Should hot biopsy forceps be abandoned for polypectomy of diminutive colorectal polyps?

Standardized approach to polypectomy of diminutive colorectal polyps (DCPs) is lacking since cold biopsy forceps have been associated with high levels of recurrence, hot biopsy forceps are considered inadequate and risky and cold snaring is currently under investigation for its efficacy and safety. This has led to confusion and a gap in clinical practice. This article discusses the usefulness and contemporary practical applicability of hot biopsy forceps and provides well-intentioned criticism of the new European guidelines for the treatment of DCPs. Diminutive colorectal polyps are a source of frustration for the endoscopist since their small size is accompanied by a considerable risk of premalignant neoplasia and a small but non-negligible risk of advanced neoplasia and even cancer. Since the proportion of diminutive colorectal polyps is substantial and exceeds that of larger polyps, their effective removal poses a considerable workload and a therapeutic challenge. During the last decade, the introduction of cold snaring to routine endoscopy practice has attempted to overcome the use of prior techniques, such as hot biopsy forceps. It is important to recognize that with the exception of endoscopic methods that are obviously unsafe and inadequate to serve their purpose, all other interventional endoscopic methods are operator-dependent in the sense that specific expertise and training are obligatory for the success of any therapeutic intervention. Since relevant publications on hot biopsy forceps are still in favor of its careful use, as it has not yet demonstrated inferiority compared with newer techniques, it would be prudent for any medical practitioner to evaluate the available tools and judge any new proposed technique based on the evidence before it is adopted.

A prospective study of pre-illness diet in newly diagnosed patients with Crohn's disease.

BACKGROUND: Environmental factors, including diet, seem to participate in the etiology of inflammatory bowel disease. The kind of dietetic habits before the appearance of the illness in patients with Crohn's disease (CD) has not been studied extensively. AIM: To prospectively assess the kind of food consumption in patients with CD exactly at the time of diagnosis and to identify dietary constituents as risk factors for development of CD. PATIENTS - METHODS: Twenty eight patients with a newly established diagnosis of CD (2-4 weeks), (12 men and 16 women), 30 patients with previously (between 2 - 11 years) established diagnosis of CD (14 men and 16 women) and 38 age- and sex-matched healthy controls (16 men and 22 women) were included in the study. Dietary intake was assessed by means of special questionnaire. RESULTS: Comparisons between controls and newly diagnosed patients showed that increased consumption of milk and yogurt (P = 0.042), fruits (P = 0.0001), citrus (P = 0.0001), vegetables (P = 0.0001), carrots (P = 0.0001), legumes (P = 0.036), fish and selfish (P = 0.001), honey (P = 0.003), and nuts (P = 0.038), was associated with decreased risk for CD. On the other hand, significantly increased intake of fat (P = 0.041), olive oil (P = 0.038), margarine (P = 0.038), sugar (P = 0.02), alcohol drinks (P = 0.009), fried food (P = 0.0001), and pasta (P = 0.0001), was noticed on recently diagnosed patients in comparison with the healthy control group. On logistic regression analysis foods remaining statistically significant were: margarine, pasta, fried foods, fat, olives, sugar (increased risk), and yogurt, honey, fruits, nuts, fish, and citrus fruits (decreased risk). Newly diagnosed patients were significantly overweighed (64%) compared to healthy people (26%) and old patients (7%). CONCLUSION: Significant differences in many kinds of food between newly diagnosed patients with CD, patients with established CD and normal people certainly exist. Our results suggest that specific dietary patterns could be associated with higher or lower risks for CD in adults. However, whether these dietary factors are important for the development of CD or modulate the effect of other environmental factors is unknown.

Randomised clinical trial: otilonium bromide improves frequency of abdominal pain, severity of distention and time to relapse in patients with irritable bowel syndrome.

