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Keywords:

  • chronic idiopathic pseudo-obstruction;
  • manometry;
  • quality of life;
  • severe functional gastrointestinal disorders;
  • small bowel motility

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Authors’ Contribution
  9. References

Background  Unlike chronic idiopathic intestinal pseudo-obstruction (CIIP), severe digestive syndromes that are not characterized by episodes resembling mechanical obstruction remain poorly characterized. The present study compared clinical features, small bowel motility, and quality of life (QoL) in patients with CIIP or severe functional gastrointestinal disorders (SFGID), compared to irritable bowel syndrome (IBS).

Methods  We enrolled 215 consecutive patients: 70 CIIP, 110 malnourished SFGID [body mass index (BMI) 17.8 ± 1.8 kg m−2] and 35 non-malnourished SFGID (BMI 22.8 ± 3.6 kg m−2).

Key Results  Abnormal motor patterns that fulfilled diagnostic criteria for small bowel dysmotility were virtually absent in IBS patients, but were recorded in69 CIIP patients (98.6%), 82 malnourished SFGID patients (74.5%;), and 23 SFGID patients without malnutrition (65.7%) (P < 0.0001). CIIP patients presented more frequently abnormal activity fronts, lack of response to feeding, and hypomotility than malnourished and non-malnourished SFGID patients (61.4%vs 42.7% and 31.4%, P < 0.05 only vs non-malnourished SFGID; 8.6%vs 0.9% and 2.9%; 21.4%vs 0.9% and 0%, P < 0.05). Quality of life mean scores were all significantly lower in CIIP patients and malnourished SFGID patients than in IBS. Bodily pain, general health, and vitality scores were lower in CIIP also compared to non-malnourished SFGID.

Conclusions & Inferences   Chronic idiopathic intestinal pseudo-obstruction and SFGIDs are frequently associated with small bowel dysmotility and marked derangements of QoL which are significantly more severe than in IBS and result particularly in being severe in patients with recurrent sub occlusive episodes or inability to maintain a normal body weight.


Abbreviations:
CIIP

Chronic idiopathic pseudo-obstruction

QoL

Quality of life

SFGID

severe functional gastrointestinal disorders

M-SFGID

malnourished SFGID

NM-SFGID

non-malnourished SFGID

BMI

body mass index

MOS SF-36

Medical Outcomes Study Short Form 36

IBS

irritable bowel syndrome

HRQoL

health related quality of life

PROs

patient-reported outcomes

PF

physical functioning

RP

role-physical

BP

bodily pain

GH

general health

VT

vitality

SF

social functioning

RE

role-emotional

MH

mental health

PCS

physical component summary

MCS

mental component summary

M

males

LSD

least significant difference

IDMMC

interdigestive migrating motor complex

SD

standard deviation

AFs

activity fronts

D

duodenum

J

jejunum

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Authors’ Contribution
  9. References

The term functional gastrointestinal disease (FGID) encompasses a variety of syndromes characterized by digestive symptoms that are not explained by any recognizable organic, systemic or metabolic cause.1 The severity of FGID spans a wide range but is generally associated with significant impairment of quality of life (QoL).2 In a minority of cases symptoms are extremely severe, reflecting major failures of digestive functions. Chronic idiopathic intestinal pseudo-obstruction (CIIP) represents a peculiar entity in FGID, being characterized by a marked derangement of gastrointestinal (GI) propulsion, mimicking mechanical obstruction in the absence of any lesion occluding the gut.3–5 In other patients symptoms of abdominal pain, fullness, early satiety, bloating/distension, constipation/diarrhea, nausea/vomiting can also be extremely severe, but never mimic episodes of intestinal occlusion. Small bowel dysmotility has been reported in some of these cases.6,7 A greater derangement of health-related QoL (HRQoL) has been recently described in CIIP, compared to patients with small bowel motor abnormalities.8 Notably, small bowel manometric findings lack specificity9,10 and manometric procedures are available only in a few specialized centers. Thus, the clinical characterization of these difficult cases remains uncertain even among specialists. The present study was undertaken to compare clinical features and small bowel motor functions in patients with chronic severe digestive syndromes with and without sub occlusive episodes and/or inability to maintain a normal body weight. We also assessed patient-reported outcomes to determine to which extent HRQoL is impaired in these different groups of patients, compared to milder forms of FGIDs.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Authors’ Contribution
  9. References

Of the 683 patients who were referred to the Laboratory of Functional Gastrointestinal Disorders of the S. Orsola-Malpighi Hospital of the University of Bologna, between 1994 and 2007 to undergo small bowel motility studies 215 were enrolled in the study (see Fig. 1 for details of exclusion criteria).

image

Figure 1.  Patients included in the study between 1994 and 2007 and causes for exclusion from the study. Only patients with chronic idiopathic intestinal pseudo-obstruction (CIIP) and severe functional gastrointestinal disorders with (M-SFGID) or without malnutrition (NM-SFGID) were included. Please note that the short-form 36 (SF36) quality of life questionnaire was completed only by patients referred to our lab since 2001. Patients with irritable bowel syndrome defined according to Rome II criteria served as disease controls in this respect.

