Chromogranin A as a biomarker of disease activity and biologic therapy in inflammatory bowel disease: a prospective observational study.

OBJECTIVE: To access the correlation of Chromogranin A (CgA) with inflammatory bowel disease (IBD) activity and responsiveness to medical therapy. MATERIAL AND METHODS: A prospective observational study was conducted in 56 patients with moderate ulcerative colitis (UC) or Crohn's disease (CD) (UC, n = 29, CD, n = 27), 17 patients with irritable bowel syndrome and predominant diarrhea (IBS-D) and 40 healthy volunteers. IBD patients were treated by biologics (infliximab or adalimumab) or conventional agents (aminosalicylates, thiopurines or methotrexate and steroids) and were classified according to their treatment in two groups. Serum CgA was measured at baseline and 4-week posttreatment period. RESULTS: Serum CgA was significantly higher in IBD patients than in those with IBS-D or healthy volunteers (p < 0.01). Furthermore, serum CgA was markedly increased in CD patients than in UC patients (p < 0.01). CgA value was significantly reduced in 'biologic' group (24 IBD patients, UC, n = 15, CD, n = 9) at 4-week posttreatment period (p < 0.01), while 18/24 (72%) patients were already in remission during that time. In contrast, CgA value was significantly increased in the 'conventional' treatment group (32 IBD patients, UC, n = 14, CD, n = 18) between the two visits (p < 0.01), although 22/32 (69%) patients were in remission during the 4-week posttreatment period. CONCLUSION: CgA appears to be a reliable marker of disease activity in IBD patients and especially in those who received biologic therapy. IBS-D patients presented normal CgA values.

Endoscopic resection of large pedunculated colonic polyps and risk of postpolypectomy bleeding with adrenaline injection versus endoloop and hemoclip: a prospective, randomized study.

BACKGROUND: Postpolypectomy bleeding is a major complication, especially in large pedunculated colonic polyps. Several endoscopic techniques have been evolved for prevention of bleeding episodes. The aim of this study is to evaluate postpolypectomy bleeding rates in large (>2 cm) pedunculated colonic polyps using either adrenaline injection alone or loop and clip application as prophylactic methods. MATERIALS AND METHODS: Patients with one pedunculated colonic polyps (>2 cm) were included in a double-blind study and studied prospectively. Exclusion criteria were coexistence of other large polyps, antiplatelet, nonsteroidal anti-inflammatory drugs or aspirin. In group A (n = 32), adrenaline (1:10,000) was injected in the base of the stalk followed by conventional polypectomy using mixed coagulation and cutting current. In group B (n = 32), a detachable snare was placed at the base of the stalk followed by conventional polypectomy and clip application in the residual stalk above the snare. We evaluate the efficacy of combined endoscopic methods in early and late postpolypectomy bleeding rate in large pedunculated colonic polyps, severity of bleeding, days of hospitalization, and required transfusions. RESULTS: Overall, bleeding complications occurred in 5/64 patients (7.81%). In group A (adrenaline injection alone), four patients (12.5%) had a bleeding episode: two (6.25%) occurred during the first 24 h and two (6.25%) between days 7 and 14 from the procedure. In group B only one patient (3.12%) had a late bleeding episode (p = 0.02). Severity of late bleeding in group B patients (one moderate bleeding) versus group A patients (one moderate and one severe bleeding) and need for transfusions (1 versus 5 blood units) were lower (p = 0.02). Hospitalization days did not differ between the two groups, but colonoscopy time was significantly higher in group B versus group A (p = 0.04). CONCLUSION: Combined endoscopic techniques seem to be more effective in preventing postpolypectomy bleeding in large pedunculated colonic polyps.

Hypofractionated accelerated radiotherapy, cytoprotection and capecitabine in the treatment of rectal cancer: a feasibility study.

BACKGROUND: This is a report on the feasibility and efficacy of hypofractionated accelerated radiotherapy combined with amifostine cytoprotection (hypoARC) and capecitabine in the treatment of rectal adenocarcinoma. PATIENTS AND METHODS: Twenty-seven patients (pts) received pre- (14 pts) or postoperative (13 pts) conformal radiotherapy with 10 consecutive fractions of 3.4 Gy in 12 days, supported with subcutaneously administered high-dose amifostine (up to 1000 mg) and capecitabine (daily dose of 600 mg/m2 twice a day, 5 days per week for 4 weeks). Ten additional patients with inoperable tumors received a higher dose (15 fractions of 3.4 Gy) as a radical intervention and 5 received a lower dose for palliation. RESULTS: Chemotherapy-related toxicity was minimal and radiation grade 2 diarrhoea and proctitis was noted in 3/42 and 4/42 cases, respectively. No peri- or postoperative complications were noted in patients receiving pre-operative radiochemotherapy. Significant tumor regression was confirmed in post- RT CT-imaging and major histological responses were noted in 85% of cases treated before surgery. Late toxicity (median follow-up 26 months) was negligible. The 2-year local relapse-free survival was 85-90% in patients treated with pre- or postoperative radiotherapy and 35% in patients with inoperable tumors. CONCLUSION: Capecitabine-based hypoARC is feasible with only minimal early and late toxicity and encouraging efficacy.

