Formalin Instillation Research Articles

Endorectal formalin instillation or argon plasma coagulation for hemorrhagic radiation proctopathy therapy: a prospective and randomized clinical trial

Radiotherapy may cause hemorrhagic radiation proctopathy (HRP). For conservative treatment of refractory HRP, argon plasma coagulation (APC) is the first-choice therapy. Endorectal formalin instillation (EFI), in turn, is an attractive treatment option because of its satisfactory results, great availability, and low cost. Nevertheless, comparative studies between these procedures are rather scarce. This study aims to make a prospective and randomized comparison of the outcomes in 2 HRP patient groups treated with either APC or EFI. Twenty-seven patients (11 women), with a mean age of 67 years (range, 36-83), were randomized to receive either APC (n= 14) or EFI (n= 13). On completion of the treatment, comparisons were made in relation to the baseline for each patient and between groups for endoscopic findings according to the Vienna score and the telangiectasia distribution pattern score (TDP); the impact of radiation proctitis on patients' lives was made according to the modified radiation toxicity score (MRTS) and hemoglobin levels. Number of sessions, duration of therapy, and adverse events were also compared between groups. The endoscopic therapeutic success (ETS) was defined by the absence or only few residual telangiectasias (TDP≤1) on conclusion. An ETS of 92.8% was achieved in patients treated with APC and 92.3% for those treated with EFI (P > .05); there was an MRTS improvement of 85.7% in APC patients and 69.2% in EFI patients (P > .05). Mild adverse events occurred, respectively, in 23% and 28.5% in the EFI and APC groups (P > .05). The study showed that APC and EFI have similar efficacy and a high safety profile for HRP treatment. (Clinical trial registration number: 3.120.353.).

AMPK Activation Improves Survivability after Toxic Gas Exposure

IntroductionInhalation injury caused by irritant gases such as smoke, ozone, chlorine and bromine (Br2) results in an environmental and occupational hazards that leads to reactive airway disease syndrome (RADS), acute lung injury (ALI), and even death from respiratory failure. Development of interventional therapeutic agents, which when given post exposure, prevent acute inhalation injury and decrease mortality are urgently needed. AMP‐activated protein kinase (AMPK) is a metabolic sensor that maintains cellular ATP levels during metabolic stress. AMPK also acts independently of AMP and enhances vascular integrity by preventing actin stress fiber formation and limiting changes in cell morphology necessary for increased endothelial permeability. Here in the current study we tested the hypothesis that a single injection of an AMPK activator, such as 5‐aminoimidazole‐4‐carboxamide‐1‐beta‐D‐ribofuranoside (AICAR), administered intraperitoneally to C57BL/6 mice, post exposure to a lethal dose of inhaled Br2, decreases lung injury and mortality.MethodsC57BL/6 mice were exposed to Br2 (600 ppm, 45min) in environmental glass chambers and then returned to room air. Control mice breathed ambient air throughout this protocol. Six hours after exposure to Br2, mice were treated with either AICAR (10 mg/kg BW, intraperitoneally) or vehicle (Earle's balanced salt solution. Next seven days mice were monitored at interval of six hours. In another set of experiments, mice were sacrificed 24 hours post Br2 inhalation and were either lavaged with one ml of normal saline for protein and inflammatory cell counts or their lungs were fixed by instillation of formalin at 25 cm H20; and processed for histology.ResultsThe analysis of the Kaplan Meier survival curve showed that Br2 exposed mice developed progressive respiratory distress. Median survival after Br2 exposure was one day. However, mice receiving AICAR had a median survival of six days. Exposure to Br2 caused significant increase in total protein and number of inflammatory cells in BALF at 24 hours post exposure, consistent with severe injury to the blood gas barrier. AICAR returned these values to their corresponding air controls. Br2 exposure significantly reduced the level of AMPK phosphorylation whereas AICAR treatment brought its level to normal in animal lungs. Lung H&E staining showed that AICAR attenuated Br2‐induced lung edema, alveolar congestion, septal thickening, neutrophil infiltration, hyaline membrane and perivascular cuffing. Results also showed that AICAR enhanced autophagy, which was significantly reduced after Br2 exposure suggesting a possible mechanism of AICAR‐mediated cyto‐protection.ConclusionsIn conclusion data suggest that activation of lung AMPK might be a useful target for a therapeutic intervention to reverse Br2‐induced acute lung injury.Support or Funding InformationThis study was supported by 1U01ES027697‐01 and 5U01ES026458‐02 to S. Matalon.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Four percent formalin application for the management of radiation proctitis in carcinoma cervix patients: An effective, safe, and economical practice.

