Abstract
Background:
In patients diagnosed with sarcopenia, the presence of chronic preoperative inflammation, assessed by the ratio of the visceral fat area (VFA) to the total abdominal muscle area index (TAMAI) (VFA/TAMAI), has been found to adversely affect wound healing. An elevated VFA/TAMAI may contribute to a higher incidence of postoperative recurrent fistulas (RFs) following definitive surgery (DS) for small intestinal fistulas accompanied by diffuse extensive abdominal adhesions. The objective of this study was to evaluate the predictive value of VFA/TAMAI for postoperative RFs.
Methods:
The study enrolled 183 sarcopenic patients, with a median age of 51 years [interquartile range (IQR): 38–61 years), a median body mass index of 19.6 kg/m2 (IQR: 18.9–21.0 kg/m2) who underwent DS for small intestinal fistulas between January 2018 and October 2022 were included in the multicenter study. The outcomes assessed were RFs and postoperative length of stay (LOS). VFA/TAMAI was examined as a potential risk factor for each outcome.
Results:
Out of the 183 patients, 20.2% (n=37) developed RFs. The multivariate regression analysis identified VFA/TAMAI as the sole factor associated with RFs [odds ratio=1.78, 95% confidence interval (CI): 1.09–2.87, P=0.02]. The multivariable Cox regression analysis demonstrated that an elevated VFA/TAMAI was linked to a reduced postoperative LOS (hazard ratio=0.69, 95% CI: 0.59–0.81, P<0.001).
Conclusion:
In sarcopenic patients, a high VFA/TAMAI predicated the occurrence of RFs after DS for small intestinal fistulas in the presence of diffuse extensive abdominal adhesions.
Keywords: body composition, fistula, length of stay, outcomes, surgery
Introduction
Highlights
Definitive surgery (DS) for intestinal fistula with diffuse extensive adhesions results in a high incidence of recurrent fistula (RF).
In patients with sarcopenia, a higher ratio of the visceral fat area (VFA) to the total abdominal muscle area index (TAMAI) indicates an inflammatory imbalance.
VFA/TAMAI was associated with RF after DS for intestinal fistula with diffuse extensive adhesions.
Abdominal adhesions are understood to be the combined effect of fiber exudation and fibrinolysis following inflammation caused by peritoneal injury1–3 due to the effusion of intestinal juice resulting from the intestinal fistula. Insufficient fluid drainage prevents rapid elimination of inflammation in the short term and can, on the one hand, lead to continuous fiber deposition exacerbating adhesion4 and on the other hand, render adhesion insoluble by inhibiting fibrinolysis, thereby increasing the degree of adhesion3,5. Severe adhesion, as an indicator of poor healing of peritoneal injury, consequently intensifies inflammation6,7. This interaction results in the persistence of chronic inflammation. Sustained chronic inflammation can impair the immune system, delay wound healing8, and negatively affect postoperative outcomes following abdominal surgery8.
In sarcopenic patients, definitive surgery (DS) for a small intestinal fistula with diffuse extensive abdominal adhesions is frequently associated with a high incidence of postoperative complications, including recurrent fistula (RF)9,10. Although intraoperative injury and stress can contribute to poor healing and thus a higher incidence of RF9,10, in these particular patients with a pathological state of persistent chronic inflammation, metabolism, immunity, and overall healing ability are compromised. As a result, it is logical to deduce that a higher incidence of RF could be observed in patients exhibiting higher levels of chronic inflammation. Notably, the ratio of the visceral fat area (VFA) to total abdominal muscle area index (TAMAI), or VFA/TAMAI, has been proposed as a common index for evaluating persistent chronic inflammation11,12.
With this in mind, the objective of the present study was to assess the predictive value of VFA/TAMAI for postoperative recurrence following DS for small intestinal fistula with diffuse extensive abdominal adhesions in sarcopenic patients.
Materials and methods
This retrospective cohort study was carried out at four large regional enterocutaneous fistula (ECF) centers, where hundreds of patients with refractory ECFs receive treatment annually. All investigations adhered to the ethical standards set forth in the Declaration of Helsinki. The study was reported in accordance with the STROCSS (strengthening the reporting of cohort, cross-sectional and case–control studies in surgery) criteria13 (Supplemental Digital Content 4, http://links.lww.com/JS9/A908).
