- Open Access
Risk factors for refractory enterocutaneous fistula following button jejunostomy removal and its treatment using a novel extraperitoneal approach in patients with oesophageal cancer: a retrospective cohort study
BMC Gastroenterology volume 22, Article number: 486 (2022)
Enterocutaneous fistula after removal of the jejunostomy tube leads to multiple problems, such as cosmetic problems, decreased quality of life, electrolyte imbalances, infectious complications, and increased medical costs. However, the risk factors for refractory enterocutaneous fistula (REF) after button jejunostomy removal remain unclear. Therefore, in this study, we assessed the risk factors for REF after button jejunostomy removal in patients with oesophageal cancer and reported the surgical outcomes of the novel extraperitoneal approach (EPA) for REF closure.
This retrospective cohort study included 47 patients who underwent button jejunostomy removal after oesophagectomy for oesophageal cancer. We assessed the risk factors for REF in these patients and reported the surgical outcomes of the novel EPA for REF closure at the International University of Health and Welfare Hospital between March 2013 and October 2021. The primary endpoint was defined as the occurrence of REF after removal of the button jejunostomy, which was assessed using a maintained database. The risk factors and outcomes of the EPA for REF closure were retrospectively analysed.
REFs occurred in 15 (31.9%) patients. In the univariate analysis, REF was significantly more common in patients with albumin level < 4.0 g/dL (p = 0.026), duration > 12 months for button jejunostomy removal (p = 0.003), and with a fistula < 15.0 mm (p = 0.002). The multivariate analysis revealed that a duration > 12 months for button jejunostomy removal (odds ratio [OR]: 7.15; 95% confidence interval [CI]: 1.38–36.8; p = 0.019) and fistula < 15.0 mm (OR: 8.08; 95% CI: 1.50–43.6; p = 0.002) were independent risk factors for REF. EPA for REF closure was performed in 15 patients. The technical success rate of EPA was 88.2%. Of the 15 EPA procedures, fistula closure was achieved in 12 (80.0%). The complications of EPA (11.7%) were major leakages (n = 3) and for two of them, EPA procedure was re-performed, and closure of the fistula was finally achieved.
This study suggested that duration > 12 months for button jejunostomy removal and fistula < 15.0 mm are the independent risk factors for REF after button jejunostomy removal. EPA for REF closure is a novel, simple, and useful surgical option for patients with REF after oesophagectomy.
Early enteral nutrition is recommended for peri-operative management of oesophageal cancers to reduce complications . Feeding jejunostomy is a common pathway for enteral nutrition after oesophagectomy, and it is not uncommon to require enteral nutrition by feeding jejunostomy for a long time, not only in the peri-operative period but also for anorexia and weight loss due to recurrences and chemotherapy adverse events [2, 3]. However, serious complications of feeding jejunostomy, such as bowel obstruction, abdominal wall infection, tube deviation, and peritonitis owing to fistula injury during replacement, have been reported [4,5,6]. In particular, enterocutaneous fistula after removal of the jejunostomy tube leads to multiple problems, such as cosmetic problems, decreased quality of life, electrolyte imbalances, infectious complications, and increased medical costs.
Button jejunostomy has cosmetic advantages and employs an easily replaceable feeding button compared with the conventional Witzel jejunostomy [7, 8]. Conversely, it has been reported that refractory enterocutaneous fistulas (REFs) are more common after removal of button jejunostomy than Witzel jejunostomy . Few studies have reported the risk factors of REFs after button jejunostomy removal. In addition, there are few reports of effective minimally invasive treatments for REFs that failed to close the defect spontaneously.
We introduced button jejunostomy in oesophagectomy for oesophageal cancer in 2010, and have been performing a novel extraperitoneal approach for closure of REFs. In this study, we examined the risk factors for REFs after removal of button jejunostomy in patients with oesophageal cancer and reported the surgical outcomes of the extraperitoneal approach (EPA) for closure of REFs.
