Improvement of treatment outcomes after implementation of comprehensive pharmaceutical care in breast cancer patients receiving everolimus and exemestane.

Combination therapy with everolimus and an aromatase inhibitor such as exemestane is an effective treatment option for advanced or recurrent breast cancer. However, the therapy is often limited because of the occurrence of severe adverse events (AEs), including oral mucositis, interstitial lung disease, diarrhea, and rash. Therefore, early management of AEs is extremely important to obtain maximum treatment outcome. We investigated here the effects of comprehensive pharmaceutical care for prevention of severe AEs on patient's quality-of-life (QOL) and continuation of therapy. QOL was assessed every month based on the five-level version of EuroQol-5-Dimension (EQ-5D-5L). AEs were graded according to the Common Terminology Criteria for Adverse Events (ver 4.0). Implementation of comprehensive pharmaceutical care remarkably reduced the incidence of severe oral mucositis as compared with those without such interventions. EQ-5D-5L health states were almost constant during 6 months after intervention, ranging from 0.850 to 0.889. Median time to treatment failure (TTF) was significantly longer after intervention than before [224.0 days, 95% confidence interval (CI): 117-331 days versus 34 days, 21-47 days, hazard ratio (HR): 0.027, 95% CI: 0.005 - 0.154, p<0.001]. These findings suggest that our comprehensive pharmaceutical care is highly effective for enhancing treatment outcome by maintaining patient's QOL.

Prognostic factors and therapeutic strategy for anaplastic carcinoma of the thyroid.

Although anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies, a few patients survive for a fairly long time after modern intensive treatment. We tried to identify prognostic factors of ATC to assist in deciding on the proper therapeutic strategy in individual patients. Of 47 patients with ATC (1976-1999), 3 patients with "incidental" ATC (largely differentiated thyroid carcinoma with a small region of ATC) were excluded because they had a favorable outcome. The 1-year survival rate of the remaining 44 patients with clinically distinct ATC was 16%. The presence of acute symptoms, large tumor (> 5 cm), distant metastasis, and leukocytosis (white blood cell count > or = 10,000/mm3) proved to be significant risk factors. Multivariate analysis by the Cox proportional hazard model showed that these four factors were independent factors for predicting death from ATC. We devised a novel prognostic index (PI) based on the number of these four unfavorable characteristics the patient possessed. Patients with a PI of < or =1 had a 62% survival rate at 6 months, whereas no patients with a PI of > or =3 survived longer than 6 months. All patients with a PI of 4 died from their disease within 3 months. Nine patients received multimodal treatment with a combination of surgery, external irradiation, and chemotherapy and had a long survival (mean 333 +/- 68 days; one patient is still alive and tumor-free), with a mean PI of 0.6. Our PI is useful as a means of selecting patients for aggressive therapy. When the PI is low, multimodal treatment should be attempted to obtain the best survival results; if it is high most patients are too seriously ill to tolerate intensive treatment and palliative therapy is recommended.

Symptomatic versus asymptomatic papillary thyroid microcarcinoma: a retrospective analysis of surgical outcome and prognostic factors.

Although the mortality rate associated with papillary microcarcinoma (PMC) of the thyroid generally is very low, some patients present with bulky nodal metastasis or distant metastasis and have an unfavorable prognosis. We retrospectively reviewed clinical aspects, surgical treatment and outcome of 178 patients with PMC in an attempt to determine the prognostic factors. The cause-specific 10-year survival rate was 96%. Three of four patients who showed signs of distant metastasis during the postsurgical period died of the disease, and another died of local recurrence. The most significant prognostic factors were the presence of clinically apparent lymph-node metastasis and hoarseness due to recurrent nerve palsy at the time of diagnosis. All distant metastases and cancer-specific deaths occurred in the 30 patients with symptomatic PMC who had either cervical lymphadenopathy, recurrent laryngeal nerve palsy or both. The 148 patients who had neither symptom had a distinctly favorable outcome. Total thyroidectomy followed by radioactive iodine treatment did not improve the final outcome in patients with symptomatic PMC. We conclude that patients with asymptomatic PMC can expect a truly favorable outcome, but some of those with symptomatic PMC may fall within a high-risk group of patients who do not benefit from aggressive treatment.

Clinicopathologic and immunohistochemical studies of papillary thyroid microcarcinoma presenting with cervical lymphadenopathy.

