Rectal versus vaginal progesterone administration for luteal phase support in the hormone replacement therapy frozen embryo transfer (HRT-FET) cycle: protocol for a non-inferiority randomised controlled trial.

INTRODUCTION: This study compares rectal administration with vaginal administration of progesterone as luteal phase support in hormone replacement therapy frozen embryo transfer (HRT-FET) cycles. The reason for comparing the two routes of administration is that rectal administration has been suggested to be more patient friendly. METHODS AND ANALYSIS: This study is a randomised controlled trial comparing the ongoing pregnancy rate (OPR) at week 12 in HRT-FET cycles after rectal administered progesterone as the only administered progesterone compared with a vaginal luteal phase support regimen. All patients are enrolled from a Danish public fertility clinic and randomised to one of two groups, with 305 patients receiving embryo transfer assigned to each group. Endometrial preparation includes 6 mg oestradiol daily. The intervention group receives rectally administered progesterone (400 mg/12 hours) and the control group receives vaginally administered progesterone (400 mg/12 hours). If P4 is <35 nmol/L on blastocyst transfer day an additional rectal luteal phase rescue regimen is started (control group). Thawing and transferring of a single autologous vitrified blastocyst is scheduled on the sixth day of progesterone administration in both groups. The power calculation is based on a non-inferiority analysis with an expected OPR in both groups of 44% and the upper limit of a one-sided 95% CI will exclude a difference in favour of the control group of more than 10.0%. An interim analysis will be conducted once half of the study population has been enrolled. ETHICS AND DISSEMINATION: The trial was approved on 21 November 2023 by the Danish National Ethical Committee and the Danish Medicines Agency and is authorised by the Clinical Trials Information System (EUCT number 2023-504616-15-02). All patients will provide informed consent before being enrolled in the study. The results will be published in an international journal. TRIAL REGISTRATION NUMBER: EUCT number: 2023-504616-15-02.

Effect of hydrogel drug delivery system for treating ulcerative colitis: A preclinical meta-analysis.

Hydrogel drug delivery systems (DDSs) for treating ulcerative colitis (UC) have garnered attention. However, there is a lack of meta-analysis summarizing their effectiveness. Therefore, this study aimed to conduct a meta-analysis of pre-clinical evidence comparing hydrogel DDSs with free drug administration. Subgroup analyses were performed based on hydrogel materials (polysaccharide versus non-polysaccharide) and administration routes of the hydrogel DDSs (rectal versus oral). The outcome indicators included colon length, histological scores, tumor necrosis factor-α (TNF-α), zonula occludens protein 1(ZO-1), and area under the curve (AUC). The results confirmed the therapeutic enhancement of the hydrogel DDSs for UC compared with the free drug group. Notably, no significant differences were found between polysaccharide and non-polysaccharide materials, however, oral administration was found superior regarding TNF-α and AUC. In conclusion, oral hydrogel DDSs can serve as potential excellent dosage forms in oral colon -targeting DDSs, and in the design of colon hydrogel delivery systems, polysaccharides do not show advantages compared with other materials.

Intrarectal formalin treatment for haemorrhagic radiation-induced proctopathy: efficacy and safety.

AIM: Pelvic radiotherapy is limited by dose-dependent toxicity to surrounding organs. The aim of this prospective study was to evaluate the efficacy and safety of intrarectal formalin treatment for radiotherapy-induced haemorrhagic proctopathy (RHP) at the Royal Marsden Hospital. METHOD: Adult patients were enrolled. Haemoglobin was evaluated before and after formalin treatment. Antiplatelet and/or anticoagulation treatment and administration of transfusion were recorded. The interval between completion of radiotherapy and the first intrarectal 5% formalin treatment was assessed and the dose of radiotherapy was evaluated. Clinical assessment of the frequency and amount of rectal bleeding (rectal bleeding score 1-6) and endoscopic appearance (grade 0-3) were classified. Complications were recorded. RESULTS: Nineteen patients were enrolled, comprising 13 men (68%) and 6 women. The mean age was 75 ± 9 years. The median time between completion of radiotherapy and the first treatment was 20 months [interquartile range (IQR) 15 months] and the median dose of radiotherapy was 68 Gy (IQR 14 Gy). Thirty-two procedures were performed (average 1.7 per patient). In total, 9/19 (47%) patients were receiving anticoagulation and/or antiplatelet medication and 5/19 (26%) received transfusion prior to treatment. The mean value of serum haemoglobin before the first treatment was 110 ± 18 g/L and afterwards it was 123 ± 16 g/L (p = 0.022). The median rectal bleeding score before the first treatment was 6 (IQR 0) and afterwards 2 (IQR 1-4; p < 0.001), while the median endoscopy score on the day of first treatment was 3 (IQR 0) compared with 1 (IQR 1-2) on the day of the last treatment 1 (p < 0.001). One female patient with a persistent rectal ulcer that eventually healed (18 months of healing) subsequently developed rectovaginal fistula (complication rate 1/19, 5%). CONCLUSIONS: Treatment with intrarectal formalin in RHP is effective and safe.

