Cytological nuclear atypia classification can predict prognosis in patients with endometrial cancer.

OBJECTIVE: Endometrial cancer is one of the leading causes of malignancy in females. Nuclear findings are important for patients with cancer, and can provide valuable information to treating oncologists. We investigated whether nuclear findings were a useful prognostic factor in patients with endometrial cancer. METHOD: We investigated 71 cases of endometrial carcinoma with paired histology and cytology at Kurume University Hospital. We classified endometrial endometrioid adenocarcinoma (EEC) G1 and G2 as type I carcinomas, and uterine papillary serous carcinoma (UPSC), clear cell carcinoma (CC) and EEC G3 as type II carcinomas. For the establishment of the cytological nuclear atypia classification, we examined the following nuclear factors on the cytological smears: mitotic figures, prominent nucleoli, nuclear area and anisonucleosis. RESULTS: There was a significant difference in mitotic figures (P < 0.001) and anisonucleosis (P = 0.026) in cytological smears between type I and type II carcinomas. Based on these findings, we categorized cytological nuclear atypia into three groups, nuclear atypia-1 (57.7%), nuclear atypia-2 (19.7%) and nuclear atypia-3 (22.5%), and this classification system correlated well with prognosis in patients with endometrial cancer (P < 0.001). Furthermore, this classification system was able to extract patients with a good prognosis from those with high-grade carcinomas, such as UPSC+CC+EEC G3, and patients with a poor prognosis from those with EEC G1. CONCLUSIONS: Our system of cytological nuclear atypia classification based on endometrial cytology can predict patient prognosis. Cytological nuclear atypia classification and histological typing may be useful for the treatment and follow-up of patients with endometrial cancer, and should be routinely incorporated into cytological reports.

A computer-aided temporal and dynamic subtraction technique of the liver for detection of small hepatocellular carcinomas on abdominal CT images.

It is often difficult for radiologists to identify small hepatocellular carcinomas (HCCs) due to insufficient contrast enhancement. Therefore, we have developed a new computer-aided temporal and dynamic subtraction technique to enhance small HCCs, after automatically selecting images set at the same anatomical position from the present (non-enhanced and arterial-phase CT images) and previous images. The present study was performed with CT images from 14 subjects. First, we used template-matching based on similarities in liver shape between the present (non-enhanced and arterial-phase CT images) and previous arterial-phase CT images at the same position. Temporal subtraction images were then obtained by subtraction of the previous image from the present image taken at the same position of the liver. Dynamic subtraction images were also obtained by subtraction of non-enhanced CT images from arterial-phase CT images taken at the same position of the liver. Twenty-one of 22 nodules (95.5%) with contrast enhancement were visualized in temporal and dynamic subtraction images. Compared with present arterial-phase CT images, increases of 150% and 140% in nodule-to-liver contrast were observed on dynamic and temporal subtraction images, respectively. These subtraction images may be useful as reference images in the detection of small moderately differentiated HCCs.

Cardioprotective effect afforded by transient exposure to phosphodiesterase III inhibitors: the role of protein kinase A and p38 mitogen-activated protein kinase.

BACKGROUND: Phosphodiesterase III inhibitors (PDEIII-Is) improve the hemodynamic status of heart failure via inotropic/vasodilatory effects attributable to the increase in intracellular cAMP level. Direct cardioprotection by PDEIII-Is and its underlying mechanisms, however, have not been identified. We tested the infarct size-limiting effect of PDEIII-Is and the roles of cAMP, protein kinase (PK) A, PKC, and mitogen-activated protein kinase (MAPK) families in open-chest dogs. Methods and Results-- Milrinone, olprinone (PDEIII-Is), or dibutyryl-cAMP (db-cAMP) was injected intravenously 30 minutes before 90-minute ischemia, followed by 6 hours of reperfusion. Olprinone was also examined with an intracoronary cotreatment with a PKA inhibitor (H89), a PKC inhibitor (GF109203X), an extracellular signal-regulated kinase kinase (MEK) inhibitor (PD98059), or a p38 MAPK inhibitor (SB203580) throughout the preischemic period. Either PDEIII-Is or db-cAMP caused substantial hemodynamic changes, which returned to control levels in 30 minutes. Collateral flow and percent risk area were identical for all groups. Both PDEIII-Is and db-cAMP increased myocardial p38 MAPK activity during the preischemic period, which was blocked by H89, but not by GF109203X. Both PDEIII-Is and db-cAMP reduced infarct size (19.1+/-4.1%, 17.5+/-3.3%, and 20.3+/-4.8%, respectively, versus 36.1+/-6.2% control, P<0.05 each). Furthermore, the effect of olprinone was blunted by either H89 (35.5+/-6.4%) or SB203580 (32.6+/-5.9%), but not by GF109203X or PD98059. H89, GF109203X, PD98059, or SB203580 alone did not influence infarct size. CONCLUSIONS: Pretreatment with PDEIII-Is has cardioprotective effects via cAMP-, PKA-, and p38 MAPK-dependent but PKC-independent mechanisms in canine hearts.

