J Neurogastroenterol Motil 2023; 29(3): 378-387  https://doi.org/10.5056/jnm22152
Natural History of Chronic Intestinal Pseudo-obstruction and Need for Palliative Care
Kosuke Tanaka,1,2 Hidenori Ohkubo,2,3 Atsushi Yamamoto,2 Kota Takahashi,2 Yuki Kasai,2 Anna Ozaki,2 Michihiro Iwaki,2 Takashi Kobayashi,2 Tsutomu Yoshihara,2 Noboru Misawa,2 Akiko Fuyuki,2 Shingo Kato,2,4 Takuma Higurashi,2 Kunihiro Hosono,2 Masato Yoneda,2 Takeo Kurihashi,5 Masataka Taguri,6 Atsushi Nakajima,2 Kok-Ann Gwee,7,8,9 and Takaomi Kessoku1,2,10*
1Department of Palliative Medicine and Gastroenterology, International University Health and Welfare Narita Hospital, Narita, Japan; 2Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan; 3Department of Gastroenterology, Toshiba Rinkan Hospital, Sagamihara, Japan; 4Department of Clinical Cancer Genomics, Yokohama City University Hospital, Yokohama, Japan; 5Department of Internal Medicine, Kanagawa Dental University Yokohama Clinic, Yokohama, Japan; 6Department of Data Science, Yokohama City University Graduate School of Medicine, Yokohama, Japan; 7Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; 8Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 9The Gastroenterology Group, Gleneagles Hospital, Singapore; and 10Department of Gastroenterology, International University Health and Welfare, School of Medicine, Narita, Japan
Correspondence to: *Takaomi Kessoku, MD, PhD
Department of Palliative Medicine and Gastroenterology, International University Health and Welfare Narita Hospital, 852 Hatakeda, Narita, Chiba 286-8520, Japan
Tel: +81-76-35-5600, Fax: +81-476-35-5586, E-mail: kessoku-tho@umin.ac.jp
Kosuke Tanaka and Takaomi Kessoku equally contributed to this study.
Received: September 5, 2022; Revised: January 25, 2023; Accepted: February 12, 2023; Published online: July 30, 2023
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Natural history of chronic intestinal pseudo-obstruction (CIPO), a rare disease characterized by episodes of non-mechanical obstruction, is unclear in adults. This study evaluates the clinical course of CIPO and palliative care needs of patients.
From October 2010 to September 2021, 74 patients who underwent cine MRI and had a definitive diagnosis of CIPO were prospectively included. We investigated disease etiology and outcomes, age at onset, nutritional status at consultation (body mass index and serum albumin), hydrogen breath test results, and total parenteral nutrition (TPN) during the disease course.
Forty-seven patients (64%) were women, with a mean age of 44 years at onset and 49 years at diagnosis. Primary CIPO was observed in 48 patients (65%). Secondary CIPO was observed in 26 cases (35%), of whom 18 (69%) had scleroderma. The mean body mass index, serum albumin level, and hydrogen breath test positivity rate were 17 kg/m2, 3.8 mg/dL, and 60%, respectively. TPN and invasive decompression therapy were required by 23 (31%) and 18 (24%) patients, respectively. Intestinal sterilization was performed in 51 (69%) patients and was effective in 33 (65%); of these, 28 (85%) were taking metronidazole. Seven (9%) patients used opioids. There were 9 deaths (12%), including 5 (56%) from infection and 2 (22%) from suicide. Of the deaths, 6 (67%) and 4 (44%) underwent TPN management and decompression therapy, respectively. Fifty-one patients (69%) wanted palliative care.
CIPO is a rare, severe, and under-recognized disease. Standardization of treatment strategies, including palliative care and psychiatric interventions, is desired.
Keywords: Decompression; Depression; Intestinal pseudo-obstruction; Palliative care; Total parenteral nutrition

Chronic intestinal pseudo-obstruction (CIPO) is a severe digestive disease characterized by the derangement of intestinal propulsive motility, resulting in clinical features such as abdominal pain, bloating, and vomiting. It mimics the symptoms of mechanical obstructions in the absence of any mechanical occlusive lesions in the gut.1-4 Patients with CIPO often remain undiagnosed for long periods of time before they almost invariably undergo repeated, unnecessary, and potentially dangerous surgical procedures due to the lack of specific laboratory findings, established noninvasive diagnostic methods, and the low recognition rate of this disease.5 This syndrome can either result from a wide variety of systemic, metabolic diseases or have an idiopathic origin, which is known as chronic idiopathic intestinal pseudo-obstruction).6

