Yutaka Yasunaga

Cancer risk after renal transplantation in Japan

Excess of cancer in patients receiving renal transplantation is well‐known in Western countries, but information in Japan remains limited. Our study examined whether excess risk is found in patients receiving renal transplantation in Japan. Between 1970 and 1995, 1155 males and 589 females underwent renal transplantation in 6 hospitals, and a total of 12,982 person‐years of observation was accumulated. Malignancies developed in 2.6% of patients; O/E ration was 2.78. Median interval from renal transplantation to tumor development was 58 months. The interval in the patients receiving medication with cyclosporine‐A (CyA) (median, 42.5 months) was significantly shorter than that with non‐CyA (median, 95.5 months). Median age at the diagnosis of malignancy was 40 years, which is much younger than that in the general population. Relative risk was highest in renal cancer, followed by thyroid cancer, malignant lymphoma and uterine cancer. A distribution of malignancies was different from that reported from Western countries. These findings showed the excess risk of malignancies in Japan with renal transplants, especially in male patients, similar to that observed in Western countries, though the types of malignancy were different. Int. J. Cancer 71:517‐520, 1997.

Malignant lymphoma of the kidney.

Primary renal lymphoma (PRL) is a rare disease, making information including etiologic factors for PRL extremely limited.

Prognostic factors of renal cell carcinoma: A multivariate analysis

Background and Objectives: To establish appropriate therapeutic modalities for renal cell carcinoma (RCC), informations on the factors affecting prognosis of patients are essential. For this purpose, multivariate analysis including a large set of variables is necessary.

Expression of Epstein-Barr virus latent infection genes and oncogenes in lymphoma cell lines derived from pyothorax-associated lymphoma

Malignant lymphomas frequently develop in the pleural cavity of patients with long‐standing pyothorax. The term pyothorax‐associated lymphoma (PAL) has been proposed for this type of tumor. Most PALs are diffuse lymphomas of the B‐cell type and contain Epstein‐Barr virus (EBV) DNA. We have established 2 lymphoma cell lines from biopsy specimens of PAL cases, OPL‐1 and OPL‐2, and examined their growth characteristics and the expression of EBV latent infection genes and oncogenes. OPL‐2 exhibited a more rapid growth and higher saturation density than OPL‐1, and only OPL‐2 exhibited colony‐forming activity in soft agar. OPL‐1 and ‐2 were positive for B‐cell differentiation markers and showed clonal surface immunoglobulins. Both lines contained a single predominant form of episomal EBV DNA, indicating clonal cellular proliferation of an EBV‐infected progenitor cell. OPL‐1 and ‐2 contained type B and A EBV genome, respectively. Expression of EBV nuclear antigen (EBNA)2 mRNA and protein was detected by Northern and Western blot analysis in OPL‐1, but not in OPL‐2. On the other hand, the expression of latent membrane protein (LMP) I mRNA in both OPL‐1 and ‐2 was extremely weak and detectable only by reverse transcription‐polymerase chain reaction. Protein expression of LMPI was not observed by Western blot analysis or immunocytochemistry. Both lines expressed c‐myc mRNA. Only OPL‐1 expressed mRNA of c‐fgr, an oncogene whose expression is upregulated by EBNA2. Both OPLs expressed bcl‐2 mRNA without detectable expression of LMPI protein.

Transition Zone Biopsy in the Detection of Prostate Cancer

Objective: About 25% of all prostate cancers occur in the transition zone (TZ). We analyzed the impact of 4 systematic TZ and 2 systematic apex (AP) biopsies in addition to systematic sextant biopsies in an effort to establish the diagnostic importance of early prostate cancer.Methods: One hundred and thirty patients underwent systematic transperineal multipoint prostate biopsy (biopsy of 12 sites, including 4 TZ and 2 AP biopsies).Results: Forty–one of 130 men (31.5%) had biopsy specimens positive for cancer, and cancer originated in the TZ alone in 4 of these 41 patients (9.8%). Fourteen patients underwent radical retropubic prostatectomy. We compare the pathological findings of radical prostatectomy specimens and biopsy results. Prostate cancers predicted to be stage T2c by TZ biopsy were all classified as pT2c or greater.Conclusions: Routine TZ biopsy does not substantially increase the prostate cancer detection rate; however, it can be useful in patients who require repeat biopsy.

INCIDENCE OF PROSTATIC INTRA-EPITHELIAL NEOPLASIA IN OSAKA, JAPAN

High‐grade prostatic intra‐epithelial neoplasia (HGPIN) is the most likely precancerous lesion for prostatic carcinoma. A high incidence of its association with cancer has been reported in Western countries. On the other hand, information regarding its incidence is limited in Japan, where the mortality due to prostate cancer is much lower. We reviewed 53 clinical stage T2 or T3 prostatic cancers of Japanese patients living in Osaka, Japan (mean age, 67.2 years). These cases were subdivided into a pre‐operatively non‐castrated group (34 cases) and a medically or surgically castrated group (19 cases). HGPIN was found in 27 cases. The incidence of HGPIN was significantly lower in the castrated group (21.0%) compared with the non‐castrated group (67.6%). In the non‐castrated group, patient age, pathological stage, Gleason score, tumor size and serum prostate‐specific antigen showed no significant correlation with HGPIN. Advanced pathological stage and tumor size tended to decrease the incidence of HGPIN, although this was not statistically significant. When the study group was limited to stage T2 tumors of the non‐castrated group, the incidence of HGPIN was 81.0%. HGPIN in Japan may also be clinically and etiologically significant as a precursor of clinical cancer. Int. J. Cancer 73:808–811, 1997.