[Clinical outcome of potassium-titanyl-phosphate (KTP/532) laser vaporization prostatectomy for benign prostate hyperplasia].

OBJECTIVE: To study the feasibility of vaporization prostatectomy by potassium-titanyl-phosphate (KTP/532) laser in men with bladder outlet obstruction due to benign prostatic hyperplasia (BPH) and to evaluate their clinical and voiding outcome 2 weeks and 6 months after operation. PATIENTS AND METHODS: Laser vaporization prostatectomy with the KTP/532 laser at 20 W was performed in 21 BPH patients varying from 56 to 75 years of age. All cases were performed under the spinal anesthesia. The laser was produced by MODEL SL20/50 and ADD/Stat side-firing fibers were used. A urethral catheter was inserted post-operatively and was removed within 6 days after operation. The hemoglobin value was examined on the first day after operation and uroflowmetry was executed 2 weeks and 6 months after operation with the examination of the residual urine volume. IPSS and QOL score were recorded by patients 2 weeks and 6 months after operation. RESULTS: The prostate volumes ranged from 22 to 52 mL (mean 37.3 +/- 10.4). None of the 21 patients had any significant blood loss or any fluid absorption. The voiding parameters improved: mean peak flow rate increased from 7.1 to 16.5 mL/s 2 weeks after operation and to 15.2 mL/s 6 months after operation and residual volume decreased from 172 to 45 mL 2 weeks after operation and to 43 mL 6 months after operation. IPSS and QOL score improved significantly in Wilcoxon signed-ranks test. The ratio of excellent and good in efficacy criteria of Kawabe group was 71.4% 2 weeks after operation and that was 71.4% 6 months after operation. Mean catheterization term was 4.5 days. Only one patient showed transient urinary retention when the catheter was removed the third postoperative day. None had incontinence postoperatively. No other significant complications were recognized. The prostate volume was more than 50 mL in 3 cases and the postoperative 6 months outcomes of the 3 cases were all poor in their symptoms in the efficacy criteria of Kawabe group. CONCLUSIONS: KTP laser vaporization prostatectomy is safe and effective for obstructive prostates up to 50 mL in volume and produces good results 2 weeks post operatively that are sustained for 6 months after operation.

[Giant epidermal cyst in the perineum extending into the pelvic space in the patient with polycystic kidney disease: a case report].

A 75-year-old man with autosomal dominant polycystic kidney disease was admitted to our hospital with the chief complaint of a giant mass in the left side of the perineum that had gradually developed in size during the previous 20 years. Palpation revealed a neonatal head-sized cystic mass with no tenderness. Magnetic resonance imaging (MRI) demonstrated a well-circumscribed homogeneous mass extended to the dorsal side of the bladder. It was excised surgically without any injury of rectum or urinary tract. The resected specimen was 23 x 18 x 12 cm in size and 1.2 kg in weight. The pathological diagnosis was epidermal cyst. Cases with an epidermal cyst extending into the pelvic space are extremely rare with few cases having been reported in the world.

Role of mitochondrial and sarcolemmal K(ATP) channels in ischemic preconditioning of the canine heart.

