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.

Pathophysiology and natural history of acquired short esophagus.

The choice of therapy--whether medical or surgical--for patients with gastroesophageal reflux (GER) is often a subject of debate. After a period in which surgery was almost the exclusive mode of treatment in patients with severe complications resulting from GER or in patients who did not respond to medical therapy, long-term follow-up showed that in 20 cases of GER in which only medical treatment was given, a progressive shortening of the esophagus--frequently in the absence of esophagitis--had developed. To investigate the pathophysiology of acquired short esophagus, we studied 34 patients--20 from the initial group and 14 who already had this condition. Clinical assessment consisted of interview, radiologic examination of the upper digestive tract, endoscopic and histologic examinations, and 24-hour home esophagogastric pH monitoring. We noted that acid GER causes shortening in the presence of severe mucosal lesions, while "nonacid" GER--a combination of gastric, pancreatic, and hepatic secretions--causes shortening of the esophagus even without evident mucosal lesions. Symptom evaluation, acid GER pH recording, and endoscopy are not sufficient for determination of the current choice of therapy. It is also important to quantify GER that results from the mixing of gastric and biliopancreatic secretions with use of the esophagogastric pH recording. This should reduce the possibility of silent shortening of the esophagus.

Wernicke's encephalopathy during total parenteral nutrition: observation in one case.

A patient operated for toxic megacolon secondary to ulcerative colitis developed a Wernicke syndrome (thiamine deficiency) during the postoperative period despite the administration of the usually recommended doses of vitamin B1 during total parenteral nutrition (TPN) treatment. Vitamin B1 deficiency should be checked in order to evaluate the patients' nutritional condition before starting TPN, especially those suffering from severe chronic malnutrition. Routine administration of vitamin B1 in repletion doses may be reasonably proposed in order to avoid the development of a Wernicke syndrome which is potentially lethal in a short time if not recognized and corrected in time.

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.

Validation of short tandem repeat analysis for the investigation of cases of disputed paternity.

This study details validation of two separate multiplex STR systems for use in paternity investigations. These are the Second Generation Multiplex (SGM) developed by the UK Forensic Science Service and the PowerPlex 1 multiplex commercially available from Promega Inc. (Madison, WI, USA). These multiplexes contain 12 different STR systems (two are duplicated in the two systems). Population databases from Caucasian, Asian and Afro-Caribbean populations have been compiled for all loci. In all but two of the 36 STR/ethnic group combinations, no evidence was obtained to indicate inconsistency with Hardy-Weinberg (HW) proportions. Empirical and theoretical approaches have been taken to validate these systems for paternity testing. Samples from 121 cases of disputed paternity were analysed using established Single Locus Probe (SLP) tests currently in use, and also using the two multiplex STR systems. Results of all three test systems were compared and no non-conformities in the conclusions were observed, although four examples of apparent germ line mutations in the STR systems were identified. The data was analysed to give information on expected paternity indices and exclusion rates for these STR systems. The 12 systems combined comprise a highly discriminating test suitable for paternity testing. 99.96% of non-fathers are excluded from paternity on two or more STR systems. Where no exclusion is found, Paternity Index (PI) values of > 10,000 are expected in > 96% of cases.

Duodenogastric and non acid gastro-oesophageal reflux in patients with reflux oesophagitis.

BACKGROUND/AIM: The role and the identification criteria of non acid gastro-oesophageal reflux (GOR) are still debated. Moreover, the relationship between nonacid GOR and gastric alkalinizations, particularly if secondary to duodeno-gastric reflux is yet to be defined. MATERIALS AND METHODS: One hundred and forty one patients affected by GORD symptoms and oesophagitis entered the study. Oesophagitis was divided into four categories, according to a modified Savary and Miller classification. Acid (pH<4), alkalacid (47), alkaline (pH>7) GOR and duodenogastric reflux were measured by means of ambulatory three channel esophago-gastric pH monitoring with a combined analysis of the pH traces recorded in the oesophagus fundus and antrum. RESULTS: Total time percentage (T%) of acid GOR was significantly greater in patients than in healthy volunteers (HV) and between groups of patients in direct relation with the severity of the oesophagitis. Alkaline GOR was hardly detectable in every class of esophagitis. Alkalacid GOR increased with the grade of severeness of oesophagitis. Alkalacid GOR occurred prevalently in the postprandial period; it was only 8% of the time in patients with mild reflux oesophagitis and even less in patients with moderate or severe oesophagitis. The 24 hr total time percentage of duodenogastric reflux was similar in the patients and healthy volunteer groups. The frequency distribution in 0.1 intervals of fundic and antral pH samples showed a greater number of them in the acid range (0.8-1.2) in the patients than in healthy volunteer group (0.00067) samples was similar in patients and in healthy volunteers. CONCLUSIONS: Our findings demonstrate that alkaline GOR is rare in GORD patients and that non acid GOR has a minor role in the pathophysiology of reflux esophagitis.

