Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

Comparison of clinical outcomes of osimertinib and first-generation EGFR-tyrosine kinase inhibitors (TKIs) in TKI-untreated EGFR-mutated non-small-cell lung cancer with leptomeningeal metastases.

BACKGROUND: Leptomeningeal metastases (LM) are devastating complications of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). Although osimertinib, a third-generation EGFR-tyrosine kinase inhibitor (TKI), has better penetration into the central nervous system than first-generation EGFR-TKIs, data on the distinct activity of EGFR-TKIs in untreated advanced EGFR-mutated NSCLC with LM are lacking. PATIENTS AND METHODS: We retrospectively reviewed patients treated with EGFR-TKIs for TKI-untreated common EGFR-mutated NSCLC with LM between July 2002 and July 2021 at the National Cancer Center Hospital. The patients were divided into two groups: patients treated with osimertinib (Osi group) and those treated with gefitinib or erlotinib [first-generation (1G)-TKI group]. RESULTS: Of the 967 patients, 71 were eligible, including 29 in the Osi group and 42 in the 1G-TKI group. The median progression-free survival (PFS) and overall survival (OS) in the Osi group were better than those in the 1G-TKI group (PFS: 16.9 months versus 8.6 months, P = 0.007, and OS: 26.6 months versus 20.0 months, P = 0.158). The LM-overall response rate (ORR) and LM-PFS were significantly better in the Osi group than in the 1G-TKI group (LM-ORR: 62.5% versus 25.7%, P = 0.007; LM-PFS: 23.4 months versus 12.1 months, P = 0.021). In the subgroup analysis of EGFR mutation status, LM-PFS for patients with exon 19 deletion was significantly longer in the Osi group than in the 1G-TKI group (32.7 months versus 13.4 months, P = 0.013), whereas those with L858R mutation in exon 21 did not differ between the two groups. In the multivariate analysis, osimertinib and exon 19 deletion were significant factors for better LM-PFS and OS. CONCLUSION: Osimertinib can be more effective for untreated common EGFR-mutated NSCLC patients with LM, especially those with exon 19 deletion, compared to first-generation TKIs.

Simultaneous immunostaining with anti-S100P and anti-SV40 antibodies revealed the origin of BK virus-infected decoy cells in voided urine samples.

BACKGROUND: Methods for determining the origin of BK virus (BKV)-infected cells (decoy cells) in clinical urine samples have not been established although they could enhance the diagnosis of BKV infection in immunocompromised patients. METHODS: We performed simultaneous immunostaining with anti-S100P (a urothelial marker) and anti-SV40 antibodies in 66 clinical urine samples exhibiting SV40 positivity and a decoy-cell appearance on Papanicolaou staining. The clinical voided urine samples included seven cases of renal transplantation, 47 cases of cancer therapy and 12 cases of non-neoplastic disease. SurePath(™) liquid-based cytology was used for the urine samples. RESULTS: BKV-infected cells were categorized as SV40(+)/S100P(+) and SV40 (+)/S100p(-). SV40(+)/S100P(-) cells were found in 55 cases (83.4%); nine cases (13.6%) carried both SV40(+)/S100P(-) and SV40(+)/S100P(+) cells. The former were identified as BKV infection in renal tubules and the latter in both the renal tubules and urothelial epithelia. The remaining two cases (3.0%) had only SV40(+)/S100P(+) cells of urothelial origin. CONCLUSION: Simultaneous immunostaining with anti-S100P and anti-SV40 is a useful method for determining the origin of BKV-infected cells in clinical urine samples from immunocompromised patients such as renal transplantation recipients.

Role of lymph node dissection in the treatment of urothelial carcinoma of the upper urinary tract: multi-institutional relapse analysis and immunohistochemical re-evaluation of negative lymph nodes.

