantly reduced the ketamine-induced increase in EEG gamma power both in awake and anesthetized rats. TAK-063 at 0.2 mg/kg (35% PDE10A occupancy in monkeys) also reduced the ketamine-induced increase in EEG gamma power in awake monkeys. In line with the EEG data, TAK-063 at 0.3 mg/kg reversed the ketamine-induced BOLD signal changes in the cortex, Bs, and Cb in a phMRI study with anesthetized rats. These data suggest that TAK-063 at about 30% PDE10A occupancy modulates activities of multiple brain regions through activation of neuronal circuits in rats and monkeys.

The Glasgow Prognostic Score (GPS), neutrophil/lymphocyte ratio (NLR) and prognostic nutritional index (PNI) are prognostic parameters for malignancies. Additionally, serum squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA 21-1) are tumor markers for squamous cell carcinoma. In the present study, the prognostic importance of these markers in patients with resectable thoracic esophageal cancer was investigated. In this retrospective study, 84 enrolled patients diagnosed with resectable clinical stage I-III thoracic esophageal squamous cell carcinomas (ESCCs) underwent thoracic esophageal resection and three-field lymph node dissection at Tottori University Hospital between January 2007 and December 2013. The correlations among preoperative patient markers (GPS, NLR, PNI, SCC-Ag and CYFRA 21-1) and the occurrence of postoperative complications and patient survival were analyzed. The operative mortality was 2.4%, and morbidity was 42.9%. Strong correlations between occurrence of postoperative complications and open thoracotomy (P=0.083) and high-serum CYFRA 21-1 (P=0.007) were observed. In 15 patients with high-serum CYFRA 21-1, postoperative complications were detected in 11 of them (73.3%); on the other hand, complications occurred in 25 of 69 (36.2%) with low-serum CYFRA 21-1. The 5-year disease-free survival rate and 5-year overall survival rate of all the patients were 52.2 and 50.8%, respectively. Among the prognostic parameters, preoperative high NLR was determined to be a poor prognostic factor, independent of the tumor stage in the multivariate analysis. These results may indicate that, in patients with preoperative high-serum CYFRA 21-1, more attention should be paid to the occurrence of postoperative complications. Therefore, in such cases, anastomosis between blood vessels of the substitute esophagus and cervical vessels would be recommended. Furthermore, in patients with high preoperative NLR, effective adjuvant chemoradiotherapy should be considered to prolong the patients' survival, even of stage I or II patients.

Stroke is the leading cause of adult disability. Recovery of function after stroke involves signaling events that are mediated by cAMP and cGMP pathways, such as axonal sprouting, neurogenesis, and synaptic plasticity. cAMP and cGMP are degraded by phosphodiesterases (PDEs), which are differentially expressed in brain regions. PDE10A is highly expressed in the basal ganglia/striatum. We tested a novel PDE10A inhibitor (TAK-063) for its effects on functional recovery. Stroke was produced in mice in the cortex or the striatum. Behavioral recovery was measured to 9 weeks. Tissue outcome measures included analysis of growth factor levels, angiogenesis, neurogenesis, gliogenesis, and inflammation. TAK-063 improved motor recovery after striatal stroke in a dose-related manner, but not in cortical stroke. Recovery of motor function correlated with increases in striatal brain-derived neurotrophic factor. TAK-063 treatment also increased motor system axonal connections. Stroke affects distinct brain regions, with each comprising different cellular and molecular elements. Inhibition of PDE10A improved recovery of function after striatal but not cortical stroke, consistent with its brain localization. This experiment is the first demonstration of brain region-specific enhanced functional recovery after stroke, and indicates that differential molecular signaling between brain regions can be exploited to improve recovery based on stroke subtype.

Port-site metastasis of hepatocellular carcinoma (HCC) is extremely rare, and only one case has been reported in the English-language literature. Contamination with malignant cells along the needle tract during percutaneous biopsy or radiofrequency ablation is a well-recognized cause of HCC recurrence. Here, we describe a case of port-site metastasis after laparoscopic liver resection of HCC. The patient, who had undergone laparoscopic partial resection of the left lateral segment of the liver 18 months earlier, was diagnosed with HCC. CT showed a nodule in the abdominal wall where the laparoscopic port had been inserted during resection. Local excision was performed, and histological examination revealed HCC consistent with recurrence after laparoscopic resection. The experience described in this report highlights the risk of port-site metastasis of HCC. Imaging for oncologic surveillance after laparoscopic resection must include all port sites.

We encountered a patient with an adult Bochdalek hernia discovered asymptomatically. A 77-year-old Japanese woman visited a local clinic with chief complaints of melena and difficulty in defecation. Based on the results of the detailed examination in our hospital, she was diagnosed with a rectal gastrointestinal stromal tumor (GIST) with a concurrent asymptomatic adult right-sided Bochdalek hernia. Because the tumor was large, laparoscopic abdominoperineal rectal amputation was performed after systemic imatinib therapy. During the surgery, we found a right diaphragmatic defect more than 13cm in long dia., through which the right hepatic lobe, colon, and greater omentum had prolapsed into the right thoracic cavity. No visceral adhesions were noted. No hernia sac was observed. Adult Bochdalek hernia is a relatively rare condition, and only three (incidentally discovered) cases of asymptomatic Bochdalek hernia, including the present case, have been reported in Japan. Here we provide a case report for the patient, who was followed-up without hernia surgery, plus a review of the literature.