We tested whether mitochondrial or sarcolemmal ATP-sensitive K(+) (K(ATP)) channels play a key role in ischemic preconditioning (IP) in canine hearts. In open-chest beagle dogs, the left anterior descending artery was occluded four times for 5 min each with 5-min intervals of reperfusion (IP), occluded for 90 min, and reperfused for 6 h. IP as well as cromakalim and nicorandil (nonspecific K(ATP) channel openers) markedly limited infarct size (6.3 +/- 1.2, 8.9 +/- 1.9, and 7.2 +/- 1.6%, respectively) compared with the control group (40.9 +/- 4.1%). A selective mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate, partially blunted the limitation of infarct size in the animals subjected to IP and those treated with cromakalim and nicorandil (21.6 +/- 3.8, 25.1 +/- 4.6, and 19.8 +/- 5.2%, respectively). A nonspecific K(ATP) channel blocker, glibenclamide, completely abolished the effect of IP (38.5 +/- 6.2%). Intracoronary or intravenous administration of a mitochondria-selective K(ATP) channel opener, diazoxide, at >100 micromol/l could only partially decrease infarct size (19.5 +/- 4.3 and 20.1 +/- 4.4%, respectively). In conclusion, mitochondrial and sarcolemmal K(ATP) channels independently play an important role in the limitation of infarct size by IP in the canine heart.

Protein tyrosine kinase is not involved in the infarct size-limiting effect of ischemic preconditioning in canine hearts.

Protein kinase C (PKC) plays an important role in ischemic preconditioning (IP). Because (1) tyrosine kinase is located at the downstream of PKC for IP in the rabbit hearts and (2) we have reported that ecto-5'-nucleotidase is the substrate for PKC and plays a crucial role for the infarct size-limiting effect, we tested whether tyrosine kinase activation contributes to either activation of ecto-5'-nucleotidase or the infarct size-limiting effect of the early phase of IP in the canine heart. In dogs, the IP procedure (4 cycles of 5-minute occlusion of coronary artery) and exposure to 12, 13-phorbol myristate acetate (PMA) each activated myocardial ecto-5'-nucleotidase and Lck tyrosine kinase. Genistein (10, 30, and 100 microg. kg(-)(1). min(-)(1) IC), an inhibitor of tyrosine kinase, attenuated the activation of Lck tyrosine kinase but did not attenuate the activation of ecto-5'-nucleotidase due to either IP or PMA. In the other canine hearts, IP attenuated infarct size (49+/-5 versus 11+/-3 or 16+/-3%, P<0.01) due to 90 minutes of coronary occlusion followed by 6 hours of reperfusion, which was not blunted by 3 or 2 (30 and 100 microg. kg(-)(1). min(-)(1)) doses of genistein (infarct sizes, 15+/-4, 13+/-4, and 13+/-3%, respectively, and 17+/-3 and 15+/-4%, respectively) or lavendustin A. Tyrosine kinase does not activate ecto-5'-nucleotidase or trigger the infarct size-limiting effect of the early phase of IP in canine hearts.

[Multicentric Castleman's disease found by a renal sinus lesion: a case report].

A 79-year-old man complained of anorexia and weight loss. Computed tomography and magnetic resonance imaging showed a solitary mass in the left renal sinus. Left nephrectomy was carried out under a clinical diagnosis of renal pelvic tumor. The pathological diagnosis was plasma cell type of Castleman's disease. The patient suffered from lymph node swelling in the right neck at age 75 and the lymph node was resected. The pathological diagnosis was lymphadenitis but it proved to be plasma cell type of Castleman's disease. The patient also had had a lymphadenectomy in the supraclavicular fossa and in the supraorbital area at age 76. Both had been diagnosed as lymphadenitis pathologically but they proved to be plasma cell type of Castleman's disease. The final diagnosis was multicentric Castleman's disease. We reviewed multicentric Castleman's disease.

Suppression-burst patterns in intractable epilepsy with focal cortical dysplasia.

We report on a patient with early-onset spasms in series and partial seizures associated with focal cortical dysplasia whose EEGs showed suppression-burst patterns during early infancy. These electroclinical characteristics suggested a diagnosis of Ohtahara syndrome, but the EEG findings were atypical because of the lack of suppression-burst patterns during wakefulness. In addition, the patient did not have severe psychomotor retardation. With high-dose pyridoxal phosphate therapy, seizures were suppressed and suppression-burst patterns disappeared at 2 months of age. Focal motor seizures recurred later and they often evolved into epilepsia partialis continua. Patients with early-onset intractable seizures associated with suppression-burst patterns on EEGs have several different etiologies, and these patients should be categorized according to their etiology in addition to their syndromic diagnosis.

Relationship between the biodistributions of radioactive metal nuclides in tumor tissue and the physicochemical properties of these metal ions.

