Genetically-regulated transcriptomics & copy number variation of proctitis points to altered mitochondrial and DNA repair mechanisms in individuals of European ancestry.

BACKGROUND: Proctitis is an inflammation of the rectum and may be induced by radiation treatment for cancer. The genetic heritability of developing radiotoxicity and prior role of genetic variants as being associated with side-effects of radiotherapy necessitates further investigation for underlying molecular mechanisms. In this study, we investigated gene expression regulated by genetic variants, and copy number variation in prostate cancer survivors with radiotoxicity. METHODS: We investigated proctitis as a radiotoxic endpoint in prostate cancer patients who received radiotherapy (n = 222). We analyzed the copy number variation and genetically regulated gene expression profiles of whole-blood and prostate tissue associated with proctitis. The SNP and copy number data were genotyped on Affymetrix® Genome-wide Human SNP Array 6.0. Following QC measures, the genotypes were used to obtain gene expression by leveraging GTEx, a reference dataset for gene expression association based on genotype and RNA-seq information for prostate (n = 132) and whole-blood tissue (n = 369). RESULTS: In prostate tissue, 62 genes were significantly associated with proctitis, and 98 genes in whole-blood tissue. Six genes - CABLES2, ATP6AP1L, IFIT5, ATRIP, TELO2, and PARD6G were common to both tissues. The copy number analysis identified seven regions associated with proctitis, one of which (ALG1L2) was also associated with proctitis based on transcriptomic profiles in the whole-blood tissue. The genes identified via transcriptomics and copy number variation association were further investigated for enriched pathways and gene ontology. Some of the enriched processes were DNA repair, mitochondrial apoptosis regulation, cell-to-cell signaling interaction processes for renal and urological system, and organismal injury. CONCLUSIONS: We report gene expression changes based on genetic polymorphisms. Integrating gene-network information identified these genes to relate to canonical DNA repair genes and processes. This investigation highlights genes involved in DNA repair processes and mitochondrial malfunction possibly via inflammation. Therefore, it is suggested that larger studies will provide more power to infer the extent of underlying genetic contribution for an individual's susceptibility to developing radiotoxicity.

[New approaches in surgical treatment of acute paraproctitis].

The results of treatment of 77 patients, ageing 18-71 yrs old, for an acute paraproctitis in 2010-2014 yrs were analyzed. A preventive puncture-flush enzymosanation of purulent foci, using immobilized bacterial proteinases (imozimase), metrogyl P in conjunction with low-intensive laser irradiation have permitted to conduct the optimal preoperative preparation of patients, to improve their state, to reduce the local inflammatory reactions intensity significantly.

Is argon plasma coagulation an effective and safe treatment option for patients with chronic radiation proctitis after high doses of radiotherapy? / ¿Es la coagulación con plasma argón una opción terapéutica eficaz y segura en pacientes con proctitis crónica actínica tras dosis altas de radioterapia?

Introduction: In severe cases refractory to medical treatment, APC appears to be the preferred alternative to control persistent rectal bleeding of patients with chronic radiation proctitis. Although successful outcomes have been demonstrated in patients previously treated with moderate doses of radiotherapy, there is reluctance towards its indication due to the concern of severe adverse events in patients treated with high doses of radiation. Objectives: The aim of this study was to assess the efficacy and toxicity of APC in the management of bleeding radiationinduced proctitis in patients treated with high doses of radiation for prostate cancer. Methods and materials: Data from 30 patients were treated with APC due to chronic radiation proctitis, were reviewed retrospectively. All cases had prostate cancer and 9 of them (30 %) underwent previous radical prostatectomy. The median dose of conformal 3D External Beam Radiotherapy (EBRT) delivered was 74 Gy (range 46-76). Median rectal D1cc and D2cc was 72.5 and 72.4 Gy respectively. Median rectal V70, V60 and V40 was 12, 39.5 and 80 %. Cardiovascular and digestive disease, diabetes, smoking behaviour, lowest haemoglobin and transfusion requirements were recorded. Indications for treatment with APC were anemia and persistent bleeding despite medical treatment. Argon gas flow was set at 1.8 l/min with an electrical power setting of 50 W. Results: Median age of all patients was 69.6 years. The median lowest haemoglobin level was 9.6 g/dL. Median time between completion of radiotherapy and first session of APC as 13 months. Ninety-four therapeutic sessions were performed (median 3 sessions). Median time follow-up was 14.5 months (range 2-61). Complete response with resolved rectal bleeding was achieved in 23 patients (77 %), partial response in 5 (16 %) and no control in 2 (6 %). No patients required transfusion following therapy. Two patients developed long-term (> 6 weeks) grade 2 rectal ulceration and grade 2 rectal incontinence, respectively. Conclusions: The argon plasma coagulation is an effective and safe management option in patients with medically refractory rectal bleeding after high doses of radiation for prostate cancer (AU)

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Evaluation of the effectiveness of 4% formalin in the treatment of hemorrhagic actinic proctitis

