[Twenty-one-year survival case of rectal GIST treated with combined therapies].

A 55-year-old man underwent Miles' operation with a diagnosis of rectal leiomyosarcoma in 1990. From 1998 to 2004, he had liver and lung metastases and local site recurrent tumors which were removed surgically. Immunohistochemically the recurrent tumor was positive for c-kit and CD34, and the diagnosis of GIST was confirmed. He took an adjuvant imatinib mesylate for half a year in 2004. In July 2005, he had a recurrent tumor in upper mediastinum. We restarted an imatinib after radiation therapy, and got a clinical CR. After he had interstitial pneumonitis in 2009, he stopped taking inmatinb. Then he took sunitinb for two months after an operation for the sixth local recurrence in February 2010. But the upper mediastium recurrent tumor occurred again in November 2010. We restarted sunitinb and got a clinical PR. The patient is now alive and well for 21 years after the initial operation by combined therapies.

Flare hypercalcemia after letrozole in a patient with liver metastasis from breast cancer: a case report.

INTRODUCTION: Tamoxifen may occasionally precipitate serious and potentially life-threatening hypercalcemia. However, to date, this has not been documented with aromatase inhibitors. CASE PRESENTATION: A 65-year-old Japanese woman with liver metastasis from breast cancer was admitted to our hospital with vomiting, anorexia, fatigue, arthralgia, muscle pain and dehydration. She had started a course of letrozole five weeks earlier. Our patient's calcium level was 11.6 mg/dL. She was rehydrated and elcatonin was administered. Our patient's parathyroid hormone and parathyroid hormone-related protein levels were not increased and a bone scintigram revealed no evidence of skeletal metastasis. After our patient's serum calcium level returned to within the normal range, letrozole was restarted at one-half of the previous dose (1.25 mg). There were no episodes of hypercalcemia. However, 84 days after restarting letrozole, our patient again complained of arthralgia and treatment was changed to toremifene. During these periods, repeated ultrasonograms revealed no progression of liver metastasis. CONCLUSION: To the best of our knowledge, this is the first case report of flare hypercalcemia after treatment with letrozole in a patient with metastatic breast cancer.

[Predictors of axillary node metastasis at breast surgery after neoadjuvant chemotherapy in patients with pre- chemotherapy-sentinel node positive breast cancer].

BACKGROUND: We investigated predictors for axillary node metastasis at breast surgery after neoadjuvant chemotherapy (NAC) in patients with pre-chemotherapy-sentinel node positive breast cancer. METHODS: Eighty-two patients were diagnosed as having positive sentinel lymph node (SLN), who had axillary lymph node dissection (ALND) performed after combination anthracycline/taxan based NAC, between 2002 and 2009. RESULTS: Eighteen (22.0%) of the 82 patients had residual axillary metastases after NAC. Multivariate analysis revealed that SLNs status before NAC was an important factor in predicting residual axillary metastases. Predictors of residual nodal disease were the number of macrometastases and the percentage (>50%) of positive SLNs in all SLNs. Among a subgroup of hormone-receptor positive and HER2-negative tumors, the risk of residual nodal metastases were high sensitivity of hormone receptor, with more than 50% of tumor cells staining positive for ER and PgR. CONCLUSION: Patients with two or more positive SLNs before NAC had a high risk of residual nodal metastasis after NAC.

[Resection of local recurrent gastric cancer following total gastrectomy].

We report a case of patient who underwent resection for local recurrent gastric cancer at the anastomotic site curatively. The patient was a 72 years old male with a history of undergoing total gastrectomy for gastric cancer located at the gastric cardia in February 2005. The histological findings of the resected tumor showed a Type 3 advanced gastric cancer invaded into subserosa in the cardia of the stomach with positive lymphatic and venous invasion and lymph node metastasis. The histological diagnosis was moderately differentiated tubular adenocarcinoma. Both the proximal and distal margins were negative for cancer. Endoscopy, 4 years after the first operation, showed a recurrent tumor at the site of esophago-jejunal anastomosis. A resection of the tumor was carried out curatively through the left thoraco-abdominal approach in June 2009. We recommend a resection of anastomotic recurrence especially if it occurs from the first operation in the long interval.

[A case with liver resection of metastasis from rectal cancer after bevacizumab treatment].

