Endoluminal calprotectin measurement in assessment of pouchitis and a new index of disease activity: a pilot study.

Pouchitis is the most common complication following proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis (UC). To provide a standardized definition of pouchitis clinical, endoscopic and histological markers were grouped and weighted in the pouch disease activity index (PDAI). However, the delay in the assessment of the final score due to the time requested for histological analysis remains the main obstacle to the index implementation in clinical practice so that the use of modified-PDAI (mPDAI) with exclusion of histologic subscore has been proposed. We tested the ability of calprotectin measurement in the pouch endoluminal content to mimic the histologic score as defined in the PDAI, the index that we adopted as gold standard for pouchitis diagnosis. Calprotectin was measured by ELISA in the pouch endoluminal content collected during endoscopy in 40 consecutive patients with J-pouch. In each patient PDAI and mPDAI were calculated and 15% of patients were erroneously classified by mPDAI. ROC analysis of calprotectin values vs. acute histological subscore ≥ 3 identified different calprotectin cut-off values with corresponding sensitivity and specificity allowing the definition and scoring of different range of calprotectin subscores. We incorporated the calprotectin score in the mPDAI obtaining a new score that shows the same specificity as PDAI for diagnosis of pouchitis and higher sensitivity when compared with mPDAI. The use of the proposed new score, once validated in a larger series of patients, might be useful in the early management of patients with symptoms of pouchitis.

Lamina Propria CD4+LAP+ Regulatory T Cells Are Increased in Active Ulcerative Colitis but Show Increased IL-17 Expression and Reduced Suppressor Activity.

BACKGROUND: A CD4+CD25- regulatory T cell population expressing the surface TGF-ß in its latent form LAP+ [latency associated peptide] cells was proved to be protective in experimental colitis and to be suppressive of human peripheral blood [PB] T proliferation. We investigated the frequency and function of lamina propria [LP] CD4+LAP+ T cells in inflammatory bowel disease [IBD] patients. METHODS: Specimens from patients undergoing colonoscopy or bowel resection for IBD and colonic cancer were used as source of lamina propria mononuclear cells [LPMC]. The ulcerative colitis [UC] group was divided according to endoscopic activity evaluated with modified Baron Score. IL-17, IFN-γ, IL-10, LAP, and Foxp3 expression in CD3+CD8- [CD4] or CD3+/CD4+ gated cell population was assessed by immunofluorescence. The ability of FACS-sorted LP CD3+CD8-[CD4] LAP+CD25- to inhibit stimulated autologous PB CD3+CD8-[CD4] LAP- CD25- cells proliferation was assessed. RESULTS: LP CD4LAP+ cells were significantly increased, when compared with controls, in active UC patients and not in Crohn's disease patients. The majority of LP CD4+LAP+ cells were Foxp3-. The percentage of IL-17+ cells in LP CD3+CD8-[CD4] LAP+ cells was significantly higher in active UC patients when compared with controls. LP CD3+CD8-[CD4]LAP+CD25- isolated from UC patients showed reduced or no ability to inhibit autologous PB CD3+CD8-[CD4]LAP-CD25- cell proliferation when compared with controls. Removal of IL-17+ cells from LP CD3+CD8-[CD4] LAP+ cells increases their suppressive ability. CONCLUSIONS: The percentage of LP CD4LAP+ cells is increased in active UC, showing reduced suppressor activity due to their increased proportion of intracellular IL-17 expression.

Adrenocortical carcinoma with inferior vena cava, left renal vein and right atrium tumor thrombus extension.

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare, but highly aggressive type of tumor with an annual incidence of 1-2 cases per million. The prognosis is poor with a five-year overall survival rate of ∼35%. The poor prognosis may be related to the advanced stage at which the majority of ACCs are detected. Complete surgical resection remains the most effective treatment. PRESENTATION OF THE CASE: A 51-year-old female patient with recent onset of dyspepsia, ascites and peripheral edema was referred to our institution. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) displayed a 8cm Ø right adrenal mass. Moreover a tumor thrombus jutted out into the IVC, left renal vein and right atrium. An echocardiographic evaluation confirmed the presence of the tumor thrombus in the right atrium. The patient underwent adrenalectomy with removal of its intravascular extension with the assistance of cardiopulmonary bypass and hypothermia. DISCUSSION: ACC is a rare malignancy and ACC with tumor thrombus extension is a rare presentation. Patients can present with a variety of sign and symptoms, depending on the extent of the tumor. CT scan of chest and abdomen represents the gold standard in ACC staging while magnetic resonance imaging (MRI) is preferred for tumor thrombus characterization. Complete surgical resection with a negative margin, R0 resection, is the only curative option for localized disease. Kidney sparing surgery should be performed when possible. CONCLUSION: We present a rare case of Adrenocortical carcinoma with tumor thrombus extending into the IVC and right atrium. Complete resection with negative margins represents the best therapeutic chance for these patients.

