Kazunori Hisamitsu

Clinicopathological significance of cathepsin D expression in gastric adenocarcinoma.

Objective: An estrogen-regulated lysosomal protease, cathepsin D, has been detected in a variety of tissues. This proteinase has been described as closely associated with tumor progression and metastasis in malignant tumors. The purpose of this study was to determine the clinicopathological and prognostic significance of cathepsin D expression in gastric adenocarcinoma. Methods: In a consecutive series of 478 patients with gastric carcinoma (median follow-up period: 93 months, range: 1–285 months), cathepsin D expression in tumors was quantitatively analyzed with immunohistochemistry using a monoclonal antibody against cathepsin D (clone: 1C11). The percentage of cathepsin-D-positive cancer cells (the CD index) was calculated. In addition, the amount of cathepsin-D-positive stromal cells was evaluated; three grades (high, intermediate, and low) were used for the classification. Results: The mean CD index of 478 tumors was 12.8% (range: 0–100%, median: 8%). The mean CD index of diffuse-type gastric carcinomas (14.9%) was significantly higher than that of intestinal-type carcinomas (10.1%, p < 0.0001). Cathepsin D expression of cancer cells was significantly associated with the depth of tumor invasion in both types. The percentage of tumors with high cathepsin D expression in stromal cells was significantly higher in well-differentiated tumors (25.5%) than in moderately differentiated (12.8%) or in poorly differentiated tumors (19.1%). Cathepsin D expression of stromal cells was significantly associated with the depth of tumor invasion in the intestinal type, in contrast to the diffuse type. Highly expressed cathepsin D in cancer cells was associated with a poor prognosis in both types of carcinoma, but in stromal cells highly expressed cathepsin D was associated to a poor prognosis in the intestinal type only. Conclusion: These results indicate that cathepsin D expression in cancer cells may play an important role in tumor progression in diffuse-type gastric carcinoma, whereas in the intestinal type of carcinoma, cathepsin D expression in stromal cells may play an important role in tumor progression.

Clinicopathological findings in patients with gastric adenocarcinoma with familial aggregation.

Background/Aims: The clinicopathological characteristics of gastric cancer (GC) with a positive family history of site-specific GC have not been well discussed. The aim of this study was to estimate the risk of familial aggregation of GC in a hospital-based case-control study and to analyze the clinicopathological characteristics of GC with familial aggregation of GC. Methods: Our series was comprised of 926 histologically confirmed patients with GC (588 males and 338 females) and 2,052 non-cancer outpatients between 1985 and 1996. The odds ratios (ORs), as estimators of relative risks, together with the corresponding 95% confidence intervals (CIs) for a family history of GC and for a family history of other cancers were calculated. Moreover, the clinicopathological findings of patients with GC who had a GC family history were compared with those of patients with GC who had no GC family history. Results: A positive family history of GC was associated with a statistically significant increase in the risk of GC (OR = 2.15; 95% CI = 1.77–2.63), while no association was observed between the risk of GC and a family history of other cancers (OR = 1.11; 95% CI = 0.91–1.36). The incidence of a multifocal occurrence of GCs was higher in patients with a family history of GC (19.4%) than in patients without a family history of GC (12%, p = 0.005). The risk (OR) of occurrence of multiple cancers in the stomach in patients who had a family history of GC was 1.77 (95% CI = 1.19–2.64). Conclusions: Our results suggest that a family history of GC seemed to be a risk factor for the development of GC. Further, a family history of GC was found to be associated with a multifocal occurrence of GC.

Unusual case of tacrolimus vascular toxicity after deceased donor renal transplantation

We report a case of tacrolimus vascular toxicity found on a protocol biopsy shortly after a deceased donor renal transplantation. The patient was immunologically high‐risk and acute antibody‐mediated rejection during post‐transplant dialysis phase was suspected on the protocol biopsy. Although the patient was stable after treatment of rejection, a further examination showed a very rare but specific side‐effect of tacrolimus. It is sometimes difficult to make a differential diagnosis during postoperative dialysis period among AMR, primary non‐functioning, drug toxicity, infection or just prolonged recovery from the damage of a long agonal phase on the non‐heart beating donor. Although the possibilities of coexistence of rejection or other causes such as infection have not been completely excluded, it is important to be aware of this unusual side effect of tacrolimus.

Biopsy findings on a stable recipient after secondary donor specific antibody (DSA) positive and ABO incompatible kidney transplantation

Using desensitization protocol, we performed a secondary donor specific antibody (DSA) positive and ABO incompatible kidney transplantation. One‐hour biopsy showed no C4d deposition. The protocol biopsy after 2 weeks showed diffuse C4d deposition with peritubulitis. After 12 weeks, however, the protocol biopsy showed disappearance of tubulitis in spite of remaining C4d deposition. The recipient was in stable condition with excellent graft function despite high titer of the DSA. Monitoring of protocol biopsy is critical while antibody titer and the interpretation of the histological findings correlating with clinical markers must be considered.