Chemokine (C-X-C motif) ligand 1 is a myokine induced by palmitate and is required for myogenesis in mouse satellite cells.

AIM: The functional significance of the myokines, cytokines and peptides produced and released by muscle cells has not been fully elucidated. The purpose of this study was to identify a myokine with increased secretion levels in muscle cells due to saturated fatty acids and to examine the role of the identified myokine in the regulation of myogenesis. METHODS: Human primary myotubes and mouse C2C12 myotubes were used to identify the myokine; its secretion was stimulated by palmitate loading. The role of the identified myokine in the regulation of the activation, proliferation, differentiation and self-renewal was examined in mouse satellite cells (skeletal muscle stem cells). RESULTS: Palmitate loading promoted the secretion of chemokine (C-X-C motif) ligand 1 (CXCL1) in human primary myotubes, and it also increased CXCL1 gene expression level in C2C12 myotubes in a dose- and time-dependent manner. Palmitate loading increased the production of reactive oxygen species along with the activation of nuclear factor-kappa B (NF-κB) signalling. Pharmacological inhibition of NF-κB signalling attenuated the increase in CXCL1 gene expression induced by palmitate and hydrogen peroxide. Palmitate loading significantly increased CXC receptor 2 gene expression in undifferentiated cells. CXCL1 knockdown attenuated proliferation and myotube formation by satellite cells, with reduced self-renewal. CXCL1 knockdown also significantly decreased the Notch intracellular domain protein level. CONCLUSION: These results suggest that secretion of the myokine CXCL1 is stimulated by saturated fatty acids and that CXCL1 promotes myogenesis from satellite cells to maintain skeletal muscle homeostasis.

Transpupillary thermotherapy for treatment of exudative age-related macular degeneration in Japanese patients.

PURPOSE: To report the therapeutic outcome of transpupillary thermotherapy (TTT) for subfoveal choroidal neovascularizarion (CNV) in brown retina using a diode-laser with the setting of lower energy level compared to the previous studies on light-pigmented Caucasian patients. METHODS: A total of 19 subfoveal CNVs in 18 patients were treated with TTT. The power of diode-laser was set 160 mW for 1.2 mm beam, 270 mW for 2.0 mm beam, and 400 mW for 3.0 mm beam, and the laser was delivered for 1 min through a slit-lamp mounted-delivery system. Patients were followed up for a mean of 8.8 months (4-12 months). Visual acuity and the fundus change as judged by funduscopic examination and simultaneous fluorescein and indocyanine green angiography were evaluated. Visual acuity was measured by a Japanese standard Landolt visual acuity chart and converted to logarithm of the minimal angle resolution (log MAR) visual acuity for statistical analysis. Improvement or decline in vision was defined as change of more than 0.2 in log MAR visual acuity. RESULTS: In eyes with minimally classic or occult only CNV, visual acuity improved in two eyes (18%) stabilized in seven eyes (64%) and worsened in two eyes (18%). In eyes with predominantly classic CNV, visual acuity improved in two eyes (25%), stabilized in four eyes (50%) and worsened in two eyes (25%). In all, 15 (84%) eyes of all studied subjects had improvement in exudation. Two (11%) and one (5%) eye(s) were noted to have a significant post-treatment haemorrhage and retinal pigment epithelial tear, respectively. CONCLUSION: In patients with brown retinal colour, the treatment outcome of TTT was comparable to that of light-pigmented Caucasian patients with approximately half the laser power energy. Further randomized control studies are warranted.

[A comparison between midline and paramedian approaches for combined spinal-epidural anesthesia].

We compared midline approach with paramedian approach for combined spinal-epidural anesthesia (CSEA) by needle through needle technique. Seventy patients undergoing elective gynecological surgery received CSEA with a 27 G Whitacre spinal needle, which protrudes 12 mm beyond the tip of the Tuohy needle. The successful subarachnoid puncture with first attempt was noted in 33 patients (94%) of midline group (M group), in 31 patients (89%) of paramedian group (P group). At the subarachnoid puncture, skin to epidural space distance (43.2 mm vs 53.4 mm) and protrusion length of spinal needle (5.5 mm vs 8 mm) were significantly longer in the P group than in the M group. Abdominal radiography revealed the flexion of epidural catheter in 19 patients (54%) of M group and in 2 patients (6%) of P group. The choice of midline or paramedian approach for CSEA did not affect the success rate of the subarachnoid puncture, but paramedian approach required longer protrusion length of the spinal needle than midline approach. To raise the success rate of subarachnoid puncture by paramedian approach, a long protruded spinal needle is recommended.

[A case of renal pelvic tumor with heterotopic bone formation].

