Hideyuki Ubukata

Evaluations of interferon-γ/interleukin-4 ratio and neutrophil/lymphocyte ratio as prognostic indicators in gastric cancer patients.

Th2‐dominant immunity and high neutrophil/lymphocyte ratios (NLRs) have been reported to reflect tumor progression, and so we examined whether the Th1/Th2 ratio and NLR can act as prognostic indicators or not.

Diverticular disease of the colon at a regional general hospital in Japan

PURPOSE: X-ray film registry records were reviewed to better understand the changing nature of diverticular disease (DD) of the colon in Japan. RESULTS: Among 6,849 patients undergoing barium enema examination during a eight-year period from 1985 to 1992, this condition was found in 1,074 patients (15.7 percent), including 702 males (65.4 percent) and 372 females (34.6 percent). During this eight-year period there was an increase in frequency from 10.7 percent in 1985 to 17.8 percent in 1992. The proportion of patients with right-sided, bilateral, and left-sided DD was 69.2 percent, 17.5 percent, and 13.3 percent, respectively. The right-sided DD was more common in the younger age group and was predominant in male patients, whereas the left-sided DD increased with age, especially in female patients. Of the 1,074 patients, 11 (1.0 percent) underwent surgery in the same period. Regarding the rightsided DD, only 2 of 743 patients received surgery (0.3 percent). On the other hand, of the 143 patients with left-sided DD, 9 patients (6.3 percent) received some form of surgery. CONCLUSION: Right-sided diverticular disease of the colon is still common in Japan. It does not appear that this tendency will change in the future. Nearly all patients diagnosed as having diverticula had either no symptoms or only mild symptoms, and only about 1 percent required surgery. Right-sided diverticular disease of the colon seems to have had no serious clinical problems compared with left-sided DD.

Increased density and diameter of Lymphatic microvessels correlate with lymph node metastasis in early stage invasive colorectal carcinoma

To determine whether lymphangiogenesis was associated with the development of colorectal carcinoma and whether the mean maximal diameter of lymphatic microvessels (LMMMD) or lymphatic microvessel density (LMVD) is associated with lymph node metastasis in early stage invasive colorectal carcinoma (T1 carcinoma), we used immunohistochemical staining with podoplanin to measure LMMMD and LMVD in intratumoral (LMMMDit, LMVDit) and peritumoral areas (LMMMDpt, LMVDpt) of T1 carcinomas (n=87). By comparing the LMMMD and LMVD in normal large intestine (n=10), adenoma (n=15), and Tis carcinoma (n=15), we found out that the LMVDpt in T1 carcinoma with lymphatic vessel invasion (LVI) was significantly high (P<0.001), and there was a significant decrease in LMMMDpt in T1 carcinoma (P=0.031). Both LMMMDpt and LMVDpt were significantly increased in the T1 carcinomas, with LVI compared with the T1 carcinomas without LVI (P=0.018, P=0.003). Multivariate analysis revealed that LVI and combined greater LMMMDpt and greater LMVDpt were associated with lymph node metastases (P=0.005, P=0.036). These results indicate that lymphangiogenesis might be induced in the surrounding tumor areas of the T1 colorectal carcinoma with LVI; thus, evaluation of the diameter and density of lymphatic microvessels is important in T1 colorectal carcinoma to predict lymph node metastases.

Rapid decrease of intracellular pH associated with inhibition of Na+/H+ exchanger precedes apoptotic events in the MNK45 and MNK74 gastric cancer cell lines treated with 2-aminophenoxazine-3-one

The effects of Phx-3 on changes in intracellular pH (pHi) in the MKN45 and MKN74 human gastric cancer cell lines were evaluated in order to determine the mechanism for the proapoptotic effects of 2-aminophenoxazine-3-one (Phx-3) on these cells. Phx-3 (100 μM) reduced pHi in MKN45 from 7.45 to 5.8, and in MKN74 from 7.5 to 6.2 within 1 min of engagement with these cells. Such a decrease of pHi was closely correlated with the dose of this phenoxazine and continued for 4 h. The activity of Na+/H+ exchanger isoform l (NHE1), which is involved in H+ extrusion from the cells, was dose-dependently suppressed by Phx-3 in these cells, and was greatly suppressed in the presence of 100 μM Phx-3. This result indicates that the decrease of pHi in MKN45 and MKN74 cells is closely associated with the inhibition of NHE1 in these cells. The morphology of these cells at 24 h after treatment with Phx-3 indicated shrinkage of the cells and condensation of the nuclear chromatin structure, which are characteristic of the apoptotic events in these gastric cancer cells. Cytotoxicity of Phx-3 against MKN45 and MKN74 cells was extensive because almost all MKN45 cells lost viability at 24 h in the presence of 20 μM Phx-3, and nearly 50% of the MKN74 cells lost viability in the presence of 50 μM Phx-3. These results suggest that rapid and extensive decrease of pHi in human gastric cancer MKN45 and MKN74 cells caused by Phx-3 might disturb intracellular homeostasis, leading to apoptotic and cytotoxic events in these cells. Phx-3 is a good candidate for therapeutics of gastric cancer that is intractable to conventional chemopreventive therapies.