Acute paraplegia after the initiation of anti-tumour necrosis factor-alpha therapy for Crohn's disease.

Therapies aimed at inhibiting tumour necrosis factor are currently successfully administered to an increasing number of patients with autoimmune diseases. Infliximab has been approved to induce and maintain remission in Crohn's disease and fistulizing Crohn's disease. We report a case of acute-onset flaccid paraplegia after the initiation of anti-tumour necrosis factor therapy (infliximab) for Crohn's disease. Neuroimaging findings revealed an extensive longitudinal myelopathy. Two months later, no abnormal signal intensity was observed in the spinal cord and after 4 months, the patient presented improvement of motor function. A possible correlation between anti-tumour necrosis factor therapy and acute myelitis is discussed. This case highlights that patients developing new neurological symptoms while on anti-tumour necrosis factor medication should be monitored closely.

Gastroesophageal reflux disease and Helicobacter pylori: lack of influence of infection on oesophageal manometric, 3-hour postprandial pHmetric and endoscopic findings.

AIM: To investigate the relationship between Helicobacter pylori and gastro-oesophageal reflux disease according to manometric and pHmetric findings. METHOD: Fifty-nine consecutive patients with reflux symptoms and endoscopic evidence of mild oesophagitis, were recruited. Manometry and ambulatory pHmetry were performed in all patients, as well as the 3-hour postprandial pHmetry, as a more flexible and well tolerable test. RESULTS: There were no significant differences between Helicobacter pylori positive and negative patients regarding age, sex ratio and endoscopic severity of oesophagitis. There was no difference in prevalence of abnormal oesophageal peristalsis between the two groups (Fisher's exact test, p=NS). Differences were also not found regarding lower oesophageal sphincter pressure between the two groups (mean PLOS 12.86+/-4.39 mmHg and 13.1+/-4.61 mmHg respectively; p=0.840). Finally, the mean values of DeMeester score were 60.38+/-48.04 and 67.64+/-51.04 respectively (p=0.576). CONCLUSION: Helicobacter pylori infection does not influence oesophageal peristalsis, the lower oesophageal sphincter pressure and the acidity of refluxates into the oesophageal lumen, in patients with established gastro-oesophageal reflux disease (esophagitis grade A and B).

Infliximab for treatment of pyoderma gangrenosum associated with clinically inactive Crohn's disease. A case report.

We report the case of a 57-year old female patient with refractory to treatment pyoderma gangrenosum associated with clinically inactive Crohn's disease. Pyoderma gangrenosum was successfully treated with Infliximab, a chimeric monoclonal antibody that inhibits tumour necrosis factor alpha (TNF-alpha). Our case report suggests that Infliximab, a therapeutic agent for refractory and fistulizing Crohn's disease, may also be safe and effective in the treatment of Crohn's disease associated pyoderma gangrenosum, even though the inflammatory bowel disease is clinically inactive and repeated infusions may be required for successful treatment.

Patients with established gastro-esophageal reflux disease might benefit from Helicobacter pylori eradication.

BACKGROUND: The aim of this study was to investigate the effect of Helicobacter pylori (H. pylori) eradication in selected H. pylori-positive patients with a primary diagnosis of gastro-esophageal reflux disease (GERD) by using the 3-h postprandial esophageal pH monitoring. METHODS: We recruited patients with erosive esophagitis at endoscopy and H. pylori infection at histology, successfully cured following eradication therapy; the selected H. pylori-positive patients had weekly reflux symptoms for at least six months and endoscopically established Grade A or B esophagitis. Twenty-nine eligible patients were initially subjected to esophageal manometry and ambulatory 3-h postprandial esophageal pH monitoring. All patients received H. pylori triple eradication therapy accompanied by successful H. pylori eradication. After successful eradication of H. pylori (confirmed by 13C urea breath test), a second manometry and 3-h postprandial esophageal pH monitoring were introduced to assess the results of eradication therapy, after a 3-month post-treatment period. RESULTS: All 29 selected H. pylori-positive patients became negative due to successful H. pylori eradication, evaluated by 13C urea breath test after a 4-week post-treatment period. Post-eradication, 62.1% patients showed similar manometric pattern at baseline; 17.2% showed improvement; 17.2% normalization; and 3.4% deterioration of the manometric patterns. The DeMeester symptom scoring in the 3-h postprandial ambulatory esophageal pH monitoring was improved after eradication of H. pylori (median 47.47 vs. 22.00, Wilcoxon's singed rank; P=0.016). On comparing the pH monitoring studies for each patient at baseline and post-eradication period, 82.8% patients showed improvement and 17.2% deterioration of the DeMeester score. CONCLUSION: By using 3-h postprandial esophageal pH monitoring, this study showed, for the first time, that H. pylori eradication may positively influence GERD symptoms. Large-scale controlled relative studies are warranted to confirm these findings.

