Functional constipation is a common functional gastrointestinal disorder with a multifactorial and incompletely understood pathogenesis.Recent studies have revealed that its development involves the interplay of multiple mechanisms,including neurogenic and myogenic dysfunction of the colon,reduction and impairment of interstitial cells of Cajal(ICCs),outlet obstruction,dysregulation of the gut-brain axis,immune activation,and gut microbiota imbalance.Slow-transit constipation is mainly associated with enteric neural abnormalities,disruption of ICC signaling,and inflammation,whereas outlet obstruction constipation often results from pelvic floor dysfunction and rectal hyposensitivity.Dysregulation of the gut-brain axis plays a central role,involving impaired central regulation,hormonal imbalance,and enhanced local immune response.Additionally,gut microbial metabolites such as short-chain fatty acids,bile acids,and methane affect colonic motility and inflammation.This review summarizes the current understanding and research progress on the pathogenesis of functional constipation,providing insights for mechanism-based and individualized therapeutic approaches.

Functional constipation is a common functional gastrointestinal disorder with a multifactorial and incompletely understood pathogenesis.Recent studies have revealed that its development involves the interplay of multiple mechanisms,including neurogenic and myogenic dysfunction of the colon,reduction and impairment of interstitial cells of Cajal(ICCs),outlet obstruction,dysregulation of the gut-brain axis,immune activation,and gut microbiota imbalance.Slow-transit constipation is mainly associated with enteric neural abnormalities,disruption of ICC signaling,and inflammation,whereas outlet obstruction constipation often results from pelvic floor dysfunction and rectal hyposensitivity.Dysregulation of the gut-brain axis plays a central role,involving impaired central regulation,hormonal imbalance,and enhanced local immune response.Additionally,gut microbial metabolites such as short-chain fatty acids,bile acids,and methane affect colonic motility and inflammation.This review summarizes the current understanding and research progress on the pathogenesis of functional constipation,providing insights for mechanism-based and individualized therapeutic approaches.

OBJECTIVETo summarize the application of staged ileostomy and closure operation combined with nutritional support therapy in the treatment of chronic radiation intestinal injury(CRII).

METHODSClinical data of patients with definite radiation history and pathological diagnosis of CRII receiving treatment at Department of General Surgery, Jinling Hospital from January 2012 to December 2016 were retrospectively analyzed. Patients who were diagnosed with tumor recurrence during operation or by postoperative pathology were excluded. Patients undergoing stageI( ileostomy and stageII( closure operation combined with nutrition support therapy were enrolled to the cohort. Detailed scheme of stage I( ileostomy and therapeutic time were determined by clinical symptoms and nutritional status. While performing ileostomy, the removal of intestinal lesions depended on range and degree of intestinal injury. Nutritional support therapy and other symptom-relieving therapy were offered after surgery. Timing for stageII( closure operation was decided according to nutritional status of patients. Lesions of remaining intestine were determined during operation, then necessary intestinal resection and closure operation were performed. Adhesion classification of radiation intestinal injury (total five levels) proposed by our center was adopted to evaluate the level and range of intestinal lesions. Level 0 indicated no adhesion between injured intestinal loop and surrounding organs; level 1 indicated that the adhesion and fibrosis were limited to right pelvis; level 2 indicated that the adhesion included all pelvis and the adhesion was severe and difficult to divide; level 3 was the forward extension of level 2 adhesion, which was between injured intestinal loop and anterior pelvic wall; level 4 was the upward extension of level 3 adhesion, which was between injured intestinal loop and anterior abdominal wall. Clavien-Dindo classification (lower level means milder symptom) and complication comprehensive index(CCI, lower CCI means milder symptom) calculated by on-line program (http:∕∕www.assessurgery. com) were applied to estimate postoperative complications. Resected intestinal length, adhesion classification of radiation intestinal injury, postoperative complications and time to total enteral nutritional (TEN) of both surgeries and nutritional status (body mass index and serum albumin) were compared between stageI( ileostomy and stageII( closure operation.

RESULTSTwenty-one patients were enrolled in the research with 2 males and 19 females. Primary tumor included 14 cervical cancers, 3 rectal cancers, 1 endometrial cancer, 1 ovarian carcinoma, 1 seminoma and 1 mixed germ cell tumor. Median interval between the end of radiation and radiation intestinal injury was 7(2 to 91) months and median interval between the incidence of radiation intestinal injury and ileostomy was 5(<1 to 75) months. Operative indications for ileostomy were obstruction in 14 cases (66.7%), intestinal internal fistula in 1 case (4.8%), intestinal outer fistula in 2 cases (9.5%), radiation proctitis in 3 cases (14.3%) and acute intestinal perforation in 1 case (4.8%). Average age of patients undergoing stageI( ileostomy was 48 (18 to 60) years with BMI (17.0±2.7) kg/m and serum albumin (36.8±5.2) g/L. Patients undergoing stageII( closure operation had significantly higher BMI [(18.4±2.0) kg/m, t=-2.747, P=0.013] and higher serum albumin [(40.8±3.6) g/L, t=-3.505, P=0.002]. Average interval between stageI( ileostomy and stageII( closure surgery was (197±77) days. Resected intestinal length of stageI( ileostomy was which was significantly longer than that of stageII( closure surgery [(74.0±56.1) cm vs. (15.5±10.4) cm, t=4.547, P= 0.000]. Abdominal adhesion classification of stageII( ileostomy plus closure operation was significantly better as compared to stage I( ileostomy(Z=-3.347, P=0.001). Morbidity of postoperative complications in stageI( ileostomy was 52.4% (11/21), which decreased to 19.0% (4/21) in stageII( operation with significant difference (χ²=5.081, P=0.024). Postoperative complication Clavien-Dindo classification and CCI scores in stageII( operation were significantly lower than those in stageI( operation (P=0.006 and P=0.002). Till June 2017, 17 of 21 patients(81.0%) were followed-up for (28±18) months. Except for 2 cases of relapse, 15 patients recovered to normal diet.

CONCLUSIONSApplication of staged ileostomy and closure operation combined with nutritional support therapy to CRII is in accordance with the principle of injury control surgery. Furthermore, this staged approach is safe and effective, can reduce the morbidity and the severity of complications, and can also be helpful to decide the margin for intestinal resection.

Adolescent ; Adult ; Anastomosis, Surgical ; Female ; Humans ; Ileostomy ; Intestinal Diseases ; etiology ; surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms ; radiotherapy ; Nutritional Support ; Postoperative Complications ; Radiation Injuries ; surgery ; Retrospective Studies ; Young Adult