Surgery for esophageal achalasia. long-term results with three different techniques.

BACKGROUND/AIMS: In surgery for achalasia, the length of the myotomy and the opportunity of associating an antireflux procedure are still debated. Prospective and comparative studies on different techniques are few. The aims of this work is to compare the long term results of three different techniques successively adopted by the same surgical group. MATERIALS AND METHODS: Between January 1955 and December 1991, 185 achalasic patients were submitted to myotomy by using in temporal sequence three different techniques. The first technique utilized (1955-1972) was a long esophagogastric abdominal myotomy (83 patients), secondly (1973-1978) a limited transthoracic myotomy (30 patients) and at last (1979-1991) a long esophagogastric abdominal myotomy associated to the Dor gastroplasty (72 patients). Since 1972, patients were prospectively followed up according to a protocol which included a clinical interview, x-rays, manometry and endoscopy at given dates. Post-operative esophagogastric transit and gastro-esophageal reflux were assessed to verify the therapeutical outcome. Results obtained with the three different techniques were analyzed and compared by using the actuarial Kaplan-Meier curves. RESULTS: The mean follow up was 193.3 months for the patient group that underwent abdominal myotomy (62/83 patients), 137.3 months for the thoracic myotomy group (30/30 patients) and 86.9 months for the abdominal myotomy plus Dor gastroplasty group (69/72 patients). Long-term results in the abdominal myotomy and in the thoracic myotomy groups were respectively poor in 51.6% and in 46.6% of patients. Major causes of failure were insufficient myotomy (6.5%), periesophageal scarring (9.6%) and reflux esophagitis (22.6%) for the abdominal myotomy group; insufficient myotomy (20%) and reflux esophagitis (23%) for the thoracic myotomy group. In the abdominal myotomy plus Dor gastroplasty group long-term results were excellent or good in 87% of patients and poor in 13%. Reflux esophagitis (10% of cases) was the principal cause of failure. CONCLUSIONS: The comparison of the actuarial curves shows a significantly better long term outcome for the abdominal myotomy plus Dor antireflux procedure than for the abdominal myotomy (p = 0.01) and for the thoracic myotomy (p = 0.002) techniques.

[Pulmonary metastasis of malignant peritoneal mesothelioma. Review of the literature and a case report]. / Metastasi polmonari da mesotelioma maligno peritoneale. Revisione della letteratura in riferimento ad un caso clinico.

The authors describe the clinical case of a 54 year old patient, affected by malignant peritoneal mesothelioma treated by chemotherapy, who subsequently developed a lung lesion, treated by surgical wedge resection. The histologic examination of the surgical specimen, which led to the diagnosis of an intraparenchymal necrotic focus, confirms the favourable result of the adjuvant therapy. A review of the literature showing the rarity of lung metastases from malignant peritoneal mesothelioma is presented.

[Intraoperative esophageal manometry]. / La manometria esofagea intraoperatoria.

Intraoperative manometry has been proposed as a supportive procedure during the execution of anti-reflux operations and in the surgical treatment of achalasia. This procedure is not necessary in preparing anti-reflux plasty such as Belsey or Nissen, the outcome of which depends mostly on the correct execution of the surgical technique. Utilization of intra-operative manometry provides considerable benefits during the surgical treatment of achalasia, both when executing the extra-mucous myotomy and for the correct preparation of the anti-reflux plasty according to Dor, which is associated to it. Manometric control has made it possible to define the various anatomical components that, at both the esophageal and gastric levels, constitute the area which functionally corresponds to the lower esophageal sphincter and therefore a correct execution of the myotomy. As demonstrated by the follow-up study of our surgical patients, the intraoperative manometric measurement of the strain and of the length of the anti-reflux plasty is the determining factor affecting outcome over time. The pressure is apt to decrease even 5 year after surgery; maintaining given length and strain standards when executing the plasty can prevent delayed complications, such as esophagitis from gastro-esophageal reflux.