Does prophylactic administration of somatostatin decrease the rates of complications after pancreatic resection?: A clinical and electron microscopy study.

OBJECTIVES: The postoperative morbidity after pancreatectomy remains high. The role of somatostatin and its analogs in reducing complications after pancreatic resection is controversial. The aim of the study was to evaluate the ability of somatostatin to influence pancreatic cell's function with consequence the decrease of postoperative complications. METHODS: Between January 2006 and December 2009, 67 patients for which pancreatectomy was indicated were randomized into 2 groups. At surgery, biopsies of the pancreas were taken to be studied by electron microscopy and analyzed for ultrastructural morphometry. RESULTS: The total mortality was 4.4% (n = 3/67; 2 patients from the control group and 1 patient from the treatment group). The overall morbidity was 35.8% (n = 24/67). Eighteen patients in the control group (n = 18/32; 56.25%) and 6 patients in the treatment group (n = 6/35; 17.14%) developed postoperative complications (2-tailed Fisher exact test; P = 0.001). The most common complication was the presence of fistula (n = 6/67; 8.95%). CONCLUSIONS: Perioperative administration of intravenous somatostatin at rates applied in this study was able to inhibit the exocrine pancreatic function. This finding supports the prophylactic effect of somatostatin on the early postoperative complications of pancreatic surgery shown in this study.

Development of primary malignant melanoma during treatment with a TNF-α antagonist for severe Crohn's disease: a case report and review of the hypothetical association between TNF-α blockers and cancer.

It is recognized that immunosuppression may lead to reduced immune surveillance and tumor formation. Because of the immunosuppressive properties of tumor necrosis factor (TNF)-alpha (TNF-α) antagonists, it is plausible that these biologics may increase the risk of the occurrence of malignancies or the reactivation of latent malignancies. TNF-α antagonists have gained momentum in the field of dermatology for treating rheumatoid arthritis and psoriasis, and they have revolutionized the treatment of other inflammatory autoimmune diseases such as refractory Crohn's disease. However, there is accumulating evidence that TNF-α inhibitors slightly increase the risk of cancer, including malignant melanoma (MM). The authors herein report the case of a 54-year-old female patient who developed a primary MM during treatment with adalimumab for severe Crohn's disease resistant to successive medical therapies. The patient had been receiving this TNF-α blocker therapy for 3 years before the occurrence of MM. After wide surgical excision of the lesion and staging (based on Breslow thickness and Clark level), evaluation with a whole-body computed tomography scan was negative for metastatic disease. The long duration of the adalimumab therapy and the patient's lack of a predisposition to skin cancer suggest an association between anti-TNF-α drugs and melanocytic proliferation. The authors also review the literature on the potential association between anti-TNF regimens and the occurrence of malignancies such as melanocytic proliferations. There is a substantial hypothetical link between anti-TNF-α regimens such as adalimumab and the potential for cancers such as melanoma. However, the risk of malignancy with biological therapy remains to be established, and most of the relevant studies have lacked the statistical power and randomization required for large clinical trials. Further long-term controlled clinical trials and registries are required to investigate this potentially serious association.

Inflammatory bowel disease: Greek patients' perspective on quality of life, information on the disease, work productivity and family support.

BACKGROUND: The aim of this study was to identify inflammatory bowel disease (IBD) patients' perspectives regarding everyday life issues. METHODS: From October 2010 till April 2011, 1,181 IBD patients completed an anonymous questionnaire through the internet (827 cases) or at the outpatient clinic of the participating centers (354 cases), aiming to identify: a) the impact of disease on social life, emotional status and work productivity; b) the source of disease information; and c) the level of support from family members and friends. RESULTS: Fifty-five percent of the patients reported that IBD interferes with their social life, while 65% felt stressed, 60% depressed and 19% tired because of it. Disease information (physician/ internet) was reported only by 31%, while 26% admitted not discussing their therapy with their gastroenterologist. Forty percent felt that the health service they receive is not satisfactory, with 76% desiring more gastroenterologists, 67% more outpatient clinics, 49% more dieticians and 42% more psychologists specialized in IBD. IBD interfered with working capacity in 40% of the participants, while 57% needed time off of work (ranging from 1-20 days per year). One of three patients (32%) has not informed his work environment about the disease; however, 88% had the support of their family and friends for coping with it. CONCLUSIONS: Greek IBD patients claim that health-related social life, emotional status and work productivity are severely affected by their disease, whereas they complain about lack of information regarding the therapy. These unmet demands call for immediate action by healthcare providers and society.

