Andrew P. Zbar

Circulating VEGF levels in the serum of gastric cancer patients: Correlation with pathological variables, patient survival, and tumor surgery

ObjectiveTo evaluate the clinical usefulness of serum vascular endothelial growth factor (VEGF) levels in gastric cancer patients. Summary Background DataVascular endothelial growth factor plays an important role in the formation of new blood vessels involved in the growth and metastatic spread of solid tumors, but there is limited information regarding the clinical significance of serum VEGF levels in cancer patients. MethodsSerum VEGF concentrations were measured by an enzyme linked immunosorbent assay in 61 healthy controls and in 58 gastric cancer patients before surgery, and then again at 7 and 30 days after surgery. The association between preoperative serum VEGF levels, clinicopathological features and patient survival, and their changes following surgery were evaluated. ResultsSerum VEGF levels in gastric cancer patients were significantly higher than those in controls. There was a significant association between serum VEGF levels and disease stage, as well as invasion depth of the tumor and the presence of distant metastases. Serum VEGF levels decreased significantly after radical resection of the primary tumor and increased in patients with unresectable tumors. Multivariate regression analysis showed that serum VEGF level is an independent prognostic factor for survival. ConclusionsSerum VEGF levels in gastric patients are significantly higher compared with normal controls and correlate with local tumor extent, disease stage, and the presence of distant metastases. Preoperative serum VEGF concentration decreases significantly after radical resection of the primary tumor and is an independent prognostic factor for patient survival suggesting that determination of serum VEGF levels may be clinically useful.

Dynamic transperineal ultrasound vs. defecography in patients with evacuatory difficulty: a pilot study

Background and aimsDefecating proctography has been traditionally used to assess patients with evacuatory dysfunction. More recently, dynamic transperineal ultrasound has been described, defining the interaction between the infralevator viscera and the pelvic floor at rest and during straining. This study compared qualitative diagnosis and quantitative measurement obtained by defecography and dynamic transperineal ultrasonography in patients with evacuatory difficulty.Patients and methodsThirty-three women were examined using both techniques with both examiners blinded to the results of the other method. Quantitative measurement was made of rectocele depth, anorectal angle (at rest and during maximal straining) and anorectal junction position at rest and movement during straining.ResultsThere was good agreement for the diagnoses of rectocele, rectoanal intususseption, and rectal prolapse. Dynamic transperineal ultrasound was more likely than defecography to make multiple diagnoses or to diagnose an enterocele when a rectocele was present. There was no difference noted between the two techniques for the measurement of anorectal angle at rest, anorectal junction position at rest, or anorectal junction movement during straining. The mean anorectal angle during straining was 123.3±4.3° as measured by defecography and 116.4±3.3° as measured by dynamic transperineal ultrasound, nearly reaching statistical significance.ConclusionDynamic transperineal ultrasound is a simple and accurate technique for assessment of the pelvic floor and soft-tissues in patients with evacuatory dysfunction.

Sex Hormone Changes in Morbidly Obese Patients after Vertical Banded Gastroplasty

Serum sex hormone levels were measured preoperatively in 57 morbidly obese patients (19 men and 38 premenopausal women) and 12 months after vertical banded gastroplasty. In the male group, there was a significant decrease in estradiol and an increase in follicle-stimulating hormone (FSH), total testosterone and sex-hormone-binding globulin (SHBG). Among female patients, a significant decrease in estradiol, total and free testosterone and an increase in FSH and SHBG was found. Irregular menses present preoperatively in 5 women were corrected after successful weight loss. In conclusion, altered sex hormonal levels and gynecologic abnormalities associated with morbid obesity are corrected with adequate weight loss following vertical banded gastroplasty.

