Establishment of Patient-Derived Pancreatic Cancer Organoids from Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsies

Background/Aims@#Three-dimensional cultures of human pancreatic cancer tissue also known as “organoids” have largely been developed from surgical specimens. Given that most patients present with locally advanced and/or metastatic disease, such organoids are not representative of the majority of patients. Therefore, we used endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to collect pancreatic cancer tissues from patients with advanced pancreatic cancer to create organoids, and evaluated their utility in pancreatic cancer research. @*Methods@#Single-pass EUS-FNA samplings were employed to obtain the tissue for organoid generation. After establishment of the organoid, we compared the core biopsy tissues with organoids using hematoxylin and eosin staining, and performed whole exome sequencing (WES) to detect mutational variants. Furthermore, we compared patient outcome with the organoid drug response to determine the potential utility of the clinical application of such organoid-based assays. @*Results@#Organoids were successfully generated in 14 of 20 tumors (70%) and were able to be passaged greater than 5 times in 12 of 20 tumors (60%). Among them, we selected eight pairs of organoid and core biopsy tissues for detailed analyses. They showed similar patterns in hematoxylin and eosin staining. WES revealed mutations in KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 which were 93% homologous, and the mean nonreference discordance rate was 5.47%. We observed moderate drug response correlations between the organoids and clinical outcomes in patients who underwent FOLFIRINOX chemotherapy. @*Conclusions@#The established organoids from EUS-FNA core biopsies can be used for a suitable model system for pancreatic cancer research

Novel Drug Screening Platform: Tumor Organoid / 대한췌담도학회지

Pancreatic ductal adenocarcinoma (PDAC) is known to be one of the most lethal cancers among all cancer types, with a relative 5-year survival rate of less than 8%. Currently, surgery is the only probable curative treatment for PDAC which is available for only 10-15% of the patients diagnosed with the cancer. Organoids resemble the original tissue in morphology and function with self-organizing capacity. Organoids can be cultured with high effectiveness from individual patient derived tumor tissue which makes them an extremely fitting model for translational uses and the improvement of personalized cancer medicine. Before personalized medicine based on organoids can be applied in the clinic, the improvement of drug screening platforms in terms of sensitivity and robustness is necessary.

Effect of Shifting from Combination Therapy to Monotherapy of alpha-Blockers or 5alpha-Reductase Inhibitors on Prostate Volume and Symptoms in Patients with Benign Prostatic Hyperplasia

PURPOSE: Combination therapy of alpha-blockers and 5alpha-reductase inhibitors (5-ARIs) is widely used for the treatment of benign prostatic hyperplasia (BPH). We aimed to study the effect on prostate volume and symptoms of shifting to monotherapy in patients who previously received a combination therapy. MATERIALS AND METHODS: A prospective study was conducted of 60 patients who were diagnosed with BPH. Patients were aged 45 years or older and had a prostate volume of 30 cc or more, International Prostate Symptom Score (IPSS) of 12 or above, maximal flow rate (Qmax) of 15 ml/s or less, and prostate-specific antigen (PSA) level of less than 10 ng/ml. The patients initially received a combination therapy of doxazosin 4 mg/day and finasteride 5 mg/day for 3 months and were then randomly assigned to receive monotherapy for 3 months. The factors were then compared. RESULTS: A total of 30 patients were assigned to doxazosin (group 1) and 30 to finasteride (group 2) after the combination therapy. The percentage changes in prostate volume, IPSS, and Qmax during the period from post-combination therapy to post-monotherapy were not significantly different between the two groups (p=0.052, 0.908, 0.081), whereas PSA significantly decreased in group 2 (p<0.001). IPSS was not significantly different at post-combination therapy and at post-monotherapy in both groups (p=0.858, 0.071). The prostate volume significantly increased from 40.97 cc at post-combination therapy to 44.29 cc at post-monotherapy in group 1 (p=0.001) and insignificantly increased from 38.32 cc to 38.61 cc in group 2 (p=0.696). CONCLUSIONS: Although the duration of drug administration was short in this study, 5-ARI monotherapy could maintain the alleviated symptoms and reduce the risk of acute urinary retention and surgery due to prostate regrowth in BPH patients whose symptoms improved with combination therapy.

