Background: Lymphedema is a significant postsurgical complication observed in the majority of breast cancer patients. These multifactorial etiopathogenesis have a significant role in the development of novel diagnostic/prognostic biomarkers and the development of novel therapies. This review aims to ascertain the epigenetic alterations that lead to breast cancer-related lymphedema (BCRL), multiple pathobiological events, and the underlying genetic predisposing factors, signaling cascades pertinent to the lapses in effective prognosis/diagnosis, and finally to develop a suitable therapeutic regimen. Methods and Results: We have performed a literature search in public databases such as PubMed, Medline, Google Scholar, National Library of Medicine and screened several published reports. Search words such as epigenetics to induce BCRL, prognosis/diagnosis, primary lymphedema, secondary lymphedema, genetic predisposing factors for BRCL, conventional therapies, and surgery were used in these databases. This review described several epigenetic-based predisposing factors and the pathophysiological consequences of BCRL, which affect the overall quality of life, and the interplay of these events could foster the progression of lymphedema in breast cancer survivors. Prognosis/diagnostic and therapy lapses for treating BCRL are highly challenging due to genetic and anatomical variations, alteration in the lymphatic vessel contractions, and variable expression of several factors such as vascular endothelial growth factor (VEGF)-E and vascular endothelial growth factor receptor (VEGFR) in breast cancer survivors. Conclusion: We compared the efficacy of various conventional therapies for treating BCRL as a multidisciplinary approach. Further substantial research is required to decipher underlying signaling epigenetic pathways to develop chromatin-modifying therapies pertinent to the multiple etiopathogenesis to explore the correlation between the disease pathophysiology and novel therapeutic modalities to treat BCRL.

Radiotherapy (RT) is the backbone of multimodality treatment of more than half of cancer cases. Despite new modern RT techniques, late complications may occur such as radiation proctitis (RP). The natural history of RP is unpredictable. Minor symptoms may resolve spontaneously or require conservative treatment. On the other hand, for similar and uncomplicated clinical contexts, symptoms may persist and can even be refractory to the progressive increase in treatment measures. Over the last decades, an enormous therapeutic armamentarium has been considered in RP, including hyperbaric oxygen therapy (HBOT). Currently, the evidence regarding the impact of HBOT on RP and its benefits is conflicting. Additional prospective and randomised studies are necessary to validate HBOT's effectiveness in the 'real world' clinical practice. This article reviewed the relevant literature on pathophysiology, clinical presentation, different classifications and discuss RP management including a proposal for a therapeutic algorithm with a focus on HBOT.

Radiation proctitis is a known complication following radiation therapy for pelvic malignancy. The majority of cases are treated nonsurgically. Rectal instillation of formalin solution has been described as a successful treatment for chronic radiation-induced hemorrhagic proctitis resistant to medical treatment. We present our results in patients undergoing treatment with application of 4 % formalin for radiation-induced injury to the rectum.

All patients were treated under anesthesia by direct application of 4 % formalin solution to the affected rectal areas. Patient gender, initial malignancy, grade of proctitis, need for blood transfusion, previous therapy, number of applications and response to treatment with formalin, complications, and length of follow-up were reviewed.

A total of 15 patients with a mean age of 68.9 (range, 48-77) years were followed for 31.3 (range, 18-51) months. The mean interval from the conclusion of radiotherapy and the onset of symptoms was 6.9 months. The mean duration of hemorrhagic proctitis before formalin application was 7.9 months. Ten patients had only one formalin application and five patients required a second application because of the persistent bleeding. Thirteen patients (87 %) had complete cessation of bleeding. No complications related to the formalin treatment were observed.

According to a revision of the literature and our experience, despite the small number of patients in our trial, we can state that the application of 4 % formalin solution is an effective, safe, and well-tolerated treatment for chronic radiation-induced hemorrhagic proctitis with minimal discomfort and no severe complications.

The aim of this study was to review the available literature and define clinical practice guidelines for the use of agents for the prevention and treatment of gastrointestinal mucositis.

A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible.

A total of 251 clinical studies across 29 interventions were examined. Panel members were able to make one new evidence-based negative recommendation; two new evidence-based suggestions, and one evidence-based change from previous guidelines. Firstly, the panel recommends against the use of misoprostol suppositories for the prevention of acute radiation-induced proctitis. Secondly, the panel suggests probiotic treatment containing Lactobacillus spp., may be beneficial for prevention of chemotherapy and radiotherapy-induced diarrhea in patients with malignancies of the pelvic region. Thirdly, the panel suggests the use of hyperbaric oxygen as an effective means in treating radiation-induced proctitis. Finally, new evidence has emerged which is in conflict with our previous guideline surrounding the use of systemic glutamine, meaning that the panel is unable to form a guideline. No guideline was possible for any other agent, due to inadequate and/or conflicting evidence.

This updated review of the literature has allowed new recommendations and suggestions for clinical practice to be reached. This highlights the importance of regular updates.

A non-randomised phase II study suggested a therapeutic effect of hyperbaric oxygen (HBO) therapy on arm lymphoedema following adjuvant radiotherapy for early breast cancer, justifying further investigation in a randomised trial.

Fifty-eight patients with ≥ 15% increase in arm volume after supraclavicular ± axillary radiotherapy (axillary surgery in 52/58 patients) were randomised in a 2:1 ratio to HBO (n=38) or to best standard care (n=20). The HBO group breathed 100% oxygen at 2.4 atmospheres absolute for 100 min on 30 occasions over 6 weeks. Primary endpoint was ipsilateral limb volume expressed as a percentage of contralateral limb volume. Secondary endpoints included fractional removal rate of radioisotopic tracer from the arm, extracellular water content, patient self-assessments and UK SF-36 Health Survey Questionnaire.