The advancement of systemic chemotherapy for colorectal carcinoma has improved a clinical response rate and expanded a possibility of resection, which we thought we could not have been operable at the initial visit. It also improved a prognosis of patients. We report here a case with liver resection of metastasis from rectal cancer followed by bevacizumab treatment.

[Two cases of venous thrombosis confirmed during the bevacizumab combination chemotherapy for colorectal cancer].

We report two cases of venous thrombosis confirmed during the bevacizumab combination chemotherapy for colorectal cancer. Case 1 was a 59-year-old man. We performed an operation for cancer of the rectum. At 2 years after the operation, he received mFOLFOX6 + bevacizumab therapy for a recurrence in the pelvis and lungs metastasis. After the 14th courses, He had a right shoulder pain and contrast enhanced computed tomography revealed deep vein thrombosis to the right arms. Case 2 was a 65-year-old man. We performed an operation for cancer of the rectum. At 6 months after the operation, he received mFOLFOX6 + bevacizumab therapy for lung metastases. After the 6th courses, contrast enhanced computed tomography revealed deep venous and pulmonary thrombosis for both sides, pulmonary thrombosis.

[A case of synchronous double cancer of stomach and lung responding to neoadjuvant chemotherapy].

A 66-year-old male was admitted to our hospital because of dyspnea in 2007. Cancerous pleural effusion and gastric cancer was diagnosed, and the chemotherapy consisted of S-1 + DOC was started for Stage IV gastric cancer. In 2009, lung cancer was found. The chemotherapy was changed to CDDP + CPT-11. This chemotherapy was effective for both lung and gastric cancers. Operation was performed for both tumors in 2010, and the pathological diagnosis revealed that gastric cancer was pStage I, Cur A, and the lung cancer was pStage IA, R0. Pathologic histology inspection of both tumors was judged to be effective for the chemotherapy prior to resection.

A chemical hemostatic technique for bleeding from malignant wounds.

BACKGROUND: Breast cancer, skin cancer, and head and neck cancer often develops a hemorrhagic malignant wound. Bleeding from the tumor impairs patients' quality of life and can be life threatening, while surgical or electrical hemostasis is often unsuccessful because of the tumor's friability. METHODS: We performed a chemical hemostatic treatment for breast cancer hemorrhage with zinc chloride paste (Mohs' paste), which is usually applied as a fixative in micrographic surgery for cutaneous neoplasms. Five patients with bleeding from breast cancer under various circumstances were treated with this technique in 2008. RESULTS: The method was successful on first application for all five patients, and hemostasis was maintained long term. CONCLUSIONS: This simple technique is effective for bleeding from malignant wounds and should be learned by health professionals performing cancer care.

[A case of urachal carcinoma with transverse colon fistula].

A 61-year-old woman was admitted to our hospital because of abdominal pain. Computed tomography showed an abscess in the anterior abdominal wall and an intraabdominal tumor. Biopsy from bladder dome presented adenocarcinoma. We diagnosed the tumor as urachal carcinoma and operation was performed. The resected specimen showed transverse fistula. In Japan, there is no report of urachal carcinoma with fistula to digestive duct. We think it is a cause of strong infiltration of the carcinoma. Curative resection for urachal carcinoma with fistula can lead to a better prognosis, in spite of its invasive character.

Vitamin K2-induced cell growth inhibition via autophagy formation in cholangiocellular carcinoma cell lines.

Vitamin K2 (MK4) has antitumor effects on various types of cancer cell lines in vitro, and its efficacy has also been reported in clinical applications for patients with leukemia, myelodysplastic syndrome, and hepatocellular carcinoma (HCC). However, details of the mechanism of the antitumor effects of MK4 remain unclear. In the present study, we examined the antitumor effects of MK4 on cholangiocellular carcinoma (CCC) cell lines and its mechanism of action using the HL-60 leukemia cell line that exerts MK4-induced cell growth inhibition via apoptosis induction and cell cycle arrest as a control. MK4 exerted dose-dependent antitumor effects on all three types of CCC cell lines. However, apoptosis occurred in a smaller percentage of cells and there was less cell cycle arrest compared with other cancer cell lines studied previously, which suggested slight MK4-induced cell growth inhibition via apoptosis induction and cell cycle arrest. On the contrary, histopathological fidings showed a large number of cells containing vacuoles in their cytoplasm, and electron microscopic findings showed a large number of cytoplasmic autophagosomes and autolysosomes. These findings suggested evidence of autophagy-related cell death. Fluorescence microscopy following acridine orange staining revealed an increase in the number of cytoplasmic acidic vesicular organelles characteristic of autophagy. Moreover, there were few cells forming autophagic vesicles in the control group, while the percentage of cells containing vacuoles in the MK4-treated group increased with the duration of culture. These results suggested that, unlike in leukemia, gastric cancer, HCC, and other cancer cells, the antitumor effects of MK4 on CCC cells are induced via autophagy formation.

