Musculoskeletal syndrome treated with global postural re-education in double-redo lung transplantation: a case report with an 8-month follow-up.

Postoperative pain and persisting fatigue represent critical concerns for patients receiving lung transplantation. The purpose of this study was to illustrate the trajectory of symptoms in a patient who presented with a posttransplant musculoskeletal syndrome after double redo-lung transplantation and attended therapeutic sessions of global postural re-education during the symptomatic phase. A 32-year-old woman with interstitial lung disease underwent double lung transplantation. At 23 months, functional parameters deteriorated, and the patient was placed on the active list for a second double-lung transplantation. Twenty months after re-transplantation, the patient reported continuous thoracic-lumbar musculoskeletal pain exacerbated by moving or performing the standard motor activities. Lower body flexibility improved during the observation period changed from -10 cm to 0 cm at the Chair Sitand- Reach Test. Leg strength improved as well, and the patient was able to perform more repetitions at the Squat Test, improving from 14 to 39. Pain intensity changed from 7 to 4 on a numerical rating scale. We observed that outcomes strictly related to treatment, with lower body flexibility, pain intensity, and physical function improving over time. As a result global postural re-education proved to be effective in this patient.

Pattern of epithelial cell proliferation in colorectal mucosa of patients with large bowel adenoma or cancer: an ECP case-control study. European cancer prevention.

Proliferative abnormalities of the normal colorectal mucosa have been proposed as a possible marker of enhanced susceptibility to colorectal cancer. A case-control study was conducted to compare the cell kinetics of normal colon mucosa through the different steps of the adenoma-carcinoma sequence. The number and position of labelled epithelial nuclei after in vitro incubation of tritiated thymidine were compared in patients with large bowel cancer (n = 39), large adenoma >1 cm (n = 47), small adenoma (n = 30) and in controls (n = 135). The distribution of tertiles between cases and controls was analysed using odds ratio (OR), comparing the second tertile (OR2) and the third tertile (OR3) to the first one. There was no significant difference in the overall cell proliferation rate when comparing cancer, large adenoma and small adenoma groups to the control group. The ratio number of labelled cells in the upper 40% of the crypt/total number of labelled cells (4h index) was found to be significantly higher only when the cancer group was compared to the control group: OR2 = 5.87 (1.33-25.90), OR3 = 9.48 (2.07-43.38), P for trend = 0.002. The upward shift of the proliferative compartment in the normal mucosa of patients with large bowel cancer suggests that this abnormality is related to cancer risk.

European trials on dietary supplementation for cancer prevention.

European institutions aimed at cancer research and control are spending sizable resources to develop preclinical and clinical chemoprevention trials. Pilot studies showed positive effect on colorectal cell proliferation from supplementation with calcium; vitamins A, C, and E; omega-3 fatty acids; and folic acid. A significant reduction in adenoma recurrence after polypectomy was found in patients randomly assigned to take vitamin A, C, and E supplementation or, to a lesser extent, lactulose. Although first reports showed a disquieting higher incidence of lung cancer in male smokers who took beta-carotene supplementation, the European Organization of Research and Treatment of Cancer (EORTC) planned a chemoprevention study on the prevention of second primary tumors in patients with curatively treated head and neck or lung cancer (EUROSCAN). Retinol palmitate or N-acetylcysteine or both are given for two years. The European Cancer Prevention Organization (ECP) is carrying out a clinical trial in patients with previous adenomas of the large bowel, to test the efficacy of calcium or fiber supplementation on adenoma recurrence. ECP in collaboration with EURONUT has also started a multinational intervention study of the effect of H. pylori eradication and/or dietary supplementation with vitamin C on intestinal metaplasia.

Cell proliferation of the duodenal mucosa in patients affected by familial adenomatous polyposis.