BACKGROUND: Otilonium bromide (OB) is a spasmolytic agent that blocks L-Type Calcium channels in human colonic smooth muscle. AIM: To study the efficacy of OB in symptom control in irritable bowel syndrome (IBS). METHODS: A total of 356 patients (46.16±19years, 71% female) with IBS participated in a double-blind, randomised, parallel placebo-controlled phase IV study. OB (40mg t.d.s.) or placebo was administered for 15weeks, and follow-up was extended 10 additional weeks. RESULTS: Otilonium bromide (n=179) and placebo (n=177) groups had comparable demographics, symptom severity and IBS subtype. Both OB and placebo reduced abdominal pain and IBS symptoms. The effect of OB was significantly greater than placebo in the reduction of weekly frequency of episodes of abdominal pain at the end of treatment period (primary endpoint, -0.90±0.88 vs. -0.65±0.91, P=0.03), reduction of abdominal bloating (-1.2±1.2 vs. -0.9±1.1, P=0.02) and global efficacy by patient assessment (1.3±1.1 vs. 1.0±1.1, P=0.047). Intensity of abdominal pain, proportion of patient responders, safety and quality of life scores were similarly affected by OB and placebo. During follow-up, the therapeutic effect of OB remained greater than placebo in terms of withdrawal rate due to symptom relapse (10% vs. 27%, P=0.009), global efficacy of treatment and relapse-free probability (P=0.038). CONCLUSIONS: This placebo-controlled double-blind study shows that otilonium bromide is safe, well tolerated and superior to placebo in reducing the frequency of abdominal pain, severity of abdominal bloating and protecting from symptom relapse in IBS. These results further confirm that patients with IBS can improve during and following treatment with otilonium bromide.

Similar response to adalimumab in patients with active Crohn's disease either naive to biologic agents or with prior loss of response or intolerance to infliximab.

UNLABELLED: The aim of this study was to investigate the efficacy of adalimumab, in patients with moderately active Crohn's disease (CD), either naive to biologic agents or with prior loss of response or intolerance to infliximab. MATERIAL AND METHOD: A total number of 30 patients with moderately active CD (14 men, 16 women, aged 38.5 +/- 14.4 yr) either naive to biologic agent treatment (19 pts (65%)) or with loss of response or intolerance to infliximab (11 pts (35%)), were enrolled to 4-wk trial with treatment with subcutaneous adalimumab 160 mg injection at week 0, 80 mg at week 2 and then 40 mg every other week. Outcome measures included the ability to tolerate adalimumab and clinical remission (defined as a CDAI score < or =150 points) and clinical response (defined as a decrease in the CDAI) > or =70 points). Eleven patients (37%) were smokers, 5(16%) ex-smokers and 14 (47%) non-smokers. Five patients (16%) had a positive family history for IBD. Duration of disease was 10.7 +/- 8.1 yr. Coexistence of extraintestinal manifestations was noticed in 12 (40%) patients. Vienna Classification of CD was A1=24 (80%), A2=6 (20%), L1=8 (26.7%), L2=6 (20%), L3=15 (50%), L4=1 (3.3%), B1=15 (50%), B2=5 (16.7%), B3=10 (33.3%). RESULTS: Remission was observed in 19 (63.3%) and clinical response in 9 (30%) patients. Two patients (6.7%) showed no response. No significant differences between patients with loss of response or intolerance to infliximab and the group of naive patients were noticed. Comparison between smokers and non smokers revealed significant difference in the response rate in favour of non-smokers (P < 0.002). A trend (P = 0.064) towards a significant difference in the response rate of the group of smokers according to the number of cigarettes smoked per day was observed. Patients with short duration of disease (<10 yr) had significantly better response compared to the group of patients with long (>10 yr) duration of disease. Similarly, patients with extraintestinal manifestations showed significantly better response (P = 0.044). None of the patients in both groups experienced acute or delayed hypersensitivity reactions during treatment with adalimumab. CONCLUSION: Adalimumab is well tolerated and appears to be a beneficial option for patients with CD who have not previously treated with biologic agents or have lost their response to, or cannot tolerate infliximab, with non-smokers, patients with short duration of CD, and patients with extraintestinal manifestations having a better clinical response.

Risk factors for colorectal polyps: findings from a Greek case-control study.

