Is the eGFR formula adequate for evaluating renal function before chemotherapy in patients with urogenital cancer? A suggestion for clinical application of eGFR formula.

BACKGROUND: Accurate evaluation of renal function is required before cancer chemotherapy. Various kinds of formula have been developed for estimating creatinine clearance (Ccr) or glomerular filtration rate (GFR) conveniently. We retrospectively examined the reliability of the GFR estimating formula using the renal function data in cancer chemotherapy. METHODS: Clinical data of 12 patients with urogenital cancer from 1998 to 2013 in Saga University Hospital were reviewed. Patients were treated with 6-21 (median 10.5) courses of chemotherapy and those patients underwent 9-29 (median 14.5) times of 24hrCcr tests before and during chemotherapy. We compared estimated GFR (eGFR) with 24hrCcr. In addition, we developed a novel method to estimate the Ccr using the patient-inherent 24hrCcr/eGFR ratio, which is calculated from initial 3 or 4 determinations of 24hrCcr and the corresponding eGFR. Those estimated Ccrs were also compared with 24hrCcr. RESULTS: The dissociation between 24hrCcr and eGFR was not constant, and a large dissociation was observed in some cases. The newly devised estimated Ccr demonstrated less dissociation from 24hrCcr compared with eGFR. CONCLUSIONS: The eGFR formula is not adequate for the clinical use in cancer chemotherapy. The absolute value of eGFR is not reliable, but clinical use of eGFR as relative value seems to be acceptable. To avoid troublesome 24hrCcr measurement in long-term cancer chemotherapy, eGFR formula can be used for estimating Ccr in combination with the specific inherent 24hrCcr/eGFR ratio, which is obtained from 3 or 4 times of actual 24hrCcr measurements.

[PROCEDURE AND FEASIBILITY OF LAPAROSCOPIC RENAL BIOPSY].

OBJECTIVES: Recently, laparoscopic surgery is the standard procedure in urological field. We report the experience of laparoscopic renal biopsy for 4 patients who have contraindication of ultrasound-guided percutaneous renal biopsy. PATIENTS AND METHODS: We retrospectively reviewed the patients who underwent laparoscopic renal biopsy (LRB) from March 2010 to June 2013 in our hospital. Four female with mean age of 54.5 years old underwent LRB. Two patients had solitary kidney and the other 2 patients had bleeding tendency. All the biopsy was performed retroperitoneal approach. We used 18-gauge biopsy needle to take renal cortical tissue in all cases. In addition, one patient underwent small wedge biopsy with a cold knife. RESULTS: Mean operative time, pneumoperitoneal time, and estimated blood loss was 63.0 min (range 48-92 min), 37.5 min (range 22-75), and 11.25 ml (range 0-30 ml), respectively. No perioperative complication was observed. In all cases, we can diagnose pathologically by LRB. CONCLUSIONS: LRB is safe, effective, and feasible procedure for the patients in whom ultrasound-guided percutaneous renal biopsy is contraindication.

Adipose tissue explants and MDCK cells reciprocally regulate their morphogenesis in coculture.

Adipokine-producing fatty tissues, composed of preadipocytes, adipocytes, and mesenchymal stem cells, surround the kidney. To study the interaction between renal tubular cells and adipose tissue, we cocultured adipose tissue fragments and MDCK cells. MDCK cells in the coculture showed a taller columnar shape with improved organization of their microvilli and basal lamina than that seen in MDCK cell monoculture. The adipose tissue-induced change in morphology was replicated when we added leptin to MDCK cells cultured alone. Adiponectin abolished the leptin effect. Adipose tissue fragments inhibited MDCK cell division and also the formation of single-stranded DNA, an indicator of apoptosis. The fragments promoted the expression of polarity-associated proteins, including the tight junction molecules, ZO-1, atypical protein kinase C, and Cdc42. Further, the fragments also accelerated the expression of pendrin, the chloride/iodide transporter in the MDCK cells. In turn, MDCK cells decreased the number of preadipocytes and CD44+/CD105+ mesenchymal stem cells in the fragments, and promoted adiponectin production from the fragments. Thus, our study shows that adipose tissue fragments promote the hypertrophy, polarization, and differentiation of MDCK cells by attenuating their growth and apoptosis through opposing endocrine or paracrine effects of leptin and adiponectin. Further, MDCK cells inhibit the regeneration of preadipocytes and mesenchymal stem cells in adipose tissue.