von Hippel Lindau disease with colon adenocarcinoma, renal cell carcinoma and adrenal pheochromocytoma.

von Hippel-Lindau (VHL) disease is an autosomal dominant inherited tumor syndrome characterized by the presence of heterogeneous tumors derived from different organs. VHL is caused by germline mutations in the VHL tumor suppressor gene located on chromosome 3p25-26. The loss of functional VHL protein contributes to tumorigenesis. VHL tumors are most frequently derived from the kidneys, adrenal gland, central nervous system, eyes, inner ear, epididymis and pancreas. We herein describe the case of a 64-year-old man carrying the VHL gene mutation affected by simultaneous colon adenocarcinoma, renal clear cell carcinoma and adrenal pheochromocytoma.

Small intestine contrast ultrasonography (SICUS) for the detection of small bowel complications in crohn's disease: a prospective comparative study versus intraoperative findings.

BACKGROUND: In Crohn's disease (CD) patients, small intestine contrast ultrasonography (SICUS) accurately assesses small bowel lesions. Its diagnostic role is not known in the assessment of intraabdominal CD complications. The aim was to assess the value of SICUS to detect intestinal complications in patients with CD. METHODS: Forty-nine CD patients (21 female, mean age 37.7 years; range 12-78 years) underwent resective bowel surgery and were included in this study. The accuracy of SICUS to preoperatively detect number, site, and length of strictures, fistulas, and abscesses was compared with surgical and pathological findings by kappa statistics. RESULTS: SICUS identified at least one stricture in 39/40 and excluded it in 9/9 (97.5% sensitivity, 100% specificity, k = 0.93); two or more strictures in 9/12 (75% sensitivity, 100% specificity, k = 0.78). The agreement by k-statistics between SICUS and surgery in identifying proximal and distal small intestine site of stricture was 1 and 0.92, respectively. The extension of strictures was 6.8 ± 5.4 cm at surgery, 6.6 ± 5.4 cm at SICUS (NS). Fistulas were correctly identified in 27/28 patients and excluded in 19/21 patients (96% sensitivity, 90.5% specificity, k = 0.88). Intraabdominal abscesses were correctly detected in 10/10 patients and excluded in 37/39 patients (100% sensitivity, 95% specificity, k = 0.89). CONCLUSIONS: SICUS is an accurate method for the detection of small intestinal complications in CD. Noninvasive SICUS is valuable as a primary investigative method for evaluating and planning proper treatment in patients with severe CD of the small bowel.

Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells.

BACKGROUND: Probiotics have anti-inflammatory effects in patients with inflammatory bowel disease and appear to regulate mucosal immune response through reductions in proinflammatory cytokines. The probiotic VSL#3 prevents pouchitis if started within a week of ileostomy closure and maintains remission following antibacterial treatment in patients with refractory or recurrent pouchitis. However, the efficacy of probiotics and their effects on regulatory cells if started at a greater time after surgery in patients undergoing ileal pouch anal anastomosis (IPAA) for ulcerative colitis are unknown. METHODS: We conducted an open-label study in which 31 patients at different periods from surgery without signs and symptoms of pouchitis were randomized to 2 sachets of VSL#3 once daily or no treatment for 12 months. Pouchitis disease activity index (PDAI) was evaluated at baseline and after 3, 6, and 12 months. The percentage of CD4+ T lymphocytes expressing CD25 and the inactive form of transforming growth factor-beta [latency-associated peptide (LAP)] were evaluated at baseline and after 3 and 6 months in peripheral-blood mononuclear cells and mucosal biopsies. Variation in tissue interleukin-1beta and Foxp3 mRNA expression was also evaluated. RESULTS: During the study period, VSL#3-treated patients showed a significant reduction in PDAI score and a significant increase in the percentage of mucosal CD4+CD25(high) and CD4+ LAP-positive cells compared with baseline values. Tissue samples at different points showed a significant reduction in IL-1beta mRNA expression, and a significant increase in Foxp3 mRNA expression. CONCLUSIONS: We conclude that VSL#3 administration in patients with IPAA modulates the PDAI and expands the number of mucosal regulatory T cells.

[Anastomotic dehiscence in colorectal surgery. Analysis of 1290 patients]. / Le deiscenze anastomotiche in chirurgia colo-rettale. Analisi su 1290 pazienti.