UNLABELLED: There is a body of evidence showing that several lifestyle and dietary factors are associated with colorectal polyps' formation; however, the magnitude of this association in diverse populations remains unclear. The aim of this study was to investigate this association in a Greek sample. MATERIAL AND METHOD: The study comprised of 52 subjects with histologically confirmed advanced colorectal polyps and 52 healthy controls. Data concerning lifestyle and dietary factors were collected using a validated questionnaire. Logistic regression analysis was used to estimate odds ratios and 95% confidence intervals after adjustment for potential confounders. RESULTS: Physical activity level (95% CI 0.032-0.953, P = 0.044) and consumption of yoghurt (95% CI 0.969-0.996, P = 0.024), cheese (95% CI 0.932-0.996, P = 0.030), fish (95% CI 0.782-0.964, P = 0.008), vegetables (95% CI 0.965-0.998, P = 0.029), and garlic (95% CI 0.005-0.671, P = 0.022) were inversely associated with colorectal polyps. Increasing age (95% CI 1.005-1.231, P = 0.039) and central obesity (95% CI 1.001-1.019, P = 0.025) were strongly associated with their presence. CONCLUSION: Our study indicates that a cluster of modifiable risk factors have significant impact on colorectal polyps' occurrence in Greek population.

Acute idiopathic pancreatitis preceding diagnosis of Crohn's disease. Description of three cases.

UNLABELLED: Acute idiopathic pancreatitis seems to represent a rare extraintestinal manifestation of Crohn's disease usually appearing after the establishment of diagnosis of the intestinal disorder. The aim of this study was to describe the clinicoepidemiological characteristics and clinical course of three patients with Crohn's disease who developed acute idiopathic pancreatitis years before the establishment of diagnosis intestinal disease. DESCRIPTION OF CASES: All patients were suffering from Crohn's disease. In all patients, an extensive work-up aiming to identify an etiological factor involved in the pathogenesis of acute pancreatitis was negative. The main clinical characteristics of the patients were the young age, the mild or moderate degree of severity of pancreatitis, and the concurrent involvement of small and large bowel from Crohn's disease in two of them. There was no preference for either male or female sex. The course of pancreatitis was favorable in all patients. During the follow-up period, ranging from 2 to 8 years, no exacerbation of pancreatitis was noticed. CONCLUSION: This case-series suggests that acute idiopathic pancreatitis could precede diagnosis of Crohn's disease. Clinicians must bear in mind the possibility of the existence of Crohn's disease when they are confronting a young patient with clinical and laboratory features of acute idiopathic pancreatitis.

Coexistence of medullary sponge kidney and ulcerative colitis in the same patient: long-term follow-up.

We describe a female patient with ulcerative colitis since the age of 17, who was accidentally diagnosed as having medullary sponge kidney 3 years after the establishment of diagnosis of inflammatory bowel disease. The diagnosis of renal disease was based on the typical appearance of both kidneys on abdominal ultrasound examination and on IV pyelography findings. All other well-known causes of medullary sponge kidney were excluded on the basis of the relevant laboratory investigation. So far, the patient experienced only one episode of urinary infection but no renal colic. Since the time of diagnosis of ulcerative colitis her renal function tests are perfectly normal. She is under maintenance treatment with mesalazine. The benign nature of the situation was explained to her. She was advised to drink at least one and a half litter of water daily, in order to reduce the risk of nephrolithiasis. The combination of the two disorders in our patient is probably the result of a chance. However, taking into account the potentially dangerous long-term results of medullary sponge kidney, we suggest that patients with ulcerative colitis must have a careful ultrasound examination of both kidneys at least at the time of diagnosis of the bowel disease, in order to exclude the possibility of medullary sponge kidney, as conservative measures could result in avoidance of potentially dangerous complications, such as renal stones and urinary infections.

Pregnancy and inflammatory bowel disease: a prospective case-control study.

