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Objective The objective of this study was to investigate whether prophylactic administration of nafamostat mesilate reduces the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP), its efficacy, and risk factors for PEP. Methods Potential subjects comprised 876 patients who underwent ERCP between September 2008 and February 2011. Of these, 58 patients were excluded after meeting exclusion criteria, and 818 patients were randomized. Patients in the nafamostat mesilate group were administered 20 mg of nafamostat mesilate dissolved in 500 mL of 5% glucose solution, whereas the control group received 500 mL of 5% glucose solution alone, over 2 hours from the start of ERCP. Results Post-ERCP pancreatitis occurred in 5.1% (41 patients) overall, with a significantly lower frequency in the nafamostat mesilate group (3.5%) than in the control group (6.7%; P = 0.0349). Analysis of the 322 patients who had undergone ERCP for the first time (n = 158 in the nafamostat mesilate group; n = 164 in the control group) found that PEP again significantly less frequently occurred in the nafamostat mesilate group (5.7%) than in the control group (13.4%; P = 0.0172). Conclusions Our randomized controlled study suggested that short-term administration of nafamostat mesilate 20 mg may reduce the incidence of PEP.

The 3(rd) English edition of the Japanese classification of biliary tract cancers was released approximately 10 years after the 5(th) Japanese edition and the 2(nd) English edition. Since the first Japanese edition was published in 1981, the Japanese classification has been in extensive use, particularly among Japanese surgeons and pathologists, because the cancer status and clinical outcomes in surgically resected cases have been the main objects of interest. However, recent advances in the diagnosis, management and research of the disease prompted the revision of the classification that can be used by not only surgeons and pathologists but also by all clinicians and researchers, for the evaluation of current disease status, the determination of current appropriate treatment, and the future development of medical practice for biliary tract cancers. Furthermore, during the past 10 years, globalization has advanced rapidly, and therefore, internationalization of the classification was an important issue to revise the Japanese original staging system, which would facilitate to compare the disease information among institutions worldwide. In order to achieve these objectives, the new Japanese classification of the biliary tract cancers principally adopted the 7(th) edition of staging system developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC). However, because there are some points pending in these systems, several distinctive points were also included for the purpose of collection of information for the future optimization of the staging system. Free mobile application of the new Japanese classification of the biliary tract cancers is available via http://www.jshbps.jp/en/classification/cbt15.html.

To investigate the clinicopathological features and postoperative survival of patients with mucinous colorectal carcinoma (MC) and to identify the factors related to long-term survival.Twenty-three patients who had undergone resection for MC at Miyazaki University Hospital from 1991 to 2006 were followed up for at least 5 years or until death. The effects of the clinicopathological variables on the 5-year cancer-specific survival were assessed by the univariate analyses. These patients' clinicopathological data were compared with those of 403 non-mucinous carcinoma (NMC) patients (102 well-differentiated adenocarcinomas, 301 moderately differentiated adenocarcinomas).The 5-year cancer-specific survival rate was significantly worse in MC (56.2 %) than in NMC (73.8 %; p = 0.008) cases. Univariate analyses showed the T factor, lymph node metastases, liver metastases, metastases to the distant peritoneum, remote metastases and curative resection to be significant factors predicting the survival. However, there were no significant differences in the postoperative survival in patients with stage II-IV disease. The rates of metastases to the distant peritoneum, M1, T4, a tumor size ≥5 cm and non-curative resection were higher in MC than in NMC patients.Patients with MC had advanced stage cancer, especially with metastases to the distant peritoneum, more frequently than did the patients with NMC. To improve the survival of these patients, it is therefore important to detect MC at an early stage and to perform curative resection.

Based on the results of first-line chemotherapy for advanced pancreatic cancer, S-1 was confirmed to be non-inferior to gemcitabine. However, the recommended regimen of 4 weeks of administration followed by 2 weeks of drug withdrawal frequently causes adverse effects. On the other hand, we experienced in clinical practice that alternate-day administration of S-1 reduced adverse effects and were tolerable for advanced pancreatic cancer patients unwilling to continue the standard daily administration. We therefore conducted a multicenter cooperative prospective study to compare daily with alternate-day administration of S-1 for advanced pancreatic cancer. Patients with advanced pancreatic cancer were eligible for enrollment in this trial. S-1 was administered at a dose of 40–60 mg twice daily, calculated according to body surface area, on Monday, Wednesday, Friday, and Sunday. Each treatment cycle was 42 days. The primary end point was overall survival (OS). Secondary end points were safety, response rate (RR), progression-free survival (PFS), and time to treatment failure (TTF). Forty-eight patients were evaluable for response. OS as the primary end point was 8.4 months (95 % CI 5.4–10.8), and the 1-year survival rate was 29.2 %. PFS was 5.5 months, and TTF was 3.9 months. RR was 10.4 %, and the disease control rate was 79.2 %. Grade 3/4 hematological and non-hematological toxicities were minor. All of these adverse reactions were tolerable and reversible. The current data demonstrate the mitigation of adverse effects with alternate-day administration of S-1, and this appears to be a more sustainable option for advanced pancreatic cancer.

Postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is a worrisome and life-threatening complication. Recently, early drain removal has been recommended as a means of preventing POPF. The present study sought to determine how to distinguish clinical POPF from non-clinical POPF in the early postoperative period after PD to aid in early drain removal. From March 2002 through December 2010, 176 patients underwent PD and were enrolled in this study to examine factors predictive of clinical POPF after PD. POPF was defined and classified according to the International Study Group of Pancreatic Surgery guideline, and grade B/C POPF was defined as clinical POPF. Grade A POPF occurred in 39 (22.2 %) patients, grade B in 19 (10.8 %) patients, and grade C in 11 (6.3 %) patients. Clinical POPF (grade B/C) occurred in 17.1 % of patients. Multivariate analysis revealed male gender and body mass index (BMI) ≥22.5 kg/m2 to be the independent preoperative risk factors predictive of POPF. Receiver operating characteristic curves showed that the combination of drain amylase ≥750 IU/L, C-reactive protein (CRP) ≥20 mg/dL, and body temperature ≥37.5 °C on postoperative day 3 could effectively distinguish clinical POPF from non-clinical POPF. Sensitivity, specificity, and accuracy were 84.6, 98.2, and 95.7 %, respectively. Male gender and BMI ≥22.5 were the independent preoperative predictive risk factors for POPF. We assume that when amylase is