Once the diagnosis is established, further tests are needed to identify the presence of any potentially curable diseases responsible for secondary forms, and to monitor the patient’s condition, particularly nutritional state, as well as mineral and vitamin deficiencies. The long-term outcomes are generally poor, and only limited reports exist regarding natural history of this severe condition.5,7

In recent years, palliative care for non-cancerous diseases, such as intractable neurological diseases,8 interstitial pneumonia,9 and heart failure,10-12 has attracted attention, but the effectiveness of palliative care in CIPO has not yet been investigated. The present study aims to evaluate the clinical course, treatment, and long-term outcomes of adult patients with CIPO, and their need for palliative care.

Materials and Methods

Ethics Approval

The institutional ethics committees approved this observational, cross-sectional, case-control study, and consent was obtained and opt-outs were performed in accordance with the respective research protocols (Approval No. B1000902016, B171000027, and B200600060). This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The URL of the online registry and clinical trial numbers are www.umin.ac.jp/ctr/index.htm and UMIN000004033, UMIN000031785, and UMIN000040669, respectively.

Study Patients

A consecutive series of patients with a presumed diagnoses of CIPO, who were referred to our hospital from October 2010 to September 2021 and investigated by cine MRI, were considered for the study. The diagnosis of CIPO was established when all the following diagnostic criteria for CIPO, which were recently updated,13 proposed by the Ministry of Health, Labour, and Welfare, were fulfilled: (1) recurrent episodes of abdominal pain and/or bloating, often associated with nausea and vomiting, and symptoms mimicking subacute mechanical intestinal obstruction, prompting hospitalization; (2) illness persisting for two months or more for new-onset cases and six months or more for cases of onset after infancy; (3) diagnostic imaging showing a dilated gastrointestinal tract and air-fluid levels; (4) no organic lesions obstructing the gastrointestinal tract; (5) If it is possible to conduct hematoxylin & eosin staining of full-thickness intestinal biopsy, this shows no morphological abnormalities in the nerve plexus, or observation of abnormal intestinal motility by cine MRI in adults; (6) exclusion of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) and segmental dilatation of the intestine (it is not applicable in adult patients; this criterion is limited to pediatric cases); and (7) exclusion of secondary CIPO. Patients satisfying criteria (1) to (7) were defined as primary CIPO, and (1) to (6) as secondary CIPO.

Seventy-four patients (47 women, 64%; mean ± SD age at entry, 48 ± 18 years) were included in the study and prospectively followed up for a mean of 4 years (max, 11 years). Data from hospital records were used to assess the frequency of pseudo-obstruction-related episodes, as well as and patient background, surgical history, nutrition, laboratory data, such as blood and hydrogen breath test (HBT), CT, cine MRI, treatment, emergency hospitalization details, long-term outcomes, mental screening, and palliative care needs. Family histories were collected, and the pedigrees were reconstructed by clinicians trained in gastroenterology and genetics. Only 3 patients (sisters) had familial forms of CIPO. At entry, each patient completed a questionnaire for clinical, nutritional, and mental evaluations, such as the Patient Health Questionnaire for Depression Screening (PHQ-2: depression screening tool), suicide attempts, and palliative care needs. Imaging (CT and cine MRI) and HBT were only performed for patients who provided consent. The effect was assessed by the attending physician based on the patient questionnaire (showing a decrease in abdominal bloating on a numerical rating scale [NRS] score of 4 or higher), patient examination, and imaging findings. Furthermore, each patient was prospectively followed up using an annual questionnaire or when clinically required. Treatments were administered at the discretion of the attending physician.

Clinical Questionnaire

A detailed questionnaire on relevant health status issues was administered to each patient during a personal interview at entry. Information was obtained from interviews and medical charts, including feeding habits (ie, free diet, modified oral/liquid nutrition, or enteral/parenteral nutrition) as measures of nutritional status, mental screening using the PHQ-2,14 suicide attempts using the Scale for Suicide Ideation,15 and the presence or absence of palliative care needs, with their respective reasons.

Blood Tests

Blood tests were performed according to the protocol of our hospital. Serum endotoxin levels were measured as previously described.16 Briefly, serum samples were heated at 75℃ for 5 minutes, and endotoxin levels were measured using a commercially available Limulus amebocyte lysate chromogenic endpoint assay (HIT302; Hycult Biotech Inc, Wayne, PA, USA), with a concentration range of 0.04-10 EU/mL.