[Monitoring esophageal pressure: comparison of various methods and a unique solution]. / Monitoraggio delle pressioni esofagee: confronto fra metodi differenti e proposta di una soluzione originale.

Ambulatory monitoring of intraesophageal pressure requires probes and techniques which are different from those used in the laboratory approach. In particular the perfusion system for the measurement of the pressure is not suitable and the development of alternative solutions is mandatory. In this perspective an accurate analysis of the theoretical basis of different methods is necessary in order to avoid incorrect results and difficulties in the subsequent phase of analysis. A prototype probe, which is based on inextensible thin plastic balloons filled with oil or saline, was tested in comparison with traditional (perfused) and microtransducer systems to outline the positive and negative aspects of the solution. The results were satisfactory as regards linear output and frequency response up to 5 Hz for the prototype probe and even superior, for instance, to the response of the perfused system to applied pressure, whose curves of the four open tips resulted different, and to the response of Millar transducer. The new prototype probe seems to be adequate to the clinical and research needs.

[Definition of a normal tracing in pH monitoring]. / Definizione di normalità di un tracciato pH-metrico.

The adoption of specific criteria for the reading of tracings, together with a comparison of the results obtained during the course of patient tests with the thresholds of normality calculated in groups of healthy volunteers, are required to determine the normality or abnormality of pH monitoring. From such comparisons performed among groups of healthy volunteers, selected especially on the basis of age or nationality, it was found that age bears no significant influence in calculating the parameters pertinent to pH monitoring. On the other hand, different dietary and life habits could be responsible for a few, albeit limited, discrepancies, such as, for instance, the number of recorded occurrences of gastro-esophageal acid reflux. Use of esophago-gastric pH monitoring, which makes it possible to identify both acid and non-acid gastro-esophageal reflux (mixed and alkaline), authorizes the diagnosis of that limited number of patients in whom this latter component of reflux only exceeds normal limits (3.3%) and an improved definition of the clinical picture in a larger share of patients (20%). Use of different statistical methods to calculate the thresholds of normalcy does not substantially improve the sensitivity of the examination, changing the thresholds by a few tenths of a unit and the fact that the examination is slightly over, or slightly under, the threshold being of ineffectual clinical significance. The study of the correlation between symptoms and pH monitoring events seems a valid interpretative criterion of these tests and capable of improving the diagnostic efficiency of the examination (0.88) when combined with mathematical evaluation.

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.

Ultrasonographic localization of occult pulmonary nodules during video-assisted thoracic surgery.

The aim of our study was to evaluate the role of ultrasonography in the localization of pulmonary nodules during video-assisted thoracic surgery (VATS). Ultrasonography was performed in 35 patients for the localization of pulmonary nodules during VATS. Indication for VATS was excisional biopsy of undetermined nodules in 22 patients, single or multiple metastasectomy in 12 patients and resection of primitive pulmonary cancer in 1 patient with reduced pulmonary reserve. A laparoscopic probe with flexible head and multi-frequency transducer (5-7.5 MHz) was used. Intraoperative ultrasonography localized 37 of 40 nodules preoperatively detected by CT and/or by positron emission tomography in 35 patients. Furthermore, ultrasonography localized two nodules not visualized at spiral CT. Eighteen nodules were not visible or palpable at thoracoscopic examination and were found by intraoperative sonography only. In 6 patients in whom thoracotomy was performed, manual palpation did not reveal more lesions than ultrasonography. In our experience, ultrasonography was very helpful when lesions were not visible or palpable during thoracoscopy, showing high sensitivity (92.5%) in finding pulmonary nodules. Since it is not possible to determine preoperatively whether a localization technique will be necessary during the operation or not, and ultrasonography is a non-invasive technique, we think that, at present, this technique can be considered as the first-instance localization technique during thoracoscopic resection of pulmonary nodules.

Surgical therapy in "early gastric cancer".