Pancreatobiliary reflux (PBR) can occur in individuals without pancreaticobiliary maljunction. The aim of this study was to elucidate the incidence of PBR in individuals with a normal pancreaticobiliary junction and its impact on the biliary tree.Data were prospectively collected from 15 centers on 420 patients with a morphologically normal pancreaticobiliary junction who had undergone bile sampling and measurement of the biliary amylase level. We investigated the incidence and predictive factors for high biliary amylase levels (HBAL), as well as the relationship of HBAL with biliary malignancy.Twenty-three patients (5.5%) showed HBAL (≥10,000 IU/L). Univariate analysis showed that risk factors for the elevation of biliary amylase levels were the existence of a relatively long common channel (≥5 mm), acute pancreatitis, and papillitis. Multivariate analysis revealed that only the existence of a relatively long common channel was a significant factor for PBR. Biliary amylase levels in patients with a relatively long common channel were significantly higher than in patients without a long common channel (12,333 vs. 2,070 IU/L, P = 0.001). The incidence of HBAL (P0.001), as well as the overall biliary amylase levels (P = 0.007) were significantly higher in patients with gallbladder cancer than in those without gallbladder cancer.The PBR was frequently observed in individuals with a relatively long common channel. Patients showing HBAL with normal pancreaticobiliary junction are at high risk for gallbladder cancer.

This study aimed at demonstrating the feasibility of retrospectively fused (18)F FDG-PET and MRI (PET/MRI fusion image) in diagnosing pancreatic tumor, in particular differentiating malignant tumor from benign lesions. In addition, we evaluated additional findings characterizing pancreatic lesions by FDG-PET/MRI fusion image.We analyzed retrospectively 119 patients: 96 cancers and 23 benign lesions. FDG-PET/MRI fusion images (PET/T1 WI or PET/T2WI) were made by dedicated software using 1.5 Tesla (T) MRI image and FDG-PET images. These images were interpreted by two well-trained radiologists without knowledge of clinical information and compared with FDG-PET/CT images. We compared the differential diagnostic capability between PET/CT and FDG-PET/MRI fusion image. In addition, we evaluated additional findings such as tumor structure and tumor invasion.FDG-PET/MRI fusion image significantly improved accuracy compared with that of PET/CT (96.6 vs. 86.6 %). As additional finding, dilatation of main pancreatic duct was noted in 65.9 % of solid types and in 22.6 % of cystic types, on PET/MRI-T2 fusion image. Similarly, encasement of adjacent vessels was noted in 43.1 % of solid types and in 6.5 % of cystic types. Particularly in cystic types, intra-tumor structures such as mural nodule (35.4 %) or intra-cystic septum (74.2 %) were detected additionally. Besides, PET/MRI-T2 fusion image could detect extra benign cystic lesions (9.1 % in solid type and 9.7 % in cystic type) that were not noted by PET/CT.In diagnosing pancreatic lesions, FDG-PET/MRI fusion image was useful in differentiating pancreatic cancer from benign lesions. Furthermore, it was helpful in evaluating relationship between lesions and surrounding tissues as well as in detecting extra benign cysts.

This study aimed to investigate whether the initial indication for surgery or type of surgery (strictureplasty or resection) performed determines recurrence patterns in patients with Crohn disease. Recurrence patterns of 41 patients (31 patients: only resection and anastomosis of the intestine, and 10 patients: strictureplasty with/without resection and anastomosis) who underwent operation for recurrent Crohn disease (June 2002–December 2010) were evaluated. Strictureplasty for nonperforating disease was performed at 17 sites, and reoperation was required at 11 sites (10 sites for nonperforating disease and 1 site for perforating disease). There was a significant difference in the recurrence pattern in patients who underwent resection and anastomosis (P < 0.01) and in patients who underwent strictureplasty with resection and anastomosis (P < 0.05) between sites at which resection and anastomosis was performed for nonperforating and for perforating disease. Initial indication for surgery, but not the type of surgery, appeared to determine recurrence patterns.

BackgroundMultifunctional redox protein human thioredoxin (TRX-1) is reduced by thioredoxin reductase (TRX-R). The aim of the present study was to examine the distribution of TRX-1 and TRX-R expressions in gallbladder carcinoma (GBC) to clarify their usefulness as prognostic factors after surgical resection.MethodsImmunohistochemical staining for TRX-1 and TRX-R was performed in GBC tissue from 38 patients who underwent surgical resection, and TRX-1/TRX-R localization in relation to outcome was examined.ResultsTRX-1 protein levels were significantly higher in GBC samples than in cholecystolithiasis samples (P= 0.0174). TRX-1 expression was observed in 100% (38/38) of tumour samples and in the nucleus in 76% (29/38), with nuclear expression in the invasion front observed in 45% (13/29). TRX-R expression was only detected in the cytoplasm of cancer cells and in the invasion front in 28 samples. In all of the samples, the depth of tumour invasion, lymph node metastasis, surgical margin, curability and nuclear expression of TRX-1 in the invasion front were significant prognostic factors by univariate analysis. In 27 selected patients who underwent curative resection, both TRX-1 nuclear expression and TRX-R cytoplasmic expression in the invasion front was a significantly prognostic factor.ConclusionTRX-1 nuclear expression in the GBC invasion front is a significant prognostic marker. Patients with both TRX-1 nuclear expression and TRX-R cytoplasmic expression in the tumour invasion front should be observed carefully even if after curative resection.

We describe a prenatally diagnosed case with congenital infantile fibrosarcoma, which is a rare malignant tumor, of which there have been only 14 cases reported in the English literature. A giant mass on the left thigh was detected at 24 weeks' gestation by prenatal ultrasonography. Because of its rapid growth and nonreassuring fetal status in utero, the baby was delivered by cesarean delivery at 27 weeks' gestation. The case was complicated by hemorrhagic anemia, coagulopathy, and cardiac failure, and a tumor resection was performed on day 3. As of age 2.5 years, he was healthy without evidence of recurrence. Because some fetal cases with congenital infantile fibrosarcoma have a poor prognosis, termination of pregnancy at an appropriate time and postnatal early treatment are crucial for successful treatment.

