Kenichi Matsuzu

Differential expression of facilitative glucose transporters in normal and tumour kidney tissues

To investigate the differences in the pattern of glucose transporter (GLUT) gene expression between normal and tumour tissues and among histological subtypes of renal cell carcinomas (RCCs), as malignant cells are characterized by increased glucose uptake and use.

Successful treatment of multiple small-bowel perforations caused by cytomegalovirus in a patient with malignant lymphoma : Report of a case

We report the successful management of multiple small-bowel perforations caused by cytomegalovirus (CMV) infection in a 60-year-old man, 1 day after CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) therapy induction for malignant lymphoma. Emergency laparotomy was performed for perforative peritonitis, but we did not resect the lesions at this time. Instead, we exteriorized the small bowel and then irrigated the peritoneal cavity and intestinal tract. His white blood cell count was low, at 200 cells/µl, so this therapy was continued until it recovered. The intestine was highly edematous, but it improved after irrigation with peritoneal dialysis solution. In the second-stage procedure, we resected the small bowel with the perforations, and constructed a jejunostomy and colostomy, then closed the abdominal cavity. Although the patient needed central venous hyperalimentation, he had a favorable postoperative course and started treatment again for the malignant lymphoma.

Outcome and characteristics of patients with malignant pleural effusion from differentiated thyroid carcinoma

Metastatic differentiated thyroid carcinoma (DTC) is an uncommon cause of malignant pleural effusion (MPE) and the characteristics and clinical course have been rarely described. Herein, we report a retrospective review of the clinical course of 18 patients (15 women and 3 men) with MPE from DTC who underwent treatment at our institution between January 2005 and December 2014. MPE from DTC was diagnosed based on cytology and/or level of thyroglobulin in the pleural fluid. Pathologically, papillary carcinoma was found in 16 patients and follicular carcinoma in 2 patients. Median ages at initial diagnosis of DTC and MPE were 64 years (range, 22-79) and 74 years (range, 39-86), respectively. All patients showed radiologically apparent lung metastases, with MPE developing after 0-212 months (median, 25). In 16 patients (88.9%), other coexistent distant metastases at the time of MPE diagnosis were found in the bone (n = 10), brain (n = 5), and skin (n = 2). All patients were treated conservatively with palliative thoracentesis or chest tube drainage with or without pleurodesis. Recurrent MPE after treatment was seen in 9 patients; discharge to home health care after treatment for MPE was possible for 14 patients. The overall survival after initial diagnosis varied considerably from 14 months to 37 years, but the median survival after appearance of MPE was 10 months (range, 1-28). Systemic therapy for iodine-resistant recurrent thyroid disease may need to be considered as a treatment option for patients with MPE.

Chemosensitivity of Anaplastic Thyroid Cancer Based on a Histoculture Drug Response Assay

The chemosensitivity of anaplastic thyroid cancer (ATC) to some cytotoxic agents was investigated by the histoculture drug response assay (HDRA). Thirty specimens from 22 patients with ATC were obtained from surgically resected subjects. The drugs tested were paclitaxel (PTX), docetaxel (DOC), adriamycin (ADM), nedaplatin (254-S), cisplatin (CDDP), carboplatin (CBDCA), etoposide (VP-16), 5-fluorouracil (5-FU), mitomycin C (MMC), and cyclophosphamide (CPA). PTX was the most effective agent, and 25 of 29 cases (86.2%) had high inhibition rates (IRs; over 70%), while DOC, another taxane, had lower IRs (median, 32.6%). 254-S had the second highest IR (median 68.1%), higher than other platins, CDDP (median 47.3%) and CBDCA (median 27.4%). The IR of 50% dose PTX (20 μg/mL, median 30.6%) was markedly decreased, while that of 50% dose 254-S (10 μg/mL, median 63.3%) still retained its inhibition effect compared to 100% dose. Most recurrent samples had higher IRs than primary lesions, but the IRs of different drugs differed between primary and recurrent lesions, even with samples from the same patients. PTX has a higher IR to ATC tissues in the HDRA, which suggests that it may be a key drug for the treatment of patients with ATC.

Clinical outcome by AMES risk definition in Japanese differentiated thyroid carcinoma patients.

OBJECTIVE This study aimed to analyse whether age, metastasis, extrathyroidal invasion and size (AMES) risk definition is valuable for Japanese patients with differentiated thyroid carcinoma (DTC). METHODS Two hundred and fifteen Japanese DTC patients (43 men, 172 women; mean age, 51.0 years; mean follow-up, 102 months) treated surgically at our institutions between 1981 and 2001 were retrospectively analysed. Clinicopathological features were compared between high-risk and low-risk patients by AMES criteria. Various risk factors were also evaluated for each group of patients. RESULTS There were 57 high-risk and 158 low-risk patients. Recurrence and mortality rates were 43.9% and 24.6% in high-risk patients and 7.6% and 0.6% in low-risk patients, respectively (p < 0.0001). Disease-specific survival rates at 5, 10 and 15 years were 84.3%, 74.0% and 63.5% in high-risk patients and 100%, 100% and 98.3% in low-risk patients, respectively (p < 0.0001). Univariate analysis revealed that curative resection, local recurrence and distant metastasis were risk factors for mortality in the high-risk group. Multivariate analysis revealed that curative resection (hazard ratio [HR], 4.68; 95% confidence interval [CI], 1.23-17.83; p = 0.024) and distant metastasis (HR, 4.79; 95% CI, 1.24-18.40; p = 0.023) were significantly related to mortality in high-risk patients. CONCLUSION AMES can identify high-risk and low-risk Japanese patients. Distant metastasis and curative resection are prognostic factors for disease-specific death.

Lenvatinib induces early tumor shrinkage in patients with advanced thyroid carcinoma

Although advanced thyroid carcinoma patients who cannot be cured by conventional therapy have lacked effective treatment, multitargeted tyrosine kinase inhibitors have recently become available. Phase 3 trials of lenvatinib showed a median time to objective response of 2 (95 % confidence interval (CI) 1.9-3.5) months, demonstrating that shrinks tumors rapidly. The phenomenon of immediate tumor shrink is known as early tumor shrinkage (ETS) which is related to clinical outcome in other malignancies. However, precisely when within 8 weeks lenvatinib starts to affect tumors remains unclear. In tumors near the carotid arteries, trachea, or esophagus, a rapid therapeutic effect can induce fistula formation or arterial bleeding. To prevent such treatment-emergent serious adverse events (SAE), early imaging evaluation seems to be very important. In this study, the point in time when lenvatinib started to shrink tumors was retrospectively investigated. The subjects were 16 patients who started lenvatinib administration between May and August 2015. Tumor size was evaluated by computed tomography (CT) scans frequently within the first 8 weeks according to the Response Evaluation Criteria In Solid Tumors (RECIST) guideline. Initial tumor response was defined as ≥ 10% tumor reduction. Serum thyroglobulin (Tg) level was monitored in 8 differentiated thyroid carcinoma (DTC) without TgAb patients. At the first evaluation, 13 patients (83.3 %) showed tumor reduction and that decreased with time. Thirteen patients (83.3 %) showed >10 % tumor reduction within 8 weeks. In all DTC patients, serum Tg level was markedly decreased. In conclusion, lenvatinib immediately shrinks tumors, the so-called ETS phenomenon. Therefore, careful attention should be paid to fistula formation from the early phase.