Patients
Four hundred seventy-nine sarcopenic patients who underwent DS for small intestinal fistula with a 9.8% RF recurrence rate (n=47) were screened between January 2018 and October 2022. One hundred ninety-three of the 479 patients with diffuse extensive abdominal adhesions were further selected, of which 10 patients were excluded from the study (including 2 younger than 18 years old and 8 without complete records). Ultimately, 183 eligible patients enrolled in the study.
The patients were followed up until discharge. The primary outcome was RF, and the secondary outcome was the postoperative length of stay (LOS). VFA/TAMAI was analyzed as a risk factor for each outcome.
Status of abdominal adhesions
The abdominal adhesion status was assessed as described by Hobson et al.14 during small intestinal fistula excision. Abdominal adhesions were classified as follows: Grade I=no adhesions; Grade II=minimal adhesions localized to one or two areas; Grade III=diffuse but not extensive adhesions; Grade IV=diffuse extensive adhesions that are easily lysed; Grade V=diffuse extensive, dense adhesions that are difficult to lyse. Grades IV and V abdominal adhesions were defined as diffuse extensive abdominal adhesions. Abdominal adhesions were further characterized more precisely. When over 50% of the intestinal tract in the abdominal cavity was adherent with poor dissociation, the term ‘diffuse extensive adhesions’ was applied. When abundant capillaries invaded more than 50% of the adhesions between the two segments of the intestine, rendering the shape of the intestine in the area indistinguishable, the term ‘dense adhesions’ was employed10.
Assessment of sarcopenia
Sarcopenia was evaluated using abdominal computed tomography (CT) with Image J software (NIH, Bethesda, Maryland, USA). For each patient, two consecutive axial CT images at the level of the L3 lumbar vertebra’s inferior endplate were processed and subsequently averaged. Sarcopenia was defined as a TAMAI of <43 cm2/m2 in males with a body mass index (BMI) of <25 kg/m2, <53 cm2/m2 in males with a BMI of ≥25 kg/m2, and <41 cm2/m2 in females15.
Preoperative management
DF was implemented following the S (sepsis control), O (optimization of nutritional status), W (wound care), A (anatomy of fistula), T (timing of surgery), and S (surgical strategy) protocol16. To provide optimal nutritional support, calorie intake was set at 30 kcal/kg. A nasojejunal tube for total enteral nutrition [(EN), Nutrison Fibre (1.0 kcal/ml), Nutricia, Wuxi, China] was preferred in each case. For patients unable to receive total EN, parenteral nutrition (PN) was provided as a supplement. DS was not considered until the patient’s condition had been controlled for over a month, along with achieving the following parameters: BMI ≥18.0 kg/m2 with normal physical strength, hemoglobin ≥100 g/l, and albumin (Alb) ≥30 g/l. Additionally, the interval should have been at least 3 months since the fistula occurrence.
Surgical strategy
The chief surgeon at each of the four centers performed the DS. During surgery, the digestive tract was progressively dissociated. For every small intestinal fistula, laterolateral end anastomosis was conducted using a linear stapler. In patients with enteroatmospheric fistula, hernia repair was performed during DS. Component separation technology, combined with onlay mesh repair, was utilized. A biological patch was applied during the procedure. A negative pressure drainage system was placed under all incisions before completing the surgery.
Postoperative management
Red blood cells and human serum Alb were infused to maintain hemoglobin at >100 g/l and/or Alb at >30 g/l. EN was implemented following defecation. The EN administration rate increased from 20 to 80 ml/h, with a daily increment of 10 ml/h. PN was administered from postoperative day 1 and was halved when EN reached a rate of 50 ml/h. PN administration was terminated once total EN was delivered. Gastroenterography was performed 14 days after DS. RF was considered the definitive diagnosis.
Data collection and statistical analysis
Demographic data (sex, age, and BMI), preoperative laboratory examination results, and fistula characteristics were recorded within 1 week before surgery. Enhanced CT was employed to assess TAMAI, VFA, and subcutaneous fat area (SFA) within 1 week before DS. Relevant data during and after DS were examined according to medical records. The Statistical Package for the Social Sciences version 26.0 for Windows (IBM, Analytics, Armonk, New York) was utilized for statistical analyses. Continuous variables were evaluated using the Mann–Whitney U and Kruskal–Wallis tests. Bonferroni correction was applied when statistical significance was detected after Kruskal–Wallis tests. Fisher’s exact test was used for categorical variables. Kaplan–Meier estimates followed by a log-rank test were used to compare the effects of different methods. Logistic regression and Cox regression were employed to assess correlations with variables with P<0.2 in univariate analysis. Multivariate linear regression was used to analyze the association between VFA/TAMAI and the postoperative inflammatory index. Statistical significance was set at P<0.05.