Chronic ischemic enteritis can cause intestinal strictures, but extensive resection of the small intestine may leave patients with short bowel syndrome. Thus, the importance of preserving diseased small bowel is now recognized. We report a case of successful side-to-side isoperistaltic strictureplasty (SSIS), performed to prevent short bowel syndrome, in a patient with ischemic enteritis caused by strangulated intestinal obstruction. SSIS is useful for preserving the intestinal absorptive function in patients with a long narrowed bowel loop caused by ischemic change. To our knowledge, this is the first report of the successful treatment of a long stricture resulting from ischemic enteritis, achieved by performing SSIS.

Adrenomedullin (AM) is highly expressed in various cancer cell lines, suggesting a possible association with cancer growth. In the present study, we examined the expression and/or concentration of AM, its related peptide, adrenomedullin2/intermedin (AM2/IMD) and their receptors in human colorectal cancer and the surrounding normal tissue. In addition, we assessed the correlation between the expression of AM and AM2/IMD with that of vascular endothelial growth factor (VEGF)-A and matrix metalloproteinase (MMP)-9. Using a specific immunoradiometric assay, we found that AM concentrations were 2-11-fold higher in colorectal cancer tissues than in the surrounding normal tissues. Moreover, real-time quantitative RT-PCR showed that the expression levels of preproAM (+548%), preproAM2/IMD (+2674%), calcitonin receptor-like receptor (CLR) (+518%), receptor activity modifying protein (RAMP)2 (+281%), RAMP3 (+178%), VEGF-A (+277%) and MMP-9 (+864%) mRNAs were significantly higher in cancer tissues than in the surrounding normal tissues, and there was a positive correlation between the gene expressions of MMP-9 and preproAM (r=0.352; p=0.005), but not with preproAM2/IMD (r=0.041, p=0.406). Both AM and AM2/IMD immunoreactivity were detected mainly within cancer cells, whereas MMP-9 immunoreactivity was mostly seen in the surrounding stroma. These findings suggest that AM produced in colorectal tumors acts in concert with MMP-9 in the stroma to contribute to the pathogenesis of colorectal cancer.

症例は63歳の男性で，右季肋部痛，黄疸を主訴に来院した．血清総ビリルビン値は9.8mg/dlと上昇，画像検査で胆嚢と胆管内に石灰化物質を認め胆嚢総胆管結石と診断した．内視鏡的経鼻胆道ドレナージにて減黄を行った後に胆嚢摘出術および経胆嚢管的結石除去術を施行した．摘出標本では胆嚢内に泥状の石灰乳胆汁を認め，頸部には1cm大のビリルビンカルシウム結石が嵌頓していた．総胆管内から除去した物質も化学分析で石灰乳胆汁であり，これが閉塞性黄疸の原因と考えた．石灰乳胆汁は胆嚢管の閉塞で生成されるが，この閉塞の原因がビリルビンカルシウム石で，かつ胆管内の石灰乳胆汁による閉塞性黄疸を合併していた報告は，我々の渉猟しえたかぎりではなかった．本症例ではビリルビンカルシウム結石が胆嚢頸部に嵌頓し胆嚢内に石灰乳胆汁が発生，その後に頸部の結石の嵌頓が解除され石灰乳胆汁が一部総胆管内に移行し，閉塞性黄疸を来したと思われた．

今回われわれは極めて稀な男性副乳癌の1症例を経験したので報告する．症例は58歳，男性．2006年より右腋窩に母指頭大の腫瘤を自覚し，2008年初旬より増大傾向となった．同年9月に皮膚科を受診し，副乳癌が疑われ，当科に紹介された．CTでは右腋窩に内部が一部不均一に造影される5.5×3.5×4.0cmの腫瘍を認めた．FDG-PET/CTでも腫瘍のみに異常集積を認め，他部位からの悪性腫瘍のリンパ節・遠隔転移は否定的であった．生検ではER，PgR陽性の腺癌の像を認めた．手術は腋窩郭清を伴う腫瘤切除術を施行し，遺残なく切除可能で，周囲のリンパ節への転移は認めなかった．摘出標本では腫瘍周囲に固有乳腺と連続しない乳腺組織の存在を確認し，免疫組織化学染色ではER，PgR，gross cystic disease fluid protein-15（GCDFP-15）陽性，CK7，CK20，CEA，p63は陰性であり，副乳癌と診断した．術後補助療法としてTamoxifenを継続し，術後28カ月の現在，無再発生存中である．

Background: GC33 is a recently developed monoclonal antibody against human glypican-3 (GPC3), which is significantly upregulated in hepatocellular carcinoma (HCC). GC33 recognizes a GPC3 ectodomain and shows significant antitumour activity in vivo. Thus, humanized GC33 antibody may be a promising tool for treating HCC having cell surface GPC3 expression. Aims: This study aims to determine the specificity, subcellular localization and prognostic impact of GPC3 immunoreactivity detected by GC33 in HCC clinical specimens. Methods: Immunohistochemical analysis was performed for 194 cases of resected HCC and prognostic analysis was performed for 185 eligible cases. Two antigen retrieval methods (autoclave and protease pretreatments) were used for immunohistochemistry and compared. The immunoscore system reflecting circumferential membranous GPC3 immunoreactivity was developed using either the autoclave or protease methods. The GPC3 mRNA level was analysed by quantitative real-time reverse transcription-polymerase chain reaction. Results: GC33 immunostaining after autoclave is a sensitive method and revealed the GPC3 expression (≥20% of tumour cells) in the majority (77%) of HCC samples tested. Alternatively, protease pretreatment showed lower sensitivity, but was superior for evaluating the intensity and subcellular localization of GPC3. Correlation between immunoscores and the GPC3 mRNA level was also confirmed. Subsequent clinicopathological analysis revealed worse prognoses in HCC patients with circumferential membranous GPC3 immunoreactivity. For HCC patients with hepatitis C virus (HCV) infection in particular, the high membranous GPC3 immunoreactivity was an independent prognostic factor for disease-free survival. Conclusions: Circumferential membranous GPC3 immunoreactivity in HCC indicates poorer prognosis particularly in patients with HCV infection.

