Vladimiro Pilotti

Reliability of 24-hour home esophageal ph monitoring in diagnosis of gastroesophageal reflux

Twenty-four-hour home esophageal pH monitoring is proposed in order to study gastroesophageal reflux (GER) so that prolonged use of costly hospital equipment and staff can be curtailed and the diagnostic accuracy of the examination improved. Eighty-six patients affected by GER symptoms and 20 healthy volunteers underwent 24-hr home esophageal pH monitoring, x-rays, and endoscopy of the upper gastrointestinal tract to investigate reliability of outpatient recording. Fifteen more patients consecutively underwent out- and inpatient recording to detect possible differences between these methods in the two daily periods. Outpatient monitoring was well tolerated in 94.7% of the patients; 14.3% of them markedly reduced their routine activities. The range of normality of outpatient recording does not differ from that of inpatients. In the 15 patients who consecutively underwent out-and inpatient monitoring, no significant differences were reported. The sensitivity of 24-hr home esophageal pH recording is 0.85, the specificity 1, the accuracy for negative prediction 0.68, and the accuracy for positive prediction 1. The reliability of 24-hr home esophageal pH monitoring is comparable to inpatient recording. It allows hospital cost reduction and is also better tolerated by patients but has not greatly improved the diagnostic accuracy of the gastroesophageal reflux pH monitoring.

Ambulatory 24-hr pH monitoring of esophagus, fundus, and antrum

A method for outpatient 24-hr simultaneous recording of pH in the distal esophagus, fundus, and antrum was developed in order to detect acid, alkaline, alkalacid gastroesophageal reflux, and duodenogastric reflux and to study these phenomena in patients complaining of gastroesophageal reflux and dyspepsia related symptoms. Two hundred ninety-four studies were performed in 42 healthy volunteers and 237 patients. Three-probe ambulatory 24-hr esophagogastric pH monitoring applicability, tolerability, and capability to determine a relationship between symptoms which occurred during the tests, gastroesophageal reflux, and duodenogastric reflux episodes were assessed. Eighty-nine percent of the three-probe esophagogastric pH studies were easily performed. The examination was tolerated well by 86.1% of the patients and poorly by 13.9%. A temporal correlation between symptoms and pH activities was recognized in 61.3% when the esophageal tracing was considered (acid gastroesophageal reflux recording) and in 95.6% when the three pH traces were simultaneously interpreted. Alkalacid gastroesophageal reflux and duodenogastric reflux total percentage times were significantly higher in patients complaining of dyspeptic symptoms than in patients only affected by typical gastroesophageal symptoms. Three-probe 24-hr ambulatory esophagogastric pH monitoring is a simple, well-tolerated test that should be routinely adopted for the study of patients complaining of unclear upper gastrointestinal tract symptomatology.

Clinical and surgical relevance of the progressive phases of intrathoracic migration of the gastroesophageal junction in gastroesophageal reflux disease

OBJECTIVE The pathophysiologic influence of progressive intrathoracic migration of the gastroesophageal junction axial to the esophagus on gastroesophageal reflux disease was investigated. METHODS A radiologic-manometric study was performed on hiatal insufficiency, concentric hiatus hernia, and short esophagus, the three radiologic steps of intrathoracic gastroesophageal junction migration, and on healthy volunteers. The distances between inferior and superior margins of the lower esophageal sphincter and the diaphragm were measured. Endoscopic, manometric, and pH-metric evaluations were performed after barium swallow in 38 patients with severe gastroesophageal reflux disease and sliding hiatus hernia with intraabdominally reducible gastroesophageal junction, in 35 patients with hiatal insufficiency, in 40 with concentric hiatus hernia, and in 19 with short esophagus. RESULTS The distance from the lower esophageal sphincter inferior margin to the diaphragm was different in healthy volunteers (-2.6 +/- 0.9 cm [standard deviation]) versus that in patients with hiatal insufficiency (-1.0 +/- 0.7 cm; p = 0.02), concentric hiatus hernia (-0.8 +/- 1.0 cm; p = 0.02), and short esophagus (4.0 +/- 2.5 cm; p = 0.0002), and in patients with short esophagus versus hiatal insufficiency (p = 0.0002) and concentric hiatus hernia (p = 0.0002). Lower esophageal sphincter tone was reduced between healthy volunteers (19 +/- 9.1 mm Hg [standard deviation]) and patients with sliding hiatus hernia (12 +/- 7.2 mm Hg;p = 0.02), hiatal insufficiency (10 +/- 5.9 mm Hg; p = 0.0001), concentric hiatus hernia (7 +/- 3.1 mm Hg; p = 0.00002), and short esophagus (7 +/- 3.7 mm Hg; p = 0.00003) and between concentric hiatus hernia versus sliding hiatus hernia (p = 0.007). Acid gastroesophageal reflux total time percent was increased between healthy volunteers (2.4% +/- 1.8% [standard deviation]) and patients with sliding hiatus hernia (12.8% +/- 7.8%;p = 0.02), hiatal insufficiency (17.2% +/- 15.8%; p = 0.0001), concentric hiatus hernia (24.0% +/- 19.6%;p = 0.00002), and short esophagus (26.1% +/- 19.6%;p = 0.00002) and between sliding hiatus hernia versus concentric hiatus hernia (p = 0.002) and short esophagus (p = 0.01). CONCLUSIONS Permanent gastroesophageal junction orad migration axial to the esophagus has greater pathophysiologic relevance on gastroesophageal reflux disease than sliding hiatus hernia with an intraabdominally reducible gastroesophgeal junction. Hiatal insufficiency, concentric hiatus hernia, and short esophagus are markers of progressively increasing irreversible cardial incontinence and therefore indications for surgical therapy.

