Successful Treatment of Intra-Arterial Peplomycin Infusion for Recurrent Oral Florid Papillomatosis

A 56-year-old woman had noticed the erosion of oral mucosa and tongue 8 years ago. The mucosal lesions had been initially diagnosed as oral lichen planus and resistant to various treatments with prednisolone, etretinate and mizoribine and so on. One year ago, rapidly growing verrucous lesion occurred on her upper lip. Although we administered intralesional radiation therapy, the tumor recurred and new whitish lesions on the buccal mucosa and hard palate occurred 9 months after treatment. We confirmed an anatomical blood supply to the tumors by a fluorescent real-time imaging system and subsequently administered the intra-arterial infusion of peplomycin through retrograde catheters from bilateral superficial temporal arteries under the final diagnosis as oral florid papillomatosis (OFP). The tumors were dramatically shrunk and did not recur 16 months after treatment. OFP is known as clinically multiple whitish and verrucous lesions over the oral cavity and lip and a subtype of SCC with high differentiation. We suppose that an intra-arterial infusion therapy of peplomycin should be considered as the curative treatment for OFP.

HIGH DOSE INTRA-ARTERIAL HEPATIC INFUSIONAL CHEMOTHERAPY WITH DRUG FILTRATION (HAI-F) FOR PRIMARY LIVER CANCER(A PRELIMINARY REPORT)

Fifteen patients with unresectable hepatocellular carcinoma were treated with unresectable hepatocellular carcinoma were treated with high dose MMC or ADR via hepatic artery with drug filtration in our hospital from April to December 1988. Among them, 11 cases (73%) had symptoms relief, 3 cases (20%) tumor minimal remission and AFP decreased in 4 cases (33%). One case dide of hep'atoma 8 months after HAI-F and another case was followed up only 2 months after treatment, the remaining 13 cases are alive for 5 to 10 months after HAI-F. The reasons of unsatisfactory results were analyzed and possible ways of improvement were suggested.

Treatment of malignant digestive tract obstruction by combined intraluminal stent installation and intra-arterial drug infusion

AIM To study the palliative treatment of malignant obstrution of digestive tract with placement of intraluminal stent combined with intra-arterial infusion of chemotherapeutic drugs.METHODS A total of 281 cases of digestive tract malignant obstruction were given per oral (esophagus,stomach, duodenum and jejunum), per anal (colon and rectum ) and percutaneous transhepatic ( biliary )installation of metallic stent. Among them, 205 cases received drug infusion by cannulation of tumor supplying artery with Seldingers technique.RESULTS Altogether 350 stents were installed in 281 cases, obstructive symptoms were relieved or ameliorated after installation. Occurrence of restenotic obstruction was 8 - 43 weeks among those with intraarterial drug infusion, which was later than 4 - 26 weeks in the group with only stent installation. The average survival time of the former group was 43 (3 - 105) weeks,which was significantly longer than 15 (3- 24) weeks of the latter group.CONCLUSION Intraluminal placement of stent combined with intra-arterial infusion chemotherapy is one of the effective palliative therapies for malignant obstruction of the digestive tract with symptomatic as well as etiological treatment.

Analysis of the Curative Effect of Preoperative Intra-Arterial Infusion Chemoembolization on Stage IB2-IIB Uterine Cervix Cancer

