Mg Of 5-fluorouracil Research Articles

Use of 5-Fluorouracil Injections in Traumatic Cicatricial Malposition of Eyelids.

Scarring in the eyelid and periocular regions has both cosmetic and functional implications. Free and unrestricted movement of the eyelids is imperative for opening and closing of the eye and for protection of the ocular surface. Among the nonsurgical modalities of scar treatment, the antineoplastic drug 5-fluorouracil has been used widely.1 We share our experience with its use in posttraumatic cicatrizing eyelid malposition. All the patients had undergone primary treatment for eyelid trauma elsewhere. The patients presented with lagophthalmos (Fig. 1), ptosis, or cicatricial ectropion. [See Figure, Supplemental Digital Content 1, which shows a patient with ptosis caused by cicatricial tethering of eyelid at the lateral orbital rim. Photograph taken 4 weeks after the injury. Lateral view shows the scar (above) and the resolution of ptosis 4 weeks after the last injection. A total of 105 mg of 5-fluorouracil was injected in three sittings. The patient did not desire surgery. Lateral view after 5-fluorouracil injection shows improvement in the scar (below), https://links.lww.com/PRS/F327.] Twelve patients (mean age, 38.3 years; SD, 12.6 years; nine male and three female) received injections before any surgical intervention at our clinic.Fig. 1.: (Above) Clinical photograph showing cicatricial lagophthalmos 4 weeks after trauma. (Below) Clinical photograph of the patient at 12 months follow-up after injection of 5-fluorouracil (total 140 mg in four sittings).Measurements and clinical photographs were taken before and after injection. We continued the injections every 3 to 4 weeks or until improvement plateaued. The earliest injections were at 4 weeks, with a mean delay of 3.08 months. All cases were performed under topical anesthesia with a mixture of lignocaine 2.5% W/W and prilocaine 2.5% W/W (Prilox cream; Neon Laboratories, Bangalore, India). We injected 5-fluorouracil 50 mg/ml (Fluracil; Zydus Cadila, Ahmedabad, India) with a 26-gauge or 30-gauge needle in 0.1-ml aliquots injected at intervals of 5 mm into and around the scar. Traction sutures were applied to facilitate lengthening of the scar. The mean interval from injury to first presentation at our clinic was 3.08 months (range, 1 to 14 months). The mean dose of injections required was 54.3 mg (range, 15 to 105 mg) in one to four sittings. Objective improvement was seen in 11 of 12 patients (91.6 percent) (Fig. 1). [See Figure, Supplemental Digital Content 1, https://links.lww.com/PRS/F327.] Reconstructive surgery could be avoided in six of 12 patients (50 percent). Patients with anterior lamellar skin deficiency required surgery. Pain and burning sensation were reported after the first injections in the first two patients. Oral paracetamol 650 mg immediately after injection kept the patients comfortable. No patient experienced 5-fluorouracil toxicity on the ocular surface. No patient showed wound dehiscence or skin ulceration, known adverse events.2 5-Fluorouracil, an antimetabolite, acts both on the phase of proliferation and the phase of maturation in the healing wound. It inhibits DNA synthesis and repair.2 It also interferes with RNA function, reduces proliferation of dermal fibroblasts, and affects transforming growth factor–β signaling and formation of type 1 collagen.2,3 Reports also show that the inhibitory effects of 5-fluorouracil on fibroblast proliferation and fibroblast action last for more than 6 weeks after a single application.4 There are few original reports of periocular use of 5-fluorouracil.5 Conventional use has been to inject weekly or biweekly, starting soon after surgery.5 For our series, the drug was injected during the phase of wound maturation, with less frequent dosing. The injections were still effective, with few adverse events. We propose that injection of 5-fluorouracil is a safe and effective modality for wound modulation in eyelid scarring and can reduce the need for surgical intervention. PATIENT CONSENT Patients provided written informed consent for the use of their images. DISCLOSURE The authors have no financial interest to declare in relation to the content of this article.