Effects of adipocytes on the proliferation and differentiation of prostate cancer cells in a 3-D culture model.

OBJECTIVE: To investigate how the mechanism of adipocyte-prostate cancer cell interaction affects the proliferation and differentiation of prostate cancer cells. METHODS: An androgen-dependent cell line (LNCaP), two androgen-independent cell lines (PC-3, DU145), and mature adipocytes harvested from male Wistar rats were used. Cancer cells were co-cultured with the isolated mature adipocytes in 3-D collagen gel matrix culture. The morphology and proliferative ability of the prostate cancer cells were examined. With regard to the activation of the phosphatidylinositol 3-kinase (PI3K) pathway, the expression of phosphatase and tensin homologue deleted on chromosome ten (PTEN), Akt and Bad were determined by immunohistochemistry. RESULTS: LNCaP cells co-cultured with adipocytes formed larger clusters than those of the control. PC-3 cells co-cultured with adipocytes did not form larger clusters, but formed spherical and spindle-shaped cells. The phosphorylation of Akt in PC-3 cells was greater in the co-cultured group compared with the controls, but there were no significant differences in the phosphorylation of Akt with regard to LNCaP and DU145 cells. CONCLUSIONS: Adipocytes could modulate the proliferation and differentiation of prostate cancer cell lines. Activation of the PI3K pathway might be involved in the prostate cancer cell-adipocyte interaction.

Microwave tissue coagulator induces renal apoptotic damage to preserved normal renal tissue following partial nephrectomy.

BACKGROUND: We assessed the extent of apoptotic damage induced by the microwave tissue coagulator (MTC) in the preserved normal renal tissue following partial nephrectomy. METHODS: Eleven patients who underwent nonischemic partial nephrectomy with MTC (group M) were enrolled in this study. The other 11 patients who underwent cold-ischemic partial nephrectomy without the use of MTC were enrolled as controls (group C). There were no significant differences in tumor size or age between the two groups. Renal damage was evaluated by counting apoptotic cells in the normal renal tissue surrounding the tumor tissue. Immunohistochemical staining with single-stranded DNA was carried out to investigate the apoptotic cells. RESULTS: The number of apoptotic cells in group M ranged from 275 to 508 per 1,000 cells, with a median value of 421. The number in group C ranged from 122 to 466 per 1,000 cells with a median value of 286. The number of apoptotic cells in group M was significantly greater than that in group C (p = 0.006). Blood loss in group C was significantly greater than that in group M (p < 0.0001). CONCLUSIONS: This study points out that renal damage induced by the use of MTC comprises not only necrosis but also apoptotic change. Although MTC is useful for controlling renal parenchymal bleeding during partial nephrectomy, we must consider that renal apoptotic damage caused by the MTC may spread beyond the coagulated necrosis area.

Trends in radical prostatectomy.

The surgical treatment of prostate cancer ideally removes the entire cancer, avoids excessive blood loss or serious perioperative complications, and results in complete recovery of continence and potency. To achieve this, the surgeon must excise sufficient periprostatic tissue to cure the cancer while preserving the cavernosal nerves required for erectile function and the neuromusculature required for normal urinary and bowel function. Here we will examine recent trends in radical prostatectomy, focusing on surgical technique.

Oncologic assessment of hand-assisted retroperitoneoscopic nephroureterectomy for urothelial tumors of the upper tract: comparison with conventional open nephroureterectomy.

