Clinical trial on the efficacy and safety of NPC-15 for patients with xeroderma pigmentosum exaggerated sunburn reaction type: XP-1 study protocol for a multicentre, double-blinded, placebo-controlled, two-group crossover study followed by a long-term open study in Japan.

INTRODUCTION: Xeroderma pigmentosum (XP) is a rare intractable disease without a fundamental treatment, presenting with severe photosensitivity, freckle-like pigmented and depigmented maculae and numerous skin cancers before the age of 10 years without strict sun protection. About 70% of the patients exhibit extremely severe sunburn reactions and most of them develop neurological symptoms, including sensorineural hearing impairment and progressive peripheral and central nervous disorders beginning from childhood ages. In the preclinical study, we found that N-acetyl-5-methoxytryptamine was effective in suppressing skin tumour development in addition to improvement of auditory brainstem response in chronically ultraviolet-irradiated XP-A model mice. METHODS AND ANALYSIS: On the bases of the preclinical study, we conduct a clinical trial on the efficacy of NPC-15 for patients with XP with exaggerated sunburn reaction type by a multicentre, double-blinded placebo-controlled, two-group crossover study followed by a 52 weeks open study. ETHICS AND DISSEMINATION: Ethics approval is overseen by the Kobe University Institutional Review Board and Osaka Medical and Pharmaceutical University Institutional Review Board, and the study is conducted in accordance with the approved protocol. All participants will be required to provide written informed consent. Findings will be disseminated through scientific and professional conferences and peer-reviewed journal publications. The data sets generated during the study will be available from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: jRCTs051210181.

A randomized crossover pilot study comparing the efficacy of an auto-demand oxygen delivery system with that of a conventional demand oxygen delivery system in patients with chronic respiratory failure.

INTRODUCTION: : When using portable oxygen, a demand oxygen delivery system (DODS), which senses the beginning of inhalation and delivers a bolus of oxygen, is often used. However, conventional DODS may not supply sufficient oxygen when reduced tidal flow fails to trigger the flow sensor. Recently, "auto-DODS," which detects the negative pressure of inhalation and switches among 3 trigger sensitivity levels (standard, high, and extra high), has been developed to improve the efficacy of oxygenation. An auto-DODS can also supply pulsed-flow oxygen when it detects apnea, whereas a conventional DODS has only standard sensitivity. This randomized, open-label, crossover pilot study compared the performance of an auto-DODS with that of a conventional DODS. METHODS: : We recruited patients with chronic obstructive pulmonary disease (COPD) or interstitial pneumonia receiving long-term oxygen therapy. Interventions were performed on 2 different days for each participant. On each day, an auto-DODS or a conventional DODS were tested at rest for 30 minutes and during the 6-minute walk test. The primary outcome was mean oxygen saturation (SpO2). Secondary outcomes were the ratios of time for each sensitivity level and pulsed-flow oxygen when using the auto-DODS, total time desaturated below SpO2 90%, percentage of time desaturated below SpO2 90%, minimum SpO2, mean and maximum pulse rate, six-minute walk distance, recovery time after 6-minute walk test, modified Borg scale, comfort, and discomfort index. RESULTS: : When using the auto-DODS at rest, a high or extra high sensitivity level was observed in addition to standard sensitivity in 6 of 8 participants. During the 6-minute walk test, only standard sensitivity was observed in 6 participants. Mean SpO2 differences between the auto-DODS and conventional DODS at rest and during the 6-minute walk test were -0.6 [-4.5, 3.4] and 0.0 [-2.5, 2.5] ([95% confidence interval]), respectively, neither of which were significant (P = .73 and P = .99). There were no significant differences in secondary outcomes. There were no adverse events when using the auto-DODS. CONCLUSIONS: : This study showed that the auto-DODS did not show superiority in oxygenation either at rest or during exercise compared to a conventional DODS. The auto-DODS was shown to supply oxygen safely and detect inhalations with various trigger sensitivities.