[A case of recurrence after resection of stage IV advanced bile duct cancer responding well to S-1/cisplatin combination chemotherapy].

The patient was a 70-year-old man who in November 2000 had undergone pancreatoduodenectomy for a diagnosis of lower bile duct cancer by his previous physician. Left cervical and intra-abdominal lymph node enlargement were detected at 3 years 4 months postoperatively, and a biopsy resulted in a histopathological diagnosis of metastasis by bile duct cancer. Intravenous S-1,120 mg/body, on days 1-14, and CDDP, 20 mg/body, on day 14 was started in April 2004. It was conducted safely on an outpatient basis with no adverse events, and it was possible to achieve survival for 29 months. S-1/CDDP therapy seemed to be capable of serving as a useful treatment for gallbladder and bile duct cancer in the future.

Vitamin K2-induced antitumor effects via cell-cycle arrest and apoptosis in gastric cancer cell lines.

Vitamin K2 (VK2) has a growth inhibitory effect on various types of cancer cells in vitro, and its efficacy has been demonstrated in clinical applications in a number of patients with leukemia and hepatocellular carcinoma. In this study, the effect of cell growth inhibition and apoptosis induction and the concomitant use of an anticancer agent by VK2 (menaquinone: MK4), on gastric cancer cell lines were examined. When 4 kinds of gastric cancer cells (KATO III, MKN7, MKN74 and FU97) were exposed to MK4, the cell growth was inhibited in an MK4 dose-dependent manner. Morphologically, apoptosis induced by MK4 was recognized in FU97, but only a slight number of apoptotic images was recognized in other cell lines. On the contrary, in all the cell lines, the percentage of APO2.7 positive cells increased significantly in the MK4-treated group as compared to the controls. Caspase-3 activity increased significantly in KATO III and FU97 as compared to the controls, while no significant differences were noted in MKN7 or MKN74. Moreover, in all the cell lines, the percentage of G0/G1-phase cells ( approximately 70% in KATO III and FU97, and > or =80% in MKN7 and MKN74) increased in comparison to the controls, suggesting that cell-cycle arrest had occurred. All of the gastric cancer cell lines were given MK4 in different concentrations and two kinds of anticancer agent, with the result that cell growth was inhibited by the anticancer agent in a dose-dependent manner when it was given with MK4 in concentrations of up to 10 microM. In conclusion, our results demonstrate that the effect of MK4 on apoptosis and cell-cycle arrest differs in differentiated (MKN7, MKN74) and undifferentiated (KATO III, FU97) gastric cancer cell lines, and that MK4 alone or with anticancer agents has an antitumor effect on gastric cancer cell lines.

Prognostic predictors in breast cancer patients with postoperative 5-fluorouracil-based chemotherapy.

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are enzymes involved in the metabolism of 5-fluorouracil (FU). To investigate the relationship of these activities with clinicopathological factors and survival, we measured TS (88 patients) and DPD (122 patients) activities in resected specimens of breast cancer by enzyme assay. Significant difference was found only in TS activity between tumors > or = 20 mm in diameter and those < 20 mm (p = 0.015). There were no significant differences in TS or DPD activity among any other factors. When patients were grouped based on the cut-off levels of TS and DPD activities, 5-year recurrence-free survival rate was 68.8% in the low TS group and 39.7% in the high TS group (p = 0.0081), and 50.8% in the low DPD group and 66.5% in the high DPD group (p = 0.1627). The Cox proportional hazard model demonstrated that in patients in whom we measured TS activity, significant prognostic factors were nodal status and estrogen receptor (ER) status by univariate analysis, and ER status was also significant by multivariate analysis. In patients in whom DPD activity was measured, the significant prognostic factor was ER status by univariate analysis, and ER and Progesterone receptor (PgR) status by multivariate analysis. These results suggested that TS activity, nodal status and hormone receptors may be possible predictors of clinical outcome in breast cancer, but further investigation on prognostic predictors in 5-FU-based chemotherapy is required.