Adjunctive Hyperbaric Oxygen Therapy promotes successful healing in patients with refractory Crohn ’ s disease 1

PURPOSE: To investigate de adjunctive effect of Hyperbaric Oxygen Therapy in a group of patients with refractory Crohn’s disease. METHODS: A total of 29 subjects with refractory Crohn’s disease were submitted to daily sessions of Hyperbaric Oxygen Therapy, in a 2800 Sechrist Monoplace Hyperbaric Chamber (Sechrist, USA) pressurized to 2.4 ATA. Each session lasted 2 hours. The endpoint was closure of enterocutaneous fistulas and complete healing of Pyoderma Gangrenosum and perineal Crohn’s disease. RESULTS: A total of 829 HBOT sessions were performed and no complications were noted. Overall success rate was 76% (22 cases). Pyoderma Gangrenosum and enterocutaneous fistulas had the highest successful healing rates (100% and 91%, respectively). Perineal Crohn’s disease healing rate was 65%. CONCLUSION: Adjunctive Hyperbaric Oxygen Therapy promoted satisfactory healing in a group of patients with refractory Crohn’s disease.


Introduction
resulting from aberrant immune system activation.The disease primarily affects the gastrointestinal system but other organs may be involved 1 .
Clinical manifestations are heterogeneous and may vary from mild cases (abdominal pain, changes in bowel habit and weight loss) to serious complications such as acute abdomen, Since CD cannot be cured, most treatment options aim the induction and maintenance of remission by controlling HBOT is a treatment modality that consists in 100% oxygen breathing in pressurized chambers.The improvement with HBOT is attributed to local events (such as neovascularization and reduced hypoxia, stem cell mobilization/differentiation and extracellular matrix formation) and systemic effects (decrease in 9-11.The purpose of this study was to evaluate the adjunctive effect of HBOT in a group of patients with of pharmaco-refractory and PG.

Hyperbaric oxygen therapy
Daily HBOT sessions were performedin a 2800 Sechrist Monoplace Hyperbaric Chamber (Sechrist, USA) pressurized to 2.4 ATA and lasted 2 hours, each.The number of sessions was not constant and varied according to the clinical outcome of patients in order to obtain the best results.Basic care of chronic cutaneous lesions was maintained throughout the entire treatment and included cleaning and dressings, antibiotics and surgical satisfactory or unsatisfactory, when improvement could not be noted.
An association between ECF and PCD was noted in 1 (3.5%) case.
Concomitant ECF and PG were found in 1 (3.5%) patient.One patient (3.5%) exhibited all three complications.Table 1 summarizes some of the patients and treatment characteristics.
The median number of sessions was 20 (range, 10-86).A total of 829 HBOT sessions were performed and no complications were noted.Overall success rate was 76% (22 cases).Figure 1 illustrates some cases before and after HBOT.PG and ECF had the highest successful healing rates (100% and 91%, respectively).PCD completely healed in 65% of the cases.The remaining patients had an unsatisfactory response and needed major surgery surgeries (intestinal diversion with proctectomy or abdominalperineal amputation of the rectum).
course of the disease is usually relapsing but some individuals may 2 .
Adjunctive Hyperbaric Oxygen Therapy promotes successful healing in patients with refractory Crohn's disease

Discussion
The complete pathogenesis of CD is unclear.Animal models of colitis have shown that intestinal hypoxia may be observed .This hypoxic microenvironment, in tissue oxygenation 14 .Measurements of oxygen tension on perineal wounds may exhibit increases up to 35 times after HBOT 15 .
Perianal disease can be found in up to 35-45% of CD Surgery is usually recommended for resistant or complex perineal wounds.Care should be taken to avoid extensive damage since poor healing may be found, specially if severe proctitis is present 22 .
Reported response rate for perineal disease treated in regimens of hyperoxygenation range from 75-100% [4][5][6][7][8] .In the present study, complete healing of PCD was obtained in the majority of patients.Although minor surgical procedures were necessary to remove devitalized tissues and control infection, no intestinal diversion or proctectomy was necessary in the group that responded to HBOT.The effects of HBOT in complex wounds include: matrix formation [23][24][25][26] .Those changes in wound microenvironment are powerful stimuli towards healing and could explain some of the results found in CD patients with complex wounds.The same rationale could be used to explain the pain relief, systemic corticosteroids reduction and accelerated healing in PG patients 27 .appropriate if output volume is low.Complicated Fistulas with higher debit, chronic course, labiate, with satellite collection and distal obstruction may have an initial conservative approach; yet, 28 .In the present study, treatment of ECF with HBOT was considerate excellent; however, patients were evaluated immediately after the HBOT sessions and there is no long-term follow-up.Healing failure was found The results of this research are encouraging sincepatients who were refractory to maximum medical treatment obtained high healing rates;however, the small number of patients, the short-term follow-up and the lack of a control group limitour conclusions.Part of the good results could be explained by the close monitoring of patients that included daily clinical evaluations, intensive wound care and optimization of medical therapy.A prospective controlled study could solve this problem; yet, it would be ethically questionable to create a control group and deny a possibility of treatmentin patients with an aggressive condition and limited therapeutic options.This pattern of limitation is shared by most studies that deal with HBOT in severe/refractory CD.The authors believe that a randomized controlled trial with HBOT in CD patients in earlier stages of disease is necessary and will contribute to reduce biases.

Conclusion
A high healing rate was observed in a group of patients with complicated and refractory CD after HBOT.No complications were found during the procedure.The results suggest that HBOT may have an adjunctive role in CD complications.Further

A
prospective institutional review board-approved study was conducted at Clinics Hospital-University of São Paulo 20 -Acta Cirúrgica Brasileira -Vol.31 (supl.1) 2016 (Ribeirão Preto, SP, Brazil).A total of 29 patients with pharmacorefractory CD associated with ECF, PCD or PG were selected to HBOT, from 2008 to 2015.An informed written consent was provided in all cases.Hyperbaric sessions were performed at Hyperbaric Medicine Center-São Paulo Hospital (Ribeirão Preto, SP, Brazil) that keeps a prospective, database of all sessions.
submitted to seton procedure and abscess drainage (E) evidencing reduction of edema and no infection after 30 sessions (F).

TABLE 1 -
Main characteristics of patients and treatment.