Radiotherapy is a very effective treatment modality for pelvic malignancies such as carcinoma of the cervix. However, it is quite common for chronic radiation proctitis (CRP) to manifest after radical radiotherapy. CRP is a source of significant morbidity, and there is a lack of effective treatment modalities. There also exists a general lack of guidelines on management of CRP. To assess the benefit from 4% formalin application for the treatment of Grade >2 CRP among patients previously treated with radical radiotherapy for cervical carcinoma. This retrospective descriptive study involved 29 eligible patients who were treated from November 2010 - November 2015 for CRP with 4% formalin application. Of the 1864 patients of carcinoma cervix treated during the said patients, 29 patients fulfilled the eligibility criteria. Eligible patients were invited telephonically for follow-up and were assessed for response and complications of the procedure. The treatment of hemorrhagic radiation proctitis with local formalin instillation is effective, well tolerated and safe procedure. The procedure is inexpensive, technically simple and can be done on an outpatient basis. 62% patients had complete freedom from rectal bleed, while 34.5% patients had partial benefit. Only one patient required diversion colostomy for persistent bleeding.

A Case of Formalin Instillation Secondary to Refractory Gross Hematuria in a Patient with Radiation Cystitis

A Case of Formalin Instillation Secondary to Refractory Gross Hematuria in a Patient with Radiation Cystitis

When Radiation Proctitis Gets Way Complicated

Radiotherapy is an essential treatment modality for prostate cancer. However, radiation proctitis (RP) is a common complication, with 40% developing rectal hemorrhage. Previous successful experiences in treating cystitis has led to the use of formalin as a treatment modality. Although there have been few published reports of formalin use for RP in the literature, most results show that it is safe and effective. Unusual complications such as fistulae, anal stenosis and colitis have been rarely reported. A 61-year-old man with medical history of prostate cancer status-post radiation therapy completed 6 months ago presented with a 2-week history of rectal bleeding and tenesmus. He denied fever, use of antibiotics, weight loss or previous GI bleeding. Digital rectal exam was painful and with evidence of blood clots. Initial labs showed iron deficiency anemia. Patient underwent colonoscopy which showed a large erythematous ulcerated lesion that extended from anal verge up to 10cm and covered 70% of diameter (Figure 1). Histologic exam was consistent with RP and negative for rectal carcinoma. Initially, patient was provided with supportive management with hydration and steroid enemas. However, he developed progression of symptoms with intractable rectal bleeding requiring multiple blood transfusions as well as severe rectal pain. Pelvic MRI showed bilaterally myositis of the obturator internus and pectineus muscles suggestive of radiation induced myositis. Given severity of symptoms, General Surgery proceeded with rectal instillation of 4% formalin which was unsuccessful for which diverting Loop Colostomy was performed. Patient showed improvement of symptoms until a few days later when he developed hematochezia, fever and leukocytosis. Abdominal CT revealed inflammatory colitis suggestive of formalin-induced colitis which resolved with antibiotics and hydration. Follow up colonoscopy was performed for possible re-connecting surgery which showed anal canal stenosis with 99% of lumen occluded (Figure 2). Patient was referred to Colorectal surgeon whom performed multiple dilations with resolution of stenosis. In this case, anal stenosis and colitis were a complication of formalin instillation as therapy for RP. Both complications are very rare and few cases have been published in which a clinical scenario mirroring our patient presentation and outcome are described. Awareness of rarely described complications is essential for early recognition and treatment.Figure: Large erythematous ulcerated lesion.Figure: Anal canal stenosis.

Involvement of neurokinin 1 receptor within the cerebrospinal fluid‑contacting nucleus in visceral pain.