PURPOSE: To evaluate the oncologic results of our operative technique, hand-assisted retroperitoneoscopic nephroureterectomy (HRNU), for the treatment of upper-tract urothelial cancer, various perioperative parameters and oncologic outcomes were compared for HRNU and conventional open nephroureterectomy (CONU). PATIENTS AND METHODS: Thirty-six patients with clinical stage T(1,2)N(0)M(0) renal-pelvic and ureteral tumors underwent HRNU. A retroperitoneoscopic nephrectomy was carried out with hand assistance via a lower-abdominal midline incision. The lower ureter was resected by open surgery through the same incision, and the operative specimen was extracted via the same incision. Thirty-seven cases of CONU were reviewed as historical controls. Various perioperative and parameters and oncologic results were compared for the two procedures. RESULTS: The HRNU was completed in all but one case, which was converted to CONU. The mean operating time (395 minutes) was longer than that for CONU (289 minutes), and the mean estimated blood loss with HRNU (497 g) was greater than that with CONU (296 g). The mean time to oral intake (1.4 days) was shorter than that after CONU (2.3 days), and the mean time to walking was shorter (2.1 days v 2.6 days). There were no statistical differences in the cause-specific survival rate, the disease-free survival rate, or the bladder recurrence-free survival rate between HRNU (median follow-up 23 months) and CONU (median follow-up 56 months). CONCLUSION: The HRNU, a combination of endoscopic and conventional open surgery, seems to be a reasonable surgical procedure, because the lower-abdominal incision can be utilized, not only as a route for hand assistance, but also as a window for open surgery when resecting the distal ureter as well as for extraction of surgical specimens. The procedure is a safe alternative to conventional open surgery for upper urinary-tract tumors from an oncologic viewpoint.

Renal-tissue damage induced by laparoscopic partial nephrectomy using microwave tissue coagulator.

BACKGROUND AND PURPOSE: The microwave coagulator is a useful instrument that enables surgeons to perform partial nephrectomy without vascular clamping. The extent of postoperative thermal damage in surgically spared renal tissue has not been well examined. The present study was conducted to evaluate the tissue damage caused by microwave coagulation in laparoscopic partial nephrectomy (LPN) for small renal tumors. MATERIALS AND METHODS: Seven cases of LPN with a microwave tissue coagulator were entered in the present study. The median tumor diameter was 1.5 cm, and the median size of the resected specimen was 2.2 cm. Postoperative tissue damage was evaluated by contrast-enhanced CT 1 month after surgery. Surgically spared renal-tissue volume and functioning renal-tissue volume were estimated from the images by NIH Image 1.62 software. RESULTS: Postoperative CT revealed unenhanced renal tissue adjacent to the surgical margin. The median estimated volumes of surgically spared and functioning renal tissue were 96.1% (range 74.3%-99.8%) and 88.4% (range 68.0%-92.7%) of preoperative normal renal tissue, respectively. The percentile volume of functioning to surgically spared renal tissue ranged from 89.9% to 96.0% (median 92.8%). CONCLUSIONS: The microwave coagulator enables us to carry out partial nephrectomy without vascular clamping. Although 96% of normal renal tissue was surgically spared, 4% to 10% of this tissue was nonfunctioning as a result of microwave-induced thermal damage.

[A modified retroperitoneal approach to the kidney in patients with a highly deformed thorax: obtaining a wide operative field through subperiosteal resection of the 10th, 11th and 12th ribs].

We herein report a technique which facilitates a retroperitoneal approach to the kidney in cases of highly deformed thorax due to kyphoscoliosis. The operation consists of a lumbar oblique incision with removal of the 11th rib, combined with the additional removal of the 12th and 10th ribs. Resection of the upper two ribs was performed subperiosteally, leaving the periosteum of the deep side untouched. However, the deep side periosteum of the 12th rib was incised caudal from the pleural margin in order to facilitate exposure of the diaphragm. The retroperitoneal space was entered through the tip of the 11th rib bed. The diaphragm was incised dorso-medially at a level 1 cm caudal from the lower margin of the pleura, to an extent necessary to enable the pleura together with the cranial diaphragm to be manoeuvred in an upward direction. Two cases with renal tuberculosis associated with high-grade kyphosis and one case with staghorn calculi accompanied with lordosis were operated on utilizing this technique. In the former two cases, the thoracic cage was in direct contact with the iliac bone and there was practically no space between the rib border and the iliac crest. This was also true of the third case, but the grade of deformity was not as extensive as in the former two cases. Removal of the 10th, 11th and 12th ribs could be achieved without injuring the pleura and a satisfactorily large operating field could thus be developed which enabled a simple nephrectomy to be performed without difficulty. The characteristic feature of the described approach is that resection of the 10th and 11th ribs is simply to facilitate manoevrability of the wound margin, without going through the rib bed. The technique could be advantageous in selected cases where there is a highly deformed thorax.

Usefulness of Blocksom vesicostomy in elderly men with chronic urinary retention and severe dementia.

