The Kurume Medical Journal Vol. 60(2013) No. 3.4

Comparative study of contrast-enhanced ultrasonography (CE-US) and histopathology of surgically resected specimens in 13 patients with pancreatic carcinoma. A time intensity curve was used to determine the percentage brightness increase in cancerous and normal regions and the patients were divided into two groups, hyperperfusion, with a percentage brightness increase over 80% (n=6) and hypoperfusion, with an increase of less than 80% (n=7) on CE-US. The hyperperfusion group included well-differentiated tubular adenocarcinoma, adenosquamous cell carcinoma and acinar cell carcinoma, while all 7 patients in the hypoperfusion group had moderately differentiated tubular adenocarcinoma. Immunological staining (α-SMA and anti-CD34) of the resected specimens showed significantly higher microartery count (MAC) in the hyperperfusion group (p<0.005) than in the hypoperfusion group or normal pancreas. In the normal pancreas, the mean vessel diameter was significantly higher (over 100 μm) than in the hyperperfusion group (30 μm; p<0.005).
It was concluded that a muscular arterial vessel density of less than 30 μm is an important factor in determining staining degree and carcinoma progression by CE-US in pancreatic carcinoma.

Using a rat laparotomy stress model, we conducted a comparative analysis of postoperative organ metastasis after administration of ulinastatin (UTI) or methylprednisolone (MP), which have an inhibitory effect on cytokine production. The subjects were classified into 4 groups: 1) minimal laparotomy group (C group), 2) major laparotomy group (L group), 3) preoperative MP intravenous administration + major laparotomy group (MP group), and 4) preoperative UTI intravenous administration + major laparotomy group (UTI group). Either MP or UTI was administered intravenously before surgery, and RI-labeled cells were injected into the portal vein immediately after laparotomy to collect tissue specimens in order to measure radiation dosage. Then, the concentrations of serum IL-2 and IL-6, liver interleukin 1 beta (IL-1β) and interleukin 10 (IL-10), and liver E-selectin were measured. In addition natural killer cell, (NK cell) activation and neoplastic nodules on the liver surface at 3 weeks after surgery were also measured. The adhesion rate of malignant cells to the liver was higher in the L group than in the C group, higher in the MP group than the L group, and lower overall in the UTI group. The concentration of IL-1β and IL-6 were decreased in the MP and UTI groups compared to the L group. IL-2 was decreased significantly in the MP group compared with the C and L groups. E-selectin expression level decreased in the UTI group compared with the L group. NK cell activation decreased in the MP group compared with the C group and L group, but no differences were observed between the UTI and L groups. The number of tumor nodules on the surface of the liver increased in the MP group compared with the L group, and decreased in the UTI group compared with the L group. Postoperative alleviation of invasive reaction was suggested in both the MP and UTI groups. However, preoperative administration of MP increased metastasis while that of UTI inhibited metastasis. MP was considered to have decreased anti-tumor immunocompetence and promoted metastasis, while UTI was considered to have inhibited the expression of adhesive molecules and decreased metastasis.

Thrombotic complications are a major cause of death in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), which are closely associated with the JAK2 V617F activating mutation. However, whether the presence of the JAK2 V617F mutation affects thrombotic risk is currently unknown, although some reports have suggested a variable association with thrombosis. Therefore, we investigated the association between JAK2 V617F and various complications, including thrombosis, in Japanese patients with MPNs. We assessed the JAK2 V617F status in 140 patients who were diagnosed or doubted as having some type of MPN by utilizing a JAK2 V617F-specific guanine-quenching probe. JAK2 V617F was detected in 31 of 51 patients (60.8%) with essential thrombocythemia, all 16 patients (100%) with polycythemia vera, 4 of 11 patients (36.4%) with primary myelofibrosis, 2 of 18 patients (11.1%) with other types of MPNs, and none of the 44 patients with doubted MPN. In the 78 patients with classical MPN, JAK2 V617F correlated with a leukocyte count ≥10,000⁄μl (p=0.046). Complications of thrombosis, hemorrhage, and leukemic transformation occurred in 21 (41.2%), 4 (25.0%), and 3 (27.3%) patients with classical MPN, respectively, and thrombotic events (TE) occurred more frequently in patients with JAK2 V617F than without (p=0.047). Based on these findings, initial screening for the JAK2 mutation and careful monitoring for thrombotic events should be performed in patients with MPN.