Influence of the Retrocolic Versus Antecolic Route for Alimentary Tract Reconstruction on Delayed Gastric Emptying After Pancreatoduodenectomy: A Multicenter, Noninferiority Randomized Controlled Trial.

OBJECTIVE: This study aimed to determine whether retrocolic alimentary tract reconstruction is noninferior to antecolic reconstruction in terms of DGE incidence after pancreatoduodenectomy (PD) and investigated patients' postoperative nutritional status. SUMMARY OF BACKGROUND DATA: The influence of the route of alimentary tract reconstruction on DGE after PD is controversial. METHODS: Patients from 9 participating institutions scheduled for PD were randomly allocated to the retrocolic or antecolic reconstruction groups. The primary outcome was incidence of DGE, defined according to the 2007 version of the International Study Group for Pancreatic Surgery definition. Noninferiority would be indicated if the incidence of DGE in the retrocolic group did not exceed that in the antecolic group by a margin of 10%. Patients' postoperative nutrition data were compared as secondary outcomes. RESULTS: Total, 109 and 103 patients were allocated to the retrocolic and antecolic reconstruction group, respectively (n = 212). Baseline characteristics were similar between both groups. DGE occurred in 17 (15.6%) and 13 (12.6%) patients in the retrocolic and antecolic group, respectively (risk difference; 2.97%, 95% confidence interval; -6.3% to 12.6%, which exceeded the specified margin of 10%). There were no differences in the incidence of other postoperative complications and in the duration of hospitalization. Postoperative nutritional indices were similar between both groups. CONCLUSIONS: This trial could not demonstrate the noninferiority of retrocolic to antecolic alimentary tract reconstruction in terms of DGE incidence. The alimentary tract should not be reconstructed via the retrocolic route after PD, to prevent DGE.

Real-time navigation during hepatectomy using fusion indocyanine green-fluorescence imaging: protocol for a prospective cohort study.

INTRODUCTION: In-vivo fluorescence imaging techniques using indocyanine green (ICG) to identify liver tumours and hepatic segment boundaries have been recently developed. The purpose of this study is to evaluate the efficacy of fusion ICG-fluorescence imaging for navigation during hepatectomy. METHODS AND ANALYSIS: This will be an exploratory single-arm clinical trial; patients with liver tumours will undergo hepatectomy using the ICG-fluorescence imaging system. In total, 110 patients with liver tumours scheduled for elective hepatectomy will be included in this study. Preoperatively, ICG will be intravenously injected at a dose of 0.5 mg/kg body weight within 2 days. To detect liver tumours intraoperatively, the hepatic surface will be initially observed using the ICG-fluorescence imaging system. After identifying and clamping the portal pedicle corresponding to the hepatic segments, including the liver tumours to be resected, additional ICG will be injected intravenously at a dose of 0.5 mg/kg body weight to identify the boundaries of the hepatic segments. The primary outcome measure will be the success or failure of the ICG-fluorescence imaging system in identifying hepatic segments. The secondary outcomes will be the success or failure in identifying liver tumours, liver function indicators, operative time, blood loss, rate of postoperative complications and recurrence-free survival. The findings obtained through this study are expected to help to establish the utility of ICG-fluorescence imaging systems, and therefore contribute to prognostic outcome improvements in patients undergoing hepatectomy for various causes. ETHICS AND DISSEMINATION: The protocol has been approved by the Kobe University Clinical Research Ethical Committee. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: UMIN000031054 and jRCT1051180070.

Anatomical variations of liver blood supply in patients with pancreaticobiliary maljunction.