AIM: In the present article, we present the usefulness of Blocksom vesicostomy in elderly men with chronic urinary retention. METHODS: We carried out Blocksom vesicostomy in four patients between January 2011 and September 2013. We followed up all patients over 6 months. We checked their general and urinary condition based on interviews with their family members. RESULTS: The etiology of urinary retention included prostate cancer and neurogenic bladder. All of the patients had severe dementia. We successfully managed the urinary treatment of all patients, although their general conditions gradually deteriorated. CONCLUSIONS: In general, this type of vesicostomy is not a popular urinary treatment; however, Blocksom vesicostomy can be useful for treating elderly men with chronic urinary retention and severe dementia.

Suture Granuloma Showing False-Positive Findings on FDG-PET.

We report a case of a 33-year-old male with a mixed germ-cell testicular tumor. Postoperative follow-up FDG-PET revealed concentration of FDG in the left inguinal area which is not tumor metastasis or local recurrence but suture reactivity granuloma. In this paper, we reviewed suture granulomas associated with false-positive findings on FDG-PET after surgery. If FDG-PET will be used more frequently in the future, it will be necessary to refrain from using silk thread in order to prevent any unnecessary surgery.

Prostate cancer topography and patterns of lymph node metastasis.

Pelvic lymph node (LN) metastasis is a well-recognized route of prostate cancer spread. However, the relationship between topography and the pathologic features of primary prostatic cancers and patterns of pelvic LN metastasis has not been well studied. We reviewed original slides of radical prostatectomies and pelvic LN dissections from 125 patients with LN metastasis and recorded a total number of LN excised/laterality of positive LN, and localization, staging parameters, lymphovascular invasion, and volume of primary tumors. LN QUANTITY AND DISTRIBUTION: 14.6 (mean) and 13 (median) LNs were resected. Seventy-six (61%), 33 (26%), and 16 (13%) cases had 1, 2, and >2 positive LNs; whereas 58, 44, and 20 cases had LN metastasis on the right, left, and bilaterally. PATHOLOGIC FEATURES: Eighty-six percent (108 of 125) and 37% (46 of 125) of the cases showed extraprostatic extension and seminal vesicle invasion, whereas 64% cases showed lymphovascular invasion. Mean and median total tumor volumes were 6.39 and 3.92 cm, with ≥50% and ≥90% Gleason patterns 4/5 in 105 (84%) and 73 (58%) cases, respectively. CORRELATION WITH DOMINANT TUMOR LOCATION: Dominant lesions on radical prostatectomy were as follows: 50 right lobe, 44 left lobe, and 31 bilateral lobe tumors. Fifteen of 50 (30%) right lobe and 18 of 44 (41%) left lobe dominant tumors had LN metastasis on the contralateral side. Only 4% (5 of 125) of the cases were associated with anterior dominant tumors. CONCLUSION: Thirty percent to 40% of LN metastases occurred contralateral to the dominant tumor. LN metastasis is overwhelmingly associated with high-grade, high-stage, and large volume disease. LN positivity is rarely associated with anterior dominant tumors.

The effects of neoadjuvant chemotherapy and chemo-radiation therapy on MRI staging in invasive bladder cancer: comparative study based on the pathological examination of whole layer bladder wall.

OBJECTIVE: We evaluated the correlation of radiological findings obtained by MRI study with pathological diagnosis in invasive bladder cancer treated with neoadjuvant chemotherapy, with or without radiation. DESIGN, SETTING, AND PARTICIPANTS: Twenty-seven patients, who underwent total or partial cystectomy for invasive bladder tumors, were enrolled into the present study. Eight cases had received neoadjuvant chemotherapy following the staging biopsy (group A), ten cases had received chemo-radiation therapy following the staging biopsy (group B), and nine cases had received preoperative staging biopsy alone (group C). As a final treatment, 12 of the 27 patients underwent total cystectomy and the other 15 patients underwent partial cystectomy. MRI was conducted prior to total or partial cystectomy in each case. The pathological stage was assessed by histological examination of the entire layer of the bladder wall. RESULTS AND LIMITATIONS: Tumor stage assessed by MRI was consistent with pathological findings in 16 of the 27 cases (59.3%), while MRI produced over-staging in 7 cases and under-staging in 4 cases. The accuracy of staging was 75.0, 30.0, and 77.8% in groups A, B, and C, respectively. The accuracy of MRI staging in group B was lower than that in group C (P < 0.05). There was no difference in the accuracy of MRI staging between groups A and C. CONCLUSION: MRI is useful for the staging of bladder cancer. However, care needs to be taken when staging invasive bladder tumors treated with neoadjuvant chemo-radiation therapy, because inflammatory infiltrations and/or fibrous changes caused by the chemotherapy or chemo-radiation therapy make precise staging with MRI difficult.

