anti-tumor effect of AlkB homolog 3 knockdown in hormone- independent prostate cancer cells.

Castrate resistant prostate cancer (CRPC) is a disease that is resistant to both hormone therapy and chemotherapy. At present, no curative therapy for CRPC has been established. Therefore, it is necessary to determine a novel molecular target for the development of therapeutic agents. We previously reported that AlkB homolog 3 (ALKBH3) is highly expressed in prostate cancer but not in benign prostatic hyperplasia or in normal prostate epithelium and that the expression levels of ALKBH3 protein are significantly correlated with the hormone-independent state of prostate cancer. Moreover, ALKBH3 regulates the invasion of prostate cancer cells via the regulation of matrix metalloproteinase 9. Here, we show that ALKBH3 gene silencing markedly induces apoptosis in hormone-independent prostate cancer cell line DU145 but not in the normal prostate epithelial cell line PNT2. Moreover, the in vivo tumorigenicity of DU145 cells was significantly inhibited by the administration of ALKBH3 siRNA. Furthermore, the anchorage-independent growth of DU145 cells was inhibited by ALKBH3 knockdown and promoted by ALKBH3 overexpression, significantly. ALKBH3 shRNA-expressing prostate cancer cells formed significantly smaller tumors than those of control shRNA transfectants in an in vivo xenograft model. These findings suggest that ALKBH3 is a promising target molecule for the development of CRPC therapeutic agents.

Short communication. Development of a fine thermocouple-needle system for real-time feedback of thermal tumour ablation margin.

Thermal tumour ablation techniques such as radiofrequency (RF) ablation are applied for radical removal of local tumours as an easier, less invasive alternative to surgical resection. A serious drawback of thermal ablation, however, is that the ablation area cannot be accurately assessed during the procedure. To achieve real-time feedback and exact and safe ablation, a superfine thermocouple-needle system (TNS) comprising a 0.25-mm diameter thermocouple embedded in a 22-G, 15-cm-long needle was devised and efficacy was tested in vitro using porcine livers (n = 15) and in vivo using rabbit back muscles (n = 2) and livers (n = 3). A 17-gauge RF electrode with a 2 cm active tip was used for ablation. The TNS was inserted 1 cm from the active tip of the RF electrode and liver temperature around the electrode was measured concurrently. The RF current was cut off when the temperature reached 60°C or after 5 min at ≥50°C. Porcine livers and rabbit back muscles were then cut along a plane passing through the axes of the electrode and the TNS. In rabbit livers, contrast-enhanced CT was performed to evaluate ablation areas. Ablation areas in cut surfaces of porcine livers exhibited well-defined discoloured regions and the TNS tip precisely pinpointed the margin of the ablation area. Contrast-enhanced CT of rabbit livers showed the TNS tip accurately located at the margin of areas without contrast enhancement. These results indicate that the TNS can accurately show ablation margins and that placing the TNS tip at the intended ablation margin permits exact thermal ablation.

CT-guided radiofrequency liver tumour ablation: use of a two-step coaxial system with a fine guide needle wire unit for high-risk cases.

Accurate radiofrequency (RF) needle targeting to liver lesions under CT guidance is technically difficult and generally requires multiple needle manipulations, which carries potential risk. This approach is hardly applicable for precariously located lesions or for patients who have difficulty holding their breath. The aim of this study was to develop a novel two-step coaxial system to facilitate CT-guided RF ablation in difficult cases. The study group comprised 11 patients with 12 hepatic lesions. The coaxial system consisted of two parts: a 21-gauge pencil-tip guide needle wire (GNW) unit comprising a 150-mm-long needle segment and a 250-mm-long wire segment; and a 140-mm-long outer cannula with its stylet, which accepts a 17-gauge RF electrode needle. The GNW was inserted until the route of the GNW was confirmed to be positioned correctly. The cannula with the stylet was then advanced along the GNW. Lesions were successfully accessed using the GNW, even in patients who could not hold their breath, and manipulation was feasible within the limited space of the CT gantry. The light GNW also facilitated step-by-step CT-guided angular manipulations, unlike heavy RF electrodes, which are unstable during hands-free use unless deeply inserted. Therefore, this system enabled sequential ablations of large tumours by ensuring three different routes in advance by using the GNW. Insertion of the cannula along the GNW was simple. In conclusion, the two-step coaxial system enabled CT-guided RF tumour ablation to be performed in cases conventionally contraindicated owing to high risk of serious complications.