BACKGROUND & AIMS: Patients affected by familial adenomatous polyposis (FAP) are at increased risk of developing duodenal adenomas. In this study, cell proliferation of duodenal mucosa was analyzed to detect kinetic abnormalities related to cancer risk. METHODS: Duodenal biopsy specimens were collected in three groups of patients: group A, 9 hospital controls; group B, 14 patients with FAP without duodenal adenomas; and group C, 6 patients with FAP and duodenal adenomas. Proliferative cell nuclear antigen was assessed through immunohistochemistry. The main labeling parameters were (1) overall labeling index (LI) and (2) LI in the upper 40% of the crypts. RESULTS: Overall LI in groups B and C was higher than in group A (both P < 0.01). LI in group C was also significantly higher than in group B (P < 0.01). Similarly, the upper 40% LI was higher in groups B and C than in group A (both P < 0.01). This value was higher in group C than in group B (P < 0.05). CONCLUSIONS: These data suggest the presence of cell kinetics abnormalities in FAP and the existence of two subgroups of patients with FAP at different risks of duodenal neoplasia. These abnormalities could be used as an intermediate biomarker for chemoprevention studies of duodenal cancer in FAP.

Folic acid supplementation and cell kinetics of rectal mucosa in patients with ulcerative colitis.

It has been suggested that colon cancer risk in ulcerative colitis (UC) is correlated to a reduced bioavailability of folate. We studied the effects of folate supplementation on the pattern of rectal cell proliferation in patients affected by long-standing UC. In the rectal mucosa of these patients, an expansion of proliferating cells to the crypt surface is found frequently. This abnormality is considered an intermediate biomarker in chemoprevention trials. Twenty-four patients (13 males; age, 26-70 years; UC duration, 7-34 years) with UC in remission for 1 month at least were assigned randomly to one of the following treatments: (a) folinic acid (15 mg/day) or (b) placebo. Cell proliferation was analyzed through immunohistochemistry on sections of rectal biopsies incubated for 1 hour in a culture medium containing bromodeoxyuridine. Fragments were taken at admission to the study and after 3 months of treatment. As compared to the baseline values, after 3 months of therapy in patients treated with folinic acid, a significant reduction of the frequency of occurrence of labeled cells in the upper 40% of the crypts (phi h value) was observed (0.1836 +/- 0.0278 versus 0.1023 +/- 0.0255; P < 0.01). On the contrary, no significant proliferative changes were observed in the placebo group. These results suggest that folate supplementation contributes to regulating rectal cell proliferation in patients with long-standing UC. These findings may be significant for chemoprevention of colon cancer in these patients.

Rectal cell proliferation and colon cancer risk in patients with hypergastrinaemia.

BACKGROUND: The influence of gastrin on the colonic mucosa is still uncertain. Some authors have suggested a stimulating effect on the growth of normal and malignant colonic epithelium, while others have shown no association between gastrin and neoplastic development. AIMS: To evaluate the effect of gastrin on colorectal cell proliferation, patients with chronic endogenous hypergastrinaemia underwent proctoscopy. Biopsy specimens were taken in order to study rectal cell kinetics. PATIENTS AND CONTROLS: Ten patients with chronic autoimmune gastritis (CAG), six patients with Zollinger-Ellison syndrome (ZES), and 16 hospital controls took part in this study. Patients with CAG and ZES had basal serum gastrin concentrations significantly higher than controls (p < 0.001). METHODS: Immunohistochemistry was performed on 3 microns sections of rectal biopsy specimens incubated with 5'-bromodeoxyuridine. RESULTS: The percentage of proliferating cells in the entire crypts (overall labelling index) was similar in all the groups. However, the labelling frequency in the upper two fifths of the glands (phi h value) was significantly higher in patients with CAG or ZES compared with controls (p < 0.01 in both patient groups versus controls). CONCLUSIONS: Endogenous hypergastrinaemia is associated with rectal cell proliferation defects, similar to those observed in conditions at high risk for colon cancer. The effect of the increased serum concentrations of gastrin on the colorectal mucosa after treatment with drugs inhibiting gastric acid secretion should be investigated.