Transanal total mesorectal excision (TaTME) in rectal cancer treatment within an expert center.

The objective of this study was to evaluate treatment outcomes in patients who underwent the TaTME procedure for cancer of the middle and low rectum in an expert center. Prospective analysis of the outcomes of all consecutive patients treated using the TaTME technique for cancer of the middle and distal rectum at the our medical center between March 1, 2015, and March 31, 2022. A total of 128 patients (34 women, 94 men; mean age 66.01 [38-85] years) with cancer of the middle and distal rectum qualified for TaTME. TaTME procedures were performed in 127/128 (99.22%) patients. Complications of surgery were observed in 22/127 (17.32%) patients. Negative proximal and distal margins were confirmed in all 127 patients. Complete (R0) resection of the mesorectum was confirmed in 125/127 (98.43%) and nearly complete (R1) resection was confirmed in 2/127 (1.57%) patients. The average follow-up period was 795 days (296-1522) days. Local recurrence was detected during the follow-up period in 2/127 (1.57%) patients. This study showed that the TaTME procedure is an effective and safe method for the minimally invasive treatment of middle and low rectal cancers, particularly within an expert center setting.

Rectal administration of tacrolimus protects against post-ERCP pancreatitis in mice.

OBJECTIVE: There is an unmet clinical need for effective, targeted interventions to prevent post-ERCP pancreatitis (PEP). We previously demonstrated that the serine-threonine phosphatase, calcineurin (Cn) is a critical mediator of PEP and that the FDA-approved calcineurin inhibitors, tacrolimus (Tac) or cyclosporine A, prevented PEP. Our recent observations in preclinical PEP models demonstrating that Cn deletion in both pancreatic and hematopoietic compartments is required for maximal pancreas protection, highlighted the need to target both systemic and pancreas-specific Cn signaling. We hypothesized that rectal administration of Tac would effectively mitigate PEP by ensuring systemic and pancreatic bioavailability of Tac. We have tested the efficacy of rectal Tac in a preclinical PEP model and in cerulein-induced experimental pancreatitis. METHODS: C57BL/6 mice underwent ductal cannulation with saline infusion to simulate pressure-induced PEP or were given seven, hourly, cerulein injections to induce pancreatitis. To test the efficacy of rectal Tac in pancreatitis prevention, a rectal Tac suppository (1 mg/kg) was administered 10 min prior to cannulation or first cerulein injection. Histological and biochemical indicators of pancreatitis were evaluated post-treatment. Pharmacokinetic parameters of Tac in the blood after rectal delivery compared to intravenous and intragastric administration was evaluated. RESULTS: Rectal Tac was effective in reducing pancreatic injury and inflammation in both PEP and cerulein models. Pharmacokinetic studies revealed that the rectal administration of Tac helped achieve optimal blood levels of Tac over an extended time compared to intravenous or intragastric delivery. CONCLUSION: Our results underscore the effectiveness and clinical utility of rectal Tac for PEP prophylaxis.

Rectal progesterone administration secures a high ongoing pregnancy rate in a personalized Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) protocol: a prospective interventional study.