Expansion of radiofrequency ablation volume by saturated NaCl saline injection in the area of vaporization.

BACKGROUND: Vaporization around the radiofrequency (RF) electrode after RF application (RFA) limits the RF ablation area. PURPOSE: To determine whether saturated saline injected into the area of vaporization after initial RFA extends ablation area after further RFA. MATERIAL AND METHODS: RFA was performed in 18 ex vivo porcine livers and four in vivo rabbit erector spinae muscles. An RF electrode was used to ablate an area with 40W of parallel current for 15 min. The ablation margin was determined using a thermocouple, and the radius of the ablated area was measured. After RF electrode removal, saturated saline was infused through a percutaneous ethanol injection needle into the site of the original RFA in 11 liver samples and two erector spinae muscles. Three minutes later, RFA was resumed for 15 min. The remaining seven control liver samples and two spinae muscles received RFA without saline injection. The radius of the final ablated area was then measured. RESULTS: In the ex vivo study, injection of saturated saline significantly decreased tissue impedance (87.7+/-9.4 to 51.1+/-9.7 Omega, P<0.0001), and increased the mean radius of the ablated area (15.9+/-3.0 to 25.0+/-3.6 mm, P<0.0001). These significant changes were not observed without injection of saturated saline. Similar trends were found in the in vivo study. CONCLUSION: Injection of saturated saline into the area of vaporization around the RF electrode, followed by additional RFA, caused concentric expansion of the final ablation area, facilitating more efficient tumor ablation.

Identification of M1 and M2 muscarinic acetylcholine receptors in the cat carotid body chemosensory system.

The carotid body is a major arterial chemoreceptor that senses low O2 tension, high CO2 tension and low pH in the arterial blood. It is generally believed that neurotransmitters, including acetylcholine (ACh), participate in the genesis of afferent neural output from the carotid body and modulate the function of chemoreceptor cells (glomus cells). Previous pharmacological studies suggest that M1 and M2 muscarinic ACh receptors (mAChRs) are involved in these processes. This study was designed to demonstrate the presence and localization of M1 and M2 mAChRs in the carotid body and in the petrosal ganglion of the cat. Since DNA sequences of the cat M1 and M2 mAChRs were not known, we first determined partial DNA sequences. These sequences and deduced amino acid sequences highly resembled those of human and the rat. Subsequent reverse transcription-polymerase chain reaction (RT-PCR)analysis has demonstrated that mRNAs for M1 and M2 mAChRs are present in the carotid body and the petrosal ganglion of the cat. Immunohistochemistry has indicated that the localization of these receptors appears different. Immunoreactivity for M1 mAChR was strong in nerves in the carotid body. Nerve endings positively stained for M1 mAChR appear to innervate glomus cells. Weak staining for M1 mAChRs was seen in glomus cells. On the other hand, M2 receptor protein seems to be present in glomus cells but not on nerve endings. One third of the neurons in the petrosal ganglion showed immunoreactivity for M1 mAChR. Many neurons and nerve fibers in the petrosal ganglion expressed M2 mAChR immunoreactivity. The results were consistent with previous pharmacological studies. Thus, activation of M1 mAChRs on afferent nerve endings may be linked to the increase in neural output during hypoxia. Further, M1 and M2 mAChRs on glomus cells modulate the release of neurotransmitters.

Effects of brushing with a dentifrice for sensitive teeth on tubule occlusion and abrasion of dentin.

