Intestinal atresia with segmental musculature and neural defect

Background/Purpose

The aim of this study was to investigate the possible etiologic factors of small bowel atresia and to detect the prognostic role of adequate resection and tapering in postoperative morbidity and mortality.

Methods

Intestinal resection specimens were obtained from 10 patients with jejunoileal atresia and 3 control subjects without any gastrointestinal disease. Intestinal specimens taken from 2-cm and 4-cm proximal sides of atresia, atretic segment, and 1-cm and 2-cm distal sides of atresia were stained with Masson trichrome and H&E. Immunohistochemical staining of the biopsy specimens with synaptophysin was also performed to ascertain the number, the intensity, and the morphology of ganglia.

Results

At the blind proximal end, there was segmental absence of muscular layers, presence of neural defects, and replacement of the muscular layers with fibrous tissue beside the relatively intact mucosa.

Conclusions

Segmental defects in muscular and neural structures of the intestinal wall observed in both the antimesenteric and mesenteric sides of the atretic small bowel were considered to support the vascular insult theory as an etiologic factor. Adequate resection rather than tapering the dilated proximal atretic intestinal segment should be included in the surgical treatment of this pathology to avoid the intestinal dysmotility, which may result in gut-related sepsis and death in the postoperative period.     

Alterations of Cajal cells in patients with small bowel atresia

Purpose

Interstitial cells of Cajal (ICC) are regarded as the pacemaker cells of the gastrointestinal tract. There are some well-designed studies investigating the structure and function of ICC subsequent to experimentally induced intestinal obstructions. However, it remains unclear whether reduction of number of ICC primarily leads to mechanical obstruction of the bowel such as seen in intestinal atresia. We aimed to investigate the number of ICC in proximal and distal parts of the atresias of patients with small bowel atresia.

Patients and Methods

Twenty-one patients (13 male and 8 female; median age, 3 days; median gestation age, 38 weeks) with jejunal or ileal atresia underwent primary repair between 2001 and 2009. The demographic data were reviewed. The specimen of the distal and proximal parts of the atretic segments was investigated according to presence and number of ICC in the myenteric plexus using immunohistochemical methods. The jejunum segments of 14 newborns who died from causes other than bowel disease were examined as a control. Scoring and count systems were developed for the evaluation of ICC. A continuous layer of CD-117 immunoreactive Cajal cells around the myenteric plexus was scored as 3, whereas discontinuous and diminished Cajal cells were scored as 2. Few and sparse Cajal cells around the myenteric ganglia and in the muscle layer were scored as 1. If there was no Cajal cell at all, it was scored as zero. In addition, the number of ICC per field was counted. The scores and the numbers of ICC per field were compared in patients with small bowel atresia and control group.

Results

All patients but one survived. One patient was lost because of congenital cardiac anomalies. The median score of control subjects was 3 (range, 1-3). Both the proximal and distal segments of the atretic bowel had a median score of 1 in patients with atresia. Twenty patients' score of proximal (95%) and 19 patients' score of distal bowel segment (90%) had an ICC score of 2 or less. Only 1 control subject (7%) had an ICC score of less than 2. Results were statistically significant in controls and patients. The mean number of ICC in the control group was 5.36 ± 2.36; in distal segments of patients with atresia, it was 1.03 ± 1.4; and in proximal s\egments, it was 0.82 ± 1.56. The difference between the control group and the patients was statistically significant (P < .05).

Conclusion

We demonstrated a remarkable decrease of ICC in small bowel wall of patients with intestinal atresia; but we could not show whether the reduction of ICC is a primary event, which also participates in the pathogenesis of intestinal atresia, or whether the mechanical obstruction caused by any unknown etiology (eg, ischemia) leads to decrease in number of ICC.     