Hiatus hernia and intrathoracic migration of esophagogastric junction in gastroesophageal reflux disease.

The prevalence and clinical presentation of reducible and irreducible hiatus hernia were investigated within a gastro-esophageal reflux disease patient population. Reflux symptoms and esophagitis data were collected on 791 patients. The barium swallow was used to assess the esophagogastric junction. Clinical and endoscopic findings were tested to predict radiographic findings. The esophagogastric junction was normal in 17% of patients, 53% had a sliding hiatus hernia with a reducible esophagogastric junction; in 23% it was irreducible although axial, and 8% had massive incarcerated hiatus hernia. The presence of reducible sliding hiatus hernia did not influence clinical presentation. Axial irreducibility presented with long-standing severe symptoms and esophagitis in 80% of cases. Clinical and endoscopic findings predicted axial irreducibility in 52% of cases. In conclusion, sliding hiatus hernia with an reducible esophagogastric junction does not influence the severity of gastroesophageal reflux disease. An irreducible esophagogastric junction is associated with long-standing severe gastroesophageal reflux disease. Clinical and endoscopic findings may only be indicative of axial esophagogastric junction irreducibility; thus barium swallow should be part of the work-up.

Indications for 24-hour gastric pH monitoring with single and multiple probes in clinical research and practice

The methodology of prolonged gastric pH monitoring has not yet been standardized with regard to the number and position of pH probes. Twenty-seven healthy volunteers and 11 patients affected by nonulcer dyspepsia have been submitted to 24-hr ambulatory simultaneous pH monitoring of the distal esophagus, fundus, and antrum. Fundic and antral pH profiles have been compared and causes of pH variations (pH>4) identified. Both in healthy volunteers and dyspeptic patients, percentile curves of fundic and antral pH were statistically different in more than one of the daily periods considered (24-hr, postprandial, interdigestive, nocturnal). Percent time of duodenogastric reflux is significantly higher in the antrum than in the fundus in both groups. Modalities of gastric alkalinization secondary to food or duodenogastric reflux were different for the fundus and for the antrum both in healthy and dyspeptic subjects and between the two groups. These differences suggest that single and multiple pH monitoring of the stomach have different indications, and the position of the probes should vary according to the purpose of the test.

Transfer Factor as an adjuvant to non-small cell lung cancer (NSCLC) therapy

The rationale for using transfer factor (TF) in lung cancer patients is that the possibility of improving their cell-mediated immunity to tumour associated antigens (TAA) may improve their survival. From Jan 1984 to Jan 1995, 99 non-small cell lung cancer (NSCLC) resected patients were monthly treated with TF, extracted from the lymphocytes of blood bank donors. In the same period, 257 NSCLC resected patients were considered as non-treated controls. The survival rates of the TF treated group appear significantly improved both for patients in stages 3a and 3b, and patients with histological subtype “large cell carcinoma” (P<0.02). Survival of TF treated patients is also significantly higher (P<0.02) for patients with lymphnode involvement (N2 disease). The results of this study suggest that the administration of TF to NSCLC resected patients may improve survival.

Do bone marrow isolated tumor cells influence long-term survival of non-small cell lung cancer?

