Search

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.

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., (© 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

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., (© 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Gemcitabine is widely used for pancreatic, lung, and bladder cancer. However, drug resistance against gemcitabine is a large obstacle to effective chemotherapy. Nucleoside transporters, nucleoside and nucleotide metabolic enzymes, and efflux transporters have been reported to be involved in gemcitabine resistance. Although most of the resistant factors are supposed to be related to each other, it is unclear how one factor can affect the other one. In this study, we established gemcitabine-resistant pancreatic cancer cell lines. Gemcitabine resistance in these cells is caused by two major processes: a decrease in gemcitabine uptake and overexpression of ribonucleotide reductase large subunit (RRM1). Knockdown of RRM1, but not the overexpression of concentrative nucleoside transporter 1 (CNT1), could completely overcome the gemcitabine resistance. RRM1 knockdown in gemcitabine-resistant cells could increase the intracellular accumulation of gemcitabine by increasing the nucleoside transporter expression. Furthermore, a synergistic effect was observed between hydroxyurea, a ribonucleotide reductase (RR) inhibitor, and gemcitabine on the gemcitabine-resistant cells. Here we indicate that RR is one of the most promising targets to overcome gemcitabine resistance in gemcitabine-resistant cells with dual resistant factors., (Copyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.)

Purpose: 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., Methods: 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)., Results: 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., Conclusions: 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.

A 49-year-old woman visited a local hospital in October 2007 with complaint of fever and melena. Abdominal ultrasonography and abdominal computed tomography revealed an irregular mass in the lower abdomen, together with multiple masses in the liver. She was admitted because of anemia, and the high fever was determined to be an inflammatory response. Blood tests revealed elevated biliary enzyme levels. Percutaneous biopsy of the liver mass was performed, which revealed liver abscesses caused by Streptococcus constellatus. On abdominal angiography, the mass was suspected to be a tumor of the small intestine. In late November 2007, laparoscopy-assisted partial small bowel resection was performed, and pathological examination of the surgical specimen confirmed gastrointestinal stromal tumor (GIST) of the small bowel. Because reports of small intestinal GIST with liver abscesses caused by Streptococcus constellatus are rare, this case description could provide valuable information.

Background & Aims: The tumour cell microenvironment, which includes local oxygen saturation, pericellular pH and stromal cells, can modulate tumour progression. This study determined the prognostic impact of infiltrating tumour-associated macrophages and the expression of monocarboxylate transporter 4 (MCT4) and glypican 3 (GPC3) in hepatocellular carcinoma (HCC) clinical specimens., Methods: A total of 225 cases of resected HCC were subjected to immunohistochemical analyses of CD68, CD204, MCT4 and GPC3. Immunoreactivities and other common clinicopathological parameters were subjected to univariate prognostic analyses for overall survival (OS, n = 225) and disease-free survival (DFS, n = 222). All variables with prognostic impact were further analysed in multivariate analysis., Results: Increased intratumoural infiltration of CD204-positive or MCT4-positive macrophages suggested shorter OS (P = 0.015 or P = 0.001 respectively), but DFS was not altered. The GPC3 score (with an emphasis on circumferential immunoreactivity) was correlated with shorter OS and DFS. Aberrant expression of MCT4 in HCC cells was observed in a subset of HCC cases (21%, 47/225). In those cases, significantly poorer OS (P < 0.0001) and DFS (P = 0.0003) were observed, and there was a positive correlation with the intratumoural infiltration of CD204- or MCT4-positive macrophages and the GPC3 score. Multivariate analysis showed that aberrant MCT4 expression in HCC cells was an independent prognostic factor for shorter OS (P = 0.018) and DFS (P = 0.006) after resection of HCC., Conclusion: Aberrant expression of MCT4 in carcinoma cells serves as a novel, independent prognostic factor for HCC, indicating a poorer patient outcome., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: 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., Methods: 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., Results: 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 (P < 0.001), 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., Conclusions: 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.