Of 53/58 (91.4%) patients with baseline assessments, 46 had 12-month assessments (86.8%). Median volume of ipsilateral limb (relative to contralateral) at baseline was 133.5% (IQR 126.0-152.3%) in the control group, and 135.5% (IQR 126.5-146.0%) in the treatment group. Twelve months after baseline the median (IQR) volume of the ipsilateral limb was 131.2% (IQR 122.7-151.5%) in the control group and 133.5% (IQR 122.3-144.9%) in the treatment group. Results for the secondary endpoints were similar between randomised groups.

No evidence has been found of a beneficial effect of HBO in the treatment of arm lymphoedema following primary surgery and adjuvant radiotherapy for early breast cancer.

Radiation proctitis is a potential complication following pelvic radiation therapy. There are no standard treatments and treatment outcomes are unpredictable. We report our experience with the use of hyperbaric oxygen treatment (HBOT) for radiation proctitis cases refractory to standard medical or laser therapy.

During the period 2000-2004, 10 patients with radiation proctitis were treated with HBOT (three males and seven females; mean age of 65). The median follow-up period was 25 months (range 6-43 months). Patient symptoms were retrospectively scored prior to, and following HBOT, based on the LENT-SOMA scale.

Prior to treatment, three patients had Grade 3 toxicity (i.e. requiring blood transfusions) and seven had Grade 2 toxicity with dominant symptoms of rectal pain and/or diarrhoea. HBOT was well tolerated and 9 of the 10 patients completed a full HBOT treatment program. Rectal bleeding completely stopped in four of nine symptomatic patients and improved in three others. Rectal pain completely remitted in three of five symptomatic patients. Diarrhea remitted completely in one of five patients and improved in three others. Of the 10 patients treated, only two did not respond to HBOT.

Significant improvement of rectal bleeding, diarrhea and rectal pain is possible using HBOT. HBOT should be offered to patients who fail conventional treatments for radiation proctitis.

Late complications are one of the major factors limiting radiotherapy treatment, and their treatment is not codified. Hyperbaric oxygen (HBO) has been used in combination with radiotherapy for over half a century, either to maximise its effectiveness or in an attempt to treat late complications. In this latter case, retrospective trials and case reports are prevailing in literature. This prompted European Society for Therapeutic Radiotherapy and Oncology and European Committee for Hyperbaric Medicine to organise a consensus conference in October 2001, dealing with the HBO indications on radiotherapy for the treatment and prevention of late complications. This updated literature review is part of the documents the jury based its opinion on. A systematic search was done on literature from 1960 to 2004, by only taking into account the articles that appeared in peer review journals. Hyperbaric oxygen treatment involving complications to the head and neck, pelvis and nervous system, and the prevention of complications after surgery in irradiated tissues have been studied. Despite the small number of controlled trials, it may be indicated for the treatment of mandibular osteoradionecrosis in combination with surgery, haemorrhagic cystitis resistant to conventional treatments and the prevention of osteoradionecrosis after dental extraction, whose level of evidence seems to be the most significant though randomised trials are still necessary. The other treatment methods are also outlined for each location.

Anal cancer is an uncommon tumour that represents 4% of all cancers of the lower gastrointestinal tract. Its pathogenesis and treatment have undergone substantial reassessment over the past two decades, and this is likely to continue. Anal cancer can be cured by synchronous chemoradiotherapy, a treatment that both enables anal continence to be retained and reserves abdominoperineal resection of the rectum and anal canal (with formation of a permanent colostomy) for recurrent or residual disease after primary chemoradiotherapy. Overall, survival from anal cancer is now around 70-80% at 5 years. Future challenges will be influenced by an increasing incidence due to human papillomavirus and HIV infection, more accurate characterisation and treatment of early (in situ) disease, and optimisation of chemoradiation regimens.

A recent case highlights one of the on-going and unresolved controversies in pediatric ethics: who makes treatment decisions for children. Children, by definition, do not have the maturity to make medical choices. Those decisions must be made for them. The issue remains by whom and on what standard those choices should be made.

Chronic radiation proctitis produces a range of clinical symptoms for which there is currently no recommended standard management. The aim of this review was to identify the various non-surgical treatment options for the management of late chronic radiation proctitis and evaluate the evidence for their efficacy. Synonyms for radiation therapy and for the spectrum of lower gastrointestinal radiation toxicity were combined in an extensive search strategy and applied to a range of databases. The included studies were those that involved interventions for the non-surgical management of late radiation proctitis. Sixty-three studies were identified that met the inclusion criteria, including six randomised controlled trials that described the effects of anti-inflammatory agents in combination, rectal steroids alone, rectal sucralfate, short chain fatty acid enemas and different types of thermal therapy. However, these studies could not be compared. If the management of late radiation proctitis is to become evidence based, then, in view of its episodic and variable nature, placebo controlled studies need to be conducted to clarify which therapeutic options should be recommended. From the current data, although certain interventions look promising and may be effective, one small or modest sized study, even if well-conducted, is insufficient to implement changes in practice. In order to increase recruitment to trials, a national register of cases with established late radiation toxicity would facilitate multi-centre trials with specific entry criteria, formal baseline and therapeutic assessments providing standardised outcome data.