STUDY QUESTION: Can supplementation with rectal administration of progesterone secure high ongoing pregnancy rates (OPRs) in patients with low serum progesterone (P4) on the day of blastocyst transfer (ET)? SUMMARY ANSWER: Rectally administered progesterone commencing on the ET day secures high OPRs in patients with serum P4 levels below 35 nmol/l (11 ng/ml). WHAT IS KNOWN ALREADY: Low serum P4 levels at peri-implantation in Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) cycles impact reproductive outcomes negatively. However, studies have shown that patients with low P4 after a standard vaginal progesterone treatment can obtain live birth rates (LBRs) comparable to patients with optimal P4 levels if they receive additionalsubcutaneous progesterone, starting around the day of blastocyst transfer. In contrast, increasing vaginal progesterone supplementation in low serum P4 patients does not increase LBR. Another route of administration rarely used in ART is the rectal route, despite the fact that progesterone is well absorbed and serum P4 levels reach a maximum level after ∼2 h. STUDY DESIGN, SIZE, DURATION: This prospective interventional study included a cohort of 488 HRT-FET cycles, in which a total of 374 patients had serum P4 levels ≥35 nmol/l (11 ng/ml) at ET, and 114 patients had serum P4 levels <35 nmol/l (11 ng/ml). The study was conducted from January 2020 to November 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients underwent HRT-FET in a public Fertility Clinic, and endometrial preparation included oral oestradiol (6 mg/24 h), followed by vaginal micronized progesterone, 400 mg/12 h. Blastocyst transfer and P4 measurements were performed on the sixth day of progesterone administration. In patients with serum P4 <35 nmol/l (11 ng/ml), 'rescue' was performed by rectal administration of progesterone (400 mg/12 h) starting that same day. In pregnant patients, rectal administration continued until Week 8 of gestation, and oestradiol and vaginal progesterone treatment continued until Week 10 of gestation. MAIN RESULTS AND THE ROLE OF CHANCE: Among 488 HRT-FET single blastocyst transfers, the mean age of the patients at oocyte retrieval (OR) was 30.9 ± 4.6 years and the mean BMI at ET 25.1 ± 3.5 kg/m2. The mean serum P4 level after vaginal progesterone administration on the day of ET was 48.9 ± 21.0 nmol/l (15.4 ± 6.6 ng/ml), and a total of 23% (114/488) of the patients had a serum P4 level lower than 35 nmol/l (11 ng/ml). The overall, positive hCG rate, clinical pregnancy rate, OPR week 12, and total pregnancy loss rate were 66% (320/488), 54% (265/488), 45% (221/488), and 31% (99/320), respectively. There was no significant difference in either OPR week 12 or total pregnancy loss rate between patients with P4 ≥35 nmol/l (11 ng/ml) and patients with P4 <35 nmol/l, who received rescue in terms of rectally administered progesterone, 45% versus 46%, P = 0.77 and 30% versus 34%, P = 0.53, respectively. OPR did not differ whether patients had initially low P4 and rectal rescue or were above the P4 cut-off. Logistic regression analysis showed that only age at OR and blastocyst scoring correlated with OPR week 12, independently of other factors like BMI and vitrification day of blastocysts (Day 5 or 6). LIMITATIONS, REASONS FOR CAUTION: In this study, vaginal micronized progesterone pessaries, a solid pessary with progesterone suspended in vegetable hard fat, were used vaginally as well as rectally. It is unknown whether other vaginal progesterone products, such as capsules, gel, or tablet, could be used rectally with the same rescue effect. WIDER IMPLICATIONS OF THE FINDINGS: A substantial part of HRT-FET patients receiving vaginal progesterone treatment has lowserum P4. Adding rectally administered progesterone in these patients increases the reproductive outcome. Importantly, rectal progesterone administration is considered convenient, and progesterone pessaries are easy to administer rectally and of low cost. STUDY FUNDING/COMPETING INTEREST(S): Gedeon Richter Nordic supported the study with an unrestricted grant as well as study medication. B.A. has received unrestricted grant from Gedeon Richter Nordic and Merck and honoraria for lectures from Gedeon Richter, Merck, IBSA and Marckyrl Pharma. P.H. has received honoraria for lectures from Gedeon Richter, Merck, IBSA and U.S.K. has received grant from Gedeon Richter Nordic, IBSA and Merck for studies outside this work and honoraria for teaching from Merck and Thillotts Pharma AB and conference expenses covered by Merck. The other co-authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER (25): EudraCT no.: 2019-001539-29.

In situ gel-forming oil as rectally delivering platform of hydrophobic therapeutics for ulcerative colitis therapy.