The patient was a 74-year-old man who was referred to our hospital with a complaint of left flank pain. Laboratory data were almost within normal limits and urine cytology was positive. X-ray examination revealed a calcification in the left kidney and abdominal CT scan confirmed the presence of a heterogenous renal pelvic mass which contained a calcification. Based on these examinations, a diagnosis of a renal pelvic cancer with heterotopic bone formation was made. Subsequently, left nephroureterectomy was performed. Grossly, the renal pelvis of the resected kidney was filled with a mass which had a white cut surface and bone-like tendency. Histopathologically, a poorly differentiated transitional cell carcinoma with massive bone formation was found. Fifty five cases of heterotopic bone formation in the kidney have been reported in Japan. Among the cases, 4 cases were complicated with renal pelvic tumor and our case was the second case of heterotopic bone formation complicated with a transitional cell carcinoma of the renal pelvis in Japan.

Virtual CT endoscopy of ossicles in the middle ear.

The purpose of this study is to evaluate how virtual computed tomography (CT) endoscopy may help in assessing ossicles in the middle ear. Our series consisted of 96 ears of 68 consecutive patients with conducting hearing loss. All examinations were performed with a high-resolution spiral CT using axial and direct coronal planes of the temporal bone. Perspective virtual endoscopy was processed using the virtual endoscopic software. Superstructure of the stapes was difficult to evaluate on the virtual endoscopy; however, virtual endoscopy of the middle ear provides further information on the pathological conditions including congenital anomaly, posttraumatic, and inflammatory processes.

[Simultaneous mitral and aortic valvuloplasty using rasping procedure for combined valvular disease: a case report].

We reported a case of successful simultaneous mitral and aortic valvuloplasty using rasping procedure. A 55-year-old woman with combined valvular disease received this operation. Postoperatively, the mitral valve area increased from 1.15 cm2 to 2.03 cm2. Mitral regurgitation improved. Aortic valve pressure gradient decreased from 21 mmHg to 0 mmHg. Aortic regurgitation also improved. Cardiac Index (CI) increased from 1.94 l/min./m2 to 2.59 l/min./m2. Ejection fraction (EF) also increased from 60% to 82%. The postoperative course was uneventful. Excellent postoperative results of this procedure may be expected, not only in single valvular disease but also in combined valvular disease.

[Clinical evaluation of combined spinal-epidural anesthesia by needle-through-needle approach in 485 surgical cases].

We analyzed retrospectively the technical and clinical consequences of combined spinal-epidural anesthesia by needle-through-needle approach over the last two years. A Tuohy-type 18-gauge epidural needle (Perican; B. Braun Co.) and long pencil-pointed 27-gauge spinal needle (Whitacre; Becton-Dikinson Co.) were selected. Spinal anesthesia was administered with 0.5% tetracaine. A total of 485 anesthesia cases included 144 cases for lower abdominal, 193 cases for gynecological and 148 cases for orthopedic surgeries. The successful subarachnoid puncture with only one attempt was recorded in 89% of abdominal, 71% of gynecological and 72% of orthopedic cases. On the other hand, in three (0.6%) cases even with several attempts, the puncture was not possible. Inadvertent dural puncture and subarachnoid catheterization occurred in six (1.2%) and four (0.6%) cases, respectively. Inadequate spinal anesthesia was supplemented with epidural anesthesia in 13% of abdominal, 21% of gynecological and 7% of orthopedic cases. No serious complication occurred. We conclude that this needle-through-needle approach facilitates subarachnoid puncture with an ultra-fine spinal needle and subsequent epidural catheterization serves for supplemental and post-operative analgesia unless inappropriate subarachnoid indwelling occurs.

Analysis of the mechanism of discrepant nuclear morphometric results comparing preoperative biopsy and prostatectomy specimens.

OBJECTIVES: To explore the mechanism for the differing nuclear morphometric results between needle biopsy and surgical specimens of the prostate. METHODS: In experiment 1, a comparison of mean nuclear area (MNA), volume-weighted mean nuclear volume (MNV), and form factor (FF) for prostatic epithelial cells was performed between preoperative needle biopsy and prostatectomy specimens from 5 patients with benign prostatic hyperplasia (BPH). In experiment 2, a scheduled, sequential ex vivo needle sampling from the enucleated prostates (at 0, 2, 6, and 24 hours after surgical resection) was also performed for 7 patients with BPH. The prostatectomy specimens were left unfixed for 2 hours until the second needle sampling was done. Nuclear morphometric parameters were measured on the needle-sampled as well as on the prostatectomy specimens. RESULTS: MNA, MNV, and FF of BPH cells measured on preoperative biopsy specimens were smaller than those of surgical specimens in all 5 of the cases. The results of nuclear morphometry on the materials obtained by ex vivo needle sampling of prostates before and during fixation revealed that the MNA, MNV, and FF for BPH cells of 0-hour specimens were significantly smaller than those for needle samples at 2, 6, and 24 hours after surgical resection as well as those for prostatectomy specimens. CONCLUSIONS: The present study provided further evidence that the ischemic damage caused by delayed fixation could result in a substantial change of the nuclear morphology of prostate cells. An immediate start, as well as a rapid completion, of the fixation procedure seems critical for an accurate nuclear morphometry of prostatectomy specimens.

