Hiroki Kurumi

Role of the preoperative usefulness of the pathological diagnosis of pancreatic diseases.

Pancreatic cancer is the fifth leading cause of cancer death and has the lowest survival rate of any solid cancer. Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is currently capable of providing a cytopathological diagnosis of pancreatic malignancies with a higher diagnostic power, with a sensitivity and specificity of 85%-89% and 98%-99%, compared to pancreatic juice cytology (PJC), whose sensitivity and specificity are only 33.3%-93% and 83.3%-100%. However, EUS-FNA is not effective in the cases of carcinoma in situ and minimally invasive carcinoma because both are undetectable by endoscopic ultrasonography, although PJC is able to detect them. As for the frequency of complications such as post endoscopic retrograde cholangiopancreatography pancreatitis, EUS-FNA is safer than PJC. To diagnose pancreatic cancer appropriately, it is necessary for us to master both procedures so that we can select the best methods of sampling tissues while considering the patient’s safety and condition.

Expression of coproporphyrinogen oxidase is associated with detection of upper gastrointestinal carcinomas by 5-aminolevulinic acid-mediated photodynamic diagnosis

BACKGROUND 5-Aminolevulinic acid is a precursor of photosensitizing protoporphyrin IX and has been applied for photodynamic diagnosis of brain and bladder tumors with few side effects. Although most upper gastrointestinal tumors can be detected during photodynamic diagnosis, some tumors containing signet-ring cells cannot be visualized. Here, we aimed to assess whether proteins involved in the absorbance, activation, and turnover of protoporphyrin IX altered the fluorescence signal in gastric cancer. METHODS Aminolevulinic acid-mediated photodynamic diagnosis was performed in 23 lesions from 20 patients using an endoscope equipped with a blue laser light that caused red fluorescence emission of photosensitizing protoporphyrin IX. Red fluorescence signal and intensity was assessed during photodynamic diagnosis procedures. Lesions were resected by endoscopic and/or laparoscopic surgery, and specimens were immunostained and assessed for the expression of ATP-binding cassette sub-family G member 2, oligopeptide transporter-1, and coproporphyrinogen oxidase. RESULTS Photodynamic diagnosis was negative in four cases (17.4%). Three cases of photodynamic diagnosis-negative lesions were signet-ring cell carcinomas, and only one case was differentiated adenocarcinoma (intestinal type). Twenty intestinal type, photodynamic diagnosis-positive lesions showed high expression of coproporphyrinogen oxidase, whereas signet-ring cell carcinomas were all negative. Oligopeptide transporter-1 immunoreactivity was significantly higher in tumors of intestinal type. ATP-binding cassette sub-family G member 2 expression tended to be higher in luminal surface tumors than in intestinal type tumors. CONCLUSION Aminolevulinic acid-mediated photodynamic diagnosis provided good detection of upper gastrointestinal tumors of intestinal type but not diffuse type tumors, such as signet-ring cell carcinomas, possibly owing to coproporphyrinogen oxidase expression.

Protoporphyrinogen oxidase is involved in the fluorescence intensity of 5-aminolevulinic acid-mediated laser-based photodynamic endoscopic diagnosis for early gastric cancer

BACKGROUND/AIM Laser-based photodynamic endoscopic diagnosis (LPDED) is a type of endoscopic diagnosis that uses the fluorescence caused by the photochemical reaction that occurs when a fluorescent substance is irradiated by a light of a specific wavelength. Although 5-aminolevulinic acid (5-ALA) can detect early gastric cancer (EGC) during LPDED, there is an unresolved issue of the differences in fluorescence intensity among histopathological types of gastric cancer. Thus, the aim of the present study was to assess whether protoporphyrinogen oxidase (PPOX), involved in the activation of protoporphyrin IX, can affect the fluorescence intensity in EGC. METHODS Thirty-three gastric tumor lesions in 30 patients were assessed by LPDED using a prototype endoscope equipped with a blue laser ray to cause excitation following oral 5-ALA administration. The tumors were then resected by endoscopic submucosal dissection or laparoscopic surgery. PPOX expression was examined immunohistochemically in the excised specimens. To explore the mechanisms of histopathological diversity in PPOX and coproporphyrinogen oxidase (CPOX) expression of EGC, immunohistochemical analysis was performed using 75 surgically resected specimens of diverse EGCs. RESULTS Among the 33 lesions, 26 tumors were detectable by LPDED, whereas seven were undetectable. Between the LPDED-positive and negative groups, there was a significant difference in histopathology. The expression of PPOX was higher in tubular adenocarcinoma (tub) than in signet-ring cell carcinoma (sig). There were significant differences in PPOX and CPOX expression scores of the surgically resected specimens among tub, poorly differentiated adenocarcinoma (por), and sig. CONCLUSION PPOX protein expression could be involved in the fluorescence intensity of LPDED in EGC, possibly reflecting histopathological features.