OBJECTIVETo investigate the short-term and long-termtherapeutic efficacy of preoperative intra-arterial infusion chemo-embolization on stage IB_2-IIB uterine cervix cancer (UCC).METHODS A total of 143 patients with Stage IB_2-IIB UCCwere divided into a clinical trial group and a control group.Thepatients in the clinical trial group(n=86)were treated with acombined therapy,i.e.,preoperative intra-arterial infusion chemo-embolization,surgical therapy and postoperative radiotherapy,and those in the control group (n=57) were given surgical therapyand post-operative radiotherapy.The adverse effects,changes inlocal lesion and pathological examinations of the cancer,and thestate during the surgery were observed after the intra-arterialinfusion chemo-embolization.The survival rate and recurrencerate between the two groups were compared.RESULTS The total effective rate of the intra-arterial infusionchemo-embolization on Stage IB_2-IIB UCC was 93.02%.Thetreatment could reduce tumor size,bring about retro-conversionsof the clinical stage of the tumors and pathological grade of thecancer cells,and decrease the quantity of intra-operative bloodloss as well as the operating time.It could significantly improvethe 5-year survival rate (P<0.05),and reduce the 2 and 5-yeartumor recurrence rates (P<0.05).Moreover,its side effects werelittle.CONCLUSION Preoperative intra-arterial infusion chemo-embolization can create conditions for radical operation,lower thepostoperative recurrence rate,and improve the prognosis in thepatients with UCC.It is an effective therapy in treating UCC.

Efficacy of intra-arterial contrast-enhanced ultrasonography during transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma

AIM To assess the usefulness of intra-arterial contrastenhanced ultrasonography(IAUS) during transarterial chemoembolization(TACE) with drug-eluting beads(DEB) for hepatocellular carcinoma(HCC).METHODS Thirty two patients with 39 HCC underwent DEB-TACE guided with IAUS, and examined by contrast-enhanced ultrasonography(CEUS) or dynamic CT after DEB-TACE were enrolled in this study. CEUS findings before DEBTACE and IAUS findings were compared. Treatments judged to be complete and incomplete for lesions were appropriate and insufficient, respectively. Findings on CEUS and/or dynamic CT performed 1, 3 and 6 mo after DEB-TACE were evaluated using m RECIST(CR/PR/SD/PD).RESULTS The treatments were complete and incomplete in 26 and 13 lesions, respectively. On imaging evaluation using CEUS and/or dynamic CT one month after treatment, 25 and 1 lesions were judged to be CR and PR, respectively, and at 6 mo after treatment, the results were CR, PR, SD and PD for 24, 1, 0 and 1 of these lesions, respectively, in the 26 completely treated lesions. Of the 13 lesions in which treatment was incomplete, the results on imaging at one month after treatment were CR, PR, SD and PD for 0, 6, 4 and 3 lesions, respectively. The overall CR rate at 6 mo after treatment was 61.5%(24/39).CONCLUSION A combination of DEB-TACE with IAUS can improve the therapeutic effects in patients with HCC.

Use of intra-arterial chemotherapy for retinoblastoma:results of a survey

·AIM: To obtain baseline knowledge about the current use of intra-arterial chemotherapy(SSOAIC) in centers worldwide.·METHODS: A survey including questions about the use of SSOAIC was emailed to retinoblastoma experts.·RESULTS:Seventy-nine(response rate 69.9%) doctors from 63 centers in 35 countries responded. Thirty-one centers from 19 countries use SSOAIC. Twelve performed more than 50 procedures. Melphalan is the most commonly used drug but 15 centers use more than one drug. First line therapy for advanced unilateral disease is the most common use of SSOAIC(74.2%). Centers with larger experience(】50 applications) were less likely using melphalan alone(P =0.06) and significantly more likely using SSOAIC in more situations such as second line in preference to radiotherapy P =0.05. Nineteen(61.2%)stated that SSOAIC improved their results and 21(77.8%)reported less toxicity compared to other treatments.Three centers reported that SSOAIC did not improve their results. There were regional variations in the use of SSOAIC which is used more frequently as secondary treatment in Europe compared to the USA and Japan.Ten centers identified cost is the major limiting factor for SSOAIC.· CONCLUSION: SSOAIC is used in an increasing number of centers worldwide with regional variations.Centers with more experience in SSOAIC use it in more situations including other drugs than melphalan. The majority of the centers using this technique reportedimproved results and few complications.

