Concurrent chemoradiation alone with curative intent for limited-disease small-cell esophageal cancer in nine Japanese patients.

Small-cell carcinoma of the esophagus is a rare and aggressive tumor with early widespread dissemination. In this retrospective study, we report clinical outcomes of limited-disease small-cell carcinoma of the esophagus from the analysis of nine patients. Between 2003 and 2006, nine consecutive patients with small-cell carcinoma of the esophagus were treated in our single institution, representing 2.8% of all esophageal malignancies treated with curative concurrent chemoradiation during this period. All the patients received four cycles of etoposide (100 mg/m(2), days 1-3), combined with cisplatin (80 mg/m(2), day 1), plus radiation therapy (50 Gy in daily doses of 2 Gy, 5 days/week). At the time of analysis, the median follow-up time was 10.8 months (range: 4.2-42.8 months) and 21.8 months in five living patients (56%). Of all the nine patients, five patients (56%) had a complete response, and the actuarial 3-year overall survival rate was 55.6%. This regimen resulted in a favorable 3-year survival rate. We conclude that the optimum treatment seems to be the same as for small-cell carcinomas of the lung, that is, a multidrug combination chemotherapy regimen used with concurrent radiation.

Prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by X-ray irradiation in rats.

1. In the present study, we investigated the prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by either single (15 Gy) or repeated (8.6 Gy x3 days) X-ray irradiation in rats. Pilocarpine hydrochloride was administered orally 90 min before each irradiation session. Then, 7 days later, salivary volume, amylase activity and protein concentration in the saliva secreted from the right parotid gland were measured before and after a subsequent administration of pilocarpine hydrochloride (intraduodenal). 2. In irradiated no-pretreatment rats, irradiation induced a significant reduction in both spontaneous and pilocarpine hydrochloride-stimulated secretion (both total salivary volume and flow rate), regardless of the protocol used for X-ray exposure. In irradiated, pilocarpine hydrochloride-pretreated rats, salivary secretion was increased after stimulation by pilocarpine hydrochloride (intraduodenal) to a degree that depended on the pretreatment dose of pilocarpine hydrochloride (p.o.) in both xerostomia models. 3. There were no differences in amylase or protein concentrations between irradiated rats pretreated with pilocarpine hydrochloride and irradiated no-pretreatment control rats. 4. A decrease in the weight of the parotid gland was observed in rats exposed to either the single dose or repeated irradiation protocols. Changes in the submandibular gland were less marked than those in the parotid gland. These changes in gland weight were not affected by pilocarpine hydrochloride pretreatment. 5. The responsiveness of the parotid gland to subsequent stimulation with pilocarpine hydrochloride was apparently preserved in both xerostomia models by pretreatment with pilocarpine hydrochloride, which itself increased salivary secretion. This suggests that pilocarpine hydrochloride may exert functional protective effects against xerostomia that occurs following irradiation therapy through a stimulation of salivary secretion.

[Clinical efficacy and reduction effect on prostatic volume of chlormadinone acetate combined with tamsulosin hydrochloride in benign prostatic hyperplasia patients insufficiently treated with tamsulosin hydrochloride only].

Alpha adrenergic blocker has become the first choice in the medical treatment of benign prostatic hyperplasia (BPH). The efficacy of alpha adrenergic blocker has been suggested to be related to the prostatic tissue components, and to be ineffective in treating the clinical symptoms caused by BPH in some cases. The efficacy and prostate reduction of an anti-androgenic agent, chlormadinone acetate, combined with alpha adrenergic blocker, tamsulosin hydrochloride, were evaluated using 40-BPH patients insufficiently treated with tamsulosin hydrochloride alone. Fifty mg of chlormadinone acetate and 0.2 mg of tamsulosin hydrochloride were administered orally once a day for 16 weeks to patients with a prostate subjective symptoms score, I-PSS, of greater than 13 or a peak flow rate of less than 12 ml/s, even after the treatment with 0.2 mg of tamsulosin hydrochloride alone for more than four weeks. Total I-PSS decreased significantly after four weeks. The total irritative symptom score did not change for 16 weeks, but the total obstructive symptom score decreased significantly, as did the total I-PSS. In objective data, the estimated volume of both total prostate and the transition zone on transrectal ultrasonogram decreased significantly at the end of the treatment, and the peak flow rate decreased significantly after 12 weeks. These findings suggest that the addition of chlormadinone acetate may be a reasonable alternative in the treatment of BPH patients responding insufficiently to tamsulosin hydrochloride alone, and that combination therapy using chlormadinone acetate and tamsulosin hydrochloride may be useful for BPH patients with serious obstructive symptoms.