By using a dentifrice or toothpaste for sensitive teeth, the brushing-induced effects on dentinal tubule occlusion and abrasion of human sound dentin were investigated with a scanning electron microscope and a scanning laser microscope. The dentifrice contained diatomaceous earth and silica as abrasives and strontium chloride hexahydrate as an active ingredient. Thirty dentin pieces of human premolar teeth with an average of 20% occluded dentinal tubules were attached to resin plates and exposed to the oral cavities of five adult subjects for 2, 4, and 8 weeks. Brushing with and without dentifrice was performed 1 min per day, respectively. Brushing with the dentifrice gradually decreased the mean average of occluded tubules from about 91 to 77% during 2 to 8 weeks, although there were no significant differences among the individual values. However, the mean abrasive loss of the dentin surfaces brushed with dentifrice significantly increased from about 52 to 143 microm in depth. The brushed surfaces of the dentin showed a rough topography with numerous toothbrush scratches but no organic pellicle was found. On the other hand, brushing without dentifrice caused about 99% of the dentinal tubules to occlude in 2 and 4 weeks and 100% in 8 weeks. The brushed dentin surfaces at 8 weeks were entirely covered with organic pellicle containing fine mineral granules derived from saliva, and the abrasive loss was about 1.4 microm in mean depth. Such results indicate that brushing with abrasive dentifrices for sensitive teeth remarkably erodes dentin, and suggest that the brushing should cause the dentinal tubules to open again for a certain period of time.

[243 cases of percutaneous nephrolithotomy--result of 5 years].

Between May, 1982 and April, 1987, upper urolithiasis of 247 kidneys of 243 patients, 174 male and 69 female, were treated by percutaneous nephrolithotomy (PNL). The main stone was successfully removed from 236 kidneys (about 95.5%). Seven cases of ureteral stone could not be removed by PNL, and were treated by traditional ureterolithotomy. In 3 cases of pelvic stone, the stone descended to the ureter during the PNL procedure, and was also removed by ureterolithotomy. In one case of pelvic stone, complete obstruction of uretero-pelvic junction after PNL occurred, and pyeloplasty was needed. One pelvic stone patient who had basical hypertension and arrhythmia died soon after PNL, because of acute myocardial infarction. Blood transfusion was needed in 31 cases (12.8%). The residual stones over 5 mm were noticed in 48 cases (20.3%). The most important point to succeed in PNL is to make a nephrostomy through the most suitable calyx to the stone. The easiest way to identify the location and connection of the aimed calyx with the stone in three dimensional position, is to take X-ray films in intravenous pyelograms not only from postero-anterior but also oblique positions. Additional transureteral lithotripsy (TUL) for the fragment descending to the ureter after PNL produces a much better result.

[The influence of percutaneous nephrolithotomy on renal function evaluated by 99m-Tc-DTPA renoscintigram].

The influence of percutaneous nephrolithotomy (PNL) on renal function was evaluated by 99m-Tc-DTPA renoscintigraphy. The renoscintigram was recorded and regions of interest of both kidneys (R) and background (BKG) were settled. Renal uptake ratio was calculated by the following formula. Renal uptake ratio = (formula; see text). The renal uptake ratio of 50 patients were compared before and up to 6 months after PNL. Most cases showed an increase or no change in post-PNL renal uptake ratio in operated kidney. Five cases (10%) showed decreased renal uptake ratio of post-PNL. No risk factors for the renal damage caused by PNL such as age, sex, stone size, number of nephrostomy and course of PNL were detected when compared with increased or no change groups. In cases of complete staghorn calculi in the decreased renal uptake ratio group, compensatory hypertrophy of contralateral kidney PNL course might occur, and the function of the operated kidney might not have recovered. More during cases and longer follow-up is necessary for the recovery of renal function.

[Clinical experience of tegafur-uracil (UFT) against bladder cancer and renal cell carcinoma].