[Intra- and postoperative heart rate changes following propofol anesthesia; a comparison with isoflurane anesthesia].

Bradycardia during propofol anesthesia is well known, but bradycardia after propofol anesthesia has not been studied well. We compared perioperative heart rates in patients who had undergone gynecological surgery under lumbar epidural anesthesia supplemented with light general anesthesia using isoflurane and nitrous oxide in oxygen (Group Iso, n = 25) with those who had received lumbar epidural anesthesia supplemented with propofol (Group Prop, n = 25). The heart rates for the Group Prop were significantly lower (P < 0.05) than those for the Group Iso after the induction of anesthesia up to 2 hours after surgery. Two patients in the Group Prop developed bradycardia below 50 bpm 1 and 2 hours after surgery. In one of them intravenous atropine was necessary to treat bradycardia. We conclude that more attention should be paid to postoperative as well as intraoperative bradycardia in patients who receive propofol.

[Two cases of nephrogenic adenoma in the bladder diverticulum].

We report two cases of a nephrogenic adenoma in the bladder diverticulum. The first patient was an 81-year-old man with gross hematuria. Cystoscopy revealed bladder diverticulum and a papillary tumor within. Bladder diverticulectomy was performed and the histopathological diagnosis was a nephrogenic adenoma. The second patient was a 50-year-old man with gross hematuria and dysuria. Transabdominal ultrasound revealed bladder diverticulum. Transurethral coagulation of the bladder diverticulum was performed. Then three papillary tumors were detected, and were resected transurethrally. The histopathological diagnosis was a nephrogenic adenoma. These are the first and second cases of a nephrogenic adenoma in the bladder diverticulum reported in Japan.

[Intra-arterial infusion chemotherapy for liver metastases of testicular tumors: report of two cases].

Two cases of testicular tumors with lymph node involvement and multiple lung and liver metastases were treated successfully with intra-arterial infusion chemotherapy. Case 1: A 30-year-old man presented with right scrotal swelling and an abdominal mass. He had a large retroperitoneal mass and multiple lung and liver metastases on computed tomographic (CT) scan and chest X-ray. Right inguinal orchiectomy was performed. Histopathological diagnosis revealed embryonal cell carcinoma and choriocarcinoma. Cisplatin, vinblastine, VP-16 and pepleomycin combination chemotherapy (PVeBV) was started and repeated for 2 courses. The retroperitoneal mass and lung tumors decreased in size, but liver tumors enlarged. Systemic and intrahepatic arterial infusion combined with chemotherapy was administered, and intra-arterial chemotherapy (cisplatin, VP-16) was added. The patient also received systemic chemotherapy (carboplatin, VP-16, ifosfamide). After chemotherapy, retroperitoneal lymph node dissection was performed. Microscopic examination revealed no viable cancer cells. On CT scan, no retroperitoneal, liver, or lung tumor was detected. Case 2: A 43-year-old man presented with right scrotal swelling and an abdominal mass. CT scan revealed a large retroperitoneal mass as well as lung and multiple liver metastases. Right inguinal orchiectomy was performed. Histopathological diagnosis revealed seminoma. Cisplatin, vinblastine, VP-16 and pepleomycin combination chemotherapy (PVeBV) was administered, but the liver tumors ware enlarged on CT scan. Intrahepatic arterial infusion chemotherapy (cisplatin, VP-16) was started and repeated for 4 courses. On CT scan, the lung metastasis seemed to have disappeared, and the retroperitoneal mass and liver metastases were decreased in size.

[Quality of life in patients with testicular cancer after high orchiectomy, radiation therapy or chemotherapy].

