Yoshiki Kida

Efficacy of Continuous Regional Arterial Infusion of a Protease Inhibitor and Antibiotic for Severe Acute Pancreatitis in Patients Admitted to an Intensive Care Unit

Abstract: To investigate the efficacy of continuous regional arterial infusion (CRAI) of a protease inhibitor and antibiotic for severe acute pancreatitis (SAP) in patients admitted to an intensive care unit (ICU). A total of 51 patients with SAP requiring admission to an ICU were studied. The patients were divided into two groups: one received the protease inhibitor nafamostat mesylate and the antibiotic imipenem by continuous regional arterial infusion (CRAI group) and the other received protease inhibitors and antibiotics by intravenous infusion (non-CRAI group). To evaluate the therapeutic usefulness of CRAI of a protease inhibitor and antibiotic for SAP, the rate of surgery and the cumulative survival rate were compared between the non-CRAI group and the CRAI group. The rate of surgery was 32% in the non-CRAI group and 9% in the CRAI group (P = 0.08). Cumulative survival rates at 1, 6, and 12 months were 77.9%, 48.9%, and 48.9% in the non-CRAI group compared with 100.0%, 100.0%, and 87.1% in the CRAI group. Outcome was thus significantly better in the CRAI group than in the non-CRAI group (P = 0.002). CRAI of a protease inhibitor and antibiotic may decrease the need for surgical therapy and reduce mortality in patients with SAP.

Hepatoid adenocarcinoma in Barrett’s esophagus associated with achalasia: First case report

We report an unusual hepatoid adenocarcinoma in Barrett’s esophagus with achalasia, which developed in a 44‐year‐old Japanese woman. The patient received an esophago‐gastrectomy after diagnosis of the tumor and achalasia at the lower esophagus, 4 months before her death due to multiple metastatic tumors of the liver. The main granular tumor removed surgically was a hepatoid adenocarcinoma, mainly composed of clear cancer cells (α‐1 antitrypsin, albumin and α‐fetoprotein positive), with elements of choriocarcinoma and tubular adenocarcinoma. Non‐neoplastic specialized columnar epithelium was present extensively near the oral side of the tumor edge in the esophagus, indicating Barrett’s esophagus. This unusual tumor was therefore considered to have originated in Barrett’s esophagus. The gastroesophageal reflux was presumed to have occurred for a long period, as there was a well‐preserved fundic gland in the stomach and a history of frequent vomiting from the patient’s youth, accounting for the appearance of achalasia.

k‐ras Point Mutations in the Supernatants of Pancreatic Juice and Bile Are Reliable for Diagnosis of Pancreas and Biliary Tract Carcinomas Complementary to Cytologic Examination

In order to clarify whether DNA analysis for K‐ras mutation can be used to diagnose cancers in supernatants of pancreatic juice and bile, samples from 29 cases of pancreatic, biliary tract, gastric, and neuroendocrine carcinomas, 1 malignant lymphoma case, 2 cases of pancreatic adenoma, 9 cases of chronic pancreatitis and 21 other non‐cancer cases were examined. Polymerase chain reaction (PCR) products for K‐ras gene codons 2 to 97 of exons 1 and 2 were generated with 33/33 (100%) pancreatic juice and 41/41 (100%) bile samples. By the single strand conformation polymorphism (SSCP) method, point mutations were detected in the pancreatic juice or bile supernatants of 13/13 (100%) pancreas cancer cases, 5/14 (35.7%) biliary tract cancer cases, 1/2 (50.0%) pancreatic adenoma cases and 3/9 (33.3%) chronic pancreatitis cases. Direct sequencing confirmed identical point mutations in the supernatants, malignant cells of cytologic smears of pancreatic juice or bile and cancer tissues. The DNA analysis demonstrated the presence of K‐ras point mutations in 3 cases of pancreatic carcinomas with false‐negative cytologic diagnoses. This novel method allows simultaneous testing for genetic abnormalities in supernatants of pancreatic juice and bile, after removing cells for cytologic diagnosis and screening for pancreatic and biliary tract tumors.