Because of their poor water-soluble properties and non-specific distribution, most hydrophobic therapeutics had limited benefit for patients with ulcerative colitis. Herein, an in-situ oil-based gel has been developed as a rectal delivery vehicle for these therapeutics. In situ gel-forming oil (BBLG) was composed of soybean phosphatidyl choline (40%, w/w), glyceryl dioleate (50%, w/w), and ethanol (10%, w/w). The hydrophobic laquinimod (LAQ) as a model drug was easily dissolved in gel-forming oil and its solubility was reaching to 7 ± 0.1 mg/mL. Importantly, upon contact with the colonic fluids, the gel-forming oil was quickly transited to a semi-solid gel, adhering to the inflamed colon mucosa and forming a protective barrier. Transmission Electron Microscopy showed that the gel network was arranged by the connected lipid spheres and LAQ was non-crystally encapsulated into the lipid spheres. Moreover, the universal adhesive test showed that the adhesive force and the adhesive energy of BBLG toward fresh colon tissues were 711 ± 12 mN and 25 ± 2 J/m2, which was 2.14-fold and 5-fold higher than that of the marketed Poloxamer 407 gel, respectively. Meanwhile, in vivo imaging confirmed that the retention time of BBLG in the colon lumen was more than 8 h after rectal administration. In vivo animal studies showed that BBLG also greatly enhanced the therapeutic impact of LAQ on TNBS-treated rats with ulcerative colitis, as evidenced by reduced disease activity index (DAI) scores and weight loss. Moreover, the colonic inflammation was significantly alleviated and the goblet cells were obliviously restored after treatment. Importantly, the gut mucosa barrier was largely repaired without any formation of fibrosis remodeling. Conclusively, in situ liquid gel may be a potential delivery system of hydrophobic medicines for ulcerative colitis.

Transition Zone Pull-through in Patients with Hirschsprung Disease: Is Redo Surgery Beneficial for the Long-term Outcomes?

INTRODUCTION: Transition zone pull-through (TZPT) is incomplete removal of the aganglionic bowel/transition zone (TZ) in patients with Hirschsprung disease (HD). Evidence on which treatment generates the best long-term outcomes is lacking. The aim of this study was to compare the long-term occurrence of Hirschsprung associated enterocolitis (HAEC), requirement of interventions, functional outcomes and quality of life between patients with TZPT treated conservatively to patients with TZPT treated with redo surgery to non-TZPT patients. METHODS: We retrospectively studied patients with TZPT operated between 2000 and 2021. TZPT patients were matched to two control patients with complete removal of the aganglionic/hypoganglionic bowel. Functional outcomes and quality of life was assessed using Hirschsprung/Anorectal Malformation Quality of Life questionnaire and items of Groningen Defecation & Continence together with occurrence of Hirschsprung associated enterocolitis (HAEC) and requirement of interventions. Scores between the groups were compared using One-Way ANOVA. The follow-up duration lasted from time at operation until follow-up. RESULTS: Fifteen TZPT-patients (six treated conservatively, nine receiving redo surgery) were matched with 30 control-patients. Median duration of follow-up was 76 months (range 12-260). No significant differences between groups were found in the occurrence of HAEC (p = 0.65), laxatives use (p = 0.33), rectal irrigation use (p = 0.11), botulinum toxin injections (p = 0.06), functional outcomes (p = 0.67) and quality of life (p = 0.63). CONCLUSION: Our findings suggest that there are no differences in the long-term occurrence of HAEC, requirement of interventions, functional outcomes and quality of life between patients with TZPT treated conservatively or with redo surgery and non-TZPT patients. Therefore, we suggest to consider conservative treatment in case of TZPT.

Rectal use of levetiracetam: best practice report for a stepwise approach for sustainable off-label decision making and treatment.

Off-label drug use is common practice in palliative care. It may pose a risk to the patient and benefit should outweigh harm. A decision and documentation aid for off-label use was developed to support practitioners in clinical practice off-label use. Using the example of the rectal administration of levetiracetam in three patient cases, the utilisation and benefits of the decision and documentation aid are presented and discussed. The rectal administration of levetiracetam clearly is an experimental treatment approach with little underlying evidence. To support and document the decision-making process for or against such an off-label use in clinical practice, it is helpful to have a structured approach in order to make this data comprehensible for a later point in time. Off-label use may be a permissible treatment alternative without underlying evidence, provided it takes place in a well-planned and well-monitored therapeutic setting and the benefits outweigh the potential risks.

Clinico-epidemiological profile and treatment outcome in adolescents and young patients of rectal cancer attending a tertiary cancer center.

