Laparoscopic versus hybrid approach for treatment of incisional ventral hernia: a 5-10-year follow-up of the randomized controlled multicenter study.

PURPOSE: In this long-term follow-up of a prospective, randomized, and multicenter study, we compare the results of a group receiving laparoscopic incisional ventral hernia repair using intraperitoneal onlay mesh (LG) to a group receiving a hybrid hernia repair where open closure of fascial defect was added to intraperitoneal mesh placement (HG). METHODS: Originally, 193 patients with 2-7 cm incisional hernias were randomly assigned to either the LG or HG during the 30-month recruitment period in 2012 to 2015. Long-term follow-up was conducted 5-10 years after surgery to evaluate hernia recurrence rate and quality of life (QoL). RESULTS: In all, 65 patients in the LG and 60 in the HG completed the long-term follow-up with a median follow-up period of 87 months. Recurrent hernia was detected in 11 of 65 patients (16.9%) in the LG and 10 of 60 patients (16.7%) in the HG (p > 0.9). Kaplan-Meier analysis demonstrated a recurrence rate approaching 20% in both groups, with similar curves. Three patients in the LG (4.6% and five patients in the HG (8.1%) had undergone re-operation due to recurrence (p = 0.48). There was no difference in patient-reported QoL measured using the SF-36 questionnaire. Mean pain scores were similar between groups, mean numeric rating scale (NRS) 0 to 10 being 1.1 in the LG and 0.7 in the HG (p = 0.43). CONCLUSION: Fascial closure did not reduce hernia recurrence rate in this study population, even though it has been shown to be beneficial and recommended in surgery guidelines. In the long term, recurrence rate for both groups is similar.

Laparoscopic versus hybrid approach for treatment of incisional ventral hernia: a prospective randomized multicenter study of 1-month follow-up results.

PURPOSE: The seroma rate following laparoscopic incisional ventral hernia repair (LIVHR) is up to 78%. LIVHR is connected to a relatively rare but dangerous complication, enterotomy, especially in cases with complex adhesiolysis. Closure of the fascial defect and extirpation of the hernia sack may reduce the risk of seromas and other hernia-site events. Our aim was to evaluate whether hybrid operation has a lower rate of the early complications compared to the standard LIVHR. METHODS: This is a multicenter randomized-controlled clinical trial. From November 2012 to May 2015, 193 patients undergoing LIVHR for primary incisional hernia with fascial defect size from 2 to 7 cm were recruited in 11 Finnish hospitals. Patients were randomized to either a laparoscopic (LG) or to a hybrid (HG) repair group. The outcome measures were the incidence of clinically and radiologically detected seromas and their extent 1 month after surgery, peri/postoperative complications, and pain. RESULTS: Bulging was observed by clinical evaluation in 46 (49%) LG patients and in 27 (31%) HG patients (p = 0.022). Ultrasound examination detected more seromas (67 vs. 45%, p = 0.004) and larger seromas (471 vs. 112 cm3, p = 0.025) after LG than after HG. In LG, there were 5 (5.3%) enterotomies compared to 1 (1.1%) in HG (p = 0.108). Adhesiolysis was more complex in LG than in HG (26.6 vs. 13.3%, p = 0.028). Patients in HG had higher pain scores on the first postoperative day (VAS 5.2 vs. 4.3, p = 0.019). CONCLUSION: Closure of the fascial defect and extirpation of the hernia sack reduce seroma formation. In hybrid operations, the risk of enterotomy seems to be lower than in laparoscopic repair, which should be considered in cases with complex adhesions. CLINICAL TRIAL NUMBER: NCT02542085.

Risk of cancer in patients with chronic pouchitis after restorative proctocolectomy for ulcerative colitis.