Results
Demographic and clinical characteristics
One hundred eighty-three eligible patients with a median age of 51 years [interquartile range (IQR): 38–61 years] and a median BMI of 19.6 kg/m2 (IQR: 18.9–21.0 kg/m2) were included in the study. Among the 183 patients, 108 (59%) were males. All continuous variables in Table 1 were not subject to normal distribution. The interval from fistula occurrence to DS was 4 months (IQR: 3.0–5.0 months). The etiology encompassed trauma (n=107), obstruction due to previous abdominal surgery (n=62), mesenteric thrombosis (n=11), and unclear perforation (n=3). Extra PN was administered in 24 of the 183 patients (Table 1).
Table 1.
Characteristics of the 183 patients.
| Characteristics | |
|---|---|
| Demographic data | |
| Male, N (%) | 108 (59) |
| Age, years (median, IQR) | 51 (31–61) |
| BMI, kg/m2 (median, IQR) | 19.6 (18.9–21.0) |
| Nutritional assessments | |
| Controlling nutritional status (CONUT) score (median, IQR) | 2 (2–3) |
| Nutrition risk screening 2002 (NRS 2002) ≥3, N (%) | 120 (65.6) |
| Fistula characteristics | |
| Interval from fistula occurred to DS, months (median, IQR) | 4.0 (3.0–5.0) |
| Distance from Treitz to the fistula, N (%) | |
| <100 cm | 22 (12.1) |
| ≥100 cm | 161 (87.9) |
| Length of small intestine, N (%) | |
| <300 cm | 33 (18.1) |
| ≥300 cm | 150 (81.9) |
| PN required, N (%) | 24 (13.1) |
| Complicated with ventral hernia, N (%) | 132 (72.1) |
| Etiology, N (%) | |
| Trauma | 107 (58.5) |
| Obstruction | 62 (33.9) |
| Others | 14 (7.7) |
| Laboratory test results | |
| Hemoglobin before DS, g/l (median, IQR) | 126.0 (117.0–132.0) |
| Albumin before DS, g/l (median, IQR) | 36.3 (33.0–38.0) |
| CRP before DS, mg/l (median, IQR) | 7.2 (6.1–15.2) |
| WBC before DS, 109/l (median, IQR) | 6.7 (6.1–8.2) |
| Intraoperative condition and postoperative care | |
| American Society of Anesthesiologists (ASA) physical classification (median, IQR) | 2 (2–3) |
| Abdominal adhesion grade V, N (%) | 77 (42.1) |
| Duration of DS, hours (median, IQR) | 4.75 (3.5–6.0) |
| Deciliter of bleeding loss during DS, dl (median, IQR) | 10.0 (9.0–17.0) |
| The amount of red blood cell suspension input during DS and within 48 h after DSa, N (%) | |
| <10 U | 105 (57.4) |
| ≥10 U | 78 (42.6) |
| The amount of albumin input during DS and within 48 h after DSb, N (%) | |
| <100 g | 99 (54.1) |
| ≥100 g | 84 (45.9) |
| Comorbidity, N (%) | |
| Hypertension | 12 (6.5) |
| Elevated fasting blood glucose | 21 (11.5) |
In order to maintain the hemoglobin >100 g/l within 48 h after definitive surgery.
In order to maintain the albumin >30 g/l within 48 h after definitive surgery.
DS, definitive surgery; CRP, C-reactive protein; IQR, interquartile range; PN, parenteral nutrition; WBC, white blood cell.
Sarcopenia and body composition
Table 2 displays the body composition characteristics. All continuous variables in Table 2 were not subject to normal distribution, except for VFA/SFA. The median TAMAI of the 183 patients was 31.6 cm2/m2 (IQR: 26.4–36.0 cm2/m2). The median VFA/TAMAI of the entire study population was 2.4 cm2/m2 (IQR: 1.8–3.1 cm2/m2).
Table 2.