Vasoconstriction induced by zooxanthellatoxin-B, a polyoxygenated long-chain product from a marine alga.

We found that zooxanthellatoxin-B from a symbiotic marine alga, Symbiodinium sp., caused a concentration-dependent contraction of the rabbit isolated aorta at concentrations of 10(-7)-10(-5) M. Verapamil (10(-6) M) and mefenamic acid (10(-5) M) significantly attenuated the contractile response to zooxanthellatoxin-B at lower concentrations (10(-7)-10(-6) M) but not at higher concentrations (3 X 10(-6)-10(-5) M). The response to zooxanthellatoxin-B was partly inhibited by phentolamine (10(-6) M), whereas it was potentiated by ouabain (10(-5) M). Tetrodotoxin (10(-6) M), methysergide (10(-6) M), chlorpheniramine (10(-6) M) or indomethacin (3 X 10(-6) M), however, did not affect it. The zooxanthellatoxin-B-induced contraction was abolished by incubation in Ca2+-free solution. The contractile response increased in a concentration-dependent fashion with Ca2+ (0.03 and 10 mM) or Sr2 + (0.10 and 10 mM). After treatment with verapamil (10(-6) or 5 X 10(-6) M), the concentration-contractile response curves for Ca2+ and Sr2+ in the presence of zooxanthellatoxin-B were shifted to the right in parallel. MgCl2 (10 mM) shifted the concentration-response curve for Ca2+ more markedly than did verapamil. Zooxanthellatoxin-B increased tissue Na+ and reduced tissue K+ contents in the aorta, suggesting that zooxanthellatoxin-B increases Na+ and K+ permeability across the plasma membrane. These results suggest that the zooxanthellatoxin-B-induced contraction of the aorta is caused mainly by a direct action on smooth muscle, i.e., an increase in Ca2+ permeability that occurs at least partly through voltage-sensitive Ca2+ channels as well as through nonselective cation channels in the cell membrane of smooth muscle.

[A case of infected renal cyst: the usefulness of magnetic resonance imaging for preoperative diagnosis].

A 22-year-old woman was admitted to our hospital with complaints of fever and left flank and back pain. Laboratory examinations showed leukocytosis and high C-reactive protein level. On the upper pole of the left kidney, two renal cysts were disclosed by ultrasonography and computerized tomography. A simple renal cyst and an infected renal cyst could be distinguished by magnetic resonance images (MRI), because the infected renal cyst was less intense than the simple renal cyst on T2 weighted MRI. Percutaneous puncture and drainage of the cyst were performed under the guidance of ultrasonography. Bacterial culture of the infected cyst fluid was positive for E. coli. Two months after treatment, computerized tomography showed no evidence of recurrence of the infected renal cyst.

[Responses of tumor cell lines and surgical specimens transplanted into chorioallantoic membrane of chick embryo to anticancer agents in combination with/without hyperthermia].

The chorioallantoic membrane of chick embryo was used to examine the responses of tumor cell lines and surgically resected specimens to anticancer agents in combination with or without hyperthermia. B16-F10 melanoma, KK-47 cell line derived from a transitional cell carcinoma of the bladder and surgical specimens from urological malignancies were transplanted onto the chorioallantoic membrane of chick embryo 10 days after fertilization. The effects of intravascularly injected cyclophosphamide, cisplatin, adriamycin, mitomycin C, vincristine and vinblastine, in combination with or without hyperthermia, on the growth of the grafts were investigated. A 15-minute 42.5 degrees C hyperthermia exhibited most favorable anticancer effects in B16-F10 grafts (P less than 0.01) of all heating conditions tested. A combined use of hyperthermia and cisplatin, cyclophosphamide or adriamycin demonstrated a significantly high tumor regression rate in B16-F10 grafts (P less than 0.01). In KK-47 grafts, a single use of cyclophosphamide and a combined use of hyperthermia and cyclophosphamide exhibited a highly significant antitumor regression (P less than 0.05). Surgical specimens from 14 urological malignancies were subjected to this assay. Growth which was adequate for sensitivity test was obtained in 11 of the 14 malignancies. The results obtained suggest that this assay system may be a useful chemohyperthermia sensitivity test.