Radiotherapy is an important discovery as to the treatment of pelvic tumors. Proctitis is frequently observed nowadays, and can be divided into acute and chronic. Treatment with 4% formalin solutions has been used with positive results in literature. Objective: To evaluate the effectiveness and morbidity rates related to the use of 4%formalin in hemorrhagic chronic actinic proctitis. Methods: We evaluated the sigmoidoscopy records and reports of 11 patients with chronic hemorrhagic actinic proctitis from February to December 2010, coming from the Serbian colorectal University Hospital of the State of Sergipe. Results: The study was comprised of 11 patients (36.36% were females and 63.63% were males). Mean age was 67.7 years. Mean time between the end of radiotherapy and the onset of symptoms was 6.6 months. The treatment was completely effective in 27.27% of the cases, and reduced rectal bleeding in 100% of patients. The following main complications were observed: chills (9%), tenesmus (18.18%) and mild stenosis (9%). Conclusions: The 4%formalin solution has fewer side effects, and its administration is very inexpensive. The treatment is effective and reduces bleeding in almost 100% of cases. (AU)

A radioterapia foi uma importante descoberta, no que tange o tratamento das neoplasias de pelve. A proctite é uma das complicações bastante observadas atualmente, podendo ser dividida em aguda e crônica. O tratamento com solução de formalina a 4% vem sendo utilizado com resultados positivos na literatura. Objetivo: Avaliar a eficácia e morbidade do uso da formalina a 4% na retite actínica crônica hemorrágica. Métodos: Foram avaliados os prontuários e laudos das retossigmoidoscopias de 11 pacientes portadores de retite actínica crônica hemorrágica entre o período de fevereiro a dezembro de 2010, oriundos do Serviço de Coloproctologia do Hospital Universitário do Estado de Sergipe. Resultados: O estudo foi composto de 11 pacientes (36,36% feminino e 63,63% masculino). A média das idades foi de 67,7 anos. O tempo médio entre o término da radioterapia e o início dos sintomas foi de 6,6 meses. O tratamento foi completamente efetivo em 27,27%, sendo reduzido sangramento retal em 100% dos pacientes. Como principais complicações foram observadas: calafrio (9%), tenesmo (18,18%) e estenose leve (9%). Conclusão: A solução de formalina a 4% apresenta poucos efeitos colaterais, sendo muito barata a sua administração. O tratamento é efetivo, reduzindo, em praticamente 100% dos casos, o sangramento. (AU)

High dose rate cobalt-60 afterloading intracavitary therapy of uterine cervical carcinomas in Srinagarind hospital - analysis of complications.

OBJECTIVES: To evaluate complications in uterine cervical cancer patients treated with teletherapy combined with high dose rate(HDR) cobalt-60 brachytherapy. MATERIALS AND METHODS: A retrospective study of uterine cervical cancer patients, stages IB-IVB (International Federation of Gynecologists and Obstetricians recommendations), treated by radiotherapy alone between April 1986 and December 1988 was conducted. The patients received teletherapy 50 Gy / 25 fractions, five fractions per week to the whole pelvis together with HDR Cobalt -60 afterloading brachytherapy of 850 cGy/ fraction weekly to point A for 2 fractions. RESULTS: The study subjects were 141 patients with uterine cervical cancer. The mean age was 49 years with a range of 30-78. The mean tumor size was 4.1 cms in diameter (range 1-8 cms ). Mean follow-up time was 2.9 years (range 1 month - 6.9 years). The treatments resulted in a 96.5% complete response rates but morbidity rates of grade 1 and grade 2 radiation proctitis of 27.0%, and 10.6 %. The grade 1 and grade 2 radiation cystitis were 1.4%, and 1.4 %. At the level of grade 3 radiation complications, 0.71% of radiation proctitis and 0.71% small bowel obstruction were observed. The mean onset time to develop radiation proctitis after complete treatment was 15 months with a range of 6-61 months, for radiation cystitis was 30 months (range 9 - 47 months) and for small bowel obstruction was 53 months in the one case it occurred. CONCLUSION: Combined teletherapy along with high dose rate Cobalt -60 brachytherapy of 850 cGy/ fraction, weekly to point A for 2 fractions for uterine cancer demonstrated a slightly higher incidence of grade 2 radiation proctitis. Therefore, treatment using HDR-60 brachytherapy less than 850 cGy per fractionation for decreasing the grade 2 and grade 3 radiation morbidity is recommended.

Rectitis actínica / Radiation induced proctitis

El aumento del uso de la radioterapia en la enfermedad oncológica pelviana ha conducido a un aumento en la incidencia de la rectitis actínica crónico. El objetivo del trabajo es analizar en una institución privada, la prevalencia de Rectitis Actínica crónico.

Evaluation of radiotherapay for localized inflammatory skin and perianal lesions in adult leukemia: A porspectively randomized double blind study.

Thirty-five episodes of localized infection among 20 patients with acute leukemia and granulocytopenia (less than 1000 cells/microliter) were treated with intensive supportive care including systemic antibiotics. In a double blind randomization, 17 of the episodes also received 400 rads of megavoltage irradiation to the site of the lesion given as a single dose and repeated 7 days later. No significant differences were observed in response rates between the irradiated and nonirradiated lesions. Overall, 65% of the irradiated infections and 44% of the nonirradiated lesions responded completely, a difference which is not significant. The median number of days required to achieve maximum clinical response was similar whether or not irradiation was given (10 versus 12 days). Management of such localized infections should include early diagnosis with prompt institution of intensive supportive care including appropriate systemic antibiotics, but low-dose irradiation cannot be recommended as part of the routine management of these lesions.