Hydrogen Breath Test

All patients who provided consent were asked to avoid high-fiber diets and foods likely to produce a high hydrogen level for 24 hours before the test, and to fast for 12 hours overnight before the breath test. Patients with CIPO were only allowed to drink only water during the 12 hours preceding the test. Patients were also informed that they should avoid exercise and smoking for 1 hour before and throughout the test period. A baseline breath sample was obtained and measured before the intake of 10 g of lactulose (Chugai Pharmaceutical Co, Ltd, Tokyo, Japan) dissolved in 250 mL of water. The patients were asked to drink the solution within 2 minutes. End expiratory breath samples were then obtained every 15 minutes for 180 minutes. Hydrogen (H2) and methane (CH4) levels were analyzed using a breath gas analyzer (BGA-1000D; Breath Biochemical Nutrition and Metabolism Research Institute Co, Ltd, Nara City, Japan) calibrated with QuinGas-3 standard at 100 parts per million (ppm) for H2, 50 ppm for CH4, and 5% for CO2. H2 and CH4 concentrations were measured in ppm; the levels of both gases in the samples were plotted graphically and analyzed. The lactulose breath test was considered to be positive for small intestinal bacterial overgrowth (SIBO) based on the following criteria: baseline values of H2 and/or CH4 > 20 ppm17-19 and/or an increase in H2 or CH4 levels to > 20 ppm above the baseline value between 15-90 minutes after lactulose ingestion.20-22

Computed Tomography

CT was performed according to the protocol of our institution. Bowel dilatation, air-fluid levels and absence of organic lesions were double-checked by 2 radiologists.

Cine Magnetic Resonance Imaging Protocol

Cine MRI was performed and measured using a previously reported protocol.23

Statistical Methods

Data are expressed as mean ± SD unless indicated otherwise. We analyzed the data using JMP 15.0 (SAS Institute Inc, Cary, NC, USA). Continuous variables were compared using the Mann–Whitney U test. Binary variables were compared using the χ2 test. All t tests were two-sided, with a significance level of 5% (P = 0.050). The survival rate was calculated as the number of deaths per 1000 person-years of follow-up, and the survival rate was estimated using the Kaplan–Meier method. The log rank test was used to determine the survival rates. GraphPad Prism 7 (GraphPad Software, Inc, La Jolla, CA, USA) was used to create the figures, and the data are shown as the mean and standard error in the figures.


Patient Characteristics

Table 1 presents the patients’ backgrounds. Before their first visit to our hospital (a tertiary medical institution), the patients presented with the following onset symptoms: abdominal bloating in 48 patients (65%) and constipation in 6 patients (8%). The mean age at onset was 44 years, the mean age at diagnosis was 49 years, and the mean time until diagnosis was 5.1 years. The mean number of regular medications administered during the first visit was 5.7. The breakdown of regular drugs administered was as follows: prokinetic agents (61%), traditional Chinese medicines (59%), antacids (51%), laxatives (49%), and probiotics (36%). Comorbidities included cardiovascular disease in 6 patients (8%), endocrine disease in 6 patients (8%), gastroesophageal reflux disease (GERD) in 6 patients (8%), cancer in 5 patients (7%), sperm disease in 5 patients (7%), and pneumatosis intestinalis in 3 patients (4%). Surgical histories included lysis of adhesions in 9 patients (12%) and ileocecal resection in 8 patients (11%). There were 48 (65%) cases of primary CIPO and 39 (81%) cases of CIPO due to an unknown cause. Secondary CIPO was present in 26 patients (35%); among them, 18 (69%) had scleroderma. The routes of nutrition were oral intake in 61 patients (82%), oral intake in combination with total parenteral nutrition (TPN) in 9 patients (12%), and TPN alone in 4 patients (5%). The mean period from symptom onset to TPN insertion was 7 years. The most common symptoms at initial visit were abdominal bloating in 71 patients (96%), abdominal pain in 40 patients (54%), diarrhea in 37 patients (50%), and constipation in 29 patients (39%). The mean abdominal bloating NRS was 8.4 and the mean abdominal pain NRS was 7.4.