PURPOSE: Pancreaticobiliary maljunction (PBM) arises from a developmental abnormality during the embryonic period; thus, these patients may have anatomical variations of the liver blood supply, including aberrant vessels and unusual locations. METHODS: We reviewed retrospectively the vascular anatomy of 52 patients with PBM, who were seen between 1998 and 2013. RESULTS: There were 11 male patients and 41 female patients. Sixteen patients had bile duct type (C-P type) PBM, 35 had pancreatic duct type (P-C type) PBM, and one had complex type PBM. Thirty-three patients had biliary dilatation. Nine (17.3 %) patients had an aberrant (replaced or accessory) hepatic artery and 2 (3.8 %) had an aberrant portal vein. Among 39 patients evaluated by contrast-enhanced computed tomography, 8 (20.5 %) had their right hepatic artery positioned on the ventral side of the common bile duct. The presence of aberrant hepatic vessels was not related to the type of confluence, biliary dilatation, type of Todani classification, or associated biliary malignancies. CONCLUSIONS: The incidence of the right hepatic artery being located on the ventral side of the common bile duct may be higher in patients with PBM than the naturally occurring incidence of about 10 % in the general Japanese population.

Clinical significance of bile reflux into the pancreatic duct without pancreaticobiliary maljunction assessed by intraoperative cholangiography.

INTRODUCTION: Bile reflux into the pancreatic duct (BRPD) is sometimes demonstrated during intraoperative cholangiography (IOC) even in patients without pancreaticobiliary maljunction. However, the clinical significance of this finding in laparoscopic and open cholecystectomy is unclear. METHODS: Among 484 patients who underwent cholecystectomy (372 laparoscopic, 112 open), patients whose pancreatic duct was depicted in IOC were selected. The value of pancreatic amylase (p-amylase) of the gallbladder bile, histological changes, and the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) in the gallbladder mucosa were analyzed in patients with BRPD. The data were then compared to those in patients without BRPD whose gallbladder bile p-amylase was measured (control group, n = 20). RESULTS: The success rate of IOC was 93.6%. The rate of BRPD in laparoscopic and open cholecystectomy was 5.2% and 5.7%, respectively. The value of gallbladder bile p-amylase in patients with BRPD was significantly higher than in the control group (790.5 vs 14.0 IU/L, P = 0.034). The value of the PCNA labeling index in patients with BRPD was significantly higher than that of the control group (15.4% vs 4.1%, P = 0.0026). Among the 24 patients with BRPD, pathological changes in the gallbladder mucosa were detected in five (two hyperplasia, three metaplasia), but there was no correlation between the presence of pathological change and PCNA labeling index or gallbladder bile p-amylase. CONCLUSIONS: IOC could detect BRPD both in laparoscopic and open cholecystectomy at a similar rate. Patients with BRPD had high levels of gallbladder bile p-amylase and PCNA labeling index, findings similar to those in patients with pancreaticobiliary maljunction.

[Resection of Initially Unresectable Gallbladder Cancer with Multiple Liver Metastases after Chemotherapy with Gemcitabine plus Cisplatin].

A 61-year-old woman was referred to our hospital for surgery for gallstones. She was diagnosed as having gallbladder cancer after a detailed radiologic examination. At the first laparotomy, gallbladder cancer with bulky invasion to the liver and multiple liver metastases were observed. Gemcitabine plus cisplatin (GC) administration was chosen. After 7 administration of GC, we changed GC to gemcitabine alone due to blood toxicity. After 7 months of chemotherapy, although CT findings showed regression of the liver invasion and the liver metastases, the serum CA19-9 level gradually increased. Because there were no obvious distant metastases on detailed radiologic examination, we performed surgery for the primary lesion after obtaining informed consent. Pathological examination demonstrated fibrosis without viable cancer cells in the metastatic liver tumor. Gemcitabine was administered as post-operative adjuvant chemotherapy. Twelve months after surgery, there was no sign of recurrence.

Preoperative bile replacement improves immune function for jaundiced patients treated with external biliary drainage.