Combined intra-arterial chemotherapy and intravitreal melphalan for the treatment of advanced unilateral retinoblastoma

●AIM:To evaluate the efficacy and safety of combined intraarterial chemotherapy(IAC)and intravitreal melphalan(IVM)for the treatment of advanced unilateral retinoblastoma.●METHODS:This retrospective study involved 30 consecutive eyes from 30 Chinese patients with advanced unilateral retinoblastoma.All patients were initially treated with IAC combined with IVM.The clinical status and complications were recorded at each visit.●RESULTS:The International Intraocular Retinoblastoma Classification groups were D in 23 eyes and E in 7 eyes.All eyes showed severe cloud vitreous seeds at the first visit.The mean number of IAC cycles and intravitreal injections was 3.2(range,3-4)and 6(range,1-14),respectively.The median follow-up time was 29 mo(range,7-36 mo).Treatment success with regression of the retinal tumor and vitreous seeds was achieved in 29 of 30 eyes(96.7%).Globe salvage was attained in 93.3%(28/30)eyes,and enucleation(n=2)was per formed due to neovascular glaucoma and persistent vitreous hemorrhage.Complications included retinal pigment epithelium(RPE)atrophy(n=13;43%),mild lens opacity(n=7;23%),vitreous hemorrhage(n=5;17%)and rhegmatogenous retinal detachment(n=1;3%).No extraocular tumor extension or metastasis occurred.●CONCLUSION:Combined IAC and IVM is effective and safe for the treatment of advanced unilateral retinoblastoma.

Intra-arterial thrombolysis for early hepatic artery thrombosis after liver transplantation

BACKGROUND Early hepatic artery thrombosis(E-HAT)is a serious complication after liver transplantation(LT),which often results in graft failure and can lead to patient deaths.Treatments such as re-transplantation and re-anastomosis are conventional therapeutic methods which are restricted by the shortage of donors and the patient’s postoperative intolerance to re-laparotomy.Due to the advances in interventional techniques and thrombolytics,endovascular treatments are increasingly being selected by more and more centers.This study reviews and reports our single-center experience with intra-arterial thrombolysis as the first choice therapy for E-HAT after deceased donor LT.AIM To evaluate the feasibility and reasonability of intra-arterial thrombolysis for EHAT after deceased donor LT.METHODS A total of 147 patients who underwent deceased donor LT were retrospectively reviewed in our hospital between September 2011 and December 2016.Four patients were diagnosed with E-HAT.All of these patients underwent intraarterial thrombolysis with alteplase as the first choice therapy after LT.The method of arterial anastomosis and details of the diagnosis and treatment of EHAT were collated.The long-term prognosis of E-HAT patients was also recorded.The median follow-up period was 26 mo(range:23 to 30 mo).RESULTS The incidence of E-HAT was 2.7%(4/147).E-HAT was considered when Doppler ultrasonography showed no blood flow signals and a definite diagnosis was confirmed by immediate hepatic arterial angiography when complete occlusion of the hepatic artery was observed.The patients were given temporary thrombolytics(mainly alteplase)via a 5-Fr catheter which was placed in the proximal part of the thrombosed hepatic artery followed by continuous alteplase using an infusion pump.Alteplase dose was adjusted according to activated clotting time.The recanalization rate of intra-arterial thrombolysis in our study was 100%(4/4)and no thrombolysis-related mortality was observed.During the follow-up period,patient survival rate was 75%(3/4),and biliary complications were present in 50%of patients(2/4).CONCLUSION Intra-arterial thrombolysis can be considered first-line treatment for E-HAT after deceased donor LT.Early diagnosis of E-HAT is important and follow-up is necessary even if recanalization is successful.