Why is the coexistence of gastric cancer and duodenal ulcer rare? Examination of factors related to both gastric cancer and duodenal ulcer

The coexistence of gastric cancer with duodenal ulcer has been found empirically to be rare, but why it is rare is difficult to explain satisfactorily. To elucidate this question, we carried out a literature review of the subject. The frequency with which the two diseases coexist is 0.1–1.7%, and the main factor associated with both gastric cancer and duodenal ulcer is Helicobacter pylori infection. However, there are marked differences between the disorders of hyperchlorhydria in duodenal ulcer, and hypochlorhydria in gastric cancer. The most acceptable view of the reason for the difference may be that the acquisition of H. pylori infection occurs mainly in childhood, so that the time of acquisition of atrophic gastritis may be the most important, and if atrophic gastritis is not acquired early, high levels of gastric acid may occur, and consequently acute antral gastritis and duodenal ulcer may occur in youth, whereas, in elderly individuals, persistent H. pylori infections and the early appearance of atrophic gastritis may be the causes of low gastric acid, and consequently gastric cancer may occur. In patients with duodenal ulcer, factors such as nonsteroidal anti-inflammatory drugs (NSAIDs) and dupA-H. pylori strains may contribute to preventing the early acquisition of atrophic gastritis, while acid-suppressive therapy and vascular endothelial growth factor and other entities may inhibit atrophic gastritis. In contrast, in gastric cancer, factors such as excessive salt intake, acid-suppressive therapy, polymorphisms of inflammatory cytokines, and the homB-H. pylori strain may contribute to the early acquisition of atrophic gastritis, while factors such as NSAIDs; fruits and vegetables; vitamins A, C, and E; and good nutrition may inhibit it.

Desmoplastic response in biopsy specimens of early colorectal carcinoma is predictive of deep submucosal invasion

PURPOSE: The aim of this study was to evaluate the role of histopathology of biopsy specimens in predicting depth of infiltration in early colorectal carcinomas before treatment. METHODS: Early colorectal carcinomas that had been resected surgically or endoscopically between 1984 and 1995 were analyzed. Histopathologic findings, including differentiation of adenocarcinoma and a desmoplastic response were investigated. RESULTS: One hundred nine early colorectal carcinomas consisted of 73 lesions of carcinomain situ, 13 submucosal carcinomas with minimum invasion, 8 lesions with moderate invasion, and 15 lesions with deep invasion. Of 73 carcinomain situ lesions, 72 (approximately 99 percent) showed well-differentiated adenocarcinomas and no desmoplastic response. Twelve (92 percent) of 13 submucosal carcinomas with minimum invasion also revealed well-differentiated adenocarcinoma without a desmoplastic response. Sixty-three percent (5/8)of lesions with moderate invasion revealed well-differentiated adenocarcinoma. None of the lesions had a desmoplastic response. Among lesions with deep invasion, 73 percent (11/15) demonstrated moderately differentiated adenocarcinoma, and 11 lesions had a prominent desmoplastic response (73 percent;P<0.01). CONCLUSIONS: These results suggest that if histopathologic findings of biopsy specimens taken from them before treatment demonstrated adenocarcinoma associated with a desmoplastic response, the lesions had at least deep invasion carcinomas. These lesions should be resected surgically. Submucosal carcinomas with minimum invasion, which have no desmoplastic response, could be treated endoscopically.