AIM: To determine the role of lymph node dissection (LND) in the treatment of urothelial carcinoma (UC) of the upper urinary tract (UUT). PATIENTS AND METHODS: [Study-1] A retrospective multi-institutional study evaluated 293 patients undergoing predominantly nephroureterectomy for UC of the UUT. Of 293 patients, 267 patients had pure UC and 26 demonstrated other histological components. Regarding the pathological node status, 130 patients had pN0 disease, 141 patients had pNx disease and 22 patients had pN+ disease. The sites of initial recurrence and time to first recurrence were reviewed. The sites of recurrence were classified as locoregional or distant recurrence. The relationship between node status and future recurrence was analyzed. [Study-2] Fifty-one patients treated by nephroureterectomy at Hokkaido University Hospital were included. All had LND and all LNs were negative on hematoxylin and eosin staining. We re-evaluated the presence of micrometastasis in LND specimens by anti-cytokeratin immunohistochemistory. RESULTS: [Study-1] Of 293 patients, 76 developed disease relapse. Regional lymph node recurrence was the most common site (34 patients). On multivariate analyses that adjusted for the effect of tumor stage and tumor grade, pNx (skipping LND) was an adverse factor not only for locoregional recurrence, but also for distant relapse. [Study-2] Immunohistochemistry identified micrometastases in 7 (14%) of 51 patients. Regarding survival, 5 of these 7 patients with micrometastases were alive at last follow-up. CONCLUSIONS: On relapse analysis, skipping LND was an adverse factor not only for locoregional recurrence, but also for distant relapse. Immunohistochemistry detected micrometastases in about 14% of patients previously diagnosed as pN0. These findings further support a potential therapeutic benefit of LND by eliminating micrometastases.

The relationship between technical parameters of external beam radiation therapy and complications for localized prostate cancer.

BACKGROUND: This study was performed to review retrospectively the clinical course of chronic rectal bleeding as a complication of external beam radiation therapy for localized prostate cancer and to analyze the relationship between technical parameters of radiation therapy and the complications. METHODS: Seventy-one patients with stages A2, B and C were treated with local-field radiotherapy (total dose 52.5-66 Gy, daily dose 2.0-3.28 Gy, field area 30-81 cm2, number of fields 3-15 ports, planning simulations X-ray or CT-based) between 1989 and 1998 at three institutions. The protocols were consistent during this same period at these institutions. RESULTS: Multivariate analysis revealed pretreatment PSA and Gleason sum to be statistically significant predictors of 5 year prostatic specific antigen (PSA) relapse-free rates in a median follow-up period of 42 months (range 12-119 months). The significant risk factors for higher grading of acute morbidity were a biological equivalent dose, alpha/beta = 10(BED10) > or =65 Gy, dose per fraction > or =3.0 Gy, field area > or =42 cm2, fewer ports and X-ray planning simulation. However, no parameter was associated with higher grading of late morbidity. Eleven patients (15.4%) experienced a late GI complication: grade 1 (4.2%), grade 2 (9.8%), grade 3 (1.4%). The median time to occurrence of rectal bleeding was 12 months after radiotherapy and the mean duration of morbidity was 11 months. CONCLUSIONS: Higher total dose and dose per fraction, larger field area, fewer ports and X-ray simulation increased the grades of acute morbidity. A majority of chronic rectal bleedings were transient and responded to conservative treatment.

The preoperative predictability of the short esophagus in patients with stricture or paraesophageal hernia.

BACKGROUND: Esophageal shortening is a known complication of advanced gastroesophageal reflux disease that may preclude a tension-free antireflux procedure. A retrospective analysis was performed to test the accuracy of preoperative testing. METHODS: From September 1993 to December 1998, 39 patients underwent esophageal mobilization with intraoperative length assessment. Patients were selected on the basis of irreducible hiatal hernia, stricture formation, or both. Patients in the upright position with a fixed hiatal hernia larger than 5 cm on an esophagram were considered to have a short esophagus. Manometric length two standard deviations below the mean for height was considered abnormally short. RESULTS: In 31 patients, intraoperative mobilization was sufficient to allow the gastroesophageal junction to lie 2 cm below the diaphragmatic crus, so no esophageal-lengthening procedure was required. Eight patients with a short esophagus required an esophageal-lengthening procedure after complete mobilization. Two patients subsequently underwent intrathoracic migration of the gastroesophageal junction (GEJ), with recurrence of symptoms and required gastroplasty during the second surgery. An esophagram had a sensitivity of 66% and a positive predictive value of 37%, whereas manometric length had a sensitivity of 43% and a positive predictive value of 25% for the diagnosis of short esophagus. The preoperative endoscopic finding of either a stricture or Barrett's esophagus was the most sensitive test for predicting the need for a lengthening procedure. CONCLUSIONS: Manometry and esophagraphy are not reliable predictors of the short esophagus. Additional tests and/or tests combined with other parameters are needed.