OBJECTIVE: Taking into account the relative confusion in the literature concerning the influence of pregnancy on the underlying inflammatory bowel disease (IBD) and vice versa, as well as the influence of drugs on the foetus and the gestation itself, we performed this prospective study, in order to further elucidate this interesting topic. PATIENTS AND METHODS: Prospective follow-up study of 9 pregnant women with previously established IBD, 4 with ulcerative colitis (UC) and 5 with Crohn's disease (CD). Results were compared to those of 9 non-pregnant women with IBD with similar clinico-demographic characteristics (disease control group), and 18 healthy pregnancy women (healthy control group). RESULTS: (a) Patients with IBD and gestation vs. healthy control group: Significantly impaired body weight in newborns from IBD mothers compared to healthy women (2530 +/- 961 g vs. 3242 +/- 582 g, P = 0.035) was found. Significantly more cases of therapeutic or spontaneous abortion and premature delivery in pregnant women with IBD compared to healthy pregnant women [5/ 9(56.6%) vs 1/18 (5.6%), P = 0.008] were also noticed. Concerning drug consumption, it was noticed that azathioprine was taken regularly in one case of spontaneous abortion and in one case of premature delivery. No significant differences concerning other parameters such as smoking habit and death of foetus were observed. (b) Patients with IBD and gestation vs. patients with IBD without gestation: No significant differences in the history of various parameters of the disease (number of operations, presence of fistulas), previous gestations, and course of the disease during the period of gestation were found. (c) Course of the disease six months after delivery: No significant differences between patients with IBD and pregnancy and disease control group were noticed. CONCLUSION: It is concluded that gestation in women with IBD is accompanied by some unwanted events such as premature delivery, therapeutic or spontaneous abortion, and reduced newborn body weight. Clinicians must bear in mind the possibility of the appearance of some unwanted events in pregnant women with IBD during their gestation.

hMSH2 is the most commonly mutated MMR gene in a cohort of Greek HNPCC patients.

Germline mutations in genes encoding proteins involved in DNA mismatch repair are responsible for the autosomal dominantly inherited cancer predisposition syndrome hereditary nonpolyposis colorectal cancer (HNPCC). We describe here analysis of hMLH1 and hMSH2 in nine Greek families referred to our centre for HNPCC. A unique disease-causing mutation has been identified in seven out of nine (78%) families. The types of mutations identified are nonsense (five out of seven) (hMLH1: E557X, R226X; hMSH2: Q158X, R359X and R711X), a 2 bp deletion (hMSH2 1704_1705delAG) and a 2.2 kb Alu-mediated deletion encompassing exon 3 of the hMSH2 gene. The majority of mutations identified in this cohort are found in hMSH2 (77.7%). Furthermore, four of the mutations identified are novel. Finally, a number of novel benign variations were observed in both genes. This is the first report of HNPCC analysis in the Greek population, further underscoring the differences observed in the various geographic populations.

Endocrine function in abetalipoproteinemia: a study of a female patient of Greek origin.

AIM: To investigate the pituary, genitalia, adrenal, thyroid, parathyroid and pancreatic endocrine function of a female patient aged 37 with abetalipoproteinemia at the time of diagnosis and 5 years thereafter (after application of a modified diet). SUBJECT-METHODS: Serum concentrations of cortisol, A4, ACTH, aldosteron, renin, dehydroepiandrosterone sulfate (DHEA-5), progesterone, 17-OH progesterone, testosterone, SH13G, estradiol, luteinizing hormone, follicle stimulating hormone, T3, T4, TSH, FT3, FT4, parathormone, osteocalcin, prolactin, proinsuline, insulin, glucagon, somatomedin-C (Insulin-like Growth Factor-1, IGF-1), IG171-13P3, 25 (OH) Vitamin D3 and 1-25 (OH) 2 Vitamin D3, were measured by radioimmunoassay. Synactlien test, and 24-hour urine cortisol, were also estimated. Serum leptin estimation was carried-out using a sensitive enzymatic technique. Ionized part of serum calcium was measured by the use of a special machine (CORNING), while bone alkaline phosphatase was measured by radioimmunoassay. RESULTS: Serum progesterone and 17-OH-progesterone were reduced in both examinations. Estimation of serum progesterone performed on the 21th day of the menstrual cycle revealed again values below the lowest normal limit. Serum prolactin was increased both in rest and during movement. The levels of both, somatomedin-C (IGF-1) and leptin were below the lowest normal limit. Despite normal serum parathormone, serum-ionized calcium and 25-OH vitamin D were low, while serum bone alkaline phosphatase was increased. Serum proinsulin was increased, and serum insulin was low. Serum thyroid hormone, glucagon, parathormone, FSH, LH, ACTH, testosterone, estradiol and SH13G were normal. The hormonal profile of the patient estimated 5 years later did not differ substantially suggesting that the metabolic improvement due to the adoption of the modified diet had not any significant impact on it. CONCLUSION: Female patients with abetalipoproteinernia have reduced production of progesterone by the corpus luteum and slightly abnormal bone metabolism. The reduced production of progesterone is probably due to the low levels of serum LDL and cholesterol, while reduced serum levels of Leptin and IG17-1 are probably due to the impairment nutritional status. The adoption of a modified diet does not alter the hormonal profile significantly.