Tumor markers and lung cancer: guidelines in a cost-limited medical organization.

The aim of our study was to evaluate the cost of the tumor marker assays most widely used in pneumological practice and the effectiveness of the percentage of DRG-based reimbursements absorbed by these assays. For this purpose we assessed the cost of lung tumor marker assays in Emilia Romagna compared to the DRG-based reimbursement of inpatients affected by lung diseases in whom the use of tumor markers is indicated. As an example, we evaluated the cost/effectiveness of the CEA assay in the differential diagnosis of 68 pleural effusions from 46 patients (20 benign diseases, 26 malignant). Because the CEA assay was not a substitute for cytology when this was not diagnostic, 41.3% of the resources were not efficiently spent. If the marker assay had been performed only in cases with negative cytology, we could have spared 14 of 46 tests. Moreover, since the expense lies predominantly in the cost of reagents (81.23%), we suggest as a routine procedure to collect and store samples for tumor marker assay in all cases; the test should be performed in a selected population of patients with negative cytology and "suspect" clinical outcome.

Colorectal cancer in patients with ulcerative colitis. A prospective cohort study in Italy.

BACKGROUND: The aim of this study was to assess the development of dysplasia or cancer in patients with ulcerative colitis and to determine the effectiveness of colonoscopy and biopsy follow-up in colon cancer surveillance. METHODS: From 1980 to 1986, 65 patients who had ulcerative colitis for 7 years or more participated in a surveillance program of colonoscopy and biopsy. This cohort was followed until December 1992. Forty-nine patients (75.4%) had extensive colitis and 16 (24.6%) left-sided colitis. The mean disease duration was 17.2 years. Three hundred four colonoscopies were performed. During each endoscopy, random biopsies were performed. RESULTS: Seven patients had definite dysplasia of the colorectal mucosa. Four of them had high grade lesions and underwent surgery. In all of these patients, colon cancer (3 Dukes' Stage A, 1 Dukes' Stage B) was found. No cancer was found in the other patients. Pedunculated adenomas were excised from 6 other patients during colonoscopy. When dysplasia was diagnosed, these patients were older than those who were dysplasia free, whereas the age at onset of colitis was significantly higher in the former (P < 0.01). Fifteen patients discontinued follow-up. Two of them developed colon cancer diagnosed at an advanced stage. CONCLUSIONS: Dysplasia, especially of high grade, is a marker of colon cancer risk in patients with longstanding ulcerative colitis. Intensive colonoscopy and biopsy surveillance can lead to the diagnosis of colon cancer at a potentially curable stage. In this series, older age appeared to be an additional risk factor. A careful selection of patients with ulcerative colitis seems mandatory to minimize the cost and optimize the benefit of colon cancer surveillance programs.

Morphologic and cytoproliferative patterns of duodenal mucosa in two patients after long-term total parenteral nutrition: changes with oral refeeding and relation to intestinal resection.

The morphologic and cytoproliferative patterns of the duodenal mucosa of two adult patients, one of whom had a short bowel, were evaluated after more than 2 months of postoperative total parenteral nutrition and 2 and 12 months after the resumption of oral alimentation. Morphometric analysis was performed on routinely processed duodenal biopsies. Cell proliferation was evaluated by means of in vitro bromodeoxyuridine uptake. The results were compared with those obtained in five healthy controls. After parenteral nutrition, patients showed significantly lower villus height and crypt depth than those of controls and a normal bromodeoxyuridine labeling index. After 2 months of refeeding, villus and crypt returned to normal, and the labeling index was increased. After 12 months of oral refeeding, labeling index, villus height, and crypt depth were similar to those of controls. The patient with the short bowel showed a number of cells per unit length of villus and crypt significantly greater than those of the controls and of the patient who underwent shorter intestinal resection. In human duodenal mucosa, (1) hypoplasia develops after long-term total parenteral nutrition; (2) mucosal recovery occurs through an increased cell proliferation after oral refeeding; and (3) extensive small bowel resection determines the development of relative hyperplasia.