BACKGROUND: Although preoperative biliary drainage in jaundiced patients is controversial, external biliary drainage (EBD) is beneficial for infection control in patients with biliary cancers. When EBD is performed, additional bile replacement (BR) has the benefit of improving impaired intestinal barrier function, but the detailed mechanism remains unknown. We examined the effect of bile replacement on immune functions over the duration of BR in jaundiced patients. METHODS: Fifteen patients were enrolled into this prospective study. BR was started soon after the total serum bilirubin concentration reached 5.0 mg/dl and was continued for 14 days. Drained bile was given two times orally (2 × 100 ml/day). Concanavalin A (Con A)- and phytohemagglutinin (PHA)-stimulated lymphocyte proliferation and serum diamine oxidase (DAO) activity were measured before starting and during BR. Twenty patients with EBD and no BR were analyzed as a control group. RESULTS: Serum liver enzymes, prothrombin time-international normalized ratio (PT-INR), and responses to Con A and PHA gradually improved over the 14 days of BR, but percentages of lymphocytes and DAO levels did not. PT-INR, and Con A and PHA responses did not improve during EBD in the control group. PT-INR significantly decreased in patients with a greater fraction of their drained bile replaced. CONCLUSIONS: Our results indicate that preoperative BR using as large a quantity of bile as possible is useful for improving blood coagulability and cellular immunity in patients with EBD.

Establishment of a novel cell line from intraductal papillary neoplasm of the bile duct.

BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a novel and increasingly-occurring disease. Its characteristics remain uncertain because of the lack of an in vitro culture system. We established and characterized a novel cell line from a human IPNB. MATERIALS AND METHODS: We obtained tumor tissue from a surgical specimen from a patient with IPNB. Cells were primary co-cultured with mouse stromal cells in serum-free medium. Tumor characteristics were compared among the primary IPNB, established cell line, and xenograft. RESULTS: We successfully established an IPNB cell line. We temporary termed this cell line Kobe Bile Duct Cancer (KBDC)-11. Xenograft formed a tumor which had ductal structures and mucus production as the primary tumor did. Overexpression of p53, MUC staining pattern, and CD133 expression were common among the primary IPNB, KBDC-11, and the xenograft. CONCLUSION: This novel cell line established from IPNB exhibited the same features as IPNB and might contribute to studies of IPNB and its process of malignant transformation.

Factors affecting survival after resection of intrahepatic cholangiocarcinoma.

PURPOSE: This study aimed at assessing the prognostic factors of resection of intrahepatic cholangiocarcinoma (IHCC), which remain unclear. METHODS: Among 70 patients with IHCC, who were admitted to our hospital between 1998 and 2011, 45 (64 %) underwent resection and 25 had unresectable tumors. Univariate and multivariate analyses were conducted retrospectively to assess the factors influencing survival of the patients who underwent resection. RESULTS: The median survival times of the patients who underwent resection versus those who did not were 16 months versus 9 months, respectively (P < 0.001). Multivariate analysis identified residual tumor status (relative risk 4.12, P = 0.04) and pathological differentiation (relative risk 5.55, P = 0.04) as independent factors predicting survival. Patients who underwent R1 resection had a significantly higher rate of local recurrence than those who underwent R0 resection (P = 0.008). With R0 resection, there were no significant differences in patterns and rates of recurrence between patients with narrow (≤ 5 mm) versus wide (>5 mm) surgical margins. CONCLUSIONS: R0/1 resection and a well-differentiated tumor were found to be independent prognostic factors for long-term survival after IHCC resection. If R0 resection was achieved, the width of the negative surgical margin did not affect the patterns and rates of recurrence.

Curative resection of hilar cholangiocarcinoma in a 25-year-old woman: report of a case.

A 25-year-old woman was referred to our hospital with persistent upper abdominal pain. Preoperative imaging studies revealed a hilar bile duct stricture with portal venous encasement, and the patient underwent curative resection involving extended left hepatectomy and segmental portal vein resection. The pathological findings demonstrated a well-differentiated tubular adenocarcinoma of the bile duct with regional lymph node metastasis (stage IIIB according to the UICC TNM classification), as well as the overexpression of p53 proteins and the K-ras gene mutation in tumor cells. The patient has shown no evidence of recurrence in the 10 months since the operation. Although there are several reports of relatively young adults with cholangiocarcinoma, the majority of such patients demonstrate either an anomalous arrangement of the pancreaticobiliary duct system or primary sclerosing cholangitis. The absence of any morphological abnormalities in this patient's biliary system implicates de novo carcinogenesis as the most likely cause of the cholangiocarcinoma.