Primary umbilical endometrioma: a rare case of spontaneous abdominal wall endometriosis.

Umbilical endometrioma is a rare condition, with an estimated incidence of 0.5%-1% in all patients with endometrial ectopia. Spontaneous abdominal wall endometriosis is an even rarer and more unusual condition with unclear pathogenetic mechanisms. A 44-year-old parous woman presented with an umbilical skin lesion, and no history of bleeding from the umbilical mass or swelling in the umbilical area. The initial clinical diagnosis was granuloma, and excision was planned. Pathology examination revealed endometrial glands with mucinous-type metaplasia surrounded by a disintegrating mantle of endometrial stroma. Clinical examination and magnetic resonance imaging did not reveal pelvic endometriosis lesions, and given that the umbilical endometrioma was totally excised, no further treatment with hormonal therapy was proposed for the patient. Three years after excision, she was free of disease and no recurrence has been observed. Complete excision and histology is highly recommended for obtaining a definitive diagnosis and optimal treatment in spontaneous abdominal wall endometriosis.

Benign post-radiation rectal stricture treated with endoscopic balloon dilation and intralesional triamcinolone injection.

Post-radiation stricture is a rare complication after pelvis irradiation, but must be in the mind of the clinician evaluating a lower gastrointestinal obstruction. Endoscopy has gained an important role in chronic radiation proctitis with several therapeutic options for management of intestinal strictures. The treatment of rectal strictures has been limited to surgery with high morbidity and mortality. Therefore, a less invasive therapeutic approach for benign rectal strictures, endoscopic balloon dilation with or without intralesional steroid injection, has become a common treatment modality. We present a case of benign post-radiation rectal stricture treated successfully with balloon dilation and adjuvant intralesional triamcinolone injection. A 70-year-old woman presented to the emergency room complaining for 2 weeks of diarrhea and meteorism, 11 years after radiation of the pelvis due to adenocarcinoma of the uterus. Colonoscopy revealed a stricture at the rectum and multiple endoscopic biopsies were obtained from the stricture. The stricture was treated with endoscopic balloon dilation and intralesional triamcinolone injection. The procedure appears to have a high success rate and a very low complication rate. Histologic examination of the biopsies revealed non-specific inflammatory changes of the rectal mucosa and no specific changes of the mucosa due to radiation. All biopsies were negative for malignancy. The patient is stricture-free 12 months post-treatment.

Non-Hodgkin lymphoma and GIST: molecular pathways and clinical expressions.

We report the case of a 64-year-old woman with a gastrointestinal stromal tumor and a diffuse large cell lymphoma. For this case, we conducted a literature review in an attempt to correlate these two neoplasms on a molecular basis. Diffuse large cell lymphoma is a subtype of non-Hodgkin lymphomas. The etiologic factor of these lymphomas is considered to be the mutations or allelic losses of the TP53 tumor suppressor gene and the overexpression of the bcl-2 oncogene. Gastrointestinal stromal tumors are mesenchymal tumors, which are typically defined by the expression of c-KIT (CD117) and CD34 genes in the tumor cells. Although there are references to dispersants in the literature about patients with both non-Hodgkin lymphoma and gastrointestinal stromal tumors, there is no common molecular pathway between these two diseases. In conclusion, there is no indication that these two neoplasms are relevant on a molecular basis.

Tuberculosis in the peritoneum: not too rare after all.

Peritoneal tuberculosis is rare with increased incidence rates in recent years. The absence of characteristic clinical features of the disease often makes its diagnosis difficult and elusive. We present the case of 61-year-old female with peritoneal tuberculosis. The patient suffered from abdominal pain for a period of 5 months prior to admission. The diagnosis was established on the basis of findings from an abdominal computed tomography scan, a chest radiograph and histopathological analysis of the laparoscopic resection of the two masses. The patient was discharged from hospital receiving a fourfold antituberculous treatment with isoniazid, rifampicin, pyrazinamide and ethambutol. A high index of suspicion and a combination of radiologic, endoscopic, microbiologic and histopathological examination achieves diagnostic accuracy and prevents clinical mismanagement.