Acute renal failure occurring from urinary retention due to a müllerian duct cyst.

A patient with a müllerian duct cyst, which caused acute renal failure secondary to urinary retention, is reported. The case was treated successfully by transurethral unroofing of the cyst.

[The natural history of renal angiomyolipoma].

PURPOSE: To make the policy of treatment with angiomyolipomas (AML) more clear, we discussed the natural history of angiomyolipomas retrospectively. PATIENTS AND METHODS: Between May 1982 and December 1997, 14 patients with AML in 18 kidneys were followed, who were 2 men in 2 kidneys and 12 women in 16 kidneys, 27 to 80 years old. No patients suffered from tuberous sclerosis. Symptoms, initial sizes and changes of the size were evaluated for these patients. RESULTS: Ten patients with AML in 14 kidneys were asymptomatic and four patients were symptomatic. But one of the 4 patients had symptoms of abdominal pain and palpable mass which were due to contralateral AML that were treated with nephrectomy, so symptoms due to small AML were seen in 3 cases (2.0 cm, 3.5 cm, 3.8 cm). Among 11 patients in 15 kidneys followed radiologically for more than 6 months, the tumors were unchanged in size in 7 kidneys, which were in all of 6 cases with unilateral solitary tumor and in 1 with bilateral multiple tumors. In other 8 kidneys the sizes of the tumors were increased, which were in the cases with multiple tumors in one kidney or in bilateral cases. Compared to the cases of unilateral solitary AML, the size of AML with multiple tumors in one kidney or in bilateral kidneys significantly increased (p < 0.01). Embolization were performed for 4 kidneys, which were in 2 cases with increased tumor in size to more than 4 cm in following period, in 1 with dull flank pain, and in 1 with the tumor more than 4 cm at diagnosis that grew to more than 5 cm. CONCLUSIONS: Unilateral solitary AML was appeared to be hard to increase in size and to have a different natural history from bilateral or multiple tumors.

Persistent vesicourethral dysfunction following radical surgery for rectal carcinoma: urodynamic features and potential abatement with modified sphincterotomy (radical transurethral resection of the prostate).

BACKGROUND: Vesicourethral function returns after radical rectal surgery during the first year but rarely progresses after 1 year. We examined the urodynamics of patients whose voiding dysfunction remained after 1 year, and treated several with a modified sphincterotomy procedure similar to radical transurethral resection of the prostate. METHODS: We analyzed the urodynamic features of vesicourethral dysfunction in 16 male patients with persistent voiding dysfunction for more than 1 year following radical surgery for rectal carcinoma. Seven patients elected to undergo radical transurethral resection of prostate (radical TUR-P) for the relief of their persistent voiding dysfunction. RESULTS: The mean bladder volume at the first desire to void was 210 mL, the mean maximal bladder capacity was 343 mL, and the mean vesical compliance (Cves) was 27.1 mL/cm H2O. All patients demonstrated either vesical denervation supersensitivity (Vds) or uninhibited contraction. The mean maximal urethral closure pressure was 43.9 cm H2O, and urethral denervation supersensitivity was found in 77.8% (7/9), and sphincter dyssynergia in 66.7% (6/9) of patients. After radical TUR-P, 5 patients became free from the use of self-catheterization, 1 patient had a reduced residual urine rate, and 1 patient was unchanged, but no patient noted a change in urinary control. CONCLUSION: Urethral dysfunction after radical rectal surgery was caused by failure of the bladder to empty along with an underactive detrusor. Radical TUR-P was effective in restoring voiding function in a selected group of these patients.

Feasibility of urodynamic study (combined cystometry and electromyography of the external urethral sphincter) under general anesthesia in children.

