Chemosensitivity and Survival in Gastric Cancer Patients with Microsatellite Instability

Introduction  Conflicting data exist regarding the relevance of high-frequency microsatellite instability (MSI-H) for predicting the prognosis and benefits of 5-fluorouracil (5-FU)-based chemotherapy. This study investigated the usefulness of MSI as either a prognostic indicator or predictor of distinct clinical attributes regarding the use of adjuvant chemotherapy with 5-FU and its analogues in gastric cancer. Materials and methods  Data and tumor specimens were collected from 240 gastric cancer patients from 1993 to 2002. Five microsatellite loci were analyzed using a high-intensity microsatellite analysis reported previously. A Cox proportional hazard model was used to compare the clinical data and survival as well as any associations between MSI and 5-FU treatment status of patients with MSI or microsatellite stability (MSS) gastric cancers. A 3-(4,5-dimethyl-2-thiazolyl) -2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted in 168 cases to investigate chemosensitivity to 5-FU. Results  This analysis identified 22 MSI-H (9.4%), 25 MSI-L (10.7%), and 193 MSS (79.9%) tumors. Gastric cancer with MSI-H tended to have increased likelihood to show higher age, antral location of the tumor, and lymph vessel involvement (P < 0.05). Univariate analyses failed to show any difference between the MSI-H and MSS/MSI-L groups with respect to overall survival. Furthermore, survival after the administration of 5-FU did not correlate with MSI status, and MSI was not associated with 5-FU sensitivity by MTT assay. Conclusion  The results of this study indicate that MSI status has no clear influence on overall survival or response to 5-FU in gastric cancer.     

Laparoscopy-assisted distal gastrectomy with 3-cm laparotomy, left hepatic lobe compression technique, and selection of automatic anastomosis device

In this study, we performed laparoscopy-assisted distal gastrectomy (LADG) and lymph node dissection with an incision of 3 cm aiming at radical cure and low invasiveness. We introduce and discuss this technique of minilaparotomy and recommend a device for anastomosis. In LADG, a skin incision of 5cm or greater is made in order to pull out the stomach in other institutes. Whether function is distinctly better after laparoscopy-assisted surgery than after abdominal section has not been elucidated so far, so we should seek an aesthetic advantage. We have used a 3-cm abdominal wound to date. If the wound is smaller than this, the body of the SDH25 cannot be inserted, and currently a wound less than 3cm may thus not be possible. The shaft of the SDH is straight, making it easy to confirm the direction even through a laparoscope. The shaft of the anvil head of the PPCEEA is too long, so that when it is connected with the body through the 3-cm incision, it is necessary to draw it through the remnant stomach to a great extent.     

Histological factors contributing to a high risk of recurrence of submucosal invasive cancer (pT1) of the colon and rectum after endoscopic therapy

We analyzed the histological high-risk factors for recurrence of submucosal invasive carcinomas (pT1) of the colon and rectum after endoscopic therapy, examining pT1 cancers treated primarily by endoscopic resection within a 23-year period. We compared recurrent and nonrecurrent cancers, evaluating the following "highrisk factors" of the primary lesion: massive invasion, a surgical margin <2 mm but negativity for cancer in the cut end, poorly differentiated adenocarcinoma (PD) (G3), undifferentiated carcinoma (G4), and/or positive angiolymphatic invasion. The following histological factors were defined as predictive of a low risk: minimum invasion, a surgical margin >2 mm, well or moderately differentiated adenocarcinoma (G1, G2), and no evidence of angiolymphatic invasion. We analyzed the records of 37 patients with pT1 cancers, including 15 with high-risk factors who underwent subsequent resection. Local recurrence with or without liver metastases developed in 4 of these 15 patients. The histological type was PD in three (75%) of the four recurrent lesions. All four (100%) lesions showed a desmoplastic response (DR). Only 1 (9%) of the 11 patients without recurrence after subsequent surgery had a lesion with a small component of PD, and only three (27%) lesions showed a mild DR. We concluded that endoscopic therapy is inadequate for pT1 cancers with a histological PD component, and/or a DR in the cancer stroma.     

Irinotecan+cisplatin and irradiation are effective for brain metastases of gastric cancer--two case reports

We treated two patients in whom irinotecan (CPT-11)+cisplatin (CDDP) and irradiation showed efficacy against brain metastases of gastric cancer. CPT-11 and CDDP were administered on days 1 and 15 of a 28-day cycle at 60 mg/m(2) and 30 mg/m(2), respectively. The first patient was a 63-year-old man,who complained of headache and weakness. In March 2003, he was diagnosed as having Stage IV gastric cancer with peritoneal dissemination (T3, Nx, P1) and underwent total gastrectomy with D1 dissection. Chemotherapy with S-1 was continued after surgery. Two years and two months later, a metastatic tumor was found in the upper lobe of the right lung. The protocol was changed to S-1+CDDP, but progression of his disease occurred. The weekly paclitaxel (PTX) therapy was tried instead. Seven months later, he developed headache and weakness, and multiple brain metastases were diagnosed by CT scanning. We performed total brain irradiation (30 Gy) and started CPT-11+CDDP therapy, which was continued on a fortnightly basis at 60 mg/m(2) and 30 mg/m(2), respectively. The brain metastases regressed (PR), and this therapy led to a marked improvement in his quality of life. The second patient was a 78-year-old man, who complained of weakness of the lower extremities and dizziness. In November 2003, he was diagnosed as having stage IB gastric cancer (T2 (ss), N0, P0), and underwent total gastrectomy and splenectomy with D2 dissection. One year and four months later, local recurrence at the anastomosis was detected, as well as a metastatic tumor in the right lung. S-1, S-1+CDDP, and weekly PTX therapy were all tried. One year later, the patient was admitted with weakness and dizziness,and brain metastases were detected by CT scanning. We then performed Cyber Knife treatment and administered CPT-11+CDDP. As a result, his brain metastases partially regressed (PR).     