The most frightening complication following colorectal surgery is the anastomotic leakage which is associated with an high mortality rate, and the analysis of risk factors for the anastomotic leak is of great interest. The aim of this retrospective study is to evaluate the risk factor for the anastomotic leakage in personal series of patients who underwent colorectal surgery. We have analyzed a consecutive series of 1290 patients who underwent colorectal open surgery from 1970 to 2004. The associations between anastomotic leak and several risk factors were studied by univariate analysis. The variables considered were the following: age; sex; type of disease; elective or emergency surgery; type of surgery; type, design and site (intra or extra peritoneal) of the anastomosis; stapled or manual anastomosis; distance from anal verge of the colorectal anastomosis; intraoperative complications; protective stoma. The rate of anastomotic leakage was 4.8% (62/1290 patients). Significant factors were: the type of surgery (higher risk after restorative proctocolectomy or rectal resection), the site extra peritoneal of the anastomosis, the type of the anastomosis (higher risk after coloanal or ileal-pouch anal or colorectal), the stapled anastomosis, the intraoperative complications. After colorectal anastomosis the risk of leakage has progressively higher for low, ultra-low and coloanal anastomosis. In these conditions a protective stoma seems to be suitable.

MR imaging in patients with Crohn disease: value of T2- versus T1-weighted gadolinium-enhanced MR sequences with use of an oral superparamagnetic contrast agent.

PURPOSE: To prospectively compare oral contrast-enhanced T2-weighted half-Fourier rapid acquisition with relaxation enhancement (RARE) magnetic resonance (MR) imaging with T1-weighted gadolinium-enhanced fast low-angle shot (FLASH) MR and standard examinations in the evaluation of Crohn disease. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Fifty-nine patients with Crohn disease underwent MR imaging after oral administration of a superparamagnetic contrast agent; RARE plain and fat-suppressed sequences and FLASH sequences were performed before and after intravenous injection of gadolinium chelate. References were endoscopic, small-bowel barium, computed tomographic, ultrasonographic, and clinical-biochemical scoring of disease activity. Two radiologists analyzed MR images for presence and extent of Crohn disease lesions, presence of strictures or other complications, and degree of local inflammation. MR findings were correlated with endoscopic, radiologic, and clinical data (kappa statistic and Spearman rank correlation test). RESULTS: T2-weighted MR was 95% accurate, 98% sensitive, and 78% specific for detection of ileal lesions. Agreement between T1- and T2-weighted images ranged from 0.77 for ileal lesions to 1.00 for colic lesions. T2-weighted MR enabled detection of 26 of 29 severe strictures, 17 of 24 enteroenteric fistulas, and all adhesions and abscesses; T1-weighted MR enabled detection of 20 of 29 severe strictures, 16 of 24 enteroenteric fistulas, and all adhesions and abscesses. Complications leading to surgery were found in 12 (20%) patients; these were assessed correctly with either T1- or T2-weighted images. T2-weighted signal intensities of the wall and mesentery correlated with biologic activity (P < .001, r of 0.774 and 0.712, respectively). Interobserver agreement was 0.642-1.00 for T2-weighted and 0.711-1.00 for T1-weighted images. CONCLUSION: T2-weighted MR can depict Crohn disease lesions and help assess mural and transmural inflammation with the same accuracy as gadolinium-enhanced T1-weighted MR. Combination of gadolinium-enhanced T1- and T2-weighted sequences is useful in the assessment of Crohn disease.

Rectal cancer surgery with sphincter preservation: functional results related to the level of anastomosis. Clinical and instrumental study.

BACKGROUND/AIMS: Unsatisfactory functional results have been reported not only after coloanal anastomosis, but also after anterior resection with colorectal anastomosis. The aim of this study is to establish functional outcome predictive factors related to surgical technique and especially the real impact of residual rectum length to identify patients who could benefit from colonic pouch reconstruction. METHODOLOGY: Sphincter preservation was achieved in 214 of 327 patients who underwent surgery for rectal cancer. Patients have been subdivided according to the level of anastomosis measured by a rigid proctoscope from the anal verge. In 93 patients functional results have been assessed by clinical control and anorectal manometry. RESULTS: Functional alterations such as leakage (13%), incontinence (5%), urgency (5%) and difficulty in evacuation (10%) appeared in patients who underwent anterior resection with anastomosis 4 to 6 cm from the anal verge. Nevertheless, comparing anterior resection with anastomosis 6 to 8 cm and that with anastomosis 4 to 6 cm rectal compliance was the only parameter whose difference is statistically significant. CONCLUSIONS: This result makes us to believe that patients who undergo anterior resection with no more than 2-3 cm of residual rectum could benefit from a colonic pouch reconstruction.