We have conducted nationwide surveys of primary central nervous system lymphoma (PCNSL) treated since 1985. In the present study, we newly collected data between 2000 and 2004 and investigated changes in clinical features and outcome over time. A total of 739 patients with histologically proven PCNSL under going radiotherapy were analyzed. Seventeen institutions were surveyed, and data on 131 patients were collected. These data were compared with updated data that were previously obtained for 466 patients treated during 1985-1994 and 142 patients treated during 1995-1999. Recent trends toward decrease in male/female ratio, increase in aged patients, and increase in patients with multiple lesions were seen. Regarding treatment, decrease in attempts at surgical tumor removal and increases in use of systemic chemotherapy and methotrexate (MTX)-containing regimens were observed. The median survival time was 18, 29, and 24 months for patients seen during 1985-1994, 1995-1999, and 2000-2004, respectively, and the respective 5-year survival rates were 15%, 30%, and 30%. In groups seen during 1995-1999 and during 2000-2004, patients who received systemic or MTX-containing chemotherapy had better prognosis than those who did not. Multivariate analysis of all patients seen during 1985-2004 suggested the usefulness of MTX-containing chemotherapy as well as the importance of age, lactate dehydrogenase level, and tumor multiplicity as prognostic factors. Thus, this study revealed several notable changes in clinical features of PCNSL patients. The prognosis improved during the last 10 years. Advantage of radiation plus chemotherapy, especially MTX-containing chemotherapy, over radiation alone was suggested.

Laparoscopic total gastrectomy is not widely performed because of the difficulty of esophagojejunal reconstruction. This study analyzed complication rates of two different methods for reconstruction by a circular stapler after totally laparoscopic total gastrectomy (TLTG). Between 2010 and 2014, clinical data of 19 patients who underwent TLTG for gastric adenocarcinoma were collected retrospectively. There were two methods to fix the anvil of a circular stapler into the distal esophagus: In the single-stapling technique (SST) group, Endo-PSI(II) was used for purse-suturing on the distal esophagus for reconstruction, and in the hemi-double-stapling technique (hemi-DST) group, the esophagus was cut by linear stapler with the entry hole of the anvil shaft opened after inserting the anvil tail. In both groups, surgical procedures were the same, except for the reconstruction. All TLTGs were performed securely without mortality. Intracorporeal laparoscopic esophagojejunal anastomosis was performed successfully for all the patients. In the hemi-DST group, four patients experienced anastomotic stenosis, three of whom required endoscopic balloon dilation. In contrast, no stenosis was seen in the SST group (p = 0.033). Anastomosis with SST is preferred to that with hemi-DST to minimize postoperative complications.

Objective. In most cases of uterine cervical carcinoma recurrence, the first site of distant metastasis or recurrence is reported to be the para-aortic region. Some reports have demonstrated that, in cases of isolated para-aortic lymph node recurrence treated by radiation therapy, patients survived for a long period, which suggests that isolated para-aortic lymph node recurrence in uterine cervical carcinoma is a regional disease rather than systemic disease. Determining the predictive characteristics of isolated para-aortic lymph node recurrence in patients at the time of the initial treatment for primary uterine cervical carcinoma is important, so we conducted the current multi-institutional study. Patients and methods. Patients ( n =3137) with uterine cervical carcinoma of stages Ia to IVa were treated in twelve Japanese hospitals between 1994 and 2003. The current study investigated the frequency and characteristics of patients with isolated para-aortic lymph node recurrence as well as the characteristics of clinical stage, histopathology, serum squamous cell carcinoma antigen level, the treatment method at the initial treatment, the duration between the initial treatment and the recurrence, and the serum squamous cell carcinoma antigen level at the recurrence. Results. Of the 3137 patients with uterine cervical carcinoma in stages Ia–IVa, 67 (2.1%) experienced recurrence in isolated para-aortic lymph nodes. Stratified by clinical stage, none of the 613 patients with stage Ia experienced recurrence in isolated para-aortic lymph nodes. However, recurrence was experienced by 14 (1.4%) of the 966 patients with stage Ib, 7 (3.5%) of the 199 patients with stage IIa, 14 (2.3%) of the 613 patients with stage IIb, 1 (2.1%) of the 48 patients with stage IIIa, 26 (4.6%) of the 538 patients with stage IIIb, and 5 (5%) of the 100 patients with stage IVa. The mean duration time between the initial treatment and isolated para-aortic recurrence was 20 months (range, 2–49 months). The correlations between duration time and the clinico-pathological factors (clinical stage, histopathology, serum squamous cell carcinoma antigen level, and treatment method) at the initial treatment were investigated. No statistically significant factors have been revealed in the current study. Conclusions. The frequency of isolated para-aortic lymph node recurrence was 2.1% and increased with increasing clinical stage at the initial treatment (stage IVa: 5%) in the current study.

