The spectrum of pneumatosis intestinalis in the adult. A surgical dilemma

Table 1 Underlying pathological conditions

Pathological conditions
Trauma[21,64-67]	Blunt/penetrating abdominal trauma
	Surgical anastomosis or bypass
Mechanical[68]	Pyloric obstruction or stenosis
	Duodenal obstruction or stenosis
	Bowel obstruction (volvulus, carcinoma, malrotation, intussusception)
Autoimmune[69-71]	Lupus enteritis
	Celiac sprue
	Polymyositis
	Dermatomyositis
	Polyarteritis nodosa
	Mixed connective tissue diseases
	Graft versus host disease
	Primary immunodeficiency
Malignancies[15]	Gastrointestinal cancer
	Leukemia
	Lymphoma
	Other malignancies
Inflammation[14,72]	Inflammatory bowel disease
	Appendicitis
	Diverticulitis
	Cholelithiasis
	Sarcoidosis
Vascular conditions[73]	Ischemia or infarction
	Diabetes
Pulmonary disease[74,75]	Chronic obstructive pulmonary disease
	Cystic fibrosis
	Asthma
Drugs[13,19,76-79]	Corticosteroids
	Chemotherapy and immunotherapy
	Immunosuppression
	Lactulose
	Trichloroethylene
	Sorbitol
	Alpha-glucosidase inhibitor
	Practolol
Diagnostic/therapeutic procedures[80,81]	Endoscopy
	Enema/colon idrotherapy
	Barium studies
Connective tissue disease/neurological[82,83]	Scleroderma
	Multiple sclerosis
	Hirschsprung disease
	Quadriplegia
	Amyloidosis
Other conditions[17,84]	Hemodialysis
	Pseudo-obstruction
	Whipple disease
	Cytomegalovirus infection
	COVID-19 infection

COVID-19: Corona virus infectious disease-2019.

Table 2 Clinical studies in patients with pneumatosis intestinalis

Author	Type of study	Patients, n	Results
Ferrada et al[39]	Prospective Multicenter	One hundred twenty-seven patients with PI at CT scan	Mortality in the pathologic PI group vs benign PI group: 34% vs 13.9%. Patients with pathologic PI had hemodynamic instability, sepsis, peritonitis. The radiographic location is significant: Small bowel has a higher incidence of transmural ischemia than colon. Hepatic portal venous gas is suggestive for pathologic PI
Treyaud et al[43]	Retrospective Monocenter	One hundred eighty-seven patients with pi at CT scan	Location of PI nor the length of intestinal involvement correlate significantly with ischemia. The radiologic features that correlate with ischemia are PMP (P =0.009) and the decreased mural contrast-enhancement (P < 0.001). Among the laboratory tests, only WBC (> 12.000/mmc) correlates with bowel ischemia (P =0.03)
Morris et al[10]	Retrospective Monocenter	One hundred four patients with PI at CT scan	Mortality rate: 22%; 52% of patients were treated conservatively, with a mortality rate of 6%. Mortality rate of patients with PMP was 43%. No difference found in laboratory values between groups
Lassandro et al[49]	Retrospective Monocenter	One hundred two patients with PI at CT scan	Fifty-two percent of patients had surgical confirmation of bowel ischemia. 42.2% of patients had a bubblelike whereas in 59% it was linear. 75.5% of patients with linear pattern had bowel infarction. Mortality rate is 30.4%; it raises to 50% when PI is associated to PMP
Pickhardt et al[85]	Retrospective Monocenter	Five thousand three hundred sixty-eight Colonography scans, 0.11% with colonic PI	PI with curvilinear configuration. No clear if it was a pre-existing condition. No significant complications
Kernagis et al[48]	Retrospective Monocenter	Fifteen patients with PI at CT scan	Nine patients (60%) of symptomatic patients had transmural bowel infarction (4 small bowel, 5 colon)
Wiesner et al[55]	Retrospective Monocenter	Twenty-three patients with PI or PMP at CT scan and bowel ischemia	Twenty-two percent of patients showed partial mural bowel infarction, 78% of patients showed transmural bowel infarction. 70% of bubblelike PI was associated with bowel ischemia instead of the 88% of linear pattern. 81% of patients with PMP showed transmural infarction. Overall mortality 53%
Shinagare et al[54]	Retrospective Monocenter	Forty-eight patients with cancer and PI at CT scan	Thirty-nine patients were receiving molecular targeted therapy. Bevacizumab and Sunitinib were the most common drugs associated with PI. Median duration of molecular targeted therapy before PI or perforation was 3 mo. Asymptomatic patients 70.8%. Conservative PI treatment 100%
Huzar et al[9]	Retrospective Monocenter	One thousand one hundred twenty-nine patients admitted to Burn ICU	PI at CT scan 1.3%. Mortality rate of patients with PI was 73%. Explorative laparotomy in 2-3 h from the CT scan in 94% of the patients. PI involved both small bowel and colon 60%. Nonsurvivors had greater base deficit (P = 0.03), open abdomen after surgery (P = 0.004)
Horowitz et al[45]	Retrospective Monocenter	Twenty-eight gynecological cancer patients and PI at CT scan	Patients symptomatic for abdominal pain 80%. Patients that did poorer were patients with preoperative acidosis, lower level of bicarbonate and lymphopenia

PI: Pneumatosis intestinalis; CT: Computed tomography; PMP: Portomesenteric pneumatosis; WBC: White blood cells; ICU: Intensive care unit.

Table 3 Risk factors in patients with pneumatosis intestinalis

Risk Factors
Anamnestic	Vascular disease
	Atrial fibrillation
Major laboratory risk factors (blood sample)	Lac > 4 mmol/L
	LDH > 400 UI/L
	pH < 7.31
	BUN > 50 mg/dL
Minor laboratory risk factor (blood sample)	WBC > 15.000/L
	Creatinine > 2 mg/dL
	HCO3- < 18 mmol/L
	Potassium 5.5 mmol/L
Radiological	Portomesenteric pneumatosis
	Pneumoperitoneum
	Free peritoneal fluid

LDH: Lactate Dehydrogenase; BUN: Blood urea nitrogen; WBC: White blood cells.