Long-term follow-up of patients with Crohn's disease. Relationship between the clinical pattern and prognosis

In a study of 615 new patients with Crohn's disease consecutively diagnosed at the Cleveland Clinic between 1966 and 1969, 592 patients were observed (mean greater than 13 yr, minimum 7 yr), giving a follow-up rate of 96.3%. The original hypothesis was that initial anatomic involvement (the clinical pattern) bears directly on clinical course and prognosis. Disease sites were as follows: 246 ileocolic, 165 small intestine, and 181 colon/anorectal. Among patients with ileocolic disease, 225 (91.5%) had surgery. For the small intestine pattern, the operative incidence was 65.5%; for the colon/anorectal pattern, it was 58%. Operations were for specific reasons: internal fistula with abscess or intestinal obstruction for ileocolic pattern; intestinal obstruction for small intestine pattern; and severe perianal disease or toxic megacolon for colon/anorectal pattern. Complications among nonoperated patients included perianal fistulas and extraintestinal manifestations. No statistical correlation existed between type and duration of medical treatment and prognosis. Seventy-five deaths occurred (12.8%), 36 of which related directly to Crohn's disease. Even after many years, symptoms continued and quality of life tended to be suboptimal among operated patients. For nonoperated patients, the most favorable quality of life was experienced by those with segmental involvement of the colon or ileum. Poor prognosis correlated with ileocolic disease and presence of sepsis because of an internal fistula.     

Percutaneous suprapubic cystolithotripsy for treatment of large bladder calculi

BACKGROUND AND PURPOSE: The treatment options available for managing bladder calculi include transurethral cystolithotripsy, open cystolithotomy, and shockwave lithotripsy. For larger calculi, transurethral treatment can be time consuming, and the manipulation has the potential to cause urethral injury. Percutaneous suprapubic cystolithotripsy represents another treatment option for bladder calculi which is effective and minimally invasive. PATIENTS AND METHODS: Fifteen patients had bladder calculi treated with percutaneous cystolithotripsy over a 3-year period. The mean stone size was 39 mm (range 10-64 mm). Stones were single in seven patients and multiple in eight patients. The indications for cystolithotripsy were stone size >3 cm, multiple stones >1 cm, and inability to perform transurethral cystolithotripsy because of patient anatomy. Percutaneous suprapubic cystolithotripsy was done through either a 30F or a 36F cystotomy tract. Fragmentation and removal was performed with a 26F rigid nephroscope and the pneumatic Swiss Lithoclast. Suprapubic and urethral catheters were placed postoperatively in all patients. RESULTS: Each patient was cleared of the stone burden with a single procedure, and there were no major complications. The mean duration of suprapubic catheterization was 2.6 (range 1-5) days. CONCLUSION: Percutaneous suprapubic cystolithotripsy is an effective and safe technique for treating large bladder calculi. It is minimally invasive, avoids urethral injury, and, in combination with the pneumatic Swiss Lithoclast, can be used to fragment and remove large and hard bladder calculi.     

B cell response to tumor antigens is associated with depletion of B progenitors in murine colocarcinoma

BACKGROUND: B cells that produce antibodies to autologous tumor antigens have been found in patients with colon cancer; the significance of this phenomenon remains unknown. Normally, the elimination of autoreactive B cells occurs in the bone marrow during their maturation. We studied the production of antibodies to syngeneic tumor antigens and the maturation of bone marrow B cells in experimental colocarcinoma model. METHODS: BALB/c mice and syngeneic CT26 colon cancer cell line were used. Reactivity of serum antibodies was tested in Western blot analysis and flow cytometry against CT26 antigens. The number of bone marrow B lineage cells was evaluated with specific antibodies and flow cytometry analysis. RESULTS: A significant decrease in the number of B cell precursors occurred in tumor-bearing mice; it normalized 3 weeks after the removal of CT26 tumors. The number of mature B cells was normal. Serum antibodies from tumor-bearing mice recognized intracellular and not surface antigens of CT26 cells. CONCLUSION: Experimental colon cancer induces B cell response to intracellular, but not surface, tumor cell antigens and restricts the B cell repertoire by depleting their precursors.     

Is Minimal Access Surgery for Cancer Associated with Immunologic Benefits?