Table 1 . Demographics

CharacteristicsCIPO patients (n = 74)
Female47 (64)
Male27 (36)
BMI (kg/m2)17.2 ± 2.3
Onset symptoms
Abdominal bloating48 (65)
Constipation6 (8)
Intestinal obstruction5 (7)
Diarrhea3 (4)
Follow-up duration (yr)4 ± 4
Age at onset (yr)44 ± 21
Age at diagnosis (yr)49 ± 18
Duration from onset to diagnosis (yr)5.1 ± 8.2
Age at the time of consultation (yr)50 ± 16
Number of regular medicines5.7 ± 3.5
Types of regular medicine
Prokinetic agents45 (61)
Chinese medicines44 (59)
Antacids38 (51)
Laxatives36 (49)
Probiotics27 (36)
Defoamers19 (26)
Antipsychotics9 (12)
Pain medicines7 (9)
Steroids5 (7)
Antidiarrheal agents5 (7)
Digestive enzyme agents3 (4)
Cardiovascular diseases6 (8)
Endocrine diseases6 (8)
GERD6 (8)
Cancers5 (7)
Mental disorders5 (7)
Pneumatosis intestinalis3 (4)
Surgical history
Lysis of adhesions9 (12)
Ileocecal resection8 (11)
Appendectomy4 (5)
Subtotal colectomy4 (5)
Family history of CIPO3 (4)
Primary48 (65)
Unknown39 (81)
After delivery6 (13)
Congenital3 (6)
Secondary26 (35)
Scleroderma18 (69)
Sjögren’s syndrome6 (23)
Hypothyroidism3 (12)
Oral61 (82)
Oral + TPN9 (12)
TPN4 (5)
Period from onset to the start of TPN (yr)7 (9)
Symptoms at initial visit
Abdominal bloating71 (96)
Abdominal bloating NRS8.4 ± 1.8
Abdominal pain40 (54)
Abdominal pain NRS7.4 ± 2.6
Diarrhea37 (50)
Constipation29 (39)
Nausea, vomiting27 (36)

CIPO, chronic intestinal pseudo-obstruction; BMI, body mass index; GERD, gastroesophageal reflux disease; TPN, total parenteral nutrition; NRS, numerical rating scale.

Data are shown as n (%) or mean ± SD.

Mental Screening and Palliative Care Needs

Table 2 summarizes the results of psychological screening and palliative care needs at the first visit. Of the 74 CIPO patients, 28 (38%) had a PHQ-2 score of 3 or higher, indicating a positive depression screening index. Of these, 28 patients (100%) had severe symptoms, 16 patients (57%) were anxious about not being cured, and 15 patients (54%) perceived a lack of understanding from the people around them. 18 patients (24%) admitted to making suicide attempts, all of whom had painful symptoms (100%), 14 of whom had anxiety about not being cured (78%), and 14 of whom had a poor understanding of the disease (78%). Overall, the need for palliative care was recognized by 51 patients (69%); of these, 35 (69%) had painful symptoms, 31 (61%) had a poor understanding of the disease, 22 (43%) felt that they “did not know how to live,” and 21 (41%) were worried about the future.

Table 2 . Mental Screening and Palliative Care Needs

Types of questionsCIPO patients (n = 74)
PHQ-2 ≥ 328 (38)
Symptoms are painful28 (100)
Anxiety that does not heal16 (57)
Poor understanding of others15 (54)
Suicide attempt18 (24)
Symptoms are painful18 (100)
Anxiety that does not heal14 (78)
Poor understanding of others14 (78)
Hope for palliative care intervention51 (69)
Symptoms are painful35 (69)
Poor understanding from others31 (61)
“I do not know how to live”22 (43)
“I am worried about the future”21 (41)

CIPO, chronic intestinal pseudo-obstruction; PHQ-2, Patient Health Questionnaire for Depression Screening.

Data are shown as n (%).

Laboratory Data

Table 3 shows a summary of the blood tests, HBT, CT, and cine MRI findings at the first visit. Blood tests showed a mean albumin level of 3.9 ± 0.6 g/dL, which was slightly lower than normal, but no liver or renal dysfunction, impaired glucose tolerance, or electrolyte abnormalities were observed. The endotoxin activity level in the blood was 0.19 ± 0.07. The HBT was performed on 50 patients, and 30 (60%) tested positive. The details were 30/30 (100%) for hydrogen-type SIBOs and 1/30 (3%) for methane-type SIBOs. Regardless, CT findings showed dilation of the small intestine in all cases. The esophagus was dilated in 3 patients (4%), the stomach in 5 patients (7%), and the large intestine in 12 patients (16%). Cine MRI findings showed a mean luminal diameter of 44 ± 16 mm and a mean contraction ratio of 19%, with a mean contraction cycle of 9.3 seconds. Hypoalbuminemia was found in 15 patients (20%), anemia in 32 patients (43%), hyponatremia in 8 patients (11%), hypokalemia in 10 patients (14%), hypocalcemia in 2 patients (3%), and hypomagnesemia in 2 patients (3%) (Supplementary Table 1).