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The diagnosis of CIIP was established when all the following criteria were fulfilled: (i) recurrent episodes resembling mechanical intestinal sub-occlusion, characterized by abdominal pain and/or distension, possibly associated with nausea and vomiting, (ii) radiologic evidence of dilated bowel loops with air–fluid levels obtained during at least one acute exacerbation, (iii) absence of mechanical causes of gut lumen occlusion, as detected by thorough endoscopic and radiologic investigation, and (iv) absence of recognizable organic, systemic, and metabolic diseases, as detected by a complete diagnostic work up.4,5

The diagnosis of severe FGID (SFGID) was established when all the following criteria were fulfilled: (i) chronic (>3 months) GI symptoms with a persistent or recurrent severity score ≥ 3 in at least two digestive symptoms on a five-point Likert scale11–13 (see below), (ii) lack of acute episodes mimicking intestinal obstruction, (iii) lack of organic, systemic, and metabolic diseases potentially causing GI symptoms, as detected by a complete diagnostic work up.4,5 The condition of malnutrition was characterized by the inability to maintain a normal body weight (BMI < 18.7 kg m−2 in women; <20.1 kg  m−2 in men and/or need of substantial modification of a normal oral feeding (need of enteral or parenteral nutrition or requiring supplementation by liquid formulae). According to these criteria 110 SFGID patients were malnourished (75.9%) while 35 were not (24.1%).

A group of 100 patients referred to our outpatient clinic (39.2 ± 13.9 years; 68 F, 68.0%) affected by irritable bowel syndrome (IBS), as diagnosed according to the Rome II criteria12,14 also answered both the clinical questionnaire (to exclude symptoms severe enough to affect usual activities or dietary habits) and the SF-36 (see below), thus serving as disease controls.

Demographic features, previous surgical procedures, nutritional conditions of the four groups of patients are shown in Table 1.

Table 1.   Clinical features recorded at entry in 70 patients with chronic idiopathic intestinal pseudo-obstruction (CIIP) and 145 patients with severe functional gastrointestinal disorders (SFGID). Data refer to number of patients (%) or mean ± SD
 CIIP (no. 70)SFGIDIBS (no. 100)
Malnourished (no. 110)Non-malnourished (no. 35)
  1. IBS, irritable bowel syndrome; BMI, body mass index.

Gender no. of women48 F (68.6%)99 F (90.0%)28 F (80.0%)68 F (68.0%)
Age at entry (years; mean ± SD)38.0 ± 13.434.0 ± 13.337.3 ± 14.139.2 ± 14.0
Surgical procedures (no./years; mean ± SD)2.89 ± 2.000.88 ± 1.101.23 ± 1.820.49 ± 0.82
BMI no. of patients with [DOWNWARDS ARROW] BMI (<18.7 kg m−2in women, <20.1 kg m−2in men)40 (57.1%)76 (69.7%)0 (0%)6 (6.0%)
Dietary habit
No or mild modification13 (18.8%)12 (10.9%)35 (100%)100 (100%)
Relevant modification of oral feeding15 (21.4%)48 (43.6%)0 
Liquid oral feeding24 (34.3%)41 (37.3%)0 
Enteral nutrition12 (17.1%)5 (4.5%)0 
Parenteral nutrition6 (8.6%)4 (3.6%)0 

Data recording

All patients underwent a small bowel manometric test (see below) and answered questionnaires on several clinical parameters, when first seen in our laboratory.12

Psychological and psychiatric disorders were assessed by formal psychiatric examination whenever clinically indicated. Specifically, anorexia nervosa was excluded in all patients with malnutrition.15 Assessment of autonomic disorders was performed in patients with suspected abnormalities of these neurological functions.16

Ethics

The study was approved by the S. Orsola-Malpighi Hospital Ethics Committee and all participating subjects gave their written informed consent.