Clinicopathological study of intestinal smooth muscles,interstitial cells of Cajal,and enteric neurons in neonatal jejuno-ileal atresia with special reference to muscle morphometry

PurposeTo assess the thickness of the intestinal smooth muscle layer and analyze the distribution and density of interstitial cells of Cajal (ICC) and enteric neurons in the proximal and distal segments of neonatal jejuno-ileal atresia.MethodsThis is an observational study done over a period of one year in which fifteen cases of jejuno-ileal atresia were included. All the cases underwent laparotomy and resection of the atretic segment with variable portions of the dilated proximal segment and distal segment. Histopathological analysis was done on the sections taken from proximal segments (at 3 cm, 5 cm & 8 cm) and the distal segment (at 2 cm) from the atretic portion. The mean thickness of the inner circular muscle layer (ICML) and outer longitudinal muscle layer (OLML) was assessed in the above segments using image morphometry. In addition, we also analyzed the distribution and density of the ICCs and enteric neurons in the different segments using immunohistochemistry for c-kit and S-100, respectively. Controls included normal jejuno-ileal segments resected from postmortem cases (n = 7) and other nonrelated surgeries (n = 3). The findings were then compared with each-other and with normal controls.ResultsMean thickness of ICML and OLML of the proximal segments at 8 cm was significantly lower than at 3 cm and 5 cm of ileal and jejunal atresias (p ? 0.5). The mean thickness of ICML and OLML of distal segments at 2 cm was similar to the controls in all the atretic cases (p ? 0.5). The mean ICML thickness at proximal 8 cm segment was similar to the distal segment of both ileal & jejunal atresias (p = 0.06 & 0.37 respectively). The mean thickness of the OLML of the proximal 8 cm segments was significantly more than that at the distal segment (p = 0.008) in ileal atresias but was similar in cases of jejunal atresias (p = 0.07). Both the proximal and distal segments of ileal as well as jejunal atresias showed reduction in distribution and density of ICCs, as compared to normal controls. The density of ICCs in proximal segments at 3 cm and 5 cm was similar in both ileal (p = 0.33) and jejunal segments (p = 0.41) but was significantly lower than the proximal 8 cm segments (p ? 0.05).The distribution of ICCs in the proximal segment at 8 cm was similar to the distal segments (p ? 0.05). S-100 staining showed dense expression of neurons and glial cells with presence of submucosal giant ganglia within the proximal dilated segments as compared to the distal segments and the controls, which were more marked at 3 cm and 5 cm levels than at 8 cm level.ConclusionMuscle morphometry using image analysis is a simple technique to assess the thickness of the intestinal smooth muscle layers. There is significant smooth muscle hypertrophy along with marked alteration in density and distribution of ICCs and ENS in the dilated proximal segments up to 5 cm, and relatively milder changes at 8 cm levels, as compared to the distal segments and the controls.Type of studyPrognosis study.Level of evidenceLevel II.     

Exogenous Sonic hedgehog protein does not rescue cultured intestine from atresia formation

Background

The mechanism of intestinal atresia formation remains undefined. Atresia in fibroblast growth factor receptor 2IIIb (Fgfr2IIIb^−/−) mutant mouse embryos is preceded by endodermal apoptosis and involution of the surrounding mesoderm. We have observed that involution of the atretic segment is preceded by the downregulation of Sonic hedgehog (SHH) in the endoderm, which is a critical organizer of the intestinal mesoderm. We hypothesized that supplementation of Fgfr2IIIb^−/− intestinal tracts with exogenous SHH protein before atresia formation would prevent involution of the mesoderm and rescue normal intestinal development.

Methods

In situ hybridization was performed on control and Fgfr2IIIb^−/− intestinal tracts for Shh or forkhead box protein F1 (FoxF1) between embryonic (E) day 11.5 and E12.0. Control and Fgfr2IIIb^−/− intestinal tracts were harvested at E10.5 and cultured in media supplemented with fibroblast growth factor (FGF) 10 + SHH, or FGF10 with a SHH-coated bead. In situ hybridization was performed at E12.5 for Foxf1.

Results

SHH and Foxf1 expression were downregulated during intestinal atresia formation. Media containing exogenous FGF10 + SHH did not prevent colonic atresia formation (involution). A SHH protein point source bead did induce Foxf1 expression in controls and mutants.

Conclusions

Shh and Foxf1 expression are disrupted in atresia formation of distal colon, thereby serving as potential markers of atretic events. Application of exogenous SHH (in media supplement or as a point source bead) is sufficient to induce Foxf1 expression, but insufficient to rescue development of distal colonic mesoderm in Fgfr2IIIb^−/− mutant embryos. Shh signal disruption is not the critical mechanism by which loss of Fgfr2IIIb function results in atresia formation.     