We evaluated the physical or psychosocial states of testicular cancer patients receiving orchiectomy, radiation therapy and chemotherapy to assess their quality of life during and after treatment. The subjects were 33 post-treatment patients with testicular cancer who responded to the questionnaire we mailed to them. The quality of life score during chemotherapy showed a decrease, which was accompanied by gastrointestinal symptoms induced by anti-cancer drugs. With regard to the difference in adjuvant treatment types, the surveillance group showed the highest score in the satisfaction of daily life. Moreover, married patients tended to be satisfied with daily life more than non-married patients. With regard to sexual or erectile function, scores of testicular cancer patients, especially in the retroperitoneal lymph node dissection group, were inferior to these of normal volunteers. In conclusion, the physical or psychosocial states after treatment for testicular cancer depend not only on treatment type but also marriage status.

[Retrovesical liposarcoma: a case report].

A case of retrovesical liposarcoma is reported. The patient was a 41-year-old man who complained of left scrotal pain and of hip discomfort. Digital rectal examination revealed a hen's egg-sized mass with an elastic hard consistency at the left side of the normal prostate. Pelvic CT and MRI showed a heterogeneous tumor in the retrovesical region. Transperineal biopsy revealed liposarcoma. Pelvic exenteration, colostomy and ileal conduit were performed. The resected weight was 1,680 grams, and the histopathological diagnosis was myxoid type of liposarcoma, grade II. Postoperatively, a metastatic lesion to vertebrae thoracicae I developed causing radiculoneuropathy of the left superior limb. Spot radiation (50 Gy) was administered to the lesion, but there was no response. Currently, the patient is being treated with combination chemotherapy consisting of dacarbazine, vincristine, adriamycin, and cyclophosphamide. Cases of retrovesical liposarcomas reported in Japan are reviewed and discussed.

[Treatment outcome of radical cystectomy during a 10-year period (June 1984-September 1994) at Department of Urology, Fukui Medical School].

The treatment outcome was evaluated in 63 patients with bladder cancer more than 2 years after cystectomy. Cisplatin-based combination chemotherapies were given to 40 patients after the operation as an adjuvant therapy and two patients with T4 or N2 bladder cancer received chemotherapy before the operation as a neoadjuvant therapy. The extent of infiltration of the removed tumors was pTa in 5, pT1 in 18, pT2 in 8, pT3a in 6, pT3b in 17, and pT4 in 9 cases. Regional lymph node metastases were present in 10 cases (16%). Nineteen patients died of tumor recurrences. The 5-year acturial survival rates at each stage were 60% for stage pTa, 78% for stage pT1, 63% for stage pT2, 83% for stage pT3a, 33% for stage pT3b and 38% for stage pT4, respectively. A significant difference (p < 0.05) in survival curve was observed between pT3a and pT3b. The prognosis of patients with tumors extending beyond the bladder muscles is extremely unfavourable, with the exception of bladder cancers infiltrating the neighboring organ (pT4a), the removal of which may result in lasting survival in a part of the cases. Effective adjuvant treatment is required for patients with bladder tumors penetrating the bladder wall.

[Clinical studies on renal pelvic and ureteral carcinoma].

We reviewed 40 patients with renal pelvic and/or ureteral transitional cell carcinomas, consisting of 24 males and 16 females with a mean age of 65 years. The histopathological stage of surgically removed specimen was pTa in 6 patients, pT1 in 7, pT2 in 5, pT3 in 11 and pT4 in 6. Three patients with Tis and 2 with T3 did not undergo surgery. Of 35 patients pathologically examined, lymphatic and venous invasions were detected in 22 (63%) and 16 (46%), respectively, and were associated with pathological stage and grade. Overall the 5-year actuarial survival rate was 57.1%. Tumor staging and vascular invasion had a prognostic significance on the treatment outcome, but not metachronous or synchronous bladder cancer, identified in 55% of the patients. Adjuvant chemotherapy appeared to improve the survival of the patients with tumors pT2 or higher, grade 3 or vascular invasion without metastases.

Normothermic cardiopulmonary bypass: effect on the incidence of persistent postoperative neurological dysfunction following coronary artery bypass graft surgery.

We retrospectively reviewed the records of 250 consecutive patients undergoing coronary artery bypass graft surgery (CABG) from January 1994 through January 1996 to determine the incidence of persistent postoperative neurological dysfunction after CABG and to compare normothermic and moderate hypothermic cardiopulmonary bypass (CPB). Normothermic CPB was used in 128 patients (36°-37°C) and hypothermic CPB (27°-28°C) in 122 patients. Postoperative neurological dysfunction included focal motor deficits, delayed recovery of consciousness (>24h) after surgery, and seizures within 1 week postoperatively. Persistent neurological dysfunction was diagnosed if complete resolution had not occurred within 10 days of surgery. The incidence of persistent postoperative neurological dysfunction was 4.1% in the hypothermic CPB group and 2.3% in the normothermic CPB group. There were no statistically significant differences between the two groups (P=NS). These results suggest that normothermic CPB did not increase the incidence of persistent postoperative neurological dysfunction compared to hypothermic CPB.