BACKGROUND: To assess the feasibility of urodynamic study under general anesthesia (GA) we performed electromyography of the external urethral sphincter (EUS-EMG) on 73 children and cystometry (CM) alone on 10 children. METHODS: Subjects were divided into 3 groups. Those in groups I and II were suspected of having voiding dysfunction with (group I) or without (group II) overt neurospinal defects, while those in group III were thought to be functionally normal. EUS-EMG was performed under light anesthesia following cystourethroscopy to examine structural abnormalities. Atropine sulfate premedication was not used for the anesthetic procedure; muscle relaxants were used only for tracheal intubation. RESULTS: Voiding was observed in 83% of the patients. Among patients who voided, detrusor-external sphincter dyssynergia (DSD) was noted in 7 (38%) group I patients and 6 (19%) group II patients; in group III, voiding was synergic in all patients. In 10 cases, CM alone was carried out both under anesthesia and in the waking state; anesthesia suppressed detrusor hyperreflexia (DH) in all 9 patients but produced no change in bladder compliance. CONCLUSIONS: In children with urinary disorders, urodynamic study under GA following cystourethroscopy is a feasible method for assessing EUS function and documenting DSD; DH is not evaluable, however. Stratifying urinary management on the basis of these examinations resulted in satisfactory clinical outcomes.

[Effective administration of recombinant granulocyte colony-stimulating factor to prevent granulocytopenia due to combination chemotherapy for testicular germ cell tumors].

A prospective randomized study on the administration of recombinant granulocyte colony stimulating factor (rG-CSF) was conducted on 15 patients with testicular germ cell tumors. The clinical stagings of all patients except one were minimal to moderate extent according to the Indiana University staging system. Combination chemotherapy using bleomycin, etoposide and cisplatinum (BEP) was performed as the initial treatment on the eligible patients. rG-CSF was administered by two different methods; 1) routine administration on the 6th day after BEP chemotherapy (group A), and 2) the same method, but after granulocytopenia of 1,500/mm3 had developed (group B). The administration of rG-CSF in group A significantly reduced the severity of leucocytopenia and also the incidence of stomatitis compared with group B. Although rG-CSF produced no significant side effects, the thrombocytopenia was prominent in the group A patients (not significant). BEP chemotherapy itself is an easily-tolerable and well established method for treating young adult patients. The method used in group B seems to be suitable in situations where thrombocytopenia and cost effectiveness.

Continence mechanism of the orthotopic neobladder: urodynamic analysis of ileocolic neobladder and external urethral sphincter functions.

BACKGROUND: The main objectives of bladder substitution are the preservation of the upper urinary tract and maintenance of urinary continence. Orthotopic bladder substitution makes it possible to achieve urinary continence as well as normal passage of urine through the urethra. Creation of a low pressure reservoir and careful preservation of the distal sphincter mechanism are considered to be of utmost importance for the maintenance of urinary continence after orthotopic bladder substitution. However, sphincter behavior after orthotopic bladder substitution has not been fully elucidated. The purpose of this study was to evaluate the vesicourethral continence mechanism after orthotopic bladder substitution in male patients. METHODS: Urodynamic evaluation was performed in 14 male patients after cystoprostatectomy for bladder cancer and an ileocolic neobladder using a cecourethral anastomosis. RESULTS: Good continence was achieved in 86% (12/14) of the patients during the day and in 79% (11/14) at night. On cystometry, maximum capacity of the neobladders was 434 +/- 21 ml (mean +/- SEM), and basal pressure at maximum capacity was 15.6 +/- 0.9 cm water. Phasic neobladder contraction with amplitudes ranging from 14 to 40 (26.6 +/- 2.7) cm water were noted in 11 of 14 patients. Sphincter electromyography demonstrated an increase in the frequency of action potentials of the external urethral sphincter during neobladder filling from empty to 80% of capacity (from 8.9 +/- 1.6 to 14.6 +/- 2.1 spikes per second; mean percentage increase, 64%, in patients with daytime continence). Maximum urethral closure pressure on urethral pressure profile was 49.9 +/- 3.5 (range, 30 to 64) cm water in patients with daytime continence, while in two patients who were incontinent during the day and at night maximum urethral closure pressure was lower (16 and 24 cm water) and the recruitment of action potentials of the external urethral sphincter during neobladder filling was impaired (percentage increase, 15% and 20%). CONCLUSIONS: An ileocolic neobladder has characteristics of a low pressure reservoir with a satisfactory continence rate. The vesicourethral continence reflex is well preserved in patients with continence after orthotopic bladder substitution.