Individualized management of upper rectal atresia

Background/Purpose

Congenital colonic atresia (CA) or stenosis is an infrequent cause of low intestinal obstruction in the neonate. Atresias can occur at any level, and the management of CA is determined by the atretic site and by the presence or absence of associated anomalies. We report our experience dealing with upper rectal atresia during a 5-year period.

Methods

Between January 2004 and December 2008, 3 female newborns with upper rectal atresia with or without associated anomalies were treated. Modes of clinical presentation, methods of diagnosis, associated anomalies, alternative management techniques, and clinical outcome were retrospectively analyzed.

Results

All 3 patients had progressive abdominal distension, bilious vomiting, and failure to pass meconium. Contrast enema showed an atresia at the upper rectum in 2 patients. At laparotomy, case 1 was found to have type III atresia of the upper rectum. Resection of the dilated portion of the proximal colon with end sigmoid colostomy was accomplished in the neonatal period followed by a transanal mucosectomy with takedown of the colostomy and a pull-through procedure at age 3 months. Case 3 had multiple jejunoileal atresias and an upper rectal atresia. The initial management was multiple resections of atretic bowel and anastomoses and an end sigmoid colostomy. The secondary procedure was a takedown of the colostomy and transanal mucosectomy with a pull-through procedure. Case 2 had type I upper rectal atresia in association with imperforate anus complicated by colon perforation during performance of a distal colostogram leading to a complicated and protracted clinical course. All the patients are currently well with voluntary bowel movements, and one has occasional soiling with follow-up of 9 months to 3 years.

Conclusions

Colon atresia, especially at the level of the upper rectum, is uncommon. Whether to proceed with an ostomy or to individualize the operative procedure according to the location of the atresia is still controversial. Transanal mucosectomy was a useful technique at the time of the definitive pull-through for the treatment of upper rectal atresia. In cases of upper CA associated with imperforate anus, delay in diagnosis and potential complications may result if the diagnosis of upper rectal atresia is missed.     

Laparoscopy-assisted surgery for prenatally diagnosed small bowel atresia: simple, safe, and virtually scar free

Purpose

The aim of this study was to describe a new technique for the surgical management of prenatally diagnosed small bowel atresia.

Methods

Under general anesthesia, a 5-mm trocar was inserted using an open technique through an intraumbilical incision. The proximal atretic bowel end was identified using laparoscopy and mobilized toward the umbilicus using an additional 3-mm trocar inserted in the left lower quadrant. The umbilical trocar then was removed, and a ring retractor was inserted into the trocar site and used to expand the wound to deliver both atretic bowel ends. The bowel was repaired and returned to the abdomen through the umbilical wound. The umbilical fascia and skin were closed conventionally.

Results

Three patients were reviewed. Two had minimal abdominal distension, and the atretic bowel ends could be identified easily; laparoscopy-assisted surgery was successful. The third case had significant dilatation, and laparotomy was required. Postoperatively, there was minimal abdominal scarring, and the umbilicus was normal in appearance.

Conclusions

Although this experience is limited to 3 patients, this technique is simple, safe, and virtually scar free and can be applied for the treatment of neonates with prenatally diagnosed small bowel atresia, especially if there is minimal abdominal distension at birth.     

The occurrence of unusual smooth muscle bundles expressing alpha-smooth muscle actin in human intestinal atresia

Background/Purpose: Intestinal dysmotility is an important problem in the postoperative management of patients with intestinal atresia (IA). Changes in the intramural components have so far been histochemically and immunohistochemically examined in both the proximal and distal segments of IA, but no detailed analysis of the muscular elements has been performed. The aim of this study was to carefully examine any alterations in the muscular elements in the intestines from patients with IA. Methods: Resected intestines were obtained from 6 patients with ileal atresia, 4 patients with jejunal atresia, and 3 controls without gastrointestinal diseases obtained by autopsy (congenital diaphragmatic hernia). All specimens were immunochemically stained with a monoclonal antibody to [alpha ]-smooth muscle actin ([alpha ]-SMA) as a smooth muscle marker. Results: In the normal small intestine, almost all the enteric smooth musculature were positive for [alpha ]-SMA antiserum, except for the bulk of the circular musculature. In the proximal segments of all cases with IA, a reduced staining intensity for [alpha ]-SMA was observed mainly in the severely hypertrophic muscle layers. In addition, some bundles of smooth muscle also were located in the submucosal connective tissue near the border of the innermost layer of the circular musculature, in which large amounts of smooth muscle fibers extended occasionally from the innermost layer of the circular musculature to the muscularis mucosae in the proximal segments of 4 cases. In the distal segments of IA, the distribution of [alpha ]-SMA[ndash ]positive smooth muscle fibers was similar to that in the control intestines, excluding mild to moderate hypertrophy of the muscular layers. Conclusions: Both severe hypertrophy and a reduced immunoreactivity for [alpha ]-SMA were observed in the circular muscle layer of the proximal segments. In addition, the occurrence of [alpha ]-SMA[ndash ]positive abnormal smooth muscle fibers was recognized in the submucosal layers of the proximal segments, thus, suggesting a delay in the intestinal muscular formation or a regressive reaction secondary to dilatation. These muscular alterations in the proximal segments might be considered to contribute to the postoperative intestinal dysmotility in IA cases. J Pediatr Surg 38:161-166.     