AIM: The aim of this study was to evaluate the consequences of chronic pouchitis after restorative proctocolectomy for ulcerative colitis. METHOD: Forty-two patients with chronic pouchitis underwent pouch endoscopy with biopsies after a median of 8.3 years of postoperative follow up. The pouchitis disease activity index (PDAI) was calculated. Morphological changes were recorded. Immunohistochemical analyses for cyclooxygenase 2 (COX-2), Ki-67 and p53 were performed, as was DNA flow cytometry. Endoscopy was also carried out in 10 patients without pouchitis and in nine healthy subjects. RESULTS: In patients with chronic pouchitis, the PDAI was 6 (standard error of the mean ± 4). Eighteen (43%) patients used continuous medication. The PDAI correlated positively with villous atrophy (P < 0.05). None of the pouch biopsies showed dysplasia. COX-2 immunostaining was detected in 35 (83.3%) patients with chronic pouchitis, in five (50%) without pouchitis, but in none of the normal controls. COX-2 expression correlated with mucosal atrophy (P < 0.01). In 15 (35.7%) of 42 patients with chronic pouchitis, Ki-67 immunostaining was increased, but no increase was observed in either control group (P < 0.002). No p53 immunopositivity was found, and DNA flow cytometry was normal in all pouches. One of the patients developed adenocarcinoma at the anal anastomosis. CONCLUSION: No dysplastic changes were detected during the first decade after surgery. Routine follow up of patients with chronic pouchitis with a hand-sewn anastomosis may not be necessary, although a small risk of cancer seems to remain at the anal anastomosis. The follow up should be focused on at-risk groups.

Expression of inducible and endothelial nitric oxide synthases in pouchitis.

To study the induction of nitric oxide synthase (NOS) in different forms of pouchitis, we divided patients in five groups: 1) ulcerative colitis, no pouch; 2) no-pouchitis; 3) chronic asymptomatic pouchitis; 4) chronic active pouchitis; and 5) acute pouchitis. Ileal biopsies were scored for NOS-2 (inducible) and NOS-3 (endothelial) immunoreactivity and acute inflammation. In group 1, most specimens lacked NOS-2 immunoreactivity. In group 2, some specimens showed NOS-2 immunoreactive epithelium. In group 3, areas of NOS-2-immunoreactive epithelium were consistently observed in most specimens. In groups 4 and 5, most specimens showed moderate-to-extensive epithelial NOS-2 staining. NOS-2 immunoreactivity scores of groups 1-5 were 0.25 +/- 0.16, 0.67 +/- 0.19, 1.19 +/- 0.40, 2.0 +/- 0.23, and 2.18 +/- 0.12, respectively. Corresponding acute inflammation scores were 0, 0.53 + 0.17, 1.00 +/- 0.33, 1.80 +/- 0.20, and 1.64 +/- 0.15. NOS-2 score correlated with acute inflammation score (p < 0.0001), indicating that NOS-2 induction correlates with both the clinical degree of pouchitis and the severity of acute inflammation. NOS-3 immunoreactivity increased in all pouchitis groups.

Quantitative comparison of growth-associated protein-43 and substance P in ulcerative colitis.

The aim of this study was to compare immunoreactivities for substance P with other enteric neuropeptides and GAP-43, a general marker for enteric nerves, in normal human colon and in different stages of ulcerative colitis. Tissue samples from normal colon and regions of ulcerative colitis colon were obtained at surgery and immunostained for substance P, vasoactive intestinal polypeptide (VIP), somatostatin, calcitonin gene-related peptide (CGRP), enkephalin, galanin, GAP-43, and neuron-specific enolase (NSE). Visual examination and semiquantitative analysis revealed a clear increase in the immunoreactivity for substance P in ulcerative colitis, whereas no differences were observed in the distribution of the other peptides. Therefore, quantitative analysis was performed only for substance P immunoreactivity in the lamina propria, circular muscle layer, and myenteric ganglia. In the lamina propria, the score of total intensity of substance P immunoreactivity was 0.55 +/- 0.15 (mean +/- SEM) in normal colon, 1.30 +/- 0.35 (p = 0.087) in least affected colon, and 2.22 +/- 0.28 (p < 0.001) in moderately affected colon, whereas no significant differences were observed in immunoreactivities for GAP-43. Similar results were obtained for the mean substance P- or GAP-43-immunoreactive area. In the circular muscle layer, the number, density, total intensity, and perimeter of substance P- and GAP-43-immunoreactive fibers were essentially similar in normal colon, and in mild or moderately affected colon. We conclude that ulcerative colitis does not change the density of gut innervation as a whole. However, the density of substance P-containing nerves is specifically increased, probably due to increased peptide synthesis leading to better visibility of the fibers.