Background: Although an antecolic duodenojejunostomy was reported to reduce post-operative delayed gastric emptying (DGE) compared with a retrocolic duodenojejunostomy after a pylorus-preserving pancreaticoduodenectomy (PPPD), the long-term effects of these procedures have rarely been studied. The aim of this prospective, randomized, clinical trial was to investigate the influence of the reconstruction route on post-operative gastric emptying and nutrition., Methods: Reconstruction was performed in 116 patients with an antecolic duodenojejunostomy (A group, n = 58) or a vertical retrocolic duodenojejunostomy (VR group, n = 58). Post-operative complications, including DGE, gastric emptying variables assessed by (13) C-acetate breath test and nutrition, were compared between the two groups for 1 year post-operatively., Results: The incidence of DGE was not significantly different between the procedures (A group: 12.1%; VR group: 20.7%, P = 0.316). At post-operative month 1, gastric emptying was prolonged in the VR versus the A group but not significantly so. At post-operative month 6, gastric emptying was accelerated significantly in the A versus the VR group. Post-operative weight recovery was significantly better in the VR versus the A group at post-operative month 12 (percentage of pre-operative weight, A group: 93.8 ± 1.2%; VR group: 98.5 ± 1.3%, P = 0.015)., Conclusions: A vertical retrocolic duodenojejunostomy was an acceptable procedure for the lower incidence of DGE and may contribute to better weight gain affected by moderate gastric emptying., (© 2013 International Hepato-Pancreato-Biliary Association.)

Purpose: 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., Methods: 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)., Results: 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., Conclusions: 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.

Background: 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., Methods: 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., Results: 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/m(2) 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., Conclusions: Male gender and BMI ≥22.5 were the independent preoperative predictive risk factors for POPF. We assume that when amylase is <750 IU/L, serum CRP is <20 mg/dL, and body temperature is <37.5 °C the drain can safely be removed, even if POPF is indicated.

Purpose: 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., Methods: 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., Results: 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., Conclusions: 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.

Background/aims: The aim of this study was to investigate the effect of 1α,25-dihydroxyvitamin D3 on proliferation of human pancreatic cancer cell lines and to identify related cell cycle regulatory proteins with antiproliferative effects., Methodology: Human pancreatic cancer cell lines SUIT-2 and its four sublines, and Panc-1, AsPC-1, and MiaPaCa-2 were treated with1α,25-dihydroxyvitamin D3. The number of cells was measured by the MTT method, and the cell cycle regulatory proteins were then analyzed by Western blotting., Results: Eight human pancreatic cancer cell lines expressed vitamin D receptor (VDR) mRNA. 1α,25-dihydroxyvitamin D3 inhibited proliferation of SUIT-2 and its sublines. We found p21 to be upregulated after 24 hours in S2-028, the cell line in which proliferation was most inhibited by 1α,25-dihydroxyvitamin D3., Conclusions: 1α,25-dihydroxyvitamin D3 inhibited proliferation of pancreatic cancer cells and is involved in the upregulation of cyclin-dependent kinase inhibitor p21.

Background: The incidence of surgical site infections (SSIs) is high after pancreaticoduodenectomy (PD)., Methods: We divided 116 consecutive patients who underwent PD into an early group (n = 58) and a later group (n = 58) according to time of surgery. In both groups, endoscopic retrograde biliary drainage was mainly employed for the patients with obstructive jaundice. In the later group, prophylactic antibiotics were selected according to the susceptibility of microorganisms isolated from SSIs in the early group. The incidence of SSIs was compared between the groups., Results: The background characteristics (including methods of preoperative biliary drainage and microorganisms in the bile obtained before or during operation) of the patients were not significantly different between the groups, except for the serum albumin level, which was lower in the later group than in the early group (P = 0.0026). The incidence of SSIs was significantly lower in the later group (24.1 %) than in the early group (46.6 %) (P = 0.0116). Belonging to the later group was one independent negative risk factor for SSI., Conclusions: Selection of prophylactic antibiotics on the basis of microorganisms isolated from SSIs in the early group contributed to the reduced incidence of SSIs in the later group after PD.

Purpose: To assess the role of positron emission tomography-computed tomography (PET-CT) and multidetector-row CT (MD-CT) in detecting the primary lesion and lymph node metastasis in patients with colorectal cancers., Methods: A collective total of 80 lesions resected from 77 patients were examined pathologically. We analyzed the significance of the standardized uptake value (SUV) and its relationship with the clinicopathologic findings of primary lesions and lymph node metastasis. The detectability of primary lesions and lymph node metastases on PET-CT images was compared with that on MD-CT images., Results: The detectability of primary lesions was better on PET-CT images than on MD-CT images (p = 0.0023). We observed no significant differences in the SUV with respect to staging, tumor grade, lymphatic or vessel invasion, and macroscopic type; however, primary tumor size analysis revealed that tumors larger than 3 cm had a higher SUV than those smaller than 3 cm. The sensitivity of PET-CT for detecting lymph node metastasis was lower than that of MD-CT, but the specificity of PET-CT was higher than that of MD-CT., Conclusions: The SUV of primary cancers tends to increase in proportion to tumor size. Although the value of PET-CT in detecting lymph node metastasis is limited, PET -positive lymph nodes can be considered metastatic.