Vesicosigmoidal Fistula Caused by Diverticulitis / 대한비뇨기과학회지

Enterovesical fistula is a relatively uncommon complication involving colorectal and pelvic malignancies, intestinal diverticulitis, inflammatory bowel disease, radiotherapy and trauma in Asian countries. A 77-year-old male was referred with complaints of difficult urination, frequency, nocturia and abdominal discomfort. On admission, fever and fecaluria were present. Various diagnostic procedures such as excretory urography, cystography, cystoscopy, rectoscopy and pelvic computed tomography (CT) scan were performed. Under the impression of vesicosigmoidal fistula, segmental resection of the sigmoid colon with partial cystectomy was performed. The histopathology revealed diverticulosis of the sigmoid colon with diverticulitis and development of a vesicosigmoidal fistula.

Primary Retroperitoneal Malignant Fibrous Histiocytoma / 대한비뇨기과학회지

A malignant fibrous histiocytoma is a rare pleomorphic tumor of the soft tissues. Primary retroperitoneal involvement of a malignant fibrous histiocytoma is very rare and often diagnosed in an advanced stage as it has no specific symptoms. Herein, a case of a malignant fibrous histiocytoma involving the retroperitoneum is reported, which was incidentally found in a 74-year-old male, who complained of pain in the right abdomen and thigh.

The Comparison between Various Formulae for Calculating the Residual Volume by Ultrasonography during Volume Change, and the Influence of Gender and Age / 대한비뇨기과학회지

PURPOSE: There have been few reports concerning the accurate formula for calculating the residual urine by ultrasonography. The aim of this study was to find the most applicable formula for measuring the quantity of the residual urine by ultrasonography in terms of capacity, age and gender. MATERIALS AND METHODS: This study was carried out on 176 of 254 patients with voiding dysfunction. The mean age of the patients was 64.3+/-17.7 yrs, ranging from 4 to 88 yrs, with a M:F ration of 1.67:1. The ultrasonographic diagnostic equipment used was the HDI35000(ATL Co Ltd, United States). 13 formulae currently used in the calculation of residual urine by ultrasonography were used, and the results compared with the actual residual urine from urethral catheterization. The accuracy, percentage volume error and statistical significance of the formulae were compared in terms of the residual urines above and below 150ml from urethral catheterization, above and below the age of 50 and gender. RESULTS: The Hakenberg formula gave the best accuracy(0.95+/-0.25), whereas the McLean formula gave the best percentage error with respect to volume(17.4+/-20.9). With the formulas of Griffiths and Hakenberg, the results had statistical significance. However, none of the formulae showed statistical significance with regard to the residual urine either above or below 150ml. Therefore, a formula constant of -4.5 was added to the Griffiths formula, as this had statistical meaning in both group. There were no differences in relation to age or gender with any of the formulae. CONCLUSIONS: The Griffiths formula was relatively accurate in the volume change among the 13 formulae used. The addition of -4.5 as a constant to the formula gave statistical meaning to the residual urine, both above and below 150ml. Age and gender did not affect the correctness of the measurement.