[Re-resection for recurrent intrahepatic cholangiocarcinoma].

INTRODUCTION: The benefits of re-resection for recurrent intrahepatic cholangiocarcinoma (IHC) are unknown. PATIENTS AND METHODS: We evaluated the comparative efficacy of different treatment schema for recurrent IHC following curative resection. RESULTS: Among 46 patients, 26 underwent R0 resection, while 20 underwent R1 resection. There were 13 cases of recurrence in R1 patients (65%), and 19 in R0 patients (61%). Recurrent IHC cases were divided into 3 groups based on the treatment received after recurrence: re-resection (n=5), chemotherapy (n=13), and best supportive care (BSC) (n=8). Survival times were evaluated for each group; median survival times (MSTs) after recurrence were 26, 14, and 4 months for the re-resection, chemotherapy, and BSC groups, respectively (p=0.030). Next, we examined the patients who only had intrahepatic recurrence; MSTs after recurrence for re-resection, chemotherapy, and BSC groups were 26, 14, and 5 months, respectively (p=0.0018). CONCLUSION: In recurrent IHC, survival time improves with re-resection or chemotherapy, when compared to BSC. In patients with intrahepatic recurrence only, re-resection is especially effective in prolonging survival.

[Long-term survivor of unresectable bile duct cancer complicated with sclerosing cholangitis treated with chemotherapy].

A 70-year-old woman was admitted to a near by hospital with complaints of epigastric pain and fever. Endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography (MRCP) revealed stenosis of the hilar bile duct and multiple stenoses in the intrahepatic bile duct; bile cytological analysis indicated adenocarcinoma. The levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were within normal limits. It was very difficult to evaluate the extent of tumor invasion; therefore, we concluded that the tumor was unresectable. The patient underwent systemic chemotherapy with gemcitabine. After 5 years, she developed obstructive jaundice and cholangitis. The patient underwent endoscopic retrograde biliary drainage (ERBD), with 3 incidents of cholangitis recurrence. Although systemic chemotherapy with gemcitabine was performed for a long time, she died 6 years after the initiation of chemotherapy. Gemcitabine was administered 140 times in total, with a total dose of 203.744 g.

Gallbladder bed pocket score as a preoperative measure for assessing the difficulty of laparoscopic cholecystectomy.

INTRODUCTION: Laparoscopic cholecystectomy (Lap-C) is a standard surgery for symptomatic gallbladder stones and acute or chronic cholecystitis. Resident surgeons often perform this operation early in their training, but they sometimes encounter difficulties for various technical reasons. Although encountering a gallbladder buried deep within the gallbladder bed is a common operative difficulty, literature on the subject scarcely exists. METHODS: Forty-two patients underwent Lap-C at our hospitals and were analyzed retrospectively. We defined the gallbladder bed pocket score (GBPS) as the maximum ratio between the height and width of the gallbladder bed measured based on multi-detector computed tomography (MDCT) images. GBPS and clinical factors were assessed in terms of their correlation with the time required for gallbladder dissection from the gallbladder bed. RESULTS: Of the 42 patients, 20 had histories of acute or chronic cholecystitis. The mean gallbladder dissection time was 14.9 min, and the mean GBPS was 0.43 in the coronal MDCT section and 0.56 in the sagittal section. The correlation coefficient between the GBPS and gallbladder dissection time was 0.40 (P = 0.01) in the coronal section and 0.38 (P = 0.02) in the sagittal section of the MDCT images. There was no statistically significant correlation between gallbladder dissection time and the surgeon's experience, patient's history of cholecystitis, gallstone size, or blood loss. However, GBPS > 0.4 predicted more difficult and prolonged dissection. CONCLUSION: GBPS is a useful tool for preoperatively predicting the time needed to dissect the gallbladder from the gallbladder bed during Lap-C. Cases with GBPS < 0.4 seem more suitable for resident surgeons who are performing gallbladder dissection early in their Lap-C training.