Regional intra-arterial polychemotherapy to increase the effectiveness of conservative treatment of locally invasive oral squamous cell carcinoma

The objective is using a clinical example to demonstrate the possibilities of intra-arterial polychemotherapy (PCT) in the combined treatment of oral squamous cell carcinoma.Clinical case. A 43-year-old oral squamous cell carcinoma patient with metastases to cervical lymph nodes, left side (T3N2bM0, stage IV) underwent 2 courses of regional neoadjuvant intra-arterial PCT (docetaxel at a dose of 105 mg, cisplatin at a dose of 105 mg), accessed through a. lingualis. A total dose of 6,800 mg of 5-fluorouracil was administered as a 96-hour infusion. PCT induced oral mucositis of grade 2, no hematological side effects were observed. Clinical examination revealed that tumor volume decreased by 60 %. Ultrasound detected no changes in lymph nodes. Second step included resection of oral cavity bottom tissues, atypical tongue resection, marginal resection of the lower jaw on the left, radical neck dissection on the left. Histological study of the surgical material of primary tumor region as well as metastases of the cervical lymph nodes on the tumor side revealed pathomorphism of 4 grade. In the postoperative period, oral cavity and neck were irradiated from 2 sides. No signs of the disease were detected within 9 months after the combined treatment.Conclusion. The clinical case demonstrates the high efficiency of regional intra-arterial PCT in patients with locally invasive oral squamous cell carcinoma. It seems relevant to further study its possibilities in the combined treatment of locally invasive forms of oral squamous cell carcinoma.

Renal collecting duct carcinoma: report of three cases and literature review

Objective To investigate the clinicopathological features, diagnosis, differential diagnosis and prognosis of renal collecting duct carcinoma (CDC). Methods The clinical data of 3 patients with renal collecting duct carcinoma, during the period from January 2015 to November 2017, were retrospectively analyzed. 3 patients were male with age ranged from 42 to 73 years old, mean of 57.5 years. Two lesions were located in the right kidney and one in the left kidney. Clinical manifestations were hematuria, abdominal mass and waist and abdomen pain. No laboratorial abnormality was found. CT examination showed the tumor diameter ranged from 3.1 to 5.1 cm, mean 3.9 cm. The tumors located in the medullary and renal pelvis with low density or mixed density.Those tumors extended to the peripheral of the kidney, which the boundary was unclear. During enhancement CT, the uneven enhancement effect could be observed. Radical nepheroectomy was performed in all patients. Results Postoperative pathological examination showed surface of incision was gray. The texture of tumor was hard. The invasive growth pattern could be noticed. Under the microscope, the tumors had small ducts and papillary structures of tubules with interstitial fibrosis and some sarcomatous differentiation. Immunohistochemical staining showed strong positive expression of vimentin, CK-L, CKpan and P504S, and positive expression of PAX-2, CK7 and EMA in different degrees. RCC, KSP, CD10, CD117, MOC-31 and TFE3 were all negative. All 3 cases were followed up from 1 to 15 months with an average of 6 months. One case was treated with chemotherapy because of extensive metastases after surgery. Chemotherapy was performed by dissolving 1 500 mg of fluorouracil in 1 000 ml of 5% normal saline and instillation. It was administered once every 10-12 hours and once a day for 5 days in one cycle. However, the outcome was poor. 1 patient died of tumor metastasis and recurrence 7 months after surgery. 1 patient had no tumor remaining after surgery. Conclusions CDC is a very rare malignant epithelial neoplasm in kidney. It has obvious clinical symptoms, strong invasive pattern and poor prognosis. Imaging and ultrasonography only play an auxiliary role in diagnosis. CDC's unique histopathology is the main basis of diagnosis and differential diagnosis. Key words: Kidney neoplasms; Collecting duct carcinoma; Immunohistochemistry; Pathological diagnosis and prognosis

Hazardous drug residue on exterior vial surfaces: evaluation of a commercial manufacturing process.

