Diagnostic Ability and Safety of Repeated Pancreatic Juice Cytology Using an Endoscopic Nasopancreatic Drainage Catheter for Pancreatic Ductal Adenocarcinoma: A Multicenter Prospective Study.

Pathological examination is essential for the diagnosis and treatment of pancreatic ductal adenocarcinoma (PDAC). Moreover, a reliable pathological diagnosis is extremely important for improving prognosis, especially in early-stage PDAC. This study prospectively evaluated the usefulness of repeated pancreatic juice cytology (PJC) using an endoscopic nasopancreatic drainage (ENPD) catheter for the diagnosis of PDAC. We enrolled 82 patients suspected of having resectable PDAC, based on imaging studies, and judged the necessity for cytology. The diagnostic yield of up to six repeated PJCs and the incidence of complications, such as pancreatitis, was evaluated. A total of 60 patients were diagnosed with PDAC. The overall sensitivity and specificity were 46.7% and 95.5%, respectively. The cumulative positivity rate increased with the number of sampling sessions, reaching 58.3% in the sixth session. The sensitivity was significantly higher in the pancreatic head than in the pancreatic tail (p = 0.043). Additionally, it was 100% in four patients with a tumor size ≤10 mm. Pancreatitis occurred in six patients (7.3%), all of whom were treated conservatively. In the diagnosis of PDAC, repeated PJC using an ENPD catheter revealed a cumulative effect of sensitivity up to six times and an excellent diagnostic yield for small PDAC.

Clinical Analysis of Early-Stage Pancreatic Cancer and Proposal for a New Diagnostic Algorithm: A Multicenter Observational Study.

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging but essential for improving its poor prognosis. We established a multicenter study to clarify the clinicopathological features, and to propose new algorithm for early diagnosis of PDAC. Ninety-six patients with stage 0 and IA PDAC were enrolled from 13 high-volume centers. Overall, 70% of the patients were asymptomatic. The serum pancreatic enzyme levels were abnormal in half of the patients. The sensitivity of endoscopic ultrasonography (EUS) for detecting small PDAC was superior to computed tomography and magnetic resonance imaging (MRI) (82%, 58%, and 38%, respectively). Indirect imaging findings were useful to detect early-stage PDAC; especially, main pancreatic duct stenosis on MRI had the highest positive rate of 86% in stage 0 patients. For preoperative pathological diagnosis, the sensitivity of endoscopic retrograde cholangiopancreatography (ERCP)-associated pancreatic juice cytology was 84%. Among the stage IA patients, EUS-guided fine-needle aspiration revealed adenocarcinoma in 93% patients. For early diagnosis of PDAC, it is essential to identify asymptomatic patients and ensure close examinations of indirect imaging findings and standardization of preoperative pathological diagnosis. Therefore, a new diagnostic algorithm based on tumor size and imaging findings should be developed.

Two Cases of Atraumatic Chylous Ascites Characterized by Hypotriglyceridemia and Partially Managed with an Oral Fat-Free Elemental Diet.

Most cases of chylous ascites occur after surgery, but it also develops in nonoperative cases, although rarely. Such cases are often difficult to treat. In this study, we treated 2 cases of atraumatic chylous ascites, which were controlled by combining diuretic treatment with an oral fat-free elemental diet (Elental®, EA Pharma Co., Ltd., Tokyo, Japan). Elental can provide oral nutrition compatible with a lipid-restricted diet, which may be useful for control of chylous ascites. We report on these cases, including literature review-based considerations.

Evaluation of antibiotic use to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis and cholangitis.