Flow cytometry and in vitro tritiated thymidine labeling in normal rectal mucosa of patients at high risk of colorectal cancer.

OBJECTIVES: To compare two different methods to evaluate rectal epithelial cell proliferation as a biomarker of risk of developing colon cancer. METHODS: Samples of normal rectal mucosa from 26 patients at increased risk for colorectal cancer (22 patients with adenoma, three with adenocarcinoma of the large bowel, and one with longstanding ulcerative colitis) were examined by means of in vitro labeling with tritiated thymidine and flow cytometry. RESULTS: We found a significant correlation between thymidine-labeling index and the percentage of cells in S-phase, measured by flow cytometry both in formalin-fixed, paraffin-embedded specimens and in frozen specimens (respectively, r = 0.7647, p < 0.001, and r = 0.4503, p < 0.01). However, using flow cytometry, the percentage of cells in S-phase was significantly higher than the thymidine-labeling index in both fixed-embedded and frozen specimens (p < 0.01). Proliferative parameters were not higher in patients with colon carcinoma, and were not related to the degree of dysplasia, the number of adenomas, or familial occurrence of colorectal cancer. Two specimens taken from normal rectal mucosa of two patients with adenomas showed aneuploidy. No aneuploidy was found in normal rectal specimens of patients with adenocarcinoma. CONCLUSIONS: These results show that the calculation of cells in S-phase with in vitro tritiated thymidine labeling or by flow cytometry produces different results. However, the significant correlation between corresponding parameters obtained with these techniques support the use of either method as "intermediate biomarkers" of colorectal cancer risk and prognosis.

Methodological problems in the use of rectal cell proliferation as a biomarker of colorectal cancer risk.

Clinical and experimental studies have shown that the carcinogenic process of colorectal mucosa is linked to the development of proliferative abnormalities which precede the occurrence of morphological abnormalities such as epithelial dysplasia. In humans, proliferative defects have been demonstrated in the normal rectal mucosa of population groups at risk for colon cancer. Several techniques are available to study cell kinetics in the gastrointestinal mucosa. Each explores different aspects of cell proliferation. We have attempted to evaluate the correlation between various techniques in the normal rectal mucosa of high-risk patients. We found a good correlation between bromodeoxyuridine (BrdU) labeling index and the mucosal activity of the enzyme ornithine decarboxylase, and between tritiated thymidine and the percentage of cells in the S phase of the proliferative cycle as determined by flow cytometry. However, these correlations concern only labeling indices, which can be influenced by physiological events, such as active inflammation or increased cell loss. It may not be the most reliable proliferative marker of cancer risk. Moreover, methods using cells isolated from homogenized tissue do not allow us to evaluate the pool of cells which are examined nor the distribution of proliferating cells within the tissue. For example, an inflamed mucosal specimen is highly infiltrated with inflammatory cells which can interfere with the measurement of epithelial cell proliferation. Nevertheless, the labeling index may be normal even in patients at high risk. For these reasons, we think that the most reliable methods are those using tissue culture, such as tritiated thymidine or BrdU uptake and proliferating cell nuclear antigen (PCNA) immunostaining.

Serum pepsinogen I and II concentrations and IgG antibody to Helicobacter pylori in dyspeptic patients.

AIMS: To investigate the association between histologically confirmed gastritis, carriage of Helicobacter pylori and pepsinogen (PG) I and PG II concentrations. METHODS: Prospective study of 81 dyspeptic patients undergoing upper gastrointestinal endoscopy was made. The extent of gastric mucosal inflammation and the presence of H pylori was determined, and serology to evaluate PG I and II concentrations and IgG titres to H pylori was carried out. RESULTS: The presence of H pylori was strongly correlated with high IgG antibody titres to H pylori and gastritis. Patients who were H pylori positive had significantly higher PG I and PG II concentrations and a significantly lower PG I:PG II ratio than patients who were negative for H pylori. In 13 patients with duodenal ulcer and H pylori positive gastritis serum PG I concentrations were significantly higher than in H pylori positive patients without duodenal ulcer. Significant correlations were found between the age of patients and serum PG II, the PG I:PG II ratio, IgG antibodies to H pylori, the severity of body gastritis and H pylori infection, and between the degree of gastritis in the body of the stomach and the PG II concentration. CONCLUSIONS: Serum PG I and II concentrations, together with a fall in the PG I:PG II ratio, could be used as predictors of H pylori infection as well as serum IgG antibody response to H pylori.