Novel mutations of the APC gene in familial adenomatous polyposis in Greek patients.

Familial adenomatous polyposis (FAP), a premalignant clinical entity inherited as an autosomal dominant trait, is characterized by the development thousands of adenomatous polyps of the colorectum during the 2nd and 3rd decade of life. Approximately 80% of patients with FAP harbor truncating germline mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. We tested 24 members of six Greek families. All patients had the FAP phenotype, and one patient had an extracolonic tumor (medulloblastoma). Our method for testing was the polymerase chain reaction (PCR) amplification from genomic DNA extracted from whole blood, followed by automated DNA sequencing. Two novel truncating mutations (2601delGA and R923X) and three already-known mutations (R876X, Q1045X, and D1822V) were found. Other polymorphisms were also found. We identified the inactivating APC mutation in 12 of 13 of our FAP patients. Our results suggest that PCR sequencing is a reliable method for screening the APC gene for germline mutations.

Favorable response to infliximab treatment in a patient with active Crohn disease and pyoderma gangrenosum.

Pyoderma gangrenosum is an extraintestinal manifestation of inflammatory bowel disease requiring meticulous medical and/or surgical treatment. We describe a 46-year-old patient who developed harsh pyoderma gangrenosum during a severe flare-up of the underlying Crohn disease of the terminal ileum. The patient responded favorably to treatment with infliximab-the chimeric antibody against tumor necrosis factor-alpha. The drug was administered intravenously at a dose 5 mg/kg/BW at baseline and weeks 2 and 6. Abdominal signs and symptoms as well as the skin lesions improved markedly before the second infusion. The patient is presently on infliximab maintenance regimen at a dose of 5 mg/kg/BW being administered as a 3 dose loading regimen at 0, 2 and 6 weeks with a treatment-free interval of 10 weeks until the next loading dose. The skin lesions remained in remission. Infliximab is a promising therapeutic modality for patients with Crohn disease and pyoderma gangrenosum.

Surgery for Crohn's disease in Greece: a follow-up study of 79 cases.