Studies have shown that the cerebrospinal fluid‑contacting nucleus (CSF‑CN) may be associated with the transduction and regulation of pain signals. However, the role of the CSF‑CN remains to be elucidated. Emerging evidence has suggested that neurokinin 1 receptor (NK1R) is important in the development of visceral pain and hyperalgesia, however, whether NK1R exists in the CSF‑CN and its exact role in visceral pain remain to be fully elucidated. In the present study, double‑labeled immunofluorescence staining and western blot analysis were performed to investigate this. It was revealed that NK1R was distributed in the CSF‑CN. Following the induction of visceral pain by formalin instillation, NK1R in the CSF‑CN was upregulated. In addition, by observing the behaviors of rats subjected to visceral pain, it was found that visceral pain was relieved by lateral intracerbroventricular injection of the NK1R antagonist, RP67580. These data provided a broader understanding of the role of NK1R in the CSF‑CN and demonstrated that the CSF‑CN was involved in acute visceral pain via the regulation of NK1R.

MP23-13 TRANSFUSION-DEPENDENT GROSS HEMATURIA REQUIRING SURGICAL MANAGEMENT: ARE OUTCOMES WORSE AMONG PATIENTS WITH PREVIOUS PELVIC RADIATION?

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II1 Apr 2017MP23-13 TRANSFUSION-DEPENDENT GROSS HEMATURIA REQUIRING SURGICAL MANAGEMENT: ARE OUTCOMES WORSE AMONG PATIENTS WITH PREVIOUS PELVIC RADIATION? Matthew D Grimes, Brady L Miller, Tyler Wittmann, Sarah E McAchran, David F Jarrard, Wade A Bushman, Daniel H Williams, Tracy M Downs, Kyle A Richards, Sara L Best, and E. Jason Abel Matthew D GrimesMatthew D Grimes More articles by this author , Brady L MillerBrady L Miller More articles by this author , Tyler WittmannTyler Wittmann More articles by this author , Sarah E McAchranSarah E McAchran More articles by this author , David F JarrardDavid F Jarrard More articles by this author , Wade A BushmanWade A Bushman More articles by this author , Daniel H WilliamsDaniel H Williams More articles by this author , Tracy M DownsTracy M Downs More articles by this author , Kyle A RichardsKyle A Richards More articles by this author , Sara L BestSara L Best More articles by this author , and E. Jason AbelE. Jason Abel More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.741AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Gross hematuria requiring blood transfusion is uncommon, and few studies have evaluated management or long term outcomes after initial surgical treatment. Here, we characterize patients undergoing surgical management of transfusion dependent hematuria and evaluate post-surgical outcomes. We hypothesized that patients who had received prior pelvic radiation would have worse postoperative outcomes. METHODS Following IRB approval, comprehensive clinical information was collected and analyzed for patients with hematuria requiring blood transfusion and inpatient surgical management from 2000-2015. RESULTS Seventy patients requiring surgery for transfusion dependent hematuria were identified, including 30 (42.9%) who had received prior pelvic radiation. Hematuria was due to radiation cystitis in 20 (28.6%), post operative bleeding in 12 (17.1%), traumatic catheterization in 10 (14.3%), benign prostatic bleeding in 6 (8.57%), bladder cancer in 5 (7.14%), prostate cancer in 5 (7.14%), hemorrhagic cystitis in 4 (5.71%), and other causes in 8 (11.4%) patients. All 70 patients underwent cystoscopy with clot evacuation and fulguration. Concomitant operations performed included formalin instillation in 7, TURBT in 8, suprapubic tube placement in 4, and ligation of the bulbar arteries in 1 patient(s). Radiated patients were on average 9.3 years older than their non-radiated counterparts (p=0.01). Otherwise no significant differences were identified in baseline characteristics or with regards to LOS, 90 day readmission rate, or likelihood of indwelling catheterization at discharge (Table). At median follow up of 10.9 (IQR 3.7-26.5) months, radiated patients required on average 1.9 additional surgical procedures compared to 1.4 without prior radiation (p=0.21). Previously radiated patients were more likely to require long term urinary diversion compared to non-radiated patients, 9 (31.0%) versus 3 (8.3%) patients (p=0.02). CONCLUSIONS Pelvic radiation is a common etiology for transfusion dependent hematuria. While initial post-operative outcomes were similar, one third of patients with transfusion dependent hematuria and prior radiation required urinary diversion for long term management. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e298 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Matthew D Grimes More articles by this author Brady L Miller More articles by this author Tyler Wittmann More articles by this author Sarah E McAchran More articles by this author David F Jarrard More articles by this author Wade A Bushman More articles by this author Daniel H Williams More articles by this author Tracy M Downs More articles by this author Kyle A Richards More articles by this author Sara L Best More articles by this author E. Jason Abel More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PWE-113 One Year Experience of A New Chronic Radiation Proctopathy Specialist Service