Analysis of histological heterogeneity in renal cell carcinoma: tumor size-related histological change and its prognostic significance.

BACKGROUND: It is well recognized that the histology of renal cell carcinoma (RCC) is often heterogeneous. It is also believed that the prognosis of patients with large tumors is generally poorer than those with small tumors. However, there has been no detailed study on changes in histological features of RCCs associated with tumor growth. This study was conducted to investigate whether there are any specific histological changes related to tumor size and to study the prognostic value of histological parameters in RCCs. METHODS: The presence or absence of each histological component (3 cell types and 5 histological architectures) was investigated in 110 RCCs. The tumor size-associated changes in the histological composition of the RCCs were evaluated, and the prognostic significance of the histological parameters was analyzed using univariate and multivariate analysis. RESULTS: The percentage of RCCs with multiple cell types increased with tumor size, whereas increases in multiplicity were not as prominent in the histological architectures. Several characteristic changes, however, were observed in both cell types and architectures. RCCs with a pure clear cell, pure alveolar pattern or cystic architectural pattern decreased, while those with granular or spindle/pleomorphic cell types, or papillary or solid architectural patterns increased with tumor size. A univariate analysis revealed that a clear cell type and an alveolar or cystic architectural pattern were associated with a better prognosis, while spindle/pleomorphic cells and a solid architecture pattern correlated with a poorer prognosis. Multivariate analysis of cell types and architectures showed, however, that only the presence of spindle/pleomorphic cell types and a solid architecture were independent prognostic variables. CONCLUSION: The histological composition of RCCs varied according to the size of the tumor. Sarcomatous components increased with tumor size and were independently associated with a poor prognosis. Further study is warranted to correlate specific genetic alterations with tumor growth-related histological changes in RCCs.

[Intracavitary bacillus Calmette-Guerin therapy for upper tract transitional cell carcinoma].

Four patients with upper urinary tract transitional cell carcinoma were treated with bacillus Calmette-Guerin (BCG) via a percutaneous nephrostomy tube or a retrograde ureteral catheter. A 68-year-old female and an 80-year-old male had carcinoma in situ (CIS) in the left upper urinary tract (cases 1 and 2). A man aged 47 had CIS in the left upper urinary tract, bladder, and prostatic urethra (case 3). CIS in the left upper urinary tract was identified in a woman aged 63 with chronic renal insufficiency (case 4). Two patients (cases 1 and 2) responded to this therapy. In the other two patients nephrectomy was performed due to residual tumor. There were extensive tuberculous granulomas in the kidneys. In one resected kidney (case 4) carcinoma had invaded the renal parenchyma. The reviewed literature showed that BCG perfusion therapy was effective in 71% (27 of 38 renal units) for the upper urinary tract tumors and that there were 5 cases of severe complication, including sepsis in 2, high fever in 2, and ureteral stricture in 1. Based on the fact that the kidney receives a profuse blood supply and that the renal pelvis and ureter have a thin wall, careful management is mandatory to prevent severe adverse effects and insidious tumor progression.

Early disease progression after intravesical bacillus Calmette-Guérin (BCG) therapy for superficial bladder cancer.

BACKGROUND: Disease progression after Bacillus Calmette-Guérin (BCG) instillation therapy for bladder cancer is not rare. The purpose of this study was to evaluate the outcome of patients treated with BCG for superficial bladder cancer, focusing on the patients who developed invasive disease during follow-up. The possible mechanism and risk factors for early progression after BCG therapy are discussed. METHODS: A total of 25 patients with superficial bladder cancer (pTa, pT1 and/or pTis) were treated with intravesical BCG instillation (80 mg in 80 ml saline) once a week for eight weeks. Four of the 25 patients received maintenance therapy with BCG (once a month for 3 to 10 months). Patients were followed every three months and underwent cystoscopy, biopsy, and urinary cytology at these intervals. Disease progression was defined as invasion to muscle or prostate, or development of metastatic disease. Clinicopathological features of the patients, especially those with progression, were analyzed. RESULTS: Progression was observed in six of the 25 patients, (including four of 19 patients with carcinoma in situ and two of five patients treated prophylactically with BCG). The average time to progression was 8.7 months. Four patients died of cancer despite intensive treatment. Two patients are alive: one without evidence of disease after cystectomy and the other with metastatic disease. CONCLUSIONS: Proper patient selection, careful follow-up, and immediate aggressive therapy in case of progression were considered to be important factors to obtain satisfactory results with BCG therapy for bladder cancer.