Squamous cell carcinoma of the urachus.

A 64-year-old man was admitted with complaints of abdominal pain and pollakisuria. A soft mass was palpable under his navel. Magnetic resonance imaging (MRI) revealed a 9 x 6 cm tumor, which was composed of a cystic lesion arising from the urachus and a solid mass component at the urinary bladder dome. Urine cytology specimens showed squamous cell carcinoma (SCC). Serum SCC level was increased and the tumor was removed surgically. Histological examination detected well-differentiated SCC, which had invaded the urinary bladder and the peritoneum. The patient has been followed up without recurrence for 6 months.

Prostate-specific antigen assay using whole blood samples spotted on filter paper and its application to mass screening for prostate cancer.

AIM: The disc assay system for prostate-specific antigen (PSA) is a novel technique using a small amount of whole blood on filter paper. The accuracy of this assay system and its feasibility for use in prostate cancer mass screening were evaluated. METHODS: In the first arm of the study, to evaluate the accuracy of the disc assay system, PSA values were determined by both a disc assay system and a standard serum assay system using the same blood samples obtained from 420 outpatients. In the second arm of the study, the feasibility and reliability of the disc assay system were examined in prostate cancer mass screening. A total of 2475 men were screened by the disc assay (disc group) and 3348 men were screened by the standard serum assay (serum group) in the first step of mass screening. In the second step of the screening in the disc group, 101 men underwent PSA tests by a standard serum assay, then the first PSA values determined by the disc assay were compared with the second PSA values determined by the standard serum assay. In the second step of the screening in the serum group, 94 men underwent additional PSA tests by a serum assay, and then the first PSA values were compared with the second PSA values. Two men in each group were excluded from analysis because the true PSA values of the first step were not available (more than 50 ng/mL). RESULTS: The PSA values determined by the disc assay closely correlated with those obtained by the standard assay (r = 0.987) in 295 outpatients with PSA levels between 1.0 and 20 ng/mL. In the PSA mass screening, the PSA values determined in the first step closely correlated with those in the second step both in the disc group (r = 0.916) and in the serum group (r = 0.845). A significant dissociation of the two PSA values was observed in seven of 99 men in the disc group and in three of 92 men in the serum group. However, there was no statistical significance in the incidence of dissociation in the two PSA values between the disc group and the serum group. CONCLUSIONS: The disc assay system seems to be a sensitive and accurate assay system. The feasibility and reliability of the disc assay system were well demonstrated in the field during prostate cancer mass screening.

Management of extrinsic malignant ureteral obstruction with urinary diversion.

OBJECTIVE: The effectiveness of urinary diversion for patients with renal insufficiency due to extrinsic ureteral obstruction was assessed. METHODS: Between 1990 and 2003, 30 males and 45 females, ranging 36-90 years of age (average, 62.7) who had secondary ureteral obstruction due to either a retroperitoneal or pelvic invasion of malignant disease, underwent nephrostomy or ureteral stenting using a double-J stent without side holes. RESULTS: Ureteral stenting was attempted as an initial procedure in 51 of the 75 cases. The remaining 24 cases had a nephrostomy at the first step. Of 51, 37 cases were successfully stented, while internal stenting was unsuccessful in the remaining 14 cases. These 14 cases were treated with nephrostomy at the second step following the unsuccessful internal stenting. Eight cases of the 37 successfully stented cases were eventually changed to a nephrostomy because of catheter trouble. As a result, 29 cases could be managed by internal ureteral stenting up until the end of their life. The follow-up period for the 75 cases who underwent urinary diversion ranged from 5 days to 19 months, averaging 5.7 months. The average period from diversion to death was 5.6 months in the internally stented group and 5.9 months in the nephrostomy group. CONCLUSION: The high patency rate of the internal ureteral stent in our cases might be due to our use of a stent without shaft vent holes.