Characteristics about sarcopenia.
| Characteristics | |
|---|---|
| N (%) | 183 (100) |
| TAMAI, cm2/m2 (median, IQR) | 31.6 (26.4–36.0) |
| VFA, cm2 (median, IQR) | 79.0 (56.9–98.0) |
| VFA/TAMAI (median, IQR) | 2.4 (1.8–3.1) |
| VFA/TAMAI, N (%) | |
| <2 | 60 (32.8) |
| ≥2 and <3 | 66 (36.1) |
| ≥3 | 57 (31.1) |
| SFA, cm2/m2 (median, IQR) | 81.0 (59.0–110.0) |
| VFA/SFA | 0.93 (0.65–1.33) |
| VFA/SFA, N (%) | |
| <1 | 97 (53.1) |
| ≥1 | 86 (46.9) |
IQR, interquartile range; SFA, subcutaneous fat area; TAMAI, total abdominal muscle area index; VFA, visceral fat area.
Among the 183 patients, 60, 66, and 57 patients had a VFA/TAMAI of <2, ≥2 and <3, and ≥3. Table 3 shows the characteristics of patients with varying VFA/TAMAI values. The characteristics were comparable, except for Alb, C-reactive protein (CRP), and white blood cell (WBC) levels before DS. CRP in patients with VFA/TAMAI of ≥3 was 16.3 mg/l (IQR=7.1–24.3) mg/l higher than that with VFA/TAMAI of <2 (7.2 mg/l [IQR=5.4–9.2] mg/l; P<0.001) and VFA/TAMAI of ≥2 and <3 (8.1 mg/l [IQR=6.3–14.5] 16.3 mg/l; P<0.001). WBC in patients with VFA/TAMAI of ≥3 was 7.8×109/l (IQR=6.6–8.6) 109/l higher than that with VFA/TAMAI of <2 (6.1×109/l (IQR=5.2–6.6) 109/l; P<0.001) and VFA/TAMAI of ≥2 and <3 (6.7×109/l (IQR=6.2–7.6) 109/l; P<0.001). Alb in patients with VFA/TAMAI of ≥3 was 33.5 g/l (IQR=31.0–36.1) g/l lower than that with VFA/TAMAI of <2 (37.0 g/l (IQR=35.3–39.0) g/l; P<0.001) and VFA/TAMAI of ≥2 and <3 (35.5 g/l (IQR=34.0–37.2) g/l; P=0.002). In addition, the Alb in patients with VFA/TAMAI of ≥2 and <3 was higher than that with VFA/TAMAI of <2 (P=0.01). Meanwhile, the CRP (P=0.29) and WBC (P=0.10) was comparable between the two groups.
Table 3.
Characteristics of the patients with different VFA/TAMAI.
| Characteristics | VFA/TAMAI <2 (N=60) | VFA/TAMAI ≥2 and <3 (N=66) | VFA/TAMAI ≥3 (N=57) | P |
|---|---|---|---|---|
| Demographic data | ||||
| Male, N (%) | 26 (43.3) | 25 (37.9) | 24 (42.1) | 0.81 |
| Age, years (median, IQR) | 50.5 (31.5–59.0) | 51.0 (33.0–59.5) | 52.0 (35.0–61.0) | 0.14 |
| BMI, kg/m2 (median, IQR) | 19.5 (19.0–20.5) | 19.9 (18.3–22.0) | 19.6 (19.0–21.0) | 0.18 |
| Nutritional assessments | ||||
| Controlling nutritional status (CONUT) score, (median, IQR) | 2 (2–3) | 2 (2–3) | 2 (2–3) | 0.64 |
| Nutrition risk screening 2002 (NRS 2002) ≥3, N (%) | 43 (71.7) | 39 (59.1) | 38 (66.7) | 0.33 |
| Fistula characteristics | ||||
| Interval from fistula occurred to DS, months (median, IQR) | 4.0 (3.0–5.0) | 4.0 (3.0–5.0) | 4.0 (4.0–5.0) | 0.25 |
| Distance from Treitz to the fistula, N (%) | 0.87 | |||
| <100 cm | 7 (11.7) | 9 (13.6) | 6 (10.5) | |
| ≥100 cm | 53 (88.3) | 57 (86.4) | 51 (89.5) | |