INTRODUCTION: The incidence of colorectal cancer in young adults is on an increasing trend. It is observed that this subgroup of patients has an aggressive disease and carries a poorer prognosis compared to its older counterpart. This study aimed to analyze the incidence, treatment outcome, and prognostic factors in adolescents and young adults with rectal cancer attending a tertiary cancer center in North India. MATERIALS AND METHODS: We retrospectively analyzed 50 patients of histologically proven rectal cancer, aged up to 30 years, treated at our center between 2015 and 2019. The clinical, demographic, and pathological parameters were studied in all these patients. Kaplan-Meier survival analysis was used to find out survival. Univariate analysis was performed to assess prognostic factors. RESULTS: The incidence was 26.4% at our center with a median age of 28 years. Bleeding per rectum was the commonest complaint. Most of them had signet ring cell histology (26%). The median overall survival was 16 months. Survival was significantly better in patients having bleeding per rectum as an initial complaint (P = 0.009), absence of lymphovascular invasion (LVI) (P = 0.005), and perineural invasion (PNI) (P = 0.002), who received complete planned treatment compared to patients who could not receive either of the modality (P < 0.001). Patients who did not receive radiotherapy (RT) had the worst outcomes compared to those who received RT in any form. RT dose of 50.4 Gy was found to be superior as compared to other schedules. There was no significant difference in survival with gender, tumor stage, grade, type of surgery, or chemotherapy regimen. CONCLUSION: The majority of patients presented in an advanced stage. Therefore, bleeding per rectum should be properly and timely investigated in all these young patients. Early detection and complete treatment are paramount to improving the outcome.

Efficacy of Combined Management with Nonsteroidal Anti-inflammatory Drugs for Prevention of Pancreatitis After Endoscopic Retrograde Cholangiography: a Bayesian Network Meta-analysis.

OBJECTIVES: To systematically evaluate the clinical efficacy of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) alone or in combination with other agents for preventing pancreatitis after endoscopic retrograde cholangiopanography. METHODS: We carried out a literature search of random controlled trials (RCTs) on preventing post-operative pancreatitis by administration of the anti-inflammatory drugs, indomethacin and diclofenac, following endoscopic retrograde cholangiopancreatography (ERCP). The databases searched for relevant publications up to July 7, 2021, included PubMed, Cochrane Library, and Embase. We screened the literature according to inclusion criteria and analyzed the extracted data. The overall population and high-risk patient groups were analyzed, with the main outcome being the incidence of PEP. RESULTS: The search identified 32 RCTs that included 15019 patients with post-ERCP pancreatitis and 9 different interventions. The results of the overall population network meta-analysis showed that NSAIDs alone, high-dose NSAIDs, and a combination of NSAIDs significantly reduced the incidence of PEP compared with placebo. However, compared with placebo, there was no statistically significant difference between the two interventions (NSAIDs + standard hydration and high-dose NSAIDs). In addition, NSAIDs + sublingual nitrates were associated with a lower incidence of PEP compared to that observed with NSAIDs alone. Probability ranking results showed that NSAIDs + sublingual nitrate had the best effect, followed by NSAIDs + standard hydration, NSAIDs + melatonin, NSAIDs + aggressive hydration, NSAIDs + somatostatin, NSAIDs alone, NSAIDs + epinephrine, high-dose NSAIDs, and placebo. In the high-risk subgroup, the results of the network meta-analysis showed that NSAIDs alone, high-dose NSAIDs, and a combination of NSAIDs showed no statistically significant difference in their ability to reduce the incidence of PEP compared with placebo. Probability ranking results showed that NSAIDs + hydration had the best effect, followed by NSAIDs + sublingual nitroglycerin and NSAIDs + aggressive hydration. CONCLUSION: Of the nine interventions, NSAIDs + sublingual nitrates had considerably better efficacy than the other drugs for reducing the incidence of PEP in the overall population. In high-risk patients, NSAIDs + standard hydration may be the best preventive treatment; however, more randomized, controlled trials are needed to validate our results. TRIAL REGISTRATION: Name of the registry: PROSPERO-International prospective register of systematic reviews. Unique identifying number or registration ID: CRD42021282205.

Meta-analysis of efficacy and safety of sustained release oxycodone hydrochloride rectal administration for moderate to severe pain.