Aluminum Contents in Dry Leaves and Infusions of Commercial Black and Green Tea Leaves: Effects of Sucrose and Ascorbic Acid Added to Infusions

Tea consumption has increased due to its beneficial effects. Results from a lab study on the effect of sucrose (5 g per cup, 150 mL) and/or ascorbic acid (2 mL per cup, 150 mL) on dissolved aluminum compounds during the infusion of two commercial types of dry tea leaves (black, green) with boiling water (5, 15 min infusion time) are presented. Factors influencing the presence of dissolved aluminum in the infusions of both tea leaves were infusion time and sugar contents, as well as the interaction between ascorbic acid and sucrose (p < 0.05). Aluminum contents found after 15 min of infusion were 0.7 mg L–1 for black tea infusions added with sugar, and 0.69 mg L–1 for green tea added with both sugar and ascorbic acid. Both concentrations are higher than the level accepted in Mexico for drinking water (there is no act concerning tea infusions), that is 0.2 mg L–1.

A mimic of soft tissue infection: intra-arterial injection drug use producing hand swelling and digital ischemia

BACKGROUND: Inadvertent intra-arterial injection of illicit substances is a known complication of injection drug use and can lead to severe complications, including infection, ischemia and compartment syndrome. Identifying complications of intra-arterial injection can be difficult, as clinical manifestations overlap with other more common conditions such as cellulitis and soft tissue infection, and a history of injection drug use is frequently not disclosed.METHODS: A 37-year-old male patient presented with 24 hours of right hand pain, erythema and swelling. Despite classic "track marks", he denied a history of injection drug use, and vascular insults were not initially considered. After failing to respond to three days of aggressive treatment for suspected deep-space infection, an arteriogram demonstrated findings consistent with digital ischemia of embolic etiology.RESULTS: As a result of the delay in diagnosis, the lesion was not amenable to reperfusion and the patient required amputation of the distal digit.CONCLUSION: Practitioners should be alert to the possibility of intra-arterial injection and resulting complications when evaluating unusual extremity infections or unexplained ischemic symptoms, even in the absence of a definite history of injection drug use.

Intra-arterial chrono-chemotherapy for liver metastasis arised from colorectal cancer

Objective To evaluate the toxic effects and efficacy of the intra-arterial chrono-chemotherapy on patients with liver metastasis arised from colorectal cancer. Methods Chemotherapy of 42 patients were randomly divided into group A (n = 20) with continuously constant arterial infusion, and group B (n = 22) with arterial chrono-modulated infusion. And the toxic effects and efficacy of two groups were compared. Results A significant difference was found in the toxic effects of digestive system between the two groups. The treatment response was similar in the two groups. Conclusions Intra-arterial chrono-chemotherapy may decrease the toxic effects and improve the life quality of these patients. (J Intervent Radiol, 2006, 15: 487-490)

Prognostic value of post-treatment ^(18)F-FDG PET/CT for advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy

Objective：To clarify the prognostic value of post-treatment 18F-fluorodeoxyglucose （FDG） positron emission tomography （PET）/computed tomography （CT） in patients with advanced head and neck squamous cell carcinoma （HNSCC） after combined intra-arterial chemotherapy and radiotherapy （IACR）.Methods：Thirty-six patients with HNSCC who underwent IACR were recruited.The period from the end of IACR to the last post-treatment 18F-FDG PET/CT examination was 8-12 weeks.Both patient-based and lesion-based analyses were used to evaluate the PET/CT images.For lesion-based analysis,36 regions （12 lesions of recurrences and 24 scars at primary sites） were selected.The Kaplan-Meier method was used to assess the overall survival （OS） stratified by 18F-FDG uptake or visual interpretation results.Results：Twelve patients with recurrence were identified by six months after IACR.The sensitivity and specificity in the patient-based analysis were 67％ （8/12） and 88％ （21/24）,respectively.The mean OS was estimated to be 12.1 months （95％ CI,6.3-18.0 months） for the higher maximum standardized uptake value （SUVmax） group （n=7） and 44.6 months （95％ CI,39.9-49.3 months） for the lower SUVmax group （n=29）.OS in the higher SUVmax group （cut-off point,6.1） or positive visual interpretation group was significantly shorter than that in the lower SUVmax or negative visual interpretation group （P＜0.001 and P＜0.05,respectively）.Conclusions：The SUVmax and visual interpretation of HNSCC on post-IACR 18F-FDG PET/CT can provide prognostic survival estimates.