BACKGROUND/AIMS: The purpose of this study was to evaluate the relationship between prophylactic antibiotic use and complications following endoscopic retrograde cholangiopancreatography (ERCP). METHODOLOGY: We retrospectively evaluated 605 consecutive patients who underwent ERCP in our hospital between September 2009 and November 2011. The antibiotic group included patients who underwent their procedure before October 2010, while the control group included patients after October 1, 2010, who did not receive antibiotics. We compared the incidence of postoperative pancreatitis and cholangitis between the groups. RESULTS: There were no significant differences in the backgrounds of the 304 control and the 301 antibiotic-treated patients. The incidence of post-ERCP pancreatitis was 4.9% in the control group and 4.3% in the antibiotic group (p = 0.72). The incidence of postoperative cholangitis was 2.0% in the control group and 1.7% in the antibiotic group (p = 0.99). Choledocholithiasis, pancreatic duct injection, and female gender were detected as significant risk factors for postoperative pancreatitis by multivariate analysis; sclerosing cholangitis and incomplete biliary drainage were significant risk factors for postoperative cholangitis. Even in cases with these risk factors, prophylactic antibiotic use did not influence the incidence of pancreatitis or cholangitis. CONCLUSION: Prophylactic antibiotics do not reduce the incidence of either pancreatitis or cholangitis following ERCP.

Occupational Radiation Exposure during Endoscopic Retrograde Cholangiopancreatography and Usefulness of Radiation Protective Curtains.

Objective. To evaluate the effectiveness of radiation protective curtains in reducing the occupational radiation exposure of medical personnel. Methods. We studied medical staff members who had assisted in 80 consecutive therapeutic endoscopic retrograde cholangiopancreatography (ERCP) procedures. Use of radiation protective curtains mounted to the X-ray tube was determined randomly for each procedure, and radiation doses were measured with electronic pocket dosimeters placed outside the protective apron. Results. When protective curtains were not used, the mean radiation doses to endoscopists, first assistants, second assistants, and nurses were 340.9, 27.5, 45.3, and 33.1 µSv, respectively; doses decreased to 42.6, 4.2, 13.1, and 10.6 µSv, respectively, when protective curtains were used (P < 0.01). When the patient had to be restrained during ERCP (n = 8), the radiation dose to second assistants without protective curtains increased by a factor of 9.95 (P < 0.01) relative to cases in which restraint was not required. Conclusions. During ERCP, not only endoscopists, but also assistants and nurses were exposed to high doses of radiation. Radiation exposure to staff members during ERCP was reduced with the use of protective curtains.

Characteristic Features of Cholangiocarcinoma Complicating Primary Sclerosing Cholangitis.

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is often complicated by cholangiocarcinoma (CCA); thus, early detection of CCA is an important way to improve PSC prognosis. METHODOLOGY: In a retrospective study, 23 cases of PSC were included. Seven cases were complicated by CCA (CCA group) and 16 cases were not (control group). Blood examinations, bile duct imagings from direct cholangiography, intraductal ultrasonography (IDUS) findings and pathological diagnosis results (bile juice cytology, brush cytology, and forceps biopsy) were referenced. RESULTS: Blood examinations showed that serum carbohydrate antigen 19-9 (CA19-9), total bilirubin, and aspartate aminotransferase were significantly higher in the CCA group, whereas cholangiography showed that the dominant stricture was significantly longer in the CCA group. No significant difference in the IDUS findings was observed between the 2 groups. Cholangioscopy enabled CCA diagnosis via identification of the papillary mucosa in sites other than the stricture. Forceps biopsy was the most useful pathological diagnostic technique, with a sensitivity of 86% and a specificity of 100%. CONCLUSIONS: The CA19-9 level and bile duct stricture morphology were useful for diagnosing CCA complicating PSC. Aggressive performance of cholangioscopy and pathological diagnostic techniques, such as brush cytology and forceps biopsy, are essential for identification.

[Malignant phyllodes tumor metastatic to the pancreas: a case report].