BACKGROUND/AIMS: The aim of this prospective study was to elucidate the clinical features, indications for surgery and long-term outcome of a series of 79 Greek patients operated on for Crohn's disease. METHODOLOGY: The clinical features and follow-up of 79 out of 155 patients with definite diagnosis of Crohn's disease (51%), who were operated on at least once during the course of their disease, are analyzed. Three main locations of the disease were identified (small bowel, large bowel and small and large bowel). The need for surgery, indications for surgery and outcome of patients were analyzed and compared separately for these three main locations. The mean follow-up period after the first operation was 8.8 +/- 6.5 years. RESULTS: The proportion of men to women was 1.55:1 (P = 0.068). The main indication for surgery was poor response to conservative treatment, followed by obstructive ileus, erroneous diagnosis of acute appendicitis and development of fistulae or abscesses. Statistically significant differences between the three main locations of the disease were found for obstructive ileus (P < 0.01), and bowel perforation (P < 0.0297). Enterectomy and end-to-end anastomosis was the most frequently performed operation. Minor surgical procedures were performed mainly for drainage of perianal abscess. Differences in the number of operations required (one, two and three or more) according to the three main locations of the disease were statistically significant (P < 0.044). Emergency operation was required in 17.3%. Most of the urgently operated patients had only small bowel involvement. Twenty-six percent of patients required a surgical procedure for perianal disease. One or more, major or minor, perioperative complications occurred in 13 out of 79 operated patients (16.4%). No perioperative deaths were noticed. Evolution to cancer was observed in 2% (3 patients). The outcome of patients after the operation was characterized by exacerbations and remissions. A mortality rate of 11.6% was noticed in the follow-up period. However, most deaths were unrelated to the underlying Crohn's disease. CONCLUSIONS: The clinicoepidemiological characteristics of patients with Crohn's disease of Greek origin operated-on for their disease do not differ significantly from those reported from other Western or neighboring Mediterranean countries. However, other parameters such as the relatively low incidence of overall surgical need, the low incidence of colorectal cancer and the low incidence of surgery for perianal disease, all underline the importance of various genetic and environmental factors on the evolution and behavior of the disease in different parts of the world.

Ulcerative colitis in the elderly: clinical patterns and outcome in 51 Greek patients.

PURPOSE: In this study, the clinical characteristics and course of all patients with ulcerative colitis in whom diagnosis of the disease was made at or after the age of 60 (older group), were analyzed and compared with those of patients with ulcerative colitis in whom diagnosis of the disease was made before the age of 60 (younger group). METHODS: The older group consisted of 51 patients (28 men and 23 women; aged 64+/-3.1 years) and the younger group consisted of 362 patients (192 men and 170 women; aged 38.4+/-14.9 years). The mean follow-up times in the two groups were 9.3 and 12.6 years, respectively. RESULTS: No significant differences between the two groups were found as far as the extent of the disease, the severity of the initial episode, and the outcome of the first episode of ulcerative colitis were concerned. However, significantly fewer elderly patients were operated on for their disease compared with younger patients (6.25% vs 22.3%; P = 0.0268). Although some differences in the course of the disease between elderly and younger patients were observed, such as the number of exacerbations and recurrences and the number of patients who developed colorectal cancer, these differences did not reach statistical significance. CONCLUSION: It is concluded that ulcerative colitis in elderly Greek patients runs a rather similar course to that in younger patients. However, some unique characteristics observed in the elderly patients (lower rate of colectomy, absence of patients with colorectal cancer, and increased death rate) could be attributed either to truly different disease behavior in the elderly people or to factors directly related to their advanced age.

Crohn's disease in the elderly: clinical features and long-term outcome of 19 Greek patients.

AIM: To study the clinical course, prognosis, treatment and follow-up of 19 patients with Crohn's disease aged 60 years or over at the time of onset of symptoms. PATIENTS AND METHODS: A series of 12 males and 7 females aged 65 +/- 4. 9 and 66. 6 +/- 6 years at the onset of symptoms and the time of diagnosis, respectively (elderly group), were studied. Another group of patients(83 males, 53 females aged 29.8 +/- 12.4 and 32.2 +/- 12.7 at the onset of symptoms and of diagnosis, respectively) served as a control group (young group). Both groups were followed-up for a mean period of 7.2 and 9.8 years, respectively. RESULTS: The most common site of involvement in the elderly group was the distal ileum (47.4%), followed by large bowel (36.6%) and concurrent large and small bowel involvement (16%). Acute presentation was significantly more common in the older group. Fever and loss of weight were significantly less common in the older group (p<0.05). A higher rate of complications especially acute abdomen, was observed in the elderly group. There were no significant differences in the indication for surgery and type of surgical procedure applied between the two groups. However significantly fewer patients in the elderly group were operated on because of perianal abscess compared to the young group (p<0.05). Follow-up data revealed that elderly patients with Crohn's disease who had been operated upon showed no significant differences in the course of their disease compared to operated young patients. CONCLUSION: Crohn's disease in elderly persons of Greek origin follows much the same pattern as in other developed countries of the world.