Background/aims: Hepatocellular carcinoma (HCC) patients often have low platelet count (LPC). The aim of this study was to determine unique features of HCC patients with LPC., Methodology: HCC patients who underwent surgery were divided into two groups: LPC group (platelet count ≤100,000/mm³, n=84) and control group (platelet count >100,000/mm³, n=240). Surgical outcomes, risk factors for postoperative complications and prognostic factors were retrospectively compared., Results: HCC patients with LPC had poorer liver function, smaller tumors, less anatomical resection and more frequent postoperative liver failure than control group patients. Postoperative survival was not different between the two groups. Tumor invasion to the main branch or trunk of portal vein (Vp3, 4) was the only risk factor for postoperative substantial complications in the LPC group. Postoperative survival was worse in patients with tumor diameter ≥4 cm or multiple tumors and in those who underwent preoperative transcatheter arterial chemoembolization (TACE) in the LPC group by multivariate analysis. Among them, preoperative TACE were not prognostic factors in the control group., Conclusions: In HCC patients with LPC, Vp3, 4 patients should be carefully monitored after surgery and preoperative TACE is not recommended for long-term postoperative survival.

Background: Multifunctional 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., Methods: Immunohistochemical 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., Results: TRX-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., Conclusion: TRX-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., (© 2012 International Hepato-Pancreato-Biliary Association.)

Background/aims: Although fecal diversion is reported to improve the quality of life (QOL) of the patients with active perianal disease, the effect of the concomitant abdominal surgery was not well studied. The aim of this study was to investigate factors that impair postoperative QOL of patients with Crohn's disease., Methodology: A SF-36v2 questionnaire was mailed to patients who underwent abdominal operation between January 2001 and February 2007. Patients were also asked about the medical therapy they were receiving., Results: Data from 50 patients were analyzed. Univariate analyses revealed that patients with active perianal disease had lower scores for role physical, bodily pain and social functioning than did patients without it. Social functioning and role emotional scores were lower in patients older than 40 years than in those younger. The physical component summary score was significantly affected in patients with active perianal disease. Fecal diversion had no effect on QOL after abdominal surgery for Crohn's disease. Multivariate analysis showed that the physical component summary score was significantly lower in patients with active perianal disease than in patients without it., Conclusions: Active perianal disease is an important factor that impairs QOL in patients who have undergone surgery for intestinal Crohn's disease.

Background/aims: The aim of this study was to investigate the effect of thrombin and the thrombin receptor protease-activated receptor (PAR)-1 on adhesion of human pancreatic cancer cell lines to extracellular matrices (ECMs) and to identify related integrins with these effects., Methodology: Human pancreatic cancer cell lines SUIT-2 and its four sublines, and Panc- 1, AsPC-1 and MiaPaCa-2 were treated with thrombin, PAR-1 agonist TRAP-6, PAR-1 antagonist SCH79797, or anti-integrin ±vβ3, ±vβ5 and β1 monoclonal antibodies. Cells were incubated for 45 minutes on micro titer plates that were pre-coated with ECMs (fibronectin, laminin, vitronectin, type IV collagen). The number of adherent cells was measured by the MTT method., Results: Eight human pancreatic cancer cell lines expressed PAR-1. Thrombin significantly enhanced adhesion of SUIT-2 and its sublines and MiaPaCa-2 to vitronectin, especially in the SUIT-2 subline S2-007. We obtained similar results on S2-007 cells through treatment with TRAP-6. However, SCH79797 inhibited the effect of thrombin. Furthermore, anti-integrin β1 antibody conspicuously inhibited 1U/mL thrombin-induced enhancement of adhesion to vitronectin., Conclusions: Thrombin significantly enhanced adhesion of pancreatic cancer cells to vitronectin through PAR- 1 depending on the presence of integrin β1. Suppression of thrombin action by anti-integrin β1 antibody will become a useful therapy against pancreatic cancer.

