[Long-term results of radical surgery treatment of patients with bladder cancer].

PURPOSE: To investigate long-term results after radical cystectomy in patients with bladder cancer. MATERIALS AND METHODS: Since 1997 to 2020 yy. we have performed 404 radical cystectomy with different methods of derivation for patients with bladder cancer in our clinic. There were 342 (86,4%) men and 62 (13,6%) women. Laboratory study, ultrasound, X-ray, CT. MRI investigations were performed in all patients. RESULTS: Mortality rate was 2,9%. Early and late postoperative complications have occurred in 136 (33,6%) and 98 (41,8%) cases, respectively. Local recurrence has occurred in 33 (8,5%) patients. 10-years overall and cancer-specific survival were 43,4% and 47,2%, respectively. In lymph-negative patients 2-years and 5-years overall survival were 81,2% and 67,2%, respectively. In lymph positive patients 2-years and 5-years overall survival were 46,9% and 13,9%, respectively. In lymph-negative patients 2-years and 5-years cancer-specific survival were 83,6% and 70,7%, respectively. In lymph positive patients 2-years and 5-years cancer-specific survival were 51,0% and 15,1%, respectively. Overall and cancer -specific survival decreased according to increasing pT-stage and histopathologic grade. CONCLUSIONS: pT-stage (pT), lymp nodes status (pN), histopathologic grade ( pG) have a significant independent influence on overall and cancer-specific survival of bladder cancer patients after radical cystectomy.

[Intestinal and appendicular ureteral substitution].

AIM: To present the technical features and results of intestinal and appendicular ureteral replacement. MATERIAL AND METHODS: From 1998 to 2020, a total of 196 patients aged 18 to 77 years (mean age 49.5 +/- 1.2 years) were undergone to intestinal and appendicular ureteral reconstruction in our clinic. There were 123 women (62.8%). The most frequent indications for surgery were complications of open and endoscopic ureteral procedures, radiation-induced ureteral stricture, and iatrogenic injuries of the ureters during gynecological and surgical interventions (81.6%). In 165 (84.2%) patients, for ureteral replacement the ileal segment was used, while in 4 (2.0%) and 27 (13.8%) cases the colon segment and the appendix were chosen, respectively. Unilateral ileal ureteral replacement was performed in 131 (79.4%) cases, while in 34 (26.6%) patients a bilateral procedure was done. Partial and complete ureteral replacement was performed in 107 (81.7%) and 24 (18.3%) cases, respectively. Laparoscopic intestinal and appendicular ureteral replacement was performed in 44 (22.4%) patients, while two patients were undergone to robot-assisted procedure (1.0%). RESULTS: Early postoperative complications were noted in 17 (8.7%) cases. The most severe included acute bowel obstruction, leakage of entero-ureteral anastomoses, necrosis of the ileal graft and bleeding in 10 (5.1%) patients. In all cases, repeat intervention was performed. There were no lethal complications. Late postoperative complications developed in 24 (14.3%) patients. CONCLUSION: Today our clinic has the worlds largest experience in intestinal and appendicular ureteral reconstruction, including original procedures, confirmed by 5 patents for inventions. The minimum number of postoperative complications, the absence of deaths and good long-term results provide the basis for the introduction of ileal and appendicular ureteral replacement into clinical practice.

[A total replacement of the both ureters and urinary bladder by ileal conduit in a woman with contracted bladder and Ormonds disease].

A description of the successful surgical treatment of a patient with irreversible changes in both ureters and bladder resulting from a severe form of Ormond's disease and interstitial cystitis, resulting in contracted bladder, is presented. For the first time in clinical practice, a one-stage cystectomy, a bilateral ureterectomy with complete replacement of both ureters and the bladder with two isoperistaltic small bowel segment was performed. The postoperative course was uneventful. Follow-up contrast-enhanced computed tomography of the kidneys and newly formed urinary tract revealed good excretory function. The patient was discharged in a satisfactory condition on the 22nd day after the procedure with recommendations for taking 10 g of an aqueous solution of soda daily. At the follow-up after 3 months, she had complaints of slight weakness and voided voluntary up to 8 times a day; clinical and biochemical blood tests were normal. This clinical observation indicates the presence of two different diseases in one patient, namely interstitial cystitis and Ormond's disease. The possibility of one-stage complete replacement of both ureters and the bladder with a good immediate result is shown.