Although most papillary thyroid microcarcinomas (PMCs) are of little clinical significance, patients with PMCs occasionally have an unfavorable outcome, especially when they present with bulky nodal metastasis or distant metastasis. We have attempted to identify "high-risk" PMCs by evaluating clinical, pathologic, and immunohistochemical prognostic factors. Among 190 patients with a PMC, 156 without clinically apparent nodal metastasis had a benign course. The remaining 34 patients, who presented with cervical lymphadenopathy of at least 1 cm, were studied. Three of the four patients who developed distant metastasis died of the disease, and the other died of local recurrence. All patients who developed distant metastasis or died of the disease had both nodal metastasis of at least 3 cm and a nonencapsulated type of primary lesion. All patients who developed distant metastasis showed both extracapsular extension of the metastatic lesions in lymph nodes and positive staining for transforming growth factor-beta3 (TGFbeta3) (a potent growth inhibitor) in the primary lesion. The Ki-67 (an indicator of cell proliferation) labeling indices in the primary and metastatic nodal lesions of patients who died of cancer were significantly higher than those of the others with nonfatal disease. None of the patients showed P53 (nuclear tumor-suppressor phosphoprotein) overexpression. In conclusion, patients with PMC who have both 3 cm or larger lymphadenopathy and a nonencapsulated type of primary lesion may be regarded as high-risk patients. Immunohistologic positivity for Ki-67 and TGFbeta3 in cancer cells is a potential indicator of aggressively malignant PMC.

Postoperative prognosis of intrathyroidal papillary thyroid carcinoma: long-term (35-45 year) follow-up study.

We performed a long-term (35 to 45 year) follow-up study on patients who underwent surgery for intrathyroidal papillary thyroid carcinoma in order to reveal the natural history of the disease. Forty-nine patients underwent primary surgery for intrathyroidal papillary carcinoma during an 11-year period, 1950-1960. Various primary surgeries were performed, including neck exploration alone, tumor enucleation, hemi-, subtotal- and total-thyroidectomy in 2, 7, 21, 5 and 14 instances, respectively. Postoperative external irradiation was performed for most patients during the latter half of the period, and TSH suppression was carried out from 1956 through 1970. Follow-up studies were done in 1958, '62, '66, '69, '76 and currently 1997. Two patients, who had had only neck exploration and external irradiation, subsequently spent nearly normal lives for 10 and 32 years. Of the 28 patients who received hemithyroidectomy or lesser surgery, cancer recurrence in the remnant thyroid occurred in nine, of whom five received reoperation. At present, of all 49 patients, 22 are alive and well, and three are alive with asymptomatic recurrence. Only one male patient who had noted the initial lymph node metastases at age 15 died of bone metastasis 22 years after neck surgery. No other patients died definitely of thyroid cancer, although the causes of three deaths were unknown and one patient was lost after incomplete resection. The results of this study strongly support the idea that the majority of intrathyroidal papillary carcinomas remain non life-threatening for over 40 years and that they can be successfully treated by complete removal of macroscopic tumors by conservative surgery, hemi- or subtotal thyroidectomy, without associated adjuvant therapies.

[Therapeutic efficacy of hepatectomy in the treatment of hepatic metastases from breast cancer].

This study was performed to evaluate whether or not surgical excision of hepatic metastases from breast cancer has any effect on the prognosis. Between September 1985 and April 1993, eight patients with hepatic metastases (solitary in four cases, multiple in four cases) underwent hepatectomy. Two patients among them had other remote recurrence besides that arising in the liver. Right hepatectomy in two cases, left hepatectomy in one, extended left hepatectomy in one and partial hepatectomy in four were done. No postoperative complications developed. Four patients incurred liver recurrence within an average period of 11.5 months after hepatectomy, with three of average period of 11.5 months after hepatectomy, with three of them dying from the disease within 16 to 36 months after hepatectomy. The other four were free of liver recurrence and remained alive for 3 to 65 months post-operatively. The 50% survival time was 36 months after hepatectomy and 40 months after the discovery of hepatic metastases. Although hepatectomy could only be applied to a restricted number of patients and these results are obviously insufficient, we believe that surgical procedure for liver metastases from breast cancer, if possible, is undoubtedly beneficial in prolonging the survival in such patients.

[A case of anaplastic carcinoma of the mediastinal goiter].

We reported a case of anaplastic carcinoma of mediastinal goiter. The initial symptom was hoarseness, and thyroid scintigram and venogram revealed mediastinal thyroid malignant tumor, although cervical tumor could not be palpated. Operation was performed with median sternotomy. The size of the tumor was 8 x 6 x 3cm. Histological examination showed papillary adenocarcinoma of left lower pole of the thyroid gland which was transformed into anaplastic carcinoma and extended to the mediastinal cavity. Anaplastic carcinoma of mediastinal goiter is very rare, and our case showed anaplastic transformation from papillary adenocarcinoma.