Symptom questionnaire

Type, severity, and frequency of GI symptoms (between sub occlusive episodes in CIIP patients) were recorded by a modified version of a validated questionnaire11 that has long been in use in our laboratory.12,13 The severity of eight GI symptoms was graded 0–4 according to its influence on patient’s usual activities: 0 =  absent; 1 =  mild (not influencing usual activities); 2 =  relevant (diverting from, but not urging modification of, usual activities); 3 =  severe (influencing usual activities markedly enough to urge modifications); 4 =  extremely severe (precluding daily activities). A global symptom score was calculated for each patient by summing up severity scores of each symptom. Bowel habits were also investigated and described as dicotomic variables (diarrhea, constipation, alternating: present or absent).

Small bowel manometry

Small bowel manometry was performed by a standard stationary technique.13,17 A 5-lumen perfusion tube (external diameter: 5 mm) was inserted through the nose, after an overnight fast. Catheters were individually perfused with distilled water via a pneumo-hydraulic pump (PIP3-8; Mui Scientific, Missisagua, ON, Canada) with a perfusion rate of 0.1 mL min−1 at a perfusion pressure of 10 psi, in the absence of air bubbles, and attached to strain gauge transducers (Type 4-237-1; Sensor Medics, Anaheim, CA, USA). Side openings were located at the tip of the tube and at 10 cm intervals proximally. Tracings were initially recorded by a paper chart recorder (Dynograph Recorder R611; Sensor Medics, Anaheim, CA, USA) and, from 1999 on, using a computerized recorder (UPS2020; MMS, Enschede, The Netherlands). The manometric probe was positioned under fluoroscopic control with at least one recording site beyond the angle of Treitz or, in patients with previous gastric surgery, with at least three recording sites along the efferent loop. Occlusive pressure activities were continuously recorded for at least 6 h before (fasting period) and 90 min after the ingestion of a test meal (fed period). In patients unable to eat the standard test meal (638 kcal; 42% carbohydrates, 37% lipids, 21% proteins)18–20 type and amount of food were adjusted to the individual feeding habits.9,21 Type and frequency of small bowel abnormal motor patterns were independently13 identified by two experienced investigators (V.S. and R.F.C.), according to previous definitions.17–21 Specifically, the following abnormalities were considered: (i) abnormal propagation (either simultaneous or retrograde over 30 cm segment of small bowel) and/or configuration (marked tonic rises of baseline pressure over 30 mm Hg amplitude, >3 min duration) of activity fronts or phase III of the interdigestive migrating motor complex (IDMMC), (ii) bursts or periods of >2 min duration with continuous high amplitude (>20 mmHg) and high frequency (10–12 min−1) phasic pressure activity that were not propagated and not followed by motor quiescence, (iii) sustained contractions characterized by prolonged (for over 30 min) and intense phasic pressure activity that occurred in a segment of intestine, while normal or reduced contractility was simultaneously recorded at other levels, (iv) inability of an adequate meal to abolish IDMMC for at least 90 min, (v) hypomotility defined as absence of any detectable contractions (i.e., contractions with amplitude <10 mmHg) or contractions with amplitude <20 mmHg also during phase III of the IDMMC and only sporadically recorded during phase II and or during postprandial periods, and (vi) clustered contractions or 3–10 regular contractions, occurring once per 5 s preceded and followed by >1 min of absent motor activity lasting for 20 min or longer. Twelve IBS patients with overlapping functional dyspepsia, but symptoms not influencing usual activities accepted to be investigated and served as disease controls (39.2 ± 13.9 years; 68 F, 68.0%). Both investigators were unaware of the results of symptom questionnaires and other diagnostic tests and, therefore, of the final diagnosis at the time of tracing analysis.

Patient-reported outcome quality of life questionnaire MOS (Medical Outcomes Study) Short Form 36 (SF-36)

The Italian version of the Medical Outcomes Study Short Form 36 health survey (SF-36) questionnaire22 was administered for the assessment of the patient-reported outcomes (PROs) on QoL and psychological distress parameters. The SF-36 questionnaire produces scores on eight dimensions each on a 0–100 range: physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH). Two summary measures, the physical component summary (PCS) and the mental component summary (MCS) that reflect the respective impacts on physical and mental health and are obtained from the eight subscales (physical component summary: PF, RP, BP, GH; mental component summary: VT, SF, RE, MH).23–25 The SF-36 questionnaire was completed by 114 patients who were referred to our laboratory starting from 2001: 37 CIIP patients (mean age 39.9 ± 11.2 years; 31 F, 83.8%), 51 malnourished SFGID patients (mean age 33.3 ± 11.9 years; 47 F, 92.2%) and 26 non-malnourished SFGID patients (mean age 34.4 ± 11.3 years; 20 F, 76.9%).

