[A case of imatinib-resistant gastrointestinal stromal tumor treated with low-dose sunitinib].

The patient was an 82-year-old man who had undergone resection of a gastrointestinal stromal tumor(GIST)of the small intestine in January 2000, when he was 69 years old. As peritoneal recurrences were diagnosed in June 2002, we performed peritoneal tumorectomy twice, and the perirectal tumor was controlled with imatinib for over 7 years. Resistance to imatinib was diagnosed in March 2011, and treatment was switched to sunitinib. Administration of sunitinib was started at 50mg/day for 28 days followed by treatment withdrawal for 14 days; however, the dose needed to be reduced twice and then discontinued owing to the occurrence of side effects and pemphigoid. During discontinuation of sunitinib, the tumor increased in size and cancer pain appeared; therefore, sunitinib was re-administered at a very low-dose of 12.5mg every alternate day. Low dose sunitinib was effective; the perirectal tumor was reduced and cancer pain disappeared.

Stromal sarcoma of the breast with lung metastases showing a clinical complete response to doxorubicin plus ifosfamide treatment: report of a case.

A 29-year-old woman presented with a painful right breast tumor, measuring 15 cm in diameter, which had progressed rapidly over 3 months. Core needle biopsy of the tumor revealed a malignant mesenchymal tumor. A mastectomy was performed, and pathological examination of the tumor showed stromal sarcoma. Solitary pleural dissemination in the right lung was suspected, based on the computed tomography image taken before the operation. Two months after surgery, bilateral multiple lung nodules were demonstrated. Systemic chemotherapy with doxorubicin plus ifosfamide was performed, and 3 months later the lung metastases had disappeared. Moreover, there is still no sign of recurrence at 5 months after the initiation of the chemotherapy. Breast stromal sarcoma is very rare, accounting for less than 1% of mammary neoplasms, and the treatment strategy is not well established, especially regarding chemotherapy. This case demonstrates the effectiveness of chemotherapy with doxorubicin plus ifosfamide for lung metastases from breast stromal sarcoma.

[A case of mammary Paget's disease with early systemic recurrence after operation].

A 66-year-old woman visited our hospital because of redness and erosion of her right breast, and was diagnosed with mammary Paget's disease by histological examination of erosive skin. The patient had a simple mastectomy. The pathological diagnosis was mammary Paget's disease (8x7.5 cm) showing intraductal spread. The resected skin margin was negative. Partially dermal microinvasion and lymphatic involvement were found. Immunohistochemical analysis of this tumor showed ER negative, PgR negative, and HER2 positive (3+). Eighteen months after the operation, she presented with redness of the chest wall with edema of the right arm. Incisional biopsy on the chest mass revealed a local recurrence of mammary Paget's disease. In addition, she had carcinomatous lymphangiosis in the bilateral lung, nodal metastases in the ipsilateral axillary and mediastinal space, and contralateral breast metastases on CT. She was treated with twelve courses of weekly paclitaxel in combination with trastuzumab. A complete response was obtained eleven months after initiation of chemotherapy. A rare case of early systemic recurrence of mammary Paget's disease after curative operation is reported with a review of the literature.

[Successful control of pancreatic cancer pain using S-1 chemotherapy--a case report].

A 59-year-old man had received chemotherapy with gemcitabine for nonresectable pancreatic cancer. After 14 months, he was hospitalized for obstructive jaundice and severe pain. Cholangioduodenostomy was performed, and the dose of opioids was increased. Although jaundice improved, the uncontrollable pain persisted. Chemotherapy with S-1 was initiated, and a dramatic improvement in the pain was observed. Consequently, the patient could be discharged from the hospital.

Repeated colon penetration by an ingested fish bone: report of a case.

A 78-year-old man was admitted to Kumamoto Rosai Hospital with right lower abdominal pain. Abdominal computed tomography (CT) showed penetration of the cecum by a foreign body, which looked like a fish bone, as well as thickening of the right lower abdominal wall. We made an initial diagnosis of penetration of the colon by an ingested fish bone and the patient was managed conservatively with fasting, peripheral parental nutrition, and intravenous antibiotics. By the next day, the right lower abdominal pain had diminished and a repeat CT scan showed that the fish bone had moved to the splenic flexure. However, 2 days later, the patient complained of pain in the left upper abdomen and another CT scan showed repeated penetration of the descending colon by the same fish bone. Thus, we removed the fish bone via endoscopic extirpation. The patient had an uneventful postoperative course and was discharged home 6 days later.