Background and aims: Treatment of anorectal sepsis requires prompt surgical drainage, but it is important to identify any associated anal fistula for preventing recurrence. We evaluated whether microbiologi- cal analysis and/or endoanal ultraso- nography could be used to predict anal fistula in patients with acute anorectal sepsis. Methods: Five hundred fourteen consecutive patients with acute anorectal sepsis were studied. Clinical data, digital exami- nation findings, endosonographic findings, and results of microbiolog- ical analysis were compared with definitive surgical findings of the presence or absence of anal fistula. Results: Anorectal abscess with anal fistula was found in 418 patients, and anorectal abscess without anal fistula was found in 96 patients. Microbio- logical examination showed that Es- cherichia coli, Bacteroides, Bacillus, and Klebsiella species were signifi- cantly more prevalent in patients with fistula (P

腹部鈍的外傷による腸管損傷は穿孔,断裂,出血など急性の発症がほとんどであるが,稀に遅発性に腸管狭窄をきたすことがある.今回われわれは,中でも稀とされる遅発性大腸狭窄を経験した.症例は77歳,女性.移動式階段にて作業中に転落.階段が体幹に落下し,胸腹部を強打,当院へ救急搬送された.臓器損傷,消化管穿孔の所見は認めず,保存的加療にて軽快し,受傷後31日目に退院.その後, 51日目に腸閉塞様症状が出現し,再入院となった.諸検査にて横行結腸肝彎曲寄りに高度の狭窄を認め,遅発性大腸狭窄と診断し,受傷後69日目に開腹手術を行った.右上腹部に右側結腸,腸間膜,大網などが一塊となった炎症性の腫瘤を形成し,横行結腸に高度な狭窄を呈していたため,結腸部分切除術を施行した.組織学的には腸管壁全層の肉芽形成,異物巨細胞の出現も認めており,穿通の存在も示唆された.腹部外傷の診療の際は本疾患も念頭に置く必要があると思われた.

Phosphodiesterase 10A (PDE10A) is a cAMP/cGMP phosphodiesterase highly expressed in medium spiny neurons (MSNs) in the striatum. We evaluated the in vivo pharmacological profile of a potent and selective PDE10A inhibitor, TAK-063 (1-[2-fluoro-4-(1 H -pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1 H -pyrazol-5-yl)-pyridazin-4(1 H )-one). TAK-063 at 0.3 and 1 mg/kg p.o., increased cAMP and cGMP levels in the rodent striatum and upregulated phosphorylation levels of key substrates of cAMP- and cGMP-dependent protein kinases. TAK-063 at 0.3 and 1 mg/kg p.o., strongly suppressed MK-801 [(5 R ,10 S )-(+)-5-methyl-10,11-dihydro-5 H -dibenzo[ a , d ]cyclohepten-5,10-imine]–induced hyperlocomotion, which is often used as a predictive model for antipsychotic-like activity in rodents. Upregulation of striatal cAMP/cGMP levels and the antipsychotic-like effect of TAK-063 were not attenuated after 15 days of pretreatment with TAK-063 in mice. The potential side effect profile of TAK-063 was assessed in rats using the clinical antipsychotics haloperidol, olanzapine, and aripiprazole as controls. TAK-063 did not affect plasma prolactin or glucose levels at doses up to 3 mg/kg p.o. At 3 mg/kg p.o., TAK-063 elicited a weak cataleptic response compared with haloperidol and olanzapine. Evaluation of pathway-specific markers (substance P mRNA for the direct pathway and enkephalin mRNA for the indirect pathway) revealed that TAK-063 activated both the direct and indirect pathways of MSNs. These findings suggest that TAK-063 represents a promising drug for the treatment of schizophrenia with potential for superior safety and tolerability profiles.

Purpose: The prognostic significance of human chorionic gonadotropin (HCG) level in central nervous system germinoma remains controversial. The purpose of this study was to compare clinical characteristics and prognosis of germinoma patients with normal and high HCG titers in the serum. Methods and Materials: We undertook a multi-institutional retrospective analysis of 103 patients with central nervous system germinoma whose serum HCG and/or β-HCG level had been measured before treatment between 1984 and 2002. All patients had been treated with radiation therapy either alone ( n = 66) or in combination with chemotherapy ( n = 37) with a median dose of 47.8 Gy. Results: HCG and/or β-HCG level in the serum was high in 39% of all patients. The proportion of HCG-producing tumors was higher in the lesions at the basal ganglia than in the lesions at the other sites. No correlation was found between tumor size and HCG level, but there seemed to be a weak correlation between size and β-HCG. The 5- and 10-year survival rates were 96% and 94%, respectively, in both patient groups with normal and high HCG ( p = 0.99). The 5- and 10-year relapse-free survival rates were 87% and 82%, respectively, in patients with normal HCG level and were both 87% in patients with high HCG ( p = 0.74). Also, no other patient-, tumor-, or treatment-related factors seemed to influence the prognosis of the patients. Conclusion: Serum HCG level does not seem to influence patient prognosis when treated with sufficient doses of radiation. Relationship between tumor size and site and HCG level should be investigated further.