Changes in distribution of three isoforms of nitric oxide synthase in ulcerative colitis.

BACKGROUND: Nitric oxide (NO) has an important role both in normal physiology and pathological events of the colon. Our aim was to study possible changes of the three nitric oxide synthases in ulcerative colitis (UC). METHODS: Tissue samples from normal colon and least and moderately affected regions of ulcerative colitis colon were obtained at surgery and immunostained for NOS-1, NOS-2, NOS-3, and GAP-43, a marker of nerve fibers. Quantitative analysis of NOS-1 immunoreactivity was performed on the circular muscle layer. RESULTS: NOS-1-immunoreactive fibers in the muscularis mucosae disappeared in least affected and moderately affected UC colon. Quantitative analysis of NOS-1-immunoreactive nerve fibers in the circular muscle showed no differences between normal and diseased colon. NOS-2 immunoreactivity appeared apically in the epithelial cells. In normal colon some specimens showed immunoreactivity in lower parts of crypts. NOS-2 immunoreactivity increased according to the severity of UC. NOS-3 immunoreactivity was exclusively localized in the vascular endothelium. The difference in NOS-3 staining intensity between the lamina propria and submucosa observed in normal tissue disappeared in moderately affected UC colon. The number of NOS-3-immunoreactive vascular profiles increased in the lamina propria of UC colon. CONCLUSIONS: All three NOS isoforms show specific changes in UC colon.

Quantitative comparison of growth-associated protein GAP-43, neuron-specific enolase, and protein gene product 9.5 as neuronal markers in mature human intestine.

This study was performed to compare GAP-43, PGP 9.5, synaptophysin, and NSE as neuronal markers in the human intestine. GAP-43-immunoreactive nerve fibers were abundant in all layers of the ileum and colon. GAP-43 partially co-localized partially with every neuropeptide (VIP, substance P, galanin, enkephalin) studied. All neuropeptide-immunoreactive fibers also showed GAP-43 reactivity. By blind visual estimation, the numbers of GAP-43-immunoreactive fibers in the lamina propria were greater than those of PGP 9.5, synaptophysin, or NSE. In the muscle layer, visual estimation indicated that the density of GAP-43-immunoreactive fiber profiles was slightly greater than that of the others. The number and intensity of GAP-43-, PGP 9.5-, and NSE-immunoreactive fibers were estimated in sections of normal human colon and ileum using computerized morphometry. In the colon, the numbers of GAP-43-immunoreactive nerve profiles per unit area and their size and intensity were significantly greater than the values for PGP and NSE. A similar trend was observed in the ileum. Neuronal somata lacked or showed only weak GAP-43 immunoreactivity, variable PGP 9.5 immunoreactivity, no synaptophysin immunoreactivity, and moderate to strong NSE immunoreactivity. We conclude that GAP-43 is the superior marker of nerve fibers in the human intestine, whereas NSE is the marker of choice for neuronal somata. (J Histochem Cytochem 47:1405-1415, 1999)

Synchronous ileal autotransplantation impairs adaptation of remaining gut in pigs with proximal small bowel resection.

This study investigates the effects of ileal autotransplantation on morphology, crypt cell proliferation, and brush border disaccharidases of the remaining jejunoileum and colon in growing pigs with 75% proximal small bowel resection. Resection was performed on 30 pigs, of which 15 underwent an autotransplantation of the remaining ileum. The autotransplanted pigs showed reduced weight gain and remnant ileal length when compared to the resected controls. In the autotransplanted pigs, small bowel diameter and weight, mucosal weight and protein content, villus height and surface area, crypt depth, and the number of proliferating crypt cells were reduced similarly both in the intact jejunum and in the autotransplanted ileal remnant. Autotransplantation also decreased the number of proliferative crypt cells of the colon. Specific activities of maltase and sucrase tended to increase in the autotransplanted ileal remnant, whereas the total enzyme activities decreased. These results suggest that ileal autotransplantation disturbs postresectional adaptation of the remaining gut.

