Cell trapping in Y-junction microchannels: A numerical study of the bifurcation angle effect in inertial microfluidics.

The majority of microfluidic technologies for cell sorting and isolation involve bifurcating (e.g., Y- or T-shaped junction) microchannels to trap the cells of a specific type. However, the microfluidic trapping efficiency remains low, independently of whether the cells are separated by a passive or an active sorting method. Using a custom computational algorithm, we studied the migration of separated deformable cells in a Y-junction microchannel, with a bifurcation angle ranging from 30° to 180°. Single or two cells of initially spherical shape were considered under flow conditions corresponding to inertial microfluidics. Through the numerical simulation, we identified the effects of cell size, cytoplasmic viscoelasticity, cortical tension, flow rate, and bifurcation angle on the critical separation distance for cell trapping. The results of this study show that the trapping and isolation of blood cells, and circulating tumor cells in a Y-junction microchannel was most efficient and least dependent on the flow rate at the bifurcation angle of 120°. At this angle, the trapping efficiency for white blood cells and circulating tumor cells increased, respectively, by 46% and 43%, in comparison with the trapping efficiency at 60°. The efficiency to isolate invasive tumor cells from noninvasive ones increased by 32%. This numerical study provides important design criteria to optimize microfluidic technology for deformability-based cell sorting and isolation.

Rapid Turnover and High Production Rate of Myeloid Cells in Adult Rhesus Macaques with Compensations during Aging.

Neutrophils, basophils, and monocytes are continuously produced in bone marrow via myelopoiesis, circulate in blood, and are eventually removed from circulation to maintain homeostasis. To quantitate the kinetics of myeloid cell movement during homeostasis, we applied 5-bromo-2'-deoxyuridine pulse labeling in healthy rhesus macaques (Macaca mulatta) followed by hematology and flow cytometry analyses. Results were applied to a mathematical model, and the blood circulating half-life and daily production, respectively, of each cell type from macaques aged 5-10 y old were calculated for neutrophils (1.63 ± 0.16 d, 1.42 × 109 cells/l/d), basophils (1.78 ± 0.30 d, 5.89 × 106 cells/l/d), and CD14+CD16- classical monocytes (1.01 ± 0.15 d, 3.09 × 108 cells/l/d). Classical monocytes were released into the blood circulation as early as 1 d after dividing, whereas neutrophils remained in bone marrow 4-5 d before being released. Among granulocytes, neutrophils and basophils exhibited distinct kinetics in bone marrow maturation time and blood circulation. With increasing chronological age, there was a significant decrease in daily production of neutrophils and basophils, but the half-life of these granulocytes remained unchanged between 3 and 19 y of age. In contrast, daily production of classical monocytes remained stable through 19 y of age but exhibited a significant decline in half-life. These results demonstrated relatively short half-lives and continuous replenishment of neutrophils, basophils, and classical monocytes during homeostasis in adult rhesus macaques with compensations observed during increasing chronological age.

[A case of bladder cancer with metastasis to the bone of the hand].

Metastasis to the bone of the hand is rare. In addition, metastasis to the bone of the hand from bladder cancer is extremely rare. We herein report a case of distal phalanx metastasis from bladder cancer. A 64- year-old man who was diagnosed with bladder cancer (cT2bN0M0) received total cystectomy (pT3bN2). Two months after the surgery, a roentgenogram revealed lung metastasis. Then we administered 2 cycles of chemotherapy using gemcitabine and cisplatin. Computed tomography revealed a partial response. However, several months after chemotherapy, we noted that his left ring finger was swollen and showed erythema. We made a diagnosis of metastasis to the distal phalanx of the left ring finger and amputated the finger. Pathological findings showed no conflict with metastasis from bladder cancer. Postoperative course was good, but he died about three months after the diagnosis of metastasis.

[Early initiation of antiplatelet therapy after urological surgery : a prospective study].