The aim of this study was to investigate the effect of various bile acids on hepatic type I 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) activity in vitro. The rat liver microsome fraction was prepared and 11beta-HSD1 activity was assayed using cortisol and corticosterone as substrates for the enzyme reaction. The substrate and various concentrations of bile acids were added to the assay mixture. After incubation, the products were extracted and analyzed using high-performance liquid chromatography. All bile acids tested except deoxycholic acid and 7-keto bile acids inhibited the 11beta-HSD1 enzyme reaction to some degree. Ursodeoxycholic acid inhibited the activity less than cholic, chenodeoxycholic, and lithocholic acids. Deoxycholic acid and 7-keto bile acids did not inhibit, but enhanced the enzyme activity. Inhibitions of dehydrogenation by corticosterone were weaker than those by cortisol. Kinetic analysis revealed that the inhibition of 11beta-HSD1 was competitive. The inhibition of 11beta-HSD1 by bile acids depended on the three-dimensional structural difference in the steroid rings and the presence of the 7alpha-hydroxy molecule of the bile acids was important for the inhibition of rat hepatic 11beta-HSD1 enzyme activity. These results suggest that bile acid administration might modulate 11beta-HSD1 enzyme activity.

A 41-year-old man without clinical symptoms was referred for treatment of an enlarging retroperitoneal tumor. Enhanced computed tomography showed a well-defined and heterogeneously enhanced tumor, 4 cm in size, in the dorsal portion of the pancreas. A low-density nodule was detected in the left adrenal gland, 10 mm in diameter. Retroperitoneal sarcoma and nonfunctional left adrenal tumor were suspected, and surgical treatment was performed. During excision of the retroperitoneal tumor, blood pressure was extremely elevated when the tumor was compressed. Blood pressure normalized after excision of the tumor; thus, a diagnosis of paraganglioma was favored over that of retroperitoneal sarcoma. The left adrenal gland was resected together with the adrenal tumor. Microscopically, the tumor cells of the retroperitoneum had round to oval nuclei, and abundant granular amphophilic cytoplasm proliferated in nest-like fashion. Extra-adrenal retroperitoneal paraganglioma was considered, and the adrenal tumor was diagnosed as cortical adenoma. In patients with retroperitoneal tumor, even in the absence of clinical symptoms, we should keep in mind the possibility of extra-adrenal paraganglioma.

PURPOSE: Side-to-side strictureplasty is a useful procedure for preserving the bowel in patients with Crohn’s disease. However, bowel resection is required in some patients, and diseased proximal bowel and disease-free distal bowel exist after resection. We performed a modified new technique called side-to-side-to-end strictureplasty. METHODS: Four patients with Crohn’s disease underwent this procedure. After resection of the diseased bowel that was not suitable for strictureplasty, side-to-side strictureplasty was performed with use of the proximal diseased loop. Thereafter, the distal end of the side-to-side stricture was anastomosed to the distal disease-free bowel in a side-to-side-to-end manner. RESULTS: The length of the small intestine requiring surgical intervention was 69.8 ± 26.4 (mean ± standard deviation) cm, and the length of the small intestine necessitating resection was 31.8 ± 12.6 cm. Side-to-side stricture was performed by use of 48.8 ± 20.2 cm of the diseased proximal bowel, which was anastomosed to the disease-free distal bowel. Intra-abdominal abscess, which was not associated with this procedure, was observed in one patient, but was treated by drainage. The recoveries of all four patients were uneventful, without recurrence, after a follow-up of 21.5 ± 16.2 months. CONCLUSIONS: Side-to-side-to-end strictureplasty may be a useful procedure when diseased proximal bowel and disease-free distal bowel are present after bowel resection in patients with Crohn’s disease.

Solitary necrotic nodule of the liver is a rare nonmalignant lesion of unknown etiology. It is defined as a nodule with a completely necrotic core enclosed by a hyalinized fibrotic capsule containing elastic fiber. We report a 74-year-old woman with a solitary necrotic nodule of the liver that mimicked metastasis from a previous rectal adenocarcinoma. She was referred to us for an asymptomatic liver nodule in segment 8 that had increased in diameter from 5 to 15 mm over the past 8 months. Ultrasonography showed a well-defined, oval, hypoechoic mass, and computed tomography showed a hypodense area without contrast enhancement except for a ring-like enhancement during hepatic arteriography. Magnetic resonance imaging revealed a mass that was hypointense on T1-weighted imaging and slightly hyperintense on T2-weighted imaging. The patient underwent hepatectomy of segment 8. The resected specimen contained an oval nonencapsulated nodule with firm and gritty consistency and a well-defined margin. Histologic findings were compatible with those of solitary necrotic nodule. Clinicians should recognize the existence of this lesion as one of the differential diagnoses of metastatic liver nodule. Solitary necrotic nodules can change size, and when enlarged, differentiation from metastasis is extremely difficult.

Surgery is one of the most effective treatment modalities for hepatocellular carcinoma (HCC). However, surgery is stressful and it is not clear whether surgery is suitable for elderly HCC patients. This issue is becoming increasingly important as the number of elderly HCC patients rises. Adequacy of surgery for elderly HCC patients has been discussed in 18 reviewed reports that retrospectively compared surgical outcomes between elderly and younger patient groups. Although deterioration of liver function and that of other organs is greater in the elderly than in younger patients, many reports demonstrated no difference between groups. We review, interpret and summarize the published reports that address surgery for elderly HCC patients as well as disclose contemporary surgical strategy and discuss issues requiring further investigation.

Antigen binding to the B-cell receptor (BCR) of pre-mature B lymphocytes induces their apoptotic cell death, but binding to the BCR of mature B lymphocytes triggers activation and proliferation. Binding to pre-mature B lymphocytes is thought not only to function as a mechanism to exclude B-cell clones that possess the ability to react with self-antigen, but also to act as a defense mechanism in auto-immune diseases. Cross-linking of BCR of pre-mature B-cell lines, including the chicken DT40 cell line, with anti-immunoglobulin IgG induces apoptotic cell death. Treatment with phorbol 12-myristate 13-acetate/ionomycin, which mimics BCR stimulation, is used to study intracellular signal transduction of B lymphocytes. Here, by analyzing the E2A-deficient DT40 cell line, E2A(-/-), we show that E2A deficiency prevents certain levels of apoptotic cell death mediated by BCR signaling. In addition, E2A deficiency-linked BCR signaling controls the mimicked pre-mature B-cell apoptosis by PMA/ionomycin through elevated survivin plus inhibitor of apoptosis 2 levels, and reduced caspase-3 and caspase-8 activities, resulting in increased amounts of ICAD (inhibitor of caspase-activated DNase), compared with those in the presence of E2A, followed by reduction of DNA fragmentation. These findings will contribute to the resolution of molecular mechanisms of negative selection of B cells and also auto-immune diseases.