Silver-binding argyrophilic nucleolar organizer regions (AgNOR) in gall-bladder cancer: Correlations with malignant grading and prognosis

Silver‐binding nucleolar organizer regions (AgNOR) were investigated and compared in 43 cases of gall‐bladder cancers and 10 normal gall‐bladder samples using an image analyzer. The mean numbers of AgNOR per nucleus (AgNOR number) were 3.28 ± 1.38 in the gall‐bladder cancers and 1.86±0.20 in the normal gall‐bladder cases. The respective mean areas of AgNOR per nucleus (AgNOR area) were 6.96±3.78 μm2 and 1.89±0.21 μm2. The differences were statistically significant (P<0.0001) for both parameters. In addition, increased frequency and enlargement were both apparently correlated with poor prognosis (P<0.011 and P < 0.046, respectively), with AgNOR number and AgNOR area showing tendencies for increase in cases of histologi‐cally high grade malignancy, advanced cancer and regional lymph node involvement.

Gastric adenocarcinoma with differentiation to sarcomatous components associated with monoclonal Epstein-Barr virus infection and LMP-1 expression

A case of gastric adenocarcinoma with sarcomatous differentiation in a 65-year-old male was investigated for possible association with the Epstein-Barr virus (EBV). The presence of EBV-DNA could be proven by the polymerase chain reaction (PCR), and EBERs signals were detected in tumour nuclei, strongly in sarcomatous areas and weakly elsewhere. Monoclonal EBV infection was evident in terms of a single band of lymphocyte determined membrane antigen demonstrated by the PCR method. Latent membrane protein 1 was strongly positive in cells of sarcomatous components but very weakly positive in carcinoma components. EBV-determined nuclear antigen-2 was absent in both. This case of adenocarcinoma suggests that EBV plays an important role in tumorigenesis, contributing in particular to sarcomatous differentiation.

Argyrophilic nucleolar organizer regions in human adrenocortical neoplasms

SummaryArgyrophilic nucleolar organizer regions (AgNOR) in human adrenocortical neoplasms, including five carcinomas and ten adenomas, were studied using a semi-automatic image analyzer. Both the number and total area of AgNOR per nucleus in the carcinomas were found to be statistically greater than in adenomas and control tissues. However, there were no statistically significant differences in total AgNOR area per nuclear area or in the mean area of individual AgNOR dots. The AgNOR of neoplastic and normal cells were of four morphological types: type 1 had a few dots at the periphery of the nucleus, type 2 a few dots at the center, type 3 a large round dot along with several small ones at the center, and type 4 numerous diffusely distributed polymorphic dots. Most type 3 and 4 cells were found in carcinoma cases. Type 1 cells decreased in proportion to the severity of biological malignancy. It follows from these findings that careful observation of AgNOR should facilitate the distinction of malignant from benign adrenocortical neoplasms.

Black pigment deposition in reticuloendothelial system in the liver: A study of five autopsy cases with pneumoconiosis.

じん肺症について,吸入された粉じんが肺以外の臓器に与える影響についてはほとんど知られていない.われわれは病理学的にじん肺症と診断された病理剖検例5例について全身の諸臓器を組織学的に検討した.全例の肝臓および脾臓において,組織学的に粉じんと考えられる黒色色素の沈着を認めた.皮膚や消化管ではそれら黒色色素は認められなかった.肝臓における主たる沈着部位は肝小葉間結合織内リンパ管,肝静脈壁リンパ管および肝被膜リンパ管に相当する脈管様構造とその周囲であり,肝小葉内では類洞壁の網内系細胞にも微量の黒色色素を認めた.電子顕微鏡学的検索では沈着黒色色素の超微形態とその元素組成の間に,基本的に3つのパターンを認めた.免疫組織化学的には,黒色色素を含有した網内系細胞はlysozymeなどが陽性を示したが,黒色色素非含有網内系細胞に比しその染色性は弱く,黒色色素含有によるそれら酵素活性の低下が示唆され,じん肺の免疫能に与える影響が推定された.