Abnormal rectal cell proliferation and p52/p35 protein expression in patients with ulcerative colitis.

We evaluated the presence of cell proliferation and antigenic abnormalities in rectal biopsies from 37 patients affected by ulcerative colitis and 15 controls. The study was carried out by thymidine labeling and immunochemistry, using antibodies against specific cytoskeletal-associated proteins (p52, p35, alpha-actinin). Among ulcerative colitis patients, 24 had an immunofluorescence pattern similar to that of controls, while 13 showed an abnormal distribution of one or more proteins (p52 alone or p52 and either p35 or alpha-actinin) within the rectal crypts. Patients showed a shift of the proliferative compartment towards the top of the rectal crypts compared with controls. This finding was more evident in patients with p52 or p35 abnormalities. Proliferative and antigenic defects were not related either to age or the duration of colitis. These phenotypic changes might be a biomarker of increased risk of colon cancer in ulcerative colitis.

Helicobacter pylori infection and gastric function in patients with chronic idiopathic dyspepsia.

Helicobacter pylori infection, histological features of the gastric mucosa, and gastric motor and secretory functions were evaluated in 45 consecutive patients with chronic idiopathic dyspepsia. H. pylori infection was found in 60% of dyspeptic patients, compared with 33% of 15 healthy controls (P = 0.1). No difference was detected in basal or stimulated gastric acid secretion between dyspeptic patients and healthy controls. Gastric emptying was significantly (P less than 0.01) delayed in dyspeptic patients compared with healthy controls when standardized for age and sex. Delayed gastric emptying was associated with a low frequency of H. pylori infection, female gender, and young age. Epigastric pain or burning and postprandial fullness were, respectively, more severe in patients with H. pylori infection (P less than 0.02) and in those with delayed gastric emptying (P less than 0.01). These findings support the existence of separate subsets of patients with chronic idiopathic dyspepsia. Despite the presence of overlaps, there appear to be partially different functional derangements and clinical features in different subgroups of dyspeptic patients.

Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis.

Short-chain fatty acid irrigation has been shown to ameliorate inflammation in diversion colitis. In this study the effect of butyrate enemas was tested in 10 patients with distal ulcerative colitis who had been unresponsive to or intolerant of standard therapy for 8 weeks. They were treated for 2 weeks with sodium butyrate (100 mmol/L) and 2 weeks with placebo in random order (single-blind trial). Before and after treatment, clinical symptoms were noted and the degree of inflammation was graded endoscopically and histologically. Rectal proliferation was assessed by autoradiography. After butyrate irrigation, stool frequency (n/day) decreased from 4.7 +/- 0.5 to 2.1 +/- 0.4 (P less than 0.01) and discharge of blood ceased in 9 of 10 patients. The endoscopic score fell from 6.5 +/- 0.4 to 3.8 +/- 0.8 (P less than 0.01). The histological degree of inflammation decreased from 2.4 +/- 0.3 to 1.5 +/- 0.3 (P less than 0.02). Overall crypt proliferation was unchanged, but the upper crypt-labeling index fell from 0.086 +/- 0.019 to 0.032 +/- 0.003 (P less than 0.03). On placebo, all of these parameters were unchanged. These data support the view that butyrate deficiency may play a role in the pathogenesis of distal ulcerative colitis and that butyrate irrigation ameliorates this condition.