Statistical analysis

Frequencies, means, SD, medians, and ranges were used as descriptive statistics. The comparison of continuous variables among the four groups of patients were carried-out by means of the analysis of variance (anova) and the least significant difference (LSD) post hoc analysis was used to adjust for multiple comparison. Association between different manometric abnormalities and presence/absence of individual severe digestive symptoms and of different clinical syndromes were also evaluated. Severe digestive symptoms, CIIP, SFGID, and malnutrition were defined as previously described. Functional digestive syndromes were defined also among CIIP and SFGID patients, by presence of symptoms or clusters of symptoms severe enough to influence usual activities (score ≥ 2), according to the Rome III criteria.26 The chi-square test and the hierarchical log-linear model were used to analyze non-dichotomous discrete data, while the Fisher’s exact test was applied to 2 × 2 contingency tables. All statistical evaluations were performed by running the SPSS for Windows (Version 13.0; SPSS Inc., Chicago, IL, USA) on a personal computer.27 A two-tailed probability value of 0.05 was selected as the level of statistical significance.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Authors’ Contribution
  9. References

Clinical features

Symptom severity reported by the different patient subgroups is summarized in Table 2. Mean global and most of individual scores of severity of symptoms were all significantly higher in CIIP patients and SFGDI patients than in IBS patients; SFGID patients had higher epigastric pain and burning scores than both CIIP and IBS patients. Global severity score and individual severity score for vomiting and fullness were higher in malnourished SFGID patients than in both CIIP patients and non-malnourished SFGID patients. Non-malnourished SFGID patients also had a lower individual score for nausea and early satiety than malnourished SFGID patients. When the frequency of individual severe symptoms (i.e., severity score ≥3) was analyzed, malnourished SFGID patients reported more frequently vomiting and fullness (50.9% and 60.0%) than CIIP patients (34.3% and 41.4%, P = 0.021 and P = 0.011, respectively, Fisher’s exact test), while non-significant differences were observed for the other symptoms (data not shown). Constipation, diarrhea, and alternating bowel affected, respectively, 48.6%, 21.4%, and 15.7% of CIIP patients, 58.2%, 11.8%, and 17.3% of malnourished SFGID patients, 65.7%, 14.3%, and 8.6% of non-malnourished of SFGID patients, 43.4%, 37.0%, and 20.1% of IBS patients. No significant differences were observed as to bowel habits among patients groups, (P = 0.210, P = 0.215, P = 0.459 for constipation, diarrhea and alternating bowel, Pearson chi-square).

Table 2.   Symptom severity score in 70 patients with chronic idiopathic intestinal pseudo-obstruction (CIIP), 145 patients with severe functional gastrointestinal disorders (SFGID), and in 100 patients with irritable bowel syndrome (IBS)
 CIIP (no 70)SFGIDIBS (no. 100)P value (anova)
Malnourished (no 110)Non-malnourished (no. 35)
  1. Least significant difference (LSD) post hoc analysis: *P < 0.05 vs CIIP; P < 0.05 vs malnourished – SFGID; P < 0.05 vs non-malnourished-SFGID; §P < 0.05 vs IBS.

Epigastric pain/burning0.91 ± 1.331.55 ± 1.39*§1.69 ± 1.23*§0.72 ± 0.78<0.001
Early satiety1.24 ± 1.47§1.52 ± 1.44§1.03 ± 1.20§0.31 ± 0.56*<0.001
Nausea1.80 ± 1.85§1.88 ± 1.53§1.26 ± 1.54§0.43 ± 0.71*<0.001
Vomiting0.63 ± 0.90§0.91 ± 1.04*§0.60 ± 0.77§0.09 ± 0.35*<0.001
Fullness1.83 ± 1.90§2.65 ± 1.52*§2.11 ± 1.79§0.81 ± 0.93*<0.001
Abdominal distension3.03 ± 1.65§3.00 ± 1.38§2.71 ± 1.54§1.53 ± 0.70*<0.001
Abdominal pain2.27 ± 1.97§2.60 ± 1.71§2.49 ± 1.60§1.57 ± 0.61*<0.001
Global severity score11.71 ± 6.03§14.10 ± 4.31*§11.89 ± 5.69§5.46 ± 2.31*<0.001

Small bowel manometry

Prolonged recordings were performed in all cases (median 8.3 h; range 4.3–16 h). Concordant results in the analysis of manometric recordings were obtained by the two investigators in 151 cases (91.0%), while the remaining tracings required consensus analysis.