Rectocele: pathogenesis and surgical management

BackgroundRectocele is a common finding in patients with intractable evacuatory disorders. Although much rectocele surgery is conducted by gynecologists en passant with other forms of vaginal surgery, many reports lack appreciation of the importance of coincident anorectal symptoms, and do not report functional and clinical outcome data. The pathogenesis of rectocele is still controversial, as is the embryological and anatomical importance of the rectovaginal septum as well as recognizable defects in its integrity and its relevance in formal repair when rectocele is operated upon as the principal condition in patients with intractable evacuatory difficulty.DiscussionThe investigation and surgical management of rectocele is controversial given the relatively small numbers of operated patients in any single specialist unit and the relative lack of prospective data concerning functional outcome in operated cases. The imaging of rectocele patients is currently in a state of change, and the newer diagnostic modalities including dynamic magnetic resonance imaging frequently display a multiplicity of pelvic floor disorders. When surgery is indicated, coloproctologists most commonly utilize an endorectal defect-specific repair, but there are few controlled randomized data regarding outcome and response criteria of specific symptoms with particular surgical approaches. A Medline-based literature search was conducted for this review to assess the clinical results of defect-specific rectocele repairs using the endorectal, transvaginal, transperineal, or combined approaches. Only the studies are included that report both pre- and postoperative symptoms including constipation, evacuatory difficulty, pelvic pain, the impression of a pelvic mass, fecal incontinence, dyspareunia or the need for assisted digitation to aid defecation.ConclusionThe history of rectocele repair, its clinical and diagnostic features and the advantages, disadvantages and indications for the different surgical techniques are presented in this review. Suggested diagnostic and surgical therapeutic algorithms for management have been included. It is recommended that a multicenter controlled randomized trial comparing surgical approaches for symptomatic evacuatory dysfunction where rectocele is the principal abnormality should be conducted.

The Rectogenital Septum: Morphology, Function, and Clinical Relevance

PURPOSE: The rectogenital septum (known in clinical literature as Denonvilliers’ fascia) forms an incomplete partition between the rectum and the urogenital organs in both men and women. It is composed of collagenous and elastic fibers and smooth muscle cells intermingled with nerve fibers emerging from the autonomic inferior hypogastric plexus. The aim of this study was to investigate the fetal development of the rectogenital septum, and the origin and innervation of the longitudinal smooth muscle cells within the septum, as well as to consider possible effects on function of operations that compromise the integrity of these structures. METHODS: Macroscopic dissections on embalmed human pelves and plastination histology of 40 fetal and newborn pelvic specimens were performed. By means of conventional and immunohistochemical staining methods using monoclonal and polyclonal antibodies for tissue analysis and neuronal labeling, the motor and sensory innervation of the longitudinal muscle bundles within the septum was defined. RESULTS: The rectogenital septum is formed by a local condensation of mesenchymal connective tissue in the early fetal period. The longitudinal muscle bundles could be traced back to the longitudinal layer of the rectal wall, and, using the septum as a guiding structure, it was possible to identify autonomic nerve fibers and ganglion cells innervating the muscle cells and crossing the midline without detectable gender differences. CONCLUSIONS: Because of a coinnervation of the rectal muscle layers and the adjacent longitudinal muscle fibers of the septum, a functional correlation between the two structures during defecation is postulated. On the basis of these findings, a safer dissection of the anterior rectal wall during rectal resection is postulated, thus limiting functional disturbance and preventing neural damage.

Conventional cutting vs. internal anal sphincter-preserving seton for high trans-sphincteric fistula: a prospective randomized manometric and clinical trial.

Abstract.Background:Cutting setons have been used in complicated perirectal sepsis with good effect, although there is a moderately high incidence of fecal leakage after their use. The aim of this study was to compare a modified cutting seton, which repaired the internal anal sphincter muscle and re-routed the seton through the intersphincteric space, with a conventional cutting seton.Methods:A total of 34 patients were randomized between 1998 and 2002. They were prospectively assessed by continence score and anorectal manometry, and for anal function, clinical sepsis and fistula recurrence.Results:There was no difference in postoperative continence score, incidence of recurrent fistula or healing time between groups after a mean follow-up of 12 months. Resting anal manometric pressures and vector volumes were consistently higher with the modified seton (although not statistically significant), as was the area under the inhibitory curve during elicitation of the rectoanal inhibitory reflex across the full sphincter length. (p<0.05).Conclusion:A larger prospective study of internal anal sphincter-preserving seton use in cryptogenic high transshincteric fistula-in-ano appears justified.

Clinical significance of serum levels of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients.