Background: This study aimed to verify diagnostic criteria and severity assessment of the Tokyo Guidelines for acute cholangitis., Methods: We re-examined whether acute cholangitis was concomitant with gallstones according to the Tokyo Guidelines in 248 patients with choledocholithiasis. Our conventional diagnoses based on physician decision were compared with diagnoses from the Tokyo Guidelines. Problems with severity grade criteria were also evaluated., Results: In total, 53 cases of acute cholangitis were determined by using the Tokyo Guidelines, including three false-negative and seven false-positive cases (acute cholecystitis or pancreatitis was concomitant with choledocholithiasis). Sensitivity, specificity, and accuracy were 94%, 96%, and 96%, respectively. Forty of the 53 patients underwent biliary drainage (mean interval between admission and drainage, 1.4 days). Severity grades were mild in 10, moderate in 30, and severe in 13 patients. Of these 13 patients with severe disease, 2 had chronic renal failure, 1 had liver cirrhosis, and 1 had severe acute pancreatitis and liver cirrhosis. No patients died, irrespective of severity grade., Conclusions: Acute cholangitis should be carefully diagnosed when other inflammatory disease is concomitant with choledocholithiasis. A few patients have absolute acute cholangitis even when they do not meet Tokyo Guidelines diagnostic criteria. Classification into mild or moderate grade using the Tokyo Guidelines is difficult when early biliary drainage is routinely performed. When determining severity grade, clinicians must distinguish between organ dysfunction associated with cholangitis itself and that associated with the underlying/concomitant disease. Apart from a few problems like these, the Tokyo Guidelines are mostly acceptable for the diagnosis and management of acute cholangitis.

Background/aims: Delayed gastric emptying (DGE) is a specific, worrisome complication after pancreaticoduodenectomy (PPPD), whereas subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) that excises the pylorus ring seems to be effective in reducing DGE. This study compared gastric emptying and nutritional status between PPPD and SSPPD over 1 year., Methodology: From June 2003 to December 2007, 41 patients (PPPD: 33, SSPPD: 8) were enrolled in this study to evaluate differences in gastric emptying and nutritional status at 1, 3, 6, 9 and 12 months after pancreaticoduodenectomy. Gastric emptying was evaluated by 13C-acetate breath test. Nutritional status (body weight, serum levels of total protein, albumin and total cholesterol) was similarly assessed., Results: At 1 month, gastric emptying evaluated at T1/2 (half-emptying time) was significantly prolonged in the PPPD but not in the SSPPD compared to the preoperative level. Thereafter, T1/2 was decreased and showed function significantly better preserved at 3, 6 and 12 months after PPPD than after SSPPD. Body weight recovery was significantly better at 6 and 12 months after PPPD than after SSPPD. Other nutritional parameters were better preserved in the PPPD during 1-year follow-up., Conclusions: PPPD seems to be a more suitable surgical procedure than SSPPD in regard to gastric emptying and nutritional status.

This study examined the efficacy and tolerability of docetaxel(DOC)in combination with epirubicin(EPI)as the first-line treatment for patients with advanced and recurrent breast cancer. A total of 56 female patients with metastatic breast cancer not previously treated for metastatic disease received DOC(60mg/m²)and EPI(60mg/m2)on day 1 every 3 weeks. The patient characteristics included a median age of 53 years. Advanced disease was present in 86% of patients, and recurrent disease was found in 14%; 3 or more metastatic sites had been diagnosed in 38% of patients, and 59% patients were ER+. The median number of courses administered was 6. The median dose intensity was 18. 7mg/m²week for DOC and EPI, and the relative dose intensities were 93. 5%and 93. 3%, respectively. The clinical responses included a complete response in 5%, a partial response in 54%, and stable disease in 33% of patients, with a disease control rate of 92%. The progression-free survival was 78. 3%, and the overall survival was 91. 9% at 1 year. Grade 3/4 toxicities included neutropenia in 82%, leukopenia in 71%, febrile neutropenia in 16%, anorexia in 9%, and anemia in 7%of the patients. Neither congestive heart failure nor toxic death occurred. The D and E combination with doses of 60mg/m2 is an active and generally well-tolerated regimen that can be used as first-line chemotherapy for patients with metastatic breast cancer.