Results obtained in SGID patients are summarized in Table 3. Manometric abnormalities that fulfilled diagnostic criteria of small bowel dysmotility were present in 69 CIIP patients (98.6%), 82 malnourished SFGID patients (74.5%;), and 23 non-malnourished SFGID patients (65.7%), (P < 0.001). A motor pattern of uncertain significance (i.e., activity fronts with a propagation velocity of less than 1 cm/min) was observed in a minority of patients (22.9% CIIP, 47.4% malnourished SFGID, 40.0% non-malnourished SFGID). Clustered contractions, that are not necessarily abnormal findings of small bowel manometry,10,18 were recorded in the absence of concomitant abnormal motor patterns in only one patient with CIIP (1.5%), but in 12 malnourished (10.9%) and five non-malnourished (14.3%) SFGID patients. Frequencies of abnormal activity fronts, lack of adequate response to meal, and hypomotility were significantly different among the three groups. In particular, CIIP patients presented significantly more frequent abnormalities of activity fronts, lack of an adequate motor response to meal and hypomotility, whereas SFGID patients without malnutrition showed a significantly lower frequency of abnormal activity fronts than any other patient group. Fig. 2 shows examples of manometric abnormalities recorded in patients from different study groups. Among the 12 IBS patients who underwent intestinal manometry only clusters were recorded in one case and one burst in another one, with the remaining tracings showing no obvious abnormality.

Table 3.   Frequencies of abnormal motor patterns in 70 patients with chronic idiopathic intestinal pseudo-obstruction (CIIP) and 145 patients with severe functional gastrointestinal disorders (SFGID)
 CIIP (no. 70)SFGIDP value*
Malnourished (no. 110)Non-malnourished (no. 35)
  1. *Comparison among the three groups: chi-square test. Observed vs expected cell frequencies: Hierarchical log-linear model.

Abnormal activity fronts (AFs)43 (61.4%)47 (42.7%)11 (31.4%)0.007
P value0.0020.6250.031
Lack of adequate response to meal6 (8.6%)1 (0.9%)1 (2.9%)0.029
P value0.0480.0950.869
Hypomotility15 (21.4%)1 (0.9%)0<0.001
P value0.0010.1660.320
Bursts44 (62.9%)68 (61.8%)19 (54.3%)0.672
P value0.5300.6360.371
image

Figure 2.  Small bowel manometric recordings during fasting in a patient with severe functional gastrointestinal disorders and malnutrition and in a patients with chronic idiopathic intestinal pseudo-obstruction, showing, respectively: (A) bursts of uncoordinated intense contractions lasting longer than 2 min and not followed by motor quiescence (B) abnormal activity front for propagation: the activity front-like motor pattern seems to migrate more or less regularly from D3 to J2, but it appears either aborally propagated or totally uncoordinated in D2, as indicated by the black arrows; also motor quiescence is virtually absent in J1. Recording sites were positioned at 10 cm intervals in proximal (D1), descending (D2), distal duodenum (D3) and in the proximal jejunum (J1, J2).

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Association between manometric abnormalities and clinical features

Analysis of the association between different manometric abnormalities and digestive symptoms/syndromes are summarized in Table 4. Hypomotility was associated with epigastric pain/burning, fullness, diarrhea, functional dyspepsia, and CIPO; bursts with abdominal pain, constipation, diarrhea, IBS; abnormal activity fronts, and lack to adequate response to meal with CIIP. Despite the large number of statistical associations, sensitivity and specificity of the different abnormal motor pattern in identifying patients with severe digestive symptoms and syndromes were rather disappointing: abnormal activity fronts and bursts showed low specificity (range: 33.5–60.0%) and sensitivity (range: 30.3–71.9%), while hypomotility and lack of adequate response to meal presented high specificity (range: 77.6–99.3%), but negligible sensitivity (range: 1.5–21.4%).

Table 4.   Association between small bowel manometric abnormalities and digestive symptoms and syndromes
 Abnormal activity frontsLack of adequate response to mealHypomotilityBursts
  1. Fisher’s exact test.