膵頭十二指腸切除術後の門脈狭窄により発達した側副血行路からの消化管出血に対して，門脈内ステント留置が有効であったまれな1例を報告する．症例は49歳の男性で，2003年6月膵頭部癌に対し亜全胃温存膵頭十二指腸切除術を施行した．術後補助化学放射線療法を追加，以後再発なく経過良好であった．2005年6月腹痛を伴う下血を認め，大腸憩室炎出血の診断で右半結腸切除術を施行したが，その後も下血を認め10月に再入院となった．門脈本幹の狭窄と肝管空腸吻合部周囲に静脈瘤を伴う側副血行路の発達を認め，小腸内視鏡で肝管空腸吻合部近傍の小腸粘膜に静脈瘤と潰瘍病変を認めた．門脈狭窄による消化管出血と診断し，経皮経肝門脈造影下に門脈狭窄部へ金属ステントを留置，側副路への血流は消失し，下血は認めなくなった．ステント留置後3年経過したが消化管出血なく門脈血流も良好で健在である．

今回われわれは，鼠径ヘルニアによる続発性大網捻転症の1例を経験したので報告する．症例は53歳，男性．右鼠径部痛を主訴に当院を受診した．右鼠径ヘルニア嵌頓を認め，整復は不可能であった．また右側腹部に自発痛，圧痛を認めた．腹部CTで右側横行結腸尾側に渦巻状の層構造を認め，その遠位側の大網は浮腫状の変化を示し，拡張した右鼠径管に連続した．右鼠径ヘルニア嵌頓および続発性大網捻転症疑いの診断で緊急手術を行った．外鼠径ヘルニアの嵌頓で，大網が索状となりヘルニア嚢に癒着していた．癒着部は時計回りに4回捻転しており，末梢側の一部に壊死を認めた．中枢側の大網に壊死を認めなかった．癒着し捻転していた壊死部大網の切除を行い，メッシュプラグ法で鼠径ヘルニアは修復した．術後8日目で退院，大網の浮腫によると思われる右側腹部痛は術後3週ほど続いたが自然に軽快した．

To examine whether vertical retrocolic duodenojejunostomy is superior to antecolic duodenojejunostomy with respect to gastric emptying in a prospective, randomized, controlled study of patients undergoing pylorus-preserving pancreaticoduodenectomy (PpPD).Thirty-five patients undergoing PpPD between March 2005 and July 2007 were enrolled in the study. All provided informed consent. During PpPD, the patients were randomly assigned to either the antecolic (antecolic group, n = 17) or vertical retrocolic route (vertical retrocolic group, n = 18) just before the reconstruction. Each patient ingested (13)C-acetate in a liquid meal before surgery and on postoperative day (POD) 30. Gastric emptying variables (Tmax, T1/2) were determined and compared between groups.Clinical delayed gastric emptying, defined as an inability of patients to take in an appropriate amount of solid food orally by POD 14, was found in 1 of 17 patients (6%) in the antecolic group and in 4 of 18 patients (22%) in the vertical retrocolic group, but the difference was not significant (P = 0.34). Tmax and T1/2 on POD 30 were prolonged in both groups in comparison to preoperative levels, but no significant difference was found between the two groups. Follow-up examinations revealed that gastric emptying had recovered to the preoperative level by POD 30 in approximately 80% of the patients, regardless of the reconstruction route.Vertical retrocolic duodenojejunostomy does not seem to offer an advantage with respect to gastric emptying.

To clarify the characteristics of hepatocellular carcinoma (HCC) with bile duct invasion, we retrospectively analyzed clinical features and surgical outcome of HCC with bile duct invasion (b(+) group, n = 15) compared to those without bile duct invasion (b(-) group, n = 256). In the b(+) group, four patients (27%) showed obstructive jaundice, and a diagnosis of bile duct invasion was obtained preoperatively in seven patients (47%). The levels of serum bilirubin and carbohydrate antigen 19-9 were significantly higher in the b(+) group. Macroscopically, confluent multinodular type and infiltrative type were predominant in the b(+) group (P = 0.002). Microscopically, capsule infiltration (P = 0.040) and intrahepatic metastasis (P = 0.013) were predominant in the b(+) group. Portal vein invasion was associated significantly with the b(+) group (P = 0.004); however, the frequency of hepatic vein invasion was similar (P = 0.096). The median survival after resection was significantly shorter in the b(+) group than in the b(-) group (11.4 vs. 56.1 months, P = 0.002), and eight of 11 intrahepatic recurrences in the b(+) group occurred within 3 months after surgery. HCC with bile duct invasion has an infiltrative nature and a high risk of intrahepatic recurrence, resulting in poor prognosis.

In enterostomy for extremely low-birth-weight infants (1000 g), the technique of anchoring the intestine for a stoma to the abdominal wall is very difficult because of the small size and fragile nature of the intestine. Here we describe a novel technique for intestinal anchoring in such infants.In our approach to enterostomy, the intestine is anchored only by a strip of gauze packed into the subcutaneous space. No suturing is performed. The efficacy of this technique was evaluated in 21 infants with less than 1000 g of body weight who have intestinal perforation or obstruction.Two patients (9.5%) had complications that were related to the enterostomy. The complications were parastomal and intrastomal intestinal prolapse, both of which were treated successfully by reoperation. Eighteen patients (86%) survived to closure of the enterostoma.Intestinal anchoring with gauze is an easy and effective technique for enterostomy in extremely low-birth-weight infants and can be applied in selected cases.