Background/aims: The aim of this study was to clarify the role of bile duct resection without hepatectomy (hilar resection) in hilar cholangiocarcinoma., Methodology: We retrospectively compared surgical results for hilar cholangiocarcinoma between 8 patients treated with hilar resection and 21 patients treated with hepatectomy., Results: All hilar resections were performed for Bismuth type I or II tumors with T2 or less lesions, whereas hepatectomy was done for type III or IV tumors excluding one type II tumor. R0 resection was equally achieved in both groups (62.5% in hilar resection group and 76.2% in hepatectomy group, p=0.469) and overall 5-year survival rates were comparable (21.9% vs. 23.6%, p=0.874). With respect to gross tumor appearance, R0 resection was achieved in all patients with papillary tumor in both groups with the excellent 5-year survivals (100% vs. 100%). In patients with nodular and flat tumors, R0 resection was achieved less frequently in the hilar resection vs. hepatectomy group (50% vs. 77.8%) mainly due to failure to clear the proximal ductal margin, resulting in poorer 5-year survival (0% vs. 18.7%)., Conclusions: Hilar resection may be indicated for papillary T1 or 2 tumors in Bismuth type I or II cholangiocarcinoma.

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.

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Since serum anti-aquaporin-4 (AQP4) antibody/neuromyelitis optica (NMO)-IgG has been detected as a specific biomarker for NMO), new diagnostic criteria have been proposed. Recently, a rare coexistence of NMO and myasthenia gravis (MG) has been documented. Here, we provide further evidence of the association of these 2 immunologic disorders and review the literature., Case Report: A 60-year-old woman, who had a history of optic neuritis at age 43, developed longitudinally extended transverse myelitis (LETM). She had repeated optic neuritis and longitudinally extended transverse myelitis attacks, which have been treated by corticosteroid pulse therapy. She was diagnosed as having definite NMO, because serum anti-aquaporin-4 antibody was positive. She had also been suffering from generalized MG since age 30 and underwent thymectomy at age 40. There have been 14 patients with NMO associated with MG, most of whom developed NMO years after thymectomy. Our patient is the seventh patient with seropositive NMO who underwent thymectomy for MG., Conclusions: The coexistence of MG with thymectomy and seropositive NMO suggests an etiopathogenic link between these 2 disorders but remains underrecognized by neurologists. Neurologists should consider this possible association when encountering atypical presentations of either MG or NMO.

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background/aims: To investigate the efficacy of infliximab for complicated perianal Crohn's disease with special reference to maintenance therapy., Methodology: Between June 2002 and April 2009, 20 patients (15 men and 5 women, aged 31.4±2.9 years old (mean ± standard error)) with complicated fistulizing anal Crohn's disease underwent seton placement. For the induction therapy, intravenous infusion of infliximab was given 3 times after surgical treatment. Thereafter, infliximab was given every 8 weeks as maintenance therapy. Patients were followed-up for 31.8±4.2 months after the first infliximab infusion. The number of the infliximab treatments given was 13.6±2.5., Results: After induction therapy, complete response (CR) was observed in 8 patients (40%), partial response (PR) in 9 and progress disease (PD) in 3. With (n=17) or without (n=3) maintenance therapy following the induction therapy, CR was observed in 15 of 20 patients (75%). Of the 17 patients who received maintenance therapy, CR was of observed in 13 patients, of whom 7 patients showed PR or PD before maintenance therapy., Conclusions: Seton drainage and infliximab therapy is effective in the patients with fistulizing perianal Crohn's disease. Maintenance infliximab therapy might be effective in patients with perianal Crohn's disease.

Solid pseudopapillary neoplasm (SPN) of the pancreas, most commonly found in young female subjects, is a rare neoplasm with low potential for malignancy. We report an unusual case of a 66-year-old male patient who had a simultaneous malignant SPN and an intraductal papillary mucinous adenoma (IPMA) of the pancreas. The patient was admitted to our department for the evaluation of the main solid tumor with calcification and small multilocular cystic lesions apart from the main tumor in the pancreatic head. We performed pylorus-preserving pancreaticoduodenectomy to treat the calcified tumor and multilocular cystic lesions. The diagnosis of malignant SPN was confirmed on the basis of histological invasion to the adjacent structures. The separate cystic lesions were diagnosed as a branch-type IPMA. The synchronous occurrence of IPMA and SPN in the present case did not demonstrate that there were tumors maintained through the common abnormal Wnt signaling pathway by immunohistochemical study. To our knowledge, this is the first known case of synchronous SPN and IPMA of the pancreas.