  2. Bold values indicate statistically significant differences.

Symptoms
 Epigastric pain/burning
 Specificity80/148 (54.1%)144/148 (97.3%)133/148 (89.9%)55/148 (37.2%)
 Sensitivity33/67 (49.3%)4/67 (6.0%)1/67 (1.5%)38/67 (56.7%)
 P value0.6610.2590.0250.451
 Early satiety
 Specificity81/143 (56.6%)138/143 (96.5%)130/143 (90.9%)55/143 (38.5%)
 Sensitivity39/72 (54.2%)3/72 (4.2%)3/72 (4.2%)43/72 (59.7%)
 P value0.1491.0000.2730.882
 Nausea
 Specificity77/141 (54.6%)137/141 (97.2%)130/141 (92.2%)58/141 (41.1%)
 Sensitivity37/74 (50.0%)4/74 (5.4%)5/74 (6.8%)48/74 (64.9%)
 P value0.5660.4511.0000.462
 Vomiting
 Specificity85/155 (54.8%)147/155 (94.8%)143/155 (92.3%)66/155 (42.6%)
 Sensitivity31/60 (51.7%)0/60 (0%)4/60 (6.7%)42/60 (70.0%)
 P value0.4470.1091.0000.119
 Fullness
 Specificity57/104 (54.8%)100/104 (96.2%)92/104 (88.5%)46/104 (44.2%)
 Sensitivity54/111 (48.6%)4/111 (3.6%)4/111 (3.6%)73/111 (65.8%)
 P value0.6821.0000.0360.162
 Abdominal distension
 Specificity37/69 (53.6%)67/69 (97.1%)65/69 (94.2%)31/69 (44.9%)
 Sensitivity69/146 (47.3%)6/146 (4.1%)12/146 (8.2%)93/146 (63.7%)
 P value1.0001.0000.7810.235
 Abdominal pain
 Specificity55/92 (59.8%)90/92 (97.8%)83/92 (90.2%)44/92 (47.8%)
 Sensitivity64/123 (52.0%)6/123 (4.9%)7/123 (5.7%)83/123 (67.5%)
 P value0.0980.4710.2990.025
 Constipation
 Specificity51/94 (54.3%)90/94 (95.7%)84/94 (89.4%)50/94 (53.2%)
 Sensitivity58/121 (47.9%)4/121 (3.3%)6/121 (5.0%)87/121 (71.9%)
 P value0.7840.7320.1250.001
 Diarrhea
 Specificity97/182 (53.3%)175/182 (96.2%)172/182 (94.5%)61/182 (33.5%)
 Sensitivity16/33 (48.5%)1/33 (12.5%)6/33 (18.2%)10/33 (30.3%)
 P value0.8521.0000.0210.001
 Alternating bowel
 Specificity97/182 (53.3%)176/182 (96.7%)168/182 (92.3%)72/182 (39.6%)
 Sensitivity16/33 (48.5%)2/33 (6.1%)2/33 (6.1%)21/33 (63.6%)
 P value0.8520.3541.0000.847
Syndromes
 Functional dyspepsia
 Specificity23/49 (46.9%)46/49 (93.9%)38/49 (77.6%)24/49 (49.0%)
 Sensitivity75/166 (48.2%)5/166 (3.0%)5/166 (3.0%)106/166 (63.9%)
 P value0.4160.3860.0010.134
 Irritable bowel syndrome
 Specificity31/48 (64.6%)46/48 (95.8%)44/48 (6491.7%)26/48 (54.2%)
 Sensitivity84/167 (50.3%)6/167 (3.6%)12/167 (7.2%)109/167 (65.3%)
 P value0.0741.0000.7600.019
 Chronic intestinal idiopathic pseudo-obstruction
 Specificity87/145 (60.0%)143/145 (98.6%)144/145 (99.3%)58/145 (40.0%)
 Sensitivity43/70 (61.4%)6/70 (8.6%)15/70 (21.4%)44/70 (62.9%)
 P value0.0040.0160.0010.776
 Malnutrition
 Specificity40/66 (60.6%)62/66 (93.9%)62/66 (93.9%)30/66 (45.5%)
 Sensitivity75/149 (50.3%)4/149 (2.7%)12/149 (8.1%)95/149 (63.8%)
 P value0.1430.2530.7810.227

Quality of life

Mean scores on the eight domains, and of physical and mental component summaries of SF-36 obtained in the three study groups and in the disease controls are reported in Table 5. Mean scores were all significantly lower in CIIP patients and malnourished SFGDI patients than in IBS patients. Bodily pain, general health, and vitality mean scores were lower in CIIP patients also compared to non-malnourished SFGID patients. Lower mean scores of physical functioning, bodily pain, and vitality characterized malnourished compared to non-malnourished SFGID patients. The physical component summary was lower in CIIP and malnourished SFGID patients than in non-malnourished patients. No difference was detected between CIIP and malnourished SFGID patients. General health, physical functioning, and physical component summary mean scores were significantly lower in non-malnourished SFGID than in IBS patients.

Table 5.   Mean ± SD of the eight domains and the two component summaries of the SF-36: comparison at entry in 37 patients with chronic idiopathic intestinal pseudo-obstruction (CIIP), 77 patients with severe functional gastrointestinal disorders (SFGID), and in 100 patients with irritable bowel syndrome (IBS)
 CIIP (n = 37)SFGIDIBS (n = 100)P value (anova)
Malnourished (n = 51)Non-malnourished (n = 26)
  1. Least significant difference (LSD) post hoc analysis: *P < 0.05 vs CIIP; P < 0.05 vs malnourished – SFGID; P < 0.05 vs non-malnourished-SFGID; §P < 0.05 vs IBS.