Regarding early gastric cancer (E.G.C.) some authors propose total gastrectomy while others believe that partial resection is the best solution especially when the site is in the distal portion. The histological characteristics of E.G.C. in 49 patients were examined: 95.9% of the EGCs were found in the antropyloric region and 4.1% in the corpus-fundus. 47 patients were submitted to distal gastrectomy and 2 to total gastrectomy due to localization in the fundus. The overall survival rate after 5 yrs. is 83%. The incidence of the antropyloric localization, the rarity of metastases to the lymph node stations of the 2nd and 3rd level, the way in which intramural spread, occurs and, above all, the optimal survival rate obtained after partial resection, indicate that partial gastrectomy for distal gastric tumors is a radical operation, with a low surgical mortality rate, followed by a prolonged symptom-free survival.

Intraoperative study on the relationship between the lower esophageal sphincter pressure and the muscular components of the gastro-esophageal junction in achalasic patients.

OBJECTIVE: The lower esophageal sphincter (LES) resting tone originates from the tension of the muscular fibers of the gastro-esophageal (GE) junction. This study determined which of the muscular structures' of the GE junction are actually responsible and to what degree for the LES resting tone in achalasic patients. SUMMARY BACKGROUND DATA: Controversy still exists as to the length of myotomy on the esophageal and gastric sides of the GE junction. Experimental and clinical studies have supposed that the anatomical complex formed by the U and the sling fibers of the lesser curvature of the stomach can be part of the LES. METHODS: The variations induced on the LES resting tone by the separate division of the esophageal and gastric muscular fibers of the GE junction were studied by means of intraoperative manometry in 32 patients who underwent myotomy for achalasia. RESULTS: After surgical preparation of the GE junction, the mean pressure was 29.3 +/- 13 mmHg. After esophageal side myotomy, the mean LES pressure decreased to 13.6 +/- 7.9 mmHg (paired t test, p < 0.0005). The residual pressure was further reduced after gastric side myotomy (3.4 +/- 1.9 mmHg; paired t test, p < 0.0005). CONCLUSIONS: In achalasic patients, 45% of the LES resting tone is maintained by the gastric side anatomical component of the GE junction. The range of variability of the gastric component of the LES is wide. This information should be taken into account when performing extramucosal myotomy as therapy for esophageal achalasia.

Analysis of disputed single-parent/child and sibling relationships using 16 STR loci.

This study describes the validation of short tandem repeat (STR) systems for the resolution of cases of disputed parentage where only a single parent is available for testing or where the claimed relationship of both parents is in doubt and also cases where sibship must be tested. Three separate multiplex systems the Second Generation Multiplex, Powerplex 1.2 and FFFL have been employed, giving a total of 16 STR loci. Both empirical and theoretical approaches to the validation have been adopted. Appropriate equations have been derived to calculate likelihood ratios for different relationships, incorporating a correction for subpopulation effects. An F(ST) point estimate of 1% has been applied throughout. Empirically, 101 cases of alleged father, alleged mother and child where analysed using six SLP systems and also using the three multiplex STR systems. Of the 202 relationships tested, 197 were independently resolved by both systems, providing either clear evidence of non-parentage or strong support for the relationship.

Peripheral venous nutrition in surgical patients: techniques, indications and results.

Peripheral venous nutrition (PVN) has been proposed to avoid complications resulting from central venous catheterization in surgical patients. Using lipid emulsions 3 standard diets (with final osmolarity not higher than 900 mOsm/1, non-protein calories from 1675 to 2177, electrolytes 110 mEq, Cal/N ratio from 130/1 to 170/1) were worked out. They are suitable for total nutrition of non-hypercatabolic patients and for nutritional postoperative maintenance of patients undergoing major digestive tract surgery. The three diets were tested in 118 patients. Frequency and type of phlebitis and the nutritional status before and after treatment were evaluated in patients submitted to PVN and in 2 groups of 10 patients who received S-D5W infusions and Protein Sparing Nutrition (N = 12.8 g, total Cal. = 690, electrolytes = 110 mEq, osmolarity = 493 mOsm/l, pH = 7) in the postoperative period. Frequency of phlebitis was significantly lower in PVN patients than in control groups. 15 day treatment did not increase the frequency of phlebitis. In medium-term treated patients the mean daily nitrogen balance was always positive. Perioperative PVN achieved a statistically significant reduction of nitrogen losses with respect to PSN and S-DSW infusion.

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.

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 lymph node involvement (N2 disease). The results of this study suggest that the administration of TF to NSCLC resected patients may improve survival.