The shoulder endurance test (SET): A reliability and validity and comparison study on healthy overhead athletes and sedentary adults.

OBJECTIVES: The primary purpose was to examine the reliability of a new shoulder physical performance test -the Shoulder Endurance Test (SET)- in young healthy overhead athletes and sedentary adults and to provide preliminary reference values. The secondary objective was to determine whether there are differences on SET scores based on groups, sides and days. The third objective was to evaluate the relationship between the SET and shoulder rotational isometric strength in both groups. DESIGN: Reliability and validity study. SETTING: Laboratory setting. PARTICIPANTS: A total sample of 92 participants volunteered to participate in this study (30 healthy overhead athletes - 62 sedentary adults). MAIN OUTCOME MEASURES: We used a two-session measurement design separated by seven days to evaluate the reliability. We calculated intraclass correlation coefficients to determine relative reliability and used standard error of measurement and minimal detectable change to quantify absolute reliability. Systematic differences in SET scores between groups, days and sides were analysed with a two-way analysis of variance (ANOVA) for repeated measures. To check for systematic differences within groups between day 1 and day 2, a Wilcoxon Signed Rank Test was performed. Relationship between shoulder rotational isometric strength and the SET was determined using the Spearman Rank test (rs). RESULTS: Relative reliability was high to very high in both groups (intraclass correlation coefficient [2,1] range = 0.78-0.93) and absolute reliability was clinically acceptable. The standard error of measurement varied from 10.7 s to 16.45 s. The minimal detectable change ranged from 29.6 s to 45.6 s. Weak correlations were found between the SET and isometric shoulder rotational strength (rs range = 0.309-0.431). RESULTS: of the ANOVA for repeated measures showed a significant two-way interaction effect for day x groups (p = 0.020) and a significant main effect for side (p= < 0.001). Results of the Wilcoxon Signed Rank Test showed no systematic differences in group 1 between day 1 and day 2 for both sides (p = 0.79 dominant side; p = 0.66 non-dominant side). CONCLUSIONS: The SET is a reliable clinically applicable shoulder physical performance test in young adult overhead athletes and sedentary adult.

[Robot-assisted radical cystectomy with neobladder formation].

INTRODUCTION: Robot-assisted radical cystectomy (RARC) with intracorporeal neobladder formation is a complex surgical procedure. AIM: To describe the main stages of RARC and to analyze its short-term results. MATERIALS AND METHODS: RARC with ileocystoplasty was performed in 16 patients, most of whom were men (n=14). In 15 patients, the indication for surgery was bladder cancer (BCa), while one patient has radiation-induced sigmoid fistula with a formation of small, contracted bladder. During radical cystectomy (RC), the lower ureters were dissected, followed by posterior dissection of the bladder with mobilization from both sides to the pelvic fascia, clipping and transection of the vesical pedicles, and suturing of the dorsal venous complex with urethral dissection. After pelvic lymph node dissection, 40 cm of the ileum was resected, after that two distal segments of 15 cm were U-shaped, and a 1.5 cm incision was made in the lower part of the bowel, followed by a formation of the urethral anastomosis. Then bowel segments were detubularized, and continuous suture on the posterior and anterior walls of the neobladder was done. Ureters were implanted in the proximal tubular part of the resected colon according to the Nesbit technique. RESULTS: The mean operation time was 380 minutes. The blood loss ranged from 80 to 200 ml; however, blood transfusion was not performed. Complications during 30-days after RARC were observed in 7 (43.7%) patients, including 4 (25%) of class I-II according to Clavien - Dindo, and 3 (18.7%) of class III-IV. In patients with leakage at the uretero- intestinal anastomosis (n=2) and urethro-neobladder anastomosis (n=1), percutaneous drainage was performed, which allowed to resolve these complications. There were no cases of bowel obstruction. One patient with gastrointestinal bleeding required blood transfusion. The 90-day late complications occurred in 6 (37.5%) patients, including 2 cases of upper urinary tract infection. One patient died of acute myocardial infarction. CONCLUSION: RARC is a contemporary minimally invasive method for muscle-invasive BCa. Stepwise approach to RARC with intracorporeal neobladder formation may reduce the operation time and the rate of complications.