[Weekly paclitaxel therapy is curative for patients with retroperitoneal liposarcoma].

In March 2004, we resected a giant retroperitoneal liposarcoma and the transverse colon, spleen and left kidney in a 58-year-old woman. In July, recurrence was detected in the right pelvis and left upper abdomen; therefore, we resected the tumor. In September 2004, computed tomography (CT) revealed multiple recurrences in the right lower abdomen, left upper abdomen, front of the left lobe of the liver, and at the back of the stomach. In October 2004, we started mesna, doxorubicin, ifosfamide, and dacarbazine therapy (MAID); however, after 1 course, the disease progressed, and the patient developed edema in the bilateral legs due to inferior vena cava (IVC) compression. In November 2004, we started weekly paclitaxel therapy (100 mg/m(2), once a week for 3 weeks followed by 1 drug-free week). CT revealed no change as a result of chemotherapy; however, IVC compression had improved, and leg edema had decreased. In August 2005, chemotherapy was stopped; therefore,the patient's condition worsened. She died in September 2005. We performed weekly paclitaxel therapy for the patient with recurrent liposarcoma. This improved her symptoms and quality of life (QOL). Therefore,we consider weekly paclitaxel therapy to be effective for liposarcoma treatment.

[Locally advanced breast cancer with a good response to sequential endocrine monotherapy--a case report].

An 81-year-old woman with a right breast tumor exposed through the skin surface visited our clinic in June 2004. Pathological findings of the resected tumor specimen indicated invasive ductal carcinoma of the breast,positive ER/PgR status,and negative HER 2/neu status. The enlarged right axillary lymph nodes were palpable. Ultrasonography and computed tomography revealed that the tumor invaded the chest wall without any metastasis to remote organs. On July 5, 2004, we started anastrozole treatment. Its effects were confirmed in the first month,and the treatment was continued for 8 months. Substituting anastrozole with exemestane was not effective. However, the exposed part of the tumor completely responded to tamoxifen that was administered for 2 months. The effect of tamoxifen continued until February 2006, and most of the subcutaneous part of the tumor became nonpalpable. Thus, sequential endocrine monotherapy proved useful for an elderly woman with locally advanced breast cancer.

[Two cases of recurrent breast cancer with regional lymph node metastases showing a complete response to trastuzumab and paclitaxel treatment].

We report two cases of recurrent breast cancer with regional lymph node metastases that responded completely to treatment with trastuzumab and paclitaxel. Case 1: A 52-year-old woman, who presented with left breast cancer, underwent mastectomy and axillary lymph node dissection in July 2002. Pathological findings were as follows: invasive ductal carcinoma (scirrhous type), 2.2 cm in size, histological grade 3, positive invasion to the lymphatic and blood vessels, negative nodal status (0/11), negative ER/PgR status, and overexpression of HER 2/neu. Left axillary lymph node metastasis was noted after five months, ie, in December 2002. Four cycles of chemotherapy with doxorubicin and cyclophosphamide were administered from January 2003; however, they were not effective. The patient showed a complete response after three months of chemotherapy with trastuzumab and paclitaxel. This treatment was stopped in September 2003. She has maintained a complete response for two and a half years and was not administered any further treatment as of February 2006. Case 2: A 59-year-old woman, who presented with right breast cancer, underwent mastectomy and axillary lymph node dissection in May 2002. Pathological findings were as follows: invasive ductal carcinoma (scirrhous type), 1.8 cm in size, histological grade 2, positive invasion to the lymphatic and blood vessels, negative nodal status (0/5), positive ER and uncertain PgR status, and overexpression of HER 2/neu. She had received adjuvant hormonal therapy with tamoxifen; however, a right supraclavicular lymph node metastasis was noted in October 2004. Treatment with exemestane was not effective. However, a complete response was observed with trastuzumab and paclitaxel for four months. She has maintained a complete response for six months and was not administered any further treatment as of February 2006.

[A case of partial response in liver metastatic lesion from gastric endocrine cell carcinoma treated with TS-1].