Table 3 . Laboratory, Hydrogen Breath Test, and Imaging Findings

ParameterCIPO patients (n = 74)
Laboratory findings
Total protein (g/dL)6.8 ± 0.7
Albumin (g/dL)3.9 ± 0.6
White blood cell count (× 103)5.9 ± 2.0
Hemoglobin (g/dL)12.2 ± 2.2
Platelet count (× 104/mm3)25.0 ± 9.3
Prothrombin Time-International Normalized Ratio1.1 ± 0.1
Activated partial thromboplastin time (second)33.5 ± 3.1
Aspartate aminotransferase (U/L)33 ± 24
Alanine aminotransferase (U/L)34 ± 48
γ-Glutamyl transpeptidase (U/L)30 ± 32
Lactate dehydrogenase (IU/L)198 ± 80
Amylase (U/L)106 ± 47
Creatine kinase (U/L)98 ± 123
Na (Eq/L)140 ± 3.7
K (mEq/L)4.1 ± 0.6
Cl (mEq/L)103 ± 5
Ca (mg/dL)9.1 ± 0.6
Mg (mg/dL)2.1 ± 0.4
Fasting blood sugar (mg/dL)103 ± 43
Hemoglobin A1c (%)5.4 ± 0.7
C-reactive protein (mg/L)0.3 ± 1.0
Endotoxin activity assay0.19 ± 0.07
HBT enforcement50
Positive30 (60)
Hydrogenic SIBO30 (100)
Methanogenic SIBO1 (3)
CT dilation site
Esophagus3 (4)
Stomach5 (7)
Small intestine74 (100)
Large intestine12 (16)
Cine MRI
Luminal diameter (mm)44 ± 16
Contraction ratio (%)19 ± 13
Contraction cycle (s)9.3 ± 1.5

CIPO, chronic intestinal pseudo-obstruction; HBT, hydrogen breath test; SIBO, small intestinal bacterial overgrowth.

Data are shown as mean ± SD or n (%).

Medical Therapy

Dietary therapy

Dietary restrictions during the observation period, including reducing the number of meals to 1 to 2 meals per day or reducing the volume of the meal to 30-50% of the normal amount, were applied to 41 patients (55%). The combination of TPN was used in 24 patients (32%), and an elemental diet (ED) at initial consultation was used for 37 patients (50%). 74 patients used an ED at least once between symptom onset and the study period. 60 patients (81%) could not tolerate an ED. Abdominal bloating was exacerbated in 39 patients (53%) with an ED. Of the 74 patients who used an ED, 39 (53%) had worsening abdominal bloating. Of these, 23 patients (59%) were positive for SIBO (Table 4).

Table 4 . Treatment and Emergency Hospitalization Details and Outcomes

TreatmentCIPO patients (n = 74)
Dietary therapy
Dietary restrictions, effective41 (55)
Combined with TPN24 (32)
Use of ED at initial consultation37 (50)
Use of ED from onset of symptoms74 (100)
Patients who could not tolerate ED60 (81)
Exacerbation of abdominal bloating with ED39 (53)
SIBO(+)23 (59)
SIBO(–)6 (15)
Intestinal sterilization51 (69)
Period from onset to the start of intestinal sterilization (yr)7 ± 9
Effective33 (65)
Metronidazole28 (85)
Vancomycin3 (9)
Rifaximin1 (3)
Ciprofloxacin1 (3)
Adverse effects of antibiotics requiring hospitalization
History of metronidazole38 (51)
Metronidazole induced encephalopathy5 (13)
Decompression therapy
Period from onset to the start of decompression therapy (yr)4 ± 5
PEG-J18 (24)
PEG-J effective rate15 (83)
Enterostomy2 (3)
Surgical therapy and transplantation0 (0)
Opioid use7 (9)
Opioid effectiveness4 (57)
Tramadol3 (43)
Tramadol + acetaminophen1 (14)
Oxycodone2 (29)
Buprenorphine transdermal preparation1 (14)
Number of emergency hospitalizations5.8 ± 7.6
Exacerbation of abdominal bloating47 (78)
Dehydration4 (7)
Infection2 (3)
Port occlusion2 (3)
History of ≥ 6 emergency hospitalizations27 (36)
TPN user11 (41)
PEG-J user8 (30)
Patient outcomes
Death (person-years)11.5
Age at death (yr)60 ± 14
Period from onset to the start of death (yr)15 ± 14
Death rate9 (12)
TPN users6 (67)
PEG-J users4 (44)
Infections5 (56)
Suicides2 (22)
Respiratory failure1 (11)
Cancer1 (11)

CIPO, chronic intestinal pseudo-obstruction; TPN, total parenteral nutrition; ED, elemental diet; SIBO, small intestinal bacterial overgrowth; PEG-J, Percutaneous endoscopic gastro-jejunostomy.