Only two cases of rectal giant inflammatory polyposis with ulcerative colitis have been reported in the English literature and both concern children. This is the first report of a case of localized giant inflammatory polyposis of the rectum in an adult with indeterminate colitis. A 71-year-old man underwent sigmoidectomy due to stenosis of the sigmoid colon. Final histological diagnosis was indeterminate colitis. Three years following the first operation, a rectal tumor with giant polyposis was observed, and abdominoperineal resection was performed. Macroscopic and microscopic examination indicated a localized giant inflammatory polyposis of the rectum.

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., (© 2010 John Wiley & Sons A/S.)

Objective: Predicting liver functional reserve is important before partial hepatectomy. However, it is difficult to predict using morphologic imaging modalities, such as CT and MRI. In this study, we assess the usefulness of galactosyl human serum albumin (GSA) scintigraphy in predicting liver function recovery., Methods: We performed 99mTc-GSA scintigraphy before operation in 56 patients. Each patient was administered 185 MBq of 99mTc-GSA by intravenous injection. Serial images were taken immediately after the administration for 40 min. SPECT images were obtained to make a functional map. We calculated the functioning parameter residual GSA-Rmax (GSA-RL) using analysis software developed by Dr.N. Shuke. In addition, we compared GSA-RL with the morphological parameter residual liver volume (RLV-CT) calculated by conventional CT and serum albumin (Alb) or cholinesterase (ChE). We analyzed the correlation between imaging parameters and the postoperative recovery periods of serum albumin (r-Alb) and cholinesterase (r-ChE) and the values at 1 and 3 months for serum albumin (1M-Alb, 3M-Alb) and cholinesterase (1M-ChE, 3M-ChE)., Results: We found significant correlations between GSARL and r-Alb, r-ChE, 1M-Alb, 3M-Alb, 1M-ChE and 3M-ChE, but not between RLV-CT and the same parameters., Conclusion: The GSA-RL calculated by 99mTc GSASPECT was a useful parameter for predicting postoperative liver function recovery that should be implemented before partial hepatectomy.

Meckel diverticulum is one of the causes of gastrointestinal bleeding; however, preoperative conclusive diagnosis is very difficult even with the use of various radiologic modalities. The development of double-balloon enteroscopy enables us to diagnose various bleeding source, including Meckel diverticulum, in the small intestine. We herein report a case of bleeding Meckel diverticulum, diagnosed by double-balloon enteroscopy and treated successfully by laparoscopic surgery, and review of the literature.

Background: Hepatocyte growth factor activator inhibitor type 1 (HAI-1), one of the Kunitz-type serine protease inhibitors, has an important role in cancer progression through regulation of the activity of hepatocyte growth factor. HAI-1 is expressed in hepatocellular carcinoma (HCC) to various degrees. Investigation of the relationship between HAI-1 expression and clinicopathological features of HCC may contribute to improved treatment outcomes for HCC through understanding the mechanism of tumor progression or improvement in the prediction of tumor malignancy., Methods: The study included 121 HCC patients treated surgically from 1996 to 2005. We performed immunohistological examination for HAI-1 in resected HCC specimens by use of anti-human HAI-1 monoclonal antibody. Clinicopathological features, including postoperative overall survival (OS) and disease-free survival (DFS) rates, were compared between the immunoreaction positive and negative groups., Results: The immunoreaction positive group included 38 patients (31%), and the negative group included 83 patients (69%). OS and DFS rates were significantly higher in the HAI-1 negative group than in the positive group. HAI-1 positivity related to multiplicity, vascular invasion, and characteristics of advanced tumor stage. In multivariate analysis, expression of HAI-1 was a significant independent prognostic tumor factor., Conclusions: Expression of HAI-1 in HCC cells is associated with poor prognosis for HCC patients. HAI-1 may be important in HCC progression and may be a new prognostic factor for HCC.

A 57-year-old woman was diagnosed as having rectal cancer. A barium enema study showed the apple-core sign at the rectosigmoid colon, and colonoscopy revealed an encircled ulcerated tumor. A laparoscope-assisted resection of the rectum was planned; however, the rectal cancer directly invaded the uterus body. The operation was converted to open surgery. An elastic hard tumor suspected of being peritoneal dissemination at the peritoneal reflection was detected and excised together with the rectum below the peritoneal reflection. A histological examination of this tumor revealed that cystic glands lined by nonmucinous columnar epithelial cells were seen on the serosal side and were embedded in the proper muscle of the rectum. This tumorous lesion was diagnosed as endometriosis.