The Comparison between Various Formulae for Calculating the Residual Volume by Ultrasonography during Volume Change, and the Influence of Gender and Age / 대한비뇨기과학회지

PURPOSE: There have been few reports concerning the accurate formula for calculating the residual urine by ultrasonography. The aim of this study was to find the most applicable formula for measuring the quantity of the residual urine by ultrasonography in terms of capacity, age and gender. MATERIALS AND METHODS: This study was carried out on 176 of 254 patients with voiding dysfunction. The mean age of the patients was 64.3+/-17.7 yrs, ranging from 4 to 88 yrs, with a M:F ration of 1.67:1. The ultrasonographic diagnostic equipment used was the HDI35000(ATL Co Ltd, United States). 13 formulae currently used in the calculation of residual urine by ultrasonography were used, and the results compared with the actual residual urine from urethral catheterization. The accuracy, percentage volume error and statistical significance of the formulae were compared in terms of the residual urines above and below 150ml from urethral catheterization, above and below the age of 50 and gender. RESULTS: The Hakenberg formula gave the best accuracy(0.95+/-0.25), whereas the McLean formula gave the best percentage error with respect to volume(17.4+/-20.9). With the formulas of Griffiths and Hakenberg, the results had statistical significance. However, none of the formulae showed statistical significance with regard to the residual urine either above or below 150ml. Therefore, a formula constant of -4.5 was added to the Griffiths formula, as this had statistical meaning in both group. There were no differences in relation to age or gender with any of the formulae. CONCLUSIONS: The Griffiths formula was relatively accurate in the volume change among the 13 formulae used. The addition of -4.5 as a constant to the formula gave statistical meaning to the residual urine, both above and below 150ml. Age and gender did not affect the correctness of the measurement.

A Case of Retroperitoneal Teratoma in an Adult / 대한비뇨기과학회지

The teratoma is made up of a variety of parenchymal cell types representative of more than one germ layer. Retroperitoneal teratoma is an uncommon neoplasm which occurs in only 10% of all retroperitoneal primary neoplasm. Primary retroperitoneal teratoma has been rarely seen in adults and 3 cases has been reported in Korea. Recently we experienced a case of retroperitoneal teratoma, which was suspected by clinical investigation and confirmed by exploration and microscopic examination. CT scan is very useful in differential diagnosis of this rare tumor. We report a case of retroperitoneal teratoma in 22 year old young woman.

Allium Sativum-mediated Therapy for Experimental Prostate Cancers with In Vivo Tumor Transduction: Effects on Tumor Growth and Development / 대한비뇨기과학회지

PURPOSE: Allium sativum (AS) has been known to have widespread benefits in reducing some human cancer risk by immune stimualtion and anticarcinogenic activity. In the present study, we evaluated the preventive and antitumor properties of AS as an effective anticancer modifier for human prostate cancer in vivo. MATERIALS AND METHODS: Subcutaneous prostate cancers were established in athymic nude mice with 5x10(5) PC-3 human androgen-indenpendent prostate cancer cells. AS was injected at the site of tumor transplantation on day 1 and one week intervals up to 5 weeks (Experiment I), and into the established tumors sized by 50-60mm(3) weekly for 5 weeks (Experiment II). Therapeutic responses and efficacies of AS for prostate cancers in vivo were determined in separate controlled experiments, and definite histopathological studies were also performed. RESULTS: In vivo studies indicated statistically significant reduction in the incidence of tumor formation with programmed and continuous AS intralesional treatment. For established prostate cancer, AS treatment also demonstrated an inhibitory effect of tumor growth compared with control. Histomorphological and immunohistochemical studies demonstrated marked apoptosis after 5 weeks-AS continuous treatment in Experiment II. CONCLUSIONS: AS had a definite antitumor activity to inhibit tumorigenesis and may modulate tumor growth of prostate cancer in vivo. It is non-toxic, readily avaliable and inexpensive. AS, in the future, may be developed as a novel and effective treatment in chemoprevention for human prostate cancer.

Extracorporeal Shockwave Lithotripsy Versus Ureteroscopic Removal for Lower Ureteral Stones / 대한비뇨기과학회지

No abstract available.