Data are shown as n (%) or mean ± SD.

Intestinal sterilization

Intestinal sterilization was performed in 51 patients (69%). The period from onset to the start of intestinal sterilization was 7 years. Intestinal sterilization was judged to be effective in 33 patients (65%), among whom metronidazole (MNZ) was administered to 28 (85%) patients, vancomycin to 3 (9%), and rifaximin to 1 (3%). As an adverse effect of antibiotics requiring hospitalization, MNZ-induced encephalopathy was observed in 5 of the 38 patients (13%) (Table 4).

Decompression therapy

Percutaneous endoscopic gastro-jejunostomy (PEG-J) insertion was performed in 18 patients (24%), with an efficacy rate of 83% (15 patients). The period from onset to PEG-J insertion was 4 years. In addition, 2 patients (3%) underwent intestinal fistula surgery (Table 4).

Surgical therapy and transplantation

Of the 74 patients, none underwent intestinal transplantation surgery for CIPO (Table 4).

Opioid use

Opioid use was judged to be effective in 4 patients (57%). Seven patients (9%) were administered opioids, with tramadol administered to 3 patients (43%) and oxycontin to 2 patients (29%) (Table 4).


Emergency admission

The mean number of emergency hospitalizations was 5.8 ± 7.6. The most common reasons were exacerbation of abdominal bloating in 47 patients (78%), dehydration in 4 patients (7%), infection in 2 patients (3%), and TPN port occlusion in 2 patients (3%).


The mortality rate was 11.5 per 1000 person-years in patients with CIPO. The survival rates are shown in Figure 1: 9 (12%) patients died, 6 of whom were using TPN, and 4 of whom were using PEG-J. The mean age at death was 60 years and the mean time from onset to death was 15 years. Five out of 9 (56%) patients died due to infection, and 2 (22%) died by suicide (Table 4). Prognoses of CIPO were further divided into the surgical treatment (including lysis of adhesions, ileal resection, sub-total colon resection, and trial laparotomy) and the non-surgical treatment group. Twenty-two patients were in the surgical group and 52 were in the non-surgical group. The analysis included 71 patients, and excluding 3 patients for whom the follow-up period was unknown. There were 0/20 (0%) deaths in the surgical treatment group and 9/51 (18%) in the non-surgical treatment group, with a significantly higher mortality rate in the non-surgical treatment group (P = 0.044, Supplementary Table 2). Survival rates were not significantly different between the 2 groups (P = 0.070, Supplementary Figure).

Figure 1. Survival rate of patients with chronic intestinal pseudo-obstruction.

Demography and Treatment Based on Presence of Small Intestinal Bacterial Overgrowth

Regarding background factors, the SIBO group had a higher rate of history of lysis of adhesions than did the non-SIBO group (SIBO vs non-SIBO, 23% vs 0%; P = 0.020) and a lower rate of history of subtotal colectomy (SIBO vs non-SIBO, 0% vs 15%; P = 0.029) (Supplementary Table 3). Blood test findings also highlighted a significantly higher rate of scleroderma complications in the SIBO group (77% vs 20%, P = 0.027). While endotoxin activity was significantly higher (0.23 vs 0.14, P < 0.001). Regarding therapeutic effects, the SIBO group had a significantly higher rate of dietary restrictions (70% vs 30%, P = 0.005) and effectiveness rate of intestinal sterilization (85% vs 21%, P < 0.001). This was significantly higher in the present study. Additionally, the exacerbation of abdominal bloating due to an ED was significantly higher in the SIBO group than in the non-SIBO group (77% vs 30%, P = 0.001). There were no significant differences in decompression therapy, number of emergency hospitalizations, or long-term outcomes with and without SIBO.