[Lower urinary tract urodynamics after reconstruction of the pelvic part of the ureter].

INTRODUCTION: The problem of impaired urodynamics of the lower urinary tract after reconstructive surgery of the pelvic ureter remains almost unexplored in modern literature. There are only a few publications about the effect of operations in the area of the ureterovesical segment on bladder function. AIM: To study the function of bladder after replacing the pelvic ureter with bladder flap, small intestine or appendix. MATERIALS AND METHODS: We performed a retrospective analysis of reconstructive operations of the distal ureter, which were performed in 273 patients. Boari flap or its modifications were used in 142 (52%) cases; ureteroappendicocystanastomosis - 23 (8.4%) patients, and replacement of the pelvic ureter with small intestine in 105 (38.5%) cases. A follow-up urodynamics was carried out on the 10-14th day of the postoperative period, after 3 months, then after 6 and 12 months. We evaluated: uroflowmetry, cystometry, and pressureflow study. RESULTS: In 75 (53%) of 142 patients who underwent Boari flap or its modifications, varying degrees of disturbance of bladder urodynamics were observed. After isoperistaltic intestinal ureteroplasty in 2 (2.5%) of 79 patients, detrusor hyperactivity was observed, which was regressed following conservative therapy. Urodynamics of bladder did not suffer after appendicoplasty. CONCLUSION: Deformation, denervation and devascularization of detrusor are the main causes of bladder dysfunction after flap operations. Ileal ureter substitution with isoperistaltic position of the graft provides physiological passage urine from the kidney to the bladder, following good bladder function. The inclusion of antiperistaltic ileal loop in the urinary tract negatively affects the urodynamics.

The "upper limb rotation test": Reliability and validity study of a new upper extremity physical performance test.

OBJECTIVES: The primary purpose was to evaluate the reliability of the Upper Limb Rotation Test (ULRT). The secondary objective was to evaluate the relationship between the ULRT and two PPTs (SMBT and CKCUEST), trunk rotation range of motion (SRT) and shoulder rotational isometric strength. DESIGN: Reliability study and correlation study. SETTING: Laboratory. PARTICIPANTS: 91 healthy adults participated to establish the reliability and validity of the ULRT. MAIN OUTCOME MEASURES: We used a two-session measurement design to evaluate the reliability of the ULRT. The SMBT, CKCUEST, SAC and the SRT were performed to determine relationships with the ULRT. RESULTS: Results showed good reliability. The SEM 95 and the MDC95 showed clinically acceptable absolute reliability values for the ULRT. A moderate correlation was found between the ULRT and CKCUEST scores. A moderate correlation was found between ULRT and SMBT scores. CONCLUSIONS: Results demonstrated good relative reliability and clinically acceptable absolute reliability values for the ULRT. Performances on the ULRT were moderately correlated with the PPTs.

[Technical features of intestinal ureteroplasty. Part 7: forming ureterointestinal anastomoses].