Endocrine cell carcinoma (ECC) of the stomach is a rare pathological type with a poor outcome. Standard chemotherapy has not yet been established. We experienced a case of partial response in the liver metastasis from the gastric ECC treated with TS-1. The patient was a 68-year-old female. An upper GI series and gastroendoscopy revealed pyrolus stenosis and CT-scan showed liver metastasis. A non-curative total gastrectomy was performed to allow oral intake. Since the histopathological examination revealed that tumor cells were partially positive for chromogranin A on immunohistochemical study, we diagnosed tumor ECC of the stomach. The patient with liver metastasis was treated using TS-1, and CT-scan showed a remarkable decrease (PR) in the metastatic lesion. TS-1 administration can improve the clinical outcome for ECC of the stomach.

Joint symptoms: a practical problem of anastrozole.

BACKGROUND: Anastrozole and tamoxifen have mild toxicity. However, we noticed that more patients treated with anastrozole complained of joint symptoms than expected. In particular, digital stiffness as is seen with rheumatoid arthritis is a problem. Some clinical trials of anastrozole in Europe and the United States reported musculoskeletal disorders as adverse events, however, joint symptoms were not described in detail. PATIENTS AND METHODS: At our clinic from August 2001 to March 2005, 53 postmenopausal women with estrogen receptor-positive breast cancer were treated with anastrozole. We calculated the incidence and classified the grade of joint symptoms by interviewing patients. We also investigated the patients' characteristics and their relevance to joint symptoms. RESULTS: Of 53 patients, 14 patients (26%) had joint symptoms (13 patients with digital stiffness and 3 patients with arthralgias of wrist and shoulders). Joint symptoms tended to occur in the patients who had previously undergone chemotherapy; however, there has no relationship between prior hormonal therapy and joint symptoms. Seven patients who discontinued anastrozole treatment showed improved symptoms. Five patients with grade 1 digital stiffness continued anastrozole treatment without additional treatment. Two patients with grade 1 digital stiffness, who took a Chinese herbal medicine showed improved symptoms and continued anastrozole treatment. CONCLUSION: Benefits to the patients may possibly be lost by discontinuation of anastrozole or changing to tamoxifen since the clinical superiority of anastrozole to tamoxifen has been reported. We should continue anastrozole in patients with low grade symptoms, while ensuring that patients are aware of the toxicity of anastrozole.

[A case of recurrent GIST successfully treated with low-dose imatinib mesilate].

A 75-year-old man underwent partial resection of the small intestine for GIST in January 2000. A recurrent tumor revealed in the intra pelvic space was removed by two operations, and imatinib (400 mg/day) was given after the third operation. As successive administration was not able to be continued due to side effects such as anorexia and fatigue, the recurrent tumor enlarged. After imatinib was given at 200 mg/day, the defecation trouble was improved and the tumor decreased partially on CT image. His partial response has continued over one year. Mutation analysis revealed deletion and point mutation in exon 11 of c-kit gene. Low-dose imatinib administration should be considered in case of side effects at the standard dose.

Onset of liver metastasis after histologically curative resection of pancreatic cancer.

PURPOSE: We assessed the possibility of predicting the time of onset of liver metastases by measuring the postoperative changes in serum carbohydrate antigen (CA)19-9 after curative resection of pancreatic cancers. METHODS: Among 28 patients who underwent histologically defined curative resection of pancreatic cancer between 1984 and 1999, liver metastasis developed in 11 patients with elevated serum CA19-9 levels. We plotted the serum CA19-9 levels against time on a semilogarithmic graph. Over the linear part of the curve, the time when log[CA19-9] equaled zero was defined as the time of onset of liver metastases. The log[CA19-9] level doubling time was then calculated and evaluated in relation to the survival period. RESULTS: The serum CA19-9 levels increased linearly in 10 of the 11 patients. The predicted time of onset of liver metastasis ranged from preoperative day 163.0 to postoperative day 27.1, being preoperative in eight patients. The doubling time until death correlated strongly with survival in the eight patients with maintained log[CA19-9] linearity. CONCLUSION: The onset of liver metastases might be preoperative in patients with advanced pancreatic cancer. Therefore, neoadjuvant chemotherapy should be mandatory even if there is no sign of liver metastases.

[Two cases of stage IV breast cancer with severe hypercalcemia].