This retrospective cohort study included 47 patients who underwent button jejunostomy removal after oesophagectomy for oesophageal cancer at the International University of Health and Welfare Hospital (Nasushiobara, Tochigi Prefecture, Japan) between March 2013 and October 2021 (Fig. 1). We aimed to assess the risk factors for REFs in them and to evaluate the surgical outcomes of EPA for closure of REFs.We retrospectively examined the primary endpoint, which was defined as the occurrence of REF after button jejunostomy removal, using a maintained database. We included patients in whom button jejunostomy was created during oesophagectomy for oesophageal cancer and removed after surgery with complete follow-up data and clinical details available. Patients who underwent direct percutaneous endoscopic jejunostomy and those who underwent Witzel jejunostomy were excluded.
This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of the International University of Health and Welfare Hospital (IR number: 22-B-16). Informed consent was taken from all patients in the form of giving opportunity to opt out their records from being used in the analyses.
Jejunostomy placement and post-operative feeding (Fig. 2a)
Button jejunostomy was performed in the same method in all patients during oesophagectomy. The details of button jejunostomy creation were described in a previous report . We inserted a 24-Fr button-type catheter (IDEAL BUTTON®; Olympus Medical Systems Co.Ltd, Tokyo, Japan) to the jejunum. The appropriate length of the button-type catheter was determined based on the thickness of the abdominal wall. Continuous enteral nutrition was initiated from the first post-operative day at a rate of 10 mL/h and gradually increased to 60–80 mL/h, according to the gradual decrease in the intravenous fluid administration. After discharge, supportive enteral nutrition at 400–800 kcal/day was continued, according to the oral intake. Replacement of the jejunostomy button was performed every 4–6 months. When it was judged that supportive enteral nutrition was not required using blood investigations, imaging, and body weight evaluation, removal of the jejunostomy button was performed.
Definition of REF (Fig. 2b)
REF was defined as a condition, in which spontaneous closure of the fistula was not achieved after removal of the button jejunostomy with continuous leakage and requirement of surgical treatment.
Measurement of the Fistula length (Fig. 2c)
The length of the fistula was measured as the vertical distance between the skin and intestinal puncture site in the coronal section using computed tomography performed within 1 month before button jejunostomy removal.
EPA for REF closure (Fig. 3)
The EPA for REF closure was performed by two surgeons, with the patient being in the supine position. Local, general, or spinal anaesthesia was administered according to the patients’ surgical tolerance.
The fistula was identified using a probe, and a spindle-shaped incision of approximately 3–5 cm around the fistula was created (Fig. 3a).
The fistula was separated from the surrounding tissue as deeply as possible, paying attention to the injury to the fistula and its arrival into the abdominal cavity (Fig. 3b).
The fistula was transected by double ligation using absorbable sutures (Fig. 3c).
The rectus abdominis muscle was released followed by covering it on the transected fistula.
The anterior layer of the rectus sheath and subcutaneous tissue were closed using absorbable sutures and the epidermis was closed using a skin stapler (Fig. 3d).
The Mann–Whitney U test, unpaired t-test, and chi-squared test were used to compare the continuous and dichotomous categorical variables. Multivariate analyses were performed using a multivariate logistic regression model. The cut-off levels of each variable in the univariate and multivariate analyses were defined as the values that maximised the Youden index for predicting the REF on each receiver operating characteristic curve. Statistical significance was set at p < 0.05. STATA/IC version 16.0 (STATA Statistical Software; StataCorp, College Station, TX, USA) was used for statistical analyses.
In total, 47 patients were enrolled in this study. The patients’ baseline characteristics and oncological and peri-operative factors are summarised in Table 1. The study included 41 men and six women, with a median age of 70.4 ± 9.4 years. The median body mass index was 19.9 ± 3.1, and the histological types were squamous cell carcinoma in 41 (87.2%) patients and others in six (12.8%) patients. Thoracic, abdominal, and cervical oesophageal cancers were present in 36 (76.6%), nine (19.2%), and two (4.3%) patients, respectively. The pathological stages were as follows: stage I, n = 26 (55.3%); stage II, n = 13 (27.7%); and stage III, n = 8 (17.0%). Post-operative adjuvant chemotherapy was administered to 28 (59.6%) patients.