AIM: To present the results and technical features of forming the ureterointestinal anastomoses in intestinal ureteral substitution. MATERIAL AND METHODS: From 1998 to December 2016, 168 patients (mean age 51 +/- 8.7 years) underwent ureteral substitution using intestinal segments at the Urology Clinic of the I.I. Mechnikov NWSMU. Of them, 76 (45.2%) were males. In 119 (70.8%) patients, intestinal segments were used to replace various parts of the ureters (iliac in 92, colonic in 4, appendix in 23), and in 49 (29.2%) patients ureteroplasty was combined with orthotopic ileocystoplasty. 96 patients underwent isolated ureteral substitution with segments of the small and large bowel. RESULTS: Among the 96 patients, early postoperative complications occurred in 8 (8.3%) patients, whereof 5 (5.2%) required reoperations. Among them, 2 (2.1%) had a proximal anastomotic failure. Late postoperative complications occurred in 7 (7.3%) patients whereof 4 (4.2%) required surgical treatment. These patients developed strictures of the proximal ureter-intestinal anastomoses over 3 or more months after the operation. The urinary flow was restored by antegrade dilation. Vesicoureteral reflux occurred in 2 (2.1%) patients. However, it was not clinically evident and was not accompanied by hydroureteronephrosis and recurrent urinary tract infection. CONCLUSION: A perfect ureterointestinal anastomoses should be easy to create and have a low risk of stenosis and reflux. These requirements are met by direct anastomosis, which is associated with a minimal risk of stricture, and with isoperistaltic positioning and sufficient length (not less than 15 cm) of the graft provides antireflux protection. It should be noted that proximal (ureterointestinal) anastomoses are vulnerable in these operations and prone to the stricture formation. Unlike proximal, the distal anastomosis of the graft with the bladder is always wider, and therefore the risk of its narrowing is minimal. Isoperistaltic positioning of the graft prevents reflux formation.

[Technical features of intestinal ureteroplasty. art 6: simultaneous ureteral and bladder substitution].

AIM: To present the results and technical features of different methods of simultaneous ileal ureteral and bladder substitution. MATERIALS AND METHODS: From 2001 to 2016, 154 patients (mean age 52+/-9.2 years) underwent ileal and appendicular ureteroplasty. Of them, 70 (45.4%) were men and 84 (54.6%) women. Among them, 49 (31.8%) patients underwent ureteroplasty concurrently with orthotopic ileocystoplasty. The Studers ileal-ureter cystoplasty and Y-shaped bladder and ureteral reconstruction were performed in 38 (77.5%) and 11 (24.5%) cases, respectively. RESULTS: Early postoperative complications occurred in 8 (16.3%) patients: 4 of them suffered recurrent bouts of pyelonephritis, 3 experienced an acute adhesive intestinal obstruction, and another one had a failure the right-sided pouch-ureteral anastomosis. Late postoperative complications occurred in 7 (14.3%) patients. Of them, 3 suffered recurrent bouts of chronic pyelonephritis, 2 developed a pouch-ureteral-pelvic reflux, and 2 had strictures of ileoureteral anastomosis, requiring antegrade dilation with ureteral stenting. CONCLUSION: Simultaneous ureteral and bladder substitution is one of the most challenging and traumatic surgical interventions. Sometimes, due to severe comorbidities, disorders of upper tract urodynamics and decreased renal function, two-stage surgery may be necessary. At the first stage, cystectomy with cutaneous ureterostomy should be performed, and then, after the patients stabilization ileal substitution of the bladder and pelvic parts of ureters may be done.

[Technical features of intestinal ureteroplasty. Part 2: right-sided ileoureteroplasty].

AIM: To present the results of intestinal ureteroplasty and technical features of right-sided ileoureteroplasty. MATERIAL AND METHODS: From 2001 to 2015, 78 patients underwent isolated reconstruction of the ureter using a segment of the ileum, of whom 57 (73%) and 21 (27%) patients had unilateral and bilateral operation, respectively. In total, isolated segments of the ileum were used to substitute 101 ureters including 45 (44.6%) right ureters. RESULTS: The follow-up period ranged from 3 months to 14 years (mean 8.3 +/- 0.8 years). Early postoperative complications occurred in 8 (10.2%) patients and 5 (6.4%) of them required reoperation. Long-term postoperative complications occurred in 7 (8.9%) patients and 4 required surgical treatment. All patients had good results of conservative treatment and reoperations. There were no deaths. All patients achieved restoration of urodynamics and normalization of kidney function. CONCLUSION: Right-sided, especially total, ileoureteroplasty is the most technically challenging among other possible options to substitute the ureter with a small bowel segment. To avoid mesenteric torsion when performing isoperistaltic ureteroplasty, the graft should be placed above and in front of the intestinal anastomosis.