OBJECTIVES:This study evaluated serum concentrations of soluble cell adhesion molecules in patients with gastric cancer and in healthy control subjects. Our objectives were to correlate these levels with clinicopathological features, established tumor markers, and patient survival, and to assess changes in serum levels of cell adhesion molecules after tumor surgery.METHODS:The serum concentrations of the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were investigated by ELISA in 57 gastric cancer patients, both before and 7 days after surgery, and in 47 healthy control subjects.RESULTS:Preoperative serum concentrations of ICAM-1 and VCAM-1 in gastric cancer patients were significantly higher when compared with those of healthy controls, whereas there were no differences regarding serum E-selectin levels. Serum levels of E-selectin, ICAM-1, and VCAM-1 correlated significantly with each other. There was a significant association between preoperative levels of all three adhesion molecules and disease stage, gastric wall invasion, lymph node involvement, and presence of distant metastases. Their concentrations decreased significantly after radical resection of the tumor, whereas they remained almost unchanged in patients with unresectable disease. Elevated preoperative serum levels of E-selectin, ICAM-1, and VCAM-1 levels were found in 24.6%, 33.3%, and 28.1% of patients, respectively. Elevated levels of all three molecules were significant prognostic factors for patient survival but not independent of disease stage.CONCLUSIONS:These findings suggest that serum concentrations of E-selectin, ICAM-1, and VCAM-1 may reflect tumor progression and metastasis, and may be clinically useful.

Perineal rectosigmoidectomy (Altemeier's procedure): a review of physiology, technique and outcome

Abstract. Perineal rectosigmoidectomy (Altemeiers procedure), as used for the surgical treatment of full-thickness rectal prolapse, has a long history. The physiological derangement in patients with rectal prolapse is complex, frequently showing impairment of the rectoanal inhibitory reflex, intermittent high-pressure rectal motor activity, disturbances in anorectal sampling and attendant pudendal neuropathy. There are currently few defined preoperative factors in patients presenting with rectal prolapse and fecal leakage which predict for the restoration of continence after surgery. This review describes our technique of Altemeyers procedure and analyzes the reported results of this operation, presenting those studies which assessed postoperative continence and prolapse recurrence in particular. The lack of prospective randomized data regarding this perineal approach makes clinical interpretation difficult at the present time.

Serum and Drainage Fluid Vascular Endothelial Growth Factor Levels in Early Surgical Wounds

Background: Wound healing relies on a coordinated expression and release of growth factors controlling angiogenesis. We measured vascular endothelial growth factor (VEGF) levels in serum and early wound fluid following primary sutured and mesh repair of abdominal hernias. Materials and Methods: Thirty-seven patients were studied measuring serum and wound drainage fluid VEGF by enzyme-linked immunosorbent assay preoperatively and on the 1st, 3rd, 5th and 7th postoperative days. Results: Serum and wound fluid VEGF levels increased significantly by the 3rd postoperative day and continued to rise during the conduct of the study with wound fluid concentrations always exceeding serum levels. The kinetics of VEGF increases were similar in both types of hernia repair; however, serum and wound levels rose slightly earlier in the mesh repair group. Conclusions: Steadily increasing levels of VEGF are detected during the early proliferative phase of wound healing in both serum and wound fluid. It is unknown whether either is predictive for delayed hernia recurrence.

Cadherins: an integral role in inflammatory bowel disease and mucosal restitution.

The intestinal epithelium is characterized by rapid cellular turnover with continuous proliferation of multipotential stem cells within Lieberkuhn’s crypts, cellular migration along the crypt–villus axis, cellular differentiation, polarization, apical apoptosis, and luminal shedding. These processes are critical for the development and maintenance of normal intestinal epithelial architecture and function and involve complex cell–cell and cell-substratum interactions, which are mediated by epithelial (E)-cadherin and the integrins, respectively. This review outlines the role of E-cadherin and its cytoplasmic binding proteins, the catenins, as well as the interplay with other mucosal adhesion and restitution molecules during physiological processes in the intestinal epithelium mediating embryogenesis, cellular differentiation, cellular migration, and mucosal repair, as well as what is known about the dysregulation of assembly of the E-cadherin–catenin adhesion complex in inflammatory bowel disease.