Comparative studies on effect of risedronate and alfacalcidol against glucocorticoid-induced osteoporosis in rheumatoid arthritic patients

Osteoporosis is a common adverse reaction induced by glucocorticoid treatment. Bisphosphonate, vitamin D(3) (VD(3)) or vitamin K(2) (VK(2)) is recommended as first or second choice of drug for treatment of glucocorticoid-induced osteoporosis. In the present study, the treatment effect of risedronate against glucocorticoid-induced osteoporosis in rheumatoid arthritic patients was compared with that of alfacalcidol. Twelve patients were randomized to receive either risedronate (2.5 mg) or alfacalcidol (0.5 microg) daily for 48 weeks. Each patient also received 800 mg of calcium supplementation (800 mg/day) daily. Bone mineral density (BMD) and the biochemical markers of bone turnover were measured before (baseline) and 12, 24, and 48 weeks after treatment with risedronate or alfacalcidol, and the percentage changes in these parameters from baseline were compared.The BMD values 12, 24 and 48 weeks after treatment with risedronate increased by 3.9%, 4.1% and 5.2%, respectively, which were significantly higher than those after treatment with alfacalcidol (2.8%, 2.1% and 2.5%, respectively). Urinary excretion of N-telopeptides of type I collagen and deoxypyridinoline after risedronate treatment were more significantly decreased than that after alfacalcidol treatment. The present findings at least suggest that risedronate is more useful for the prevention and treatment of glucocorticoid-induced osteoporosis in patients with rheumatoid arthritis than alfacalcidol, although the number of patients studied was small.     

Brain metastases from urachal carcinoma

We present a case of brain metastases of the urachal carcinoma, which is extremely rare and malignant. Contrast-enhanced MRI was employed to detect them. A large mass was removed surgically and 4 other small metastases were treated by gamma knife radiosurgery. Six weeks after radiosurgery, the 4 lesions had disappeared on MRI. We emphasise the importance of early diagnosis using MRI and treatment by radiosurgery for this rare condition.     

The anti-pruritic efficacy of TS-022, a prostanoid DP1 receptor agonist, is dependent on the endogenous prostaglandin D2 level in the skin of NC/Nga mice

TS-022 is a prostanoid DP(1) receptor agonist, originally developed as a novel anti-pruritic drug for atopic dermatitis. The drug has been shown to suppress scratching and improve the skin inflammation in the NC/Nga (NC) mouse, a model of atopic dermatitis. Corticosteroids are commonly used as effective agents for the treatment of atopic dermatitis. We examined the anti-pruritic efficacy of TS-022 in NC mice cohabited with skin-lesioned NC mice, which showed spontaneous scratching without skin lesions in the early phase and chronic itching with severe dermatitis in the late phase, in comparison with that of dexamethasone. We have previously reported that prostaglandin D(2) might have a physiological role in the inhibition of pruritus. While after 2 weeks of cohabitation with skin-lesioned NC mice (early phase of dermatitis, characterized by the appearance of spontaneous scratching), topically applied TS-022 exhibited a weak anti-pruritic effect in the NC mice, after 6 weeks of cohabitation (late phase, characterized by both chronic scratching and dermatitis), the drug exerted potent anti-pruritic activity. In contrast, dexamethasone exerted potent anti-pruritic effect in both the early and late phases. Indomethacin aggravated the scratching in the early phase, but had no effect in the late phase. The skin prostaglandin D(2) level was significantly increased in the early phase, to subsequently declined and return to the basal level in the late phase. The cutaneous ability for prostaglandin D(2) production following topical application of arachidonic acid or mechanical scratching was decreased in the late phase. Moreover, the expression level of the prostanoid DP(1) receptor in the skin was increased in the late phase. These findings suggest that the potent anti-pruritic activity of TS-022 in the late phase might be attributable to the decrease of endogenous prostaglandin D(2) production and increase of prostanoid DP(1) receptor expression.     

Survival of bacteria, and release of the endotoxin from the bacterial cells in the dialysates]

Survival of bacteria and release of the endotoxin from the bacteria with and without ultraviolet irradiation in three kinds of dialysate were investigated. The results obtained are as follows: (1) No growth of S. aureus, E. coli, P. aeruginosa, Aspergillus and C. albicans in the saturated dialysates tested were observed. (2) All of the bacterial cells tested here is gradually, and naturally spontaneously inactivated in all the dialysates. (3) Among the dialysates tested, the saturated dialysate, AF-2, is the most effective for inactivating P. aeruginosa ATCC, but the effect depends upon the isolates of P. aeruginosa. (4) The inactivating effect was somewhat decreased when the saturated AF-2 solution was diluted, but the killing effect was still maintained. (5) The bacterial cells are constantly and significantly inactivated by UV irradiation, especially by the direct irradiation. The indirect irradiation, i.e., through glass, has remarkably less effective than the direct one. However, a tendency of the decrease of bacterial cells by the indirect irradiation is maintained with the killing effect of the dialysated, especially in the case of AF-2 solution. (6) No significant increase of endotoxin was observed, even when the bacterial cells were killed by UV irradiation. Therefore, it is recommended to use UV irradiation for inactivating the bacteria. From the results obtained here, it is indicated that there is no possibility of the growth of naturally contaminated bacteria in the dialysates, and is an effectiveness of the use of UV irradiation for inactivating the bacteria cells, in terms of release of the endotoxin from the dead cells.