Hepatocellular carcinoma (HCC) frequently metastasizes to the adrenal glands. The surgical strategy for HCC associated with bilateral adrenal gland metastasis is complicated because of the possibility of both postoperative hepatic failure and adrenal insufficiency. We herein report a patient with HCC with synchronous bilateral adrenal gland metastasis that was treated successfully with a two-stage operation. A 58-year-old man with HCC (12 cm in diameter) in the right lobe of the liver and bilateral adrenal gland tumors (right, 4 cm in diameter; left, 5 cm in diameter) was admitted to our hospital. Extended right hemihepatectomy and right adrenalectomy were performed simultaneously. The postoperative course was uneventful. Three months after this operation, left adrenalectomy was performed via a retroperitoneal approach. Hydrocortisone supplement was given, and the postoperative course was again uneventful. No recurrence was observed during the 10-month follow-up period. Two-stage surgery is a safe treatment option for giant HCC with synchronous bilateral adrenal gland metastasis.

外傷性肝細胞癌破裂の報告は16例とまれであり, 経験した1例に文献的考察を加え報告する. 症例は69歳の男性で, 交通事故で腹部を打撲し近医にショック状態で搬送された. 腹部CTで肝S8の肝細胞癌 (hepatocellular carcinoma; 以下, HCC) 破裂による出血性ショックと診断され, 緊急血管造影検査およびTAEを施行された. TAE後は腹膜播種やviableなHCCを認めなかったが, 7か月後の腹部CTで, TAE治療による腫瘍壊死部周囲に癌再発を認め手術を行った. 大網がHCC破裂部を覆うように横隔膜と肝臓に癒着しており, 肝S8亜区域切除と横隔膜合併切除を施行した. 術中腹腔内洗浄細胞診は陰性であった. 病理組織学的検査所見ではTAEで壊死に陥ったHCCの周囲にviable lesionを認めた. 術後問題なく14日目に退院した.骨転移を認めたが放射線治療し, 術後8か月の現在健在である.

膵癌(浸潤性膵管癌)の生存率は, Gemcitabineの使用により改善してきている. 今回, 教室における切除, 非切除膵癌例で化学療法および化学放射線療法の有用性を検討した. 1992年から2006年までに経験した140例の膵癌を対象とした. 切除例は41例でそのうち切除時遠隔転移と肉眼的に癌遺残を認めた8例, 上皮内癌1例の9例を除いた32例を切除群, 非切除99例を非切除群とし, 各群で治療の有無における予後を比較した. 切除群で術後補助療法を施行した群と施行しなかった群の術後3年生存率はそれぞれ47%と19%, 3年無再発率は48%と20%で術後補助療法群で有意に良好であった. 非切除例でも1年生存率は26%と6%で, 治療を施行した群が有意に良好であった. 膵癌では, 積極的な根治的外科切除に加えて術後補助療法を行うことによってさらに予後が改善し, 非切除膵癌でも化学療法を中心とした治療により予後の延長を認め, その有用性が示された.

Curative resection is the only treatment for biliary tract cancer that achieves long-term survival. However, patients with advanced biliary tract cancer have only a limited prognosis even after radical surgical resection. Thus, to improve the longterm results, the early detection of biliary tract cancer and subsequent cure seem to be essential. The purpose of this study was to review the literature concerning the risk factors for cancerous and precancerous lesions of the biliary tract, and prophylactic surgery for these factors. It has been reported that pancreaticobiliary maljunction (PBM) with bile duct dilatation is a risk factor for gallbladder cancer and bile duct cancer, while PBM without bile duct dilatation is a risk factor for gallbladder cancer. Thus, in the former group, a prophylactic excision of the common bile duct and gallbladder should be recommended, while in the later group, a prophylactic cholecystectomy without bile duct resection may be the appropriate surgical procedure. It has also been reported that primary sclerosing cholangitis (PSC) is a risk factor for cholangiocarcinoma. Patients with PSC often develop advanced cholangiocarcinoma with a poor prognosis. In patients with PSC, therefore, strict follow-up should be recommended. Adenoma and dysplasia have been regarded as precancerous lesions of gallbladder cancer. A polypoid lesion of the gallbladder that is sessile, has a diameter greater than 10 mm, and /or grows rapidly, is highly likely to be cancerous and should be resected. Although gallstones seem to be closely associated with gallbladder cancer, there is no evidence of a direct causal relationship between gallstones and gallbladder cancer. Thus, a cholecystectomy is not advised for asymptomatic cholecystolithiasis. Controversy remains as to whether adenomyomatosis of the gallbladder and porcelain gallbladder are associated with gallbladder cancer. With respect to ampullary carcinoma, adenoma of the ampulla is considered to be a precancerous lesion. This article discusses the risk factors for cancerous and precancerous lesions of the biliary tract and prophylactic treatment for these factors.

極めてまれな胃原発顆粒細胞腫の2切除例を経験したので報告する. 症例1は40歳の男性で, 主訴は胃検診での異常. 内視鏡検査で胃底部大彎側に直径約1.5cm大の大臼歯様の粘膜下腫瘍を認め, 生検で顆粒細胞腫と診断された. 悪性が否定できないため腹腔鏡下胃楔状切除術を施行した. 症例2は42歳の女性で, 主訴は心窩部痛. 内視鏡検査で胃体下部小彎側に直径約1.5cm大の粘膜下腫瘍を認めた. カルチノイドを否定できなかったため小開腹下胃楔状切除術を施行した. 切除標本の病理組織学的検査所見では2症例とも腫瘍は粘膜下層に存在し, 細胞質内に小胞巣や束状構造を伴う明瞭な顆粒を有し, これらの細胞質内顆粒はPAS陽性, 免疫組織染色でS-100蛋白陽性で, 顆粒細胞腫と診断した. 本邦報告例は自験2例を含め34例とまれな疾患であり, 文献的考察を加え報告する.