Expression of SPARC (secreted protein, acidic and rich in cysteine) in healing intestinal anastomoses and short bowel syndrome in rats.

Due to the proposed functions in soft tissue repair, we evaluated the spatial and temporal distribution of SPARC, a counteradhesive, matricellular glycoprotein in healing intestinal anastomoses and short bowel syndrome (SBS) in rats. Intestinal anastomoses were performed in the jejunum of male Wistar rats. SBS was induced by resecting 70% of the small bowel. In situ hybridization was performed to localize SPARC mRNA and immunohistochemical studies for locating the SPARC protein. The granulation tissue in the anastomotic area exhibited immunoreactivity for SPARC at all time points. The level of expression was maximal at seven to nine days. Endothelial cells of capillaries, smooth muscle cells, fibroblastic cells, and macrophages, as well as mesothelial cells on the serosal surface, were stained. The immunoreactivity was mostly intracellular. SPARC mRNA transcripts were localized to the edges of the anastomotic area at days 1 and 4 and on the newly formed granulation tissue later. The expression of SPARC mRNA was maximal at seven days and decreased thereafter. Both in normal controls and in SBS, SPARC was expressed in endothelial cells of submucosal capillaries and in smooth muscle cells but not in epithelium. Based on the restricted temporal and spatial distribution during the healing of intestinal anastomoses and in SBS we propose that SPARC plays a significant role in intestinal repair and adaptation.

Nerve terminals containing neuropeptides decrease in number after massive proximal small bowel resection in the piglet.

The aim of this study was to evaluate possible changes in the neuropeptide innervation pattern of the remaining porcine ileum following 75% proximal resection of the small intestine. Three-month-old piglets were operated on and two months postoperatively full-thickness specimens of the proximal part of the distal ileum wall were taken. Age-matched 3- and 5-month-old unoperated piglets were used as controls. The number and intensity of VIP-, galanin-, enkephalin-, substance P-, and somatostatin-containing nerve fibers were estimated in sections processed for immunofluorescence microscopy and subjected to quantitative scoring. The VIP-, galanin-, and enkephalin-immunoreactive fibers of the circular muscle layer and villi were also quantitated by computer-assisted morphometry. The number and intensity of VIP-immunoreactive fibers in the mucosa and circular muscle layer markedly decreased after resection as compared to 3-month-old and 5-month-old controls (P < 0.05). The galanin immunoreactivity index decreased significantly after resection in the circular muscle layer as compared to both control groups (P < 0.05). The increase in the number of enkephalin-immunoreactive nerve fibers that normally occurred from 3 to 5 months of age was inhibited by the resection. We were not able to see any differences in somatostatin or substance P immunoreactivity between the groups. The results suggest that massive resection induces significant changes in the neuropeptide-containing innervation of the remaining small intestine. These findings are compatible with altered motor activity and mucosa function in the remain intestine.

Intestinal adaptation after massive proximal small-bowel resection in the pig.

BACKGROUND: Small-intestinal adaptation to resection has been extensively studied in rats. The present study investigates morphology, crypt cell proliferation, and disaccharidase activities of the remaining small intestine and colon after 75% proximal resection of porcine small intestine. METHODS: Specimens were obtained from the proximal jejunum, middle and distal ileum, and proximal colon preoperatively (n = 5) and 14 weeks after small-bowel transection (n = 5) or resection (n = 5). Proliferation was analyzed immunohistochemically with the Ki-67 antigen MIB-1. Disaccharidase activities were determined in accordance with the method of Dahlqvist. RESULTS: In addition to macroscopic enlargement, resection markedly increased the villi and crypts of the remaining small bowel. Crypt cell proliferation decreased with advancing age after transection but remained at the preoperative level after resection. Specific, but not total, activities of maltase and sucrase in the mid-ileum decreased after resection. CONCLUSION: Small-intestinal adaptation in the pig involves macroscopic enlargement and a prompt increase in villus size, which is associated with high crypt cell proliferation.

Adaptive lipid metabolism after ileal autotransplantation in pigs with proximal gut resection.