[Fibroepithelial polyps of renal pelvis and ureter].

AIM: To analyze the results of surgical treatment of patients with long ureteral fibroepithelial polyps (FEP). MATERIALS AND METHODS: From 2005 to 2014 three patients (1 man and 2 women) with large FEP were observed in our hospital. In 2 patients the base of the polyp was located in the proximal ureter and in 1 patient in the middle calyx of the single kidney. The fibroepithelial polyps were long and extended down to the lower third of the ureter (2) or protruded into the bladder (1). Endoscopic resection of the polyp was made in 1patient, resection of parenchyma in the middle calyx along with the base of FEP in 1 patient with the single kidney, and another patient underwent laparoscopic nephrectomy due to the absence of kidney function. RESULTS: Endoscopic resection was successful; the operation lasted 45 minutes without complications. In the patients with a single right kidney operative time was 3.5 hours; during the operation, she received a blood transfusion. In the postoperative period, she underwent two hemodialysis sessions due to acute renal failure. Subsequently, her kidney function was restored. No FEP recurrences occurred in cases of organ sparing operations during follow-up. The postoperative period of the third patient submitted to laparoscopic nephrectomy was uneventful, creatinine levels remained in the normal range. CONCLUSION: For long, large ureteral FEPs with a broad base the choice of surgical option depends on possibility of tumor visualization and functional state of the kidney.

[Technical features of intestinal ureteroplasty. Part 4: YANG-MONTI ureteric reconstruction with reconfigured ileal segment].

AIM: To present the results of ureteroplasty and technical features of ureteric replacement using the Yang-Monti procedure. MATERIAL AND METHODS: From 2001 to 2016, 105 patients underwent intestinal appendiceal ureteroplasty. In 5 (4.8%) cases, ureteric replacement using the Yang-Monti procedure was performed. Among them, 2 and 3 patients had left and right ureter replacement, respectively. RESULTS: Postoperative complications occurred in 2 of the 5 operated patients, and one of them required re-surgery. Repeat operations were successful; there were no deaths. CONCLUSIONS: The advantages of ureteric replacement using the Yang-Monti procedure include the ability to replace any ureteral defects 5-6 cm in length by using one ileal segment. However, this may result in an ileal segment with insufficient blood supply and partially lost contractility included in the urinary tract. For this reason, for more than a decade, this operation has not been widely adopted, and Yang-Monti procedure needs to be further assessed in larger comparative studies with longer follow-up.

[Technical features of intestinal ureteroplasty. part 5: bilateral ureteroplasty].

AIM: To present the results and the technical features of the various methods of bilateral ileal ureteroplasty. MATERIALS AND METHODS: From 2001 to 2016, 154 patients (mean age 52+/-9.2 years) underwent ileal and appendicular substitution of the ureter and urinary bladder. Study participants comprised 70 (45.4%) men and 84 (54.6%) women. All patients underwent comprehensive examination, including ultrasound, X-ray, radioisotope and endoscopic tests. Bilateral isolated ileal ureteroplasty was performed in 20 patients (40 substituted ureters) whereof in 14, 5 and 1 cases U-shaped, 7-shaped and two separate grafts were used, respectively. RESULTS: Postoperative complications occurred in 2 (10%) of 20 patients who underwent bilateral intestinal ureteroplasty. Acute small bowel obstruction occurred in a patient after a U-shaped substitution of extended defects of both ureters. He underwent relaparotomy, bypass ileotransverse side-to-side anastomosis. Another patient developed right-sided ureteral-intestinal anastomotic leak following bilateral 7-shaped ureteroplasty. After relaparotomy and right ureter ligation, the breakdown site of the graft was closed with suturing. Repeat operations were successful; there were no deaths. CONCLUSION: Bilateral ileal ureteroplasty is much more complicated surgery than a unilateral operation. For proper collection and preparation of ileal graft in isoperistaltic position without mesenteric torsion, one should know how to place it in relation to intestinal anastomosis. Depending on this, several types of bilateral ileal ureteroplasty may be used: U-shaped, bilateral 7-, J- or L-shaped or separate isoperistaltic ileoureteroplasty.