Introduction Chronic radiation proctopathy (CRP) is a recognised complication of pelvic radiotherapy. Symptoms include diarrhoea, rectal pain, bleeding and tenesmus. In 2014, we set up an enhanced, dedicated, multidisciplinary, specialist service for managing the gastro-intestinal (GI) complications of CRP, based on The Royal Marsden Protocol. 1 Here we review the management of CRP at a tertiary referral centre over one year. Methods Patients with CRP reported at lower GI endoscopy (December 2014–15), were identified by an Endoscopy Database search for ‘radiation’. Case notes were reviewed. Indication for procedure, previous cancer and radiotherapy, endoscopy findings, treatment and outcomes were recorded. Results 86 patients had endoscopic evidence of CRP. M:F ratio 8:1. Cancer history: prostate 87% (75), cervical 6% (5), rectal 4% (3), bladder 1% (1), ovarian 1% (1), endometrial 1% (1). Mean time since radiotherapy: 4.5 years (range: 1–13 years). 24% (21) were referred via the 2 WW pathway and 16% (14) by the bowel cancer screening program (BCSP). 23% (20) were identified during surveillance colonoscopies for cancer/ polyps or colitis. 36% (31) were referred from GI clinic. Indications: rectal bleeding 47% (40), change in bowel habit 5% (4), iron deficiency anaemia (IDA) 8% (7) and faecal occult blood 16% (14). 41% (35) were asymptomatic. 27% (23) required intervention for CRP (haemorrhagic angiectasia with rectal bleeding causing anaemia and/or significant impact on quality of life). Sucralfate enemas 2 g bd, ± metronidazole oral 400 mg tds, ± Normacol were prescribed. 65% (15/23) were referred to a Specialist Nurse for follow up, 53% (8/15), of which, responded to medical therapy within 8 weeks. One patient was unable to tolerate sucralfate enemas. 13% (3/23) patients required escalation to rectal formalin instillation. ‘ Off protocol’, 7% (6) were treated with Argon Plasma Coagulation (APC) as their index therapy. A solitary rectal ulcer was found in 5% (4) of patients, two were a complication of APC. Two patients were referred for hyperbaric oxygen therapy. 62% of patients did not require any therapeutic intervention. Conclusion A significant number of patients with CRP are now referred via 2 WW and BCSP. Full colonoscopic assessment is appropriate to exclude other pathology, however, the majority do not require medical or endoscopic intervention, many are asymptomatic and few have IDA. For patients that require intervention for CRP, a multidisciplinary approach should be employed, medical therapy is effective and well tolerated, endoscopic intervention should be reserved for individuals who fail medical treatment. APC should only be used in carefully selected cases due to risk of ulceration. CRP services should be audited to ensure appropriate management and minimise complications. Reference 1 Frontline Gastroenterol (2015) 6 (1): 53–72. Disclosure of Interest None Declared

Endoscopic and non-endoscopic approaches for the management of radiation-induced rectal bleeding.

Pelvic radiation is a commonly utilized treatment for malignancy of the genitourinary and lower gastrointestinal tract. Radiation proctitis and the resultant clinical picture varies from asymptomatic to potentially life threatening. Similarly, treatment options also vary greatly, from medical therapy to surgical intervention. Commonly utilized medical therapy includes sucralfate enemas, antibiotics, 5-aminosalicylic acid derivatives, probiotics, antioxidants, short-chain fatty acids, formalin instillation and fractionated hyperbaric oxygen. More invasive treatments include endoscopic-based, focally ablative interventions such as dilation, heater and bipolar cautery, neodymium/yttrium aluminum garnet argon laser, radiofrequency ablation or argon plasma coagulation. Despite its relatively common frequency, there is a dearth of existing literature reporting head-to-head comparisons of the various treatment options via a randomized controlled approach. The purpose of our review was to present the reader a consolidation of the existing evidence-based literature with the goal of highlighting the comparative effectiveness and risks of the various treatment approaches. Finally, we outline a pragmatic approach to the treatment of radiation proctitis. In light of the lack of randomized data, our goal is to pursue as least invasive an approach as possible, with escalation of care tailored to the severity of the patient's symptoms. For those cases that are clinically asymptomatic or only mildly symptomatic, observation or medical management can be considered. Once a patient fails such management or symptoms become more severe, invasive procedures such as endoscopically based focal ablation or surgical intervention can be considered. Although not all recommendations are supported by level I evidence, reported case series and single-institutional studies in the literature suggest that successful treatment with cessation of symptoms can be obtained in the majority of cases.