Hazardous drug residue on the exterior surface of drug vials poses a potential risk for exposure of health care workers involved in handling these products. The purpose of this article is to heighten the awareness of this serious issue and to evaluate a commercial manufacturing process for removing and containing hazardous drug (HD) residue on exterior vial surfaces. Additionally, findings from this study are interpreted, incorporated into the current body of evidence, and discussed by experts in this field. This study includes separate evaluations for the presence or absence of surface drug contamination on the vials of 3 HD products: 5-fluorouracil, cisplatin, and methotrexate. The drug products were packaged in vials using a patented prewashing/decontamination method, application of a polyvinylchloride (PVC) base, and use of clear glass vials. An additional step of encasing the vial in a shrink-wrapped sheath was used for 5-fluorouracil and cisplatin. Of all 5-fluorouracil (110 vials), methotrexate (60 vials), and cisplatin (60 vials) tested, only 2 had detectable amounts of surface residue. One 5-fluorouracil vial was found to have approximately 4 mg of 5-fluorouracil on the surface of the vial. The second contaminated vial was cisplatin, which was discovered to have 131 ng of platinum, equal to 200 ng of cisplatin or 0.2 μL of cisplatin solution, on the vial sheath. Using validated extraction and analytic methods, all but 2 of the 230 tested vials were found to be free of surface drug contamination. Pharmacy leaders need to take an active role in promoting the need for clean HD vials. Manufacturers should be required to provide their clients with data derived from externally validated analytic studies, reporting the level of HD contamination on the exterior of their vial products.

Formulation, in vitro drug release and in vivo human X-ray investigation of polysaccharide based drug delivery systems for targeting 5-fluorouracil to the colon

The purpose of this research study was to develop 5-fluorouracil compression coated tablets by using biodegradable polysaccharide polymer locust bean gum (LBG) and hydroxyl propyl methyl cellulose (HPMC) as coating materials. The fast disintegrating core tablets containing 50 mg of 5-fluorouracil were compression coated with LBG and HPMC in different ratios (8:1, 7:2 and 6:3) with a coat weight of 300, 400 and 500 mg. In vitro dissolution data indicated that the formulation (CLH63) with a coat weight of 500 mg containing LBG and HPMC in the ratio 6:3 gave the best release profile (0% in first 5 hour and 96.18% in 24 hours). DSC and FTIR results indicated no possibility of interaction between drug and polymers or other excipients. In vivo human X-ray studies revealed that formulation CLH63 was able to resist breakdown in the stomach and small intestine. The disintegration of the tablet occurred in the colon between 8 to 16 hours of post dose. By the present study, it can be concluded that the LBG and HPMC based compression coated tablets of 5-fluorouracil will be useful strategy for colonic delivery of 5-fluorouracil without being released in upper gastrointestinal region for the safe and effective management of colon cancer.

A randomized, controlled, multicenter study comparing intensity-modulated radiotherapy plus concurrent chemotherapy with chemotherapy alone in gastric cancer patients with D2 resection

Background and purposeThe role of postoperative chemoradiotherapy in the treatment of patients with gastric cancer with D2 lymph node curative dissection is not well established. In this study, we compared postoperative intensity-modulated radiotherapy plus chemotherapy (IMRT-C) with chemotherapy-only in this patient population. Materials and methodsWe randomly assigned patients with D2 lymph node dissection in gastric cancer to IMRT-C or chemotherapy-only groups. The adjuvant IMRT-C consisted of 400mg of fluorouracil per square meter of body-surface area per day plus 20mg of leucovorin per square meter of body-surface area per day for 5days, followed by 45Gy of IMRT for 5weeks, with fluorouracil and leucovorin on the first 4 and the last 3days of radiotherapy. Two 5-day cycles of fluorouracil and leucovorin were given 4weeks after the completion of IMRT. Chemotherapy-only group was given the same chemotherapy regimens as IMRT-C group. ResultsThe median overall survival (OS) in the chemotherapy-only group was 48months, as compared with 58months in the IMRT-C group; the hazard ratio for death was 1.24 (95% confidence interval, 0.94–1.65; P=0.122). IMRT-C was associated with increases in the median duration of recurrence-free survival (RFS) (36months vs. 50months), the hazard ratio for recurrence was 1.35 (95% confidence interval, 1.03–1.78; P=0.029). COX multivariate regression analysis showed that lymph node metastasis and TNM stage were both the independent prognostic factors. Rates of all grade adverse events were similar in the two treatment groups. ConclusionsIMRT-C improved RFS, but did not significantly improve OS among patients with D2 lymph node dissection in gastric cancer. Using IMRT plus chemotherapy was feasible and well tolerated in patients with gastric cancer after D2 resection.