Survival in unresectable sinonasal undifferentiated carcinoma treated with concurrent intra-arterial cisplatin and radiation

We report the successful use of RADPLAT to treat a patient with an unresectable T4N0 sinonasal undifferentiated carcinoma. This patient received 4 cycles of weekly intra-arterial cisplatin together with thiosulfate infusion with concurrent radiation therapy. Radiation therapy was given in 28 daily fractions to 54 Gy using intensity-modulated radiation therapy followed by a hypofractionated stereotactic boost of 3 fractions to 13 Gy to a total dose of 67 Gy in 31 fractions to the nasal sinus and bilateral neck. Intra-arterial cisplatin was administered using a bilateral approach due to the midline site of this tumor. Within days of the first intra-arterial cisplatin, there was an obvious decrease in tumor size. She has been followed with magnetic resonance imaging and positron emission tomography, and remains disease-free 47 mo post-treatment. Centers with expertise in intra-arterial chemotherapy could consider the RADPLAT approach for patients with unresectable sinonasal undifferentiated carcinoma.

Accidental Intra-Arterial Injection during Test Dose of Injection of Benzyl Penicillin: Complications and Management—A Case Report

An 18 years old female patient was given a test dose of Benzyl penicillin in the Antecubital Area on the right forearm by a staff nurse of the department. After the injection, the patient complained of severe pain in the right forearm distal to the injection site. This was followed by blanching of the right forearm and hand. She was immediately heparinised followed by other symptomatic treatments. After 12 hours, a bluish discoloration developed on the hand, both on dorsal and palmar aspect, sparing the thumb. This recovered with medication, except the late development of dry gangrene of the tip of distal phalanx of the little finger which got shrivelled later on. Color Doppler flow study, echocardiography, and CT angiography of the right upper limb were done. Understanding of the pathogenesis and prompt action can help in saving a limb. Education of the medical professionals involved in administering injection is necessary so that they become aware of abnormal course or anomalous anatomy of vessels of upper limb. This can help to prevent the complications.

Effect of local massage on prevention and treatment of intra-arterial polymethyl methacrylate embolism complications:An experimental animal study

Background:Massage is generally believed to be a simple and effective method for preventing necrosis when intravascular injection emboli are suspected.Due to its good dispersive properties,polymethyl methacrylate(PMMA)was used as the test filler.The main purpose of this study was to observe whether local massage as a simple remedial measure can promote the diffusion of filler and reduce the necrosis rate for intra-arterial embolism.Methods:Rabbit ears with the central ear artery(CEA)main trunk totally or segmentally obstructed 5 min after PMMA injection were studied.In order to simulate the massage effect of the fingers,the massage group was treated with a small beauty massage bar with a fixed vibration frequency along the direction of the blood flow.CEA blood flow and skin lesions were also analyzed.Results:The baseline data were similar between the control and massage groups.Compared to the control group,the recanalization rate of the CEA trunk in the treatment group increased significantly after massage.However,there was no significant difference in the visible rate of transparent embolus on the 1st day after treatment,nor in the necrosis degree or area of soft tissue damage on the 7th day after treatment.Further analysis showed that massage tended to have a positive effect on segmentally obstructed cases at 5 min after injection but a negative effect on totally obstructed ears at 5 min.Conclusion:Local massage cannot reduce the complications of tissue necrosis after intra-arterial PMMA injection.Prevention is key to reducing complications.