The safety of prolonged administration of UFT in which tegafur and uracil were mixed in a ratio of 1:4 in molar fraction was studied in 44 cases of bladder cancer and 10 cases of renal cell carcinoma. Daily doses of UFT were 300-600 mg, and average total doses administered were 102.0 g for bladder cancer and 116.6 g for renal cell carcinoma cases. Incidence of adverse effects were 25.0% in bladder cancer and 18.5% in renal cell carcinoma cases. Anorexia, nausea, vomiting and decrease in WBC were observed, but rates of having discontinued the administration of UFT were very low, being 9.1% in bladder cancer and 10.0% in renal cell carcinoma. Thus, UFT was considered to be tolerable during prolonged use in bladder cancer and renal cell carcinoma and also a drug in which more usefulness is expected in multidisciplinary treatments in future.

[A case of signet ring cell carcinoma of the urinary bladder].

A 60-year-old female complained of gross hematuria and urinary frequency on November 27th, 1982. Cystoscopic examination revealed papillary invasive tumor around the bladder neck and a transurethral biopsy showed signet ring cell carcinoma. Since there was no adenocarcinoma in any other organs, we diagnosed it as primary signet ring cell carcinoma of the urinary bladder. Total cystectomy with ileal conduit and post-operative irradiation were performed, but she died on May 13th, 1983. We summarize 16 cases of primary signet ring cell carcinoma of the urinary bladder including this case and discuss this rare condition.

[A case of seminoma with epididymal swelling].

A 36-year-old man noticed a discomfort in the right scrotum since January, 1981, and came to our hospital in October of the same year. Palpation detected a hard and painless tumor in the right epididymal tail and exploratory excision revealed an induration measuring 3 X 2 X 1 cm. The rapid diagnosis of tumors by frozen section was made and we diagnosed it as right epididymal seminoma. Right high inguinal orchiectomy was performed and histopathologically, tumor cells which mainly occupied the testis were observed. This case was diagnosed as seminoma which showed epididymal swelling as the clinical symptom.

[Chemotherapy of metastatic renal cell carcinoma with cis-diamminedichloroplatinum and other drugs].

Seven patients were entered in this study between November 1978 and February 1983. All patients had histologically proven renal cell carcinoma with widespread metastases. Patients ranged in age from 27 to 69 years, with an average of 54 years. All those studied had measurable radiological lesions of malignant disease. One patient was treated with only CDDP and the other 6 patients were treated with CDDP and other anti-cancer drugs (vinblastine, ifosfamide, bleomycin and/or adriamycin). Total doses of CDDP ranged from 20 to 250 mg, with an average of 99 mg. Four cases showed no change and 3 patients had progressive disease. Symptomatic improvement was obtained in only 2 patients. Management of metastatic renal cell carcinoma is discussed briefly.

[Case of immature teratoma of the testicle metastasizing as completely mature teratoma].

A case of immature teratoma of the testicle metastasizing as completely mature teratoma is presented. A 23-year-old man underwent right inguinal orchiectomy for an immature teratoma of the testicle on September 14, 1982. At retroperitoneal lymph node dissection, 12 lymph nodes were removed, all of which were negative for cancer. He was well until March 1983, when bloody sputum and left chest pain occurred. Since full lung tomography revealed two pulmonary nodules, he was treated with a course of VP-16 and three courses of vinblastine, bleomycin and CDDP. In September 1983, after completion of the combination chemo-therapy, the two pulmonary nodules were noticed to be slightly enlarging. A thoracotomy was scheduled to remove these nodules, since they were believed to be his only remaining tumors. Pathologic examination of the extirpated nodules disclosed completely benign teratoma. Mediastinal lymph nodes had no metastatic involvement histologically. It is our intention in this paper to emphasize, by means of several case reports, the frequently benign nature of these residual lesions and also to emphasize a recently recognized phenomenon--the apparent induction of benign teratomas by this intensive chemotherapy.

[A case of a congenital unilateral multicystic kidney and a review of 126 cases in Japan].