Development of Novel Combined Time and pH-Dependent based Drug Delivery Systems for Targeting 5-Fluorouracil to the Colon

The present work is aimed to develop new oral drug delivery systems of 5-fluorouracil for the treatment of colorectal cancer by using hydrophilic swellable polymer hydroxy propyl methyl cellulose (HPMC) and pH responsive soluble polymer Eudragit L100 (ED) as coating materials. Core tablets containing 50mg of 5-fluorouracil were prepared by direct compression. The core tablets compression coated with different ratios (9:1, 8:2, 7:3, 6:4 and 5:5) of HPMC and ED with a coat weight of 300 and 400mg. All the formulations were evaluated for the hardness, friability, drug content uniformity and in vitro drug release studies in media of different pH 1.2, 7.4 and 6.8. The formulations released 0 to 7% of the drug in physiological environment of stomach and small intestine depending upon proportion of HPMC and ED used in the coat. Among the different ratios used for coating with HPMC:ED combination, ratio 9:1 gave the best release profile with the coat weight of 300mg (1.34% in the initial 5h and 87% in 24 h). Further increase in the coat weight to 400mg with different ratios of 9:1, 8:2, 7:3, 6:4 and 5:5 led to drug release of 0%, 0%, 0%, 3.47% and 6.25%, respectively in the initial 5 h and 73.52%, 87.03%, 92.18%, 96.33% and 97.61%, respectively, in 24 h. Thus, based on the results of in vitro drug release studies, the ratio 7:3 with a coat weight of 400mg was found to be suitable for targeting 5-fluorouracil to the colon without being released in physiological environment of stomach and small intestine. The formulation showed no change in physical appearance, drug content or in vitro release pattern after storage at 40° C / 75% RH for 3 months. The release of 5-fluorouracil from developed formulation was directly proportional to amount of ED used in the coat. The DSC and FTIR studies indicated no possibility of interaction between 5-fluorouracil and excipients.

Micronucleus induction by metronidazole in rat vaginal mucosa

Metronidazole (MTZ) is used for the treatment of many infectious diseases, including vaginal infections. While data indicate that MTZ is mutagenic and induces micronuclei in rodents, there is no information on the genotoxicity of MTZ in epithelial vaginal cells or cervical cells. In the present study, we have instilled MTZ into the vagina of rats and evaluated the micronucleus (MN) frequency in proestrus rat vaginal mucosal cells. The first identified proestrus before treatment was used to establish basal proestrus micronucleated cell (PMNC) frequencies. Rats then were assigned to one of five groups: a negative control, three MTZ treatment groups (30, 50, or 100 mg/kg MTZ), and a positive control treated with 2.5 mg of 5-fluorouracil (5-Fu) per rat. Following treatment for five consecutive days, vaginal cell samples were taken daily until three cycles of estrus were completed. Smears prepared from the samples were evaluated for micronuclei in proestrus cells. No differences were found between the PMNC frequencies of the negative control and the 30 and 50 mg/kg MTZ groups. The group treated with 100 mg/kg MTZ, however, had significantly elevated PMNC frequencies in the first and second proestrus samples, while 5-Fu treatment produced significant increases in PMNC frequency in the second and third proestrus. These results indicate that topical administration of relatively high concentrations of MTZ is genotoxic in rat vaginal mucosa cells.

Local and Sustained Delivery of 5-Fluorouracil from Biodegradable Microspheres for the Radiosensitization of Malignant Glioma: A Randomized Phase II Trial

This study was a randomized, multicenter Phase II trial comparing the effect of perioperative implantation of 5-fluorouracil-releasing microspheres followed by early radiotherapy (Arm A) and early radiotherapy alone (Arm B) in patients with gross total resection of high-grade glioma. Patients were randomized on clinical and radiological assumption of supratentorial high-grade glioma. All patients underwent surgery, and after resection and histological confirmation, patients randomized to Arm A received multiple injections of microsphere suspension (130 mg of 5-fluorouracil). Conventional fractionated radiotherapy (59.4 Gy) was initiated between the second and the seventh day after surgery for both arms. A total of 95 patients were randomized. Seventy-seven patients were treated and analyzed in intention to treat for efficacy and safety. Overall survival was 15.2 months in Arm A and 13.5 months in Arm B. In the subpopulation of patients with complete resection, overall survival was 15.2 months in Arm A versus 12.3 months in Arm B. However, these differences were not significant. Safety was acceptable with prophylactic high doses of corticosteroids. It may be hypothesized that the implantation of 5-fluorouracil-loaded microspheres in the wall of the cavity resection did increase the overall survival, but the present study was not designed and sufficiently powered to demonstrate this.