[Endourology update].

In urology, endoscopic surgery and laparoscopic surgery are generally named as endourology. Transurethral endoscopic surgery was originated in mid 19th century, and established by 1950s. At present, transurethral resection of the prostate, transurethral resection of the bladder tumor, transurethral incision of the urethral stricture, transurethral vesicolithotripsy, and transurethral ureterolithotripsy, were commonly performed in many urological clinics. Percutaneous nephrolithotripsy and extracorporeal shock wave lithotripsy were introduced in 1980s, and now, open operation for urolithiasis are rarely performed. In 1990s, as a new endourologic procedure, laparoscopic operations are being increasingly applied to the treatment of urological diseases; for example, laparoscopic pelvic lymphadenectomy, laparoscopic varicocelectomy, laparoscopic exploration of non-palpable testis, laparoscopic nephrectomy, and laparoscopic adrenalectomy etc. Of the variety of treatment modalities available, the most effective and least invasive method should be selected appropriately. So, we anticipate the further advancement in minimally invasive therapy, interdependently with our sufficient experience and skills.

Fascial sling for the management of urinary incontinence due to sphincter incompetence.

The surgical management of urinary incontinence due to sphincter incompetence is still a challenging issue for urologists to date. We reviewed our experience with the fascial sling performed in 10 male and 3 female patients 3 to 72 years old (median age 13 years) with sphincter incompetence, including 11 with a neurogenic bladder (8 with myelodysplasia, 2 after pelvic operation and 1 after spinal cord injury), 1 after transurethral resection of the prostate and 1 after surgical injury to the bladder neck. Patient selection for a sling procedure was based on cystography (an open bladder neck) and urodynamic findings (underactive external urethral sphincter on electromyography and low maximum urethral closure pressure). A free graft of fascia was harvested from the rectus fascia in 8 patients and from the fascia lata in 5, and the fascial sling was placed around the bladder neck in 11 and the bulbous urethra in 2. Augmentation cystoplasty was performed concomitantly in 9 patients with poor bladder compliance (8 ileocystoplasty and 1 gastrocystoplasty). Postoperative followup ranged from 4 to 63 months (mean 36). Nine patients became continent and 3 improved significantly but remain damp. Of these 12 patients 10 with a neurogenic bladder were placed on intermittent catheterization, while the 2 without a neurogenic bladder are able to void normally. The remaining patient with surgical failure due to inadvertent wound infection received an indwelling urethral catheter. In all but this patient preoperative and postoperative maximum urethral closure pressures were 34.3 +/- 5.7 and 37.2 +/- 3.8 cm. water, respectively, without a significant increase. However, postoperative simultaneous measurements of intravesical and intraurethral pressure demonstrated a dramatic increase in intraurethral pressure during coughing or straining because of the action of the sling. Postoperative upper urinary tract deterioration has not been documented to date. Although various surgical options have been available, the fascial sling seems to be promising in the management of refractory urinary incontinence due to sphincter incompetence.

Preoperative cystometrography in patients with clinical benign prostatic hypertrophy.

Preoperative water cystometrograms obtained from 437 patients with benign prostatic hyperplasia (BPH) were examined in a retrospective study. The cystometrographic results were analyzed regarding the preoperative clinical features: the patients' age, presence or absence of urinary incontinence, history of urinary retention, and rate of residual urine. Their prognostic value in terms of improvement in voiding difficulty and postoperative urinary incontinence was also analyzed at 1 and 6 months after elective transurethral resection of the prostate (TURP). Of these patients, 263 (60.2%) had detrusor instability (group I), whereas 174 did not (group II). Vesical denervation supersensitivity (Vds) to bethanecol chloride was noted in 47 (12.5%) of 375 patients. The observed difference in clinical features was significant between the two groups, with group I being older (P < 0.01) and showing a greater incidence of urinary incontinence (P < 0.001) and retention (P < 0.001). The difference seen between groups I and II in terms of mean bladder capacity (P < 0.01), compliance (P < 0.01), and a greater positive rate of Vds (P < 0.001) was also significant. The clinical and cystometrographic parameters studied worsened with advancing age of the patients. Although the majority of the patients (94.7%) were relieved of obstructive symptoms after TURP (6 months later), 113 (25.9%) showed no relief at 1 month.(ABSTRACT TRUNCATED AT 250 WORDS)

[Laparoscopic pelvic lymphadenectomy--experimental operation using young pigs and clinical experience in 21 cases with prostate and bladder cancer].