Reduced Neuronal Innervation in the Distal End of the Proximal Esophageal Atretic Segment in Cases of Esophageal Atresia with Distal Tracheoesophageal Fistula

Background Esophageal dysmotility is a common occurence after surgical repair of proximal esophageal atresia (EA) and distal tracheoesophageal fistula (TEF). The etiology of this motility disorder, however, remains controversial. Esophageal dysmotility also is present in isolated TEF or EA before surgery, suggesting a congenital cause. However, there is no information available in the literature with regard to the intramural nervous system of the human esophagus in EA-TEF. Patients and Methods We examined the distal end of proximal esophageal atretic segment of neonates undergoing EA-TEF repair for intrinsic neuronal innervation. Using specific antibodies, we studied neuronal markers of specimens from nine cases of EA-TEF and 9 cases of normal esophagus by immunohistochemistry using neurofilament (NF), synaptophysin (SY), S100, and glial cell line-derived neurotrophic factor (GDNF). Results In the atretic segment, specimens staining with hematoxylin and eosin showed that there were marked hypoganglionosis and immature ganglion cells in the myenteric plexus. GDNF immunoreactivity in the atretic esophagus were markedly reduced in both the muscular layer and myenteric plexus. SY and NF-immunorective nerve fibers were distributed throughout the myenteric plexus of the normal esophagus, but the scarcity of these immunoreactive nerve fibers in the atretic esophagus was apparent. In contrast, the density of immunorective nerve fibers for S100 in the myenteric plexus and muscular layer was increased in the distal end of the atretic esophagus. Conclusion We concluded that the distribution of ganglion cells and some nerve fibers in the distal end of the atretic esophageal segment is deficient. Inadequate and abnormal neuronal innervation of the esophagus could be related to the esophageal dysmotility seen in EA. Because GDNF is a survival factor for central and peripheral neurons, defective expression of GDNF could have an important role in the defective and/or abnormal neuronal innervation of atretic esophageal segment.     

Gastrointestinal bleeding as a complication of serial transverse enteroplasty

Purpose

Serial transverse enteroplasty (STEP) lengthens and tapers bowel in patients with intestinal failure. Evaluation and treatment of serious late gastrointestinal bleeding (GIB) in three STEP patients are described.

Methods

Patients participating in an interdisciplinary intestinal rehabilitation program were reviewed to identify those who underwent STEP and had GIB requiring transfusion.

Results

Of 296 patients, 23 underwent STEP, and 3 (13%) had subsequent GIB requiring transfusion. Diagnoses were vanishing gastroschisis/atresia, malrotation/atresia, and gastroschisis.. STEP was performed at ages 3–5 months, using 5–15 stapler-firings with an increase in mean bowel length from 39 to 62 cm. GIB was diagnosed 5–30 months post-op and resulted in 1–7 transfusions per patient. Endoscopy demonstrated staple-line ulceration in two patients and eosinophilic enterocolitis in the third. All were treated with enteral antibiotics, sulfasalazine, and luminal steroids. Those with ulcers responded to bowel rest, and the patient with eosinophilic enterocolitis stabilized with luminal steroids. In all three, hemoglobin levels improved despite persistent occult bleeding.

Conclusions

Significant GIB is a potential late complication of STEP. Endoscopy identified the underlying source of GIB in all three patients. A combination of enteral antibiotics, anti-inflammatory medications, and bowel rest was effective in treating post-STEP GIB, without the need for additional bowel resection.     