Intra-arterial infusion of fluorouracil as adjuvant chemotherapy by using removable catheters with shape-memory alloy following curative hepatectomy of metastatic colorectal carcinoma

3721 Background: Although there are some reports that adjuvant hepatic arterial infusion (HAI) chemotherapy reduces the hepatic recurrence following curative resection of colorectal liver metastases, a problem of indwelling catheters after cessation of the chemotherapy remains unsolved. The authors investigated the usefulness of adjuvant HAI by using a removable port-catheter system which was recently developed. Methods: A W spiral catheter was tried to place in 17 patients who underwent curative hepatectomy. The catheter was postoperatively inserted into the hepatic artery via the right femoral artery by percutaneous method. A W spiral catheter has a special shape-memory alloy in its apical portion, which allows stable fixation of the catheter in the vascular wall without coiling and removal of the catheter if necessary. 1500 mg of 5-fluorouracil (5-FU) was intra-arterially administered for 5 hours once a week for 8 weeks by using disposable infusion pumps, and the total dose was 12g. Results: A W spiral catheter was successfully placed into the aimed portion of the hepatic artery in 82% of the patients, and dislocation of the catheter was not observed throughout the period. All patients received the scheduled courses of chemotherapy without serious adverse events. The port-catheter system was removed easily and uneventfully after termination of the chemotherapy. Three-dimensional CT angiography revealed that the patency of the hepatic artery was well preserved in most cases. Postoperative hepatic recurrence was observed only in 3 patients. With the median follow-up time of 18.1 months, the 1- and 2-year hepatic disease free survival were 80% and 67%, respectively and the accumulative survival was 93% and 93%, respectively. Conclusions: Prophylactic HAI of 5-FU by using a W spiral catheter and subsequent extirpation of the catheter is a promising strategy following curative resection of colorectal liver metastases. No significant financial relationships to disclose.

Radiotherapy combined with transarterial infusion chemotherapy and concurrent infusion of a vasoconstrictor agent for nonresectable advanced hepatic hilar duct carcinoma.

The treatment of patients with advanced hepatic hilar duct carcinoma is a challenging problem. The current study was performed to evaluate the outcome of patients with advanced hepatic hilar duct carcinoma who received external beam radiotherapy (EBRT) combined with transarterial chemotherapy and infusion of a vasoconstrictor. Between April 1993 and December 2002, 23 patients with histopathologically confirmed hilar duct carcinoma entered the study. The median total dose of EBRT was 41.4 grays (Gy). Transarterial chemotherapy was performed twice during EBRT. It was comprised of an infusion of a cocktail of 20 mg of epirubicin, 10 mg of mitomycin C, and 500 mg of 5-fluorouracil and was administered 1 minute after injection of epinephrine via a catheter introduced in the hepatic arteries. After the combined treatment, the patients underwent biliary endoprosthesis after evaluation of the initial response to treatment by percutaneous transhepatic cholangiography (PTC). The initial responses based on PTC were classified into four categories: CR, no stenosis; PR, relief of stenosis/obstruction; NC, no change; and PD, progressive stenosis/obstruction. The outcome parameters were survival rates and time, as well as frequency and type of complications. Excluding 1 patient who discontinued the treatment, the initial responses of 22 patients were 1 CR (5%), 8 PR (36%), 11 NC (50%), and 2 PD (9%). The response rate was 41%. The overall survival rates at 1 year, 2 years, and 3 years after treatment were 59%, 36%, and 18%, respectively. The combination of radiotherapy, transarterial infusion chemotherapy, and concurrent infusion of a vasoconstrictor can be delivered safely with good efficacy for patients with advanced hilar duct carcinoma.

