Pilot Study of Irinotecan and S-1 (IRIS) for Advanced and Metastatic Breast Cancer.

BACKGROUND/AIM: Irinotecan is rarely used on the metastatic breast cancer (MBC) setting. S-1 is an oral mixture of tegafur, gimeracil and oteracil. We conducted this pilot study to assess efficacy and safty of chemotherapy with combined irinotecan and S-1 (IRIS). PATIENTS AND METHODS: Irinotecan was given intravenously at 80 mg/m2 on days 1 and 8 and S-1 was given orally at 80-120 mg/day depending on body surface area for 2 weeks, repeating the cycle every 3 weeks. RESULTS: Twenty-two patients were enrolled in the study. Median age was 50.5 years (range=26-72). Nineteen patients were evaluable for response. Median overall survival and progression-free survival were 672 days (95% CI=420-967) and 166 days (95% CI=76-814), respectively. CONCLUSION: The IRIS regimen has an acceptable safety profile and modest efficacy against MBC in patients previously heavily treated with chemotherapy. This regimen has potential to treat MBC.

Can the use of intraoperative intact parathyroid hormone monitoring be abandoned in patients with hyperparathyroidism?

BACKGROUND: Ultrasound (US) and technetium-99m sestamibi scintigraphy (MIBI) are used to determine the localization of abnormal glands in cases of primary hyperparathyroidism (PHPT). Intraoperative intact parathyroid hormone (iPTH) monitoring is a reliable examination used to cure PHPT. The aim was to assess the necessity of intraoperative iPTH monitoring. METHODS: Sixty patients were examined using preoperative MIBI and US. iPTH was measured at 3 time points: (1) at the start of surgery; (2) 10 minutes after gland resection; and (3) more than 60 minutes after surgery. We defined a decreased iPTH level as an iPTH measured 10 minutes after resection that was less than 50% of the preoperative level. RESULTS: The iPTH of 55 patients with concordant lesions decreased to within the normal range more than 60 minutes after surgery. CONCLUSIONS: It is not necessary to monitor intraoperative iPTH when single concordant lesions are preoperatively identified on both MIBI and US.

A case of mixed medullary and follicular cell carcinoma of the thyroid.

A medullary thyroid carcinoma is a malignant tumor derived from the C-cells of the thyroid. Despite their distinct embryological origin, medullary thyroid carcinomas are exceptionally accompanied by a tumor derived from the follicular cells; this is defined as mixed medullary and follicular cell carcinoma. There have been controversies regarding the origin of this rare mixed thyroid carcinoma questioning whether or not a mixed carcinoma originates from a common cancer stem cell. We present a case of mixed medullary and follicular cell carcinoma in which two thyroid carcinomas were found intermingled in the thyroid as well as in the metastatic cervical lymph nodes. We examined the tumor by immunostaining with thyroglobulin, calcitonin, and thyroid transcription factor-1, and also reviewed the literature and discuss the origin of this rare mixed thyroid carcinoma.

Dedifferentiation of human primary thyrocytes into multilineage progenitor cells without gene introduction.

While identification and isolation of adult stem cells have potentially important implications, recent reports regarding dedifferentiation/reprogramming from differentiated cells have provided another clue to gain insight into source of tissue stem/progenitor cells. In this study, we developed a novel culture system to obtain dedifferentiated progenitor cells from normal human thyroid tissues. After enzymatic digestion, primary thyrocytes, expressing thyroglobulin, vimentin and cytokeratin-18, were cultured in a serum-free medium called SAGM. Although the vast majority of cells died, a small proportion (∼0.5%) survived and proliferated. During initial cell expansion, thyroglobulin/cytokeratin-18 expression was gradually declined in the proliferating cells. Moreover, sorted cells expressing thyroid peroxidase gave rise to proliferating clones in SAGM. These data suggest that those cells are derived from thyroid follicular cells or at least thyroid-committed cells. The SAGM-grown cells did not express any thyroid-specific genes. However, after four-week incubation with FBS and TSH, cytokeratin-18, thyroglobulin, TSH receptor, PAX8 and TTF1 expressions re-emerged. Moreover, surprisingly, the cells were capable of differentiating into neuronal or adipogenic lineage depending on differentiating conditions. In summary, we have developed a novel system to generate multilineage progenitor cells from normal human thyroid tissues. This seems to be achieved by dedifferentiation of thyroid follicular cells. The presently described culture system may be useful for regenerative medicine, but the primary importance will be as a tool to elucidate the mechanisms of thyroid diseases.

Parenchymal leiomyoma of the breast: a case report with special reference to magnetic resonance imaging findings and an update review of literature.

Parenchymal leiomyomas of the breast are extremely rare, with only 25 cases reported in the literature. We report the 26th case of parenchymal leiomyoma of the breast in a 63-year-old woman who presented to us with a right breast tumor detected on her screening mammography. This tumor was evaluated by mammography, ultrasonography, and MR imaging. To the best of our knowledge, this is the first case of a parenchymal leiomyoma of the breast examined by MR imaging. MR imaging revealed an oval mass with circumscribed margins that appeared as a high-intensity lesion in both T1 and T2. A dynamic MRI study showed a gradual increase pattern on the mass. Excisional biopsy revealed a growth pattern of interlacing fascicles of spindle cells without atypia or mitoses, consistent with parenchymal leiomyoma of the breast. Here we report a case of parenchymal leiomyoma of the breast, and describe the clinical, pathological, and immunohistochemical findings. In addition, we review the literature on parenchymal leiomyoma of the breast with regard to clinical characteristics and pathological features of this entity.

Incomplete inside-out growth pattern in invasive breast carcinoma: association with lymph vessel invasion and recurrence-free survival.