[Chemosensitivity studies of urological malignancies].

Chemosensitivity tests to anticancer agents using human tumor clonogenic assay (HTCA), novel dye exclusion method (NDE assay), sub-renal capsule assay (SRCA), and chick embryo method (CE method) were utilized to measure the sensitivity of urological malignancies. Surgical tumor specimens from 67 patients with urological malignancies were subjected to HTCA developed by Hamburger and Salmon. An appreciable growth of colonies was obtained in 20 out of 33 renal cancers, 20 out of 30 urothelial cancers and 1 out of 4 testicular tumors examined and colonial growth adequate for chemosensitivity was obtained in 30 of the 67 patients. More than 70% decrease in the plating efficiency after anticancer drug exposure according to Von Hoff's definition, or more than 1.0 value of the "in vivo -in vitro therapeutic index" in terms of the ratio of IC90 to the peak plasma concentration of the drug tested was defined as susceptible. According to Von Hoff's definition, susceptibility to vinblastine (VBL) and cis-dichlorodiammine platinum (CDDP), was seen in 4 out of 11 patients with renal cancer, in 4 out of 15 patients with urothelial cancer and 1 out of 4 patients with renal cancer, respectively. With adriamycin (ADM) it was seen in 3 out of the 15 patients with urothelial cancer, 2 out of 10 patients with renal cancer and 1 patient with testicular tumor. According to TI, susceptibility to VBL was seen in 3 out of 7 patients with renal cancer, and with CDDP it was seen in 2 out of 12 patients with urothelial cancer, and 1 out of 2 patients with renal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

[An in vitro chemosensitivity study using the human tumor clonogenic assay in urological malignancies: a preliminary report].

Surgical tumor specimens from 67 urological malignancy patients were subjected to a human tumor clonogenic assay (HTCA) developed by Hamberger and Salmon. Appreciable growth of colonies was obtained in 20 of the 33 renal cancers, 20 of the 30 urothelial cancers and 1 of the 4 testicular cancers examined. Using HTCA, a plating efficiency ranging from 0.01 to 0.5% was obtained in these urologic malignancies. However, colonial growth adequate for chemosensitivity was obtained in 30 of these 67 patients. According to Von Hoff's definition, more than a 70% decrease in the plating efficiency after anticancer drug exposure was defined as susceptible. Susceptibility to vinblastine (VBL) was seen in 4 of the 11 patients with renal cancer. Susceptibility to cis-dichlorodiamine platinum (CDDP) was seen in 4 of the 15 patients with urothelial cancer, 1 of the 4 patients with renal cancer, and that to adriamycin (ADM) was seen in 3 of the 15 patients with urothelial cancer, 2 of the 10 patients with renal cancer and 1 patient with testicular cancer. For comparison, the ratio of IC90 to the peak plasma concentration of the drug tested was used as the "in vivo-in vitro therapeutic index (TI)". According to TI, susceptibility to VBL was seen in 3 of the 7 patients with renal cancer, and that to CDDP was seen in 2 of the 12 patients with urothelial cancer, and 1 of the 2 patients with renal cancer. Susceptibility to ADM was seen in 3 of the 15 patients with urothelial cancer, and 1 of the 6 patients with renal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

[A new treatment of simple renal cyst: percutaneous instillation of minocycline hydrochloride into simple renal cyst].