Clinical Experience of Extracorporeal Shock Wave Lithotripsy with Tripter Compact(R) Lithotriptor / 대한비뇨기과학회지

PURPOSE: Extracorporeal shock wave lithotripsy(SWL) is currently prorposed for the first line treatment of most renal and ureteral stones. In general, SWL is very effective and non-invasive method than open surgery or endoscopic lithotripsy. We experienced 350 cases of SWL for 46 months and announced it. MATERIALS AND METHODS: We retrospectively reviewed the data of 324 patients(350 stones) who had been diagnosed as renal or ureteral stones and underwent SWL using Tripter Compact(R) lithotriptor from September 1994 to July 1998. Male to female ratio was 1.9:1 and patient`s ages ranged from 18 to 82 years(mean 43.7 years). We underwent SWL only with parenteral analgesics for pain control. RESULTS: In 350 stones, renal stones were 90 cases(25.7%) and ureteral stones were 260 cases(74.3%). In 90 renal stones, calyceal stones(include 1 staghorn stone) were 62 cases(68.9%) and renal pelvic stones were 28 cases(31.1%). In 260 ureteral stones, upper ureteral stones were 209 cases(80.4%), mid ureteral stones were 10 cases(3.8%), and lower ureteral stones were 41 cases(15.8%). The stones from 10 to 19mm in diameter were the majority of renal stones(53.3%), whereas in ureter, the stones smaller than 10mm in diameter were most common(41.5%). Less than 3 treatment sessions were needed for 147 cases(93.0%) of stones smaller than 10mm and for 146cases(76.0%) stones larger than 10mm. Less than 3 sessions were needed for 68 cases(75.6%) of renal stones and for 225 cases(86.5%) of ureteral stones. All renal stones were fragmented and the success rate for upper ureteral stones was 93.3%(195/209), for mid ureteral stones was 80.0%(8/10), and for lower ureteral stones was 80.5%(33/41). According to the size of stone, the success rate for the stones smaller than 10mm in diameter was 96.2%(152/158) and for the stones larger than 10mm was 90.6%(174/192). Total success rate was 93.1%(326/350). The complications after SWL were gross hematuria over 24hours(64 cases, 18.3%), flank pain(52 cases, 14.9%), gastrointestinal disturbances(7 cases, 2%), and Steinstrasse(31 cases, 8.9%). The causes of failure were incomplete fragmentation(21 cases, 87.5%) and mucosal impact(3 cases, 12.5%) of stones. Re-treatment rate was 59.7% and auxiliary procedure rate was 8.0%(efficiency quotient was 0.56). CONCLUSIONS: Our experiences shows extracorporeal shock wave lithotripsy is a safe and effective method for the treatment of renal and ureteral stones, and we expect the better outcome by development of techniques and equipments.

Ureteroscopic Removal of Stone: Results and Complications / 대한비뇨기과학회지

PURPOSE: This study examined the efficacy of ureteroscopic stone manipulation with comparing the success rates and complications rates. MATERIALS AND METHODS: The manipulation of calculi can be done under the direct vision of ureteroscope using dormia baskets with increasing safety and efficacy. The results of ureteroscopic removal of stones were reviewed in 636 cases. From January 1992 to October 1997, 636 patients underwent ureteroscopic removal of stones. RESULTS: There were 236 female and 400 male patients between 16 and 75 years old. The success rates of ureteroscopic removal of stones were related to location of the calculus: 95.8% in lower ureter, 87.7% in mid ureter and 90% in upper ureter(overall success rate was 95%). 35 cases(5.8%) of complication occurred in 604 cases of success: Severe ureteral mucosal injury in 25 patients, gross hematuria(>48hours) in 4 patients, ureteral mucosal prolapse in 3 patients, flank pain(>48hours) in 2 patients, ureteral perforation in 1 patient. CONCLUSIONS: Ureteroscopic removal of stones can be successful and safe treatment modality for lower urethral stones, especially with plentiful experience and good surgical skill.