Esophageal atresia without distal tracheoesophageal fistula: high incidence of proximal fistula

Background

This retrospective study was performed to test our suspicion that the incidence of esophageal atresia with proximal fistula in our institution is much higher than is generally reported.

Methods

The charts of all patients with esophageal atresia and/or tracheoesophageal fistula admitted in the period 1982 to 2000 were analyzed. The type of atresia and/or tracheoesophageal fistula was noted, and the relative incidence was calculated and compared with the relative incidence in a cumulative series of 3492 patients taken from 9 published studies.

Results

In the period under study, 123 patients with esophageal atresia and/or tracheoesophageal fistula were identified. The relative incidence of esophageal atresia without distal fistula was statistically not different (10.6% in the present series against 8.49% in the reference group). A statistically significant difference in the relative incidence of esophageal atresia with proximal fistula, however, was found: 5.69% in the present series against 1.05% in the reference group (P < .0001). Looking at the subgroup of patients without a distal fistula, more than half of the patients did have a proximal fistula.

Conclusions

The relative incidence of esophageal atresia with proximal fistula in this series of children with esophageal atresia and/or tracheoesophageal fistula is significantly higher than reported in the literature. This is on the account of the subgroup of patients without a distal fistula in which the incidence of a proximal fistula is more than 50%. Especially in this subgroup, the existence of a proximal fistula should be ruled out preoperatively.     

Citrulline levels following proximal versus distal small bowel resection

Purpose

Citrulline, a nonprotein amino acid synthesized by enterocytes, is a biomarker of bowel length and the capacity to wean from parenteral nutrition. However, the potentially variant effect of jejunal versus ileal excision on plasma citrulline concentration [CIT] has not been studied. This investigation compared serial serum [CIT] and mucosal adaptive potential after proximal versus distal small bowel resection.

Methods

Enterally fed Sprague-Dawley rats underwent sham operation or 50% small bowel resection, either proximal (PR) or distal (DR). [CIT] was measured at operation and weekly for 8 weeks. At necropsy, histologic features reflecting bowel adaptation were evaluated.

Results

By weeks 6–7, [CIT] in both resection groups significantly decreased from baseline (P < 0.05) and was significantly lower than the concentration in sham animals (P < 0.05). There was no difference in [CIT] between PR and DR at any point. Villus height and crypt density were higher in the PR than in the DR group (P ≤ 0.02).

Conclusion

[CIT] effectively differentiates animals undergoing major bowel resection from those with preserved intestinal length. The region of intestinal resection was not a determinant of [CIT]. The remaining bowel in the PR group demonstrated greater adaptive potential histologically. [CIT] is a robust biomarker for intestinal length, irrespective of location of small intestine lost.     

In vitro smooth muscle contractility before and after relief of experimental obstruction in the rat: Application to the surgical management of ileal dilatation

Purpose

Bowel dilatation occurs proximal to an obstruction and predisposes to intestinal dysmotility. The present study sought to determine whether or not changes in smooth muscle contractility and the thickness of the proximal, dilated bowel wall can be reversed following relief of the obstruction.

Materials and methods

Three groups of seven male Wistar rats were studied. In 8-week-old animals in a control group and a sham-operated group, a small segment of bowel (designated as R1 for controls and R2 for shams) was resected 5.0 cm from the cecum. In the third (operated) group, a narrow, isoperistaltic intestinal loop was created proximal to an end-to-end anastomosis of the ileum in 4-week-old animals. When these animals were 6 weeks old, the loop was re-anastomosed to the distal small bowel (after resection of the loop's distal portion, referred to as R3). Two weeks later, a small segment of bowel was resected proximal to the anastomosis (R4). We evaluated the thickness of the smooth muscle layers and the in vitro contractile responses of circular smooth muscle ileal strips (R1–R4) to electrical stimulation and pharmacological stimulation (with KCl, acetylcholine (ACh), substance P, N^G-nitro-l-arginine methyl ester (L-NAME) and histamine).

Results

The amplitudes of contraction in response to electrical and Ach-mediated stimulation were higher for R3 than for R4 (P < 0.001), R1 and R2 (both P < 0.05). Compared with R1 and R2, the smooth muscle layer was three times as thick in R3 (P < 0.001) and 2.5 times as thick in R4 (P < 0.01).