はじめに:当科で経験した腹部外科手術症例について，年齢別，緊急・待期手術別，併存疾患別に術後合併症発生率と術後30日以内死亡率を検討し，90歳以上の高齢者の手術における問題点を検討した．対象:2003年4月から2006年3月までの3年間に腹部手術を行った1,534例を対象とし，うち80歳代が240例，90歳以上の超高齢者は52例であった．結果:90歳以上の超高齢者群では，90歳未満群と比べて女性が多く，併存疾患を有する率も高率で，術後合併症発生率は44％と90歳未満の20％と比べ有意に高値であった．90歳以上の超高齢者群における術後死亡率は9.6％と，79歳以下と80～89歳の2群の死亡率と比較して高値を示し，待期・緊急手術両方とも90歳以上の超高齢者群で有意に高率であった．特に，術前併存疾患がある場合と術後合併症発生例において，超高齢者群で術後死亡率が有意に高かった．多変量解析で超高齢者の術後死亡に影響する有意な要因は，術後呼吸器合併症であった．考察:90歳以上の超高齢者の手術で，術前併存疾患を伴う症例や術後合併症を伴う症例では術後死亡率が高く，慎重な手術適応と術後管理を要するものと考えられた．

Long-term postoperative survival and prognostic factors were examined retrospectively in patients with hepatocellular carcinoma (HCC) with serum hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCVAb) and in those without virus infection. Subjects were 265 consecutive HCC patients treated surgically at one institution during the period 1990 to 2006. Postoperative survival was analyzed and compared between HBsAg-positive (B-HCC), HCVAb-positive (C-HCC), and hepatitis B- and C-negative (NBNC-HCC) patients. Prognostic factors for overall and recurrence-free survival were also analyzed. Overall and recurrence-free survival rates were significantly higher in the NBNC-HCC group than in the C-HCC group. Significant prognostic factors for overall survival identified by univariate and multivariate analyses were age, serum alkaline phosphatase (ALP) level, tumor multiplicity, portal vein invasion (Vp), hepatic vein invasion (Vv), and operative blood loss in the B-HCC group; serum albumin level, ALP level, tumor size, and Vv in the C-HCC group; and tumor multiplicity in the NBNC-HCC group. Significant factors for recurrence-free survival were age, ALP level, tumor multiplicity, Vp, and operation time in the B-HCC group; ALP level, prothrombin time, tumor size, Vv, and width of the surgical margin in the C-HCC group; and age, tumor size, tumor multiplicity, and Vp in the NBNC-HCC group. Thus, postoperative survival and prognostic factors in cases of HCC differ according to the presence of serologic viral markers.

Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized entity representing a spectrum of benign and malignant neoplasms of the pancreas. Preoperative distinction between benign and malignant IPMNs remains difficult. Reported predictive factors for malignancy are size of the main pancreatic duct, cystic neoplasm, and mural nodule. We report herein the case of a 50-year-old woman in whom a large mural nodule (30 mm) in the dilated main pancreatic duct (16 mm in diameter) was detected by ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography. Because the large mural nodule and dilatation of the main pancreatic duct were also detected by endoscopic ultrasonography (EUS) and intraductal ultrasonography (IDUS), the main-duct IPMN was considered to have malignant potential. Thus, pylorus-preserving pancreaticoduodenectomy with lymph node dissection was performed. The resected intraductal tumor appeared polypoid with a broad stalk and comprised a proliferation of mucin-containing columnar epithelial cells with papillary structures without malignant features. The final diagnosis was intraductal papillary mucinous adenoma of the pancreas. The size of the mural nodule and the final diagnosis in this case suggest that the introduction of a novel molecular-biological approach might be necessary for the precise preoperative diagnosis of main-duct IPMN and adequate surgical treatment.

Modification of transcription factors by anticancer agents plays an important role in both apoptotic and survival signaling. Here we report that both DNA topoisomerase I and II inhibitors such as SN-38 and etoposide, but not cisplatin, 5-fluorouracil or actinomycin D, can induce phosphorylation of the transcription factor Sp1. Furthermore, DNA topoisomerase inhibitors were shown to transactivate GC-box-dependent promoters such as the SV40 and vascular endothelial growth factor promoters. The phosphorylated form of Sp1 was detectable within 30 min of etoposide treatment and was greatly diminished by the presence of the PI3K inhibitor wortmannin and by DNA-dependent protein kinase (DNA-PK) knockdown. We also confirmed that the phosphorylated form of DNA-PK was increased by treatment with both etoposide and SN-38. Taken together, these findings demonstrate a novel genomic response to anticancer agents that induce Sp1 phosphorylation, and might contribute to tumor progression and drug resistance.

The aim of this study was to evaluate the results of our series of 90 operations for gallbladder carcinoma according to the Japanese Society of Biliary Surgery (JSBS) classification system and to clarify the appropriate surgical strategy for advanced gallbladder carcinoma based on the depth of primary tumor invasion and lymph node metastasis. Generally, only a surgical resection can achieve a prognostic improvement of the advanced gallbladder carcinoma. The survival of patients with this neoplasm depends strictly on the depth of histological primary tumor invasion and lymph node metastasis. A retrospective analysis was conducted on 90 patients from 1990 to 2004 who underwent a surgical resection of gallbladder carcinoma. The factors influencing survival were examined. Thirty-nine patients with palliative treatment (not resected cases), which was diagnosed as T3 or T4 by preoperative imagings, were also included in this study. The significance of the variables for survival was examined by the Kaplan-Meier method and the log-rank test followed by multivariate analyses using Cox's proportional hazard model. Portal invasion, lymph node metastasis, the surgical margin (+ vs. -) and the final curability (fCurA, B vs. C) were all found to be independent prognostic factors in the multivariate analysis. In pT2 gallbladder carcinoma, a better survival was achieved in an aggressive surgical approach, in order of a S4a+S5 hepatic resection, an extended cholecystectomy and a cholecystectomy. In pT3 and pT4, although radical extended surgery did not provide the opportunity for good survival even after lobectomy of the liver, the survival of patients with curative surgery was statistically better than in those without curative surgery. In addition, the nodal involvement of pN1 to pN2 was better than that with pN3. A S4a+S5 hepatectomy, therefore, appears to be adequate for the treatment of pT2 gallbladder carcinoma. Even in patients with pT3 and pT4 gallbladder carcinoma, long-term survival can be expected by an operation with a tumor-free surgical margin. The role of radical surgery, however, is considered to be limited in patients with pN3 lymph node metastasis.