Innovative use of intravesical tacrolimus for hemorrhagic radiation cystitis

Hemorrhagic cystitis is a rare and severe late complication of pelvic radiation, and there is no regulatory-approved drug treatment. We present an 81-year-old man with a history of localized prostate cancer, which was treated with external beam radiation therapy and subsequently developed severe hemorrhagic radiation cystitis for which he has failed several treatments. We present the novel use of intravesical tacrolimus for the treatment of refractory radiation cystitis and gross hematuria. The patient tolerated the treatment well, and it resulted in the resolution of his gross hematuria without further consideration for formalin instillation or cystectomy and diversion. Intravesical tacrolimus is a safe, minimally invasive, and promising treatment option for radiation hemorrhagic cystitis.

Radiation Induced Cystitis and Proctitis - Prediction, Assessment and Management.

Cystitis and proctitis are defined as inflammation of bladder and rectum respectively. Haemorrhagic cystitis is the most severe clinical manifestation of radiation and chemical cystitis. Radiation proctitis and cystitis are major complications following radiotherapy. Prevention of radiation-induced haemorrhagic cystitis has been investigated using various oral agents with minimal benefit. Bladder irrigation remains the most frequently adopted modality followed by intra-vesical instillation of alum or formalin. In intractable cases, surgical intervention is required in the form of diversion ureterostomy or cystectomy. Proctitis is more common in even low dose ranges but is self-limiting and improves on treatment interruption. However, treatment of radiation proctitis is broadly non-invasive or invasive. Non-invasive treatment consists of non-steroid anti-inflammatory drugs (NSAIDs), anti-oxidants, sucralfate, short chain fatty acids and hyperbaric oxygen. Invasive treatment consists of ablative procedures like formalin application, endoscopic YAG laser coagulation or argon plasma coagulation and surgery as a last resort.

COMPARISON OF ARGON PLASMA COAGULATION AND FORMALIN INSTILLATION IN THE TREATMENT OF RADIATION INDUCED HAEMORRHAGIC PROCTOCOLITIS

Background: Radiotherapy is routinely used in the treatment of pelvic malignancies and about 2–5% of these patients develop radiation-induced proctitis or proctocolitis. This complication of radiotherapy is treated in different ways. Two of these treatments, argon plasma coagulation (APC) and formalin instillation, have both been reported as to be successful modalities, but data comparing them are scarce. We conducted this study to compare these two treatment options. Methods: We reviewed the charts of patients who had radiation-induced proctocolitis and who were treated endoscopically at our tertiary care cancer centre with either APC or formalin instillation. Outcomes of the two treatments were compared in terms of bleeding control after the first session of treatment, the number of sessions required and the nal response to therapy. Results: Out of a total of 26 patients presenting with haemorrhagic radiation proctocolitis, 11 were treated with APC and 15 with formalin instillation. Success after the rst session was 53% in the formalin instillation group compared to 18% in the APC-treated group. On repeated sessions, the final response to both treatment modalities was comparable. Conclusion: Efficacy of APC and formalin instillation in the treatment of haemorrhagic radiation proctocolitis is comparable although formalin showed a better outcome after the first session. Key words: Argon plasma coagulation, formalin instillation, proctitis, radiation-induced colitis

Formalin therapy for hemorrhagic radiation proctitis.

Radiotherapy within pelvis is a vital component of curative therapy for urological, gynecological and rectal malignances. Rectum is especially vulnerable to secondary radiation injury resulting in proctitis. The most common and life-threatening symptom is rectal hemorrhage. Formalin application into the rectum causes local cauterization of telangiectatic mucosal vessels. The aim of our study was to assess the efficacy of local formalin application in patients with hemorrhagic radiation proctitis. A solution of 4.0% formalin was used in the treatment of 20 patients with clinical and proctoscopic evidence of radiadion proctitis. Treatment involved direct application of 4.0% formalin into the rectum. All patients were followed-up in terms of complete resolution of symptoms or recurrences of bleeding. A total of 20 patients with a mean age of 69.7 (range, 57-80) years were followed for 51.2 (range, 1-93) months. The mean duration of symptoms was 4.5 (range, 1-10) months and the interval between the end of radiotherapy and symptoms was mostly between 5 and 30 months. Patients required an average of 2 (range, 1-5) formalin treatments. Of the 20 patients, 10 had complete resolution of their symptoms after their first treatment. In 10 patients bleeding recurred and they were offered another formalin instillation and/or 5-ASA suppositories and argon therapy. Complete resolution of symptoms was achieved in all patients. Topical formalin instillation is effective, safe, and well-tolerated method for the patients with radiation proctopathy. This therapy may be repeated in case of recurrent bleeding and combined with other methods of treatment.