The granulocyte/lymphocyte ratio as an independent predictor of tumour growth, metastasis and progression : its clinical applications

Several investigators have suggested that the granulocyte/lymphocyte (G/L) ratio is a good indicator for the evaluation of the condition of a tumour-bearing host, although its prognotic significance is unclear. To further investigate the clinical applications of the G/L ratio, we injected 1x105 and 1x106 Lewis lung carcinoma cells (3LLc) into the feet of 4-week-old C57BL/6 mice separated into groups A, B, C and D (1x105 cells) and E, F, G and H (1x106 cells). For the observation of tumour metastasis and G/L ratio, the mice in groups A-D were sacrificed on days 11, 14, 17 and 21 after inoculation with the 3LLc cells, and the mice in groups E-H on days 7, 11, 14 and 17. The results suggest that in mice the number of granulocytes increases with time after 3LLc cell injection (P<0.05). We also retrospectively investigated the correlation between G/L ratio, clinicopathologic features and prognosis in 62 patients with gastric carcinoma. There was a significant correlation between the G/L ratio and tumour weight (r=0.746, P<0.05), as well as a significant difference between the G/L ratio and the extent of metastases (P<0.05). Additionally, the G/L ratio was significantly associated with lymph node metastasis and higher tumour stage, tumour progression (P=0.017) and 5-year survival (P=0.013). In conclusion, the G/L ratio is associated with tumour progression and shorter survival. The close correlation between G/L ratio and tumour stage or lymph node status suggests that it could be used to predict tumour metastasis, prognosis and overall survival in patients with gastric carcinoma before they undergo surgical treatment.

Prednisolone therapy for intra-abdominal desmoid tumors in a patient with familial adenomatous polyposis

The management of intra-abdominal desmoid tumors in patients with familial adenomatous polyposis (FAP) is very difficult. Non-steroidal anti-inflammatory drugs (NSAIDs), anti-estrogenic agents, and steroids are most commonly used, because surgical removal of these tumors may result in severe morbidity, with local recurrence being common. We report a patient with FAP and intra-abdominal desmoid tumors that regressed markedly after prednisolone therapy. The patient, a 38-year-old woman, had undergone total colectomy and ileorectal anastomosis with a diagnosis of FAP with colon cancer. Approximately 17 months after the surgery, she noticed an elastic firm lump in the abdominal wall. She also experienced lower abdominal distension. Computed tomography (CT) of the lower abdomen showed an invasive heterogenous low-density mass occupying the intra-abdominal space. She was treated with sulindac, NSAID, at 300 mg/day, the diagnosis being intra-abdominal desmoid tumors. She exhibited an intestinal obstruction about 9 months after the initiation of sulindac therapy. We changed the treatment and began prednisolone (initial dose, 40 mg/day). This treatment was continued for two years; subsequently the lesions regressed markedly. She is currently well, more than 3 years after the withdrawal of prednisolone.

Intra-abdominal bronchogenic cyst with gastric attachment: Report of a case

We report a rare case of an intra-abdominal bronchogenic cyst. An abnormal lesion was detected on an ultrasonogram, done as part of a physical checkup, in an 81-year-old woman. Computed tomography and magnetic resonance imaging showed a cystic mass attached to the lesser curvature of the stomach. Initially, we suspected a congenital cyst without malignant components; however, as the patient wished to have the lesion removed, we performed a minilaparotomy. The cystic lesion was firmly attached to the lesser curvature by fibrous tissue. Microscopic examination subsequently revealed the 26-mm mass to be a benign bronchogenic cyst with a bronchial element. We compared our findings with those of 50 previously reported cases of intraabdominal bronchogenic cysts. None of these patients was older than ours, and lesions attached to the esophagus or stomach were extremely unusual. Bronchogenic cysts are difficult to diagnose preoperatively based on imaging findings, but surgery may be indicated if malignant components are suspected, or if the lesion is enlarging or causing symptoms.

Spinal Destruction Induced by Chronic Contained Rupture of an Abdominal Aortic Aneurysm: Report of a Case

We report a case of spinal destruction caused by chronic contained rupture of an abdominal aortic aneurysm (AAA). The patient was a 73-year-old man who had undergone coronary artery bypass grafting, sigmoidectomy for colon cancer, and axillofemoral bypass with AAA resection within months of each other, 3 years earlier. Abdominal computed tomography and magnetic resonance imaging showed destruction of the 12th thoracic and 1st lumbar vertebrae. The possibility of a metastatic spine tumor prompted us to consult the orthopedic surgeons, who recommended a spinal percutaneous needle aspiration biopsy. However, the cardiovascular surgeons diagnosed chronic contained rupture of an inflammatory AAA. The patient gradually improved with antimicrobial treatment, but died of disseminated intravascular coagulation the following year. The definitive diagnosis was confirmed by autopsy. We report this case for its educational value, considering the serious consequences that might have occurred had we attempted to biopsy the lesion.