Poor nutrition and weight loss are important factors contributing to poor quality of life (QOL) after gastrectomy in patients with gastric cancer. Ghrelin is a hormone produced by the stomach that, plays a role in appetite increase and fat storage. The present study aims to clarify the location of ghrelin mRNA in the stomach, changes in blood ghrelin concentrations after gastrectomy and whether or not they are associated with the reconstruction method in patients with gastric cancer. We collected seven normal mucosa samples from different parts of six totally resected stomachs with gastric cancer. We extracted RNA from the normal mucosa, synthesized cDNA from total RNA (1 μg), and then quantified ghrelin mRNA using quantitative real-time polymerase chain reaction (Q-PCR). Ghrelin blood concentrations were measured using enzyme-linked immunosorbent assay (ELISA) kits in 74 patients with gastric cancer (total gastrectomy (TG), n=23; distal gastrectomy (DG), n=30; proximal gastrectomy (PG), n=11; pylorus preserving gastrectomy (PPG), n=10). In order, the ghrelin gene was expressed most frequently in the gastric body, followed by the fornix, cardia, antrum and pylorus ring. Blood ghrelin concentrations after surgery similarly changed in all groups. The average blood ghrelin concentrations were significantly higher in the DG and PPG groups than in the TG group on postoperative days (POD) 1, 7, 30, 90 and 180. However, blood ghrelin concentrations did not significantly differ between the DG and TG groups on POD 270 and 360. Cells that produce ghrelin are supposed to be located mostly in the fundic gland of the stomach. We speculate that the production of ghrelin from other organs increases from around nine months after total gastrectomy. Therefore, evaluating the nutritional status and the weight of patients at nine months after total gastrectomy is important to help these patients improve their QOL.

Isolated gastric varices (IGV) have a lower risk of bleeding than esophageal varices, however IGV bleeding is associated with a higher mortality than bleeding of esophageal varices. In recent years, two widely used treatments for IGV have been balloon-occluded retrograde transvenous obliteration (B-RTO) and endoscopic injection sclerotherapy (EIS) using cyanoacrylate or ethanolamine oleate (EO). This study compared these two treatment methods for IGV.
The subjects were 112 patients who were treated at our hospital for IGV bleeding between October 1990 and December 2003. Forty-nine (49) patients were treated with B-RTO and 63 patients with EIS. These two patient groups were compared as regards content of treatment, post-treatment incidence of variceal bleeding, incidence of IGV rebleeding, survival rate, cause of death, and complications. Multivariate analysis was performed on post-treatment variceal bleeding and survival.
Although EO was used in higher amounts in the B-RTO group than in the EIS group, the B-RTO group had a significantly lower number of treatment sessions and a significantly shorter treatment period (p<0.05). The EIS group had significantly more patients with IGV rebleeding after treatment than the B-RTO group. Treatment method was the only independent prognostic factor of IGV bleeding after treatment (p=0.024). The two groups did not differ significantly in the percentage of patients with aggravated esophageal varices after treatment. Bleeding from ectopic varices was not observed in any patient. There was no significant difference in survival by treatment method. The presence of hepatocellular carcinoma was the only independent prognostic factor for survival (p=0.003).
It is concluded that B-RTO was more effective than EIS in the eradication of IGV and prevention of IGV recurrence and rebleeding.

Ebstein’s anomaly (EA) is a rare congenital heart disease of the tricuspid valve, and less than 5% of patients with EA survive beyond the age of 50. We report two unoperated cases of EA in adult patients aged over 50 years. Two patients, a 70-year-old Japanese woman and a 59-year-old Chinese woman, were referred to us for tachyarrhythmias. Transthoracic echocardiography demonstrated apical displacement (>8 mm⁄m² body surface area) of the septal leaflet of the tricuspid valve from the atrioventricular ring with tricuspid regurgitation in both patients. The former suddenly expired 20 months later after suffering from repetitive supraventricular tachyarrhythmias and/or heart failure, and the latter is alive with minimal signs of heart failure 12 months after the diagnosis of EA. Although the natural history of EA is extremely variable, these two patients are exceptional in that they tolerated EA well for over 50 years without any surgical intervention.