[Endoscopic ultrasound-guided fine-needle biopsy for diagnosis of pancreatic metastases producing parathyroid hormone-related protein].

A 66-year-old man was admitted to our department with hypercalcemia, pancreatic and liver tumors, and periportal lymph node enlargement. Contrast-enhanced computed tomography revealed a tumor in the pancreatic tail and the right hepatic lobe along with periportal lymphadenopathy. Laboratory data revealed hypercalcemia and high serum parathyroid hormone-related protein (PTHrP) levels. Using a 22-gauge Franseen needle, we performed endoscopic ultrasonography-guided fine-needle biopsy of the pancreatic mass and an enlarged lymph node. Histopathological examination of the biopsy specimen revealed moderately to well-differentiated pancreatic adenocarcinoma with poorly differentiated squamous cell elements, as well as squamous cell carcinoma of the lymph node. Immunohistochemical examination showed that the pancreatic tissue was weakly immunopositive and the lymph node was strongly immunopositive for anti-PTHrP antibody. We diagnosed the patient with pancreatic adenosquamous carcinoma with liver and lymph node metastasis, associated with hypercalcemia of malignancy secondary to PTHrP secretion. We administered systemic chemotherapy comprising gemcitabine and nab-paclitaxel. Unfortunately, the patient died 8 months after being diagnosed with this malignancy. PTHrP-producing adenosquamous carcinoma of the pancreas is rare;only 14 cases are reported in the literature. Based on immunohistochemical evaluation, this case report suggests that metastatic lymph nodes may lead to the overproduction of PTHrP in such cases.

Clinical characteristics of adult T-cell leukemia/lymphoma infiltration in the gastrointestinal tract.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type 1. The clinical course of ATLL is very heterogeneous, and many organs, including the gastrointestinal (GI) tract, can be involved. However, there are few detailed reports on ATLL infiltration in the GI tract. We investigated the clinical characteristics of ATLL infiltration in the GI tract. METHODS: This retrospective observational single-center study included 40 consecutive ATLL patients who underwent GI endoscopy. The patients' demographic and clinical characteristics and endoscopic findings were analyzed retrospectively. Patients with ATLL who were diagnosed by histological examination were divided into two groups based on GI tract infiltration. RESULTS: Multivariate analysis revealed that the absence of skin lesions was significantly associated with GI infiltration (P < 0.05). Furthermore, the infiltration group tended to have similar macroscopic lesions in the upper and lower GI tracts, such as diffuse type, tumor-forming type, and giant-fold type. CONCLUSIONS: GI endoscopy may be considered for ATLL patients without skin lesions.

Verification of the effectiveness of fucosylated haptoglobin as a pancreatic cancer marker in clinical diagnosis.

BACKGROUND: Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL) that had specificity for fucose α1-6 was reported as an effective biomarker for several gastrointestinal diseases. The aim of this study was to verify Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL-HP) as a pancreatic cancer (PC) marker using a new method of PhoSL-ELISA. METHODS: PhoSL-HP in sera from 98 PC patients and 158 non-PC samples including 32 intraductal papillary mucinous neoplasm (IPMN) patients, 21 chronic pancreatitis (CP) patients and 105 non-pancreatic disease controls (NPDC) were measured. We compared sensitivities, specificities and areas under the curves (AUC) of PhoSL-HP, CA19-9 and CEA as single markers. We also evaluated PhoSL-HP as combination marker by comparing AUC of CA19-9 combined with PhoSL-HP or CEA. RESULTS: The sensitivities of PhoSL-HP, CA19-9 and CEA for PC were 58%, 76% and 42%, respectively. Although the specificity of PhoSL-HP for NPDC was inferior to both of CA19-9 and CEA, that for pancreatic diseases was higher than both of CA19-9 and CEA. Combined CA19-9 with PhoSL-HP, the AUC was significantly higher at 0.880 than single use of CA19-9 at 0.825 in case of distinguishing PC from other pancreatic diseases. In contrast, the AUC of CA19-9 was not elevated significantly when combined with CEA. CONCLUSION: PhoSL-HP would be a useful marker for PC and have sufficient complementarity for CA19-9.

Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent: a pilot study.

BACKGROUND: Detecting superficial head and neck squamous cell carcinoma (HNSCC) by endoscopy is challenging because of limited morphological hallmarks, and iodine cannot be applied to head and neck lesions due to severe mucosal irritation. γ-glutamyltranspeptidase (GGT), a cell surface enzyme, is overexpressed in several cancers, and it has been reported that γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent targeting agent which can be enzymatically activated and becomes fluorescent after cleavage of a GGT-specific sequence, can be activated within a few minutes after application to animal models. We investigated whether early HNSCC can be detected by applying gGlu-HMRG to clinical samples. METHODS: gGlu-HMRG was applied to four HNSCC cell lines, and fluorescence was observed by fluorescence microscopy and flow cytometry. Immunohistological examination was performed in three recent cases of endoscopic submucosal dissection (ESD) to investigate GGT expression. Fluorescence imaging with gGlu-HMRG in eight clinical samples resected by ESD or surgery was performed, and fluorescence intensity of tumor and normal mucosa regions of interest (ROI) was prospectively measured. RESULTS: All four gGlu-HMRG-applied cell lines emitted green fluorescence. Immunohistological examination demonstrated that GGT was highly expressed in HNSCC of the recent three ESD cases but barely in the normal mucosa. Fluorescence imaging showed that iodine-voiding lesions became fluorescent within a few minutes after application of gGlu-HMRG in all eight resected tumors. Tumor ROI fluorescence intensity was significantly higher than in the normal mucosa five minutes after gGlu-HMRG application. CONCLUSIONS: Fluorescence imaging with gGlu-HMRG would be useful for early detection of HNSCC.

Endoscopic ultrasound-guided choledochoduodenostomy vs. transpapillary stenting for distal biliary obstruction.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) has gained popularity as an alternative to percutaneous biliary drainage for patients in whom endoscopic retrograde cholangiopancreatography has failed. There are no previous studies comparing EUS-CDS with endoscopic transpapillary stenting (ETS) as first-line treatment for distal malignant obstruction. The aim of this study was to compare the clinical efficacy and safety of EUS-CDS and ETS as first-line treatment in patients with distal malignant biliary obstruction. PATIENTS AND METHODS: A total of 82 patients with distal malignant biliary obstruction underwent initial biliary drainage using self-expandable metal stents at a tertiary care university hospital. ETS was performed between June 2009 and May 2012, and EUS-CDS was performed between May 2012 and March 2014. Clinical success rates, adverse event rates, and reintervention rates were retrospectively evaluated for EUS-CDS and ETS. RESULTS: A total of 26 patients underwent EUS-CDS and 56 underwent ETS. Clinical success rates were equivalent between the groups (EUS-CDS 96.2 %, ETS 98.2 %; P = 0.54). The mean procedure time was significantly shorter with EUS-CDS than with ETS (19.7 vs. 30.2 minutes; P < 0.01). The rate of overall adverse events was not significantly different between the groups (EUS-CDS 26.9 %, ETS 35.7 %; P = 0.46). Post-procedural pancreatitis was only observed in the ETS group (0 % vs. 16.1 %; P = 0.03). The reintervention rate at 1 year was 16.6 % and 13.6 % for EUS-CDS and ETS, respectively (P = 0.50). CONCLUSIONS: EUS-CDS performed by expert endoscopists was associated with a short procedure time and no risk of pancreatitis, and would therefore be feasible as a first-line treatment for patients with distal malignant biliary obstruction.