OBJECTIVE: This study aims to evaluate the efficacy and safety of oxycodone hydrochloride (OxyContin) rectal administration in cancer pain patients. This is geared towards providing the research evidence for a novel route of OxyContin administration. METHODS: Relevant randomized controlled trials (RCTs) were searched in electronic databases, including PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wanfang Data Knowledge Service Platform, and Chinese Biomedical Literature Database (CBM). Moreover, unpublished academic data were obtained by contacting the colleague, professor, or Institute of Traditional Chinese Medicine. The RCTs of transrectal Oxycodone administration of sustained-release tablets for moderate and severe pain patients were searched in the databases from inception to December 2020. RESULTS: According to the inclusion criteria, a total of 8 RCTs were included, with a total of 648 patients. Meta analysis results showed that there was no statistically significant difference in the efficacy of moderate to severe pain control between the rectal administration group and the oral administration group (RR = 1.04, 95%CI: 0.99-1.10, p = 0.13>0.05). At the same time, the incidence of adverse reactions in the rectal administration group was low. In terms of constipation, the rectal administration group was less than the oral administration group, with a statistically significant difference (RR = 0.43, 95%CI: 0.31-0.58, p< 0.00001). In terms of nausea and vomiting, the rectal administration group was less than the oral administration group, and the difference was statistically significant(RR = 0.30, 95%CI: 0.21-0.42, p<0.00001). In terms of sleepiness, there was no significant difference between the two groups(RR = 0.54, 95%CI: 0.26-1.15, p = 0.11>0.05). In terms of dizziness, there was no statistically significant difference between the two groups (RR = 0.43, 95%CI:0.27-0.68, p = 0.31>0.05). In terms of dyuria, there was no statistically significant difference between the two groups (RR = 0.37, 95%CI: 0.02-7.02, p = 0.51>0.05). In terms of KPS scores there was no significant difference was noted between the rectal and oral administration groups (RR = 1.04, 95%CI: 0.89-1.21, p = 0.63>0.05). CONCLUSION: In summary, we found no significant differences in efficacy between rectal administration of OxyContin and oral administration. Thus, rectal administration should be considered in managing cancer pain among patients with difficulty in oral OxyContin administration. PROSPERO REGISTRATION NUMBER: CRD42021209660.

Transrectal povidone-iodine efficiency in reducing infections occurring after transrectal ultrasound guided biopsy of the prostate.

ABSTRACT: The present study aimed to compare infectious complications in men undergoing transrectal ultrasound-guided prostate biopsy (TRUS-Bx) with and without povidone-iodine transrectal injection using a gavage syringe.The records of 112 patients, who underwent TRUS-Bx between January 2016 and December 2019, were retrospectively reviewed. The biopsy indication was considered high prostate-specific antigen (PSA) level and/or suspicious digital rectal prostate examination findings. Patients' ages, underlying diseases, PSA levels, prostate volumes, pathologic results, and infectious complications after the biopsy were investigated. All the patients received 1500 mg of ciprofloxacin (750 mg twice a day) for 5 days, starting from the day before the procedure. Forty-seven (41.96%) patients received ciprofloxacin prophylaxis with povidone-iodine transrectal injection, while 65 (58.03%) only received ciprofloxacin prophylaxis. All the patients, who were readmitted to the hospital after the procedure, especially with a temperature of higher than 37.8°C, were detected. For the purposes of the study, the priority was placed on the emergence of the rate of febrile infectious complications. Differences in febrile infectious complications in patients, who received ciprofloxacin prophylaxis with transrectal povidone-iodine, and those, who received ciprofloxacin prophylaxis alone before TRUS-Bx, were studied.Febrile infectious complications developed in 10 cases (15.38%) in patients, who received ciprofloxacin antibiotics prophylaxis alone. In the povidone-iodine rectal disinfection group, there was only 1 case of febrile infectious complication (2%). There was no significant difference by clinicopathologic features, age, PSA level, and cancer detection rate between both groups (P > .05). Multivariate logistic regression analysis did not identify any patient subgroups at a significantly higher risk of infection after prostate biopsy. There was no significant side effect associated with povidone iodine.In addition to the use of prophylactic antibiotics, transrectal povidone-iodine was useful in reducing the febrile infection complications following TRUS-Bx.

Anesthesia and surgery induce a functional decrease in excitatory synaptic transmission in prefrontal cortex neurons, and intraoperative administration of dexmedetomidine does not elicit the synaptic dysfunction.

Postoperative delirium (POD), a syndrome of confusion and inattention, frequently occurs after anesthesia and surgery. The prefrontal cortex (PFC) plays key roles in executive functions and cognitive controls. However, the neuropathogenesis of POD in the PFC remains largely unknown. We investigated whether anesthesia and surgery induced neurofunctional changes in the mouse PFC. After laparotomy was performed under isoflurane anesthesia, PFC neuronal activities were compared at the synaptic level using whole-cell patch-clamp recordings. A battery of behavioral tests measuring natural and learned behaviors, and effects of intraoperative dexmedetomidine were also examined. In the anesthesia/surgery group showing changes in natural and learned behaviors, the frequency of excitatory synaptic responses in PFC pyramidal neurons was decreased after the surgery without any changes in the response kinetics. On the other hand, neuronal intrinsic properties and inhibitory synaptic responses were not changed. In the anesthesia/surgery group administered intraoperative dexmedetomidine, the excitatory synaptic transmission and the behaviors were not altered. These results suggest that anesthesia and surgery induce a functional reduction selectively in the PFC excitatory synaptic transmission, and intraoperative dexmedetomidine inhibits the plastic change in the PFC excitatory synaptic input.