Physical functioning59.9 ± 22.8§55.5 ± 24.8§71.4 ± 29.179.2 ± 26.9*<0.001
Role-physical37.2 ± 42.3§32.8 ± 40.8§42.0 ± 37.9§78.0 ± 32.2*<0.001
Bodily pain31.3 ± 29.2§31.6 ± 17.9§46.0 ± 30.0*§57.2 ± 23.9*<0.001
General health27.1 ± 16.5§33.1 ± 17.4§42.4 ± 24.6*§52.6 ± 21.4*<0.001
Vitality33.4 ± 21.8§35.7 ± 22.9§47.1 ± 21.5*55.6 ± 22.2*<0.001
Social functioning41.2 ± 31.7§40.9 ± 29.1§53.4 ± 25.960.9 ± 27.9*<0.001
Role-emotional47.3 ± 44.0§53.3 ± 41.1§58.9 ± 41.473.7 ± 37.7*0.001
Physical component summary33.5 ± 9.2§33.9 ± 7.9§39.61 ± 10.2*§46.0 ± 8.4*<0.001
Mental component summary36.9 ± 12.1§37.2 ± 13.2§38.9 ± 10.643.2 ± 11.4*0.006
Mental health50.5 ± 44.0§45.5 ± 23.6§51.5 ± 21.960.1 ± 20.7*0.001

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Authors’ Contribution
  9. References

This study identifies clinical and pathophysiological differences existing among subgroups of patients with apparently similar type of functional digestive symptoms. Specifically, it demonstrates that patients with pseudo-obstruction or severe forms of functional digestive disorders have substantial abnormalities of intestinal motility in the vast majority of cases and marked derangements of QoL, compared with milder functional digestive syndromes. Furthermore, it suggests that recurrent sub occlusive episodes and inability to maintain a normal body weight while on an oral diet may help to identify subsets of patients with the highest probability to present intestinal dysmotility and the most severe impairment of bodily and psychological perceptions.

Digestive syndromes are currently classified according to the type of their clinical manifestation, based on the observations that digestive symptoms tend to spontaneously cluster into separate groups both in the general population and in patients.1 Digestive symptoms may vary from mild to severe and from intermittent to continuous. However, little attention has been paid so far to symptom severity despite the fact that both health care utilization and clinical decision making are often guided by severity rather than type of symptoms.28 The present study focused on the most severe cases of FGIDs identified in patients reporting at least two chronic or recurrent symptoms severe enough to urge modifications or even prevent daily activities. Frequency and severity of symptoms were measured by a questionnaire with appropriate psychometric features.11–13 The global symptom score was higher in malnourished than in both CIP and non-malnourished SFGID patients, with vomiting and fullness being particularly severe. Weight loss had already been shown to be associated not only with some digestive symptoms including nausea and vomiting in particular, but also postprandial fullness and early satiety and, therefore, it was proposed as a marker of dyspepsia.29 Weight gain, in turn, may represent a clinically relevant indicator of treatment effectiveness in patients with gastroparesis.30 Weight loss is also a potential marker of malignancies of the alimentary canal, although with limited predictive value,31,32 but organic diseases were thoroughly ruled out in all patients included in the present study. Our results demonstrate that inability to maintain a normal body weight is often associated with symptoms suggestive of diffuse involvement of the alimentary canal and represents a marker of severity of functional digestive syndromes.

Small bowel manometry was performed by a stationary technique with relatively prolonged recording times that has long been used for research and clinical purposes in our laboratory13,14,21,33 to identify abnormal motor patterns, as originally defined by a similar technique.21,22 Obvious motor abnormalities were detected in almost all CIIP patients, and in about 75% of malnourished and 65% of non-malnourished SFGID patients. Severe motor abnormalities including abnormal activity fronts, inability of the meal to convert fasting into fed motor patterns and severe hypomotility were more frequently recorded in CIIP patients. Thus, CIIP confirms to be the most severe form of small bowel dysmotility. However, small bowel abnormal motor patterns are not sufficiently sensitive and specific to achieve clinical utility in distinguishing different subgroups among patients with pseudo-obstruction and/or digestive symptoms severe enough to urge modifications or even prevent usual activities. Notably, none of the above-mentioned abnormalities that are thought to reflect underlying neuromyopathy of the gut have been recorded in patients with ‘typical’ (i.e., not particularly severe) IBS symptoms.9,10,34 In the small series of IBS patients who underwent prolonged intestinal manometry we recorded normal tracings in all, but clustered contractions in one case, and an isolated burst in another one. Therefore, although we confirm that the technique lacks specificity, a major gap exists between degree of derangement of peripheral functions between severe and mild forms of FGID. Particularly intriguing remains the interpretation of those cases in whom manometry could not detect any obvious motor abnormality in SFGID patients. Insufficient sensitivity of stationary manometry is a possibility, but ambulatory manometry with computer-assisted analysis is unlikely to substantially improve the results9,33 and development of new diagnostic tools is warranted to identify more subtle underlying pathophysiological mechanisms.