Minimal-access surgical techniques have been shown to be beneficial to patients in terms of shorter convalescence, reduced pain, and improved cosmesis. Although systemic immune function is better preserved following laparoscopic procedures when compared with their respective open approaches, CO₂ pneumoperitoneum may significantly affect local (i.e., infra-abdominal) cellular immunity by reducing regional macrophage function. Results to date are conflicting with regard to the impact of closed and open methods on intraabdominal immunity. Impaired cellular immunity after CO₂ pneumoperitoneum may have significant undesirable intra-abdominal effects on tumor surveillance after oncological surgery; however, at present, there is no clinical evidence to support this position. The VATS techniques avoid the use of CO₂ insufflation, which may offer some advantages from the immune function perspective over laparoscopic procedures accomplished with CO₂ pneumoperitoneum. Better preservation of early postoperative cellular immune function and attenuated disturbance in the inflammatory mediators are likely contributing factors to the clinical benefits that follow laparoscopic surgery and VATS. Larger multi-center randomized trials are needed to confirm the potential benefits of minimal-access surgery on patient survival after cancer surgery. Future research should focus on the effects of minimal-access surgery on other mediators (such as MMP-9, IGFBP-3, IL-12, IL-17, and IL-23) that may be important in tumor cell dissemination, deposition, and propagation in the early postoperative period. Furthermore, additional searches for other factors or mediators, heretofore unrecognized, should be carried out. Such studies will, we hope, increase our knowledge and understanding of the impact of surgery on immune and other physiologic functions.     

Increased tumor establishment and growth after open vs laparoscopic bowel resection in mice

Background: Surgery can suppress immune function and facilitate tumor growth. Several studies have demonstrated better preservation of immune function following laparoscopic procedures. Our laboratory has also shown that tumors are more easily established and grow larger after sham laparotomy than after pneumoperitoneum in mice. The purpose of this study was to determine if the previously reported differences in tumor establishment and growth would persist in the setting of an intraabdominal manipulation. Methods: Syngeneic mice received intradermal injections of tumor cells and underwent either an open or laparoscopic cecal resection. In study 1, the incidence of tumor development was observed after a low dose inoculum; whereas in study 2, tumor mass was compared on postoperative day 12 after a high-dose inoculum. Results: In study 1, tumors were established in 5% of control mice, 30% of laparoscopy mice, and 83% of open surgery mice (p < 0.01 for all comparisons). In study 2, open surgery group tumors were 1.5 times as large as laparoscopy group tumors (p < 0.01), which were 1.5 times as large as control group tumors (p < 0.02). Conclusion: We conclude that tumors are more easily established and grow larger after open laparoscopic bowel resection in mice. Received: 27 October 1997/Accepted: 19 January 1998     

Mechanics of wound healing and importance of Vacuum Assisted Closure in urology

PURPOSE: We discuss the mechanisms of wound healing and our experience with the Vacuum Assisted Closure device (Kinetic Concepts, Inc., San Antonio, Texas) for complex urogenital wounds. MATERIALS AND METHODS: The literature obtained from a Medline search on wound healing, wound failure and vacuum assisted closure was reviewed. In addition, we reviewed our experience with negative pressure wound therapy. RESULTS: Wound healing is a complex interaction between the reticuloendothelial and immune systems, in addition to correctable internal and external factors. Understanding the healing process improves outcomes and decreases patient morbidity. Negative pressure wound therapy has hastened wound healing and it adds significant improvement in the arsenal of choices available. CONCLUSIONS: Vacuum Assisted Closure is a therapeutic alternative that complements surgical and medical intervention in patients with complex wounds.     

Malignant round cell tumours of bone: atypical clinical and imaging features

Objective.To describe the clinical, radiological and MRI features of six atypical cases of histologically proven appendicular Ewing sarcoma/ primitive neuroectodermal tumour (PNET). Design. Retrospective review of case notes and available imaging was carried out. Patients. Six patients (4 male, 2 female; mean age 27years, range 19–44 years), presenting over a 77-month period, were identified from the Bone Tumour Register. All had unusual clinical and imaging features for Ewing sarcoma/PNET. Results and conclusions. Four tumours were centred on the distal femoral metaphysis, one in the proximal tibial metaphysis and one in the distal tibial metaphysis. Plain radiographs were available in four cases and showed minor cortical changes. MRI demonstrated a relatively small, eccentrically located intraosseous component with a large, eccentric extraosseous component. Extension into the epiphysis was seen in three cases and into the adjacent joint in two cases. Intraosseous ”skip” metastases were present in three cases. The clinical and imaging features were atypical for conventional intraosseous Ewing sarcoma/PNET and the exact site of origin (intraosseous, periosteal or soft-tissue) was unclear. Received: 6 December 1999 Revision requested: 7 February 2000 Revision received: 20 July 2000 Accepted: 4 August 2000     

Scintigraphic evaluation of colonic transit in two patients with idiopathic chronic constipation

Bowel transit in two women with protracted constipation was evaluated after oral administration of In-111 DTPA in water. Serial abdominal images were obtained for as long as 96 hours to assess transit through the stomach, small bowel, and colon. In both patients, large bowel transit was delayed. A pattern of colonic inertia was observed in one patient, whereas retention in the distal colon was seen in the other patient. Both patients underwent total colectomy with marked symptomatic relief. Colonic transit studies of these patients are presented, and the literature is reviewed.     