Marked Improvement in Severe and Refractory Formalin Colitis with Retinyl Palmitate Suppositories

Purpose: To describe clinical usage of retinyl palmitate suppositories for the treatment of severe formalin colitis. Description: An 80-year-old male developed chronic radiation proctopathy (CRP) after receiving external beam radiation for prostate cancer. This was characterized by periodic rectal bleeding that did not respond to 5-aminosalicylic acid suppositories or short-chain fatty acid enemas. Rectal instillation of formalin was performed under general anesthesia using two aliquots of 100 and 200 ml of unknown concentration with three-minute contact time for each instillation, followed by removal with irrigation and suctioning. Formalin instillation was immediately followed by hospitalization for fever and abdominal pain, requiring IV fluids and antibiotics. Sigmoidoscopy revealed diffuse severe inflammation of the rectum and sigmoid colon (Figure 1). A subsequent perforation occurred and was managed conservatively during a prolonged hospitalization. Despite 50 hyperbaric oxygen sessions and a laparoscopic diverting loop ileostomy, the patient continued to have debilitating rectal pain and tenesmus. He received retinyl palmitate suppositories 20,000 IU daily as part of an open-label study of this treatment for CRP. He had resolution of all symptoms with a decrease in Radiation Proctopathy Symptom Assessment Score from 21 to six. Sigmoidoscopy performed after 90 days of therapy revealed only mild colonic inflammation (Figure 2). No adverse events or change in serum vitamin A occurred during the trial. He has since undergone ileostomy closure and has remained symptom-free on daily suppository treatment. Retinyl palmitate suppositories represent a useful, well-tolerated therapy for formalin colitis.Figure 1Figure 2

Acute Colitis Induces Neurokinin 1 Receptor Internalization in the Rat Lumbosacral Spinal Cord

Substance P (SP) and its receptor, the neurokinin 1 receptor (NK1R), play important roles in transmitting and regulating somatosensory nociceptive information. However, their roles in visceral nociceptive transmission and regulation remain to be elucidated. In the previous study, moderate SP immunoreactive (SP-ir) terminals and NK1R-ir neurons were observed in the dorsal commissural nucleus (DCN) of the lumbosacral spinal cord. Thus we hypothesized that the SP-NK1R system is involved in visceral pain transmission and control within the DCN. The acute visceral pain behaviors, the colon histological changes and the temporal and spatial changes of NK1R-ir structures and Fos expression in the neurons of the DCN were observed in rats following lower colon instillation with 5% formalin. The formalin instillation induced significant acute colitis as revealed by the histological changes in the colon. NK1R internalization in the DCN was obvious at 8 min. It reached a peak (75.3%) at 30 min, began to decrease at 90 min (58.1%) and finally reached the minimum (19.7%) at 3 h after instillation. Meanwhile, formalin instillation induced a biphasic visceral pain response as well as a strong expression of Fos protein in the nuclei of neurons in the DCN. Finally, intrathecal treatment with the NK1R antagonist L732138 attenuated the NK1R internalization, Fos expression and visceral nociceptive responses. The present results suggest that the visceral nociceptive information arising from inflamed pelvic organs, such as the lower colon, might be mediated by the NK1R-ir neurons in the DCN of the lumbosacral spinal cord.