Post-operative pneumonia was observed in 12 (25.3%), anastomotic leakage in seven (14.8%), recurrent laryngeal nerve paralysis in 12 (25.5%), ileus in six (12.8%), and REF in 15 (31.9%) patients. The median length of the fistula was 16.3 ± 6.4 mm, and the median duration for button jejunostomy removal was 12.6 ± 7.0 months. The mean follow-up period was 46.4 (2.4–91.2) months. During the follow-up period, nine (19.2%) patients relapsed and 11 (23.4%) patients died.
Risk factors for REF
The 47 patients were divided into the REF and non-REF groups (Table 2). In the univariate analysis, REF was significantly more common in patients with albumin level < 4.0 g/dL (p = 0.026), duration for button jejunostomy removal > 12 months (p = 0.003), and fistula < 15.0 mm (p = 0.002). All variables that demonstrated a significant difference in the univariate analysis were included in the multivariate analysis using a logistic regression model. In the multivariate analysis, duration for button jejunostomy removal > 12 months (odds ratio [OR]: 7.15; 95% confidence interval [CI]:1.38–36.8; p = 0.019) and fistula length < 15.0 mm (OR: 8.08; 95% CI: 1.50–43.6; p = 0.002) were found to be independent risk factors for REF.
Outcomes of EPA for REF closure
The baseline characteristics and peri-operative clinical outcomes of patients with REF who underwent REF closure with EPA are presented in Table 3. The mean age was 72.2 years (61–91 years), and all were men. The mean length of the fistula was 12.7 (8.8–17.3) mm, and the mean duration for jejunostomy removal was 18.2 (2–29) months. The mean albumin level was 3.6 (3.0–4.2) g/dL. EPA was performed in 15 patients (17 procedures), and the conversion to bowel resection due to unexpected laparotomy during EPA was performed in two (11.7%) patients.
The technical success rate of EPA was 88.2% (15/17 cases). Two patients required bowel resection owing to a short fistula length (< 11.0 mm) and injury to the fistula. Local, epidural, and general anaesthesia was administered in five (29.4%), three (17.6%), and 10 (66.7%) patients (with duplication), respectively. The fistula closure was achieved in 12 (80.0%) of 15 EPAs. The mean operation time was 38 (14–114) min, and the mean length of hospital stay was 9.5 (1–42) days. The complication of EPA was major leakages (n = 3, 13.3%), and for two of them, EPA was re-performed, and fistula closure was finally achieved. All four patients, including one patient who had undergone bowel resection, with major leakage had (1) American Society of Anaesthesiologists score ≥ 3 points with coronary artery disease or chronic obstructive pulmonary disease, (2) cancer recurrence, (3) serum albumin level < 3.3 g/dL at the time of button jejunostomy removal, and (4) heavy smoking history.
Button jejunostomy is a novel jejunostomy creation technique first reported in 1989 [7,8,9,10]. There are some advantages of the button jejunostomy, including the simplicity of the procedure, ease of replacement, low risk of tube deviations and obstructions, patient’s aesthetic outcomes, and a high quality of life. However, a common complication is REF after button jejunostomy removal. No studies have shown the risk factors for RFF after button jejunostomy removal and the outcomes of the EPA for REF closure, until now.
In this study, the duration for button jejunostomy removal (> 12 months) and fistula length (< 15.0 mm) were found to be the independent risk factors for REF, and minimally invasive REF closure by the EPA had good outcomes.
There is no consensus on the timing of jejunostomy removal because the amount of oral intake varies depending on the patient’s primary disease stage and the presence of post-operative complications. However, according to a previous report , the risk of REF increased when the duration of jejunostomy removal was > 1 year, and the results of this study also supported the previous report. Epithelialisation of the fistula was considered to gradually form > 1 year, resulting in REF .
Since the fistula length was measured as the vertical distance between the skin and the intestinal puncture site, it was defined as the sum of the subcutaneous fat thickness plus the rectus abdominis muscle. However, the body mass index or presence of sarcopenia, which is an index of skeletal muscle mass, does not show a significant difference in the risk of REF; therefore, the fistula length should be considered as an independent risk factor. It has been reported that enterocutaneous fistulas, which close spontaneously, have long fistula tracts (> 2 cm) , and our results could be a useful cut-off value for REF in button jejunostomy with a short fistula length.
