Adjuvant endocrine therapy effects on bone mineral density and microstructure in women with breast cancer.

INTRODUCTION: Although aromatase inhibitors (AIs) are typical drugs for cancer treatment-induced bone loss, their effects on the bone microstructure remain unclear. In this study, we evaluated changes in the bone mineral density (BMD) and bone microstructure associated with AI treatment using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with early breast cancer. MATERIALS AND METHODS: This prospective, single-arm, observational study included non-osteoporotic, postmenopausal women with hormone receptor-positive breast cancer. Patients underwent dual-energy X-ray absorptiometry (DXA), HR-pQCT, and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide measurements at baseline and 6 and 12 months after AI therapy. The primary endpoint was changes in the total volumetric BMD (Tt.vBMD), trabecular vBMD (Tb.vBMD), and cortical vBMD (Ct.vBMD) longitudinally at the distal radius and tibia. RESULTS: Twenty women were included (median age 57.5 years; range 55-72 years). At 12 months, HR-pQCT indicated a significant decrease in the Tt.vBMD (median distal radius - 5.3%, p < 0.01; distal tibia - 3.2%, p < 0.01), Tb.vBMD (- 3.2%, p < 0.01; - 1.0%, p < 0.05, respectively), and Ct.vBMD (- 3.2%, p < 0.01; - 2.7%, p < 0.01, respectively). Estimated bone strength was also significantly decreased. The DXA BMD value in the total hip (p < 0.01) and femoral neck (p = 0.03), but not in the lumbar spine, was significantly decreased. The TRACP-5b levels was significantly negatively associated with changes in the Tt.vBMD in both the distal radius and tibia (r =  - 0.53, r =  - 0.47, respectively) CONCLUSION: Postmenopausal women who received AIs for early breast cancer experienced significant trabecular and cortical bone deterioration and a decrease in estimated bone strength within only 1 year.

[A case of refractory pancreatic fistula following pancreaticoduodenectomy treated successfully by intestinal decompression catheter insertion to jejunum under local anesthesia].

The case was an 80-year-old woman with inferior bile duct cancer. The patient had undergone subtotal stomach-preserving pancreaticoduodenectomy with end-to-side pancreaticojejunostomy. Postoperative pancreatic fistula was observed in a short period and was treated by somatostatin analog administration and abscess drainage. Despite these conservative therapies, pancreatic fistula resulted in abdominal bleeding from the branch of dorsal pancreatic artery, which stopped by emergent transcatheter arterial embolization. Because pancreatic fistula had become refractory, the intestinal decompression catheter insertion was performed under local anesthesia to the jejunum located directly below abdominal wall. After this surgery, pancreatic fistula was resolved over a few weeks. This technique could be safely performed and avoided the injury of drainage fistula, and was considered to be an option for treating refractory pancreatic fistula.

[A complete response of locally-advanced poorly differentiated adenocarcinoma of the rectum to pre-operative chemo-radiation therapy].

A 71-year-old woman with peri-anal pain and anal bleeding was found to have a tumor in lower rectum in colonoscopic examination, which was histologically diagnosed as poorly differentiated adenocarcinoma. Computed tomography and magnetic resonance imaging showed a tumor 5 cm in diameter deeply infiltrating mesorectum, and swelling of intra-pelvic lymph nodes. At the first operation, infiltration of the tumor was so deep that a complete surgical resection was considered to be difficult, and only a sigmoid colostomy construction was done. After chemo-radiation therapy of 50.4 Gy and 5-FU plus levofolinate calcium (Isovorin) infusion, the tumor was reduced in size and lymph nodes were extremely decreased. The patient underwent an abdominoperinial resection 6 weeks after the end of chemo-radiation, and pathological examination revealed a complete replacement of tumor with necrosed tissue, and no viable tumor cell was found. Poorly differentiated adenocarcinoma of the colon is reported to be highly malignant and associated with poor prognosis. Preoperative chemo-radiation therapy can be a promising candidate for adjuvant treatment of locally-advanced poorly differentiated adenocarcinoma of the rectum.

Adjuvant hepatic arterial infusion after curative resection of colorectal liver metastases using removable intra-arterial catheters with shape-memory alloy.

BACKGROUND AND OBJECTIVES: Although there are some reports that adjuvant hepatic arterial infusion (HAI) chemotherapy reduces the hepatic recurrence following curative resection of colorectal liver metastases, problems of indwelling catheters after chemotherapy cessation remains unsolved. The usefulness of adjuvant HAI was investigated using a removable port-catheter system. METHODS: Spiral catheterstrade mark were attempted to be placed in 17 patients who underwent curative hepatectomy. The catheter contains a special shape-memory alloy at its tip, which allows stable fixation to the vascular wall without coiling so the catheter can be removed if necessary. 5-fluorouracil (5-FU) in total dose of 12 g was intra-arterially administered. RESULTS: W spiral catheterstrade mark were successfully placed in the hepatic artery by percutaneous approach in 82% of the patients. All patients underwent scheduled chemotherapy without serious adverse events. Reservoir-catheter system was removed easily and uneventfully after discontinuation of the chemotherapy. 3D-CT angiography revealed that the hepatic artery was well preserved with short-term chemotherapy. Postoperative hepatic recurrence was observed only in 18% of the patients with the median follow-up time of 19.9 months. CONCLUSIONS: Prophylactic 5-FU HAI using W spiral cathetertrade mark and subsequent catheter extirpation is a promising strategy following curative resection of colorectal liver metastases.

Polymorphism in the thymidylate synthase promoter enhancer region is not an efficacious marker for tumor sensitivity to 5-fluorouracil-based oral adjuvant chemotherapy in colorectal cancer.

Thymidylate synthase (TS) is the target enzyme of 5-fluoropyrimidines. The TS gene promoter enhancer region (TSER) possesses tandem, repeated, regulatory sequences that are polymorphic in humans. This polymorphism has been reported to influence TS expression in vitro and in vivo. In this study, we assessed whether or not the TSER genotype is an efficacious marker for tumor sensitivity to 5-fluorouracil (5-FU)-based oral adjuvant chemotherapy for colorectal cancer. One hundred and thirty-five Japanese patients who received curative resection and 5-FU-based oral adjuvant chemotherapy were studied. TSER genotypes of the tumors were analyzed by PCR. The numbers of repeated sequences of representative bands were determined by direct sequence. The genotypes of two-/two-repeats (TSER 2/2), two-/three-repeats (TSER 2/3), three-/three-repeats (TSER 3/3), and three-/five-repeats (TSER 3/5) were found in 11 (8.1%), 32 (23.7%), 85 (63.0%), and 7 (5.2%) tumors, respectively. Patients were classified into two groups: TSER 2/2 or 2/3 group; and the TSER 3/3 group. The relationship between the TSER genotype group and disease-free intervals was analyzed by univariate and multivariate analyses. Five-year disease-free survivals of the TSER 2/2 or 2/3 group and the TSER 3/3 group were 77% and 75%, respectively (P = 0.89). Multivariate analysis revealed that stage was the only independent prognostic factor and that the TSER genotype did not have a prognostic significance (hazard ratio for TSER 3/3, 0.91; P = 0.84). In conclusion, TSER genotype is not an efficacious marker for tumor sensitivity to 5-FU-based oral adjuvant chemotherapy for Japanese colorectal cancer patients after curative resection.