Diagnostic usefulness of KL-6 concentration of bile in biliary tract cancer

The sensitivity of bile cytology for biliary tract cancer varies from 6-64%, and hence remains unsatisfactory. Sialylated carbohydrate antigen KL-6 mucin is positive in biliary tract cancer tissues and serum KL-6 levels are significantly increased in intrahepatic ductal adenocarcinoma patients compared with healthy individuals. The aim of the present study was to evaluate the usefulness of the KL-6 concentration of bile for the diagnosis of biliary tract cancer. Bile cytology and measurements of bile KL-6 concentration were conducted for 43 patients (25 biliary tract cancers and 18 benign biliary disease). The concentration of KL-6 in the bile of the biliary tract cancer group was compared with the benign biliary disease group. The diagnostic ability was assessed by using receiver operating characteristic curves (ROC). The mean KL-6 concentration of bile for biliary tract cancer (34.6±51.6 U/ml) was increased compared with benign biliary disease (5.2±3.9 U/ml, P<0.001). The area under the ROC for diagnosis of biliary tract cancer was 0.84 for benign biliary disease. When the cut-off level of the KL-6 concentration of bile was 8.6 U/ml, the sensitivity, specificity, and accuracy of the KL-6 concentration of bile alone for the diagnosis of biliary tract cancer were 72, 89, and 79%, respectively. Adding the bile KL-6 concentration to bile cytology measurements, the sensitivity for the diagnosis of biliary tract cancer was increased significantly (100%, P=0.0184). The KL-6 concentration of bile may strengthen the sensitivity of bile cytology for biliary tract cancer.

Probe-based confocal laser endomicroscopy of the gastric mucosa with curcumin dripping

Probe-based confocal laser endomicroscopy (pCLE) is an innovative endoscopy that can visualize biological tissues to the cell level by intravenously administering a fluorescent dye.1 Fluorescein, a fluorescent dye with established safety,2 is used worldwide not only in the ophthalmological field but also for confocal endoscopy. However, its use is limited in Japan, because pharmaceutical approval for its application to endoscopy has not been obtained. This article is protected by copyright. All rights reserved.

Efficacy and safety of pancreatic juice cytology by using synthetic secretin in the diagnosis of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is difficult to detect in its early stages with the poorest prognosis of all cancers. To improve the prognosis, a precise diagnosis is needed when we suspect PDAC. Although endoscopic ultrasound‐guided fine‐needle aspiration biopsy (EUS‐FNA) is a widely accepted modality for the diagnosis of PDAC, its sensitivity is 85–89%, and approximately 10% of PDAC cases cannot be diagnosed. The main causes that interrupt the diagnosis of PDAC by using EUS‐FNA are tumor size, presence of a vessel or the main pancreatic duct along the puncture route, and difficulty in withdrawing anticoagulant. Pancreatic juice cytology (PJC), the sensitivity of which is 33.3–65.8%, is a method for the diagnosis of PDAC cases in which carrying out of EUS‐FNA is difficult. To diagnose PDAC appropriately, we need to improve the diagnostic ability of PJC.

Management of non-curative endoscopic submucosal dissection for early gastric cancer: do we have enough data to support this?

Gastric cancer is one of the most common cancers. Early gastric cancer (EGC) detection is critical for its curative or even non-curative treatment. Gotoda et al . provided important information on the risks of lymph node metastasis (LNM) in a large EGC series (1). Based on their analyses, the expanded criteria for the endoscopic resection of EGC was proposed as follows mucosal cancer without ulcer findings irrespective of tumor size; mucosal cancer with ulcer findings less than 3 cm in diameter; and minute (<500 μm from the muscularis mucosae) submucosal invasive cancer less than 3 cm in size due to their nominal risks of LNM. Endoscopic submucosal dissection (ESD) has been developed worldwide as an endoluminal therapeutic technique for EGC (2). ESD allows precise histological assessment of the resected one-piece specimens in order to guide further management and to stratify a patient’s risk for developing metastasis including LNM. The long-term outcome of curative EGC patients treated by ESD can be excellent; our previous study showed for the first time that the 5-year overall survival (OS) and disease specific survival (DSS) rates of EGC patients treated by ESD were 97.1% and 100%, respectively (3).