Conclusion

Our study provides evidence of the possible recovery of intestinal motility (in response to neurotransmitters involved in gut function) after the relief of an obstruction. If ileal motility can conceivably return to normal values, conservative surgical procedures in pediatric patients should be preferred (in order to leave a sufficient length of bowel and avoid short bowel syndrome).     

An alternative management option for colonic atresia preventing loss of the ileocecal valve

Purpose

Management of colonic atresia is contentious, with primary anastomosis having a notable risk of anastomotic leak. In addition, resection of the terminal ileum and ileocecal (i-c) valve is frequently performed, risking side effects such as diarrhea, vitamin B₁₂ deficiency, and gall stone formation.

Methods

The hospital coding system was searched for all patients with a diagnosis of colonic atresia between July 2005 and July 2008. Four term neonates were managed by formation of an ileostomy, a “blow hole” stoma just proximal to the atresia, and a mucus fistula distal to the atresia.

Results

Average time to full feeds was 7.5 days (range, 3-12 days), and average length of stay was 23 days (range, 13-47 days). Stoma management, problematic in 2 infants, was individualized by a specialist stoma nurse. Ileostomy output was refed into the mucus fistula. Complications included 3 episodes of prolapse of the blow hole stoma in infant 2. All of the infants returned to the operating theater at 1 to 3 months of age for restoration of bowel continuity and closure of the ileostomy. The atretic segment was resected, and an end-to-end anastomosis was performed. Recovery was straightforward in all cases.

Conclusion

A procedure that retains the i-c valve and most of the colon through creation of a blow hole stoma in the distended proximal colon with a diverting ileostomy and mucus fistula is described. The technique is recommended in selected infants as bowel length and anatomy can be preserved, despite the use of multiple stomas.     

Gastrointestinal manometric findings in a patient with total intestinal aganglionosis

Background/Purpose

The authors studied gastrointestinal motility in a patient with total intestinal aganglionosis (TIA) and the effect of octreotide (OCT) on ileal motility in this patient.

Methods

The 3200-g girl received ileostomy at 50 cm proximal to the ileocecal site and jejunostomy at 15 cm distal to the ligament of Treitz because of severe ileus owing to TIA. Histology of the intestines, including jejunostomy, showed no ganglion cells. Gastro-duodeno-jejunal and distal ileal manometries were done 8 months after birth.

Results

In upper gastrointestinal manometry, sporadic contractions and clusters consisting of 3 to 5 contractions were observed in the duodenum and jejunum, but no typical phase 3 was observed during the 3-hour recording period. In ileal manometry, long-lasting repetitive contractions were recorded at 2 distal sites. In the most proximal ileum, the frequency of contractions was less than in the 2 distal sites. OCT administration induced a decrease in the amplitude of contractions during the first 20 minutes. The amplitude increased thereafter and reached a level higher than that before OCT administration.

Conclusions

In this patient, the predominant manometry finding was the remarkable hypermotility of the ileum. OCT induced a transient decrease in ileal motility and an increase in motility thereafter.     

Lower limb peripheral NIRS parameters during a vascular occlusion test: An experimental study in healthy volunteers

Objectives

The aim of the study was to compare NIRS parameters in combination with a vascular occlusion test (VOT) at a proximal (leg) and a distal (foot) site in male and female.

Study design

A prospective experimental study in healthy subjects.

Patients and methods

Twenty volunteers (10 male, 10 female, 28 ± 4 years) were investigated during 4 experimental steps: baseline, ischemia, reperfusion, and baseline. For each volunteer, 3 NIRS optodes were placed on right and left calves and the left arch of the foot. Blood pressure, heart rate and peripheral pulse oxymetry were monitored.

Results

Significant differences were observed at baseline between regional oxygen saturation (rSO₂) values according to the site of measurement (proximal rSO₂ 81 ± 9% vs distal rSO₂ 60 ± 5%, P < 0.001) but not according to gender. Both decreases in proximal and distal rSO₂ during ischemia and increases over baseline values during reperfusion depended on group membership (male or female). NIRS parameters during the VOT were significantly higher in male when compared with female at the proximal site: desaturation rate 5.6% (IQR: 5.5) vs 2.5% (IQR: 0.8), P = 0.001; resaturation rate 40.7% (IQR: 6.6) vs 21.7% (IQR: 5.4), P = 0.003; and ΔrSO₂ 10.0% (IQR: 7.0) vs 5.5% (IQR: 6.0), P = 0.041.

