Colorectal Crohn's disease: indications to surgical treatment

Colorectal Crohns Disease (CRCD) represents the 25% of all cases of Crohns Disease (CD). Between January 1984 and December 2000 we have operated 68 patients with CRCD, that represent 10.3% of the patients operated for CD. Thirtythree patients (48.5%) were men and 35 (51.5%) were women. The median age at diagnosis was 37.3 +/- 13.1 years, with the highest incidence during the fourth decade. In most cases the disease involved the left colon and rectum (65.9%), while in 6.3% and in 3.8% of cases the right and the transverse colon respectively. In the 27.9% of cases the entire colon was involved. At the time of surgery, the disease behaviour was stenosing in 30.9% of patients, inflammatory in 22.1%, and penetrating in 47% of cases with the presence of fistulae (coloenteric in 6 patients, colo-bladder in 2 cases, rectouretral in 1 case, colo-cutaneous in 4 cases and intramesenteric in 2 cases) and abscesses (23.5% of patients). In three patients the CRCD had led to neoplastic transformation. Fourteen patients had undergone an emergency surgical procedure for severe acute colitis, 2 for toxic megacolon, 1 for an intraabdominal abscess and one for intestinal occlusion. In the segmentary forms we have always practiced a resection of the diseased colonic segment without total colectomy. In the cases with diffuse colonic involvement in which the rectum was free from disease a total colectomy with ileorectal anastomosis was performed. In the cases with rectal disease (26 cases) the sphinteric function was preserved with low rectal resection or with colo-anal anastomosis. In 4 patients with rectal disease and in 4 cases with fistulae, we complited the intervention with a permanent stoma. During the median follow-up of 83.7 months (12-207) the surgical relapse was of 27.3%. We suggest to treat CRCD with resections limited to the diseased segment. Moreover, it is possible to preserve the sphinteric function every time the rectum or the anal canal are normal, without postoperative complications or early relapses.     

Treatment of desmoids and mesenteric fibromatosis in familial adenomatous polyposis with raloxifene

BACKGROUND: Among the great variety of extracolonic manifestations of familial adenomatous polyposis, the most serious are desmoids and fibromatosis of the abdominal cavity. These may be a danger to the patient and a concern to the clinician. Pharmacological management of this relentless problem is favored by surgical intervention. At present, however, beneficial actions of medical therapy are not separable from undesirable side effects. METHODS: We studied the effects of 120 mg daily of raloxifene, a non-steroidal benzothiophene, on progressive desmoid tumors and mesenteric fibromatosis by evaluation of lesion size and symptoms in 13 patients with familial adenomatous polyposis, selected on the basis of intra-abdominal localization of the lesion, on refractoriness to other medical treatments, and on estrogen receptor-alpha expression. RESULTS: The patients had a significant response to raloxifene therapy, with complete remission in 8 cases and partial response in 5 cases, evaluated by regression of symptoms and tumor size. Serum biochemical parameters did not show any significant changes. Side effects were never observed. CONCLUSIONS: Although the number of patients included in the study is limited and in spite of some limitations, the available results support that, in the evaluation of response, daily therapy with raloxifene decreases desmoid tumor and mesenteric fibromatosis size and symptoms and does not cause side effects. These findings offer a novel option in the pharmacological treatment of desmoids, leading to medical therapy of these neoplastic lesions in familial adenomatous polyposis patients.     

Analysis of sequential aliquots of hypertonic saline solution-induced sputum from clinically stable patients with cystic fibrosis

STUDY OBJECTIVES: Sputum induction (SI) is a noninvasive tool for sampling inflamed airways. The purpose of this study was to determine the optimal duration of collection in patients with cystic fibrosis (CF). The hypothesis was that the duration of SI collection would quantitatively and qualitatively alter the content of the induced sputum. METHODS: In 10 clinically stable patients with CF (mean +/- SD age, 28 +/- 7 years; mean FEV(1), 2.6 +/- 0.7 L), SI was performed with 3% hypertonic saline solution at five time points over 20 min. RESULTS: SI was well tolerated, with an average maximum fall in FEV(1) of 7 +/- 7%. The sample volumes, urea concentrations, interleukin-8 concentrations, total cell counts, and nonsquamous cell counts remained constant (p > 0.05). The percentage of neutrophils decreased from 89 +/- 5% to 86 +/- 4% (p = 0.03), and the percentage of alveolar macrophages increased 5 +/- 2% to 8 +/- 4% (p < 0.01). The mean quantitative microbiological counts of nonmucoid Pseudomonas aeruginosa and Staphylococcus aureus decreased over the 20-min time period each by half a log (p = 0.05 and p < 0.01, respectively). Surfactant protein-A concentration increased from 1.6 +/- 0.3 to 2.4 +/- 0.4 ng/mL (log(10); p < 0.001). CONCLUSIONS: We conclude that aliquots of induced sputum are similar in clinically stable patients with CF during 4-min intervals, although there is more alveolar sampling after 20 min. When induced-sputum samples are fractionated for research monitoring of inflammatory or microbiologic indexes, power calculations accounting for these variations over time are required.     