A Case of Extra-adrenal Pheochromocytoma / 대한비뇨기과학회지

Pheochromocytoma is one of the surgically curable hypertensive diseases and can arise wherever chromaffin cells are located. Herein, a case of extra-adrenal pheochromocytoma developed in a 51 year-old male is presented with brief review of literatures.

Initial Experience of the Effect of Laser CHRP (Coagulation and Hemostatic Resection of the Prostate) for Benign Prostatic Hyperplasia / 대한비뇨기과학회지

Laser CHRP (coagulation and hemostatic resection of the prostate) is a new acceptable treatment modality for benign prostatic hyperplasia. A total of 14 patients with symptomatic bladder outlet obstruction due to benign prostatic hyperplasia was entered into a prospective trial of laser prostatectomy performed with the right- angle firing neodymium: YAG laser fiber and the contact tip firing neodymium: YAG laser fiber at 60 watts power setting. Mean estimated prostatic weight was 36.3gm. Six patients (43%) were in urinary retention requiring catheterization before treatment. Mean energy delivery was 34,442 joules (range 25,360 to 45,000) with a mean operative time of 41 minutes. Efficacy of treatment was assessed at 1, 6 and 12 months postoperatively by Madsen symptom scores, peak urinary flow rates and ultrasonic assessment of prostatic volume. At preoperative baseline the mean symptom score was 19.9, mean peak urinary flow rate 8.6cc per second, and mean ultrasonic assessment of prostatic volume 36.3gm. At 1 year postoperatively mean symptom score was 6.1, mean peak urinary flow rate was 18.3cc per second and mean ultrasonic assessment of prostatic volume was 26.4 gm. One patient required retreatment for residual tissue. There was one bladder neck contracture requiring incision.

A Case of Female Epispadias / 대한비뇨기과학회지

Female epispadias is an uncommon congenital anomaly in genitourinary tract. We experienced a case of female epispadias with total urinary incontinence which was improved with periurethral injection of Glutaraldehyde Cross-Linked Collagen(GAX-Collagen) into the area of the bladder neck. The procedure was simple to perform and without significant complications. Herein we report a case of female epispadias in 29-year old female.

Clinical Observation for Complications of Non-Surgical Treatment of Benign Prostatic Hyperplasia / 대한비뇨기과학회지

Non-surgical treatment of benign prostatic hyperplasia (BPH) have been under investigation with interesting in recent years although transurethral resection of the prostate (TURP) seems to be accepted as a standard treatment of BPH. But the significance of post operative mortality and morbidity of TURP still remains as problem will be solved. We observed complications of non-surgical treatment of BPH from November 1989 to November 1994 including intraprostatic stenting (Prostakath , 13 cases), transurethral balloon dilation of prostate (TUDP, 19 cases), transurethral radiofrequency thermotherapy (FURT, 87 cases) and transurethral radiofrequency thermoablasion (TURTA, 23 cases) and the result revealed as below; 1. Over-all complication rate of intraprostatic stenting is 92.3%(12/13) consisting of hematuria (4 cases), acute urinary retention(1), vesical irritation(1), stone formation(1), stent displacement(1), urge incontinence(3), urinary tract infection(1) and severe bleeding(1). 2. Over-all complication rate of TUDP is 47.4%(9/19) consisting of hematuria (5 cases), acute urinary retention(3) and vesical irritation(1). 3. Over-all complication rate of TURT is 19.5%(17/87) consisting of hematuria (5 cases), acute urinary retention(6), weak stream(4) and urgency(2). 4. Over-all complication rate ofTURTA is 65.2%(15/23) consisting of hematuria (4 cases), acute urinary retention(4), epididymitis(1), urge incontinence(3) and painful urination(2). 5. The subjective improvement rate of patient 3 months after treatment in intraprostatic stenting, TUDP, TURT and TURTA were 46%, 42%, 38% and 70%, respectively. 6. More than 30% of uroflow improvement rate 3 months after treatment in intraprostatic stenting, TUDP, TURT and TURTA were 76.9%, 74%, 60.9% and 82.6%, respectively. As we see above, TURT revealed the lowest over-all complication rate compare to others and it means most safest treatment modality among them but if we consider with the subjective improvement rate of patient and the uroflow improvement rate TURTA seems better treatment modality than others even though high complication rate because no serious complication developed. We suggest that TURTA could be a first choice of treatment modality among non-surgical treatment of BPH in case of non-surgical approach is being considered at any reasons.