| Length of small intestine, N (%) | 0.84 | |||
| <300 cm | 12 (20) | 12 (18.2) | 9 (15.8) | |
| ≥300 cm | 48 (80) | 54 (81.8) | 48 (84.2) | |
| PN required, N (%) | 10 (16.6) | 8 (12.1) | 6 (10.5) | 0.59 |
| Complicated with ventral hernia, N (%) | 44 (33.3) | 50 (37.9) | 38 (28.8) | 0.52 |
| Etiology, N (%) | 0.36 | |||
| Trauma | 37 (61.7) | 33 (50) | 37 (64.9) | |
| Obstruction | 18 (30) | 26 (39.4) | 18 (31.6) | |
| Others | 5 (83.3) | 7 (10.6) | 2 (3.5) | |
| Laboratory test results | ||||
| Hemoglobin before DS, g/l (median, IQR) | 126.5 (120.5–131.8) | 125.0 (118.0–132.5) | 123.0 (115.5–130.0) | 0.17 |
| Albumin before DS, g/l; (median, IQR) | 37.0 (35.3–39.0) | 35.5 (34.0–37.2) | 33.5 (31.0–36.0) | <0.001* |
| CRP before DS, mg/l (median, IQR) | 7.2 (5.4–9.2) | 8.1 (6.3–14.5) | 16.3 (7.1–24.3) | <0.001** |
| WBC before DS, 109/l (median, IQR) | 6.1 (5.2–6.6) | 6.7 (6.2–7.6) | 7.8 (6.6–8.6) | <0.001*** |
| Intraoperative condition and postoperative care | ||||
| American Society of Anesthesiologists (ASA) physical classification (median, IQR) | 2 (2–3) | 2 (2–3) | 2 (2–3) | 0.71 |
| Abdominal adhesion grade V | 27 (45.0) | 27 (40.9) | 23 (40.4) | 0.85 |
| Duration of DS, hours (median, IQR) | 4.0 (3.5–6.0) | 4.5 (3.5–6.0) | 5.0 (3.5–5.5) | 0.62 |
| Deciliter of bleeding loss during DS, dl (median, IQR) | 11.5 (9.0–15.5) | 10.5 (9.0–18.0) | 11.0 (9.0–17.0) | 0.85 |
| The amount of red blood cell suspension input during DS and within 48 h after DSa, N (%) | 0.29 | |||
| <10 U | 39 (65) | 37 (56.1) | 29 (50.9) | |
| ≥10 U | 21 (35) | 29 (43.9) | 28 (49.1) | |
| The amount of albumin input during DS and within 48 h after DSb, N (%) | 0.15 | |||
| <100 g | 38 (63.3) | 35 (53.1) | 26 (45.6) | |
| ≥100 g | 22 (36.7) | 31 (46.9) | 31 (54.4) | |
| Comorbidity, N (%) | ||||
| Hypertension | 4 (6.7) | 5 (7.6) | 3 (5.3) | 0.88 |
| Elevated fasting blood glucose | 3 (5) | 8 (12.1) | 10 (17.5) | 0.10 |
VFA/TAMAI <2 vs. VFA/TAMAI ≥2 and <3 P=0.01; VFA/TAMAI <2 vs. VFA/TAMAI ≥3 P<0.001; VFA/TAMAI ≥2 and <3 vs. VFA/TAMAI ≥3 P=0.002.
VFA/TAMAI <2 vs. VFA/TAMAI ≥2 and <3 P=0.29; VFA/TAMAI <2 vs. VFA/TAMAI ≥3 P<0.001; VFA/TAMAI ≥2 and <3 vs. VFA/TAMAI ≥3 P<0.001.
VFA/TAMAI <2 vs. VFA/TAMAI ≥2 and <3 P=0.10; VFA/TAMAI <2 vs. VFA/TAMAI ≥3 P<0.001; VFA/TAMAI ≥2 and <3 vs. VFA/TAMAI ≥3 P<0.001.
In order to maintain the hemoglobin >100 g/l within 48 h after definitive surgery.
In order to maintain the albumin >30 g/l within 48 h after definitive surgery.
CRP, C-reactive protein; DS, definitive surgery; IQR, interquartile range; PN, parenteral nutrition; TAMAI, total abdominal muscle area index; VFA, visceral fat area; WBC, white blood cell.