Background: Total parenteral nutrition (TPN) increases the risk of severe infectious complications such as septic shock, which are believed to be the result of a breakdown of intestinal barrier function and subsequent bacterial translocation. Toll-like receptors (TLRs) comprise a family of membrane proteins that serve as pattern recognition receptors for a variety of microbe-derived molecules and stimulate innate immune responses to microbes. Alteration of intraepithelial lymphocytes (IELs) to TPN administration has been studied extensively. However, few studies have examined the effect of TPN administration on intestinal TLRs. We hypothesized that the expressions of intestinal TLRs and cytokines may change with TPN administration and a lack of enteral feeding., Materials and Methods: TPN-treated mice and sham operation mice (control) were killed at 10 days after operation. mRNA expression of intestinal cytokines and TLRs were analyzed with reverse transcription-polymerase chain reaction (RT-PCR) methods. Change in IEL populations was analyzed with flow cytometry., Results: RT-PCR showed varying expression levels of TLRs at different sites on the small intestine and colon. TLR4, TLR5, TLR7, and TLR9 mRNAs were up-regulated in response to TPN administration, particularly in the distal small intestine., Conclusions: Up-regulation of TLRs in intestine in response to TPN administration and a lack of enteral nutrition may be associated with an increased risk of septic shock due to bacterial translocation caused by Interferon gamma-mediated intestinal epithelial cell apoptosis., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

The protein products of the Dickkopf (DKK) genes are antagonists of Wnt glycoproteins, which participate in tumor development and progression by binding to frizzled receptors. In this study, the expression of DKK-1 was analyzed in a panel of 43 human cultured carcinoma cell lines. DKK-1 expression was consistently and significantly upregulated in pancreatic carcinoma cell lines. Low level of DKK-3 expression was also seen. In contrast, the expression of DKK-2 and -4 was not detectable in most pancreatic carcinoma cell lines. The overexpression of DKK-1 was confirmed in surgically resected human pancreatic cancer tissues, in which the mRNA level was evaluated in paired samples from cancerous and noncancerous pancreatic tissues. In ductal adenocarcinomas (23 cases), DKK-1 mRNA levels were significantly upregulated compared to corresponding noncancerous tissues in a statistically significant level. To test the biological role of DKK-1 in pancreatic carcinoma cells, we performed a knockdown of DKK-1 in SUIT-2 human pancreatic adenocarcinoma cell line and S2-CP8, its metastatic subline, using a retroviral short hairpin RNA expression vector. DKK-1 knockdown resulted in reduced migratory activity of SUIT-2 in vitro. The in vitro growth rate and Matrigel invasion were also suppressed by DKK-1 knockdown in S2-CP8 cells. Collectively, the evidence suggests that, despite of its presumed antagonistic role in Wnt signaling, DKK-1 may have a role in the aggressiveness of pancreatic carcinoma cells and could, therefore, serve as a novel biomarker of pancreatic cancer.

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., (Copyright 2009 Elsevier Inc. All rights reserved.)

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.

A 59-year-old man was admitted to our hospital for the treatment of gastric cancer with synchronous and multiple metastatic liver tumors. After total gastrectomy in February 2005, partial resection of the posterior segment of the liver was carried out in the next month. Pathological study of both the resected specimens showed moderately differentiated adenocarcinoma. The postoperative treatment with S-1 was initiated without any evidence of recurrence. However, CT scans showed recurrent multiple liver tumors after 4 courses of treatment with S-1. Subsequently, a combination chemotherapy of S-1 (80 mg/m(2) over day 1-14 with a 2-week rest) and paclitaxel (PTX) (120 mg/m(2), day 1 and 15) was applied. After 3 courses, CT scans showed reduced liver metastases, judged as a partial response(PR)on Response Evaluation Criteria in Solid Tumors (RECIST). However, metastatic liver tumors showed progressive disease (PD) after 7 courses of treatment. The treatment was changed to combination chemotherapy with S-1 (80 mg/m(2) over day 1-21 with a 2-week rest) and CPT-11 (80 mg/m(2) day, day 1 and 15) for 6 courses, but the legions showed PD. He was then treated with combined chemotherapy with S-1 (70 mg/m(2) over day 1-14 with a 1-week rest)and cisplatin (CDDP) (10 mg/m(2), day 1 and 8). However, his condition became worse and he was treated at the palliative care unit. There were no adverse effects greater than grade 4 throughout the treatment period, and his treatment was continued as an outpatient for more than two years. This case suggests that after failure of S-1 therapy, S-1 combination chemotherapy might be an effective treatment for recurrent gastric cancer.