In recent times, the number of patients receiving antiplatelet drugs for the prevention of cardiovascular and cerebrovascular diseases has been increasing. We examined the possibility of early initiation of antiplatelet therapy after urological operations. Between April 2008 and February 2009, 62 patients who received antiplatelet drugs and underwent urological surgeries (open surgery, transurethral surgery and laparoscopic surgery) and prostate biopsies were examined. Of the 62 patients, 59 were randomized into 2 groups ; 32 patients receiving antiplatelet treatment initiation within 24 hours (early group) and 29 patients receiving this treatment more than 24 hours (late group) after the urological operation. The end point of this study was the re-cessation of antiplatelet therapy because of the development of postoperative complications (hematuria, blood loss, etc.) and cardiovascular and cerebrovascular events within 1 month. There was no significant difference in the urological events observed between these groups, including 2 of the 32 (6.3%) patients in the early group and 3 of the 27 (11.1%) in the late group. Cardiovascular and cerebrovascular diseases were not noted in any of the patients within 1 month. In conclusion, we think that it is possible to initiate antiplatelet therapy within 24 hours after urological operations and prostate biopsies in the absence of active blood loss. Early initiation may prevent the risk of cardiovascular and cerebrovascular disease in the future.

[Clinical studies on renal cell carcinoma].

PURPOSE: We reviewed 193 patients of renal cell carcinoma treated at Osaka Police Hospital between 1990 and 2006. METHODS: The patients consisted of 140 males and 53 females. The median age was 62 years, ranging from 26 to 88 years. Median follow-up period was 53 months. TNM system and pathologic findings were classified in accordance with the Japanese General Rules for Clinical and Pathological Studies on Renal Cell Carcinoma. Survival rates were calculated using the Kaplan-Meier method, and differences in survival curves were estimated with the log-rank test. Independent prognostic factors were analyzed using the Cox proportional hazards model. RESULTS & CONCLUSIONS: The overall 3, 5, 10 and 15-year cause-specific survival rates were 92.6, 91.1, 86.1, 72.2%, respectively. Univariate analysis indicated age, chief complaint, performance status, tumor size, anemia, CRP, tumor extent, grade, infiltrating pattern, venous involvement, lymph node metastasis, distant metastasis, stage to be significant prognostic factors. Moreover, multivariate analysis with Cox's proportional hazard model revealed high age (60 < or =), positive CRP, and T4 to be independent poor prognosticators for cause specific survival. Using these three risk factors, patients with 0, 1, 2, and 3 poor risk factors were classified as 0, 1, 2, and 3 risk groups, respectively. The overall 5 and 10-year cause specific survival rates in 0, 1, 2, and 3 risk groups were 100 and 100%, 90.8 and 83.8%, 71.6 and 34.1%, 0 and 0%, respectively. The overall 5 and 10-year cause specific survival rates (69.2 and 33.0%) especially in 2 and 3 risk groups were significantly poor prognosis, comparing with those (94.8 and 91.9%) in 0 and 1 risk group (p< 0.0001). Thus, the intensity of the follow up period and the necessity of postoperative adjuvant therapy for a patient are recommended for 2 and 3 risk groups.

[A case report: retroperitoneoscopic nephrectomy for a giant hydronephrosis of a horseshoe kidney].

A 30-year-old female was referred to our hospital complaining of left flank pain. She was diagnosed with a giant hydronephrosis in a horseshoe kidney. We performed a retroperitoneoscopic nephrectomy on the non-functioning moiety of the horseshoe kidney. After the placement of a ureteral catheter, she underwent a retroperitoneal nephrectomy. The feeding vessels consisted of four arteries and four veins. The thin isthmus of the horseshoe kidney was divided using scissors, without the need for electrocautery, and hemostasis was achieved using monopolar shears. Laparoscopic nephrectomy on a horseshoe kidney is a difficult surgery given the aberrant vessels and isthmus, so it tends to be avoided for reasons of safety. However, if appropriate preoperative imaging is carried out and the procedure is conducted in a careful manner, it can be made a safe and minimally invasive operation.