To our best knowledge, this is the first study to investigate both the natural history and the psychiatric consultation and palliative care needs of many adult patients with CIPO. To date, most studies investigating the long-term clinical course of CIPO in adults have originated from Europe,7 with most of these being case reports or case series.6,24

Compared to previous reports in Italy, there are similarities, including a follow-up of about 4 years and a high use of intestinal peristaltic drugs, and some differences, including a diagnostic method of manometry and full thickness biopsy (FTB) which we have not been able to do (Supplementary Table 4). As stated in Italian paper, manometric study and histopathologic findings of FTB can play a supportive role in defining the diagnosis, but these alone cannot make a diagnosis of CIPO.5 Although the Japanese diagnostic criteria mention H&E staining, it is actually supplemental. In practice, the number of surgeries for CIPO patients including small bowel resection has drastically decreased in Japan in recent years since the previous Japanese report.25 Therefore, in Japan we rarely perform FTB as a result. In our practice, we perform cine-MRI which also plays supportive role in defining the diagnosis, an alternative. The time to diagnosis in our study is slightly shorter than previously reported; we guess this is mainly because of the increasing awareness of the disease in recent years.

Novelties of our study are that we (1) focused on the early psychiatric consultation and the needs for palliative care in CIPO patients, and (2) investigated the efficacy of PEG-J and SIBO interventions. Our result showed that palliative care needs are very high among CIPO patients, and PEG-J and SIBO interventions are effective in symptom management.

As reported by Stanghellini et al,7 abdominal surgery is often dangerous and ineffective. Masaki et al25 also reported that resection of the small intestine should be performed cautiously, as it is often ineffective and can lead leads to exacerbation. Therefore, unnecessary surgery was not performed in any of our cases. The average number of surgeries per patient is as low as 0.5. Twenty patients in this study underwent surgery and there were no deaths, which may be due to the decreased number of unnecessary surgeries. On the other hand, small bowel transplantation for end-stage CIPO has been shown to improve long-term survival and may become more widely performed in the future.26 In this study, none of the patients underwent small intestinal transplantation. This was primary because appropriate intestinal decompression therapy, including intestinal sterilization and PEG-J, was performed in most of the cases where it was necessary. Secondary, very few institutions in Japan are equipped to perform small intestinal transplantation.

Our results affirmed previous observations indicating that CIPO is an extremely severe and potentially life-threatening.24,27-30 The mortality rate of 12% found in this study was similar to that in recent reports.24,28 Nonetheless, in a case series published more than 30 years ago, over a third of patients died.30 The lower mortality rate in our series than in the study 3 decades prior can be attributed to the widespread use of intestinal sterilization, nutritional therapy using TPN, and decompression therapy using PEG-J. In particular, our previous study reported that PEG-J therapy can contribute significantly to the improvement of short-term abdominal symptoms and nutritional status in CIPO patients.31 Notably, in our study, cases of TPN and PEG-J were associated with a higher mortality rate. This may be because patients with a greater clinically severity of CIPO are more likely to need these therapies. Moreover, these procedures are certainly necessary for adequate nutrition and intestinal decompression at the appropriate time, especially in more severe cases.

In addition to death, a common outcome is acute exacerbation and need to for unexpected hospitalization, which is challenging in clinical practice. In our study, a mean of 5.8 patients required urgent hospitalization. Of these, patients receiving TPN or PEG-J treatment had a high frequency of emergency hospitalization. Therefore, TPN and PEG-J insertion warrants caution due to the associated high mortality and emergency hospitalization rates.

Previous studies have reported that one-fifth of CIPO patients complained of intractable pain or opioid dependence.7 However, we used opioids only in 9% of cases. One of the reasons why low percentage of cases used opioids is that in Japan using opioids for non-cancer pain has not been common in clinical practice until recently, and the use of oxycodone for non-cancer pain was approved in 2020. We plan to use them actively in the future. Although we cannot make a conclusion at this time because of the small number of cases, it seems to be better to use opioids in patients with particularly severe pain.