Minocycline hydrochloride was percutaneously instilled into simple renal cysts to prevent recurrence of renal cysts after the puncture and aspiration of cystic fluid. Fifty-six simple renal cysts in 51 patients were punctured with an 18-gauge needle under ultrasonographic guidance, and the cystic fluid was aspirated under fluoroscopic control. A single 100 mg or 200 mg dose of minocycline hydrochloride dissolved in 5 ml of distilled water was instilled through the needle into the renal cyst. The patients were followed up by computed tomographic (CT) scan and ultrasonography 1, 3, 6 and 12 months after the treatment. Efficacy was evaluated after 3 months or longer. Of 20 renal cysts instilled with 100 mg of minocycline, efficacy was excellent in 10, good in 6 and poor in 4. Of 22 renal cysts instilled with 200 mg of minocycline, efficacy was excellent in 10, good in 9 and poor in 3. No significant difference was noted between the efficacy rate of 100 mg and 200 mg treatments. Complications attributable to treatment were observed in 15 patients: moderate pain in one, slight pain in 6, slight fever in 8 and slight hematuria in one. Neither severe adverse reactions nor infections were observed in any of the patients. These results suggest that the percutaneous instillation of minocycline into simple renal cysts is a new, simple, safe and effective treatment to prevent recurrence of the cyst and additionally to prevent infection following the puncture.

Chemosensitivity study of urological malignancies using a novel dye-exclusion method.

The chemosensitivity of several urological malignancies was determined using a novel dye-exclusion method. The tests proved to be successful in 22 out of 33 urothelial transitional-cell carcinomas, 21 out of 29 renal-cell carcinomas, and in 8 out of 13 testicular tumors, but in 0 out of 4 Wilms' tumors. At 10% of the peak plasma concentration of anticancer drugs achievable after single bolus injection, the sensitivity rates of urothelial transitional-cell carcinomas for cis-platinum, adriamycin, and carboquone were 27.3%, 13.3%, and 5.6%, respectively. At the peak plasma level, urothelial transitional-cell carcinomas were 'susceptible' to cis-platinum, carboquone, and adriamycin, the sensitivity rates being 60%, 50%, and 30%, respectively. The number of these carcinomas susceptible at the peak plasma level was significantly larger than that at 10% of the peak plasma level (P less than 0.01). However, renal-cell carcinomas exhibited a low sensitivity rate of 38% even when exposed to the peak plasma level. A similar trend was observed when tumor chemosensitivity was determined using a modified human tumor clonogenic assay. These results suggest that urothelial transitional-cell carcinomas may show good responses when anticancer drugs are given at high concentrations using methods such as intra-arterial infusion and intravesical instillation.

[An in vitro chemosensitivity study using human tumor clonogenic assay in urologic malignancies].

A soft agar colony formation assay, so called human tumor clonogenic assay (HTC assay) similar to that originally described by Salmon and colleagues, was utilized to measure the sensitivity of a total of 85 urologic malignancies including 36 urothelial cell carcinomas, 41 renal cell carcinomas, 5 testicular tumors, and 3 Wilms' tumors to anticancer drugs. In addition, the results obtained were compared with those of a novel dye exclusion method (NDE assay) described by Weisenthal and colleagues. The NDE assay was utilized to measure the sensitivity of a total of 63 urologic malignancies including 28 urothelial cell carcinomas, 25 renal cell carcinomas, 6 testicular tumors, and 4 Wilms' tumors to anticancer agents. In both assay series, the concentration of anticancer drugs tested was approximately one tenth of the maximum serum level achievable after single bolus injection. The colony forming rate inhibition of 70% or more in the HTC assay and the cell survival rate of 30% or less in the NDE assay were defined as "sensitive." Sixteen of the 36 urothelial cell carcinomas, 11 of the 41 renal cell carcinomas, and 1 of the 5 testicular tumors had both more than 30 colonies grown in control plates and enough cells in the specimens to provide at least one drug sensitivity testing. In urothelial cell carcinomas, 3 out of 13 tumors were "sensitive" to adriamycin, 3 out of 16 to cis-platinum, and 4 out of 15 to carboquone. In renal cell carcinomas, 2 out of 9 tumors were "sensitive" to adriamycin, 4 out of 11 to vinblastine, and none of 4 to Interferon alpha.(ABSTRACT TRUNCATED AT 250 WORDS)