The association between VFA/TAMAI and RF
Out of the 183 patients, 20.2% (n=37) developed RFs. The recurrence rates for the three subgroups were 11.7% (seven patients), 15.2% (10 patients), and 35.1% (20 patients) (P=0.003). Patients with RFs demonstrated a higher VFA/TAMAI [3.09 cm2/m2 (IQR: 1.9–3.5 cm2/m2) vs. 2.4 cm2/m2 (IQR: 1.6–3.0 cm2/m2), P=0.001]. Twenty-five independent variables were assessed in the univariate regression (Supplementary Table 1, Supplemental Digital Content 1, http://links.lww.com/JS9/A905). Of these variables, seven were included in further multivariate regression, VFA/TAMAI (OR=1.78, 95% CI: 1.09–2.87, P=0.02) and the amount of albumin input ≥100 g during DS and within 48 h after DS (OR=2.49, 95% CI: 1.07–5.79, P=0.03) were associated with RFs (Table 4).
Table 4.
Multivariable logistic regression for RF.
| Characteristics | OR (95% CI) | P |
|---|---|---|
| Male | 0.48 (0.24–1.11) | 0.11 |
| CRP before DS | 1.03 (0.97–1.09) | 0.31 |
| Deciliter of bleeding loss during DS | 1.04 (0.96–1.13) | 0.32 |
| The amount of albumin input ≥100 g during DS and within 48 h after DSa | 2.49 (1.07–5.79) | 0.03 |
| Elevated fasting blood glucose | 1.59 (0.52–4.83) | 0.42 |
| VFA/TAMAI | 1.78 (1.09–2.87) | 0.02 |
| SFA | 1.00 (0.99–1.01) | 0.45 |
In order to maintain the albumin >30 g/l within 48 h after definitive surgery.
CRP, C-reactive protein; DS, definitive surgery; RF, recurrent fistula; SFA, subcutaneous fat area; TAMAI, total abdominal muscle area index; VFA, visceral fat area.
No postoperative deaths were reported in this study. Among the 37 patients with RFs, 30 (81.1%) experienced spontaneous closure within 90 days following surgery. A VFA/TAMAI of >3 was observed in six of the seven patients. However, VFA/TAMAI was not associated with spontaneous closure (OR=2.03, 95% CI: 0.73–5.68, P=0.17).
The association between VFA/TAMAI and postoperative LOS
For the 183 patients, the postoperative LOS was 17 days (IQR: 13–32 days). The multivariable Cox regression demonstrated that an elevated VFA/TAMAI was linked to a reduced postoperative LOS [hazard ratio (HR)=0.69, 95% CI: 0.59–0.81, P<0.001; Table 5]. Patients with a VFA/TAMAI of <2, ≥2 and <3, and ≥3 exhibited postoperative LOSs of 14 days (IQR: 12–19 days), 17 days (IQR: 13–23 days), and 24 days (IQR: 17–69 days) (P<0.001), respectively. According to the Kaplan–Meier estimates, patients with a VFA/TAMAI of ≥3 experienced a lengthier postoperative LOS than those with a VFA/TAMAI of <2 (P<0.001) and ≥2 and <3 (P<0.001), while the postoperative LOS remained similar between patients with a VFA/TAMAI of <2 and ≥2 and <3 (Fig. 1).
Table 5.
Multivariable Cox regression for LOS.
| Characteristics | HR (95% CI) | P |
|---|---|---|
| Hemoglobin before DS | 0.99 (0.97–1.01) | 0.26 |
| The amount of albumin input ≥100 g during DS and within 48 h after DSa | 0.84 (0.59–1.04) | 0.09 |
| Elevated fasting blood glucose | 0.81 (0.50–1.28) | 0.36 |
| VFA/TAMAI | 0.69 (0.59–0.81) | <0.001 |
In order to maintain the albumin >30 g/l within 48 h after definitive surgery.
DS, definitive surgery; HR, hazard ratio; LOS, length of stay; TAMAI, total abdominal muscle area index; VFA, visceral fat area.
Figure 1.
The postoperative length of stay in patients with VFA/TAMAI <2; 2 ≤VFA/TAMAI <3, and VFA/TAMAI ≥3. TAMAI, total abdominal muscle area index; VFA, visceral fat area.