The length and thickness of the fistula are considered to be the reasons for frequent development of REF after button jejunostomy removal than after Witzel jejunostomy. The jejunostomy button used in our hospital is 24 Fr with a diameter of 8.0 mm, whereas the jejunal tube used in the Witzel jejunostomy is 10–12 Fr with a diameter of 4.0 mm. The diameter of the fistula was longer in button jejunostomy than in Witzel jejunostomy. Furthermore, in button jejunostomy, a fistula is formed vertically to the abdominal wall, but in Witzel jejunostomy, a diagonal fistula is formed; therefore, the length of the fistula in button jejunostomy is shorter than that in Witzel jejunostomy. It has been reported that enterocutaneous fistula that can be expected to spontaneously close have a diameter of ≤ 1 cm and length of ≥ 2 cm . This report supports our hypothesis that REF occurs more frequently after button jejunostomy removal. In addition, ‘free distal flow’ has been reported as an important factor in spontaneous closure . Button jejunostomy has an acute bending angle between the jejunostomy and abdominal wall compared with Wizel jejunostomy , which may interfere with the natural flow of intestinal fluid to the distal intestinal tract and lead to REF.
Spontaneous closure usually can be expected after removal of the jejunostomy tube; however spontaneous closure often requires 4–6 weeks [4, 11, 12]. Immediate fistula closure can be an effective option for patients waiting for spontaneous fistula closure that require a long period of time to close or those suffering from REF. There are some reports of minimally invasive treatments for REF, such as the use of over-the-scope clip  and fibrin glue . The success rate is reported to be approximately 50–87.5%, but the applicable fistula is a small enterocutaneous fistula with a diameter of approximately 5 mm or a low-output enterocutaneous one. It is difficult to treat a high-output fistula with a large diameter, such as REF, after removing the jejunostomy button. Although bowel resection, including the fistula, is highly curative, it can be a highly invasive treatment for patients after oesophagectomy with severe intra-abdominal adhesions, malnutrition, and poor surgical tolerance.
For the aforementioned reasons, we devised an EPA to treat the REF. This procedure is simple, has a short operative time, can be performed even under local anaesthesia, does not reach the abdominal cavity, and has the advantage of not being affected by adhesions from the previous surgery. The fistula was transected by separating and ligating it as deep as possible on the intestinal side, reducing the pressure on the intestinal side of the fistula, and closing it by causing scarring at the transected point. In this procedure, we consider that the fistula can be easily separated from the surrounding tissue as deeply as possible with good visual field, and aesthetic outcomes of the wound can be improved along the skin dividing line by creating a spindle-shaped incision of approximately 3–5 cm around the fistula.
The success rate of EPA for REF was 80%, with good results. If the patient was judged to be operable under general anaesthesia, EPA was performed under general anaesthesia in case of unexpected fistula injury or laparotomy.
This study had some limitations. First, it was retrospective and was conducted at a single centre with a small number of patients. Further studies using data from a large-scale, multicentre registry should be conducted in the future. Second, this study is limited to button jejunostomy and may not be applicable to REF in other jejunostomy creation methods. Third, fistula closure using a single EPA may not be effective in high-risk patients with cancer recurrence or poor nutrition. In addition, the definition of REF remains controversial, and in this study, the timing of performing the EPA was not unified. Finally, considering that the high incidence rate of REF after removal of the button jejunostomy (31.9%), instead of performing button jejunostomy routinely, early removal of the button jejunostomy or Witzel jejunostomy should be considered depending on the patients’ risk.
This study suggested that duration > 12 months for button jejunostomy removal and fistula < 15.0 mm are the independent risk factors for REF after button jejunostomy removal. The technique used in this study, EPA for REF closure, is a novel, simple, and useful surgical option for patients with REF after oesophagectomy.
The datasets generated and/or analysed during the current study are not publicly available due to the anonymity of the participants but are available from the corresponding author on reasonable request.