Intra-Arterial Chemotherapy for Retinoblastoma

The management of retinoblastoma is challenging and complex. Preservation of the eyeball as well as vision, with minimum morbidity, is the aim in the initial stages. This has been made possible by the use of chemotherapy that is targeted to the eye in the form of selective intravitreal and intra-arterial chemotherapy which has shown promising results. The efficacy and safety of intra- arterial chemotherapy have been reported by many specialized centers. The aim of this article was to review the role of intraarterial chemotherapy in the management of retinoblastoma and its clinical outcomes. In addition, we will review the possible complications of the procedure. We were able to collect articles relevant to our research objectives by reviewing the title and abstract of each article. Irrelevant articles and those that did not meet the inclusion criteria were excluded. This yielded a total of 19 studies. The results indicated that intraarterial chemotherapy is an effective and new modality of treatment for retinoblastoma to salvage the eyeball and helps in the prevention of enucleation with minimal local and systemic complications that are mostly transient. For future work, we recommend conducting more prospective studies with large samples and the long duration of follow-up. Also, we recommend future studies focusing on assessing visual acuity, as most of the currently available studies did not assess the visual acuity, making the judgment on vision preservation with IAC difficult.

Different effects of mechanical embolus removal and intra-arterial thrombolysis on neural functional recovery in patients with acute middle cerebral artery occlusion

Objective:To study the different effects of mechanical embolus removal and intra-arterial thrombolysis on neural functional recovery in patients with acute middle cerebral artery occlusion.Methods: Patients with acute middle cerebral artery occlusion who were treated in the First Hospital of Yulin between September 2013 and October 2017 were selected and retrospectively studied, and the differences in reperfusion therapies in history data were referred to divide them into study group A and study group B who underwent mechanical embolus removal and intra-arterial thrombolysis respectively. The levels of neurocyte damage markers, apoptosis markers and stress markers in serum as well as the expression of Wnt pathway molecules in peripheral blood were determined before treatment and 24 h after treatment.Results: Compared with those of same group before treatment, serum NSE, S100B, VILIP1, sFas, sFasL, ET-1 and MDA levels as well as peripheral blood GSK3β, LC3-II and Beclin1 expression intensity of both groups were decreasing whereas serum BDNF, NTF, sLivin and SOD levels as well as peripheral bloodβ-catenin and mTOR expression intensity were increasing, and serum NSE, S100B, VILIP1, sFas, sFasL, ET-1 and MDA levels as well as peripheral blood GSK3β, LC3-II and Beclin1 expression intensity of study group A after treatment were lower than those of study group B whereas serum BDNF, NTF, sLivin and SOD levels as well as peripheral bloodβ-catenin and mTOR expression intensity were higher than those of study group B.Conclusion: Mechanical embolus removal for acute middle cerebral artery occlusion can be more effective than intra-arterial thrombolysis to reduce the nerve function damage as well as the corresponding oxidative stress and apoptosis.

Accelerated infliximab infusions for inflammatory bowel disease improve effectiveness