[Primary signet-ring cell carcinoma of the urinary bladder: a case report].

We report a case of signet-ring cell carcinoma of the urinary bladder. A 60-year-old man was hospitalized because of total macrohematuria. Cystoscopic examination revealed a non-papillary sessile tumor on the posterior wall of the urinary bladder. The pathological diagnosis was stage pT1 signet ring cell carcinoma. Upper gastrointestinal endoscopy and computed tomographic scanning revealed no involvement of other organs. Radical cystectomy and creation of an ileal neobladder were performed. The histopathological stage was pT3aN0M0. Adjuvant chemotherapy (TS-1) was performed and the patient is currently free from disease at eight months after the surgery. This disease is usually diagnosed at an advanced stage and has a poor prognosis. To our knowledge, this is the first case report on the creation of an ileal neobladder for the treatment of primary signet-ring cell carcinoma of the urinary bladder.

[Scrotal hematoma associated with idiopathic thrombocytosis: a case report].

We report a case of acute scrotal hematoma associated with idiopathic thrombocytosis. A 75-year-old man visited our hospital for the treatment of a left scrotal mass that had been increasing in size; the mass had developed after the puncture of left testicular hydrocele. The patient was diagnosed with acute scrotal hematoma on the basis of ultrasonography findings. The patient underwent an emergency operation for the removal of the hematoma. On 2 days after the surgery we noticed an increase in the size of the hematoma. The patient had a 4-year clinical history of idiopathic thrombocytosis for which he had not received any treatment. Although the platelet count was slightly high at the time of the operation, complete hemostasis did not occur because of the existence of platelet dysfunction. The second hematoma was treated conservatively. To our knowledge, this is the first case report on the acute scrotal hematoma associated with idiopathic thrombocytosis.

Effects of respiratory rate and tidal volume on gas exchange in total liquid ventilation.

Using a rabbit model of total liquid ventilation (TLV), and in a corresponding theoretical model, we compared nine tidal volume-respiratory rate combinations to identify a ventilator strategy to maximize gas exchange, while avoiding choked flow, during TLV. Nine different ventilation strategies were tested in each animal (n = 12): low [LR = 2.5 breath/min (bpm)], medium (MR = 5 bpm), or high (HR = 7.5 bpm) respiratory rates were combined with a low (LV = 10 ml/kg), medium (MV = 15 ml/kg), or high (HV = 20 ml/kg) tidal volumes. Blood gases and partial pressures, perfluorocarbon gas content, and airway pressures were measured for each combination. Choked flow occurred in all high respiratory rate-high volume animals, 71% of high respiratory rate-medium volume (HRMV) animals, and 50% of medium respiratory rate-high volume (MRHV) animals but in no other combinations. Medium respiratory rate-medium volume (MRMV) resulted in the highest gas exchange of the combinations that did not induce choke. The HRMV and MRHV animals that did not choke had similar or higher gas exchange than MRMV. The theory predicted this behavior, along with spatial and temporal variations in alveolar gas partial pressures. Of the combinations that did not induce choked flow, MRMV provided the highest gas exchange. Alveolar gas transport is diffusion dominated and rapid during gas ventilation but is convection dominated and slow during TLV. Consequently, the usual alveolar gas equation is not applicable for TLV.

Androgen decline in patients with nonobstructive azoospemia after microdissection testicular sperm extraction.