Refractory enterocutaneous fistula
Barlow R, Price P, Reid TD, Hunt S, Clark GWB, Havard TJ, et al. Prospective multicentre randomised controlled trial of early enteral nutrition for patients undergoing major upper gastrointestinal surgical resection. Clin Nutr. 2011;30:560–6.
Atkins BZ, Shah AS, Hutcheson KA, Mangum JH, Pappas TN, Harpole DH Jr, et al. Reducing hospital morbidity and mortality following esophagectomy. Ann Thorac Surg. 2004;78:1170–6.
Gupta V. Benefts versus risks: a prospective audit. Feeding jejunostomy during esophagectomy. World J Surg. 2009;33:1432–8.
Choi AH, O’Leary MP, Merchant SJ, Sun V, Chao J, Raz DJ, et al. Complications of feeding jejunostomy tubes in patients with gastroesophageal cancer. J Gastrointest Surg. 2017;21:259–65.
Koterazawa Y, Oshikiri T, Hasegawa H, Yamamoto M, Kanaji S, Yamashita K, et al. Routine placement of feeding jejunostomy tube during esophagectomy increases postoperative complications and does not improve postoperative malnutrition. Dis Esophagus. 2020;33:doz021.
Kamada T, Ohdaira H, Takeuchi H, Takahashi J, Marukuchi R, Ito E, et al. Vertical distance from navel as a risk factor for bowel obstruction associated with feeding jejunostomy after esophagectomy: a retrospective cohort study. BMC Gastroenterol. 2020;20:354.
Ruiz-Elizalde AR, Frischer JS, Cowles RA. Button-loop feeding jejunostomy. J Gastrointest Surg. 2009;13:1376–8.
Shinohara T, Fujita T, Suzuki Y, Sano Y, Kashiwagi H, Yanaga K. Interim results of nutritional support through a button-type jejunostomy after total gastrectomy. Am Surg. 2009;75:148–51.
Ishikawa Y, Nishikawa K, Fukushima N, Takahashi K, Hasegawa Y, Yuda M, et al. Assessment of button-type jejunostomy for nutritional management after esophagectomy in 201 cases. Int J Clin Oncol. 2021;26:2224–8.
Stellato TA, Gauderer MW. Jejunostomy button as a new method for long term jejunostomy feedings. Surg Gynecol Obstet. 1989;168:552–4.
Lloyd DAJ, Gabe SM, Windsor ACJ. Nutrition and management of enterocutaneous fistula. Br J Surg. 2006;93:1045–55.
Graf D-P, JI, Kumpf VJ, de Aguilar-Nascimento JE, Hall AM, McKeever L, Steiger E, et al. ASPEN-FELANPE clinical guidelines: Nutrition support of adult patients with enterocutaneous fistula. Nutr Hosp. 2020;37:875–85.
Zhang J, Da B, Diao Y, Qian X, Wang G, Gu G, et al. Efficacy and safety of over-the-scope clips (OTSC®) for closure of gastrointestinal fistulas less than 2 cm. Surg Endosc. 2022;36:5267–74.
Rábago LR, Ventosa N, Castro JL, Marco J, Herrera N, Gea F. Endoscopic treatment of postoperative fistulas resistant to conservative management using biological fibrin glue. Endoscopy. 2002;34:632–8.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Ethics approval and consent to participate
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. The study was approved by the Institutional Review Board of the International University of Health and Welfare Hospital (approval no: 22-B-16). All the data were subjected to strict privacy policies, and the patients or their family members had the option to drop out of the study at any time. The requirement for acquisition of informed consent from patients was waived by the Institutional Review Board of the International University of Health and Welfare Hospital because of the retrospective design of this study and anonymised data.
Consent for publication
Written informed consent was obtained from the patient for publication of this paper and accompanying images.
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Kamada, T., Ohdaira, H., Nakashima, K. et al. Risk factors for refractory enterocutaneous fistula following button jejunostomy removal and its treatment using a novel extraperitoneal approach in patients with oesophageal cancer: a retrospective cohort study. BMC Gastroenterol 22, 486 (2022). https://doi.org/10.1186/s12876-022-02524-2
- Button jejunostomy
- Refractory enterocutaneous fistula
- Fistula closure