The change in allograft function among long-term kidney transplant recipients

Long-term kidney allograft survival continues to remain an elusive goal. Kidney transplant recipients are believed to be at high risk for loss of allograft function, and new, potentially non-nephrotoxic immunosuppressive medications are advocated to improve long-term allograft survival. To evaluate the efficacy of such therapeutic interventions, information regarding the change in GFR among kidney transplant recipients with long-term allograft survival is needed. We studied 40,963 transplant recipients between 1987 and 1996 with allograft survival of at least 2 yr in the United States Renal Data System. Linear regression methods were applied to serial GFR estimates after transplantation. The baseline mean GFR at 6 mo after transplantation was 49.6 +/- 15.4 ml/min per 1.73 m(2). During the mean follow-up of 5.7 +/- 2.3 yr, the mean +/- standard error of the change in GFR was -1.66 +/- 6.51 ml/min per 1.73 m(2) per year (median, -0.94 L/min per 1.73 m(2) per year). A total of 12,583 (30%) of patients had improvement in GFR, 8133 (20%) patients had no change in GFR, and 20,247 (50%) patients had decline in GFR. It is concluded that, although most patients had significant impairment of GFR at baseline, the decline in GFR was slow and many patients had either no change or improvement in GFR. Strategies to improve long-term kidney allograft survival that increase baseline allograft function may be more effective than strategies to slow the decline in GFR.     

Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease

Limited data suggest that HMG-CoA reductase inhibitors (statins) may slow loss of renal function in individuals with chronic renal insufficiency. This study was conducted to determine whether pravastatin reduced rates of loss of renal function in people with moderate chronic renal insufficiency. This was a post hoc subgroup analysis of a randomized double-blind placebo controlled trial. Data were analyzed from the CARE study (a randomized trial of pravastatin versus placebo in 4159 participants with previous myocardial infarction and total plasma cholesterol < 240 mg/dl). Participants with estimated GFR (MDRD-GFR) < 60 ml/min per 1.73 m(2) body surface area at baseline were considered to have moderate chronic renal insufficiency. Multivariate regression was used to calculate rates of decline in MDRD-GFR for individuals receiving pravastatin and placebo, controlling for prospectively determined covariates that might influence rates of renal function loss. Change in renal function could be calculated in 3384 individuals, of whom 690 (20.4%) had MDRD-GFR < 60 ml/min per 1.73 m(2) and were eligible for inclusion. Among all individuals with MDRD-GFR < 60 ml/min per 1.73 m(2)), the MDRD-GFR decline in the pravastatin group was not significantly different from that in the placebo group (0.1 ml/min per 1.73 m(2)/yr slower; 95% CI, -0.2 to 0.4; P = 0.49). However, there was a significant stepwise inverse relation between MDRD-GFR before treatment and slowing of renal function loss with pravastatin use, with more benefit in those with lower MDRD-GFR at baseline (P = 0.04). Rate of change in MDRD-GFR in the pravastatin group was 0.6 ml/min per 1.73 m(2)/yr slower than placebo (95% CI, -0.1 to 1.2; P = 0.07) in those with MDRD-GFR < 50 ml/min, and 2.5 ml/min per 1.73 m(2)/yr slower (95% CI, 1.4 to 3.6 slower; P = 0.0001) in those with MDRD-GFR < 40 ml/min per 1.73 m(2)/yr. Pravastatin also reduced rates of renal loss to a greater extent in participants with than without proteinuria at baseline (P = 0.006). It is concluded that pravastatin may slow renal function loss in individuals with moderate to severe kidney disease, especially those with proteinuria. These findings require confirmation by a large randomized trial conducted specifically in people with chronic renal insufficiency.     

Identification of the B-cell tumor-specific molecular fingerprint using non-radiolabelled PCR consensus primers

Background:The complementarity determining region 3 (CDR3)of the immunoglobulin (Ig) heavy chain variable region (V_H)is the most reliable molecular fingerprint for most if not all human Bcells. The nucleotide sequence encoding for any B-cell tumor-specificV_H CDR3 is currently identified by PCR sequencing based onprocedures involving the usage of either radioactive materials,patient/family-specific primers, or bacterial cloning. Patients and methods:In six consecutive patients withfollicular lymphoma we assessed the feasibility of a method that allowsfor identification of the tumor-specific V_H CDR3 usingconsensus primers while avoiding both radioactive materials andbacterial cloning procedures. Results:Thetumor-specific V_H CDR3 was successfully identified in all sixpatients in nearly half the time typically required by any other methodcurrently utilized. The feasibility of the proposed method was notsignificantly affected either by the tumor-specific Ig isotype, or bythe tumor infiltration in the original biopsy specimen. In the threepatients for whom tumor specimen-derived hybridomas were available, thetumor-specific V_H CDR3 was also found in at least 8 of 10 ofthem. Conclusions:The proposed method allows theability to quickly identify the B-cell tumor-specific V_H CDR3using consensus primers while avoiding radioactive materials andbacterial cloning procedures.