Colonic drug delivery of 5-fluorouracil: an in vitro evaluation

Compression coating has been found to be useful for colonic drug delivery. The aim of the present investigation was to design a formulation with a considerably reduced coat weight and gum concentration for colonic delivery of 5-fluorouracil for the treatment of colorectal cancer. Rapidly disintegrating core tablets containing 50 mg of 5-fluorouracil were prepared and compression coating with 175 mg of granules containing a mixture of xanthan gum (XG) and guar gum (GG) in varying proportions was done. With this coat weight, a highly retarded drug release was observed. After 24 h of dissolution the mean percent drug release from the compression coated XG:GG 20:20, 20:10 and 10:20 tablets were found to be around 18±1.23%, 20±1.54% and 30±1.77%, respectively. So, the coat weight was further reduced to 150 mg. It was observed that reduction of coat weight did not affect the initial drug release rate in simulated upper gastrointestinal tract (GIT) conditions. At the end of 24 h of dissolution the amount of drug released increased to 25±1.22%, 36.6±1.89% and 42.6±2.22%, respectively in XG:GG 20:20, 20:10 and 10:20 tablets. Studies of XG:GG (10:20) tablets in presence of colonic contents showed an increased cumulative percent drug release of 67.2±5.23% in presence of 2% cecal content and 80.34±3.89% in presence of 4% cecal content after 19 h of incubation.

Transient, profound cataract associated with intracameral 5-fluorouracil

PurposeTo report a transient cataract after bleb needling and subconjunctival injection of 5-fluorouracil. DesignObservational case report. MethodsA 51-year-old man had an encapsulated bleb after filtering surgery. The bleb was needled, and 5 mg of 5-fluorouracil was injected adjacent to the bleb. ResultsWithin 5 minutes, vision fell to finger counting at 1 foot owing to anterior lens capsule opacification. The next day, acuity and lens clarity had returned to their preneedling status. Best-corrected acuity 7 months later was 20/15. ConclusionEntry of 5-fluorouracil into the anterior chamber after bleb needling can cause transient lens opacification. Recently, intracameral 5-fluorouracil was reported as a new treatment for epithelial ingrowth. Given the transient cataract observed in this case, the use of 5-fluorouracil for epithelial ingrowth should be considered with caution for phakic patients.

After-cataract and secondary glaucoma in the aphakic infant rabbit

Purpose To study the association between after-cataract and secondary glaucoma after lensectomy and 5-fluorouracil treatment in an experimental infant rabbit model. Setting St Erik Eye Hospital, Karolinska Institute, Stockholm, Sweden. Methods Lensectomy was performed in both eyes of 16 3-week-old rabbits. One randomly selected eye in each rabbit was injected with 2.5 mg of 5-fluorouracil (5-FU) at surgery and 5.0 mg the day after surgery to reduce the formation of after-cataract. Axial length, corneal thickness, corneal diameter, and intraocular pressure were measured preoperatively and 4 times during the 6 months following surgery. Six months after surgery, the wet weight of the after-cataract was determined. Results In 16 aphakic eyes treated with 5-FU, no or a minimal amount (<0.001 g) of after-cataract developed. None of the eyes showed signs of secondary glaucoma. Of 16 aphakic eyes not treated with 5-FU, 10 developed considerable amounts of after-cataract (>0.10 g); 8 of these developed glaucoma. The other 6 eyes had no or minimal after-cataract and did not develop secondary glaucoma. The relationship between after-cataract and secondary glaucoma was statistically significant. Conclusion A significant relationship between the amount of after-cataract and the development of secondary glaucoma was found in aphakic infant rabbit eyes.

Synergistic effects of hyperthermia in preoperative radiochemotherapy for rectal carcinoma.