OBJECTIVES: Microdissection testicular sperm extraction (TESE) is the ideal procedure for obtaining a high sperm retrieval rate. However, few studies of the postoperative endocrinologic course have been reported. We evaluated the endocrinologic course for 1 year after microdissection TESE and compared the results with the testicular histologic findings. METHODS: A total of 69 patients with nonobstructive azoospermia who had undergone microdissection TESE were included. The overall sperm retrieval rate was 50.7%. The endocrinologic data were evaluated before and 3, 6, and 12 months after surgery. RESULTS: The mean serum total testosterone level in patients with hypospermatogenesis decreased postoperatively and had recovered by 12 months (102%). The mean serum total testosterone level in patients with Klinefelter syndrome also decreased postoperatively but had recovered to only 50% of the baseline value at 12 months after microdissection TESE. At 12 months, the mean serum total testosterone level in patients with maturation arrest was 93.1% of the preoperative level and that in patients with Sertoli cell-only syndrome was 80.6% of the preoperative level. The preoperative serum luteinizing hormone and follicle-stimulating hormone in patients with Klinefelter syndrome was high and remained high after microdissection TESE. The mean serum luteinizing hormone and follicle-stimulating hormone levels in patients with hypospermatogenesis did not change, and those in patients with maturation arrest increased continuously after microdissection TESE. Finally, those in patients with Sertoli cell-only syndrome increased up to 6 months after surgery and decreased after that. CONCLUSIONS: The results of our study indicate that long-term endocrinologic follow-up is necessary after microdissection TESE, particularly for patients with Klinefelter syndrome to detect hypogonadism.

[Immunohistochemical studies of p53, Ki-67, E-cadherin and beta-catenin on renal pelvic and ureteral cancers].

PURPOSE: We reviewed prognosis and bladder recurrence of 31 patients with renal pelvic and ureteral cancer concerning clinicopathological and immunohistochemical factors. METHODS: The patients consisted of 19 males and 12 females. The median age was 69 years, ranging from 43 to 84 years. Median follow-up period was 79 months. Immunohistochemistry for p53, Ki-67, E-cadherin and beta-catenin was performed on sections from tumor tissue. RESULTS & CONCLUSIONS: The overall 5-year cause-specific survival rate was 77.4%. Univariate analysis indicated tumor number, grade, infiltrating pattern, lymphatic involvement to be significant prognostic factors. Moreover, multivariate analysis with Cox's proportional hazard model revealed tumor number and lymphatic involvement to be independent prognostic factors for cause-specific survival rate. The overall 5-year bladder recurrence free rate was 60.9%. Univariate analysis revealed expression of E-cadherin to be a significant factor for bladder recurrence free rate.

Rare case of the hyaline vascular type of Castleman's disease of the kidney.

Castleman's disease (CD) is a rare disorder characterized by a benign proliferation of lymphoid tissue. Most cases tend to present as a mediastinal mass. A few extrathoracic cases involving nodal and extranodal locations have previously been reported. To the best of our knowledge, however, only one case of CD of the kidney has been published in an English report. We herein report a rare case of CD presenting as a left renal tumor. A 70-year-old male was examined by computed tomography for a follow-up for colonic diverticulitis and a left renal mass measuring 2.0 cm in diameter was incidentally found. The patient underwent a left partial nephrectomy for a left renal mass and a histopathological analysis demonstrated the hyaline vascular type of CD. Based on our findings, CD should be included in the differential diagnosis of renal tumors.

Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems.

We describe a microfabricated airway system integrated with computerized air-liquid two-phase microfluidics that enables on-chip engineering of human airway epithelia and precise reproduction of physiologic or pathologic liquid plug flows found in the respiratory system. Using this device, we demonstrate cellular-level lung injury under flow conditions that cause symptoms characteristic of a wide range of pulmonary diseases. Specifically, propagation and rupture of liquid plugs that simulate surfactant-deficient reopening of closed airways lead to significant injury of small airway epithelial cells by generating deleterious fluid mechanical stresses. We also show that the explosive pressure waves produced by plug rupture enable detection of the mechanical cellular injury as crackling sounds.

[Liposarcoma of the spermatic cord associated with rectum cancer: a case report].

We report a case of liposarcoma of the spermatic cord associated with rectum cancer. A 78-year-old man visited our hospital with a complaint of painless left inguinal mass. He also showed constipation and bloody bowel discharge, rectum cancer was diagnosed by further evaluation. Ultrasonography, computed tomography and magnetic resonance imaging revealed a 2 x 4 x 6 cm mass in the left spermatic cord. Left high orchiectomy for the left inguinal tumor and Hartmann's procedure for rectum cancer was performed. Histologically, the mass in the left spermatic cord was well differentiated liposarcoma and rectum cancer was poorly differentiated adenocarcinoma. He died from rectum cancer with no evidence of recurrence of liposarcoma of the left spermatic cord after follow up for 6 months.