[Subcutaneous nephrovesical bypass in ureteral obstruction].

We performed subcutaneous bypass draining (SBD) of the upper urinary tract (UUT) in 12 patients (3 males, 9 females, mean age 64 years) in 2006-2008. Ureteral obstruction was caused by a tumor in 11 patients, one patient had extended obliteration of the left ureter after resection of the abdominal aorta aneurysm and two plastic operations on the UUT. All the patients with ureteral tumor obstruction had only one functional kidney. For SBD of the kidney we used Detoure stent in 2 cases, the nephrovesical bypass - in the rest cases. Surgery was made in the lateroposition of the patient which provided sumaltenous establishment of the renal and vesical ends of the stent. The kidney was also drained by the nephrostoma in 8 patients. The nephrostoma was removed after antegrade pyelography and pyelomanometry. Intraoperative complications were not registered. Suprapubic urine leak in 3 patients previously given radiotherapy was stopped by a long drain of the bladder. Obstruction of the distal stent part by a progressive tumor was diagnosed in 1 patient 3 months later. The bypass was removed and a nephrostomic drainage was made. The nephrovesical stent was changed in one case 5 months after SBD. Upon 6-32 month follow-up 3 patients died of cancer progression, the rest are still alive. Thus, SBD is indicated if stenting, ureteral endoprosthesis, constant nephrostomic drainage are impossible. In some cancer patients with ureteral obstruction in UUT drainage SBD is a method of choice with promising short- and long-term results.

[Treatment of epithelial tumors of the upper urinary tracts]. / Operativnoe lechenie épitelial'nykh opukholei verkhnikh mochevyvodiashchikh putei.

The authors present the results of different operative treatments of tumors of the upper urinary tracts (UUT). A total of 116 patients with UUT tumors were examined and treated from 1990 to 2002 (age 19-80 years, mean age 61.3+/- 1.3 years; males 82, females 34). Tumors of the renal pelvis and the ureter were detected in 76 (65.5%) and 40 (34.5%) patients, respectively (8.0 and 4.3% of a total number of patients with tumors of the kidneys and UUT). 107 (92.2%) patients were operated. Nephroureterectomy and ureterectomy with resection of the urinary bladder were performed in 73 (68.2%) patients, TUR of the urinary bladder wall, ureteral ostium with pelvic part of the ureter and nephroureterectomy (including endovideosurgery) in 22 (20.6%), nephroureterocystectomy in 4 (3.7%), resection of the pelvic ureter with Boari's operation in 5 (4.7%), nephroscopy, ureteroscopy with removal of urothelial tumor in 3 (2.8%) patients. Postoperative complications (most of them infectious-inflammatory) developed in 10 (9.3%) patients. Lethality was 0.9%. Tumor recurrences occurred in 27 (25.2%) patients within 5-year follow-up. 15 (14.0%) patients were reoperated. 5-year survival reached 67.0%. Conventional and radical method of treating patients with tumors of the renal pelvis and ureter is nephroureterectomy with urinary bladder resection and its modification. In invasion of the tumor in the muscular layer of the bladder wall surgery should be extended and supplemented with cystectomy. Conservative surgical interventions are indicated in tumors of the sole kidney, bilateral process, benign or surface tumor of the urothelium.

[Short-term results of radical cystectomy]. / Blizhaishie rezul'taty radikal'nykh tsistéktomii.