A 3-year-old boy was admitted to our hospital with complaints of left flank mass and growth retardation. Examinations with IVP (Fig. 1), retrograde pyelography (Fig. 4) and cystoscopic examination (Fig. 3) showed a left nonopacified kidney, and right hydroureteronephrosis due to stenosis of the midureter. Two large cystic patterns were found in the left kidney by ultrasonic scanning tomography (Fig. 2); and, the left kidney was found to be occupied by a round and homogeneously low density mass by CT scanning (Fig. 6). The left renal artery was not demonstrated on the aortogram (Fig. 5). The patient was diagnosed to have a left congenital unilateral multicystic kidney, and laparotomy was performed. The left kidney was easily removed, and the part with stenosis in the right ureter was removed, then end-to-end anastomosis was performed. Grossly, two large cysts (upper and lower part) and connective tissues were found in the left kidney (Fig. 7), and the vessels of the renal pedicle were filiform. No luminal formation of the renal pelvis or ureter was found. The epithelium of the cyst wall (Fig. 8) was deciduated leaving the connective tissue and smooth muscle, as shown by the histological examination. Histological examination of the parenchymal tissue (Fig. 9) between the two cysts showed primitive glomeruli and renal tubules among abundant connective tissue, but no cartilage tissue. Statistic examination and discussion have been made of 126 cases of congenital multicystic kidney reported in Japan.

[A clinical case of secondary tumor of the penis from the rectum, with malignant priapism].

We report a clinical case of carcinoma of the rectum. A 45-year-old patient had undergone resection of the rectum and proctostomy 22 months ago. Carcinoma caused metastasis to the corpora cavernosa of the penis in this patient, and caused local recurrence of the carcinoma of the rectum, pulmonary metastasis and malignant priapism. A statistical analysis of 62 cases of secondary tumor of the penis in Japan was also made. The present clinical case was the 62nd case of secondary tumor of the penis in Japan, and the 4th case of secondary penile tumor from the rectum. The primary foci of the secondary tumor of the penis are mostly in the urinary bladder and the prostate, followed by the rectum, kidney, pelvis of the kidney and the ureter. Primary sites in the urogenital organs were found in 82.3% and in the neighboring organs in 85.2%. As the route of metastasis of the secondary tumor of the penis, arterial blood, retrovenous, retro-lymph and direct infiltrating metastasis may be possible. Secondary tumor of the penis is mostly found in aged persons, and the major symptoms may be penile nodule and mass, malignant priapism, penile pain and tenderness, and difficulty in urination and retention of urine. Regardless of the length to metastasis and difference in the treatment of the metastatic focus, the secondary tumor of the penis is poor in prognosis, and survival period may be up to 7 months. From the findings of post-mortem examination, secondary tumor of the penis should be regarded as a secondary sign due to recurrence of the primary tumor or presence of metastasis in other organs, and careless surgical operation should be avoided.

[A case report of retroperitoneal Schwannoma].

A 37-year-old man with complaints of lassitude and slight lumbal pain, who had been found to have a low abdominal median mass and was referred to our hospital by a practitioner, was admitted for further examination. IVP, examination of the gastrointestinal tract by the oral procedure and re-examination of the colon by a double contrast procedure revealed deviation of the right ureter, the urinary bladder and the alimentary tract. This mass was found to be a retroperitoneal tumor with central necrosis by low abdominal CT scanning and the low abdominal echography. The mass was removed easily, though it was slightly adherent to the anterior surface of the sacral bone. Pelvic lymphadenectomy was also done simultaneously. The removed mass was encapsulated by fibrous tissue, round in shape, 750 grams in weight (13 by 12 by 12 cm), evenly flat, elastic soft and contained 230 ml bloody exudate at the center. Histologically this mass contained areas where oval and spindle cells made palisading arrangement and areas where the tumor cells had no communication with each other and stroma was edematous. However, hyperchromatism of nuclei of tumor cells and high cellularity indicated this mass to be a malignant Schwannoma. Dissected lymph nodes had no metastatic involvement. Since the surgical margin was detected to be invaded by tumor cells, postoperative prophylactic irradiation of Linac (10 Me V-X, total doses 4,750 rads) was performed on the whole pelvis. This patient has been well and has had no signs of recurrence of tumor for 23 months after the operation. Ninety-four cases of benign retroperitoneal Schwannoma and thirty-six cases of malignant retroperitoneal Schwannoma reported in Japan are reviewed.