Another important aspect of the present study is represented by the comparison of HRQoL in digestive syndromes characterized by different clinical features and severity of symptoms. As disease-specific QoL questionnaires have not been developed for CIP or SFGIDs, we adopted the SF-36, a well-validated generic questionnaire with proven discriminative function between individuals having different medical conditions.35 The only study we are aware of investigating HRQoL in patients with CIP and other severe digestive syndromes adopted other questionnaires8 so that a direct comparison of the results is unfeasible. However, in keeping with the results by Iwarzon et al.,8 our study showed marked derangements of all dimensions of HRQoL in the different types of severe digestive syndromes investigated. All subgroups of patients showed significant deteriorations of HRQoL compared to Italian norms. Both CIP and SFGIDs with and without malnutrition showed significantly more deteriorated QoL than patients with IBS, but while malnourished SFGIDS had QoL virtually identical to CIP patients, non-malnourished SFGID patients presented QoL values intermediate between IBS and the other severe digestive syndromes. Irritable bowel syndrome is traditionally considered a very frequent and severe condition. In fact, HRQoL deterioration in IBS patients has been reported to be similar to or even more severe than that observed in patients affected by other severe pathological conditions including diabetes,36 asthma,37 migraine,37,38 ulcerative colitis.39 Furthermore, IBS severe enough to ‘impose some life restrictions’ has also been reported to cause more unhealthy days than arthritis, breast cancer, diabetes, heart disease/stroke, and class III obesity.40 Indeed, a significant correlation has been repeatedly shown between symptom severity and degree of HRQoL deterioration in IBS.41,42 In keeping with our results, recent studies from Korea indicate that significant impairments of HRQoL in IBS can be detected only in patients with severe and not mild or moderate symptoms.43 Furthermore, a large study from France included one-third of IBS patients reporting severe to very severe digestive symptoms and confirmed that IBS is associated with lower HRQoL and involves large medical costs.44 Similar results were also reported in a study from UK including only patients with severe IBS non-responsive to usual treatments,45 while HRQoL has been shown to be more impaired in IBS female patients seen in referral centers than in those managed in primary care, independently from their bowel habits.46 Taken together these studies suggest that major attention should be paid on not only type, but also degree of severity of symptoms, unlike what is recommended by current classifications of FGIDs.1 It is also important to keep in mind that HRQoL is related not only to intensity and frequency (i.e., severity) of symptoms,47 but also to other components including psychosocial factors, health-care utilization, behavior and patient-doctor relationship.19,48,49 In this respect our study shows that CIIP patients have deterioration of HRQoL similar to malnourished SFGID despite somewhat lower severity of symptoms, probably due to greater psychological uncertainties determined by repeated admissions for emergency surgeries in the former group.

In conclusion, this study demonstrates that the presence of recurrent sub occlusive episodes or at least two digestive symptoms severe enough to urge modifications of usual activities, and inability to maintain a normal body weight on an oral diet identify subsets of patients who have a marked derangement of their QoL and a very high probability to present small bowel dysmotility, and deserve an early referral to centers with a specific interest in these rare digestive syndromes. These findings also indicate that not only the differences among symptoms and clusters of symptoms, but also their severity need to be taken into consideration in future studies on digestive syndromes.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Authors’ Contribution
  9. References

This work was supported by grants from the Italian Ministry of University, Research, Science and Technology (PRIN 2007, 2009) to RDeG and GB by funds from the University of Bologna (RFO 2007-2010) to VS, RDeG, GB, and RC. RDeG and GB are recipient of grants from ‘Fondazione Cassa di Risparmio di Bologna’, Bologna, Italy and RDeG from ‘Fondazione Del Monte di Bologna e Ravenna’.

Authors’ Contribution

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Authors’ Contribution
  9. References

VS and RFC designed the research study and wrote the article; RFC, AA, CF, and LC performed the research and acquired manometric data; AMM-L contributed with statistical analysis; RDG, GB, CC, RP, and RC contributed to drafting and revising the study design and manuscript.

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  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Authors’ Contribution
  9. References
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