Achievements in Thermosensitive Gelling Systems for Rectal Administration.

Rectal drug delivery is an effective alternative to oral and parenteral treatments. This route allows for both local and systemic drug therapy. Traditional rectal dosage formulations have historically been used for localised treatments, including laxatives, hemorrhoid therapy and antipyretics. However, this form of drug dosage often feels alien and uncomfortable to a patient, encouraging refusal. The limitations of conventional solid suppositories can be overcome by creating a thermosensitive liquid suppository. Unfortunately, there are currently only a few studies describing their use in therapy. However, recent trends indicate an increase in the development of this modern therapeutic system. This review introduces a novel rectal drug delivery system with the goal of summarising recent developments in thermosensitive liquid suppositories for analgesic, anticancer, antiemetic, antihypertensive, psychiatric, antiallergic, anaesthetic, antimalarial drugs and insulin. The report also presents the impact of various types of components and their concentration on the properties of this rectal dosage form. Further research into such formulations is certainly needed in order to meet the high demand for modern, efficient rectal gelling systems. Continued research and development in this field would undoubtedly further reveal the hidden potential of rectal drug delivery systems.

Comparación del bloqueo periprostático con lidocaina y supositorio de diclofenac y placebo en la biopsia prostática / Comparison of periprostatic block with lidocaine and diclofenac suppository and placebo in prostate biopsy

El bloqueo del nervio peri prostático con lidocaína, proporciona un buen alivio del dolor en la realización de la biopsia prostática guiada por ultrasonido, pero el dolor post-procedimiento, puede llegar a ser significativo, la adición del supositorio de diclofenac, podría proporcionar alivio adicional. Se asignaron al azar pacientes en 2 grupos el grupo 1 bloqueo con lidocaína del plexo peri prostático + supositorio de diclofenac sódico y el grupo 2 bloqueo con lidocaína del plexo peri prostático + supositorio de placebo, realizando biopsia doble sextante, el dolor a varios intervalos después del procedimiento se registró en una escala visual análoga (EVA) de 0 a 10. Los 2 grupos fueron similares en cuanto a edad, volumen de próstata, antígeno prostático específico, diagnóstico histopatológico. Los pacientes que recibieron diclofenac tuvieron puntajes de dolor significativamente más bajos que los que recibieron placebo (2 frente a 3,35) p 0,02. La administración rectal de diclofenac antes de la realización de la biopsia de próstata es un procedimiento simple que alivia significativamente el dolor experimentado sin aumento en la morbilidad(AU)

The peri-prostatic nerve block with lidocaine, provides good pain relief in performing ultrasoundguided prostate biopsy, but the postprocedure pain can be significant, the addition of diclofenac suppository, could provide additional relief. Patients were randomly assigned in 2 groups to group 1 blockade with lidocaine of the prostatic peri plexus + suppository of diclofenac sodium and group 2 blockade with lidocaine of the prostatic peri plexus + placebo suppository, performing double sextant biopsy, pain at several intervals after the procedure was recorded on a visual analog scale (EVA) from 0 to 10. Thee 2 groups were similar in terms of age, prostate volume, prostate-specific antigen, histopathological diagnosis. Patients who received diclofenac had pain scores significantly lower than those who received placebo (2 vs. 3.35) p 0.02. Rectal administration of diclofenac before performing a prostate biopsy is a simple procedure that relieves significantly pain experienced without increased morbidity(AU)

Anorectal application of 5% lidocaine cream reduces pain prior to periprostatic nerve block during transrectal ultrasound guided prostate biopsy: Randomized, prospective controlled study.