Pulsatile blood flow and gas exchange across a cylindrical fiber array.

The pulsatile blood flow and gas transport of oxygen and carbon dioxide through a cylindrical array of microfibers are numerically simulated. Blood is modeled as a homogeneous Casson fluid, and hemoglobin molecules in blood are assumed to be in local equilibrium with oxygen and carbon dioxide. It is shown that flow pulsatility enhances gas transport and the amount of gas exchange is sensitive to the blood flow field across the fibers. The steady Sherwood number dependence on Reynolds number was shown to have a linear relation consistent with experimental findings. For most cases, an enhancement in gas transport is accompanied with an increase in flow resistance. Maximum local shear stress is provided as a possible indicator of thrombosis, and the computed shear stress is shown to be below the threshold value for thrombosis formation for all cases evaluated.

[Clinical survey of prostate cancer].

OBJECTIVES: Treatment trends and outcomes for prostate cancer in our hospital were reported. MATERIAL AND METHODS: A total of 482 patients with prostate cancer treated in our hospital between January, 1990 and December, 2004. RESULTS: The age distribution was from 51 to 99 years-old, with the mean age of 72.9 years-old at onset. The number of prostate cancer patients, especially asymptomatic patients with PSA elevation, have increased recently. As for the clinical stage, 92 cases (19.1%), 238 cases (49.4%), 48 cases (10.0%) and 104 cases (21.6%) were stage A, B, C and D, respectively. 425 cases (88.2%) received some form of endocrine therapy. Retropubic prostatectomy or external beam radiation therapy was performed in 77 and 57 cases, respectively all cases. The cause-specific 5-year survival rate of the 482 cases was 79.7%, comprising 100% for stage A1, 96.8% for stage A2, 89.4% for stage B, 79.9% for stage C and 42.9% for stage D. The cause-specific 5-year survival was significantly better in the latter patients (1997-2004) than the former patients (1990-1996) in stage C (p = 0.0226), D (p = 0.0448). In stage C patients, the retropubic prostatectomy (with endocrine therapy) group, increased in the latter period and showed longer cause-specific 5-year survival than the endocrine therapy group (p = 0.0027). In stage D2 patients, chemo-endocrine therapy with VP-16, ADM and CDDP refractory and cause-specific 5-year survival was longer than endocrine therapy alone (p = 0.0467, P = 0.0381). CONCLUSION: Our results suggest that retropubic prostatectomy with endocrine therapy and chemo-endocrine therapy are useful for stage C and D prostate cancer patients, respectively.

[Urethral disruption treated by echo guided endoscopic management: a case report].

We report a case of 63-years-old man with a chief complaint of urinary retention and urethral meatal bleeding due to straddle injury. Urological examination revealed proximal bulbous urethral disruption with 1 cm gap, and then cystostomy was placed. Afterwards, urethral disruption was treated by echo guided endoscopic urethroplasty. Transurethral resection of scar tissue was performed twice for postoperative urethral stricture. Postoperative voiding cystourethrography revealed no urethral stricture. The patient voids well without urinary incontinence and erectile dysfunction. Recently, endoscopic urethroplasty, which is easy, minimally invasive, and repeatable in comparison with open urethral reconstruction, has been frequently performed for urethral disruption as endoscopic instruments functionally develop. Echo guided image in the present case is so useful that proximal and distal end of urethral disruption can be shown in same plane, indicating that primary urethral tract can be reconstructed without injury of rectum and urethra.

[Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder associated with left renal pelvic carcinoma: a case report].