A woman in her 50s was admitted with obstructive jaundice due to a pancreatic mass. She had a history of a right breast phyllodes tumor treated with mastectomy 3 years previously. Diagnostic imaging (endoscopic ultrasonography (EUS), CT, and MRI) demonstrated a well-demarcated mass in the pancreatic head. EUS-FNA showed spindle shaped tumor cells. The pancreaticoduodenectomy specimen showed a malignant spindle cell tumor consistent with a metastatic malignant phyllodes tumor. In addition, immunohistochemical staining demonstrated that the staining pattern of pancreatic tumor was similar to that of the breast phyllodes tumor. Pancreatic metastases from breast phyllodes tumors have rarely been reported in the literature.

Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells.

Given the poor prognosis for cholangiocarcinoma, new and effective treatments are urgently needed. HMG-CoA reductase inhibitors (statins) reportedly exert anticancer effects in a variety of diseases, but there have been no reports of these effects in cholangiocarcinoma. In this study, we investigated the utility of statins for cholangiocarcinoma treatment. Proliferation suppression by pitavastatin and atorvastatin was investigated in the human cholangiocarcinoma cell lines HuCCT1 and YSCCC while changes in the cell cycle and intracellular signals were examined by FACS and Western blotting, respectively. Additive proliferation suppression by statins and pre-existing anticancer drugs was also investigated. HuCCT1 and YSCCC cell proliferation was dramatically suppressed by incubation with statins for 72 h or longer. Cell cycle analysis revealed a reduction in the G2M fraction and an increase in the sub-G1 fraction in statin-treated cells, while Western blotting showed increased levels of cleaved caspase-3 and a reduction in p-ERK. Furthermore, statins in combination with gemcitabine, cisplatin and 5-FU showed additive proliferation suppression. In this study, treatment of human cholangiocarcinoma cells with statins induced apoptosis via suppression of the classical MAPK pathway. Together, these results suggest that statins may be a new cholangiocarcinoma treatment option that could potentially enhance the anticancer effect of pre-existing anticancer drugs.

Expression of multidrug resistance-associated protein 2 is involved in chemotherapy resistance in human pancreatic cancer.

Despite the recent introduction of the new anticancer agents gemcitabine (GEM) and TS-1, as well as combination regimens such as GEM plus cisplatin (CDDP), pancreatic cancer treatment remains relatively ineffective. Both intrinsic and acquired resistance to chemotherapy are major roadblocks to the successful treatment of pancreatic cancer patients. The aims of this study were to examine the expression of multidrug resistance-associated proteins (MRPs) MRP1, MRP2 and MRP3 and to evaluate the correlation between MRP2 expression and CDDP resistance in human pancreatic cancer. Five human pancreatic cancer cell lines and several surgically resected pancreatic cancer tissues were subjected to reverse-transcriptase (RT)-PCR, real-time PCR and immunohistochemical analysis. While MRP1 and MRP2 mRNA was expressed in all cell lines, MRP3 mRNA was only detected in two cell lines. In resected pancreatic cancer tissues, only MRP2 mRNA was expressed and it was overexpressed compared with normal pancreatic tissues. MRP2 protein expression was observed in 77.5% (31/40) of cancer tissues, primarily in the cytoplasm of cancer cells, but was not observed in normal pancreatic tissue. Two CDDP-resistant pancreatic cancer cell line SUIT-2 variants, SUIT-2-CD3 and SUIT-2-CD4, were established by continuously administering 10 nM CDDP to SUIT-2 cell lines for 3 and 4 months, respectively. Incubation of these cells with CDDP in the presence of anti-MRP2 antibody or the MRP2 inhibitor MK-571 in a growth inhibition assay demonstrated that the CDDP-resistant variants were more resistant to CDDP than the parent cell line and this resistance was diminished by either anti-MRP2 antibody or MK-571. Moreover, RT-PCR and real-time PCR revealed that while induction of MRP2 mRNA expression was increased in CDDP-resistant compared with parent cells, MRP1 and MRP3 expression remained unchanged. These observations suggest that MRP2 may correlate to intrinsic and acquired resistance for CDDP in human pancreatic cancer.