OBJECTIVES: Trans rectal ultrasound guided prostate biopsy with periprostatic nerve block (PPNB) is performed following probe insertion and manipulation leaving these initial maneuvers uncovered in terms of pain control. We evaluated whether topical analgesia reduces pain during early stages of the procedure. PATIENTS AND METHODS: Seven group prospective, randomized controlled study: groups 1-3: nerve block with 5 ml 1% lidocaine bilaterally plus perianal topical application of 10 ml 5% lidocaine cream. Groups 4-6 as in 1-3 plus digital application of 10 ml 5% lidocaine cream internally on rectal walls. For each approach exposure times were 5 (groups 1 and 4), 10 (groups 2 and 5) and 20 (groups 3 and 6) min, respectively. The control group (7) received PPNB only. Patients filled a 0-10 visual analogue scale (VAS) at five points: after probe insertion, during probe manipulation, following PPNB, after prostate biopsies and a global pain estimation. RESULTS: Two hundred and fifty-two patients were enrolled. Significant differences in VAS between all study groups and controls were observed at the pre-biopsy stages of the procedure. In multivariate analysis adjusted for prostate specific antigen, diabetes mellitus status, spinal disease, abnormal digital rectal examination and non- benign prostate hyperplasia histology, significance remained for probe insertion and intra-rectal manipulation. For each exposure time no significant differences were observed between topical application and topical + intra-rectal application. After PPNB, differences between study and control groups disappeared. CONCLUSION: Topical anesthesia significantly reduces pain during early stages of prostate biopsy. Perianal application sufficed whereas intra-rectal application of local anesthetics does not add to pain control. Perianal application for 10 min seems to be optimal.

A Nucleotide Analog Prevents Colitis-Associated Cancer via Beta-Catenin Independently of Inflammation and Autophagy.

BACKGROUND & AIMS: Chronic bowel inflammation increases the risk of colon cancer; colitis-associated cancer (CAC). Thiopurine treatments are associated with a reduction in dysplasia and CAC in inflammatory bowel disease (IBD). Abnormal Wnt/ß-catenin signalling is characteristic of >90% of colorectal cancers. Immunosuppression by thiopurines is via Rac1 GTPase, which also affects Wnt/ß-catenin signalling. Autophagy is implicated in colonic tumors, and topical delivery of the thiopurine thioguanine (TG) is known to alleviate colitis and augment autophagy. This study investigated the effects of TG in a murine model of CAC and potential mechanisms. METHODS: Colonic dysplasia was induced by exposure to azoxymethane (AOM) and dextran sodium sulfate (DSS) in wild-type (WT) mice and mice harboring intestinal epithelial cell-specific deletion of autophagy related 7 gene (Atg7ΔIEC). TG or vehicle was administered intrarectally, and the effect on tumor burden and ß-catenin activity was assessed. The mechanisms of action of TG were investigated in vitro and in vivo. RESULTS: TG ameliorated DSS colitis in wild-type but not Atg7ΔIEC mice, demonstrating that anti-inflammatory effects of locally delivered TG are autophagy-dependent. However, TG inhibited CAC in both wild-type and Atg7ΔIEC mice. This was associated with decreased ß-catenin activation/nuclear translocation demonstrating that TG's inhibition of tumorigenesis occurred independently of anti-inflammatory and pro-autophagic actions. These results were confirmed in cell lines, and the dependency on Rac1 GTPase was demonstrated by siRNA knockdown and overexpression of constitutively active Rac1. CONCLUSIONS: Our findings provide evidence for a new mechanism that could be exploited to improve CAC chemoprophylactic approaches.

Rectal administration of carbon monoxide inhibits the development of intestinal inflammation and promotes intestinal wound healing via the activation of the Rho-kinase pathway in rats.

The inhalation of carbon monoxide (CO) gas and the administration of CO-releasing molecules were shown to inhibit the development of intestinal inflammation in a murine colitis model. However, it remains unclear whether CO promotes intestinal wound healing. Herein, we aimed to evaluate the therapeutic effects of the topical application of CO-saturated saline enemas on intestinal inflammation and elucidate the underlying mechanism. Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. A CO-saturated solution was prepared via bubbling 50% CO gas into saline and was rectally administrated twice a day after colitis induction; rats were sacrificed 3 or 7 days after induction for the study of the acute or healing phases, respectively. The distal colon was isolated, and ulcerated lesions were measured. In vitro wound healing assays were also employed to determine the mechanism underlying rat intestinal epithelial cell restitution after CO treatment. CO solution rectal administration ameliorated acute TNBS-induced colonic ulceration and accelerated ulcer healing without elevating serum CO levels. The increase in thiobarbituric acid-reactive substances and myeloperoxidase activity after induction of acute TNBS colitis was also significantly inhibited after CO treatment. Moreover, the wound healing assays revealed that the CO-saturated medium enhanced rat intestinal epithelial cell migration via the activation of Rho-kinase. In addition, the activation of Rho-kinase in response to CO treatment was confirmed in the inflamed colonic tissue. Therefore, the rectal administration of a CO-saturated solution protects the intestinal mucosa from inflammation and accelerates colonic ulcer healing through enhanced epithelial cell restitution. CO may thus represent a novel therapeutic agent for the treatment of inflammatory bowel disease.