The role of extended total gastrectomy in advanced gastric cancer.

BACKGROUND/AIMS: Extended total gastrectomy represents, in our experience, 52 out of 443 (11.7%) surgical resections for gastric cancer (1976-1998, 269 total gastrectomies). METHODOLOGY: Enlarged resections were performed on left liver lobe (5 cases), transverse colon (8 cases), pancreas body-tail (35 cases), mesocolon (4 cases), diaphragm (6 cases), jejunum (1 case), and adrenal gland (1 case). RESULTS: Morbidity rate was 18 out of 52 cases (34.60%); 1 esophagus-jejunum anastomosis leakage, 6 cases of pneumonia, 1 pancreatic fistula, 1 p.o. pancreatitis, 3 subphrenic abscesses, 4 cardiocirculatory complications, successfully resolved with conservative therapy. There was one case of postoperative death (1.9% due to cardiac failure). There was a 5-year survival rate for 36.5% of the patients, with follow-ups from 6 months to 11 years. The authors, based on their data, international literature (Roder 1993, Cordiano 1996, Shchepotin 1998) and taking into account mortality and morbidity rates estimate a 5-year survival rate in 30-52% of the cases. CONCLUSIONS: In conclusion, we believe that major surgical procedures for gastric cancer are indicated for every case of suspected neoplastic infiltration of contiguous organs.

[Carcinoma of the pancreatic remnant developing after pancreaticoduodenectomy for adenocarcinoma of the head of pancreas]. / Carcinoma del moncone pancreatico dopo duodenocefalopancreasectomia per adenocarcinoma della testa.

In November 1996 a 44-year-old man with an adenocarcinoma of the pancreatic head (T2 N1 Mx- UICC 1998 Stage III) underwent a Traverso-Longmire pancreaticoduodenectomy. Early reoperation was required owing to postoperative acute pancreatitis and haemorrhage of the pancreatic remnant, after which he received chemo- and radiotherapy. Twenty-nine months later, an increase in the level of CA19.9 was observed with neither clinical nor radiological evidence of cancer recurrence. Forty months later, there was evidence of a new neoplasia of the pancreatic remnant. Since the recurrence involved only the pancreatic remnant with no evidence of metastases and the patient was in good condition and enough time had elapsed since surgical eradication of the primary cancer, we decided to perform an en bloc resection of the pancreatic body and tail and the spleen. Histologically, the tumour proved to be a pancreatic adenocarcinoma (T2). It is difficult to assess whether this cancer of the pancreatic remnant was a recurrence or a second primary cancer because of the long recurrence-free survival period, the absence of neoplastic invasion of the resection margins of the two surgical specimens and the absence of multicentricity both of the portion of the gland removed by the first operation and that removed by the second.

Billroth I versus Billroth II versus Roux-en-Y after subtotal gastrectomy. Prospective [correction of prespective] randomized study.

BACKGROUND/AIMS: The aim of this study was to evaluate functional results after Billroth I, Billroth II and Roux-en-Y reconstruction in subtotal gastrectomy. METHODOLOGY: Forty-five patients were randomized between 1990 and 1995 and stratified in 3 different groups: 15 BI, 15 BII and 15 Roux. They were investigated by esophagogastroduodenoscopy with multiple biopsies and upper gastrointestinal scintiscanning, to evaluate gastroesophageal reflux and dynamics of gastric emptying. They also answered a questionnaire: Gastrointestinal Quality of Life. Index. RESULTS: A reflux esophagitis was found in 5 BI, in 7 BII and in 2 Roux (p < 0.001). No gastric lesions were found in 6 BI, in 5 BII and in 12 Roux, (BI vs. Y, p < 0.05; BII vs. Y, p < 0.001). Chronic superficial gastritis was present in 9 BI, in 4 BII and in 3 Roux (BI vs. Y, p < 0.05). Dynamic scintiscan demonstrated the presence of gastroesophageal reflux in 5 BI and gastric emptying was fast (37' < T 1/2 < 86'), but incomplete (60' residual activity: 49-62%). Gastroesophageal reflux was evident in 7 BII with slow (28' < T 1/2 < 143') and incomplete (60' residual activity: 48-72%) gastric emptying. Gastroesophageal reflux was detected in 2 Roux and radioactive bolus progression in the Roux limb was fast (24' < T 1/2 < 53') and complete (60' residual activity: 42-52%) (BI vs. Y; BII vs. Y, p < 0.001). There was no statistical significance between Gastrointestinal Quality of Life Index score in the 3 groups. CONCLUSIONS: The Authors affirm that Roux-en-Y is the technique of choice in subtotal gastrectomy, if compared with BI and BII.