Conclusions

Values of rSO₂ at the lower limb varied according to the anatomical site of measurement. A VOT induced major changes in rSO₂ that differed between male and female. These results should be taken into account in further clinical studies.     

Multifocal humeral fractures

Introduction

Multifocal humeral fractures are extremely rare. These may affect the neck and the shaft, the shaft alone, or the diaphysis and the distal humerus. There is no classification of these fractures in the literature.

Materials and methods

From 2004 to 2010, 717 patients with humeral fracture were treated surgically at our department. Thirty-five patients presented with an associated fracture of the proximal and diaphyseal humerus: synthesis was performed with plate and screws in 34 patients, and the remaining patient had an open fracture that was treated with an external fixator.

Results

Mean follow-up was 3 years and 3 months. A classification is proposed in which type A fractures are those affecting the proximal and the humeral shaft, type B the diaphysis alone, and type C the diaphysis in association with the distal humerus. Type A fractures are then divided into three subgroups: A-I, undisplaced fracture of the proximal humerus and displaced shaft fracture; A-II: displaced fracture of the proximal and humeral shaft; and A-III: multifragmentary fracture affecting the proximal humerus and extending to the diaphysis.

Discussion

Multifocal humeral fractures are very rare and little described in the literature, both for classification and treatment. The AO classification describes bifocal fracture of the humeral diaphysis, type B and C. The classification suggested in this article mainly concerns fractures involving the proximal and humeral shaft.

Conclusions

A simple classification of multifocal fractures is suggested to help the surgeon choose the most suitable type of synthesis for surgical treatment.     

Retrograde ejaculation after anterior lumbar interbody fusion with and without bone morphogenetic protein-2 augmentation: a 10-year cohort controlled study

Background context

Retrograde ejaculation (RE) is a complication of anterior lumbar interbody fusion (ALIF) techniques. Most commonly, this results from mechanical or inflammatory injury to the superior hypogastric plexus near the aortic bifurcation. Bone morphogenetic protein-2 (BMP-2) has been used in spinal fusions and has been associated with inflammatory and neuroinflammatory adverse reactions, which may contribute to RE development after anterior lumbar surgery.

Purpose

While controlling for anterior approach technique, we compared the incidence of RE with and without rhBMP-2 exposure, in large, matched cohorts of patients after ALIF.

Study design

Retrospective analysis of 10 years of prospectively gathered outcomes data on consecutive-patient cohorts having the same anterior exposure technique for ALIF with and without rhBMP-2 use.

Patient sample

All male patients without baseline sexual incapacity and having ALIF for lumbar spondylosis or spondylolisthesis of the lowest one or two lumbar levels with and without rhBMP-2, from 2002 through 2011.

Outcome measures

Diagnosis of RE as a new finding after ALIF compared against BMP-2 exposure, comorbid conditions, and other urological complications after ALIF surgery.

Methods

From the comprehensive surgical database at a high volume, university practice, male subjects having ALIF at one (L5/S1) or two levels (L4/5, L5/S1) from 2002 to 2011 were identified. Baseline comorbid factors, postoperative urinary catheter/retention events, and RE events were recorded and comparative incidence compared.

Results

There were four consecutive-patient cohorts identified: one before rhBMP-2 use was adopted (n=174), two cohorts in which BMP-2 use was routine (n=88 and n=151), and one final cohort after BMP-2 use was discontinued from routine use (n=59). The cohorts with and without BMP-2 exposure were closely comparable for age, approach, levels of surgery, comorbid factors affecting RE. Of 239 patients with ALIF and exposure to BMP-2, RE was diagnosed in 15 subjects (6.3%), compared with an RE diagnosis rate of two of 233 control patients without BMP-2 exposure (0.9%; p=.0012). Urinary retention after bladder catheter removal was also more frequently observed in patients exposed to BMP-2 (9.7%) compared with control patients (4.6%; p=.043). Of the baseline comorbid factors, medical or surgical treatment for prostatic hypertrophy disease was associated with an increased risk of RE in the BMP-2 patients (p=.034).

