The risk of adverse events of CPT- 11.

Irinotecan is a camptothecin analog used worldwide for a broad range of solid tumors, including colorectal cancer. It can cause severe adverse drug reactions, such as neutropenia or diarrhea. Recent pharmacogenetic studies on irinotecan have revealed the impact of UGT1A1 polymorphisms on severe adverse effects. The concurrence of UGT1A1*28 and UGT1A1*6, even when heterozygous, markedly alters the disposition of irinotecan, potentially increasing toxicity. For patients showing homozygosity for UGT1A1*28, *6 or compound heterozygosity for UGT1A1*6 and *28, dose reduction of irinotecan is strongly recommended. But dose reduction criteria or effect of dose reduction have not been clarified. If prediction accuracy of expression risk of adverse reaction improve, It is expected to be possible to appro- priate therapeutic indications and drug selection, dose setting.

[A case of progressive gastric carcinoma accompanied by disseminated carcinomatosis of bone marrow (DCBM)due to bone metastasis, with DIC recovery by administration of S-1 and docetaxel].

A 63-year-old- female was admitted to our hospital complaining of cough. Based on CT, bone centigram and peripheral blood findings, a diagnosis of gastric carcinoma accompanied by bone marrow metastasis was made. As DIC developed following hospital admission, S-1 and docetaxel(DOC)therapy was initiated(daily oral administration of 80 mg/m(2) S-1 for 14 days and DOC at 40 mg/m(2) on day 1, q3w). Recovery from DIC was achieved. S-1 and DOC therapy is considered to be effective for DIC due to bone marrow metastasis of gastric carcinoma. S-1/DOC is thought to be an effective chemotherapy against progressive gastric carcinoma accompanied by disseminated carcinomatosis bone marrow with DIC.

[Medical treatment for gastrointestinal stromal tumor (GIST) in Japan].

To facilitate an optimal diagnosis and treatment of GIST in Japan, the Japanese Clinical Practice Guideline for GIST was proposed by the GIST Guideline Subcommittee. Multidisciplinary treatment planning is needed(involving pathologists, radiologists, surgeons and medical oncologists)for patients with GIST. Medical treatment is usually selected for unresectable GIST, metastatic GIST at the initial examination, and recurrent GIST. Imatinib is strongly recommended for patients with KIT-positive GIST; the standard dose of imatinib mesylate(Glivec)is 400 mg/day. For patients with imatinib-resistant GIST, Sunitinib (Sutent)is now approved in Japan and is covered by medical insurance. However, high-dose imatinib(>400mg/day)has not yet been approved in Japan.

[Skin toxicity].

It has been suggested that skin symptoms may cause psychological distress associated with change in appearance, and affect patients' quality of life(QOL). Also, there is a correlation between the severity of skin disorder resulting from treatment with epidermal growth factor receptor(EGFR)inhibitors(cetuximab, panitumumab, erlotinib)and their clinical effects. Treatment with EGFR inhibitors needs to be continued as long as possible while treatment-related skin symptoms are managed appropriately. Adherence to this approach will benefit the patients. Daily self-skin care(keeping the skin surface clean, maintaining moisture retention, and preventing irritation)is the most important countermeasure for hand-foot syndrome resulting from oral administration of fluorinated pyrimidine anticancer drugs(capecitabine, S-1). An early introduction of effective countermeasures including dose reduction/establishment in the rest period is essential for management of such syndrome.

[Clinical development of oral chemotherapeutic agents for advanced gastric cancer].

5-fluorouracil (5-FU) has been the mainstay of systemic therapy since its initial development 50 years ago for gastrointestinal cancer. In Japan, the development of orally administered fluoropyrimidines that maintain or improve the effectiveness of intravenous 5-FU, has been advanced. In the JCOG9912 trial, S-1 demonstrated significant non-inferiority to 5-FU. In the SPIRITS trial, S-1+CDDP combined chemotherapy showed significant statistical superiority to S-1 monotherapy. On the basis of these results, S-1+CDDP combination therapy was adopted as the standard cancer chemotherapy regimen for inoperable and recurrent gastric cancer. The ACTS-GC trial suggested that adjuvant chemotherapy with S-1 should be adopted as the standard treatment for stage II/III gastric cancer after curative D2 gastric dissection. This manuscript describes the clinical development of oral fluoropyrimidines (S-1, capecitabine) and their modulators for gastric cancer.