Clinicopathological factors influencing the survival and the effect of chemotherapy with special reference to S-1 were retrospectively analyzed in 41 patients who underwent gastrectomy for stage IV gastric cancer. Significantly better outcomes were observed in patients with H0, P0 or M0 than those with H1, P1 or M1, respectively. Curability B surgery showed a significantly better result than curability C. A significantly better result was demonstrated in patients treated with S-1 alone than those treated with chemotherapy other than S-1 or in patients without chemotherapy. Multivariate analysis revealed that H0, M0 and chemotherapy with S-1 were significant and independent prognostic factors. Moreover, the patients treated with S-1 for more than 12 months showed a significantly better outcome than those treated with S-1 for less than 12 months. It is concluded that curative resection (curability B) and the longer period of postoperative chemotherapy with S-1 is the treatment of choice to improve the outcome of patients with stage IV gastric cancer.

Rationale: Surgical strategy for patients with hepatocellular carcinoma and portal vein tumor thrombus (PVTT) remains to be established., Methods: From 1990 to 2008, 48 hepatocellular carcinoma patients with PVTT detected by preoperative imaging underwent hepatic resection, and their clinical data were retrospectively analyzed. Possible prognostic factors for survival were analyzed with postoperative survival curves, and significant factors were determined by univariate and multivariate analysis. The frequency of postoperative severe complications was investigated for each prognostic factor., Results: Significant prognostic factors included patient age <60 years, serum total bilirubin (T-Bil) >0.8 mg/dl, serum aspartate aminotransferase >30 IU/L, serum alkaline phosphatase (ALP) >300 IU/L, tumor size >4 cm, PVTT in the main trunk (Vp4), and a surgical margin <1 mm by univariate analysis, and independent prognostic factors were serum T-Bil, ALP, and Vp4. No patient with Vp4 survived for more than 400 days after surgery, and frequency of postoperative severe complications in these Vp4 patients was significantly higher than in other Vp1-3 patients., Conclusion: Hepatic resection as a first-choice treatment should be carefully selected in patients with Vp4 unless emergent removal of the PVTT is required.

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.

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.

Background/purpose: 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)., Methods: 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., Results: 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., Conclusions: Vertical retrocolic duodenojejunostomy does not seem to offer an advantage with respect to gastric emptying.

An 80-year-old woman who had undergone both a cholecystectomy and an appendectomy presented with intermittent abdominal pain. Computed tomography (CT) revealed an encapsulated circumscribed cluster of jejunal loops in the left upper quadrant. The hernia orifice was adjacent to the left side of the superior mesenteric artery and vein. An upper gastrointestinal series also revealed a cluster of jejunal loops, suggesting the possibility of an internal hernia. Laparoscopic surgery was performed. The hernia orifice was found to be caused by abnormal adhesion between the transverse mesocolon and the jejunum mesentery. An adhesiotomy reduced the jejunum entrapped in the hernia. The hernia space was a large mesocolic fossa composed of transverse mesocolon and mesentery, continuing to the splenic flexure. The hernia was classified as a variant of paraduodenal hernia.

A 77-year-old woman with a complaint of itching was shown to have an elevated serum bilirubin level. She had no history of liver disease. Computed tomography and magnetic resonance cholangiopancreatography revealed a 17-mm-diameter cystic lesion obstructing the main hepatic duct at the hepatic hilum. Drip infusion cholangiographic computed tomography and endoscopic retrograde cholangiography showed that the cyst did not communicate with the biliary tree; thus, a peribiliary cyst was diagnosed. Cystectomy was performed, and the jaundice resolved. Peribiliary cysts are generally asymptomatic and rarely cause obstructive jaundice. They are usually multiple and caused by an underlying liver disorder with a poor prognosis. Our case suggests that peribiliary cysts can arise in healthy liver and cause symptoms. Cystectomy is the treatment of choice if the cyst is solitary.