In order to gain the technical skills for performing laparoscopic pelvic lymphadenectomy, we selected the young pigs (12-15 kg) as the experimental model. Five pigs (male 2, female 3) underwent laparoscopic pelvic lymphadenectomy under intravenous anesthesia. Postoperatively, the pigs were euthanized, and laparatomy was performed to demonstrate the area of dissection. Operation time was from 50 to 80 minutes, and no complication occurred in all cases, mastery came rapidly. Following experimental operation, 21 cases with prostate and/or bladder cancer underwent laparoscopic pelvic lymphadenectomy for staging operation from Nov. 1991 to Oct. 1993. Operation time was from 60 to 310 minutes (mean 137). In one of 21 cases, lymph node metastasis was proved. Eighteen of 21 cases underwent radical prostatectomy or cystectomy between 6 to 24 days after laparoscopic pelvic lymphadenectomy. On radical operation, the adhesion of the post-lymphadenectomy was severe in the patients 8 days after laparoscopic pelvic lymphadenectomy, compared with those within 7 days. Radical operation was seemed to be recommended within 7 days after laparoscopic pelvic lymphadenectomy.

Preexisting neurogenic voiding dysfunction in children with imperforate anus: problems in management.

We evaluated 22 boys and 2 girls 1 month to 8 years old with imperforate anus to determine the relationship between neurogenic voiding dysfunction and bony sacral or spinal cord anomalies. Lower urinary tract function before anorectoplasty was normal in 12 children (group 1), abnormal (detrusor-sphincter dyssynergia) in 9 (group 2) and not evaluated in 3 (group 3). High lesions of imperforate anus were present in 22% of the patients in group 1 and in 100% of those in group 2. Plain radiography revealed partial sacral agenesis in 1 child in group 1 and 4 in group 2. Magnetic resonance imaging detected occult spinal dysraphism in 1 patient in group 1 and 2 in group 2. (Occult spinal dysraphism included sacral lipoma, tethered cord, syringomyelia and thick filum terminale.) Seven children in group 2 had vesicoureteral reflux before anorectoplasty. All children in group 2 were placed on clean intermittent catheterization for the management of neurogenic voiding dysfunction. Normal upper urinary tract function was maintained in all patients in group 1 and 6 in group 2. The remaining 3 children in group 2 had high grade reflux at presentation associated with severe renal damage or noncompliance with clean intermittent catheterization. These findings indicate that in children with imperforate anus lower urinary tract function should be evaluated before anorectoplasty because of the high incidence of associated congenital neurogenic voiding dysfunction and the potential risk for renal deterioration. When possible, neurogenic voiding dysfunction should be managed with clean intermittent catheterization to prevent renal damage.

Relevance of detrusor hyperreflexia, vesical compliance and urethral pressure to the occurrence of vesicoureteral reflux in myelodysplastic patients.

Bladder pressure in the storage phase is considered to be relevant to the changes in the upper urinary tract. We analyzed retrospectively detrusor hyperreflexia, vesical compliance and maximum urethral closing pressure to determine which is the most significant factor relevant to the incidence of vesicoureteral reflux in 91 myelodysplastic patients. Vesicoureteral reflux was demonstrated in 29 of 91 patients. Cystometry and urethral pressure profilometry were performed in 69 and 27 patients, respectively. Vesicoureteral reflux was observed in 43% of the female patients, which was significantly greater than in the male patients (20%). Detrusor hyperreflexia was noted in 43 patients. Average vesical compliance was 11.3 +/- 8.3 ml./cm. water in 58 evaluable patients. Maximum urethral closing pressure was 56.7 +/- 25.8 cm. water. Vesical compliance in the patients with vesicoureteral reflux was 10.2 +/- 7.5, which was not significantly lower than in those without vesicoureteral reflux (12.2 +/- 8.8). The incidences of vesicoureteral reflux were 38% in the patients with vesical compliance of less than 10, 40% in those with vesical compliance of greater than 10 but less than 20 and 36% in those with vesical compliance of more than 20. The differences were not significant among these patients. Urethral pressure in the patients with vesicoureteral reflux was significantly higher than in those without vesicoureteral reflux (73.8 +/- 23.5 versus 48.2 +/- 23.0, p less than 0.05). The incidence of vesicoureteral reflux was 53% in the patients with urethral pressure of greater than 50, while it was only 8%, significantly less (p less than 0.05), in the lower urethral pressure group. Vesicoureteral reflux was noted in 44% of the patients with detrusor hyperreflexia, which was not significantly greater compared to 31% in the patients without detrusor hyperreflexia. These results suggest that in myelodysplastic patients maximum urethral closing pressure is highly relevant to the incidence of vesicoureteral reflux, while vesical compliance and detrusor hyperreflexia are not. The incidence of vesicoureteral reflux was significantly greater in female patients (43%, p less than 0.05) than in male patients (20%), although urethral pressure values showed no difference between them, indicating that female patients may be another risk factor for vesicoureteral reflux.