[First/second/third-line chemotherapy with molecular targeted drugs for colorectal cancer].

According to the Japanese Colorectal Cancer Treatment Guideline by the Japanese Society for Cancer of the Colon and Rectum, the recommendation for recurrent colorectal cancer consists of 2 options according to the number of metastatic organs and surgical curability. In Japan, oxaliplatin was approved for patients with metastatic colorectal cancer in 2005, bevacizumab was approved in 2007, cetuximab was approved in 2008. Then most of the standard regimens in western countries became available in Japan. Therefore, Japanese standard regimens in patients with recurrent colorectal cancer are considered according to the standard western regimen. This review paper introduce the major regimens in the first-, second-, and third-line settings in patients with recurrent colorectal cancer in Japan, and comments on several chemotherapy issues in Japan.

Proliferating potential and apoptosis in the development of secondary hyperparathyroidism: a study based on Ki-67 immunohistochemical staining and the terminal dUTP nick-end labeling assay.

Secondary hyperparathyroidism (SHPT) is a common complication in hemodialysis (HD) patients. SHPT progresses from initial diffuse hyperplasia (diffuse) to early nodularity (early), then to multinodular hyperplasia (nodular), and finally to a single nodule (single) consisting of uniform parenchymal cells. We analyzed the roles of proliferation and apoptosis in SHPT progression. Seventy-four parathyroid glands from 36 HD patients with SHPT, and 10 parathyroid glands from 10 non-HD patients without SHPT were used for analysis. The former were classified as diffuse (N = 17), early (N = 22), nodular (N = 20), and single (N = 15); the latter were classified as normal (N = 10). To analyze proliferating cells we used Ki-67, and to detect apoptotic cells, we used the terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick-end labeling (TUNEL) assay. Concerning the Ki-67 labeling index (LI), the incremental order was single, nodular, early, diffuse, and normal. Oxyphilic cells and around the central portion of each lesion were distinctly stained by Ki-67. Concerning the TUNEL LI, the incremental order was early, diffuse, nodular, single, and normal. Chief cells and around the peripheral portion of each lesion were distinctly stained by TUNEL. In the progression from early to nodular, for oxyphilic cells, the Ki-67 LI increased and the TUNEL LI decreased; for chief cells, the Ki-67 LI decreased and the TUNEL LI showed no significant change. We considered that proliferative activity increases and that the apoptosis rate decreases as SHPT progresses from diffuse to single. Moreover, the specific differences in the rate of proliferation and apoptosis between oxyphilic and chief cells might be associated with SHPT progression.

Immunohistochemical analysis of nestin and c-kit and their significance in pancreatic tumors.

The purpose of the present study was to clarify the difference of expression of two stem cell markers, nestin and c-kit, among various pancreatic epithelial tumors and evaluate their utility. Immunohistochemistry was done for 99 surgically resected pancreatic tumor specimens, including 20 ductal adenocarcinoma (DAC), two undifferentiated carcinomas (UC), 31 intraductal papillary-mucinous neoplasms (IPMN), six mucinous cystic neoplasms (MCN), five serous cystadenomas (SCA), six acinar cell carcinomas, two pancreatoblastoma (PB), eight solid-pseudopapillary neoplasms (SPN), and 19 endocrine neoplasms (EN). Nestin was widely expressed in four SPN, one PB, one SCA, sarcoma areas in two UC, one MCN, and one DAC, and an area of oncocytic component in one IPMN. Some of these SPN, SCA and sarcomatous or oncocytic components in which nestin was expressed, also coexpressed c-kit. Additionally, partial (scattered) expression of c-kit was observed in ductal elements of 16 DAC, eight IPMN, five MCN, and one UC, one SCA, and three EN. The eight c-kit-positive IPMN included four of 23 adenoma-to-border lesions and four of eight non-invasive-to-invasive carcinomas. The three EN were all carcinomas. These indicate that expression of two stem cell markers is different by tumor type, but the utility of judging direction or degree of differentiation and malignant grade on the basis of their expression status is suggested.