The paper presents the results of 114 radical cystectomies made in 1996-2002. The age of 114 patients (103 males, 11 females) ranged from 37 to 78 years (mean age 57.5 years). Transient cell carcinoma was diagnosed in 81.5% patients. Supravesical urine derivation was conducted by means of ureterocutaneostomy and transureteroureteronephrostomy in 9 (7.9%) patients, ureterosygmoanastomosis--in 43 (37.7%) patients, artificial orthotopic urinary bladder was created in 7 (6.1%) patients of a gastric segment and in 55 (48.2%) patients of the ileum. Postoperative complications were observed in 28 (24.6%) patients, intestinal obstruction being a prevailing complication. Five patients died: 2 of pulmonary artery thromboembolism, 1 of acute cardiac failure, 1 of sepsis and 1 of gastric bleeding. Continent methods of urine derivation were preferred, such as ureterosygmoanastomosis by Mainz-Pouch II and creation of orthotopic urinary bladder of the stomach or of the ileum.

Effects of indomethacin, cisplatin and delta 12-prostaglandin J2 on growth of oral squamous carcinoma cells.

The effect of indomethacin, cisplatin and delta 12-prostaglandin J2 (PGJ2) on the inhibition of cell growth and DNA Synthesis (i.e. cell proliferation), was evaluated in vitro on human oral squamous carcinoma cells(SCC-25). The rank order of their inhibitory potency at 10(-5) M was delta 12-PGJ2 > cisplatin > indomethacin. However, delta 12-PGJ2 at 10(-7) and 10(-6) M induced a significant stimulatory effect on cell growth as well as DNA synthesis. The sefindings suggest that delta 12-PGJ2 is a promising novel chemotherapeutic agent for oral cancer and potential candidate for future clinical investigations.

Effect of vitamin C and vitamin E on prostaglandin synthesis by fibroblasts and squamous carcinoma cells.

Dietary levels of vitamins C and E have been associated with cancer prevention and to a lesser extent with therapeutic enhancement of cancer treatment. Inhibition of prostaglandins (PGs) by pharmacological agents has been demonstrated to enhance immunocompetence, and to suppress growth of tumors in animals and humans. We report here on the effect of vitamins C and E on PGE2 production by human gingival fibroblasts and SCC-25 oral squamous carcinoma cells. The results indicate: 1. vitamins C and E exert a dose-dependent effect on arachidonic acid (AA) release and PGE2 synthesis; 2. vitamin E has a biphasic effect which is stimulatory at 1 and 10 microM and inhibitory at 100 microM; 3. vitamin E is considerably more potent than vitamin C in its inhibitory effect on AA and PGE2 in both cell types; 4. a combination of the two vitamins has a consistent dose-dependent inhibitory effect on AA and PGE2; 5. vitamin C stimulates PGE2 synthesis from exogenous AA in fibroblasts, and inhibits it in SCC-25 cells. The in vivo significance of these findings requires further investigation.

Prostaglandin synthesis by squamous carcinoma cells of head and neck, and its inhibition by non-steroidal anti-inflammatory drugs.

The purpose of this study was to determine the nature and amounts of prostaglandins (PGs) produced by squamous carcinoma cells (SCC) and the sensitivity of these cells to non-steroidal anti-inflammatory drugs. SCC of four lines of the tongue and one line of facial epidermis of humans were incubated in phosphate buffer solution with 14C-arachidonic acid (AA). Radioactive metabolites in aqueous methanol were chromatographed on Sep-Pack C18 cartridges, separated and quantitated by means of TLC, autoradiography, and liquid scintillation counting. The results showed that cyclooxygenase products, PGs, were the major products formed by all cell lines, and PGE2 was predominant among the PGs detected. Two radioactive bands corresponding to PGF2 alpha and three unseparated standards of PGA2, 15-keto-PGE2, and 13,14-dihydro-15-keto-PGE2 were detected in lesser amounts. Very small amounts of the lipoxygenase products 12- and 15-HETE were found. The concentrations of indomethacin, ibuprofen and aspirin required to inhibit 50% of PGE2 synthesis (IC50) by SCC lines were .008-.080, .080-6.4 and 32-88 microM, respectively.