Experimental study of renal disorder caused by oxaliplatin in rat renal cortical slices.

BACKGROUND: Oxaliplatin is a newly developed antitumor platinum complex that is known to have low nephrotoxicity. The inhibitory effects of oxaliplatin on several tubular functions were compared with those of cisplatin and carboplatin, using a renal cortical slice system. METHODS AND RESULTS: Rat renal cortical slices were incubated with 0.25 mM to 2.0 mM of oxaliplatin, cisplatin, on carboplatin at 37 degrees C for 120 min. Para-amino hippuric acid (PAH) accumulation, gluconeogenesis, and ATP content in the rat renal slices were determined. PAH accumulation was not inhibited by carboplatin, but it was significantly inhibited by oxaliplatin and cisplatin. Inhibition of PAH accumulation by cisplatin was greater than that by oxaliplatin. Gluconeogenesis was not decreased by carboplatin, but it was suppressed by oxaliplatin and cisplatin in a dose-dependent manner. The decrease in gluconeogenesis induced by oxaliplatin was significantly greater than that induced by cisplatin. ATP content in the renal slices was decreased by oxaliplatin, cisplatin, and carboplatin to almost the same extent. As an in vivo experiment, 21.6 mmole/kg of oxaliplatin, cisplatin, or carboplatin was injected into rats; then blood urea nitrogen (BUN) and serum creatinine were determined on day 4. Significantly elevated levels of BUN and serum creatinine were observed only in the rats injected with cisplatin. CONCLUSIONS: Oxaliplatin did not cause nephrotoxicity in the in vivo study; however, the nephrotoxic pattern of oxaliplatin observed in the renal cortical-slice system resembled that of cisplatin. The reason why oxaliplatin is less nephrotoxic than cisplatin in vivo could not be fully elucidated in the present experiment using the renal cortical-slice system.

Annual PSA tests are not necessary for men with a PSA level below 2 ng/mL: findings of the Imari prostate cancer screening program.

BACKGROUND: Annual changes in prostate specific antigen (PSA) levels detected by the Imari prostate cancer screening program were evaluated to establish a more efficient and cost-saving screening system, especially for men with low PSA levels. METHODS: Prostate specific antigen-based annual mass screenings for prostate cancer were conducted for men aged 60-69 in the Imari district, Saga, Japan. Between 1992 and 2000, 1822 men had their PSA levels tested. A total of 4661 PSA tests were conducted. Changes in PSA levels over the following 1 to 5 years were analyzed in men with PSA levels of 3 ng/mL or less, a range in which the detection rate of prostate cancer would seem to be negligibly low. RESULTS: The overall detection rate of prostate cancer between 1992 and 2000 was 0.73%. The detection rate in men with a PSA level between 3.1 and 3.9 ng/mL, and between 4 and 9.9 ng/mL was 1.6% and 8.3%, respectively. Of 4661 determinations of PSA, 2553 (54.8%) were found to be < or = 1 ng/mL, 1273 (27.3%) were between 1.1 and 2 ng/mL, and 401 (8.6%) were between 2.1 and 3 ng/mL. Four hundred and thirty-four men (9.3%) had PSA levels > or = 3.1 ng/mL, with possible indications for prostate biopsy. Of the men tested, 1.4% with an initial PSA level of < or = 2 ng/mL and 22.3% with an initial level between 2.1 and 3 ng/mL had a PSA level of > or = 3.1 ng/mL after 1 year. Almost the same rate of PSA increase was observed between the two PSA tests conducted at 2 to 5-year intervals. Of the men tested, 2.2% with an initial PSA level of < or = 2 ng/mL, and 21.9% with an initial level between 2.1 and 3 ng/mL, had a level of > or = 3.1 ng/mL after 5 years. CONCLUSION: Levels of PSA in men with an initial level below 2 ng/mL remained stable for up to 5 years. Levels of PSA in 97.8- 98.8% of men remained below 3 ng/mL after 1 to 5 years. In contrast, 18-35.3% of men with an initial PSA level between 2.1 and 3 ng/mL showed PSA progression to 3.1 ng/mL or more within 5 years. Our present data suggest that annual PSA testing is not necessary for men with a PSA level below 2 ng/mL. Prostate specific antigen testing could therefore be conducted at longer intervals in such individuals.