Purpose: Results of radiation therapy for primary central nervous system lymphoma (PCNSL) were poor in the 1970 –1980s, with most reported 5-year survival rates being less than 10%. To investigate whether the prognosis of PCNSL patients treated by radiation alone remains still poor, we investigated the results of radiation monotherapy in the 1990s. Methods and Materials: We collected data on 132 patients with histologically proven PCNSL treated by radiation alone in the 1990s from three nationwide or regional multiinstitutional studies conducted by the Japanese Society for Therapeutic Radiology and Oncology (JASTRO) Lymphoma Study Group or the Chubu Radiation Oncology Group. Follow-up data were updated as far as possible. Eleven patients who did not complete planned radiotherapy were included. The data were analyzed in relation to patient and tumor characteristics. The median patient age was 63 years, and the World Health Organization performance status (PS) was 3 or 4 in 40% of the patients. Multiple tumors were seen in 34%. Whole-brain irradiation with or without focal boost was used in 92%. The median radiation dose to the tumor site was 50 Gy (range, 8 –74 Gy). Results: For all 132 patients, the median survival time was 18 months and the 5-year survival rate was 18.0%. For 62 patients with PS 0 –3 and aged 16 – 65 years (i.e., those eligible for the European Organization for Research and Treatment of Cancer 20962 study), the median survival was 26 months and 5-year survival was 24%. The 5-year survival was 25% for patients 63 years old or younger, and 9.8% for those older than 63 years (p 0.0005). The 5-year survival was 22% for patients with PS 0 –2 and 13% for those with PS 3 or 4( p 0.0040). Multivariate analysis confirmed the negative influence of higher age on patient prognosis. Conclusions: The results of radiation monotherapy for PCNSL appear to have improved as compared with those reported previously. The results of new treatment should be evaluated in light of this finding. Since most prospective studies on the combined treatment exclude poor PS and high-age patients, the 5-year survival rate of 30% may not be regarded as a marked improvement over radiation alone. © 2005 Elsevier Inc.

原発巣不明の腺癌腹腔内リンパ節転移例に膵頭部腫瘍との鑑別が困難であったためPDを施行したが原発巣不明のまま再発兆候なく8年経過した症例を経験した.症例は85歳,女性.食欲不振,体重減少のため消化器精査を行った.腹部CT, USで膵頭部に4.2×3.6cmの腫瘤を認めた. ERCPでは膵管に異常なく,腹部血管造影で腫瘍濃染を認めた. USガイド下穿刺細胞診は陽性で術前膵島細胞腫瘍を疑った.手術所見では5×3cmの腫瘍が総肝動脈を巻き込み膵頭部より外方に発育しNo.8リンパ節との鑑別が問題になったがPDを行った.術後の病理組織診断では腫瘍は膵と連続性はなくリンパ節に限局し転移性腺癌と診断された.膵,胆管内に原発巣は認めなかった.原発不明癌でも腹腔内リンパ節転移の場合他臓器の合併切除が必要なこともあり,根治性をどこまで追及するか苦慮する点であるが,本症例ではこの手術でcurative operationを行い得たと考えている.

Hepatobiliary cystadenoma was suggested to be uncommon and it is often difficult to make a differential diagnosis. We report a case of a 65-year-old woman who presented with changes in the structure of a cyst that had been observed for the previous 10 years. Diagnostic imaging revealed a 7-cm-diameter cystic lesion with internal septations and papillary projections in her liver. All laboratory test results were normal; however, cystic fluid carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were raised, at 160 ng/ml and over 200 000 U/ml, respectively. Owing to changes in the structure of the cyst and the difficulty of differential diagnosis from cystadenocarcinoma, a complete surgical excision was performed. The histological findings indicated that the tumor consisted of a multilocular cyst lined by glandular cells (with cuboidal or tall columnar cystoplasm), which were immunohistochemically positive for cytokeratin, CEA, epithelial membrane antigen, and CA 19-9. The underlying stroma was composed of proliferating primitive spindle cells which were immunoreactive for vimentin, alpha-smooth muscle actin, muscle-specific actin, and desmin, and resembled ovarian stroma. From these findings, this tumor was diagnosed as hepatobiliary cystadenoma with mesenchymal stroma. Even though the tumor was previously diagnosed as a simple liver cyst, it was necessary to pay special attention to the changes in the structure of the cyst, using ultra sonography and/or computed tomography, bearing in mind hepatobiliary cystadenoma with mesenchymal stroma. The malignant potential of this tumor is stressed, and complete surgical resection is the recommended therapy.

目的:胃癌の術中腹腔洗浄細胞診において, 癌細胞数の多寡が予後に与える影響を検討した.方法:肉眼的腹膜転移陰性・腹腔洗浄細胞診陽性 (PO, CY1) の61例を, プレパラート上の癌細胞数によって少数群と多数群に分けた. それら癌細胞数の多寡, 術中・術後腹腔内補助療法施行の有無によって予後を比較検討した.結果:PO, CY1症例は肉眼的腹4膜転移陽性症例とほぼ同じ生存率であった. PO, CY1, 少数群とPO, CY1, 多数群の予後は同じであったが, PO, CY1, 少数群に腹腔内補助療法を施行した場合, 予後は肉眼的腹膜転移陰性・腹腔洗浄細胞診陰性症例に匹敵するぐらい良好となった.結語:腹腔洗浄細胞診における癌細胞数の多寡を計測することによって, 胃癌の術中・術後腹腔内補助療法の効果および予後を予測できる可能性があることが示唆された.