[Long-term follow up of transurethral resection of the prostate--a review of 137 patients].

For assessing the long-term outcome of patients after transurethral prostatic resection (TUR-P), telephone interview in terms of the urinary symptom and the sexual function was conducted on 191 cases who underwent TUR-P in Hokkaido University Hospital from 1982 to 1988. Adequate replies were obtained from 137 patients (71.7%), whose mean age was 70.2 years old and mean follow up period was 4.8 years. Subjective urinary symptoms, which are mainly classified as dysuria, frequency and incontinence, were improved in 114/120 (95.0%), 99/108 (91.7%), and 20/21 (95.2%) respectively. Overall symptom-free rates of dysuria, frequency, and incontinence were 85.1% (114/134), 86.6% (116/134), and 90.3% (121/134). Morbidity of incontinence following TUR-P was only 6/134 (4.5%). There was one deaths (0.7%) at 2 weeks after TUR-P, but was not attributable to the operative procedure itself. Although 82 cases (59.9%) had risk factors such as the cardiovascular disease, malignancy or other systemic disorders, they did not jeopardize the postoperative course nor were attributed to the mortality. Uninhibited contraction and/or vesical denervation supersensitivity on perioperative cystometrogram were found in 53/84 (63%). These urodynamic abnormalities were not considered to be postoperative urinary symptoms. Postoperatively, the decrease in libido was noted in 12/63 (19%), but its causal relation to the procedure was obscure in most of the patients. We believe TUR-P can offer a satisfactory outcome in the majority of the patients with minimum risk.

[Early experience with an ileocolic bladder substitution (Mainz pouch) in 11 cases].

In the last decade, many continent urinary diversions have been developed for the cystectomy patients. Mainz pouch, which seems to be a sophisticated one without using an alloplastic prosthesis, was adopted in our clinic. We preliminarily report our result in 11 patients who underwent a Mainz pouch procedure in the last 2 years: 1 for bladder augmentation, 5 for total bladder substitution after cystoprostatectomy and 5 (including 2 females) for continent urinary diversion. The mean age of them was 54 years old and the follow up periods ranged from 6 to 24 months. The antimesenteric longitudinal incision of the ileum and cecum and their sutures were performed similarly to the usual detubularized intestinal pouch. The ureteral reimplantation to the colonic segment was accomplished by the submucosal tunnel method. Although the ureteral hiatus was initially positioned at the anal edge of the colon, a new hiatal creation by stabbing the more oral portion of the colon according to the Goodwin's ureterocolic anastomosis was subsequently employed to avoid the trouble of closure of this portion. When the urethral anastomosis was achieved by 4-5 interrupted sutures between the most dependent portion of the cecum and the urethral stump after cystoprostatectomy, the mucosa was everted to the colonic serosa to prevent the stricture. The continent stoma was created by an intussusception of the proximal ileum, which was stabilized by the seromuscular stripping and 2-3 rows of external metal staples. Complication of the alimentary system occurred in 6 of 11 cases (55%), though they were successfully treated by an appropriate conservative management except one who suffered an ileostomy and nephrostomy because of severe panperitonitis.(ABSTRACT TRUNCATED AT 250 WORDS)