For patients (146) without RFs, the postoperative LOS was 16 days (IQR: 13–21 days). VFA/TAMAI also impacted postoperative defecation [8 days (IQR: 6–12 days); HR=0.76, 95% CI: 0.63–0.89, P=0.001; Table 6], thus reducing the postoperative LOS (HR=0.77, 95% CI: 0.66–0.91, P=0.002; Table 7). However, in the remaining 37 patients with RFs, VFA/TAMAI showed no association with the postoperative LOS [80 days (IQR: 64–90 days); univariate HR=0.84, 95% CI: 0.44–1.94, P=0.32].
Table 6.
Multivariable Cox regression for postoperative defecation in patients without RFs (n=146).
| Characteristics | HR (95% CI) | P |
|---|---|---|
| Deciliter of bleeding loss during DS | 0.98 (0.94–1.13) | 0.67 |
| The amount of albumin input ≥100 g during DS and within 48 h after DSa | 0.93 (0.66–1.32) | 0.52 |
| VFA/TAMAI | 0.76 (0.63–0.89) | 0.001 |
In order to maintain the albumin >30 g/l within 48 h after definitive surgery.
DS, definitive surgery; HR, hazard ratio; RFs, recurrent fistulas; TAMAI, total abdominal muscle area index; VFA, visceral fat area.
Table 7.
Multivariable Cox regression for LOS in patients without RFs (n=146).
| Characteristics | HR (95% CI) | P |
|---|---|---|
| The amount of albumin input ≥100 g during DS and within 48 h after DSa | 0.71 (0.51–0.99) | 0.002 |
| VFA/TAMAI | 0.77 (0.66–0.91) | 0.002 |
In order to maintain the albumin >30 g/l within 48 h after definitive surgery.
DS, definitive surgery; HR, hazard ratio; LOS, length of stay; RFs, recurrent fistulas; TAMAI, total abdominal muscle area index; VFA, visceral fat area.
The association between VFA/TAMAI and the postoperative inflammatory index
Postoperative day 1 CRP and WBC levels were evaluated as the postoperative inflammatory index. In patients with a VFA/TAMAI of <2, ≥2 and <3, and ≥3, the postoperative CRP levels were 116 mg/dl (IQR: 102–130 mg/dl), 130 mg/dl (IQR: 118–142 mg/dl), and 157 mg/dl (IQR: 128–169 mg/dl), respectively. According to the multivariable general linear model analysis, postoperative CRP exhibited an association with VFA/TAMAI (R 2=0.401; Std. Error of the Estimate=16.35; β=12.61, P<0.001; Supplementary Table 2, Supplemental Digital Content 2, http://links.lww.com/JS9/A906).
In patients with a VFA/TAMAI of <2, ≥2 and <3, and ≥3, the postoperative WBC counts were 13×109/l (IQR: 12×109/l–15×109/l), 16×109/l (IQR: 15×109/l–18×109/l), and 18×109/l (IQR: 15×109/l–22×109/l), respectively. The multivariable general linear model analysis also revealed an association between the postoperative WBC count and VFA/TAMAI (R 2=0.441; Std. Error of the Estimate=2.78; β=2.03, P=0.001; Supplementary Table 3, Supplemental Digital Content 3, http://links.lww.com/JS9/A907).
Discussion
In this study, the association between VFA/TAMAI and DS outcomes for small intestinal fistula with diffuse extensive abdominal adhesions in patients with sarcopenia is reported. VFA/TAMAI has emerged as a risk factor for adverse outcomes following abdominal surgery in recent years. Jang et al.17 found a relationship between VFA/TAMAI and postoperative pancreatic fistula after pancreaticoduodenectomy. Pecorelli et al.18 proposed that VFA/TAMAI was linked to postoperative death, although it did not predict the occurrence of pancreatic fistula. Ratnayake et al.19 demonstrated that VFA/TAMAI could be a significant independent predictor of postoperative morbidity following pancreatic resection. Zhang et al.20 identified an association between VFA/TAMAI and severe postoperative complications after gastrectomy.
The connection between high VFA/TAMAI and preoperative chronic inflammation has been cited as the reason for VFA/TAMAI’s impact on these unfavorable phenomena. Chronic inflammation is reportedly related to the pathological metabolism of adipose tissue, indicating an imbalance in body composition. This condition promotes the transition from myoblasts to adipocytes, with myoblasts exhibiting (pre)adipocyte-like characteristics21. Preoperative VFA/TAMAI increases in patients with chronic inflammation, as shown in Table 3, and patients with higher VFA/TAMAI had elevated CRP and WBC levels and lower Alb before surgery, suggesting greater chronic inflammation. Persistent preoperative chronic inflammation has consistently led to immune system imbalance and affected the body’s healing capacity8,22, resulting in delayed wound healing and a high incidence of postoperative complications. In conclusion, higher VFA/TAMAI and an increased risk of postoperative complications were observed in patients with chronic preoperative inflammation. In this context, patients with diffuse extensive abdominal adhesions following abdominal infections due to ECFs remained in a state of chronic inflammation22, thereby revealing the clinical association between high VFA/TAMAI and postoperative RFs.