Abstract —Heme oxygenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress. We demonstrated that mildly oxidized LDL markedly induces HO-1 in human aortic endothelial and smooth muscle cell cocultures and that its induction results in the attenuation of monocyte chemotaxis resulting from treatment with mildly oxidized LDL in vitro. To elucidate the role of HO-1 in the development of atherosclerotic lesions in vivo, we modulated HO-1 expression in LDL-receptor knockout mice fed high-fat diets. During 6-week high-fat diet trials, intraperitoneal injections of hemin (H group) or hemin and desferrioxamine (HD group) to induce HO-1, Sn-protoporphyrin IX to inhibit HO-1 (Sn group), and saline as control (C group) were performed. Both the H and HD groups showed significantly less mean atherosclerotic lesions in the proximal aorta compared with the C group, whereas the Sn group showed larger lesion compared with the C group. Modulation of HO expression and HO activities were confirmed by Northern blot analysis and HO activity assay. Immunohistochemical studies revealed significant HO-1 expression in atherosclerotic lesions, where oxidized phospholipids also localized. Major cell types expressing HO-1 were macrophages and foam cells in the lesions. HO modulations affected plasma lipid hydroperoxide (LPO) levels and nitrite/nitrate levels. These results suggest that HO-1, induced under hyperlipidemia, functioned as an intrinsic protective factor against atherosclerotic lesion formation, possibly by inhibiting lipid peroxidation and influencing the nitric oxide pathway.

Tubular carcinoma of the breast is a rare type of breast carinoma which has characteristic histologic findings, especially pure type tubular carcinoma in that lymp node metastases rarely occur and the prognosis is good. We report a case of resected pure type tubular carcinoma of the breast with lymph node metastasis. A 55-year-old woman was referred to the hospital because of a tumor formation at her left breast. The tumor shadow with spicula was identified by a mammogram, but the tumor could not be diagnosed as malignancy by an aspiration cytology. By an excisional biopsy, the tumor was diagnosed as tubular carcinoma. The patient underwent a mastectomy with lymph nodes dissection. Postoperative histological findings revealed pure type tubular carcinoma with axillary lymph node metastasis. Since lymph node metastasis is detected in a pure type tubular carcinoma like in this case, tubular carcinoma should be dealt with the same manner as other invasive carcinomas of the breast are treated.

This study was designed to elucidate the significance of preoperative computed tomography during arterial portography (CTAP) in surgical treatment of hepatocellular carcinoma (HCC). Eighteen patients with HCC whose minute lesions had been pointed out by CTAP preoperatively (CTAP positive group) were compared with another eight patients with HCC having postoperative recurrence in a region at where no tumors had been detected by preoperative CTAP (CTAP negative group) for preoperative location of tumor and postoperative pattern of recurrence. In the CTAP positive group, 11 patients had recurrence and the remaining seven patients had not. Disease-free periods up to recurrences were 8.7 months in an average in the 11 CTAP positive patients and 16.6 months in the CTAP-negative group, showing a significantly shorter interval in the CTAP positive patients. In recurred cases from the CTAP positive group, tumors identified by imaging procedures other than CTAP were solitary in four and multiple in seven cases, while all solitary in nonrecurred cases. In the recurred CTAP positive cases, actual recurrence occurred in the same segment where a tummor had been pointed out by CTAP alone in five out of six cases of solitary recurrenc; or involved the same segment where CTAP detected tumor (s) in four out of five cases of multiple recurrence. It is indicated that the possibility of postoperative recurrence of HCC is high in cases having minute lesions visualized by CTAP alone in addition to multiple lesions visualized by imaging procedures other than CTAP. We think that periodical imaging methods including CTAP are required for HCC patients.

The objective of this study was to report three cases with an accumulation of (131)I in the nasolacrimal duct after radioiodine therapy for papillary thyroid cancer. A whole-body scan was taken 3 days after the administration of 3.7 GBq of (131)I. Single-photon emission computed tomography (SPECT)/CT images were added when the location of a focal tracer uptake was undetermined on whole-body scans. In case 1, a 62-year-old woman complained of epiphora of the left eye after nine radioiodine therapies with a cumulative dose of 31.08 GBq. The left nasolacrimal duct was visualized at her tenth treatment with (131)I. In case 2, a series of three radioiodine therapies had been given to a 73-year-old woman with a cumulative dose of 11.1 GBq. The accumulation of (131)I was noted in the left nasolacrimal duct at her fourth treatment. She complained of epiphora of the left eye. In case 3, bilateral nasolacrimal ducts were visualized at the second radioiodine therapy in a 75-year-old woman. The patient had received 3.7 GBq of (131)I at the first therapy. She did not complain of epiphora. It is possible that radiation from (131)I that is secreted in tears and/or actively accumulated in the nasolacrimal duct may induce nasolacrimal duct obstruction. (131)I in tears would be responsible for the visualization of nasolacrimal duct in the first two cases. (131)I actively accumulated in the nasolacrimal duct might have been visualized in the third case. In summary, (131)I is excreted in tears and is actively accumulated in the nasolacrimal duct. Obstruction of the lacrimal drainage system could occur after high-dose radioiodine therapy.

Microwave coagulation therapy (MCT) was applied to 3 patients with synchronous metastatic liver tumors from colon cancer. After resection of colon cancer, MCT was administered to the liver lesions at 60-90W for 20-90 seconds per bout. We used the monopolar needle electrodes of various length, including an electrode which coagulates the tissue around only the tip. A total of 22 sessions was applied to the 3 tumors. Each patient received intrahepato-arterial chemotherapy after surgery. Abdominal computed tomography showed no blood flow in tumors undergoing MCT. Two of 3 patients are alive without recurrence 17 months highly effective for patients with metastatic liver tumors from colon cancer.