For the treatment, we first limited the patient’s diets to 1 to 2 times daily or 30-50% once daily, and used pharmacological treatments such as prokinetic agents, traditional Chinese medicines, antacids, and laxatives. Out of 74 patients, 39 (53%) of patients had exacerbated abdominal bloating after an ED. Since 59% of these patients had SIBO, an ED may exacerbate abdominal bloating. MNZ was the most frequently used antibiotic for intestinal sterilization, and was effective in 85% of patients with SIBO, which was a significantly higher than that for patients without SIBO (Supplementary Table 3). Nevertheless, with MNZ use, encephalopathy was found in 13% of hospitalized patients; thus, caution regarding the adverse effects of MNZ is necessary. The HBT used for SIBO diagnosis is generally glucose-based or lactulose-based. We performed a HBT using lactulose. In general, HBT with glucose is reported to have higher sensitivity and specificity compared with lactulose in a meta-analysis32 and false positives are reported to be higher when lactulose is used in the hydrogen breath test.33 Glucose is usually quickly absorbed in the small intestine, so at best we can only diagnose SIBO in the proximal small intestine.34 Lactulose is a nonabsorbable sugar, so it usually flows to the large intestine. Each has its own merits and demerits, but in this case, we avoid to use glucose because we are targeting a disease with poor intestinal peristalsis like CIPO.34

In addition, the investigation of palliative care needs in this study is a novel approach. In general, palliative care can improve the quality of life for patients and their families facing life-threatening diseases, pain, as well as other physical, psychosocial, and spiritual problems.35 This is just an observational study and only demonstrated the existence of palliative care needs. However; we found that more than two-thirds of CIPO patients wanted to receive palliative care for symptom relief, which is an important result of this study. It is necessary to perform interventional study to investigate whether pain is relieved or not by the palliative care in the future.

Based on the results of this study, we propose the following treatment strategy, as presented in Figure 2. The first step is to perform nutritional therapy using dietary restrictions. In parallel, it is desirable to consult the psychiatrist for the purpose of psychological checks, such as symptom relief, depression, and suicide attempts. If this treatment does not bring about sufficient improvement, physicians consider HBT, and if positive, intestinal sterilization might be performed. If intestinal sterilization is ineffective, TPN and PEG-J may be considered for nutritional improvement and abdominal symptom relief. If SIBO is negative or abdominal symptoms are intolerable, TPN and PEG-J should be considered.

Figure 2. Treatment strategy for patients with chronic intestinal pseudo-obstruction. HBT, hydrogen breath test; SIBO, small intestinal bacterial overgrowth; MNZ, metronidazole; VCM, vancomycin; RFX, rifaximin; TPN, total parenteral nutrition; PEG-J, percutaneous endoscopic gastro-jejunostomy.

The limitations of this study are as follows: (1) its single center, retrospective, observational design, (2) its limitation to a Japanese adult population, (3) the lack of manometric and histopathological findings, and (4) the palliative care team did not intervene in the cases actually. Future studies with a larger number of cases, including children, and with palliative care team intervention are needed for the development of treatment strategies, and specific intervention methods for palliative care.

The study demonstrates the clinical course and palliative care needs of patients with CIPO. Patients with CIPO are likely to have uncontrolled symptoms and psychiatric disorders. Therefore, standardization of treatment strategies, including early psychiatric interventions, and demonstrating the effectiveness of palliative care team interventions is desired.

Supplementary Materials

Note: To access the supplementary tables and figure mentioned in this article, visit the online version of Journal of Neurogastroenterology and Motility at http://www.jnmjournal.org/, and at https://doi.org/10.5056/jnm22152.


We would like to thank the participating patients and their families. The skillful technical assistance of Kyoko Kato, Hiroyuki Abe, and Machiko Hiraga is also gratefully acknowledged, as is the administrative assistance of Naho Kobayashi, Ayako Ujiie, and Yoshiko Yamazaki. The authors have not received any specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.

Financial support


Conflicts of interest

Atsushi Nakajima receives grants and research support from Gilead, Mylan EPD, EA Pharma, Kowa, Taisho, and Biofermin, and is a consulting adviser for Gilead, Boehringer Ingelheim, BMS, Kowa, Astellas, EA Pharma, and Mylan EPD. The remaining authors declare no conflicts of interest.

Author contributions

Kosuke Tanaka, Takaomi Kessoku, and Atsushi Nakajima contributed to the study design; Hidenori Ohkubo, Atsushi Yamamoto, Kota Takahashi, Yuki Kasai, Anna Ozaki, Yuma Takeda, Michihiro Iwaki, Takashi Kobayashi, Tsutomu Yoshihara, Noboru Misawa, Akiko Fuyuki, Shingo Kato, Takuma Higurashi, Kunihiro Hosono, Masato Yoneda, Takeo Kurihashi, and Kok-Ann Gwee were responsible for data collection; Masataka Taguri was involved in the data analysis; and Kosuke Tanaka, Takaomi Kessoku, Hidenori Ohkubo, and Atsushi Nakajima were responsible for the preparation of the tables and figures. All authors contributed to the review and writing of this manuscript.

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