We investigated the effectiveness of hyperthermia added to preoperative radiation and chemotherapy for the treatment of rectal carcinoma. Forty-one patients receiving preoperative radiation were divided into two groups, Group A (20 patients; receiving radiation, hyperthermia, and chemotherapy) and Group B (21 patients, receiving no hyperthermia). Total dose of radiation was 40.5 Gy. Hyperthermia was administered using 8 MHz of radiofrequency. Rectal temperature reached 42 degrees C. A total dose of 3,400 mg of 5-fluorouracil given by suppository was used as the chemotherapeutic agent. Effect of the preoperative treatment was assessed by tumor reduction on barium enema, histologic findings of the resected specimens, area measurement of the residual cancer tissue, and by silver-staining nucleolar organizer region (AgNOR) score. Tumor reduction on barium enema was significantly greater in Group A than in Group B (P < 0.01). Excluding two cases of mucinous carcinoma because a large acellular mucinous accumulation added materially to the cancerous area, the ratio of residual cancer area to total lesion size in Group A was significantly smaller than in Group B (P < 0.05). AgNOR score of the resected tumor tended to be smaller in Group A than in Group B. Addition of hyperthermia resulted in a greater degree of tumor necrosis and was considered to be useful as a preoperative treatment for rectal carcinoma.

Small Incision Trabeculectomy Avoiding Tenon's Capsule: A New Procedure for Glaucoma Surgery

Wound healing at the level of Tenon's capsule is a common cause of trabeculectomy failure. The purpose of this study is to present a new technique for glaucoma filtering surgery in which an injury to Tenon's capsule is minimized. A 2.5-mm conjunctival peritomy was performed without cutting Tenon's capsule. A partial-thickness incision was made at the limbus and a scleral pocket was dissected 2 to 3 mm posteriorly. The subconjunctival space was entered with a cystotome passed through the scleral pocket, and balanced salt solution (BSS, Alcon Laboratories, Ft. Worth, TX) was injected, forming a subconjunctival bleb. In patients considered high risk, 5-fluorouracil (5 mg) was mixed with the BSS injected. The anterior chamber was entered at the initial limbal incision. A 1.5- by 1-mm fragment of the floor of the pocket was excised, followed by a peripheral iridectomy. The scleral wound, as well as the conjunctiva, was closed with separate 10-0 nylon sutures. This procedure was performed in 30 glaucomatous eyes. Seven high-risk eyes received four to seven postoperative injections of 5 mg of 5-fluorouracil. Preoperative intraocular pressure (IOP) was 34.5 +/- 8.1 mmHg. Postoperative IOP was 13.2 +/- 4.1 at 6 months (P < 0.01), and 90% of the eyes had IOP less than or equal to 18 mmHg without medication. Mean follow-up was 7.6 months (range, 6-14 months). Blebs were low-lying and diffuse. No serious complications were encountered. This new technique is a safe procedure that effectively reduces IOP. It is done through a small incision without sophisticated instruments. More cases and a prospective trial are needed to ascertain its potential advantages over those of conventional trabeculectomy.

Autoradiographic imaging of the distribution of 5-fluorouracil through cervical tissue following in vitro surface application of a bioadhesive cervical patch.

The distribution of 5-fluorouracil through cervical tissue has been assessed following the in vitro application of a bioadhesive patch to excised human cervix. The bioadhesive matrix contained a total of 20 mg of 5-fluorouracil spiked with 5-fluorouracil-6-3H and was applied for fixed periods of either 4 or 24 hours. Tissue slices were sectioned perpendicular to the plane of the applied patch and the autoradiographic image developed by placing a frozen tissue slice on Hyperfilm with subsequent instant thawing and refreezing, the resulting bilayer being maintained at -18 degrees C for 24 hours. The developed image was analysed by scanning densitometry and raster scans were visualised with three-dimensional contouring software. The autoradiograms showed darker areas surrounding tissue ducts, suggesting that 5-FU was spilling from the lumen into the surrounding stroma. Transport of 5FU via aqueous channels may thus make an important contribution to the rapid penetration of the drug through the cervical stroma. Three-dimensional autoradiographic images showed that, for a 4-hour patch application, there were areas of relatively low drug concentration within the upper 5 mm of tissue, where CIN lesions can exist in the glandular tissue or cervical crypts. However, extending the application time to 24 hours produced areas of high drug concentration extending throughout this region.