Instilação de formalina endoluminal como opção terapêutica da retite actínica hemorrágica

A retite actínica hemorrágica é um quadro grave que pode ocorrer em qualquer paciente submetido à radioterapia pélvica, por vezes, sendo necessária terapia transfusional e internação hospitalar. A abordagem terapêutica ainda é bastante controversa. Tanto para o tratamento inicial como para casos refratários, uma das opções é a aplicação de formalina. Este método é barato, facilmente disponível, de simples execução e eficaz no controle da hemorragia. Os autores relatam dois casos de retite actínica hemorrágica de pacientes tratados com instilação de formalina endoluminal, e sua eficácia terapêutica e complicações são discutidas

A comparison of fixation methods on lung morphology in a murine model of emphysema

Emphysema is characterized by enlargement of the alveoli, which is the most important parameter to assess the presence and severity of this disease. Alveolar enlargement is primarily defined on morphological criteria; therefore, characterization of this disease with morphological parameters is a prerequisite to study the pathogenesis. For this purpose, different methods of lung fixation were evaluated in a murine model of LPS-induced lung emphysema. Five different methods of lung fixation were evaluated: intratracheal instillation of fixatives, in situ fixation, fixed-volume fixation, vascular whole body perfusion, and vacuum inflation. In addition, the effects of three different fixatives (10% formalin, Carnoy's, and agarose/10% formalin solution) and two embedding methods (paraffin and plastic) were investigated on the murine lung morphology. Mice received intranasal administration of LPS to induce alveolar wall destruction. Quantification of air space enlargement was determined by mean linear intercept analysis, and the histological sections were analyzed for the most optimal fixation method. Additionally, routine immunohistological staining was performed on lung tissue of PBS-treated mice. Intratracheal instillation of formalin or agarose/formalin solution, in situ fixation, and fixed-volume fixation provided a normal lung architecture, in contrast to the lungs fixed via whole body perfusion and vacuum inflation. Formalin-fixed lungs resulted in the most optimal lung morphology for lung emphysema analysis when embedded in paraffin, while for Carnoy's fixed lungs, plastic embedding was preferred. The histological findings, the mean linear intercept measurement, and the immunohistochemistry data demonstrated that fixation by intratracheal instillation of 10% formalin or in situ fixation with 10% formalin are the two most optimal methods to fix lungs for alveolar enlargement analysis to study lung emphysema.

Management of radiation cystitis

Acute radiation cystitis occurs during or soon after radiation treatment. It is usually self-limiting, and is generally managed conservatively. Late radiation cystitis, on the other hand, can develop from 6 months to 20 years after radiation therapy. The main presenting symptom is hematuria, which may vary from mild to severe, life-threatening hemorrhage. Initial management includes intravenous fluid replacement, blood transfusion if indicated and transurethral catheterization with bladder washout and irrigation. Oral or parenteral agents that can be used to control hematuria include conjugated estrogens, pentosan polysulfate or WF10. Cystoscopy with laser fulguration or electrocoagulation of bleeding points is sometimes effective. Injection of botulinum toxin A in the bladder wall may relieve irritative bladder symptoms. Intravesical instillation of aluminum, placental extract, prostaglandins or formalin can also be effective. More-aggressive treatment options include selective embolization or ligation of the internal iliac arteries. Surgical options include urinary diversion by percutaneous nephrostomy or intestinal conduit, with or without cystectomy. Hyperbaric oxygen therapy (HBOT) involves the administration of 100% oxygen at higher than atmospheric pressure. The reported success rate of HBOT for radiation cystitis varies from 60% to 92%. An important multicenter, double-blind, randomized, sham-controlled trial to evaluate the effectiveness of HBOT for refractory radiation cystitis is currently being conducted.

Severe pain and hypertension following intravesical instillation of formalin necessitating epidural analgesia

Severe pain and hypertension following intravesical instillation of formalin necessitating epidural analgesia

Is it Safe to Use Aluminum in the Treatment of Pediatric Hemorrhagic Cystitis?

In pediatric oncology patients, hemorrhagic cystitis can be a life-threatening complication of bone marrow transplantation, chemotherapy, and radiation therapy. The treatment of this condition is often challenging and includes intravesical irrigation with aluminum, embolization, endoscopic laser coagulation, hydrostatic pressure, use of hyperbaric oxygen, instillation of formalin, prostaglandins, and oral sodium pentosan polysulfate. Although the efficacy of aluminum irrigation is well documented for the management of hemorrhagic cystitis in adults, there are limited reports describing its use in children. The potential multisystem toxic effects of aluminum are well described and the range and progression of aluminum toxicity can be devastating. We report a case of a 9-year-old girl suffering from acute lymphocytic leukemia with hemorrhagic cystitis. Although the symptoms resolved after intravesical aluminum treatment, she developed significant aluminum toxicity. We have reviewed the literature relating to aluminum toxicity in the pediatric age group and present our recommendations for the effective and safe use of aluminum in this cohort of patients.