The aim of our study was to analyze changes over time in the characteristics, treatment, and outcome of patients with primary central nervous system lymphoma (PCNSL). Data on 315 patients with histologically proven PCNSL undergoing radiotherapy between 2005 and 2009 were collected from 20 Japanese institutions using a questionnaire. These data were then compared with data on 273 patients treated during the period 1995–2004 and those on 466 patients treated during the period 1985–1994. In terms of patient and tumor characteristics, we found a significant increase in mean patient age in the 2005–2009 period compared to the 1985–2004 period (63 vs. 58–59 years, respectively) and in the percentage of patients with better performance status (PS) during the 2005–2009 period compared with the 1995–2004 period (World Health Organization PS 0–2: 73 vs. 65 %, respectively). Regarding treatment, relative to the 1995–2004 period, significant changes in the 2005–2009 period were (1) decreased rate of attempting tumor resection (23 vs. 44 %); (2) increased use of chemotherapy (78 vs. 68 %), and (3) increased use of methotrexate (MTX)-containing regimens (84 vs. 53 %). The 5-year overall survival rates were 15.3, 30.1, and 36.5 % for patients seen during the 1985–1994, 1995–2004, and 2005–2009 periods, respectively, but relapse-free survival did not improve between the 1995–2004 and 2005–2009 periods (26.7 vs. 25.7 % at 5 years, respectively). Patients receiving MTX-containing chemotherapy had 5-year survival rates of 19, 50, and 44 % during these three periods, respectively. Although patient backgrounds differed among the study periods, recent trends were a high patient age, better PS, avoidance of extensive tumor resection, more frequent use of chemotherapy, and improved survival. The recent improvement in survival may be due to improvements in second-line treatment and supportive care.

Background The purpose of this study is to analyze the outcome of patients with early glottic cancer (GC) treated with radiotherapy (RT) with or without chemotherapy at 10 institutions in the Tokai District, Japan. Methods Ten institutions combined data from 279 patients with T1-T2 GC treated with RT with or without chemotherapy between 2000 and 2005. The overall survival rate, disease-specific survival rate, and local control rate were evaluated in 270 patients, except for incomplete cases due to issues such as discontinuation, using the method of Kaplan-Meier and compared using the log-rank test. Results were considered statistically significant at the level of p < 0.05. Results For 122 patients, the tumors were classified as T1a, while 64 patients had T1b tumors, and 84 patients had T2 tumors. In three cases of T1 tumors, the subtype was unknown. Combined chemoradiotherapy (CRT) was administered during each stage, and various chemotherapy drugs and regimens were used. The median follow-up period was 55.4 months. The 5-year LC rates for T1a, Tb, and T2 tumors in all patients were 87.9%, 82.7%, and 74.1%, respectively. The difference between T1a and T2 was statistically significant (p = 0.016). The 5-year LC rates for T1a, Tb, and T2 with CRT were 92.7%, 78.6%, and 80.7%, respectively, while the rates with radiation alone were 86.5%, 83.8%, and 64.4%, respectively. The difference between CRT and RT alone was not statistically significant in each stage. Conclusions In this survey, CRT was performed for early GC at most institutions in clinical practice. Our data showed no statistical difference in the LC rates between CRT and RT alone in each stage. However, there was a tendency for the LCRs of the CRT group to be more favorable than those of the RT group in the T2-stage.

目的:直腸肛門指診などの理学的所見が診断の中心となっている直腸肛門領域に超音波検査を施行し,その客観的評価を疾患の存在および質的診断に利用する.対象・方法:1992年4月より1994年8月に当院受診し,指診では正確に診断し得なかった569例を対象にリニア式プローブを用いた経肛門的超音波検査を施行した.さらに超音波ガイド下穿刺生検をも試みた.成績:本法にて直腸肛門周囲膿瘍は,cystic patternを呈し明確に診断できた.また膿瘍・痔瘻の病期を超音波画像によって急性期・中間期・慢性期の3つに分類し治療方針を決定した.本法ガイド下穿刺生検は,正確に施行できた.結論:(1)本法の最も良い適応は,直腸肛門周囲膿瘍であった.(2)本法による客観的評価が膿瘍・痔瘻の治療方針を決定する根拠となり得た.(3)本法ガイド下穿刺生検は,肛門部腫瘤の質的診断に有効であった.

We isolated adherent fibroblastic cells after collagenase and dispase treatment of human dental pulp. When human dental pulp cells (hDPCs) were cultured in the presence of basic fibroblast growth factor (bFGF), the ratio of hDPCs in the S-phase was significantly higher in comparison with incubation without bFGF. The ratio of hDPCs expressing STRO-1 as a marker of stem cell populations increased approximately eightfold in the presence of bFGF as opposed to that in the absence of bFGF. We demonstrated the characterization and distinctiveness of the hDPCs and showed that, when cultured with the medium containing serum and bFGF, they were highly proliferative and capable of differentiating in vitro into osteoblasts, chondrocytes, and adipocytes. Furthermore, the in vitro differentiation was confirmed at both the protein and gene expression levels. Transplantation of hDPCs -- expanded ex vivo in the presence of bFGF into immunocompromised mice -- revealed the formation of bone, cartilage, and adipose tissue. The donor hDPC-derived cells were labeled in the bone tissues located near the PLGA in the subcutaneous tissues of recipient mice using a human-specific Alu probe. When cultured with a serum-free medium containing bFGF, the hDPCs strongly expressed STRO-1 immunoreactive products and sustained self-renewal, and thus were almost identical in differentiation potential and proliferation activity to hDPCs cultured with the medium containing serum and bFGF. The present results suggest that the hDPCs cultured in the presence of bFGF irrespective of the presence or absence of the bovine serum are rich in mesenchymal stem cells or progenitor cells and useful for cell-based therapies to treat dental diseases.