AIM:To study the safety and effectiveness associated with accelerated infliximab infusion protocols in patients with inflammatory bowel disease(IBD).METHODS:Original protocols and infusion rates were developed for the administration of infliximab over 90-min and 60-min.Then the IBD patients on stable maintenance infliximab therapy were offered accelerated infusions.To be eligible for the study,patients needed a minimum of four prior infusions.An initial infusion of 90-min was given to each patient;those tolerating the accelerated infusion were transitioned to a 60-min infusion protocol at their next and all subsequent visits.Any patient having significant infusion reactions would be reverted to the standard 120-min protocol.A change in a patient's dose mandated a single 120-min infusion before accelerated infusions could be administered again.RESULTS:The University of Virginia Medical Center's Institutional Review Board approved this study.Fifty IBD patients treated with infliximab 5mg/kg,7.5mg/kg and 10mg/kg were offered accelerated infusions.Forty-six patients consented to participate in the study.Nineteen(41.3%) were female,five(10.9%) were African American and nine(19.6%) had ulcerative colitis.The mean age was 42.6 years old.Patients under age 18 were excluded.Ten patients used immunosuppressive drugs concurrently out of which six were taking azathioprine,three were taking 6-mercaptopurine and one was taking methotrexate.One of the 46 study patients used corticosteroid therapy for his IBD.Seventeen of the patients used prophylactic medications prior to receiving infusions;six patients received corticosteroids as pre-medication.Four patients had a history of distant transfusion reactions to infliximab.These reactions included shortness of breath,chest tightness,flushing,pruritus and urticaria.These patients all took prophylactic medications before receiving infusions.46 patients(27 males and 19 females) received a total of fifty 90-min infusions and ninety-three 60-min infusions.No infusion reactions were reported.There were no adverse events,including drug-related infections.None of the patients developed cancer of any type during the study timeframe.Total cost savings for administration of the both 90-min and 60-min accelerated infusions compared to standard 120-min infusions was estimated to be $53 632($116 965 vs $63 333,P=0.001).One hundred and eighteen hours were saved in the administration of the accelerated infusions(17 160 min vs 10 080 min,P=0.001).In the study population,overweight females [body mass index(BMI)>25.00kg/m2] were found to have statistically higher BMIs than overweight males(mean BMI 35.07±2.66kg/m2 vs 30.08±0.99kg/m2,P=0.05),finding which is of significance since obesity was described as being one of the risk factors for Crohn's disease.CONCLUSION:We are the first US group to report substantial cost savings,increased safety and patient satisfaction associated with accelerated infliximab infusion.

Efficacy of second-course intra-arterial chemotherapy in children for advanced retinoblastoma recurrence after intra-arterial chemotherapy

Purpose: The present study determined the efficacy and toxicity of second-course intra-arterial chemotherapy(IAC) in advanced retinoblastoma(RB) recurrence in children following failed initial IAC. Materials and Methods: A total of 24 child patients with unilateral or bilateral intra-ocular advanced RB(IIRC Group D and Group E) undergoing second-course IAC treatment after initial intra-arterial chemotherapy between September 2011 and November 2016 were enrolled. Global salvage, ocular adverse events, and systemic adverse events were assessed. Results: Following second-course IAC, 15(62.5%) showed complete control at 34 months follow-up, while 8 cases(33.3%) failed the treatment and 1 patient with metastatic disease(4.2%) eventually died of brain metastasis after refusing treatment. Ocular adverse events included eyelid edema(n=12), ptosis(n=5), forehead erythema(n-5), enophthalmos(n=3), and cataract(n=2). None of the patients had systemic adverse events, such as stroke or sepsis. Also, no secondary neoplasms and technical complications were observed. Conclusion: Second-course IAC is a potential alternative to enucleation in children with advanced RB, who fail an initial course of IAC. However, patients with advanced RB should be managed at experienced centers in order to consider all the alternatives before enucleation.

Real-Time Analytical Solutions as Series Formulas and Heaviside off/on Switch Functions for Multiple Intermittent Intravenous Infusions in One- and Two-Compartment Models

Pharmacokinetic compartment models are the only models that can extract pharmacokinetic parameters from data collected in clinical studies but their estimates lack accuracy, explanations and physiological significance. The objective of this work was to develop particular solutions to drug concentration and AUC in the form of mathematical series and Heaviside functions for repetitive intermittent infusions in the one- and two-compartment models, as a function of dose number and total time using differential calculus. It was demonstrated that the central and peripheral compartment volumes determined from regression analysis of the aminoglycoside antibiotic Sisomicin concentration in plasma represent the actual physiological body fluid volumes accessible by the drug. The drug peak time and peak concentration in the peripheral compartment were also calculated as a function of dose number. It is also shown that the time of intercompartmental momentary distribution equilibrium can be used to determine the drug’s apparent volume of distribution within any dosing interval in multi-compartment models. These estimates were used to carry out simulations of plasma drug concentration with time in the one-compartment model. In conclusion, the two-compartment open mammillary pharmacokinetic model was fully explained for the aminoglycoside antibiotic sisomicin through the new concept of the apparent volume of distribution.