Prevention of Experimental Proliferative Vitreoretinopathy With a Biodegradable Intravitreal Implant for the Sustained Release of Fluorouracil

To test the efficacy of a biodegradable device for the intravitreal sustained release of fluorouracil in the treatment of tractional retinal detachment due to proliferative vitreoretinopathy. A 6 x 0.9-mm (20-gauge) cylindrical solid implant molded from copolymers of lactide and glycolide admixed with 1 mg of fluorouracil was placed in the vitreous cavity of rabbits in which retinal detachment with proliferative vitreoretinopathy had been initiated. Comparisons of the control (drug-free polymer) and experimental (fluorouracil polymer) groups were made with weekly indirect ophthalmoscopic examinations. In another experiment, the intravitreal concentration of fluorouracil was tested at each time point. Retinas of eight (89%) of nine rabbits that received the polymer with fluorouracil remained attached compared with only one animal (11%) that received the control polymer without the drug. The therapeutic effect of the drug-containing implant was associated with sustained intravitreal concentrations of fluorouracil between 1 and 13 mg/L for at least 14 days, and fluorouracil concentrations remained above 0.3 microgram/mL for almost 21 days. No evidence of the toxic effects of the drug or polymer implant was observed with electroretinographic and histopathologic study. Intravitreal implantation of biodegradable polymers containing fluorouracil can prevent proliferation of epiretinal membranes resulting in complicated retinal detachment in an animal model of proliferative vitreoretinopathy and indicate their possible usefulness for intravitreal delivery of therapeutic agents.

Liquid scintillation spectrometry of 5-fluorouracil in cervical tissue following in vitro surface application of a bioadhesive cervical patch.

The potential use of bioadhesive technology for the treatment of cervical intraepithelial neoplasia was investigated. A cervical patch was designed containing 5-fluorouracil in a bioadhesive matrix and polyvinyl chloride as the backing layer. The concentration of 5-fluorouracil at specified tissue depths from the cervical surface was determined in vitro in relation to the ability of the drug to reach precancerous foci in cervical crypts up to 4 mm below the tissue surface. Thus, tissue was exposed to drug-loaded patches spiked with 5-fluorouracil-6-3H and subsequently sectioned to obtain tissue slices at different depths. The concentration of 5-fluorouracil was determined by liquid scintillation spectrometry. Drug penetration into cervical tissue exceeded a depth of 5.5 mm. Furthermore, the concentration in the tissue depended on the drug loading in the patch. Patches containing 10 and 20 mg of 5-fluorouracil produced a linear drug gradient that was established after a 4 hour application of the patch and persisted over 24 hours. However, patches containing 3.5 mg of 5-fluorouracil displayed signs of drug exhaustion after 24 hours. The penetration characteristics of 5-fluorouracil through cervical tissue using the cervical patch delivery system were sufficiently favourable to warrant further clinical investigations.

Effects of hepatic arterial infusion chemotherapy on unresectable or recurrent hepatocellular carcinoma.

We performed hepatic arterial infusion chemotherapy (HAI) on 86 patients with unresectable hepatocellular carcinoma (HCC, 61 patients) or unresectable recurrent HCC after hepatectomy (25 patients). As drug therapy, 250 mg of 5-fluorouracil was injected daily for 14 days using a reservoir embedded in the subcutaneous layer. During this period, 0.4 mg/kg of doxorubicin and 0.12 mg/kg of mitomycin C suspended in Lipiodol Ultra-Fluide were also injected twice intra-arterially. This was defined as one course of HAI, and it was repeated every 3 months. In the patients with unresectable HCC, the 1-, 2-, and 3-year survival rates were 31.5%, 22.4%, and 10.7%, respectively, and the numbers of cases showing a complete response (CR), a partial response (PR), a minor response (MR), no change (NC), and progressive disease (PD) according to the Criteria for the Evaluation of the Clinical Effects of Solid Cancer Chemotherapy established by the Japan Society for Cancer Therapy were 1 (1.6%), 20 (32.8%), 5 (8.2%), 28 (45.9%), and 7 (11.5%), respectively. On the other hand, the 1-, 2-, and 3-year survival rates of the patients with unresectable recurrent HCC were 69.6%, 34.8%, and 14.9%, respectively. The rate of catheter patency after 1 year was 64.1%, and the mean catheter-patency period was 311.9 days. Patients in group A (CR+PR, n = 21) survived significantly longer than those in group B (MR+NC+PD, n = 40; P < 0.05). In conclusion, since responders to HAI achieve longer survival than nonresponders, the selection of effective drugs is important for this therapy.