We describe an 11-year-old female patient who presented with a 7-day history of diplopia and difficulty walking. On examination she had ataxia, areflexia and ophthalmoplegia, and a diagnosis of Miller Fisher syndrome (MFS) was made after the exclusion of other conditions. Monocyte chemotactic protein-1 (MCP-1) and interleukin (IL)-8 chemokine levels in the cerebrospinal fluid (CSF) were significantly increased in the acute phase. We believe MFS in this patient was due to both peripheral nervous system dysfunction, and central nervous system (CNS) involvement. The cause of MFS in this patient was suggested by the localized chemokine production in the CSF. The high expression of MCP-1 and IL-8 chemokines suggest that macrophages and T cells may stimulate inflammation of the CNS in MFS.

This study compared the clinical and physiological results of non-sphincter splitting fistulectomy (N-SSF) with those of sphincter splitting fistulotomy (SSF) for treatment of high trans-sphincteric fistula-in-ano.A prospective, observational study was undertaken in 70 consecutive patients with high trans-sphincteric fistula treated by SSF (n = 35) or N-SSF (n = 35). Anal manometry was performed before and 3 months after surgery. Anal continence was assessed using the Cleveland Clinic Florida Incontinence Score.There was no difference between the two groups in age, gender, presence of horseshoe extension, preoperative incontinence score and manometric values. The incidence of recurrence was similar between the two groups. The postoperative incontinence score of the SSF group was significantly higher than that of the N-SSF group (1.9 +/- 2.9 vs 1.1 +/- 2.9, P = 0.0347). Maximum resting pressure showed significant decrease after surgery in both groups (83.2 to 56.1 mmHg, P = 0.0001 and 85.1 to 58.4 mmHg, P = 0.0001). Voluntary contraction pressure and functional anal canal length did not change after N-SSF (137.6 to 138.2 mmHg, P = 0.9524 and 4.06 to 4.07 cm, P = 0.9524), but significantly decreased after SSF (120.2 to 96.7 mmHg, P = 0.0085 and 4.12 to 3.74 cm, P = 0.0183).Non-sphincter splitting fistulectomy for high trans-sphincteric fistula provided better functional results than fistulotomy. Less impairment of anal continence was achieved possibly not only by maintenance of the external anal sphincter function but also by preservation of the length of the high-pressure zone.

This study was undertaken to determine the incidence of and risk factors for anal incontinence after fistulotomy for intersphincteric fistula-in-ano. We also evaluated the role of anal manometry in preoperative assessment of intersphincteric fistula.A prospective, observational study was undertaken in 148 patients who underwent fistulotomy for intersphincteric fistula between January and December 2004. Functional results were assessed by standard questionnaire and anal manometry. Possible factors predicting postoperative incontinence were examined by univariate and multivariate regression analyses.The mean follow-up period was 12 months. Postoperative anal incontinence occurred in 30 patients (20.3%), i.e., soiling in 6, incontinence for flatus in 27, and incontinence for liquid stool in 4. Fistulotomy significantly decreased maximum resting pressure (85.9 +/- 20.4 to 60.2 +/- 18.4 mmHg, P0.0001) and length of the high pressure zone (3.92 +/- 0.69 to 3.82 +/- 0.77 cm, P = 0.035), but it did not affect voluntary contraction pressure (164.7 +/- 85.2 to 160.3 +/- 84.8 mmHg, P = 0.2792). Multivariate analysis showed low voluntary contraction pressure and multiple previous drainage surgeries to be independent risk factors for postoperative incontinence.Fistulotomy produces a satisfactory outcome in terms of eradicating sepsis and preserving function in the vast majority of patients with intersphincteric fistula with intact sphincters. However, sphincter-preserving treatment may be advocated for patients with low preoperative voluntary contraction pressure or those who have undergone multiple drainage surgeries. Preoperative anal manometry is useful in determining the proper surgical procedure.

We analyzed the therapeutic results and prognostic factors of 46 primary central nervous system lymphoma (PCNSL) patients who were treated at twelve institutions in the Tokai district of Japan between 1995 and 1999. We compared the results with those of a Japanese nationwide survey performed in the past.We sent each institution a questionnaire about the state of patients' disease, pathological type, method and doses of radiotherapy, regimen and intensity of chemotherapy, and patients' prognoses. The range of patients' ages was 33 to 93 years (median, 61 years). Thirty-one were men and 15 were women. The most prevalent histology was diffuse large B cell type (33 patients). We used the Kaplan-Meier method to calculate the survival rate and Cox's proportional hazards model to analyze the prognostic factors.The five-year cumulative survival rate was 25%, and the median survival time was 22.7 months. The five-year disease-free survival rate was 23%. In monovariate analysis, patients who were both younger than 60 years old and had a WHO performance status (PS) score equal to or less than 2 showed a better survival rate. Furthermore, the patients receiving systemic chemotherapy showed a significantly better local control rate. In addition, patients who received systemic chemotherapy achieved a higher complete remission rate than those not receiving it. However, no factors that significantly influenced survival rate were identified in multivariate analysis.We demonstrated that the therapeutic outcome of PCNSL patients has recently improved. In particular, patients with good PS showed better local control than those with poor PS. However, we could not identify any significant prognostic factors in PCNSL patients.