This study was undertaken to elucidate the relationship between the biodistribution of radioactive metal nuclides in tumor tissue and its physicochemical properties. Potassium analogs (86Rb, 134Cs, 201Tl) were taken up into viable tumor tissue, although 22Na concentrated in necrotic tumor tissue. 67Ga and 111In were more predominant in inflammatory tissue than in the viable and necrotic tumor tissue. 169Yb and 167Tm accumulated in viable tumor tissue and tissue containing viable and necrotic tumor tissue. 67Ga, 111In, 169Yb and 167Tm were bound to the acid mucopolysaccharide with a mol. wt. of about 10,000 daltons in the tumor tissue. 46Sc, 51Cr, 95Zr, 181Hf, 95Nb, 182Ta, and 103Ru were highly concentrated in inflammatory tissue and were bound to the acid mucopolysaccharides with a mol. wt. exceeding 40,000 daltons. 65Zn and 103Pd concentrated in viable tumor tissue and were bound to the protein in the tissue. The results suggest that the difference in intra-tumor distribution of these elements is caused by a difference in the binding substances (or status) of these elements in the tissues, and the binding substance is determined by physicochemical properties of the elements. We therefore conclude that the biodistribution of radioactive metal ions in tumor tissue is determined by its own physicochemical properties.

[Two cases of cavity formation in prostatic urethra after transurethral microwave thermotherapy (TUMT) with Prostatron].

The Prostatron device, developed by Dr. Devonec, provides microwave heating of the prostate and simultaneous conductive cooling of the urethra. Treatment with Prostatron (transurethral microwave thermotherapy: TUMT) of BPH can be performed in a single session, and the urethra, the rectum and the surrounding tissue are protected with the temperature monitoring system. TUMT with Prostatron may be more suitable for a small adenoma with mild symptoms than a large adenoma with severe symptoms, because objective improvement is rarely observed compared with subjective improvement. We have treated 40 cases of BPH with Prostatron (Prostasoft 2, max. energy: 50 watt, max. urethral temperature: 44.5 degrees C, max. rectal temperature: 42.5 degrees C) since March 1993. Among them, there were 2 cases of large cavity formation involving the prostatic urethra. With cavity formation, TUMT may have its place in the treatment of a large adenoma with severe urinary symptoms, but loses its advantage in the prevention of persistent urinary infection and retrograde ejaculation, especially in the treatment of a small adenoma in a younger patient with mild urinary symptoms. It is unknown why such cavity formation occurred only in 2 patients among 40 equally treated cases, but the causes of cavity formation and safety of TUMT should be evaluated again, even though no injury to the rectum and the external urethral sphincter were detected. We report these 2 cases, and causes of cavity formation and discuss the prospects of TUMT.

Tumour affinity of 203Pb-chloride: comparison with 67Ga-citrate and 201Tl-chloride.

The radionuclide 203Pb decays completely by electron capture to stable 203Tl with a half-life of 52 h. The primary radiation from the decay is gamma-ray radiation 280 keV (80%). 203Pb is produced easily from the natural metal thallium by the method described below. 203Pb-chloride is a promising imaging agent for tumour scanning because of the large retention value for tumour tissue and the small value for normal organs, but the large value for the kidney and bone is a shortcoming when considering it as an imaging agent. The retention value of 203Pb in tumour tissue is larger than that of 201Tl and smaller than that of 67Ga. The tumour/inflammatory lesion retention ratio for 203Pb is very large in comparison with those for 67Ga and 201Tl. 203Pb accumulates to a large extent in viable tumour tissue, and less in necrotic tumour tissue and in inflammatory lesion. Therefore, 203Pb-chloride is far better for visualization of viable tumour tissue than 67Ga and 201Tl if the large retention values for the kidney and bone were reduced.

Computer-aided diagnosis: development of automated schemes for quantitative analysis of radiographic images.

Preliminary results obtained with computer-aided diagnosis (CAD) from various radiographic examinations are very encouraging. However, CAD is still at an early stage of its development. It will be necessary to increase further the understanding of image features of normal and abnormal patterns, to establish databases, and to devise specific approaches for particular types of pathology. Although the existing schemes are designed to be applied to digital radiographs, similar techniques can be applied in the future to cross-sectional images such as CT, MRI, and ultrasound. We believe that CAD will become clinically practical in the near future.

[Hematuria: an initial sign of cecal carcinoma].