A Case of Sparganosis Infesting in the Scrotum / 대한비뇨기과학회지

Sparganum mansoni is an animal parasite infesting principally in cats and dogs, but sometimes it also infests human bodies. We have experienced a case of sparganosis in scrotum. Herein we report this case with a brief review of the literatures.

A Case of Malignant Renal Hemangiopericytoma / 대한비뇨기과학회지

Hemangiopericytoma of the kidney is rare. It seems to be slowly progressive and grows locally with 5cm consistency and well encapsulation, and may infiltrate surrounding tissue but the incidence and degree of its malignancy appears to be low. Herein we report a case of malignant renal hemangiopericytoma associated with asymptomatic hypoglycemia and presenting radiologically as a hypovascular mass which was developed from the left kidney in 32 years old sea man who was treated with radical nephrectomy and chemotherapy.

Accuracy of Residual Urine Volume Determination by Ultrasonography / 대한비뇨기과학회지

The determination of the residual urine volume is an essential part of the investigation of many urological patients. particularly those with suspected urinary outflow obstruction. In 31 patients, we measured 3 internal bladder diameters ( height, width and depth) by transabdominal ultrasonography and calculated the residual urine volume by formula for ellipsoid (V= phi /6 xH xW xD).The real volume was obtained by the catheterization and compared with the sonographic measurement. There was a best correlation (r=0.9748) between calculated and true volumes provided a correction factor of 1.15 was applied. The advantages of ultrasonography for assessing residual urine volume are that it is simple, quick, harmless, non-invasive and readily repeatable. If the basic equipment is available, the ultrasonography should replace the catheterization.

Initial experience of transurethral radiofrequency thermotherapy for benign prostatic hyperplasia / 대한비뇨기과학회지

Transeurethral Radiofrequency (TURF) Thermotherapy is a new acceptable treatment modality for benign prostatic hyperplasia. We treated 70 cases of BPH patients by TURF Thermotherapy (THERMEX-II). Among them, we got a follow-up observation on 37 patients (urinary retention: 16 cases, non-urinary retention:21 cases) each at 1 month and 3 months after treatment. Mean age of patients was 69.1 years and their mean prostatic weight was 40.5gr by transrectal prostatic ultrasonogram. All patients were treated single session for 2 hours without any sedation, and well tolerated with the temperature of 47-48degree. We evaluate patients with Boyarsky symptom score, urine flow rate, volume of residual urine and patient`s subjective symptoms before and after treat- The results were as follows ; 1. The mean Boyarsky symptom score was 15.4 before treatment, it became 9.9 at 1 month and 8.8 at 3 months after treatment. 2. In the retention patients : Mean maximal flow rate was 6.53ml/sec at 1 month. 8.47ml/sec at 3 months, and residual urine was 70ml at 1 month, 57ml at 3 months after treatment. 3. In the non-retention patients : Mean maximal flow rate increased from 4.74ml/sec to 10.29ml/ sec at 1 month. 10.76ml/sec at 3 months, and residual urine decreased from 60.7ml/ to 20ml at 1 month. 17.2ml at 3 months after treatment. 4. Complications were acute urinary retention (14.3% ) and gross hematuria (8.1%), but it was resolved by conservative treatment. There were no urinary tract infection, bladder spasm or other complications after treatment. We conclude TURF thermotherapy is one of the good and safe treatment in benign prostatic hyperplasia.