Purpose: Most patients who had any recurrent sites of cancer have been considered to be in their last stage of life. However, recent advances of clinical research reveal some patients achieve long-term survival even in recurrence. Furthermore, for patients who had only one recurrent region, radiation therapy could play an important role. As for uterine cervical carcinoma, the most common recurrent site other than the pelvis is the para-aortic lymph nodes. Thus we conducted the current study. Patients and Methods: Between 1994 and 2003, more than 5,000 uterine cervical carcinoma patients were treated with curative intended treatments at 13 Japanese hospitals. Of these patients, 84 developed para-aortic lymph node recurrence as the only site of initial tumor progression. These patients were treated with external beam radiation therapy. Radiation therapy protocol was as follows: 1.7–2.0 Gy per fraction, 5 fractions per week, and the mean total dose was 50.8 Gy (25–60 Gy). Results: Three- and 5-year overall survival rates of all patients were 49.5% and 31.3%, respectively. Stratified by symptom sign, 3-year overall survival rate of symptom positive was 27.6% and those of the negative was 56.1% ( p = 0.018). Three-year overall survival rates of the total dose ≥51 Gy and that of ≤50 Gy were 58.0% and 42.8%, respectively ( p = 0.07). As for morbidity, no patients received Grade 3 or greater late toxicity. Conclusions: The current study suggested that radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma could have a significant impact on survival.

This study was undertaken to determine the incidence of and risk factors for urinary retention after surgery for benign anorectal disease.We reviewed 2,011 consecutive surgeries performed under spinal anesthesia for benign anorectal disease from January through June 2003 to identify potential risk factors for postoperative urinary retention. In addition, we prospectively investigated the preventive effect of perioperative fluid restriction and pain control by prophylactic analgesics on postoperative urinary retention.The number of procedures and the urinary retention rates were as follows: hemorrhoidectomy, 1,243, 21.9%; fistulectomy, 349, 6.3%; incision/drainage, 177, 2.3%; and sliding skin graft/lateral subcutaneous internal sphincterotomy, 64, 17.2%. The overall urinary retention rate was 16.7%. With hemorrhoidectomy, female sex, presence of preoperative urinary symptoms, diabetes mellitus, need for postoperative analgesics, and more than three hemorrhoids resected were independent risk factors for urinary retention as assessed by multivariate analysis. With fistulectomy, female sex, diabetes mellitus, and intravenous fluids1,000 ml were independent risk factors for urinary retention. Perioperative fluid restriction, including limiting the administration of intravenous fluids, significantly decreased the incidence of urinary retention (7.9 vs 16.7%, P0.0001). Furthermore, prophylactic analgesic treatment significantly decreased the incidence of urinary retention (7.9 vs 25.6%, P=0.0005).Urinary retention is a common complication after anorectal surgery. It is linked to several risk factors, including increased intravenous fluids and postoperative pain. Perioperative fluid restriction and adequate pain relief appear to be effective in preventing urinary retention in a significant number of patients after anorectal surgery.

The purpose of this study is to evaluate the stem cell mobilization capacity, anti-tumor effect, and feasibility of ifosfamide/carboplatin/etoposide (ICE) for transplant-eligible patients with medulloblastoma.Six patients (23 months to 18 years old) with high-risk or relapsed medulloblastoma received one cycle of ICE, which consisted of ifosfamide at 1.8 g/m(2) for 5 days, carboplatin 400 mg/m(2) for 2 days, and etoposide 100 mg/m(2) for 5 days. Stem cells were mobilized with ICE followed by granulocyte colony-stimulating factor at 10 microg kg(-1) day(-1).After one cycle of ICE, the median number of harvested CD34+ cells per apheresis session was 11.85 x 10(6) cells/kg (range, 0.2 to 71.2 x 10(6) cells/kg). Two patients obtained a complete response and three patients a partial response. All patients experienced severe myelosuppression, and three infectious toxicities were observed.These results suggest that ICE is optimal for mobilizing stem cells, effective for high-risk or relapsed medulloblastoma, and tolerable with limited non-hematological toxicity.

Inhibitory responses of slowly adapting pulmonary stretch receptor (SAR) activity to CO(2) inhalation (maximal tracheal CO(2) concentration ranging from 9.5 to 12.5%) for approximately 60 s were examined before and after administration of acetazolamide (a carbonic anhydrase inhibitor) or 4-aminopyridine (4-AP, a K(+) channel blocker). The experiments were performed in 35 anesthetized, artificially ventilated rats after unilateral vagotomy. Sixty-eight of eighty-four SARs were inhibited by CO(2) inhalation. The SAR inhibition was attenuated by pretreatment with either acetazolamide (20 mg/kg, n = 10) or 4-AP (0.7 and 2.0 mg/kg, n = 10). In other series of experiments, stainings to show the existence of carbonic anhydrase (CA) enzymatic reaction were not found in the smooth muscle of either extrapulmonary or intrapulmonary bronchi. Protein gene product 9.5 (PGP 9.5)-immunoreactive SAR terminals to form leaflike extensions were found in the bronchioles at different diameters and were smooth-muscle-related receptors. But in the same sections, CA isozyme II-like (erythrocyte CA) immunoreactive SAR terminals were not identified. These results suggest that CO(2)-induced inhibition of SARs may be involved in the CA-dependent CO(2) hydration in addition to the activation of 4-AP sensitive K(+) currents.