Background: Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a small nuclear protein abundantly expressed in the gastrointestinal epithelium. However, its functions remain unknown. Aims: To investigate the expression and localisation of H2RSP in normal, injured and neoplastic human intestinal tissue. Methods: Immunohistochemical examination and in situ hybridisation for H2RSP were performed using normal and diseased intestinal specimens. Its subcellular localisation and effects on the cellular proliferation and invasiveness were examined using cultured cells. Results: In the normal intestine, H2RSP was observed in the nuclei of surface epithelial cells and this nuclear localisation was impaired in regenerating epithelium. In vitro, the nuclear translocation of H2RSP was observed along with increasing cellular density, and an overexpression of H2RSP resulted in a reduced growth rate and enhanced invasiveness. H2RSP expression was down regulated in well-differentiated colorectal adenocarcinomas. However, a marked up regulation of the cytoplasmic H2RSP immunoreactivity was observed in cancer cells at the invasive front. These cells showed low MIB-1 labelling, an enhanced p16 expression and nuclear β-catenin. The number of H2RSP-positive cells in the invasive front of well-differentiated adenocarcinomas was considerably higher in the cases with lymph node metastases than in node-negative ones. Conclusion: In the normal intestine, the nuclear accumulation of H2RSP is a marker of differentiated epithelial cells. Although H2RSP was down regulated in colorectal adenocarcinomas, a paradoxical up regulation was observed in actively invading carcinoma cells. H2RSP immunoreactivity at the invasive front may serve as a marker of invasive phenotype of well-differentiated colon cancers.

下血を主訴とし, 術前血管造影検査と病変部へのコイルの留置が出血源の診断および術中の病変同定に有用であった, 稀な小腸Dieulafoy血管奇形の1切除例を経験したので報告する. 症例は44歳, 男性. 繰り返す多量の下血と血圧低下を主訴に近医に入院したが, 消化管の造影検査, 内視鏡検査, 腹部CTでも原因不明で紹介入院となった. 腹部血管造影検査で小腸の末梢の血管に血管外漏出を認め, コイルを留置して緊急手術を施行した. 術中遠位空腸に腫瘤様病変を認め, さらに透視下で塞栓したコイルを確認することで出血部位を同定し, 病変部の小腸部分切除を行った. 摘出標本で小さな赤色の隆起性病変を認め, 病理組織検査で病変の粘膜下に異常血管を認め, 粘膜面で破裂していた. 小腸のDieulafoy血管奇形の破裂による下血と診断した. 原因不明の消化管出血では, Dieulafoy血管奇形など稀な小腸病変が原因である可能性に注意を払う必要があると考えられた.

慢性膵炎にともなう膵石症は難治性疼痛と膵機能の低下を示す場合が多い．今回，体外衝撃波結石破砕療法（ESWL）単独で治療した膵石症22例を対象に治療効果と平均3年（0.5-8年）の追跡結果を検討した．11例で完全砕石，10例で不完全砕石，1例で破砕効果を認めず，結石破砕率は95.5%で完全砕石率は50%であった．疼痛緩和率は95.5%で，疼痛の完全寛解率は81.8%であった．主膵管狭窄を有する場合や結石が大小多発している場合，完全砕石率が有意に低かった．偶発症は急性膵炎と急性胆嚢炎の2例でいずれも保存的治療で軽快した．膵の内·外分泌機能は治療前後で有意な変化を認めなかった．完全砕石例では結石の再発を認めなかった．完全砕石11例では疼痛は全例消失したが，一方不完全砕石10例中8例でも疼痛は消失した．ESWLは単独治療でも結石破砕効果，症状緩和効果が高く膵石症に対する有効な治療法であることが示唆された．

症例は21歳, 男性. ビルの3階より転落し, 踵より着地後にしりもちをついて転倒した. 仙骨レントゲンでは第2および第3仙骨が骨折し, 第3仙骨以下は前方に転位していた. また右仙骨孔に沿って縦骨折がみられた. 入院時には肛門周囲の皮膚感覚低下, 便の貯留感覚低下, 便・ガス失禁があった. 受傷後6, 14日目の直腸肛門内圧検査では, 随意収縮圧は認めなかった. 受傷後32日目にS2-4の全周性神経除圧術を施行, 受傷後49日目には随意収縮圧は4.9mmHgと若干の改善がみられた. 受傷後83日目には随意収縮圧は28.6mmHgと上昇, 固形便の失禁はなくなった. 受傷後200日目には随意収縮圧は53.8mmHgと改善し, ガス失禁もみられなくなった. 直腸肛門内圧測定で症状の改善に先行して肛門管随意収縮圧の改善をとらえることができ, 以後, 症状の改善を客観的に評価することができた.

症例は77歳の男性で, 褐色尿と皮膚掻痒感を主訴に近医を受診し, 閉塞性黄疸を指摘され紹介入院となった. 逆行性内視鏡的胆管膵管造影検査で下部胆管に不整な狭窄像を認め, 胆汁細胞診で腺癌が疑われた. 経内視鏡的胆道ステントによる減黄後, 幽門輪温存膵頭十二指腸切除術を行った. 腫瘍は下部胆管にあり, 2.3×1.5cm大の結節浸潤型で, 病変の粘膜面近傍では腺癌の像を呈したが, 浸潤部では紡錘形細胞の錯綜配列 (いわゆる紡錘形細胞癌) と血管肉腫類似の構造が混在する像を呈し, 肉腫様変化を伴った下部胆管癌と診断した. 手術半年後のCTで多発肝転移を認め, 化学療法を行ったが, 術後約1年6か月癌で死亡された. 肝外胆管に発生した肉腫様変化を伴う腺癌あるいは紡錘形細胞癌の報告は今まで15例と少なく, 本例を含めた臨床病理組織学的特徴を報告する.

Background The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract and ampullary carcinomas in 2008. Novel treatment modalities and handling of clinical issues have been proposed after the publication. New approaches for editing clinical guidelines, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, also have been introduced for better and clearer grading of recommendations. Methods Clinical questions (CQs) were proposed in seven topics. Recommendation, grade of recommendation and statement for each CQ were discussed and finalized by evidence-based approach. Recommendation was graded to grade 1 (strong) and 2 (weak) according to the concept of GRADE system. Results The 29 CQs covered seven topics: (1) prophylactic treatment, (2) diagnosis, (3) biliary drainage, (4) surgical treatment, (5) chemotherapy, (6) radiation therapy, and (7) pathology. In 27 CQs, 19 recommendations were rated strong and 11 recommendations weak. Each CQ included the statement of how the recommendation was graded. Conclusions This guideline provides recommendation for important clinical aspects based on evidence. Future collaboration with cancer registry will be a key for assessment of the guidelines and establishment of new evidence. Free full-text articles and a mobile application of this guideline are available via http://www.jshbps.jp/en/guideline/biliary-tract2.html.