BACKGROUND: Transplantation of the small intestine impairs intestinal absorptive function, but the adaptive response of a segmental graft is unknown. The aim of this study was to investigate the effects of ileal autotransplantation on the adaptive absorption and metabolism of lipids in pigs that had undergone proximal gut resection. METHODS: Serum lipids, plasma vitamins A and E, absorption and excretion of cholesterol, bile acids and fat, plasma cholesterol precursor and plant sterol proportions to cholesterol (respective markers of cholesterol synthesis and absorption), enteric structure, and transit were determined 4, 8, and 14 weeks after 75% proximal resection with (n = 15) or without (n = 15) autotransplantation of the remaining ileum. RESULTS: As compared with pigs that underwent proximal gut resection, the additional autotransplantation reduced the adaptive increase in total serum and high-density lipoprotein cholesterol, plasma plant sterol proportions and vitamin E concentrations, cholesterol and fat absorption efficiency, and villus height (p < 0.05 for all) during the 14 postoperative weeks and resulted in increases of up to 4.6, 2.7, 1.3, and 2.1 times the plasma cholesterol precursors (p < 0.005), fecal excretion of bile acids (p < 0.0005), neutral steroids (p < 0.005), and net elimination of cholesterol (p < 0.0005), respectively. Cholesterol and fat absorption and plasma plant sterols were significantly enhanced between 8 and 14 weeks after autotransplantation (p < 0.05, p < 0.005, and p < 0.05, respectively), whereas fecal elimination of cholesterol remained increased until the end of the follow-up. CONCLUSIONS: Autotransplantation of the ileum in pigs that have undergone proximal small bowel resection disturbs the adaptive absorption of cholesterol, bile acids, fat, and fat-soluble vitamins, resulting, through increased fecal elimination of cholesterol, in decreased serum cholesterol despite a marked compensatory increase in cholesterol synthesis.

Effect of ileal autotransplantation on cholesterol, bile acids, and biliary lipids in pigs with proximal small bowel resection.

Our major aim was to investigate the consequences of ileal autotransplantation in pigs with proximal small intestinal resection on biliary lipids and metabolism of bile acids. Biliary lipid secretion rates and bile acid absorption were assessed by measuring dietary and biliary lipids, fractional cholesterol absorption, and fecal excretion of cholesterol and bile acids. In addition, serum bile acids and cholesterol, biliary and fecal bile acid species, and ileal villus height were determined after resection of the proximal 75% of the jejunoileum (n = 15) and autotransplantation of the remaining ileum with systemic venous drainage (n = 15) or transection (n = 5). Autotransplantation further increased fecal excretion of neutral and acidic steroids and serum concentration of bile acids after proximal resection (P < .05 for all); autotransplantation significantly decreased serum cholesterol, ileal villus height, fractional bile acid and cholesterol absorption, and biliary molar percentage of total and primary bile acids, whereas biliary secretion of bile acids, enriched by secondary bile acids, and cholesterol remained unchanged. At 14 weeks, ileal villus height, fractional bile acid and cholesterol absorption, biliary molar percentage of bile acids, and proportion of secondary biliary bile acids were altered by transplantation from the respective postresection values of 864 +/- 22 microm, 97.9 +/- 0.6%, 26.9 +/- 3.9%, 91.8 +/- 1.2% and 9.2 +/- 1.3% to 428 +/- 21 microm, 91.1 +/- 1.5%, 9.5 +/- 1.1%, 83.9 +/- 1.4% and 52.5 +/- 3.5% (P < .005 for all). Posttransplantation biliary bile acid secretion correlated positively with fractional reabsorption (r = .70) and biliary molar percentage (r = .73) of bile acids and ileal villus height (r = .65; P < .01 for all). Decreased absorption efficiency and biliary molar percentage of bile acids, increased biliary secondary bile acids, and short ileal villi point to bacterial overgrowth-induced bile acid malabsorption, which with decreased absorptive area may contribute to malabsorption of other lipids after ileal autotransplantation. Compensatory increase in cholesterol synthesis in the pigs with autotransplanted ileum appeared sufficient for constant biliary secretion of cholesterol and bile acids.