Indication and Usefulness of Bile Juice Cytology for Diagnosis of Gallbladder Cancer.

AIM: We examined the effectiveness of bile juice cytology for distinguishing between benign and malignant gallbladder lesions of the protruding type with various sampling points, sampling methods, and macroscopic forms in order to discuss the effectiveness of the endoscopic transpapillary gallbladder drainage (ETGD) cytology. METHODS: We studied 162 cases of patients with a lesion localized within the gallbladder. At first, we examined the effectiveness for diagnosis of ETBD cytology using ERC and then that of the first ETGD cytology after placing the ETGD. Next, we examined the diagnostic effectiveness of the washed ETGD cytology by using the ETGD. Finally, we examined complications. RESULTS: In the final diagnoses, we identified 33 cases of adenocarcinoma, 10 cases of adenoma, 63 cases of ADM, 35 cases of nonneoplastic polyp, and 21 cases of chronic cholecystitis. It was found that the sensitivity of ETBD cytology was 3.6% and that of ETGD cytology was 59.1%. In the comparison of diagnostic effectiveness of cytologic diagnosis using samples of bile juice from the gallbladder collected by different methods, the sensitivities were 38.9% and 73.3% for the first and washed ETGD cytologies, respectively. In the comparison of the diagnostic effectiveness of gallbladder bile juice cytology using samples collected for different forms of lesion and by different methods, the sensitivities were 38.9% and 73.3%, respectively, for the first and washed ETGD cytologies for flat gallbladder wall thickening, while it was impossible to diagnose for lesions of GB polyp. CONCLUSION: For diagnosis of gallbladder cancer, we consider that the ETGD cytology should be taken into consideration for lesions of flat gallbladder wall thickening, for which it is difficult to distinguish between benign and malignant lesions.

[An epidermoid cyst derived from an intrapancreatic accessory spleen].

A 43-year-old female patient had high levels of CA19-9 marker; an abdominal ultrasound revealed a cyst. Further investigations with computed tomography (CT), magnetic resonance imaging, and endoscopic ultrasound CT identified a multilocular cystic lesion on the pancreatic tail. An abnormal wall was noted, and different signal strengths were measured in each cyst. Thus, a mucinous cystic tumor was diagnosed, and distal pancreatectomy combined with splenectomy was performed. During the surgery, we identified a multilocular pancreatic cyst with internal bleeding at its distal end. The lesion was ultimately diagnosed as an epidermoid cyst of an intrapancreatic accessory spleen. This diagnosis was based on the histological observation that the vascular construction of the cystic wall was equivalent to that of the spleen, and that its internal tissue was covered by squamous epithelium.

[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.

Assessment of trypsinogen-2 levels as an early diagnostic for post-endoscopic retrograde cholangiopancreatography pancreatitis.

OBJECTIVES: The objective of the present study was to assess the use of serum trypsinogen-2 (TRY-2) measurements in early diagnosis of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). METHODS: In this prospective study, investigation 1 involved collection of blood serum both before and at 2, 4, and 18 hours after ERCP, whereas investigation 2 involved collection before and 1, 2, 3, 4, 6, and 18 hours after ERCP. Total amylase, pancreatic amylase, and TRY-2 levels were measured from serum samples, and values from patients with pancreatitis after ERCP were compared to those from healthy control patients after ERCP. RESULTS: In investigation 1, 8 of the 68 cases examined were diagnosed as post-ERCP pancreatitis. In the healthy group, total- and pancreatic-amylase levels peaked 4 hours after ERCP, and TRY-2 levels peaked at 2 hours after ERCP. In contrast, cases of post-ERCP pancreatitis demonstrated prolonged periods of high total-amylase, pancreatic-amylase, and TRY-2 levels. In investigation 2, none of the 23 cases was diagnosed as post-ERCP pancreatitis: Pancreatic amylase levels peaked 4 to 6 hours after ERCP and TRY-2 levels peaked 1 hour after ERCP. CONCLUSION: These results suggest that TRY-2 is a more sensitive marker than amylase, and it can be useful in early diagnosis of post-ERCP pancreatitis.

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.

[A case of pancreatic solid-pseudopapillary tumor without cystic component in an elderly man].

We encountered a solid pseudopapillary tumor (SPT) without any cyst component in an elderly man. A literature survey of SPT without cystic component suggested that the size and vascularity of a tumor were related to lack of cystic component. The prognosis of this disease was comparatively good, but elderly or middle aged case and cases without capsule seem to have high malignant potential.