Invasive micropapillary carcinoma (IMPC) is a rare subtype of epithelial tumor of the breast listed in the 2003 World Health Organization histologic classification of tumors of the breast. It is characterized by inside-out micropapillary morphology, frequent lymph vessel invasion (LVI), and lymph node metastasis; however, its etiology remains unknown. This study investigated the incomplete inside-out growth pattern (IGP) in invasive ductal carcinoma, not otherwise specified (NOS), and examined the association between incomplete IGP and clinicopathologic features, including the presence of intratumoral lymph vessels (ILV), LVI, nodal metastasis, and prognosis. Tumor tissues from 166 invasive duct carcinomas NOS and 10 IMPCs were immunostained using an anti-epithelial membrane antigen antibody to detect IGP and with D2-40 antibody to determine the presence of ILV and LVI. Incomplete IGP was detected focally in 88 (53%) of 166 invasive duct carcinomas NOS. Transition areas between IMPC and invasive duct carcinoma NOS also showed prominent incomplete IGP in 9 (90%) of 10 IMPCs. Incomplete IGP in invasive duct carcinomas NOS was associated with larger tumor size, higher frequencies of ILV, LVI, nodal metastasis, and poorer recurrence-free survival by univariate analysis. Incomplete IGP, ILV, and tumor size independently affected LVI by multivariate analysis. These findings indicate that incomplete IGP of tumor cell clusters is not uncommon and is a useful tool for predicting LVI in invasive duct carcinoma NOS of the breast.

Cyclin E low-molecular-weight isoform as a predictor of breast cancer in Japanese women.

Overexpression of low-molecular-weight isoforms (LMWI) of cyclin E in breast cancer cells is associated with poor prognosis and could serve a novel role in breast cancer progression. LMWI originate from proteolytic processing of cyclin E, which is deregulated and hyperactive. In this study, levels of full-form/LMWI cyclin E were determined with the use of Western blot analysis in 69 Japanese breast cancer patients. LMWI cyclin E levels were significantly correlated with known parameters such as tumor grade and estrogen/progesterone receptor expression. In multivariate analysis, patient survival was significantly correlated with tumor grade but not with either form of cyclin E. LMWI was not as strong a predictor as tumor grade in this study, whereas some cases of early relapse with LMWI overexpression and lower tumor grade were reported. Thus, LMWI might be a good complementary factor to other predictors for early relapse of breast cancer.

Diagnostic performance of ADC for Non-mass-like breast lesions on MR imaging.

We assessed the usefulness and limitations of utilizing apparent diffusion coefficient (ADC) values on diffusion-weighted imaging (DWI) for the differential diagnosis of benign and malignant non-mass-like breast lesions. We retrospectively reviewed 27 such lesions (16 malignant, 11 benign) detected on magnetic resonance (MR) imaging and analyzed the enhancing patterns of dynamic contrast-enhanced DCE-MRI (distribution and internal enhancement), kinetic curve patterns, and ADC values. All images were obtained with a 1.5-tesla MR unit, with patients supine. On DCE-MRI, malignant lesions tended to show either segmental or branching-ductal distribution, and when lesions with these patterns were considered malignant, sensitivity was 68.8%; specificity, 63.6%; positive predictive value (PPV), 73.3%; negative predictive value (NPV), 58.3%; and accuracy, 66.7%. Kinetic curve analysis did not reliably differentiate benign and malignant non-mass-like lesions. There was no significant difference between the mean ADC value of the malignant lesions, 0.968 × 10(-3) mm(2)/s at b=1000 s/mm(2), and that of benign lesions, 1.207 × 10(-3) mm(2)/s (P=0.109). Receiver operating characteristic (ROC) analysis revealed the most effective threshold of ADC value for differentiating tumors as 1.1 × 10(-3) mm(2)/s; values lower than this were observed more often in malignant than benign lesions (P=0.054). Us of this threshold yielded sensitivity of 68.8%; specificity, 72.7%; PPV, 78.6%; NPV, 61.5%; and accuracy, 70.4%. Combining the ADC value criteria with the analysis of DCE-MRI pattern increased sensitivity to 93.8%, negative predictive value (NPV) to 85.7%, and accuracy to 77.8% but decreased specificity to 54.5%. Use of ADC values does not adequately improve DCE-MRI performance for differential diagnosis of non-mass-like breast lesions, but adding the ADC value criteria to the DCE-MRI pattern analysis improves sensitivity, NPV, and accuracy.

Clinical significance of categorisation of mammographic density for breast cancer prognosis.

Mammographic density reflects comprehensive changes in the mammary gland. The condition of the tumour microenvironment is a possible factor affecting tumour progression, as well as a tumour risk factor. This study aimed to determine whether mammographic density correlates with tumour clinicopathological features and prognosis in breast cancer patients. The analysis involved 163 Japanese women who underwent surgery for breast cancer between 1999 and 2003 in the Nagasaki University Hospital, Japan. Mammographic density was classified according to the breast imaging reporting and data system (BI-RADS) categories 1-4. Age, tumour size, axillary lymph node involvement, steroid receptor (SR) status, histological grade and Nottingham prognostic index (NPI) were analysed by density category and tested for statistically significant differences across categories. A significant difference (P<0.05) by breast-density category was found only for age. SR-negative tumours had significantly worse NPI scores than SR-positive tumours in breast-density categories 2 (P=0.03) and 4 (P<0.001). A high distant-metastasis frequency was observed in category 4 SR negatives (44%) versus category 4 SR positives (4.3%). These findings reveal that although the BI-RADS breast-density category alone is not associated with prognosis in breast cancer, patients who are both category 4 and SR negative have an extremely poor prognosis.