[A case involving long-term survival following bile duct cancer with para-aortic lymph node metastasis that was treated by multidisciplinary therapy].

Complete resection of advanced bile duct cancer is difficult due to the anatomical location of the tumor and invasion into other organs. Even if a complete resection is achieved, the survival rates of patients with bile duct cancer after surgery are lower as compared to those associated with other gastrointestinal tumors. Certain cases with para-aortic lymph node metastasis have a poor prognosis. In the present report, we describe a case involving long-term survival following bile duct cancer that was treated by multidisciplinary therapy (particle radiotherapy, surgical resection, chemotherapy). In the present case, we detected lymph node (LN) metastasis only in LN#16, but not in LN#13 or LN#17. We believe that particle radiotherapy, consisting of proton and carbon-ion, can be used to control the lymphatic metastasis around the pancreas head and hepatoduodenal ligament. Our findings suggest that particle radiotherapy can be a standard neoadjuvant therapy for bile duct cancer.

[A case of initially unresectable gallbladder cancer with surgical resection after chemotherapy with gemcitabine].

A 75-year-old woman was admitted to our hospital with elevated serum hepatic enzyme levels. After evaluation with imaging studies, she was diagnosed as having gallbladder cancer, which had invaded the liver and hepatic artery, with lymph node metastases. The tumor was considered unresectable, and the patient received chemotherapy with gemcitabine (GEM)alone. Six months later, computed tomography(CT)indicated shrinkage of the gallbladder tumor and disappearance of lymph node metastases. Surgical resection was planned. However, liver metastasis was suspected on the basis of macroscopic findings, and the patient underwent gallbladder bed resection. Pathological examination indicated that almost all of the tumor cells in the gallbladder were viable; however, there were no tumor cells in the liver nodule and lymph node. The postoperative course was uneventful. The patient received adjuvant chemotherapy with GEM and was alive without recurrence 17 months after tumor resection. Immunohistochemical analysis showed that 80.9% of the tumor cells were positive for CD133, a cancer stem cell marker. This case illustrates a possible relationship between cancer stem cells and chemoresistance.

[Three cases of recurrent bile duct cancer diagnosed and treated by double-balloon endoscopy].

Local recurrences often develop after the resection of bile duct cancer. Imaging modalities do not have sufficient sensitivity or specificity to enable the definite diagnosis of recurrent bile duct cancer, and it may be difficult to decide when to start chemotherapeutic treatment. It is difficult to obtain specimens by conventional endoscopy after Roux-Y biliary reconstruction. The double-balloon endoscope(DBE) has 2 balloons: one at the tip of the endoscope and the other at the over- tube. The 2 balloons are inflated alternately and the endoscope can move through the small intestine in a caterpillar-like manner. DBE simplifies the approach to Roux-Y choledochojejunostomy and to obtaining a pathological specimen. Moreover, endoscopic biliary drainage and cholangiography can be performed with the DBE. Recently, the DBE has enabled systemic chemotherapy to be started after obtaining pathological evidence of malignancy, as well as biliary drainage instead of percutaneous transhepatic biliary drainage in cases with recurrent bile duct cancers. Here, we present 3 cases of recurrent bile duct cancer diagnosed and treated by a DBE.

[A case of postoperative liver metastasis from pancreatic carcinoma treated with percutaneous isolated hepatic perfusion(PIHP)].