Conclusions

This study confirms previous reports of a higher rate of RE in ALIF procedures using rhBMP-2 and an open anterior approach to the spine. This effect may be associated with an increased risk of postoperative urinary retention after BMP-2 exposure. The magnitude of the RE effect may be increased with concomitant prostatic disease treatments.     

Suburothelial Myofibroblasts in the Human Overactive Bladder and the Effect of Botulinum Neurotoxin Type A Treatment

Background

An increasing body of evidence suggests a possible role of suburothelial myofibroblasts (MFs) in bladder mechanosensation and in the pathophysiology of detrusor overactivity (DO).

Objective

To determine whether markers of MFs, including gap junction protein connexin43 (Cx43) and c-kit have altered immunohistochemical expression in the suburothelium of patients with neurogenic DO (NDO) or idiopathic DO (IDO) and whether this is affected by successful treatment of DO with botulinum neurotoxin type A (BoNTA).

Design, setting, and participants

Patients with NDO (n = 10) or IDO (n = 11) were treated in a single-centre, open-label study of intradetrusor BoNTA injections. Control tissue was obtained from 10 patients undergoing pelvic-floor repair procedures who had no overactive bladder (OAB) symptoms. This study is registered with ClinicalTrials.gov, number NCT00662064.

Interventions

Bladder biopsies performed with flexible cystoscopes were obtained from control subjects and from NDO and IDO patients before BoNTA treatment and at 4 wk and 16 wk after treatment. They were studied with quantitative immunofluorescence using antibodies to connexin 43 (Cx43), vimentin, and c-kit.

Measurements

Differences in Cx43, vimentin, and c-kit immunoreactivity between control subjects and NDO or IDO patients (primary outcomes). Changes in NDO or IDO, Cx43 immunoreactivity, and c-kit immunoreactivity after BoNTA treatment (secondary outcomes).

Results and limitations

Cx43 immunoreactivity was increased in both IDO and NDO patients compared to controls, but remained unchanged after BoNTA treatment. C-kit immunoreactivity was similar in NDO/IDO patients and controls and remained unchanged after BoNTA treatment.

Conclusions

Increased gap junction formation in the suburothelium has been demonstrated in biopsies from humans with DO. It is hypothesised that this change could have a significant role in the pathogenesis of the detrusor abnormality. Successful treatment of NDO or IDO does not appear to be associated with changes in the expression of Cx43 or c-kit on suburothelial MFs.     

Lovastatin prevents discography-associated degeneration and maintains the functional morphology of intervertebral discs

Background context

Discography is an important diagnostic approach to identify the painful discs. However, the benefit of discography, a procedure involving needle puncture and injection of the diagnostic agent into the intervertebral disc, is controversial and has been reported to be associated with accelerated degeneration.

Purpose

To investigate the effect of lovastatin on the prevention of degeneration caused by a discography simulation procedure in rat caudal discs.

Study design

In vivo study using rat caudal discs.

Methods

A single flexible 27-gauge needle puncture into rat caudal discs was performed under fluoroscopic monitoring. Different concentrations (0.1, 1, 5, and 10 μM) of lovastatin were prepared and injected into randomly chosen caudal discs. RNA expression of selected genes, histologic, and immunohistochemical staining were performed to evaluate the phenotypic effects of lovastatin on rat caudal discs.

Results

Simulation of the discography procedure by puncturing the rat caudal discs with a 27-gauge needle and injection of saline solution induced degenerative changes in the nucleus pulposus with minimal damage to the annulus fibrosus. Aggrecan, Type II collagen, and SOX9 expressions were upregulated, whereas Type I collagen expression was significantly suppressed in discs treated with 5 and 10 μM lovastatin. Discs treated with 5 and 10 μM lovastatin were subjected to alcian blue staining and immunohistochemistry that revealed higher levels of glycosaminoglycans and an increase in the number of cells producing S-100 proteins, Type II collagen, and bone morphogenetic protein-2 (BMP-2), respectively. The most effective phenotypic repair was observed in discs treated with 10 μM lovastatin.

Conclusions

Intradiscal administration of lovastatin solution upregulated the expressions of BMP-2 and SOX9 and promoted chondrogenesis of rat caudal discs after needle puncture and substance injection. Therefore, we suggest that lovastatin promotes disc repair and can be used as a potential therapeutic agent for biological repair of disc degeneration after the diagnostic discography procedure.