We report a case of primary mucosa-associated lympoid tissue (MALT) lymphoma of the urinary bladder associated with left renal pelvic carcinoma. A 84-year-old woman showed microscopic hematuria during follow up for hypertention. Left renal pelvic tumor was found and she was referred to our hospital for further evaluation and managemant. She showed pyuria and Escherichia coli was detected by urine culture. Intravenous pyelography and computed tomography revealed the left renal pelvic tumor and solid bladder tumor. Transurethral resection of bladder tumor and left total nephroureterectomy were performed. Histologically, the left renal pelvic tumor was urothelial carcinoma > > adenocarcinoma, G2, pT2 and the bladder tumor was MALT lymphoma. Ga-scintigraphy showed no hot uptake suspicious of metastatic lesion. Then, external beam radiotherapy (36 Gy) was performed to the urinary bladder. She has been alive for 14 months with neither renal pelvic tumor nor MALT lymphoma showing any evidence of disease progression.

Papillary cystadenocarcinoma of the prostate: a case report.

A 91-year-old man presented with nocturnal frequency and urge incontinence of a few days duration due to involvement of prostate cancer (PCa) accompanied by a large cyst in the left lobe of the prostate gland and urinary bladder wall. Channeling transurethral resection of prostate was performed to relieve the main symptoms and the resected material was histologically diagnosed as papillary cystadenocarcinoma arising from the epithelium of microscopic retention cysts. Following shrinkage of the large cyst, the patient is doing well on a combination regimen of a luteinizing hormone-releasing hormone analogue and bicaltamide. Papillary cystadenocarcinoma of the prostate was originally defined as papillary PCa arising from, not accompanied by, prostatic cysts. Cysts associated with PCa are subdivided into primary (or true) and secondary (or pseudo) cysts. Cancer cells in primary cysts originate from the epithelial lining. Papillary growth type cysts belong to this group and are regarded as papillary cystadenocarcinoma. The secondary (or pseudo) cysts, which have no epithelial lining and consist of hemorrhagic and/or necrotic contents are associated with invasive PCa. In the present case, the microscopic retention cysts revealed by histologic examination were of the primary type. This case of papillary cystadenocarcinoma, arising from a primary cyst, is the 13th such report from among previously reported cases in Japan.

[Significance of multiple biopsies obtained from bladder mucosa in renal pelvic and ureteral carcinoma].

PURPOSE: We reviewed significance of multiple biopsies obtained from bladder mucosa in 59 patients of renal pelvic and ureteral carcinoma treated at Osaka Police Hospital between 1990 and 2003. MATERIALS & METHODS: The patients consisted of 41 males and 18 females. The median age was 68 years, ranging from 42 to 91 years. Multiple biopsies were carried out in principle to examine the following 5 cystoscopically normal-appearing bladder mucosal sites: (1) trigone, (2) posterior wall, (3) left lateral wall, (4) right lateral wall and (5) dome. Positive case of multiple biopsies was defined as patients having abnormalities in at least one biopsy specimen such as bladder tumor (BT) or dysplasia. Median follow-up period was 54 months. RESULTS & CONCLUSIONS: Of the 59 patients, 6 had positive multiple biopsies. Among them 3 had carcinoma n situ (CIS), and others had dysplasia. 4 patients with positive multiple biopsies had past or concurrent history of BT and received adjuvant intravesical instillation therapy. Positive rate of multiple biopsies significantly differed between patients with and without past and/or concurrent BT (4/15: 27% vs 2/44: 5% p = 0.03), indicating that multiple biopsies were useful to detect abnormal lesion accompanied with past and/or concurrent BT. 3-year bladder recurrence free rate was 61%. Postoperative bladder recurrence rate did not significantly differ between positive (1/6 17%) and negative (20/53: 38%) cases of multiple biopsies. Univariate analysis indicated stage (p = 0.03) and venous involvement (p = 0.02) to be significant prognostic factors for bladder recurrence free rate, but not multiple biopsies, although multivariate analysis with Cox's proportional hazard model revealed no independent prognosticators. Low recurrence rate of patients with positive multiple biopsies was possibly due to adjuvant intravesical instillation therapy to prevent bladder recurrence.