The primary cause of postoperative complications is believed to be the postoperative inflammatory response. The significant risk for RFs and prolonged LOS following major abdominal surgery has been attributed to a high postoperative inflammatory response by Boelens et al.23 and Tian et al.9,24. Massive bleeding, exudation, and trauma are inevitable during surgery in patients with diffuse extensive abdominal adhesions, making the postoperative inflammation more severe compared to regular major abdominal surgery. It was initially hypothesized that preoperative chronic inflammation, represented by VFA/TAMAI, might still possess the ability to alter the postoperative prognosis in the situation of unavoidable severe postoperative inflammation. However, an intriguing finding from the current study was the association between VFA/TAMAI and postoperative inflammatory indicators. This finding is important because it suggests that preoperative chronic inflammation might indirectly influence postoperative inflammation in addition to having a direct impact on the prognosis. Preoperative chronic inflammation and postoperative inflammatory reaction appeared to be linked. Higher preoperative chronic inflammation would indicate abdominal fat accumulation, increased abdominal organ fragility, and higher surgical trauma15, resulting in higher postoperative inflammation.
This study has certain limitations. First, the deviation might be explained by the retrospective nature and limited sample size of the study. However, cases of small intestinal fistula with diffuse extensive abdominal adhesions are scarce; thus, the number of patients enrolled in this study might be sufficient. Second, the patients were followed up until they were discharged. As a result, delayed RFs occurring in a few patients might not be recorded, leading to bias. However, delayed fistula is relatively rare in gastrointestinal surgery, and gastroenterography was performed within 14 days after surgery for each patient. Most RFs were identified using gastroenterography. Therefore, it can be concluded that the probability of a delayed RF is rather low. Third, existing knowledge does not allow for a precise exploration of the direct micro-mechanism between preoperative chronic inflammation and postoperative inflammation. The theory behind this phenomenon is that chronic abdominal inflammation might increase abdominal organ fragility and surgical trauma during surgery. However, the acute systemic inflammation following trauma during the DS may be exacerbated by the immune system alteration brought on by chronic inflammation. This matter warrants further laboratory investigations.
In conclusion, a high VFA/TAMAI predicated the occurrence of RFs after DS for small intestinal fistulas in the presence of diffuse extensive abdominal adhesions. Referring to the relationship between VFA/TAMAI and preoperative inflammation, this study indicated that preoperative inflammation could be a new insight into the challenging problem of RF after DS. Additionally, the present study can provide a reference for the prevention and treatment of RF in the future.
Consent
Written informed consent was obtained from the patient for the publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
Sources of funding
None.
Author contribution
R.Z., Y.Z., W.L., and T.T.: provide research objects; X.X. and R.Z.: collected and analyzed the data; M.H., X.X., and W.T.: wrote the main manuscript text; X.X.: prepared figures and revised the manuscript; Z.Y.: designed the research; W.T. and X.X.: revised the manuscript; X.X. and W.T. were the first authors; Z.Y. and R.Z. were the corresponding authors.
Conflicts of interest disclosure
The authors declare that they have no conflicts of interest.
Research registration unique identifying number (UIN)
Name of the registry: Thai Clinical Trials Registry.
Unique identifying number or registration ID: Researchregistry9084.
Hyperlink to your specific registration (must be publicly accessible and will be checked): https://www.researchregistry.com/browse-theregistry#home/registrationdetails/6474baed1614e200292318f9/
Guarantor
Zheng Yao.
Data availability statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Supplementary Material
Acknowledgements
We would like to thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript.
Footnotes
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal’s website, www.lww.com/international-journal-of-surgery.
Published online 17 August 2023
Contributor Information
Weiliang Tian, Email: 546686766@qq.com.
Xin Xu, Email: rn_xuxin@163.com.
Risheng Zhao, Email: dr_zhaorisheng@163.com.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.