We report a case of postoperative liver metastasis arising from pancreatic carcinoma treated with a novel procedure that we developed-percutaneous isolated hepatic perfusion (PIHP). A 69-year-old man diagnosed with pancreatic body cancer(pT3, pN0, pStage III) was treated using distal pancreatectomy and adjuvant therapy with gemcitabine(GEM). Six months later, a metastasis to the medial segment of the liver was found using computer tomography(CT). The patient was treated by chemotherapy with S-1, but the liver metastasis grew, and we therefore employed PIHP as the third-line therapy, using 80 mg doxorubicin (DXR) and 62 mg mitomycin C (MMC). Six weeks after PIHP, the tumor marker carbohydrate antigen 19-9( CA19-9) had decreased from 44,469 to 4,268 U/mL, and the carcinoembryonic antigen(CEA) level decreased from 28.8 to 5.4 U/mL. Although the size of the carcinoma remained the same on CT, some cells had liquefied as a result of necrosis. However, the patient died about 1 year after PIHP due to the growth of liver metastasis, peritoneal metastasis, and local recurrence, reflected by a progressively increasing level of tumor marker. In this case, PIHP seemed to be ineffective due to local recurrence and peritoneal metastasis as well as early enlargement of liver metastasis. However, the reduction in tumor marker levels and the observed tumor necrosis, suggest that PIHP is a potentially effective and promising treatment for liver metastasis arising from pancreatic carcinoma.

[Long-term survival in 2 cases with unresectable hilar bile duct cancer and sclerosing cholangitis].

Case 1: A 69-year-old man was admitted to a nearby clinic due to upper abdominal pain. Computed tomography revealed stenosis of the hilar bile duct and dilation of the intrahepatic bile duct in both lobes of the liver. A percutaneous transhepatic biliary drainage tube was inserted in the right anterior segment branch, and an endoscopic naso-biliary drainage tube was inserted in the left hepatic duct. He was referred to our hospital because of suspected hilar bile duct cancer. Radiographic examination showed severe stenosis of the hepatic hilar duct and tapering of the entire intrahepatic bile duct. The extent of invasion could not be evaluated and we concluded that the tumor was unresectable. Although systemic chemotherapy with gemcitabine was performed, the patient died at 37 months after the start of chemotherapy. Case 2: A 70- year-old woman was admitted to a nearby hospital due to epigastric pain and fever. Endoscopic retrograde cholangiopancreatography revealed stenosis of the hilar bile duct and a wide range of multiple stenosis in the intrahepatic bile duct. Bile cytology showed adenocarcinoma. Therefore, we decided the tumor was unresectable. Systemic chemotherapy with gemcitabine was started. She is in good health 57 months after the start of chemotherapy.

Distinctive expression of CD133 between intraductal papillary neoplasms of the bile duct and bile duct adenocarcinomas.

AIM: Intraductal papillary neoplasm of the bile duct (IPNB), a novel entity of biliary disease, is recently advocated as the counterpart of pancreatic intraductal papillary mucinous neoplasm (IPMN) because both are in common with a large amount of mucin production and papillary growth. Based on our recent finding that expression of CD133, a cancer stem cell marker, is lacking in pancreatic IPMN, we herein focused on CD133 expression of IPNB in comparison with intrahepatic cholangiocellular carcinoma (IHCCC) or hilar bile duct cancer (HBDC). METHODS: Expression of CD133 protein was immunohistochemically determined in patients with IPNB (n = 7), IHCCC (n = 16) or HBDC (n = 8). In addition, morphological and immunohistochemical mucin expression patterns were characterized in IPNB, and clinicopathological features including prognosis were compared between IPNB and other biliary tumors. RESULTS: The IPNB group included significantly more females than the other two groups, and had a longer survival time. While no CD133 expression was observed in IPNB tumor, 16.4% of cancer cells in IHCCC and 17.2% of cells in HBDC expressed CD133. Among seven patients with IPNB, six (86%) were morphologically the pancreatobiliary type and four of six showed mucin expression pattern of the typical pancreatobiliary type (MUC1+/MUC2-/MUC5AC+). CONCLUSION: Loss of CD133 expression supports the hypothesis that IPNB is a counterpart of pancreatic IPMN with a differing carcinogenesis from conventional bile duct adenocarcinomas.