INTRODUCTION Inconsistent information on the prognostic significance of non-small cell lung cancer (NSCLC) isolated tumor cells (ITC) has been reported to date. We sought to evaluate the survival for NSCLC in a group of patients in which the presence of bone marrow isolated tumor cells and their DNA ploidy was assessed. MATERIALS AND METHODS Seventy patients (58 males [83%]; median age 70 years, range 49-89) with T1-4, N0, M0 clinical staging entered the study; 68 who underwent complete resection, were included in the follow-up. Two patients with clinical stage T2 and T4, N0, M0 were excluded because of pleural carcinosis discovered at thoracotomy. Recruitment ended in 2002. None received neoadjuvant therapy. The rib bone marrow was extracted and assessed for ITC by hematoxylin and eosin (H&E) staining, immunohistochemistry and flow cytometry. The latter was regarded as positive when >10% of cells reacted to pan-cytokeratin antibody MNF116. DNA ploidy was studied by propidium iodide staining. Patient follow-up was with chest X-ray and abdominal US every 6 months, and CT-PET scan every 12 months for at least 5 years after surgery. Causes of death were assessed. RESULTS Rib bone marrow ITC were documented in 17 patients (25%), 6 with DNA euploidy (p stage: I 4; III 2), and 11 with DNA aneuploidy (p stage: I 5; II 4; III 2) while 51 (75%) patients were free of ITC (p stage: I 32; II 8; III 9; IV 2). The median follow-up was 61 months, 21 patients died from causes unrelated to NSCLC and 12 patients died from causes related to tumor relapse. Significant survival differences were observed according to stage, presence of ITC and DNA aneuploidy. In particular free from recurrence survival was significantly reduced in stage IA and IB patients presenting aneuploid ITC (Wilcoxon (Gehan) test p=0.031). CONCLUSIONS The prognostic role of bone marrow ITC seems to be corroborated by DNA ploidy studies. Patients with bone marrow ITC with abnormal DNA content showed a significantly reduced survival particularly in stage I NSCLC.

Iliac crest biopsy versus rib segment resection for the detection of bone marrow isolated tumor cells from lung and esophageal cancer

OBJECTIVE The presence of isolated tumor cells in the bone marrow affects the prognosis of both esophageal cancer and non-small cell lung cancer (NSCLC). Therefore, preoperative assessment of isolated tumor cells may be useful to plan multimodality treatment. Rib segment resection at surgery provides adequate amounts of bone marrow for the detection of isolated tumor cells while bone marrow aspirate from the iliac crest does not. The iliac crest biopsy according to the Jamshidi technique procures a core of tissue apt for histology and not simply for cytology. The aim of this study was to compare the accuracy of iliac crest biopsy versus rib segment resection in the diagnosis of isolated tumor cells in order to obtain a useful preoperative approach. MATERIAL AND METHODS Twenty-one consecutive patients (18 NSCLC, three esophageal cancer) were evaluated. None had chemotherapy prior to evaluation. Bone marrow was obtained preoperatively by iliac crest biopsy using the Jamshidi needle and at surgery by rib segment resection. Positive cytokeratin neoplastic cells were searched by immunohistochemistry on tissue sections from the iliac crest biopsies and by flow cytometry on cell suspensions from the rib segments. RESULTS Isolated tumor cells were detected in the rib segments of ten patients. In all cases the Jamshidi needle biopsy was not diagnostic. CONCLUSION Our results suggest that, if the diagnosis of bone marrow isolated tumor cells has clinical relevance, the preoperative assessment should be performed by rib segment resection or methods other than iliac crest aspirate or biopsy. Further investigation is needed to determine whether isolated tumor cells have a preferential spread to chest bones other than distant bone sites.

Gastroesophageal and Duodenogastric Reflux: Simultaneous Twenty-Four-Hour Home Recording with a Three-Probe System (3EGpH)

In our experience two-probe 24-h home esophagogastric pH-monitoring has shown to be very effective in identifying acid and non-acid gastroesophageal reflux (GER): almost 50% of patients resulted in being affected by abnormal non-acid reflux (particularly the “alkalacid” GER 4>pH<7 resulting from the mixing of gastric and duodenal contents) [1]. Moreover, gastric fundus percentage total reflux time with pH≧4 was higher in GER patients than in controls [1].

Results of Surgical Therapy of Achalasia with Three Different Techniques

From 1955 to date our group has adopted three different surgical techniques for the therapy of achalasia [1]. Until 1972 a long transabdominal esophagogastric myotomy (group AM) was performed in 72 patients. In 13 patients an antireflux procedure according to Lortat Jacob was also associated. A complete follow-up of these patients in 1972 showed that postoperative reflux was present in 41.1 %; the Lortat Jacob procedure had not reduced reflux. The second cause of failure in this group was periesophageal scarring (7.1 %). In order to avoid reflux and its serious complications, in 1973 we started to perform a transthoracic myotomy, limiting the incision on the stomach to only 1/2 cm [2]. However, our results were not satisfactory since the recurrence for insufficient myotomy was 20.8%. For these reasons, in 1979 we adopted a new technique, which consists of a long transabdominal esophagogastric myotomy with the addition of an anterior hemifun-duplication according to Dor [1]. In June 1986 a complete follow-up of the patients operated on from 1955 to June 1985 was completed to evaluate the results achieved with the three surgical techniques.