Minimally invasive colon resection is associated with a transient increase in plasma sVEGFR1 levels and a decrease in sVEGFR2 levels during the early postoperative period

Introduction  Plasma vascular endothelial growth factor (VEGF) levels are elevated for 2–4 weeks after minimally invasive colorectal resection (MICR). VEGF induces wound and tumor angiogenesis by binding to endothelial cell (EC)-bound VEGF-receptor 1 (VEGFR1) and VEGFR2. Soluble receptors (sVEGFR1, sVEGFR2) sequester VEGF in the blood and decrease VEGF’s proangiogenic effect. The importance of the MICR-related VEGF changes depends on the effect of surgical procedures on sVEGFR1 and sVEGFR2; this study assessed levels of these proteins after MICR for benign indications. Methods  Blood samples were taken (n = 39) preoperatively (preop) and on postoperative days (POD) 1 and 3; in most cases a fourth sample was drawn between POD 7 and 30. sVEGFR1 and sVEGFR2 levels were measured via enzyme-linked immunosorbent assay (ELISA), which detects free and VEGF bound soluble receptor. Late samples were bundled into POD 7–13 and POD 14–30 time points. Results are reported as mean and standard deviation. The data was assessed with paired-samples t-test. Results  Preop, mean plasma sVEGFR2 level (9,203.7 ± 1,934.3 pg/ml) was significantly higher than the sVEGFR1 value (132.5 ± 126.2 pg/ml). sVEGFR2 levels were significantly lower on POD 1 (6,957.8 ± 1,947.7 pg/ml,) and POD 3 (7,085.6 ± 2,000.2 pg/ml), whereas sVEGFR1 levels were significantly higher on POD 1 (220.0 ± 132.8 pg/ml) and POD 3 (182.7 ± 102.1 pg/ml) versus preop results. No differences were found on POD 7–13 or 14–30. Conclusions  sVEGFR2 values decreased and sVEGFR1 levels increased early after MICR; due to its much higher baseline, the sVEGFR2 changes dominate. The net result is less VEGF bound to soluble receptor and more free plasma VEGF.     

Colorectal resection,both open and laparoscopic-assisted,in patients with benign indications is associated with proangiogenic changes in plasma angiopoietin 1 and 2 levels

Introduction  Plasma vascular endothelial growth factor (VEGF) levels are increased after surgery and may stimulate tumor growth after cancer resection. Angiopoietin 1 (Ang 1) and Ang 2 are proteins that impact VEGF-related angiogenesis (VRA). Ang 1 stabilizes mature vessels and inhibits VRA, whereas Ang 2 destabilizes vessels and promotes VRA. The ratio of Ang 1 to Ang 2 reflects the net effect; a low ratio promotes VRA. This study’s purpose was to determine the impact of open and minimally invasive (MIS) colorectal resection (CR) for benign indications on plasma Ang 1 and 2 levels. Methods  A total of 30 patients operated by MIS and 26 operated by open procedure were studied. Plasma was obtained preoperatively (PO) and on postoperative days (POD) 1 and 3. Plasma Ang 1 and Ang 2 levels were assessed via enzyme-linked immunosorbent assay (ELISA) in duplicate. Data were compared using Wilcoxon’s matched-pair test and the Mann–Whitney U-test (significance p < 0.05). Results  Indications, types of resection, and morbidity for the groups were similar. The mean MIS incision length was 4.7 ± 1.6 cm while it was 16.8 ± 7.1 cm for the open group (p = 0.0001). For both groups Ang 2 levels were significantly higher and the Ang 1 to Ang 2 ratio was significantly lower on POD 1 and 3 compared with preoperative results. Ang 1 levels were significantly decreased on POD 1 and 3 in the MIS group but only on POD 1 in the open group. For unclear reasons, preoperative Ang 1 levels and Ang 1 to Ang 2 ratios were significantly different between the groups, which precludes comparison of the postoperative results between groups. Conclusion  CR for benign pathology results in higher Ang 2 levels, lower Ang 1 levels, and lower Ang 1 to Ang 2 ratios early after surgery. These alterations are proangiogenic. These results, plus the already noted VEGF increases, suggest that surgery results in proangiogenic plasma protein changes that may stimulate tumor growth early after surgery. The duration of the Ang 1 and 2 changes needs to be determined. An erratum to this article can be found at