Case 1: A 34-year-old woman,who had a right breast cancer with axillary lymph node metastasis and multiple bone metastases, was referred to our clinic. She developed paralysis of lower extremities and disorder of the bladder and rectum due to metastasis to the thoracic vertebra, and also had renal dysfunction due to severe hypercalcemia and hemorrhagic cystitis. Correcting the serum calcium level with intravenous infusion, elcatonin, pamidronate and betamethasone, she underwent radiation therapy for the vertebral metastasis. The first hormonal therapy (leuprorelin/exemestane) had been effective for about 4 months, however the second hormonal therapy (leuprorelin/tamoxifen) was not effective. Chemotherapy with paclitaxel (80 mg/m(2), day 1, 8, 15, every 4 weeks) brought about a stable general condition and a normal level of serum calcium with zoledronate in the ninth month of treatment. Case 2: A 32-year-old woman, who had a right breast cancer with multiple bone metastases and axillary and hilar lymph node metastases, came to our clinic, complaining of nausea due to severe hypercalcemia. After successful correction of hypercalcemia by the intravenous infusion and administration of elcatonin, pamidronate and dexamethasone, the hormonal therapy(goserelin/tamoxifen) caused rapid re-elevation of serum calcium and tumor marker, so that a tumor flare was suspected. After 3 cycles of EC therapy (EPI 90 mg/m(2), CPM 600 mg/m(2), every 3 weeks), 2 cycles of paclitaxel therapy (80 mg/m(2), day 1, 8, 15, every 4 weeks) brought about tumor reduction and the normal level of serum calcium. After 7 cycles of paclitaxel therapy,the hormonal therapy (goserelin/tamoxifen) proved effective for several months. To achieve tumor reduction and stabilize the serum calcium level, we need to start immediately the treatment of breast cancer with severe hypercalcemia, considering the general condition of the patient.

[PyNPase and DPD expression potentially predict response to 5'-DFUR treatment for node-positive breast cancer patients].

Pyrimidine nucleoside phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) activity may be related of the antitumor effect of 5'-deoxy-5-fluorouridine (5'-DFUR). To select patients for adjuvant setting of 5'-DFUR, we assessed PyNPase and DPD activity in 41 primary tumors (PTs) and 227 lymph nodes (LNs) of breast cancer patients. Fifty-one patients were involved in this investigation (mean age 54 +/- 12 years). LN metastasis was positive in 23 cases (node-positive group). Metastatic cancer cells were positive in 65 lymph nodes (In + group). PyNPase and DPD activity were measured by ELISA. PyNPase activity in PTs of the node-positive group was significantly higher than in the node-negative group. PyNPase activity in LNs of In + group was also significantly higher than in the negative metastatic cancer cell group. However, no significant differences were noted between these groups in DPD activity. PyNPase/DPD ratio in LNs of the In + group was marginally higher than in the negative metastatic cancer cell group. These data suggest that 5'-DFUR is preferably sensitive in breast cancer patients with lymph node metastasis.

Implication of micrometastases of lymph nodes in patients with extended operation for pancreatic cancer.

INTRODUCTION: Accurate evaluation of lymph node metastases is very important in planning treatment for pancreatic cancer. AIM: To detect micrometastases in lymph nodes dissected from patients with pancreatic cancer. METHODOLOGY: We used cytokeratin staining of negative lymph nodes in routine hematoxylin-eosin (HE) staining. We examined by cytokeratin staining 239 HE-negative nodes from 7 patients with no pathologic evidence of lymph node metastasis (n0 cases) and 718 HE-negative group 2 nodes from 23 patients with metastasis in group 1 lymph nodes (n1 cases) who underwent extended operation combined with intraoperative radiation therapy (IORT). RESULTS: Cytokeratin staining identified 15 positive nodes among the 239 HE-negative nodes from the 7 n0 cases and 8 positive nodes among the 718 HE-negative nodes from the 23 n1 cases. Among the 7 n0 cases, 5 (71.4%) had positive n1 nodes and 2 (28.3%) also had positive n2 nodes. Among the 23 n1 cases, 4 (17.4%) had positive n2 nodes. Patients with micrometastases in n2 nodes died within 25 months. CONCLUSION: Cytokeratin staining is very useful to evaluate the involvement of lymph nodes in pancreatic cancer. Prognosis of pancreatic cancer should be determined in conjunction with evaluation of nodal status by cytokeratin staining. Extended operation was not useful for pancreatic cancer patients with micrometastases of group 2 nodes.