Characteristics of non-Hodgkin's lymphoma complicated by renal cell malignancies

Previous epidemiological studies showed an increased risk for the development of renal cell carcinoma (RCC) after adjuvant therapy or simultaneous discovery of non-Hodgkin’s lymphoma (NHL). However, clinicopathological features of NHL complicated by RCC are not well known. We summarized the clinicopathological features of 42 cases with malignant lymphoma complicated by renal tumors collected in a nationwide study in Japan. There were 27 males and 15 females, and the age at initial diagnosis of NHL ranged from 51 to 85 years (median 69 years). The clinical stages of NHL were stage I in 13 patients, stage II in 8, stage III in 8 and stage IV in 13 patients. RCC was simultaneously detected in 4 patients, within 1 year after the diagnosis of NHL in 20 and after more than 1 year in 13 patients. In the remaining 3 patients, NHL was diagnosed 1 year (2 cases) or 6 years (1 case) after nephrectomy. Histologically, all but 2 cases of NHL were diagnosed as diffuse lymphoma, with the large-cell type being the most common. The remaining 2 cases were follicular lymphoma. NHL in 35 cases (85%) were immunophenotyped as B cell type and 4 (10%) as T cell type. Renal tumors in all but 2 cases were classified as RCC: clear-cell type in 29, chromophobic type in 3, chromophilic type in 7 and Bellini duct carcinoma in 1 case. All RCC showed a cellular malignancy of grade II or III. When compared to sporadic autopsy cases of NHL in Japan, the frequency of extranodal lymphoma and B cell type was higher in the current cases (p = 0.06). In addition, leiomyosarcoma occasionally occurred among complicated renal tumors.

One-month relative dose intensity of not less than 50% predicts favourable progression-free survival in sorafenib therapy for advanced renal cell carcinoma in Japanese patients

BACKGROUND Sorafenib is a multikinase inhibitor used as a second-line treatment for metastatic renal cell carcinoma (mRCC). However, it is very difficult to estimate sorafenib dosage because it is difficult to maintain stable administration and dosage intervals due to several side-effects. We examined the correlation between relative dose intensity (RDI) and clinical outcome of sorafenib therapy in a multi-institutional study. METHODS A study population of 70 first-line therapy-refractory patients with pathologically confirmed RCC was eligible for this investigation. Clinical outcomes were evaluated according to clinicopathological features and RDI for 1 month (1M-RDI). RESULTS There was significant difference in progression-free survival (PFS) time but not overall survival (OS) time when the 1M-RDI cut-off value was ≥ 50%. In 15 patients (21.4%) with 1M-RDI of <50%, median PFS time was 4.1 months (95% I collagen (95% CI): 2.0-6.2), whereas it was 10.5 months (95% CI: 7.6-13.4) in the patients with 1M-RDI of ⩾50% (P=0.022). Multivariate analysis showed 1M-RDI status to be significantly associated with PFS (HR: 3.838, 95% CI: 1.658-8.883, P=0.002) but not OS (P=0.328). CONCLUSION Although this study was retrospective, a 1M-RDI cut-off value of ≥ 50% for sorafenib may be the first factor to predict PFS but not OS in cytokine pretreated mRCC patients. The data indicate that a dose of 400mg/day of sorafenib administered successively for the first one month was necessary to prolong disease stabilisation and could be tolerated by Japanese patients.

UTILITY OF IMMUNOHISTOCHEMICAL DETECTION OF HIGH MOLECULAR WEIGHT CYTOKERATIN FOR DIFFERENTIAL DIAGNOSIS OF PROLIFERATIVE CONDITIONS OF THE PROSTATE

Background: Differential diagnosis of adenocarcinoma from other proliferative conditions in the prostate is often problematic. lmmunohistochemistry using an antibody (34βE12) to high molecular weight cytokeratin, specifically present in basal cells of the prostate, could clearly demonstrate the presenceor absence of these cells in the proliferating glands and thus provide an important clue in cancer diagnosis.

Antiplatelet therapy and spontaneous perirenal hematoma

Abstract  This case report clarifies an adverse reaction of antiplatelet therapy which has been a standard prophylactic method for patients harboring significant risks of thromboembolic events. A 71‐year‐old Japanese man who had been taking aspirin tablets (81 mg) for a year presented with sudden colic pain in the left flank region. An abdominal computed tomography scan revealed a significant perirenal hematoma of the left kidney. There were no pathological kidney conditions, such as renal tumors, calculi or vascular diseases, found by magnetic resonance imaging examination. After cessation of aspirin administration followed by conservative management, the hematoma completely disappeared 6 months later. This is the first documented case of spontaneous perirenal hematoma secondary to low‐dose aspirin treatment. While such unpleasant events occur extraordinarily, this should be noted as a severe risk of antiplatelet therapy.