A 79-year-old female was seen with hematuria, cystoscopy showed a non-papillary, broad-based tumor arising from the right anterolateral wall of the bladder. Transurethral biopsy revealed adenocarcinoma. Pelvic CT scanning revealed that the tumor extended from the bladder wall to the wall of the ileo-caecal intestine. Gastrointestinal series revealed no abnormal findings although the cecum could not be visualized clearly, and we could not distinguish whether the primary site was the bladder or intestine. Surgical exploration was performed. The main tumor seemed to arise from the cecum, extended downward and invaded the bladder wall. Right hemicolectomy and en bloc partial cystectomy were performed. The final diagnosis was adenocarcinoma of the cecum invading the bladder. We could find no reports on adenocarcinoma of the cecum in which hematuria was the initial symptom, as in this case, in Japan.

Biodistributions of radioactive alkaline metals in tumor bearing animals: comparison with 201Tl.

The retention values for 42K, 86Rb and 134Cs in the tissues and blood were quite similar to those for 201Tl, but were very different from those for 22Na. In an experiment for subcellular fractionation of tumors, most of these nuclides were localized in the supernatant fraction, with small amounts in other fractions. The concentration ratios for these nuclides in each fraction were approximately constant regardless of the time after administration. Radioactive alkaline metals in the supernatant fraction of the tumor homogenate existed mostly as free ions and were bound to protein in other fractions of tumor tissue. These results were essentially the same as those for 201Tl. Ouabain suppression studies indicated that 201Tl is taken up into the tumor cells partly through Na+, K+-ATPase of their membranes. Ionic radii of alkaline metals and thallium were related to their blood and tumor retention values. This relationship suggested that monovalent cations whose ionic radii exceed 0.133 nm, and which exist as free ions in the tissue fluids, behave like the potassium ion. Potassium and K analogs (Tl, Rb, Cs) are avidly taken up into viable tumor cells whose Na+, K+-ATPase activity is elevated. Therefore, suitable radionuclides of K and K analogs can be excellent agents for visualization of viable tumor tissues.

[Two cases of adrenal myelolipoma].

Myelolipoma of the adrenal gland is a benign oligosymptomatic tumor composed of various proportions of fat and bone marrow elements. We report two operated cases found incidentally in a 76-year-old man and 49-year-old man.

[Clinical experience of epididymovasostomy and vasovasostomy for obstructive azoospermia].

PIP: 14 patients with obstructive azoospermia were treated with microsurgical vasovasostomy or epididymovasostomy. A total of 11 patients underwent 2-layer vasovasostomy, 6 cases following bilateral vasectomy and 5 cases suffering from bilateral vasal disruption by inguinal herniorrhaphy. 3 patients underwent end-to-end epididymovasostomy with Silber's specific tubule technique following bilateral epididymitis. After the operation, fertility was restored in 6 of 14 cases. The recovered sperm density was greater than 20 x 10 6/ml and sperm motility exceeded 50%. Pregnancy was achieved in 1 case following inguinal herniorrhaphy. Preoperative testicular biopsies carried out in 11 cases disclosed slight deterioration of spermatogenesis. Johnsen's mean score was 8.20 +or- 0.38 (mean +or- S.D.). The mean scores of the biopsies obtained from the cases obstructed for more than 20 years were significantly lower than those with less than a 20-year time period. After inguinal herniorrhaphy, reanastomosis of the vas deferens was difficult in order to restore fertility. This was due to the presence of longterm obstruction, defects in the vas deferens, or the absence of sperm granuloma at the vasectomy site. Epididymovasostomy restored fertility in 67% of the cases. The specific tubule technique was the most effective in the management of such pathological conditions. (author's modified)^ieng

Biodistributions of 201Tl in tumor bearing animals and inflammatory lesion induced animals.

The accumulation of 201Tl in tumor and inflammatory tissues were small. However, this nuclide showed a high concentration in viable tumor tissue, less in connective tissue (containing inflammatory tissue), and was not seen in necrotic tumor tissue regardless of the time after administration of 201Tl(I)-chloride. In inflammatory lesions, 201Tl accumulated in subcutaneous tissue infiltrated with neutrophils and macrophages, and quite large amounts of this nuclide were accumulated in subcutaneous tissue and sites where neutrophils were crowded. Most 201Tl existed in a free form in the fluid of tumor and inflammatory tissues regardless of the time after administration. A small amount of this nuclide was localized in the nuclear, mitochondrial and microsomal fractions in these tissues, and the nuclide was bound to protein in these fractions. The distribution of 201Tl(III)-chloride in tumor bearing animals was essentially the same as that of 201Tl(I)-chloride.